Cell Phones Effect on Society

RBMOnline – Vol 18. No 1. 2009 148-157 Reproductive BioMedicine Online; www. rbmonline. com/Article/3628 on web 3 November 2008 Review Cell phones: modern man’s nemesis? Ashok Agarwal is a Professor in the Lerner College of Medicine at Case Western Reserve University and the Director of Center for Reproductive Medicine, and the Clinical Andrology Laboratory at The Cleveland Clinic, Cleveland, Ohio, United States.He has published over 400 scientific articles, reviews and book chapters in different areas of andrology, male/ female infertility and fertility preservation. His research program is known internationally for its focus on disease-oriented cutting edge research in the field of human reproduction. His team has presented over 700 papers at national and international meetings and more than 150 scientists, clinicians and biologists have received their training in his laboratory.Dr Ashok Agarwal Kartikeya Makker1, Alex Varghese1, Nisarg R Desai1, Rand Mouradi2, Ashok Agarwal1,3 1 Center for Reproductive Medicine, Cleveland Clinic, Cleveland, Ohio, USA; 2Department of Electrical Engineering and Telecommunications, Cleveland State University, Cleveland, Ohio, USA 3 Correspondence: Tel: +1 216 444 9485; Fax: +1 216 445 6049; e-mail: [email  protected] org Abstract Over the past decade, the use of mobile phones has increased significantly.However, with every technological development comes some element of health concern, and cell phones are no exception. Recently, various studies have highlighted the negative effects of cell phone exposure on human health, and concerns about possible hazards related to cell phone exposure have been growing. This is a comprehensive, up-to-the-minute overview of the effects of cell phone exposure on human health.The types of cell phones and cell phone technologies currently used in the world are discussed in an attempt to improve the understanding of the technical aspects, including the effect of cell phone exposure on the cardiovascular system, sleep and cognitive function, as well as localized and general adverse effects, genotoxicity potential, neurohormonal secretion and tumour induction. The proposed echanisms by which cell phones adversely affect various aspects of human health, and male fertility in particular, are explained, and the emerging molecular techniques and approaches for elucidating the effects of mobile phone radiation on cellular physiology using high-throughput screening techniques, such as metabolomics and microarrays, are discussed. A novel study is described, which is looking at changes in semen parameters, oxidative stress markers and sperm DNA damage in semen samples exposed in vitro to cell phone radiation.Keywords: biophysics, cell phone, general health, infertility, radiofrequency electromagnetic waves, RF-EMW Introduction Cell phone usage has increased by leaps and bounds in the past decade and a half. From being a luxury limited to the wealthy, cell phones have b ecome a commodity, virtually indispensable in daily lives. However, every technological advance and its overuse have a negative aspect. The increase in popularity of cell phones is accompanied by a growing concern regarding the harmful effects of cell phone radiation (radiofrequency electromagnetic waves; RF-EMW) exposure on human health.An earlier report of the Independent Expert Group on Mobile Phones, established by the UK government, summarized the relevant studies on the biological effects of RF-EMW (Huber et al. , 2000). Since then, a flurry of scientific activities has attempted to define and quantify the adverse effects of RF-EMW. Despite the increasing number of reports concerning the effects of RF-EMW on various biological systems, no satisfactory mechanism has been proposed to explain the effects of this radiation (Feychting, 2005).Although cell phone companies constantly reassure their subscribers about the safety of their product, reports based on animal and human exper iments showing adverse effects of cell phones on biological systems have surfaced. According to various reports, excessive cell phone usage has led to fatigue, headache, decreased concentration and local irritation and burning (Sandstrom et al. , 2001). The possible role of cell phone exposure on tumour induction also has been proposed in an epidemiological study (Hardell et al. , 2006).Recent studies also have highlighted the role of cell phone exposure on sperm motility, morphology and viability, thus proposing a reduction in male fertilizing potential (Agarwal et al. , 2008). Other reports suggest that RF-EMW may lead to DNA damage and chromosomal instability (Diem et al. , 2005). Even though the current research may have been inconclusive, it still has been successful in providing preliminary data and identifying trends on both sides of the argument that cell phone exposure may lead to harmful effects on human health.These 148  © 2009 Published by Reproductive Healthcare Ltd, Duck End Farm, Dry Drayton, Cambridge CB23 8DB, UK Review – Cell phones: modern man’s nemesis? – K Makker et al. studies have been handicapped by many drawbacks in design and methodology. In particular, comparing animal models with humans (Cairnie and Harding, 1981) is impractical. Differences in geometry, size and physiological responses between man and experimental animals imply that the results in animal studies should be interpreted with caution.Experimental approaches involving animal studies and in-vitro studies, along with high-throughput screening techniques like transcriptomics, proteomics and metabolomics, can augment the validity of epidemiological studies addressing the effect of RF-EMW on reproductive tissues, cells and functions. Recent studies using these approaches have yielded interesting clues on the effect of RF-EMW at the cellular and molecular levels. This article highlights the adverse affects of RF-EMW on human biological systems by review ing relevant studies and recent research to aid in deeper understanding of this important health issue.The novel study currently being carried out in the centre is briefly discussed. 1900 MHz), and they have the capacity to switch automatically among these four frequencies. Specific absorption rate (SAR) is the energy flow per unit of mass (watts/kg; W/kg). It is a measurement of the power or heat absorbed by the tissue either in a local area of a human tissue or averaged over the whole body. In the USA, the SAR of cell phones varies from 0. 12–1. 6 W/kg. Standards are designed to limit the SAR in the body to safety levels. The Federal Communications Commission has set a SAR safety limit of 1. W/kg, averaged over a volume of 1 g of tissue, for most parts of the body (see website). Exposure guidelines for RF protection had adopted the value of 4 W/kg averaged over the whole body (SARWB) ‘as the threshold for the induction of adverse thermal effects associated with an inc rease of the body core temperature of about 1 °C in animal experiments’ (Barnes and Greenebaum, 2007). Cell phone radiation output power is measured in units of watts or dBm (decibel referenced to 1 mW). Usually cell phones with higher frequency are assigned less output power. Cell phones commonly used these days operate at an output power of less than 1 W.Power density is a term for characterizing an RF electromagnetic field. It is defined as the power per unit area and is measured in units of mW/m2 or  µW/cm2 (Food and Drug Administration website). Maximum permissible exposures are based on SAR and power density measurements. The Federal Communications Commission has established safety standards on power density for cell phone base station antenna using 1900 MHz band for the general population an uncontrolled exposure of 1000  µW/cm2, and for the 850 MHz band the maximum exposure allowed is about 580  µW/cm2, as averaged over any 30-min period.Recent studies demonst rated that RF-EMW emitted from commercially available cell phones have no thermal effects (Straume et al. , 2005; Anderson and Rowley, 2007; Yan et al. , 2007). An overview of cell phone technology Telecommunications technology has advanced rapidly and explosively in recent years. The earliest, fully automatic cellular phone systems that were used were called Nordic mobile telephone, now classified as first-generation cellular phones. Introduced in the late 1970s and early 1980s, they were based on analogue technology.The second-generation cell phones that replaced the older analogue type are based on digital technology. These digital models have increased voice capacity, provided faster data transfer speeds, longer battery life, less power use and better signal quality than the firstgeneration cell phones. The cell phone technologies that are commonly used nowadays are the global system for mobile communication (GSM) and code division multiple access (CDMA). Both of these technolog ies are used by cell phone companies in the USA.The GSM technology uses narrow-band time division multiple access (TDMA), whereas CDMA incorporates the wider band that allows more users without interference and better security by providing every user with a unique code. The third-generation cell phones, which may be available for general use in the near future, consist of universal mobile telecommunications system (UMTS)/wideband code division multiple access (W-CDMA) and the high-speed downlink packet access (HSDPA) phones.The UMTS utilizes a GSM infrastructure with a W-CDMA air interface (the specification of the radio transmission between a mobile phone and the base station), which adds advantages to UMTS over GSM technology. The HSDPA is based on the W-CDMA technology with improved downlink speed that allows even higher data transfer speeds and capacity. Cell phones in the USA operate on the frequency bands of 850 MHz and 1900 MHz. In most other parts of the world, the frequency bands used are 900 MHz and 1800 MHz.The newer phones offer a quad-band feature, which means that they can operate on the four common frequencies (850/900/1800 and RBMOnline ® Effect of RF-EMW on general health This section provides a discussion of the various aspects of human health that have been proposed to be, or actually are, affected by cell phone radiation (RF-EMW) (Figure 1). Effect on cardiovascular system (CVS) Braune et al. (1998) exposed human volunteers to RF-EMW and reported an increase in blood pressure (both systolic and diastolic) on exposure to RF-EMW at 900 MHz for 35 min.Blood pressure increased by 5–10 mmHg, accompanied by a significant decrease in capillary perfusion due to vasoconstriction. They demonstrated, however, that autoregulatory blood pressure mechanisms were intact, as shown by a decrease in heart rate to nullify the increase in blood pressure. In a follow-up study done by the same group to corroborate their previous findings, a statisticall y significant increase in blood pressure was shown, but the analysis of variance showed that the changes were independent of EMW exposure (Braune et al. , 2002).Later, Tahvanainen et al. (2004) demonstrated cell phone exposure does not acutely change arterial blood pressure and heart rate. 149 Review – Cell phones: modern man’s nemesis? – K Makker et al. Figure 1. Effect of electromagnetic radiation from cell phone usage on various human systems. OS = oxidative stress. In an animal study, Ozguner et al. (2005) reported increase in oxidative stress in rat myocardium on exposure to 900 MHz RF-EMW (30 min/day, for 10 days). kit or using a landline phone to reduce cell phone exposure (Oftedal et al. , 2000).The generation of reactive oxygen species by RF-EMW exposure is still to be proven convincingly, although many groups have provided evidence in animal-based studies. An increase in kidney tissue malonaldehyde and urine N-acetyl-? d-glucosaminidase and decrease in renal superoxide dismutase, catalase and glutathione peroxidase were reported by Oktem et al. (2005). Similar results were shown by another investigator (Irmak et al. , 2002), who provided evidence in favour of EMW-induced oxidative stress. They showed an increase in superoxide dismutase activity and a decrease in nitric oxide concentrations in sera.Conversely, no change was seen in the concentration of intracellular oxidants [oxidized form of glutathione (GSSG) accumulation, oxidation of thiol] and antioxidants (CuZn-superoxide dismutase, catalase) in cells exposed to radiofrequency radiation (CDMA and GSM, 835– 847 MHz for 20–22 h) (Hook et al. , 2004). Effect on sleep Despite concerns that sleep patterns are disturbed due to excessive cell phone usage, Huber et al. (2000) did not report any significant change in sleep quality, sleep latency and rapid-eye-movement sleep latency in healthy young men exposed to 900 MHz for 30 min.The only effect reported was an increa se in electroencephalogram power density during the first 30 min of non-rapid-eye-movement sleep, especially ? waves and sleep spindles (the type of sleep waves seen with an electroencephalogram). They concluded that the effect of RF-EMW exposure was transitory, limited to the initial phase of sleep and outlasting the RF-EMW exposure. Recently, Perentos et al. (2007) found no significant change in resting electroencephalogram on human volunteers exposed to RF-EMW. Cell phones and neurohormonal secretionVarious epidemiological studies have highlighted effects of cell phone usage on neurohormonal secretion. Conflicting results have been reported by different groups regarding the effect of cell phones on melatonin secretion. De Seze et al. (1999) reported no change in maximum serum concentration (P = 0. 63), the time of peak concentration (P = 0. 49) and area under curve (P = 0. 56) of the hormonal profile. On the other hand, Burch et al. (2002) concluded that subjects with cell phone usage >25 min/day had lower creatinine-adjusted mean nocturnal concentrations of a melatonin metabolite, 6-hydroxymelatonin sulphate (6-OHMS), (P = 0. 5) and lower overnight 6-OHMS excretion (P = 0. 03). They concluded that prolonged usage of cell phones may lead to reduced melatonin production. Djeridane et al. (2008) demonstrated 900 MHz RFEMW would not significantly affect endocrine functions in men. RBMOnline ® Local and general adverse effects Sandstrom et al. (2001), in a questionnaire-based study involving some 17,000 respondents, showed that cell phone usage led to complaints such as warmth on and behind the ear (31%), fatigue (28%), headache (21. 4%), decreased concentration (15%), dizziness (10%), memory loss (9%), and tingling and numbness (6. 7%).They also concluded that a statistically significant positive trend was shown by warmth and neurasthenic symptoms (headache, fatigue) with calling time and number of calls per day. They proposed that these changes were due to either radiofrequency exposure or thermal effects of EMW. Of all the people who attributed these symptoms to cell phone usage, 45% of them took steps such as reducing calling time, changing cell phone model, using a hands-free 150 Review – Cell phones: modern man’s nemesis? – K Makker et al. Effects on cognitive function Preece et al. (1999) exposed human volunteers to RF-EMW and reported that the nly cognitive function test that altered post-RF-EMW exposure is choice reaction time, leading to an increase in responsiveness. They reported no change in word, number or picture recall or any change in spatial memory. They proposed that the increase in responsiveness was due to a mild local thermal effect of EMW on angular gyrus (the interface between visual and speech centres) or to mechanisms mediated by heat shock proteins. They also concluded that memory is not commonly affected by cell phone exposure as the memory area of the brain (hippocampus) is deep seated i n the medial temporal lobe of the brain.Later, Regel et al. (2007) demonstrated RFEMW exposure reduces reaction speed and increased accuracy in working-memory tasks. As discussed previously, recent studies reported that RF-EMW emitted from commercially available cell phones have no thermal effect (Straume et al. , 2005; Anderson and Rowley, 2007; Yan et al. , 2007). However, several views were proposed to elucidate the disruption of metabolic pathways by RF-EMW. Some of these views are based on experimental evidences and some on hypothetical models. Isocitrate dehydrogenase, an important enzyme in the citric acid cycle, is one of the targets of cell phone radiation.Alteration in the enzyme activity leads to decreased production of adenosine triphosphate (ATP) in mammalian cells (Nylund and Leszczynski, 2004). Since sperm motility depends on the active generation of ATP, such a mechanism might cause the decline in sperm motility during RF exposure. Spermatozoa lose their cytoplasm po st-spermiation, leading to the loss of their antioxidant protective mechanism and rendering them inherently vulnerable to induction of DNA damage. They are differentiated to the point that they cannot undergo apoptosis in response to any form of severe genetic damage (Aitken, 1999).In addition, during the process of maturation, spermatozoa are separated from the Sertoli cells, their nursing cells. Several investigators have demonstrated an increase in DNA fragmentation in a variety of human and animal cells following cell phone exposure (Lai and Singh, 1996; Diem et al. , 2005; Panagopoulos et al. , 2007). Lai and Singh showed that exposing rats (n = 16) for 2 h to pulsed 2- µs pulse width, 500 pulses/s and continuous wave (2450 MHz) leads to an increase in breaks of single-stranded DNA (P < 0. 01) and double-stranded DNA (P < 0. 01) in rat brain cells.They proposed that this could be due to either direct EMWmediated effects or a defect in DNA repair mechanisms. In contrast, sever al studies found no effect of EMW on genotoxicity. Stronati et al. (2006) demonstrated no effects of RF exposure on DNA strand breakage (assessed by COMET assay), unstable chromosomal alterations (assessed by metaphase analysis) or alterations in the speed of in-vitro cell cycling (assessed by nuclear division index) in lymphocytes in their experiment involving exposure of human blood samples to RF (24 h, 935 MHz). A large-scale in-vitro study conducted by Sakuma et al. 2006) concluded that RF-EMW from mobile phone radio base stations do not act as a genotoxicant (at SAR up to 800 mW/kg). The induction of DNA damage in spermatozoa has been associated with male infertility, early pregnancy loss and morbidity in the offspring, including childhood cancer (Aitken, 1999). Aitken et al. (2005) demonstrated that exposure of mice to RF-EMW, 900 MHz, 12 h/day for 7 days led to damage to both the mitochondrial and nuclear genome of epididymal spermatozoa (P < 0. 01). However, currently no hum an studies are available demonstrating DNA damage in sperm cells by RF radiation exposure.Several animal studies have attempted to highlight histological changes in testicular tissue on exposure to RF-EMW. Dasdag et al. (1999) demonstrated a decrease in mean seminiferous tubule diameter in rats (n = 18) by exposing them to an 890–915 MHz cell phone, 2 h/day for 30 days (P < 0. 05). However, a similar study carried out later by the same group did not reveal any statistically significant result of cell phone exposure on seminiferous tubular diameter, lipid composition, malonaldehyde Tumorigenesis Carcinogenic potential of cell phone radiation is one of the most conflicting aspect in various studies conducted by several groups.Following public concern that cell phone exposure may lead to cancer, Hardell et al. (2006) conducted an epidemiological questionnaire-based study and concluded that astrocytoma (grade III–IV) and acoustic neuroma did show a positive correlation wit h cell phone usage, and the odds ratio increased with latency (10 years). However, no increased risk was shown with astrocytoma (grade I–II), non-Hodgkin lymphoma, salivary tumours or testicular tumours. With regard to testicular tumours, they concluded that the risk of seminoma and non-seminoma was not increased, a dose–response effect was not observed, and he location of the cell phone was not associated with testicular cancers (Hardell et al. , 2007). Other scientists have concluded that the current evidence for a causal association between cancer and EMW exposure is weak and unconvincing (Colonna, 2005). Cell phone and effects on male fertility Pathophysiology Despite reports from numerous groups suggesting a possible role of cell phone exposure in male infertility, the exact mechanism of the effects of EMW on male reproductive system is yet to be elucidated. Though various effects have been proposed, foolproof experimental evidences are lacking to substantiate it. Human testes need physiological temperatures 2 °C lower than body temperature for optimal spermatogenesis. Highintensity RF has heating properties that lead to thermal effects on the testes. An increase in testicular or body temperature on exposure to EMW may cause reversible disruption of spermatogenesis (Kandeel and Swerdloff, 1988; Jung and Schill, 2000). EMW can also affect reproductive function via an EMW-specific effect (a ‘microwave’ effect produced by an increase in tissue temperature less than its normal temperature fluctuation) or in combination with the thermal molecular effect (Blackwell, 1979). 51 RBMOnline ® Review – Cell phones: modern man’s nemesis? – K Makker et al. concentration, sperm count or sperm morphology (Dasdag et al. , 2003). Ribeiro et al. (2007) also did not find any significant adverse effect of cellular phone exposure (GSM 1835–1850 MHz exposure, 1 h/day for 11 weeks) on rat testicular histology and function . However results of in-vitro studies are conflicting. An in-vitro study divided neat semen samples from healthy volunteers (n = 27) into two parts and one part was exposed to 900 MHz EMW for 5 min.Compared with the unexposed sample, the exposed sample was found to have a significant decrease in rapid progressive motility (Grade A, P = 0. 0007), an increase in slow progressive motility (Grade B, P = 0. 0007) and an increase in the percentage of immotile spermatozoa (Grade D, P = 0. 0003) (Erogul et al. , 2006). Recently, Falzone et al. (2008) studied the effect of pulsed 900 MHz radiation on various kinetic parameters and mitochondrial membrane potential (MMP)of purified human spermatozoa (by percoll density gradient). They found significant decrease in straight-line velocity and beatcross frequency at an SAR of 5. W/kg. However, at an SAR of 2. 0 W/kg they found no significant change in any kinetic parameters, including MMP. Significant changes in sperm morphology were not reported in the animal studies carried out by Dasdag et al. (1999, 2003). Similarly no significant (P > 0. 05) alteration in morphology was reported by another group based on their animal experiment (Yan et al. , 2007). However, the same group reported that 80% of the slides in the exposed group showed large clumps of sperm cells that were able only to turn about in their position and were not able to break free.On the other hand, significant data were brought out in a study in which 15. 3% of men using cell phones sporadically for 1–2 years had only 10–19% normal spermatozoa, and 15. 3% had total azoospermia, whereas men frequently using cell phones for >2 years had only 8. 3% normal spermatozoa, and 22. 9% showed total azoospermia (Wdowiak et al. , 2007). EMW and semen parameters The effects of cell phone exposure on male fertility have been studied exhaustively in recent years (Deepinder et al. , 2007).The effects on sperm concentration, motility and morphology have been ev aluated in many animal and human studies, but results are inconclusive. Motility is the only parameter that the majority of studies have shown to be significantly affected. The need to further evaluate the effects of EMW on sperm morphology, viability and concentration still exists. Dasdag et al. (1999) reported a decrease in sperm count; however, the decline was not statistically significant (P > 0. 05), and they were not able to repeat the same results later in a similar study (Dasdag et al. 2003). Another group reported that exposure of rats (n = 16) to a 1. 9 Hz cell phone from a distance of 1 cm for 6 h/ day for 18 weeks did not lead to significant decline in sperm concentration. The exposure group had a mean sperm count of 7. 45 ? 107  ± 1. 03 ? 107 sperm cells/ml, and the non-exposed group had a mean sperm count of 7. 7 ? 107  ± 8. 11 ? 106 sperm cells/ml (P > 0. 05) (Yan et al. , 2007). In an epidemiological study, researchers concluded that no statistically significant (P > 0. 05, chi-squared test = 1. 8) difference in sperm count resulted from cell phone exposure (Wdowiak et al. , 2007). In a study carried out by this centre, a significant decline in sperm count was demonstrated in men who used cell phones for >4 h/ day (n = 114, count 50. 30  ± 41. 92 ? 106/ml) as compared with those who did not use cell phones at all (n = 40, count 85. 89  ± 35. 56 ? 106/ml) (P < 0. 0001) (Agarwal et al. , 2008). As mentioned earlier, motility is the only parameter that consistently has been shown to decline in studies carried out by various groups.In a study involving 371 men presenting for an infertility workup, duration of possession and daily transmission time of cell phones correlated negatively with the proportion of rapid progressive motile spermatozoa (r = –0. 12 and r = –0. 19, P < 0. 01) and positively with the proportion of slow progressive motile spermatozoa (r = 0. 12 and r = 0. 28, P < 0. 01) (Fejes et al. , 2005). The same group also concluded that low transmitter (60 min/ day) groups also differed in the proportion of rapid progressive motile spermatozoa (48. 7% versus 40. 6%, P < 0. 01).Wdowiak et al. (2007) reported that 65. 7% of men not using cell phones had >50% (WHO category A + B) sperm motility, whereas only 35. 4% of men who frequently used cell phones had >50% (A + B) sperm motility. Agarwal et al. (2008) had shown a significant reduction in motility of spermatozoa in men using cell phones >4 h/day versus men not using them at all (67. 80  ± 6. 16% versus 44. 81  ± 16. 30%, P < 0. 0001). In an animal-based study, a significant decrease in sperm motility on exposure to cell phone (n = 16, P < 0. 05) was reported (Yan et al. , 2007).The researchers also reported that the majority of sperm cells in the exposure group were dead (live cells 44. 88  ± 20. 66%); in the control group, the majority of sperm cells were alive with constant, active motility (live cells 70. 93  ± 12. 94%). Transcript omics and proteomics in elucidation of biological response of cell phone radiation Research over the last two decades on the effect of RFEMW has yielded controversial results. It is said that even an extensive epidemiological study might not be sufficient to elucidate the health effects of electromagnetic radiations because of the low sensitivity of this approach.Hence, to validate the results from epidemiological studies, further data from animal and in-vitro studies needs to be analysed. Several lines of evidences suggest that the novel methodologies such as transcriptomics, proteomics and metabolomics could help in the search for clues to the negative impact of cell phone radiation on human health. High-throughput screening techniques combined with modern bioinformatics could be used to pick up minute variations, like those caused by RF-EMW affecting protein or gene expression, that might be of insufficient magnitude to alter cell physiology or give any phenotypic alteration (Fig ure 2).Heat shock proteins (Hsp), which are molecular chaperones, comprise a group of highly conserved, abundantly expressed proteins with diverse functions, including the assembly and sequestering of multiprotein complexes, transportation of nascent polypeptide chains across cellular membranes, and regulation of protein folding. Protein phosphorylation is a first line of cellular response to any stimuli by either RBMOnline ® 152 Review – Cell phones: modern man’s nemesis? – K Makker et al. Figure 2. A proposed model to study the effect of cell phone radiation using the high-throughput technologies.These techniques combined with modern bioinformatics could be helpful to find minute variations caused by RF-EMF in protein or gene expression changes that might be of insufficient magnitude to alter cell physiology or give any phenotypic alteration. MALDI-TOF = matrixassisted laser desorption/ionization time of flight; SAGE = serial analysis of gene expression. int ernal or external factors. By using western blots or mass spectrometry, the phosphoproteins could be located after cellular irradiation from a mobile phone to check for any alterations in cell response.By using this approach, Hsp27 was determined to be a molecular target event of RF-EMW (Leszczynski et al. , 2002). A study using matrix-assisted laser desorption/ionization-mass spectrometry found statistically significant altered expression levels of 38 various proteins in human endothelial cell lines following GSM 900 MHz irradiation (Nylund and Leszczynski, 2004). Two of the affected proteins were determined to be isoforms of cytoskeletal vimentin and might have an effect on the physiological functions that are regulated by the cytoskeleton.Results from a study using human lens epithelial cells (HLEC) cell lines indicate that exposure to non-thermal dosages of RF for wireless communications can induce no or repairable DNA damage and the augmented Hsp70 protein expression in HLEC oc curred without change in the cell proliferation rate (Nylund and Leszczynski, 2004). The induction of Hsp70 by extremely low frequency (ELF) EMW also involves elements of the mitogen-activated phosphokinase (MAPK) family of cell response cascades, which are recognized signal transduction systems present in eukaryotes.MAPK pathways consist of distinct cascades of regulator enzymes that serially activate one another to control the expression of specific sets of genes in response to growth factors, cytokines, tumour promoters and other major biological stimuli. The authors suggest that nonthermal stress response of Hsp70 protein increased on RF exposure might be involved in protecting HLEC from DNA damage and maintaining the cellular capacity for proliferation (Lixia et al. , 2006). RBMOnline ®The phosphorylated Hsp27 (activated) has been shown to inhibit apoptosis by forming a complex with the apoptosome (complex of Apaf 1 protein, procaspase 9, and cytochrome c) or some of its comp onents and preventing proteolytic activation of the procaspase 9 into active form of caspase 9 (Concannon et al. , 2001). This, in turn, prevents activation of procaspase-3, which is activated by caspase 9. Apaf-1 plays an important role in the induction of apoptosis (Zou et al. , 1997). Cytochrome c release from mitochondria occurs when there is a DNAdamaging stimuli-induced apoptosis.Together with dATP/ATP, cytochrome c initiates formation of an apoptosome consisting of Apaf 1 oligomers. The Apaf 1 apoptosome recruits and activates caspase 9, which in turn activates the executioner caspases, caspase 3 and caspase 7 (Zou et al. , 1997). The induction of the increased Hsp27 activation by the RF-EMW exposure might lead to inhibition of the apoptotic pathway that involves apoptosome and caspase 3. It is proposed that such events occurring in RF-EMW-exposed cells that had undergone either spontaneous or external factor-induced transformation or damage could support survival of the tran sformed/damaged cells (Leszczynski et al. 2004). The exposure of the EA. hy926 human endothelial cell line to 900 MHz RF-EMW induces activation of the p38 MAPK stress response pathway and leads to an increase in expression and phosphorylation of the small stress response protein Hsp27 (Leszczynski et al. , 2002). Other studies have shown that the phosphorylated form of Hsp 27 has the ability to translocate to the nucleus and to induce changes in gene expression (Geum et al. , 2002). The evidence suggests that different types of cells from different species might respond differently to mobile phone radiation 53 Review – Cell phones: modern man’s nemesis? – K Makker et al. or might have different sensitivity to this weak stimulus. The results from the studies by (Nylund and Leszczynski, 2006) show that gene and protein expression were altered in multiple cell lines in response to 1-h mobile phone radiation exposure at an average specific absorption rate of 2. 8 W/ kg. However, the same genes and proteins were affected differently by the exposure in each of the cell lines. This suggests that the cell response to mobile phone radiation might be genome- and proteome-dependent.The magnitude of the genetic background for some stimulus-specific responses was highlighted by some studies comparing different cell lines (Czyz et al. , 2004). It is postulated that the genetic constitution, as well as carrier frequency of the modulation schemes and exposure duration, may play a substantial role in responsiveness of cells to RFEMW. These findings might also explain, at least in part, the origin of discrepancies in reproducibility of studies among different laboratories (Nylund and Leszczynski, 2006).Some evidence has suggested that RF-EMW may change expression of DNA transcription factors and cause changes in cell cycle kinetics. Litovitz et al. (1993) have shown that exposure of mouse L929 fibroblasts to 915 MHz at an SAR of 2. 5 W/kg induced the express ion of ornithine decarboxylase protein, an enzyme important in cell cycle regulation. Natarajan et al. (2002) reported that exposure of a monocytic cell line to 8. 2 GHz pulse-modulated RF-EMW increased the binding of the nuclear factor kappa light chain gene to its consensus DNA sequence.Later on, relative expression and localization of bone morphogenetic proteins (BMP) and their receptors (BMPR), major endocrine and autocrine morphogens involved in renal development, were investigated by Pyrpasopoulou et al. (2004) in newborn kidneys from RF-EMW-exposed pregnant rats. The kidneys of newborns from the RF-exposed rats showed up-regulation of BMP4 and BMPR1A and down-regulation of BMPR2. This study suggests that RF-EMW might interfere with gene expression during early gestation and result in aberrations of BMP expression in the newborn (Pyrpasopoulou et al. 2004). RF-EMW has also been reported to affect the expression of Jun, a proto-oncogene (Ivaschuk et al. , 1997). Using serial an alysis of gene expression (SAGE), Lee et al. (2005) reported that in-vitro exposure of HL-60 cells to pulsemodulated 2. 45 GHz RF fields at an SAR of 10 W/kg for 6 h resulted in the differential expression of more than 750 genes. In contrast, many other recent studies have failed to find evidence of RF-field-induced changes in Hsp expression after RF-EMW exposure at frequencies ranging from 900–1950 MHz and SAR from 2–10 W/kg (Capri et al. 2004a,b; Laszlo et al. , 2005). Qutob et al. (2006) also reported no evidence relating nonthermal RF field on gene expression using microarray analysis in cultured U87 MG cells. Studies done on Drosophila melanogaster developmental potential by exposure to non-thermal radiation from the GSM mobile phone found increased numbers of offspring and elevated Hsp70 levels (Weisbrot et al. , 2003). This study also reported increased serum response element DNA-binding and induction of the phosphorylation of the nuclear transcription factor EL K-1 by cell phone radiation.The rapid induction of Hsp70 within minutes by a non-thermal stress, together with identified components of signal transduction pathways, could provide sensitive and reliable biomarkers that could serve as the basis for practical mobile phone safety guidelines (Weisbrot et al. , 2003). The indications to date that certain genes are influenced by EMW suggests that genome-wide scans of the transcriptome are necessary. Among the several technologies used for genomewide gene expression analysis, SAGE is one promising method that seems particularly applicable for EMW research.SAGE has been used in many biological and medical studies involving various eukaryotic species. So far, more than 19 million copies of SAGE tags have been collected from humans (Wang, 2006). In a recent study by Remondini et al. (2006), which was part of the Fifth Framework Programme project REFLEX (Risk Evaluation of Potential Environmental Hazards From LowEnergy Electromagnetic Field Ex posure Using Sensitive InVitro Methods), six human cell types, immortalized cell lines and primary cells were exposed to 900 and 1800 MHz.RNA was isolated from exposed and sham-exposed cells and labelled for transcriptome analysis on whole-genome cDNA arrays. NB69 neuroblastoma cells, T lymphocytes, and CHME5 microglial cells did not show significant changes in gene expression. In EA. hy926 endothelial cells, U937 lymphoblastoma cells and HL-60 leukaemia cells, between 12 and 34 genes were up- or down-regulated (including bcl-2-associated transcription factor BTF gene). The findings conclude that analysis of the affected gene families does not point towards a stress response, and no consistent RF-EMF signatures could be detected.However, following RF-EMW exposure, some but not all human cells might react with an increase in expression of genes encoding ribosomal proteins and therefore up-regulating the cellular metabolism (Remondini et al. , 2006). Theoretical approaches also have b een proposed to elucidate the mechanism behind the stimulation of biosynthesis by EMW (Blank and Goodman, 2008). Electrons have been shown to move in DNA and biochemical reactions could be modulated by EMW (Blank, 2005). Interaction with electrons could explain the activation of DNA by weak, low-frequency EMW, as well as the more energetic high frequencies.Evidence from biochemical reactions suggests that electromagnetic fields can accelerate electron transfer. Interaction with electrons could displace electrons in H bonds that hold DNA together, leading to chain separation and initiating transcription. The electron transfer would favour separation of base pairs, and DNA geometry is optimized for disaggregation under such conditions. The initial interaction could involve the displacement of electrons in the H bonds that hold DNA together, thereby causing chain separation and initiating transcription and translation.EMWinitiated DNA separation can set in motion the interconnected bio chemical signalling pathways that are activated in the stress response (Blank and Goodman, 2008). The effects of lowfrequency EMW on Na/K-ATPase activity (Blank, 2005) to generate ATP is another pertinent field to explore in the context of spermatozoal motility. The Na/K-ATPase is an enzyme of the plasma membrane of most animal cells that uses the free energy from the hydrolysis of ATP to mediate the exchange of cytoplasmic Na+ for extracellular K+ in a 3:2 ratio (Kaplan, 2002; Sanchez et al. , 2006).The Na/K-ATPase plays a key role in numerous cell processes that depend directly or indirectly on the transmembrane gradients of Na+ and K+. The enzyme is essential in maintaining cell osmotic balance, volume, pH and the cell resting membrane potential and in providing the chemical energy for the secondary Na+-coupled transport of other ions, solutes and water across the cell membrane (Skou and Esmann, 1992). This enzyme has an important role, along RBMOnline ® 154 Review – Cel l phones: modern man’s nemesis? – K Makker et al. with Na+/H+ exchanger, in human sperm motility (Woo et al. 2002; Sanchez et al. , 2006) These cellular pathways should be further analysed in the context of EMW. More recently Friedman et al. (2007) found significant increase in plasma membrane NADH oxidase activity of mammalian cells (HeLa cells) after exposure to 875 MHz EMF. Although the use of the discovery science approach employing high-throughput screening techniques will not yield foolproof evidence of a health hazard or its absence, it will be essential in unravelling the complexities of the biological effects potentially exerted by RF-EMF exposure. upport of previous studies, they also will open opportunities for groundbreaking research in this area. References Agarwal A, Deepinder F, Sharma RK et al. 2008 Effect of cell phone usage on semen analysis in men attending infertility clinic: an observational study. Fertility and Sterility 89, 124–128. Agarwa l A, Desai NR, Makker K et al. 2008 Effects of radiofrequency electromagnetic waves (RF-EMW) from cellular phones on human ejaculated semen: an in vitro pilot study. Fertility and Sterility Epub ahead of print. Aitken RJ 1999 The Amoroso Lecture. The human spermatozoon – a cell in crisis?Journal of Reproduction and Fertility 115, 1–7. Aitken RJ, L. E. Bennetts, Sawyer D et al. 2005 Impact of radio frequency electromagnetic radiation on DNA integrity in the male germline. International Journal of Andrology 28, 171–179. Anderson V, Rowley J 2007 Measurements of skin surface temperature during mobile phone use. Bioelectromagnetics 28, 159–162. Barnes FS, Greenebaum B 2007 Bioengineering and biophysical aspects of electromagnetic fields. In: Barnes FS, Greenebaum B (eds) Handbook of Biological Effects of Electromagnetic Fields 3rd edn. CRC Press, Boca Raton, USA.Blackwell RP 1979 Standards for microwave radiation. Nature 282, 360. Blank M 2005 Do electromagne tic fields interact with electrons in the Na,K-ATPase? Bioelectromagnetics 26, 677–683. Blank M, Goodman R 2008 A mechanism for stimulation of biosynthesis by electromagnetic fields: charge transfer in DNA and base pair separation. Journal of Cellular Physiology 214, 20–26. Braune S, Riedel A, Schulte-Monting J et al. 2002 Influence of a radiofrequency electromagnetic field on cardiovascular and hormonal parameters of the autonomic nervous system in healthy individuals.Radiation Research 158, 352–356. Braune S, Wrocklage C, Raczek J et al. 1998 Resting blood pressure increase during exposure to a radio-frequency electromagnetic field. Lancet 351, 1857–1858. Burch JB, Reif S, Noonan CW et al. 2002 Melatonin metabolite excretion among cellular telephone users. International Journal of Radiation Biology 78, 1029–1036. Cairnie AB, Harding RK 1981 Cytological studies in mouse testis irradiated with 2. 45-GHz continuous-wave microwaves. Radiation Researc h 87, 100–108. Capri M, Scarcella E, Bianchi E et al. 004a 1800 MHz radiofrequency (mobile phones, different global system for mobile communication modulations) does not affect apoptosis and heat shock protein 70 level in peripheral blood mononuclear cells from young and old donors. International Journal Radiation Biology 80, 389–397. Capri M, Scarcella E, Fumelli C et al. 2004b In-vitro exposure of human lymphocytes to 900 MHz CW and GSM modulated radiofrequency: studies of proliferation, apoptosis and mitochondrial membrane potential. Radiation Research 162, 211–218. Colonna A 2005 Cellular phones and cancer: current status. Bull Cancer 92, 637–643.Concannon CG, Orrenius S, Samali A 2001 Hsp27 inhibits cytochrome c-mediated caspase activation by sequestering both pro-caspase-3 and cytochrome c. Gene Expression 9, 195–201. Czyz J, Guan K, Zeng Q et al. 2004 High frequency electromagnetic fields (GSM signals) affect gene expression levels in tumor suppressor p53-deficient embryonic stem cells. Bioelectromagnetics 25, 296–307. Dasdag S, Zulkuf Akdag M, Aksen F et al. 2003 Whole body exposure of rats to microwaves emitted from a cell phone does not affect the testes. Bioelectromagnetics 24, 182–188. Dasdag S, Ketani MA, Akdag Z et al. 999 Whole-body microwave exposure emitted by cellular phones and testicular function of rats. Urological Research 27, 219–223. Cleveland Clinic pilot study To validate the results of recent epidemiological studies and to establish a cause and effect relationship between cell phone usage and decrease in semen parameters, a novel in-vitro experiment was designed. Semen samples were exposed to EMW from a commercially available cellular phone (GSM network, 850 MHz,), and the effect of EMW on semen parameters, DNA integrity [using TdT (terminal deoxynucleotidyl transferase)mediated dUDP nick-end labelling assay] (Tesarik et al. 2006; Ozmen et al. , 2007) and disturbance in reactive oxygen species metabolism was assessed post exposure. In this study, healthy donors were enrolled to provide semen samples. The semen sample obtained from each volunteer was divided into two parts: EMW-exposed group and control group. Environmental condition was monitored throughout the experiment. The frequency emitted by the cell phone was also confirmed with help of a radiofrequency spectrum analyser. One portion of the sample was exposed to radiation from a commercially available cell phone.A second portion was kept non-exposed for the same time duration. Measurement of sperm concentration, motility and viability was carried out as described by the World Health Organization (1999). Samples also were assessed for reactive oxygen species, total antioxidant capacity and DNA damage (Agarwal et al. , 2008). Conclusion As highlighted above, many aspects of human health have been proposed to be affected by cell phone exposure. Ranging from mild local warmth to possible tumour inductio n, EMW have been suspected of involvement in many health concerns.At this time, evidence is lacking to strongly prove or disprove any of the proposed harmful effects of EMW. However, the significance of these studies and their possible implications in the future cannot be ignored. Findings and trends available from these studies provide a strong indication to carry out further studies to establish a clearer and more evidence-based conclusion. Both human and animal-based studies have provided a hint that EMW may be involved in the pathogenesis of male infertility, but considerable work is required to provide scientific support for this view.More importantly, studies must be carried out in human semen samples as data from animal studies are limited in their applicability in humans. High-throughput screening techniques may be an important tool to evaluate the molecular effects of EMW on the biological system. Not only will these techniques provide evidence in RBMOnline ® 155 Review à ¢â‚¬â€œ Cell phones: modern man’s nemesis? – K Makker et al. de Seze R, Ayoub J, Peray P et al. 1999 Evaluation in humans of the effects of radiocellular telephones on the circadian patterns of melatonin secretion, a chronobiological rhythm marker.Journal of Pineal Research 27, 237–242. Deepinder F, Makker K, Agarwal A 2007 Cell phones and male infertility: dissecting the relationship. Reproductive BioMedicine Online 15, 266–270. Diem E, Schwarz C, Adlkofer F et al. 2005 Non-thermal DNA breakage by mobile-phone radiation (1800 MHz) in human fibroblasts and in transformed GFSH-R17 rat granulosa cells in vitro. Mutation Research 583, 178–183. Djeridane Y, Touitou T, de Seze R 2008 Influence of electromagnetic fields emitted by GSM-900 cellular telephones on the circadian patterns of gonadal, adrenal and pituitary hormones in men.Radiation Research 169, 337–343. Erogul O, Oztas E, Yildirim I et al. 2006 Effects of electromagnetic radiation from a cellular phone on human sperm motility: an invitro study. Archives of Medical Research 37, 840–843. Falzone N, Huyser C, Fourie F et al. 2008 In-vitro effect of pulsed 900 MHz GSM radiation on mitochondrial membrane potential and motility of human spermatozoa. Bioelectromagnetics 29, 268–276. Federal Communications Commission Available at www. fcc. gov and www. fcc. gov/oet/rfsafety/cellpcs. html [accessed 4 August 2008]. Fejes I, Zavaczki Z, Szollosi J, et al. 005 Is there a relationship between cell phone use and semen quality? Archives of Andrology 51, 385–393. Feychting M 2005 Non-cancer EMF effects related to children. Bioelectromagnetics Suppl. 7, S69–74. Food and Drug Administration Cellular Phone Facts, Questions and Answers. Available at www. fda. gov/cellphones/qa. html [accessed 4 August 2008]. Friedman J, Kraus S, Hauptman Y et al. 2007 Mechanism of shortterm ERK activation by electromagnetic fields at mobile phone frequencies. Biochemistry Journal 405, 559–568. Geum D, Son GH, Kim K 2002 Phosphorylation-dependent cellular localization and thermoprotective role of eat shock protein 25 in hippocampal progenitor cells. Journal of Biological Chemistry 277, 19913–19921. Hardell L, Carlberg M, Ohlson CG et al. 2007 Use of cellular and cordless telephones and risk of testicular cancer. International Journal of Andrology 30, 115–122. Hardell L, Mild KH, Carlberg M, Soderqvist F 2006 Tumour risk associated with use of cellular telephones or cordless desktop telephones. World Journal of Surgical Oncology 4, 74. Hook GJ, Spitz DR, Sim JE et al. 2004 Evaluation of parameters of oxidative stress after in-vitro exposure to FMCW- and CDMAmodulated radiofrequency radiation fields.Radiation Research 162, 497–504. Huber R, Graf T, Cote KA et al. 2000 Exposure to pulsed highfrequency electromagnetic field during waking affects human sleep EEG. Neuroreport 11, 3321–3325. Irmak MK, Fadillioglu E, Gulec M et al. 2002 Effects of electromagnetic radiation from a cellular telephone on the oxidant and antioxidant levels in rabbits. Cell Biochemistry and Function 20, 279–283. Ivaschuk OI, Jones RA, Ishida-Jones T et al. 1997 Exposure of nerve growth factor-treated PC12 rat pheochromocytoma cells to a modulated radiofrequency field at 836. 55 MHz: effects on c-jun and c-fos expression.Bioelectromagnetics 18, 223–229. Jung A, Schill WB 2000 [Male infertility. Current life style could be responsible for infertility]. MMW Fortschritte der Medizin 142, 31–33. Kandeel FR, Swerdloff RS 1988 Role of temperature in regulation of spermatogenesis and the use of heating as a method for contraception. Fertility and Sterility 49, 1–23. Kaplan JH 2002 Biochemistry of Na,K-ATPase. Annual Review of Biochemistry 71, 511–535. Lai H,. Singh NP 1996 Single- and double-strand DNA breaks in rat brain cells after acute exposure to radiofrequency electromagnetic radiation.Inte rnational Journal of Radiational Biology 69, 513–521. Laszlo A, Moros EG, Davidson T et al. 2005 The heat-shock factor is not activated in mammalian cells exposed to cellular phone frequency microwaves. Radiation Research 164, 163–172. Lee S, Johnson D, Dunbar K et al. 2005 2. 45 GHz radiofrequency fields alter gene expression in cultured human cells. FEBS Letters 579, 4829–4836. Leszczynski D, Nylund R, Joenvaara S, Reivinen J 2004 Applicability of discovery science approach to determine biological effects of mobile phone radiation. Proteomics 4, 426–431. Leszczynski D, Joenvaara S, Reivinen J et al. 002 Non-thermal activation of the hsp27/p38MAPK stress pathway by mobile phone radiation in human endothelial cells: molecular mechanism for cancer- and blood-brain barrier-related effects. Differentiation 70, 120–129. Litovitz TA, Krause D, Penafiel M et al. 1993 The role of coherence time in the effect of microwaves on ornithine decarboxylase activi ty. Bioelectromagnetics 14, 395–403. Lixia S, Yao K, Kaijun W et al. 2006 Effects of 1. 8 GHz radiofrequency field on DNA damage and expression of heat shock protein 70 in human lens epithelial cells. Mutation Research 602, 135–142. Natarajan M, Vijayalaxmi, Szzliagyl M et al. 002 NF-kappaB DNAbinding activity after high peak power pulsed microwave (8. 2 GHz) exposure of normal human monocytes. Bioelectromagnetics 23, 271–277. Nylund R, Leszczynski D 2006 Mobile phone radiation causes changes in gene and protein expression in human endothelial cell lines and the response seems to be genome- and proteomedependent. Proteomics 6, 4769–4780. Nylund R, Leszczynski D 2004 Proteomics analysis of human endothelial cell line EA. hy926 after exposure to GSM 900 radiation. Proteomics 4, 1359–1365. Oftedal G, Wilen J, Sandstrom M, et al. 2000 Symptoms experienced in connection with mobile phone use.Occupational Medicine (London) 50, 237–245. Oktem F, Oz guner F, Mollaoglu H et al. 2005 Oxidative damage in the kidney induced by 900-MHz-emitted mobile phone: protection by melatonin. Archives of Medical Research 36, 350–355. Ozguner F, Altinbas A, Ozaydin M et al. 2005 Mobile phone-induced myocardial oxidative stress: protection by a novel antioxidant agent caffeic acid phenethyl ester. Toxicology and Industrial Health 21, 223–230. Ozmen B, Caglar CS, Koster F et al. 2007 Relationship between sperm DNA damage, induced acrosome reaction and viability in ICSI patients. Reproductive BioMedicine Online 15, 208–214.Panagopoulos DJ, Chavdoula ED, Nezis IP, Margaritis LH 2007 Cell death induced by GSM 900-MHz and DCS 1800-MHz mobile telephony radiation. Mutation Research 626, 69–78. Perentos N, Croft RJ, McKenzie RJ, et al. 2007 Comparison of the effects of continuous and pulsed mobile phone like RF exposure on the human EEG. Australasian Physical and Engineering Sciences in Medicine 30, 274–280. Preece AW, Iwi G, Davies-Smith A et al. 1999 Effect of a 915-MHz simulated mobile phone signal on cognitive function in man. International Journal of Radiation Biology 75, 447–456. Pyrpasopoulou A, Kotoula V, Cheva A et al. 004 Bone morphogenetic protein expression in newborn rat kidneys after prenatal exposure to radiofrequency radiation. Bioelectromagnetics 25, 216–227. Qutob SS, Chauhan V, Bellier PV et al. 2006 Microarray gene expression profiling of a human glioblastoma cell line exposed in vitro to a 1. 9 GHz pulse-modulated radiofrequency field. Radiation Research 165, 636–644. Regel SJ, Tinguely G, Schuderer J et al. 2007 Pulsed radio-frequency electromagnetic fields: dose-dependent effects on sleep, the sleep EEG and cognitive performance. Journal of Sleep Research 16, 253–258. Remondini D, Nylund R, Reivinen J et al. 006 Gene expression changes in human cells after exposure to mobile phone microwaves. Proteomics 6, 4745–4754. RBMOnline ® 156 Revi ew – Cell phones: modern man’s nemesis? – K Makker et al. Ribeiro EP, Rhoden EL, Horn MM et al. 2007 Effects of subchronic exposure to radio frequency from a conventional cellular telephone on testicular function in adult rats. Journal of Urology 177, 395–399. Sakuma N, Komatsubara Y, Takeda H et al. 2006 DNA strand breaks are not induced in human cells exposed to 2. 1425 GHz band CW and W-CDMA modulated radiofrequency fields allocated to mobile radio base stations.Bioelectromagnetics 27, 51–57. Sanchez G, Nguyen AN, Timmerberg B et al. 2006 The Na,K-ATPase alpha4 isoform from humans has distinct enzymatic properties and is important for sperm motility. Molecular Human Reproduction 12, 565–576. Sandstrom M, Wilen J, Oftedal G, Hansson Mild K 2001 Mobile phone use and subjective symptoms. Comparison of symptoms experienced by users of analogue and digital mobile phones. Occupational Medicine (Lond) 51, 25–35. Skou JC, Esmann M 1992 The Na,K-ATPase. Journal of Bioenergetics and Biomembranes 24, 249–261. Stronati L, Testa A, Moquet J et al. 2006 935 MHz cellular phone radiation.An in-vitro study of genotoxicity in human lymphocytes. International Journal of Radiation Biology 82, 339–346. Straume A, Oftedal G, Johnsson A et al. 2005 Skin temperature increase caused by a mobile phone: a methodological infrared camera study. Bioelectromagnetics, 26, 510–519. Tahvanainen K, Nino J, Halonen P et al. 2004 Cellular phone use does not acutely affect blood pressure or heart rate of humans. Bioelectromagnetics 25, 73–83. Tesarik J, Mendoza-Tesarik R, Mendoza C 2006 Sperm nuclear DNA damage: update on the mechanism, diagnosis and treatment. Reproductive BioMedicine Online 12, 715–721.Wang SM 2006 Applying the SAGE technique to study the effects of electromagnetic field on biological systems. Proteomics 6, 4765–4768. Wdowiak A, Wdowiak L, Wiktor H 2007 Evaluation of the effect of using mobile phones on male fertility. Annals of Agricultural and Environmental Medicine 14, 169–172. Weisbrot D, Lin H, Ye H et al. 2003 Effects of mobile phone radiation on reproduction and development in Drosophila melanogaster. Journal of Cellular Biochemistry 89, 48–55. Woo AL, James PF, Lingrel JB 2002 Roles of the Na,K-ATPase alpha4 isoform and the Na+/H+ exchanger in sperm motility. Molecular Reproduction and Development 62, 348–356.World Health Organization 1999 WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction. Cambridge University Press, Cambridge. Yan JG, Agresti M, Bruce T, et al. 2007 Effects of cellular phone emissions on sperm motility in rats. Fertility and Sterility 88, 957–964. Zou H, Henzel WJ, Liu X et al. 1997 Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90, 405–413. Declaration: The authors report no financia l or commercial conflicts of interest. Received 21 April 2008; refereed 6 May 2008; accepted 28 July 2008. 157 RBMOnline ®

MIS answer

Most of the mobile devices such as phone and ‘pad provide convenient social networking applications helping people communicate, collaborate and obtain essential information via e-mail, typing messages. These easy-used applications can let people get along with each other anywhere they like no matter between colleagues or families easily.Based on a fast and high-efficiency data-obtained function; people tend to use these handy applications making business decisions day by day. A true application of app used by Gee's Mobile Center help decision makers mom in from the map to a specific transformer getting all key performance Indicators and diagnostic information. 2. Some specific examples by using Phone to achieve a better control In the production line are a lot.For example, TECH chocolate company make their integration industry come true since getting to use phone in order to quickly change temperature with an alert, turn-on or off the chocolate machine and achieve faster time-c ontrol; GE employees use pad to access email, contacts people and help them find patterns and trends in large volumes of data; Dhow Corning's Analytics get results f sales conditions for the silicon products, data analysis by using the App devices, and their employees use phone to check email, exchange information, presenting ideas too; Sunbelt Rentals start to use a single data package system for sales team with a smart equipment of Mobile Salesperson. It's appeared with a clear and complete system reports listed integrates data from different basic functions which takes a shortcut for sales managers to make any decisions in time; SAP's business develops a one time applications for users to stay connected with customers and business anytime after work and get the information of products inventory and sales discount. 3.Nordstrom, a top shopping place, improves their price-check and check-out time under the help of the connection between phone and leader-computer. Just using the Phon e to scan the bar code is ready to go. The employees also use the smart phones to clock on and off in one time. 4. There Is no denying the fact that mobile devices really did a good Job In cost down among business field. It not only let market sales get a maximum profit but also shows an easy and fast way for customers and sellers to get along with each other. So, business Industry has gotten a huge improvement In working efficiency, products and service quality, time control and so on when we use these high technology tools.Except that, it did a very important role in assisting person's social life, no matter in communication or team work. If we lose those precious applications, we do nothing to develop our industry and quality for people's life. Location of each stop, shipping time, package tracking information. Processing include basic package transform information, customer online account, and central computer. Output is composed of pick up, delivery efficiency, tracking routes, delivery mime and so on. 2. UPS uses Aids, barded scanning system, center computer. UPS uses the high- tech software to track packages and shipments, and do a cost calculation. Each of them can help UPS save time getting a better service by cutting down paper usage, transportation costs. 3.Service (try best to meet their customers need): Customers can download their order details whether they want to replace order or make a refund back. This process is fast and easy to do. Cost (save costs but keeping service quality): â€Å"340 Methods† is used to optimize performance from lifting and loading boxes to select a package; this teeth increase cost savings and goods safety. Competitive advantage (a leadership among global delivery service): by using high tech installment, UPS has been the leadership for many years since Faded and USPS appear. Their supply chain let them achieve a standardized service and build a reliable brand image among competitors and customers at the same ti me. 4.The scanning device like barded, Aids software, handheld devices and other methods keeping Pup's management system fast and precise for inventory checking, fees calculation, customers accounts management. That is the key why this company till remains strong competitive advantages. 5. If the technology is not available for the UPS, they will lose thousands of customers and stay at the original place keeping awkward step without any competitive advantages among the whole delivery companies. Because of losing technology, they will spend tons of dollars on costs and the time they use isn't proportional as what they want. 1 . This case illustrates the reasons why health care fees are so expensive in United States. One big reason is that the medicine records are currently paper-based, making it difficult to be shared and accessed.Another reason is to achieve an automatic electronic medicine record system still tough before 2015. Not only for a privacy concern by using these devices, but also unreliable data available for doctors to gain main points which they need. As a result, to improve a valuable electronic health device is still the main topic for us to explore so that our health organization can do a better Job with efficiency and control resources lost. 2. People factors are involved by physicians, government agencies, patients and insurance company. Physicians will easily be tired and exhausted by adding extra erasures of 20 hours learning and training if we use the electronic medicine system.Government's goal is letting this high technology system used in national wide in combination difficulty within several distinct systems. Patients all strongly need their privacy information being kept properly. Organizations are including the EMMER systems to be built. To get a complete set of patient information in full national wide is still a long-term way to go. Because different companies have different systems for health record, and to integrate all the syst ems without privacy leakage, unusable information of each patient yet pretty formidable. At the same time, a high-tech system needs a high-level doctor or physician to accommodate, how to train our doctors in limited time is also a key point to emphasize.For the technology factors, how to use EMMER systems to report the same data from government agencies to another one without a key is not easy. One of the most headache things is totally keeping patients' data proper and safe. 3. The business will trends to traditional way by continue using thousands of papers; and health care will be more and more expensive due to the personal records peeping. So, government has to spend thousands of money each year for those patients who can't afford their health fees helping them solve their financial problems. The insurance industry may also grasp such a big chance to earn money for those unaffordable patients. The other industries will also be affected because of the monopoly of medical institu tions.Competition among social industry will be more and more ruthless. 4. Digitizing medical reconsidering can bring a fresh working efficiency for both companies and social industries. As a reason of convenient and swift operational yester, people no long dare their high cost of health care fees but a comfortable price instead. Governments no more nervous for the low income payments and health care bonus each year. Insurance companies can go on carrying out their insurance friendly plan in order to keep on their original industry purpose of ensure people's life but not prolong people's lifespan. 5. In my points, I like this solution to use electronic systems to solve health problems.One reason is that this system solves an expensive system for person's health care and does huge contributions to doctors' diagnostic time before looking up the specific information they need. Another reason is that this kind of perfect system can bring good news to governments to ensure people's life quality and economy stability at the same time. Under the economic prosperity times, we need to try our best to use the high technology helping us improve working efficiency and get maximum profits day by day. So, the above details tell us a fact that this system definitely helps us solve several chain problems of economy monopoly, peaceful development, working productivity by increasing service and quality attitudes for a long time.

Unaids Report On Hiv / Aids Essay -- AIDS, HIV, Human sexual behavior

NURS 420- Policy Brief HIV/AIDS in Zambia In 2014, UNAIDS estimated that around 1,200,000 people are living with HIV/AIDS in Zambia. According to the UNAIDS report, the prevalence rate for adults aged 15 to 49 is 12.4%. About 1 million women aged 15 and up are living with AIDS and roughly 100,000 children aged 0 to 14 are living with HIV. (UNAIDS) The most affected populations are men who have sex with men (MSM), migrants, sex workers, women, children and orphans. Some of the risk factors are having multiple and concurrent sexual partnerships, mother to child transmission, and low condom use. HIV/AIDS is impacting the economy by reducing labor supply and increasing costs. It is socially impacting the community by weakening the workforce, and increasing social issues. Providing education of sexually transmitted infections, the practice of safe sex and of information regarding mother to child transmission is a low cost effective approach in tackling the HIV/AIDS epidemic. The number of people living with HIV in Zambia, a relatively small country in southern Africa, is steadily rising. UNICEF estimates that 226 new adult infections and 25 new child infections occur each day. According to AVERT, an international AIDS and HIV charity, 27,000 people were accounted for AIDS related death in 2013. Life expectancy is 58.1 years, which is an increase from the year 2012 where the life expectancy was 49.4 years. (AVERT) Men who have sex with men, sex workers, migrants, women, children and orphans are more vulnerable to HIV/AIDS than other groups. In Zambia, it is illegal for men to have sex with men so there is little data about the HIV epidemic of this population. It is reported that elsewhere (Sub Saharan Africa) HIV preva... ... middle of paper ... ...hild transmission would do this. This is a low cost prevention approach to HIV/AIDS epidemic. A study done in Kenya showed that sexually transmitted disease control and condom promotion was 8-12 U.S dollars in cost per case averted. (Marseille, 20012) It was less than $1 in U.S in cost per disability adjusted life year (DALY). Doing something similar in Zambia would be cost effective too. By promoting positive attitudes and behavior towards women’s health, one is ensuring long-term improvements. Increasing awareness and overcoming the stigma of the disease is the first step to taking action. Helping the women in the community have a voice in practicing safe sex and becoming an advocate of the use of condoms and being knowledgeable in mother to child transmission can mitigate the chances of HIV transmission in various fields (i.e. marriages, sex work, migrant work).

The Role of Curriculum Design in Learning Experiences Research Paper

The Role of Curriculum Design in Learning Experiences - Research Paper Example The influences of thinking about curriculum & topics & issues relating to schooling and/or society on the enacted learning experiences of the educators and determine whether this statement can be agreed or disagreed upon with presenting appropriate facts and reasons. Prior to analyzing the above-provided statement in terms of agreeing or disagreeing the same, there lays the necessity of acquiring a brief idea about the nature of the topics as well as the issues linked with schooling or society that have a major influence on the learning experiences enacted by the educators. Contextually, the nature of the topics and the issues linked with schooling or society can be apparently noted as promoting willingness and strengthening basic reading as well as writing skills (Malaguzzi, 1994, p. 1-75). Justifiably, by focusing on these features, the learning experiences enacted by the educators will become quite result oriented (SAGE Publications, n.d., p. 2-36). There lays the requirement of understanding the socio-cultural factors that influence a curriculum and its implementation while agreeing that the enacted learning experiences of the educators get influenced by how they think about a specific curriculum and the topics along with the issues relating to schooling or society. In this regard, the socio-cultural factors that influence a curriculum and its implementation include cultural identities, population and diversified living standards among others. These factors positively influence the enacted learning experiences of the educators by making them focus on developing the undeviating curriculum standards (SAGE Publications, n.d., p. 2-36). Apart from understanding the socio-cultural factors that influence a curriculum and its implementation, there also lays the necessity of comprehending the knowledge and strategies that support students’ engagement with a specific curriculum.

Air Carrier Maintenance Program Review Thesis Example | Topics and Well Written Essays - 1750 words

Air Carrier Maintenance Program Review - Thesis Example Figure 3. Indicative maintenance costs for aircraft models. Reprinted from "The Relationship Between an Engine’s Value and it’s Maintenance Status", by Aircraft Commerce, 2012, Aircraft Commerce, 35 (June/July), pp 5-9, Copyright 2012, by the Aircraft Commerce. 23 This document evaluates two important elements of aircraft carrier maintenance, personnel training, and record keeping. The findings indicate that regular training of personnel is essential to help in the maintenance and overhaul complex aircraft systems such as engine, structural, landing gear, and systems. Record keeping is very crucial since FAA makes it mandatory for aircraft carriers to maintain detailed maintenance records; otherwise, the airplane is not given an airworthiness certificate. Flying machines such as aircraft and helicopters face high failure risks, and these risks include failure of engine, fuel system, structural failure, systems failure, and other types of failures (Kinnison & Siddiqui, 2012, p. 3). To ensure that only air worthy aircraft can fly, The Federal Aviation Administration - FAA, a US government body that oversees commercial aviation safety in US, has provided a number of guidelines and regulations concerning the maintenance and overhaul of all types of aircraft. These are covered under the program continued analysis and surveillance system - CASS. Each aircraft manufacturer provides its own maintenance schedule, the Air Carrier Maintenance Program, for each model of aircraft, and the FAA regulations support these regulations (FAR/AIM, 2012, p. 12-14). This paper examines two important elements of this program, and discusses several important subjects on maintenance. The main types of maintenance are routine and preventive maintenance, and hard-time maintenance. Routine and preventive maintenance involves cleaning, changing the oil, changing filters, and activities, where the full engine and critical components of the engine, propeller,

Security of Big Data Research Paper Example | Topics and Well Written Essays - 1500 words

Security of Big Data - Research Paper Example Big Data are pivotal in many organizations because it allows respective stakeholders to view and analyze data. Before the advent of Big Data, information about customers and business were overwhelming. With Big Data, stakeholders can truly take this raw information and convert into data that can assist them in making real-time decisions. The challenge in many organizations is the fact that majority of decisions are made based on estimated guesses. One of the best elements of Big Data is the fact that it reduces any ‘guesswork’. Moreover, it allows the organization to understand customer behavior in a much meaningful way. Another huge aspect of Big Data is the collaboration aspect as it allows users to interact and use this data. Imagine an organization in which the marketing department requires key reports from the technology department. Clearly, the issue of latency can be a factor that can delay essential decision making. Hence, it is only evident that securing Big Dat a is essential because it holds true information because securing data is not only regulated by compliance, but can potentially fall into wrong hands. Securing data saves organization from financial implications that can have detrimental effects for everyone. One of the worst vulnerabilities for user domains are insider attacks. Insider attacks occur. For instance, denial of service and spoofing are one the most common themes that occur. The problem is the fact that intercepting authentication or other sensitive information can be executed with the current WAN technology in Big Data. Moreover, spoofing can also be conducted since an intruder can deceive the network that it recognizes a possible unauthorized access. The problem with installing firewalls in a user domain is the fact that they are fully feasible. Insider attacks occur when one user domain gains more privilege than the other user and

Learning Goals in a Pluralistic Society Research Proposal

Learning Goals in a Pluralistic Society - Research Proposal Example All children are entitled to an experience that is variant because each child has a distinct need. The notion that all children can learn in no way embraces the theory that they learn in the same manner or at the same time or at the same level of achievement. Schools began as simple institutions often run by churches and teachers advanced through the leadership chain with out training. (Murphy 1998). Accordingly, as a principal, one must expect to see different outcomes within the same time frame. Against that backdrop, there is a dramatic change in the role of principals and their duties to their students. (Shipman 2007) Simply having knowledge of the educational system is not enough for a principal to be considered an effective leader. (Shipman 2007) This paper seeks to discuss the first standard of the ELCC standards, the knowledge of the principal. The principal has a deep understanding of diversity and its implications for education. Knowledge of the learning goals of a pluralistic requires that a principal assess the goals which are immediate and long term. Firstly, a principal must be able to have a working definition of what a pluralistic society actually is. Banks and Banks (2006) defined the obligations of a leader in a pluralistic society as those that envision: â€Å"Maintaining a democratic society and preserving and enlarging freedom require citizens who embrace democratic values and recognize their responsibilities to help narrow the gap between real and idealized American values† (Banks and Banks p.46). Naturally, a principal has the obligation to teach these values to his/her students. A leadership principal clearly values individuals who are diverse in terms of race, ethnicity, exceptionality, religion, sexual orientation, socioeconomic status or gender. In teaching the staff, the principal must also keep an open and professional relationship with the teachers of his/her school which is revolved

HISTORY Article Example | Topics and Well Written Essays - 1250 words

HISTORY - Article Example This theory emphasis on mass communication as an agent to change. This theory is another example of planned change. Planned change has high probability of relapse and regression. Emergent change is sudden and not anticipated. The societies as well as individuals are always prone to change. Change basically refers to making or becoming different in some particular way without losing permanently the original characteristics. It may also mean, to become different in essence. Change can either be sudden or might be planned such that it is bound to happen, at one time or another. Change can either be individual, intergroup or social. In individuals change is further categorized into emotional, behavioral and cognitive. In inter-personal or relationships, change involves; contact hypothesis, de categorization and re-categorization and also acknowledgement, mourning and forgiveness. (Zaltman, 1977, p. 45). Basically, change can be emergent or planned; this whole issue depends on the type of change that we are talking about. If for instance we are talking about individual change management, Kurt Lewin in his model of change states that, there are 3 stages in this process. The first stage is called 'unfreezing'. (Harris 2004, p56.). According to Kurt, this stage involves overcoming inertia and dismantling the existing mindset of the individual. At this stage the natural defense mechanisms have to be by passed. Change occurs in the second stage. ... The final stage according to Kurt is known as the "Re-freezing" stage. The new mind step is beginning to get into place and one's comfort level is returning to the earlier levels. (Macredie 1998, p.53). An example in this model would be a drug addict who is determined to quit drugs. During the initial stages or otherwise known as the unfreezing period, the person is trying hard to stop the abuse. He/she has to contend with withdrawal symptoms and some are even likely to go back to drugs. They enter the second stage. The second stage is characterized by confusion. One doesn't know what they want. They are out of drugs but still looking for alternative replacements. The 'unfreezing' stage marks the complete metamorphosis form drugs to a drug free person. One is also comfortable with his/her new life style. (Bennis 1976, p.38). According to this theory, we can therefore see that change was planned because it has to undergo all those stages. According to Kubler-Ross's model change can also be emergent. The stages in this model describe the personal and emotional states that a person encounters when dealing with loss of a loved one. This type of change happens without prior arrangements or plan. Indeed, in some cases, people have gone mad after learning that their dear ones have died. The impact of that news is so strong that someone who was jolly and completely happy may even faint after hearing bad news. (Zaltman, 1977, p.63). Other people's lives never remain to be the same after such an ordeal. A young man, who was always happy and kind to almost anyone, developed emotional problems as well as temperament problems after he had an accident and realized that he was never going to walk again because he had been paralyzed. The derivatives of Ross's model can

Oppositional Defiant Disorder (ODD) Research Paper

Oppositional Defiant Disorder (ODD) - Research Paper Example ODD is not a very common disorder, though a significant population of children suffers from it. â€Å"There are various statistics on the incidence of Oppositional Defiant Disorder in the U.S. Numbers range from 2-16% of children and teens in the U.S. have ODD† (Healthy Place, 2012). Children generally start acquiring the ODD at the age of 8 years (Healthy Place, 2012). In a vast majority of cases, children acquire the ODD before the start of teenage, though in certain cases, children may acquire the ODD in the late teenage. The effects of ODD start showing up gradually and aggravate with the passage of time. Causes of ODD A number of theories have surfaced that explain the causes of ODD in children. One of the main causes of ODD in children commonly identified by these theories is the development of temperament in the child and the response made by family to it. Some children have an inherited predisposition to ODD. Children in families where at least one parent contains a hi story of mood disorder have increased susceptibility to ODD. There is a whole range of parental mood disorder that can make a child vulnerable to ODD. Such mood disorders include but are not limited to conduct disorder, depressive disorder, antisocial personality disorder, attention deficit or hyperactivity disorder (ADHD), and substance abuse. Families that frequently migrate from one place to another make it difficult for the children to adjust in the new locality. As a result of this, children express their discomfort through anger and hostility. ODD may also be caused by a chemical imbalance in the brain or because of a head injury. In addition to that, tension between parents may also be a significant cause of ODD in children. In some families, parents have bad terms with each other which affects the psychology of the children in a negative way. In many cases, such tensions lead the marriage to the point of breakup and a child may acquire ODD as a consequence of the divorce bet ween the parents. Symptoms of ODD Differentiating between a child who is just emotional and another child who has ODD is complicated since the display of oppositional behavior is an integral feature of certain stages of development. However, there exists a range between the ODD and the normal oppositional behavior of a child. Children with ODD display a range of behaviors that include but are not limited to stubbornness, rudeness, short-temperedness, frequent defiance from the family principles and rules, placing the blame of their own mistakes on others, resentfulness, and irritability. However, they do not become violent to the physical extent or to the level that they start violating others’ rights. Actually, the hostile behavior of the children with ODD results from their lack of ability to distinguish between the appropriate and inappropriate behaviors. Children with ODD do not realize that they are overreacting or expressing unnecessary anger. Instead, they think that t heir parents are demanding too much from them or are placing unreasonable demand on them. Accordingly, these children may feel guilty for having done something seriously wrong if they realize. Diagnosis of ODD A psychologist or psychiatrist diagnoses a child with ODD if he/she displayed the symptoms of ODD. There are numerous disorders which may

Discuss Issues Related with the Police and Use Force Policies Essay

Discuss Issues Related with the Police and Use Force Policies - Essay Example As per the City of Edmonds Police Policy Manual section 1.3.1 use of force should be reasonable and needed to either arrest a person or control a situation. Officers should follow the rules and regulations of the department while using force. The manual differentiates between the words â€Å"force†, and â€Å"deadly force†. Force is â€Å"Physical action taken by an officer to assist that officer in controlling a situation or the behavior of others†, while deadly force is â€Å"The intentional application of force through the use of firearms or any other means reasonably likely to cause death or serious bodily injury† (MRSC). According to the Seattle Police Department Directives (2005) the use of force is applied as per the provisions of the RCW 9A. 16.010 and 9A16.020, depending on the overall situation emerging out of the circumstances. Types of situations demanding the use of force can be identified but upcoming scenarios cannot be guessed prior to their happening compelling the police officers to use force (Seattle Police Department). Police use of force, according to Engel (2008) has been an issue of research by different methods and statistical techniques that include not only official data sources but data from keen social observations, ethnographic research, officer surveys, citizen surveys and their analysis. Yet the scholarly research has not produced a comprehensive picture of the use force policies, leave alone the regular monitoring of the police use of force. Scholars like Garner, Maxwell, and Heraux, 2002; Hickman et al., 2008; Terrill and Mastrofski, 2002, have acknowledged the different parameters of monitoring the use of force. As a result it becomes difficult to explain the differences in results on the studies made on these subjects. The issue of monitoring the use of force is related to use force policies. Although these differences in the concept and monitoring of use of force have been identified by the

Uncontrolled Blood Pressure Essay Example for Free

Uncontrolled Blood Pressure Essay Physical assessments including fluid balance, skin and weight Life style changes including weight and stress management Mr. Debourg is 62 year old male. In 2013, during routine physical with his physician, he was referred to a cardiologist for further evaluation. Patient was diagnosed with high blood pressure and started on Lisinopril 10mg daily. Due to stress from work, he started having palpitation and shortness of breath. On 4/13/2014, patient started feeling hot and dizzy. When his wife  noticed patient’s face was turning pale, she took his blood pressure. Patient states he’s blood pressure at that time was around 200/100, heart rate above 150. Mr. DeBourg drove himself to the hospital where he was admitted for further evaluation and tests. Angiogram showed 2 blocked arteries and he received Cardiac stent placement. Patient is now on 4 blood pressure medications and sees cardiologist every 3 months for stress test. Patient’s blood pressure is not well controlled due to lack of physical exercise, poor diet, smoking and stress. By the evidence is current diagnosis and history obtained by the patient, Mr. DeBourg is at risk for decreased cardiac output and at risk for having myocardial ischemia if his blood pressure is not controlled by life style changes. According to Elsevier health, cardiac patients require blood pressure monitoring daily, assessment of peripheral pulses, cold clammy skin, fluid retention levels and weight (Gulanick,n.d). Nursing goals and proprieties for this patient is to maintain cardiac function by monitoring t to prevent further complications and support patient with life style changes. Mr. DeBourg will need education on the importance of exercise to improve circulation, and healthy diet plans to control his weight. Patient understands smoking and stress is contributing to his health condition but continue to smoke. Patient will need support from his spouse and children to quit smoking and engage in activities like hobby or relaxation methods. I will provide information on smoking cessation support group called The Freedom from Smoking in Las Vegas, and counseling information at perfect image for life with the nutritionist to go over his diet plans and exercise program.

Edgar Allen Poe Essay Example for Free

Edgar Allen Poe Essay Five Paragraph Essay Have you ever wondered about Edgar Allen Poes literary elements or themes? Read the stories called The Tell-Tale Heart , The Cask of Amontillado , Annabell Lee, and The Bells . Poes desired effects was to scare the audience from the story, Poe used a writing style called gothic horror. The first literary element seen by Poe was death. In the story of The Cask Of Amontillado the Fortunado suffocates . Another death occurs in the story of The Tell-Tale Heart , when the narrator kills the old man in the middle of the night. The story called The Bells the mother died of a disease. Poe creates horror because the deaths in the stories are unexpected. The second literary element seen by Poe was obsession. The Cask of Amontillado the Montresor is obsessed with getting his revenge. In The Tell-Tale Heart the narrator is obsessed over the old mans eye. The story of Annabell Lee he was obsessed with his wife. This creates horror because obsession is not a usual thing seen in other stories. The third literary element seen by Poe was insanity. The Tell-Tale Heart the narrator goes insane over the old mans eye. The story The Bells , the people in the town grow insanity from bells chiming.

The complex nature of human relationships

The complex nature of human relationships Introduction Human relationships are complex in their nature. People coexist with each other in the world where conflict and differences in their lives occur and learning how to effectively manage those problems can have a great impact on the quality of the relationshipe. Conflicts gives people the opporunity to find the appropriate decisions and finding ways to find a solution to the problemswith minimal negative events. That is why, the issue of marital counseling is worth emphasizing (Cook, 29-67). In other words, marriage, is the unity of a man and a woman and unresolved conflict situations have an impact on marital satisfaction and longevity. It also directly impacts the quality of the relationship, but also on the overall satfisifcation of eac partner that is in the relationship. The aim of the present paper is to identify the notion of marriage, conflict, satisfaction, longevity, and find out the relationship between these concepts. The urgency of the paper is determined by globalized way of human relationships that has changed human life which is observed through the role of marriage, the way of coping with difficulties and longevity on the whole. Marriage and Conflict The definition of marriage can change from person to person, that is why its vital to select a defitition that the majority of the population will agree on. The term marriage is a mutual desire of a man and a woman to compose a family (Lewis, 54).. The unity of people in a family causes new types of relationships in which the members of that family develop coping skills to interact with eachother. At this point is where it can lead to different in opnions and differences in the way conflict is handled, Conflict happens. Every couple argues and stresses out (Lewis, 63). In order to understand their role on longevity, it is important to give a definition to the term conflict and its impact on longevity. There are various definitions of conflict, but they all emphasize the existence of contradictions, which take on the form of disagreement. This is the point in the relationship were positive outcomes can happen or negative interactions can set the relationship back.. Conflicts can be hidden or obvious, but their basis always lies in the lack of consent. Therefore, the conflict is defined as the absence of agreement between two or more parties individuals or groups. The lack of agreement is due to the presence of a variety of opinions, views, ideas, interests, and viewopints. It is important to remember when discussing conflict resolution that the couple be able to see both sides of the argument, no just from their viewpoint. This happens only when the existing contradictions and differences disrupt the interaction of people, and disrupt the advancement of goals for the couple. In this case, people simply are forced into a situation that they try to overcome their differences and enter into open conflict interaction. If conflicts contribute to informed decision-making process and development of relationships, then they are called functional. The conflicts that impede effective communication and decision-making process are called dysfunctional. It is necessary to be able to analyze conflicts, understand their causes and possible consequences. When a couple struggles with finding a healthy way to communicate and find a ways of ending the conflict it can have greater consequences for future problems. Conflict usually arises in the process of emotional convergence of spouses, especially when one or both of them violate personal boundaries of a partner without visible intention. This is one reason why it is important at the start of the relationship that both couples are aware of the boundaries and limitations of the other person. When these boundaries are not seen or when a person oversteps these boundaries conflict will arise. Then the conflict allows couples to increase the distance away from each other for a definite period. Conflicts in family are caused by inadequate and conflicting family-marriage expectations and perceptions. The most common myth is that one partner expects to see the other as an attachement of themselves, going everywhere together, not having any free time for oneself This expectation may be contrary to the interests of a partner who wants to realize his or her personal aspirations and interests and that type of expectation would would damper the relationship and would restrict the freedom and opportunities for development and fulfillment of both partners. Spouses need to understand whether they can accept each other as they are, take with respect to the views of partner and his or her traditions, which he or she brought from the parent family, without any attempt to alter partners behavior and attitude for other views and expectations of another partner. The majority of marital conflicts that occur frequently have hidden purpose, that is, the struggle for leadership. Signs of the struggle for leadership in marriage are the following ones: 1. conflict arises out of nowhere, literally out of nothing; 2. conflicts occur frequently on the basis of different issues; 3. both spouses are older children in their families, wife is the eldest child in her parental family, or her husband is younger. It is possible that in such types of families the leading position is occupies by parents of a couple; 4. conflicts occur with increasing frequency over definite period, and they are accompanied by accusations, or even insults, and the period of rest in the family is declining. There are no winners in these conflicts. Both spouses are characterized by low self-esteem. Crises and conflicts are normal for the family as a developing system. Crises may be associated with certain life-cycle of the family, such as marriage and the need to separate from their parents, birth, adolescence of a child, the separation of children from their parents and the last the death of a spouse. All people are sometimes in conflict. All people are arguing. This is necessary, because conflicts generate liability and resoluteness. This means that people are not indifferent to the problem and each other. If a conflict is recognized and understood, if the parties are prepared to resolve it, so that both sides have won, then such a conflict leads to the renewal of relationships and improves communication. If conflicts are frequent and sharp, a family went through a period of crisis in the marriage. It is necessary to allocate crises stages of marriage (years, three years, seven years, adolescent), as well as crises, based on a stressful family circumstances (adultery, death of relatives, loss of a spouse, etc.). The crisis is a test of the family for strength of their relationships. Many problems can be avoided if to know how to resolve them. Fortunately, some steps are made in the present paper. Thus, many problems can be solved if sincerely want this and be prepared for them. Conflicts in the family can create mental environment for the spouses, their children, parents, as the result of which they acquire a number of negative traits of personality (Pitt-Catsouphes et al. 2006). A conflict family is characterized by the establishment of negative experiences, lost faith in the possibility of the existence of friendly and affectionate relationships between people, accumulation of negative emotions that lead to psycho-trauma. Psycho-traumas are often manifested in the form of experiences, which, because of severity, duration or frequency strongly influence personality. It is necessary to distinguish such traumatic experiences as a state of total dissatisfaction with the family, family anxiety, neuro-psychic tension and condition of guilt. The condition of a full family dissatisfaction arises because of conflict situations where there is a noticeable discrepancy between the expectations of the individual to the family and real life. It is expressed in boredom, colorless of life, the absence of joy and nostalgic memories of the time before marriage, complaints to the surrounding people concerning the difficulties of family life. Accumulating from conflict to conflict, this dissatisfaction is expressed in emotional explosions and hysterics. Family anxiety often appears after a major family conflict. Signs of anxiety are doubts, fears, and concerns, related primarily to the actions of other family members. Mental stress is one of the major traumatic experiences. It arises because of 1. creating constant psychological pressure, a difficult or even hopeless situation for the spouse; 2. creating the obstacles for the manifestation of spouses major feelings and satisfaction of needs; 3. creating a situation of constant internal conflict in the spouse. Mental stress is manifested through irritability, bad mood, sleep disorders, rage. Condition of guilt depends on the personal characteristics of the spouse. The person feels a hindrance to others, guilty of any conflict, quarrels and failures, he/she tends to perceive the relationship of other family members as accused and blaming to himself/herself despite the fact that in reality they are not such. Relationships in Marriage The increased interest in family and marriage is due to a number of reasons. One third of all marriages is unviable. The issue of strengthening marriage and the improvement of marital structure of the population is of overriding public importance in connection with the problem of fertility. Addressing such issues is impossible without studying the mechanisms of family relationships. Socio-psychological climate in the family determines the stability of these relations, it has a decisive influence on the development of both children and adults. The psychological climate of the family is not something unchangeable, given once and for all. It was created by members of each family and their efforts depend on how it will be, a favorable or unfavorable. Every single person is a personality, unique and unrepeatable, with her worldview, which affects the establishment of mutually satisfactory relationships. Modern marriage is based on the compatibility of modern humans as individuals. Satisfaction with marriage is the main parameter characterizing the conjugal relationship. Definition of happy marriage is the following one: both husband and wife share the view that they are found or reached the golden mean or special universal balance in individual needs, desires and expectations, balance sheet, which they consider a unique and probably irreplaceable. This feeling of the golden mean, is achieved by joint efforts, and it is created thanks to creativity and it is developed by a married couple in the process of moving, ever-changing interactions within the family. It has many sources: the values shared by both spouses, when the importance of marital relations is recognized, and their marriage they believe exactly as they wanted to create. This balance incorporates experience of childhood and adolescence, and especially it is fueled by powerful unconscious transformations, hopes, fears and fantasies that each person brings to the marriage. The balance is based on the realities of present and past both within the family and social environments surrounding it. It is also created due to the ability to emotional maturation, the growth of individual consciousness, and the same ability to more deeply understand a partner and show empathy. And it is always an ongoing creative process which is discussed in terms of psychological problems that should be solved in a marriage. The essence of this concept lies in the fact that it is the totality of these problems compose the basic problem of human interaction in the family; they need to be addressed in family couple throughout their lives, otherwise the marriage is counter-productive and is in danger of collapse. It is this basic context, including the power and flexibility of family union, created by two persons, distinguishes a marriage that satisfies both partners. The special emphasis deserves the issue that shown the necessity to detach oneself emotionally from the family of childhood in order to be able to fully invest the strength and feeling in their marital union, but at the same time, overestimate the possible points of contact with both parents families. Moreover, the dependence of a husband on the parents is more important and more likely to lead to problems than the affection of his wife to her parents. Under the emotional department, the study considers the absence of an exaggerated sense of guilt, mistrust, anxiety, responsibility, resentment and anger from both spouses in relation to their mothers. The degree of adaptation to the new family life of a wife largely depends on the degree of independence of a husband from his parents. Marital satisfaction can be achieved through implementation of several items: 1. Creation of a full and happy sexual relationship and their protection from intrusions from the liabilities associated with the implementation of household and other works. 2. Combining efforts, involving the frightening obligations in connection with the birth of the child, the ability to survive in a dramatic appearance of a baby in the family, and protecting individual rights and the proximity of the couple. 3. The ability to withstand and overcome the inevitable crises of life, maintain the power of family ties in the face of adverse circumstances. 4. Creating a safe space within the family in order to express and resolve differences, anger and conflict. 5. Use laughter and humor in clarifying the true state of affairs, and also avoid boredom and alienation. 6. Providi ng the conditions of care and comfort for a partner, as well as meeting the continuing need of a partner in getting emotional and other types of support. 7. Saving of the romantic, idealized notions of love when they met the sobering realities encountered on the path of life. Unresolved Marital Conflicts and Longevity Chapman (2007) writes that Unresolved conflict in a marriage can also be a source of defensiveness. If we have not resolved our differences, we feel somewhat estranged from each other and are therefore more vulnerable to being defensive. Some couples who fail to resolve conflicts over a period of years draw the conclusion that they are not compatible and, in fact, are enemies (Chapman, 157). Health of people is directed connected to human activity and his or her relationships with the surrounding people. Consequently, marriage is the main factor that has a direct impact on human life and longevity. It can be explained by the fact that emotions of people cause different feelings such as happiness, grief, etc. These feelings force people to experience different situations during a long period that frequently cause stressful situation in the case of unresolved conflicts in marriage. Stress can provoke different diseases that obviously lowering the duration of human life. Garner (2009) stresses that to attain to a lengthened life, to enjoy ease and tranquility in lifes decline, and immunity from pain, debility, and other forms of suffering, are objects worthy of far more earnest attention than they usually receive. Since we have more accurately investigated the constitution of man, body and mind, the conditions of life, health, disease and death, the nature and relations of things around us, we are able to form more rational aims, and to pursue them with better hopes of success (13-14). Self-assessment of health is deteriorating in every person. However, this deterioration is more rapid in the marriages with dissatisfaction, particularly in old age. Marriage is the most important factor of social contact for human health. The years of tension spend in marriage may slowly undermine the health. Age also affects the activity of the immune system, leaving older people vulnerable to stress. Older people are more likely to have chronic health problems that stress can increase. In addition, older people may attach more importance to marriage, as they lose their other social connections. Chapman (2007) adds that After several months or years of unresolved conflicts, we begin to hear inner voices that say: I know I married that wrong person. How could I have let myself get into such a mess? I cant believe that my mate is so inconsistent. The unresolved conflicts lead us to think that we are incompatible and that our spouses is not really on our side. The unresolved conflicts push us toward making broad generalizations about our spouse and our marriage (Chapman, 158). Prevention of Marital Conflict Constructive of marital conflict resolution primarily depends on the ability of spouses to understand, forgive and concede. There is one of the conditions for ending the family conflict. It is not to seek victory. The victory as the result of a loved defeat can be hardly called an achievement. It is important to respect others despite the level of guilt. It is necessary that the spouse is able to honestly ask himself/herself what he/she is really cared about. It is necessary to dwell separately on such a radical way to resolve marital conflict as divorce. According to psychologists, a process consisting of three stages precedes divorce: a) an emotional divorce, manifested in alienation, indifference of the spouses to each other, the loss of trust and love, and b) the physical separation that leads to separation, c) a legal divorce, which requires legal registration of divorce. Divorce brings freedom from animosity, hate, deceit and everything that prevented from being happy in marriage to the majority of people. A woman, with whom children are usually remained, is the most vulnerable to divorce. She is more than a man, subjected to the neuro-psychiatric disorders. It is important to note that many recommendations for the normalization of the marital relationship and prevention of disputes from escalating into conflicts have been developed. Most of them are summarized as follows: 1. Respect yourself and others. Remember that he (she) is the closest to you. Try not to accumulate errors, wrongs and sins, but immediately respond to them. It will prevent the accumulation of negative emotions. 2. Do not criticize each other in the presence of others (children, friends, guests, etc.). 3. Do not exaggerate your own abilities and dignity; do not consider yourself always right in all. Trust your spouse more and minimize jealousy. Be careful, know how to listen and hear the spouse. Always take care of your physical attractiveness, work over your own weaknesses. Do not generalize even obvious shortcomings of the spouse; lead a conversation only about a specific behavior in specific situations. 4. Treat the hobbies of the spouse with interest and respect. In family life, it is sometimes better not to know the truth, than try to establish the truth. Try to find time to take a rest from each other at least sometimes. This will help removing the emotional and psychological heaviness of communication. In other words, When conflict happens and communication starts to break down, take a break from each other to cool off and think through the issues. There are some ways to resolve the conflict and how you can avoid battling about the same issues again. For example, I need to listen to you more and not read into what youre saying. Ill try to be more patient with you. I wont say harsh or unkind words to you. Get back together and talk. Remember, your goal is to resolve the conflict. Take turns so that you both can speak and both actively listen. Share what you wrote while you were cooling down. You might need to give a little more to compromise, so humility and cooperation are important. Spend time in prayer together to end your discussion (Lewis, 63). It is necessary to keep in mind some key points that can be used in everyday communication that helps to avoid conflict situation in marriage and resolve different cases. Firstly, it is important to talk about everyday affairs every day. In this case, couples learn to trust each other and then they share their problems with each other that creates mutual understanding. Secondly, it is essential to find time for talking; it may be a family meal. Thirdly, it is important to be approachable. It is necessary to empathize and listen to each other. The main suggestion for successful family communication is to be intentional. This means that couples should not avoid conversation with their children, give time and space for it. Communication is not only words; it may be expressed in tone, body language or some actions. Therefore, it is important to listen carefully and try to understand not only words but also feelings behind them. Sometimes, a conversation may be tough. It is better to think about it in advance, prepare possible questions or do something. It is essential to invest in family communication, for instance, by writing a letter, sending a card, or making a phone call that will result in opening a friendly dialogue. It is better to build relationships during good times that will help at bad times. Besides, the knowledge of likes and dislikes of the closest relatives will contribute to successful everyday communication in the family. Conclusion The problem of conflict has always been more or less relevant to any society. Life proves that conflict does not apply to events that can be effectively managed on the basis of life experience and common sense. The issue of family conflicts is worth emphasizing because family is the oldest institution of human interaction, a unique phenomenon. Its uniqueness lies in the fact that several people intimately interact for a long time (tens of years), that is, for the greater part of human life. Disputes, conflicts and crises cannot arise in such a system of intensive interaction as family. Divorce leads to the fact that the society receives an incomplete family, because of which the number of adolescents with divergent behavior is constantly increasing and leading to crime expansion. This creates additional difficulties for the society. Key role in family conflict relations belongs to marital conflict (Pitt-Catsouphes et al. 2006). They arise because of unmet needs of the spouses. Most conflict situations are the crisis periods in the development of the family. Family conflicts have traumatic consequences: a state of total dissatisfaction with the family, family anxiety, neuro-psychological tension and state of guilt. The experts have made recommendations on regulation of marital conflict in order to prevent conflict situation within the family and increase the importance of family in the future. It is necessary to add that Unresolved conflict does not mean that these couples never discuss conflicts. Periodically, they may have long and heated discussions about conflicts. The problem is they never reach a solution. After the heat has intensified to a certain point, they drop the conversation and withdraw from each other, leaving the conflict unresolved. Then when the spouse says something that is emotionally tied to this unresolved conflict, the person will have another defensive response (Chapman, 158). In summing up, the obvious connection between conflict situations in marriage and human life, that is, longevity, is supported by different research studies. People living in the marriages with obvious dissatisfaction because of unresolved conflicts, demonstrate health problems that affects longevity of couples (Amato, 77).