Models of exposure therapy, one of the key components of cognitive behavioral therapy for anxiety disorders, suggest that attention may play an important role in the extinction of fear and anxiety. Evidence from cognitive research suggests that individual differences may play a causal role in the onset and maintenance of anxiety disorders and so it is also likely to influence treatment. We review the evidence concerning attention and treatment outcomes in anxiety disorders. The evidence reviewed here suggests that that attention biases assessed at pre-treatment might actually predict improved response to treatment, and in particular that prolonged engagement with threat as measured in tasks such as the dot probe is associated with greater reductions in anxious symptoms following treatment. We examine this research within a fear learning framework, considering the possible role of individual differences in attention in the extinction of fear during exposure. Theoretical, experimental and clinical implications are discussed, particularly with reference to the potential for attention bias modification programs in augmenting treatment, and also with reference to how existing research in this area might inform best practice for clinicians. Neverthfits-all . There iDisorders such as specific phobia, social anxiety disorder (SAD), panic disorder (PD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD) are characterized by excessively intense, frequent and enduring fear or anxiety concerning the possible occurrence of something terrible. Fear is often an adaptive response to threat, wherein there is a rapid, involuntary, physiological reaction that facilitates the selection and production of an appropriate behavioral or cognitive response . AnxietyCognitive-behavioral therapy for anxiety disorders therefore seeks to reduce fear and anxiety as well as the neurocognitive mechanisms that underlie them . HoweverFirst we will explain our conceptualisation of attentional biases, whilst also addressing the literature concerning individual differences in attentional biases within anxiety disorders. Second, we will consider the role of attention in the learning that underlies exposure therapy. Then, we will conduct a critical examination of the literature concerning the moderating influence of attentional biases, and any related neurophysiological correlates, on treatment outcomes for anxiety disorders. The results of these studies will be considered within the context of models of the underlying mechanisms involved in exposure . Finally, the theoretical, experimental, and clinical implications of this examination will be presented. The research in this area remains in its infancy, thus precluding a meta-analysis of the data available, but we hope that by collating and reviewing the present evidence and providing the most up-to-date theoretical perspective, that we might provide inspiration for clinical and research developments.shifting between stimuli, thoughts or responses; updating attentional selection based on changes in goals; and inhibiting attentional engagement with irrelevant stimuli or thoughts : engagement with threat, disengagement with threat, and an attentional avoidance of threat . As such there is a body of research concerning the effects of manipulations of distraction on exposure efficacy. Distraction is typically defined as insufficient attention to the source of a potential threat. It can involve overt redirection of attention toward some threat-irrelevant task, stimulus or non-threatening features of a feared stimulus; or covert redirection of attention and attempts to not think about potential threats . There anatural exposure without a specific therapist-initiated attention manipulation and so they are likely to show similar fear reduction as clients who are distracted by the therapist. Research concerning the effects of distracted versus focused exposure has produced mixed findings. A recent meta-analysis found that overall there was no difference between distracted versus focused exposure in terms of treatment outcome  showed evidence of a trend-level correlation between pre-treatment Stroop interference (SI) scores and behavioral avoidance following treatment . We might tentatively interpret this finding as suggesting that greater interference from disorder-relevant words on color-naming in a Stroop task was associated with greater behavioral avoidance following treatment. Put otherwise, a threat-related attention bias was associated with worse treatment outcome. In another study, there was no significant difference in pre-treatment SI scores for social threat words between clients who responded to treatment and those that did not (N = 33). Participants in this study were given either a pharmaceutical intervention, pill placebo or 12-weeks of group CBT . However, the authors did not test whether treatment response was differentially related to SI scores for each of these treatment modalities separately. This makes it impossible to conclude as to the specific relationship between CBT or the exposure component within and SI. N = 37) who received a single session of exposure treatment. N = 24) that a greater proportion of treatment responders (78%) showed SI at pre-test relative to non-responders (50%) who “did not show any Stroop Interference before treatment,” although this was not statistically tested. However, the authors did not provide detail on the components of their CBT programs limiting the conclusions that can be made concerning the relationship between attention biases and exposure. In their investigation into the effects of different psychological treatments on SI on motor-vehicle accident related PTSD (N = 23), Research in this area began indirectly with a number of studies that explored the effects of exposure  on attention biases. These studies measured attention biases in terms of performance interference on a color naming Stroop task when the words included in the task were disorder-relevant .  did not ; N = 33.N = 131; age range 8–16 years) who presented with a primary diagnosis of Separation Anxiety Disorder, GAD, SAD, or Specific Phobia were randomized into group or individual  CBT programs. The authors reported that response latencies to a Dot Probe target that followed a severe threat image in severe/neutral image pairings predicted 10–13% of the variance in treatment outcome (p = 0.001), even when controlling for pre-treatment anxiety severity. Contrary to their hypotheses, treatment responders were less likely to engage their attention toward threat images than non-responders, who were more likely to show difficulties in disengaging their attention from threat. According to the authors, people who tend to inhibit negative information and avoid processing threatening stimuli in detail may respond better to CBT.In light of these methodological problems, N = 91) had a similar demographic and diagnostic profile to participants in their previous study. Initial responders no longer met diagnostic criteria after 10 sessions of CBT alone and four sessions with their parent; secondary responders were those who continued to meet diagnostic criteria after these initial sessions but who later responded following 10 subsequent sessions of combined child and parent sessions. They found that initial responders showed slower responses on congruent trials where the target followed the threat image in threat/neutral image pairings, than on incongruent trials where the target followed the neutral image. Put otherwise, initial responders showed selective attention away from threat, attending more toward neutral images than to threat images. Secondary responders showed selective attention toward threat with slower responses on incongruent trials than on congruent trials. Treatment non-responders showed no evidence of an attentional bias toward or away from threat before or after treatment. Following treatment, initial and secondary responders showed difficulties disengaging from threat. This confirmed N = 24) who underwent eight sessions of CBT including virtual reality exposure. Attentional bias was assessed using a neutral/threat (angry) face Dot Probe task. Mean response times in congruent trials, when the target followed the threat image, were subtracted from incongruent trials, where the target followed the neutral image. Participants with a positive score on this index were classified as being vigilant toward threat whereas a negative score meant they were avoidant of threat. Avoidant attention biases at pre-treatment were associated with worse post-treatment symptom scores relative to vigilant threat biases. A tendency to attend more toward threat was associated with improved outcomes relative to attending away from threat. The authors reasoned that avoidance of threat was analogous to distraction and poor engagement with exposure and worsened extinction learning. Further analysis suggested that the effect of an avoidant attention bias on treatment outcome was independent of the severity of this bias. However, for those with a vigilant threat bias, higher scores were associated with worse response to treatment. These findings suggest that even though generally attending toward threat may be beneficial, there is also variability within this bias, such that being highly vigilant and perhaps not being able to attend anywhere other than toward threat can be detrimental.N = 35) that received a group CBT program (The findings of  program . After 1N = 22) a 12-session course of CBT or ACT for social phobia. They used a Spatial Cuing task to measure attentional biases. In their variant of the Spatial Cuing task, threatening (angry or disapproving) faces or images of neutral household objects were presented in the center of the screen and this was then followed by a target letter above, below, or to the left or right. The time participants took to identify the target letter was then averaged across both threat categories. Participants who showed slower reaction times identifying targets that were preceded by a threatening face (interpreted as difficulty disengaging from threat) also showed greater improvement in clinician-rated fear and avoidance scores after treatment, relative to participants who showed no response slowing. There was also a trend toward the same relationship with self-report symptoms too. Attention toward threat, and in particular difficulty disengaging with threat, was associated with improved response to treatment relative to if a client showed no threat-related attention bias.Finally, monitoring coping style in managing their anxiety and who seek knowledge about sources of threat and make greater attempts at processing threat stimuli . There are a number of studies which illustrate how a tendency to selectively attend toward threat is predictive of improved response to exposure treatment relative to attending away from threat  can improve treatment response relative to CBT alone  and CBT However, in these studies the ABMT is administered concurrently with each CBT session making it impossible to conclude as to the effects of ABMT and changes in attention on subsequent learning during treatment. Also, the authors did not include an additional comparison group wherein attention was trained toward threat, although it was not within the purpose of their studies to include such a control. This would allow us to conclude as to whether attentional training in either direction leads to better treatment response relative to placebo-ABMT or no ABMT, or whether a bias in a particular direction leads to better response. Nevertheless, there is some promising evidence that augmenting CBT with ABMT might lead to improved outcomes and in particular that training people to attend away from threat might be most beneficial. Future research must now explore how changes in attention biases, as a result of ABMT, might influence the way people learn during other aspects of CBT such as during exposures.An interesting adjunct to this is that some of the studies reviewed here suggest that not all anxious people possess a threat-related attention bias and if they do it may not be in the same direction. Unaccounted for variability in the direction and extent of pre-existing individual differences in attentional biases in participants of ABMT trials might explain why ABMT shows such small effect sizes as it may be more difficult to train people’s attention in the opposite direction to their existing biases and where there is already an attention bias away from threat it might be more difficult to influence anxiety symptoms by reinforcing this bias . It is mAlthough it is beyond the scope of the present review to consider how similar processes might operate within other treatments for anxiety, it is worth mentioning that similar processes might operate in treatments such as acceptance and commitment therapy (ACT). In ACT exposure to the sources of one’s fears and reductions in avoidance of fear-evoking stimuli are crucial. The evidence reviewed here has several implications for clinical practice. We present one example of how individual difference variables can influence treatment outcomes. This has rather broad implications for clinical practice in suggesting that greater care should be taken in tailoring treatment to individual neurocognitive profiles rather than to try and fit everyone into the same treatment. More specifically, similar to One important omission in the existing literature concerns whether any of the observed effects of attention on treatment outcome are preserved at follow-up assessments. This is particularly important because it has often been shown that people who respond best to treatment also often continue to show selective attention toward threat after treatment , 2010. EHowever, preferentially attending to previously feared stimuli instead of neutral stimuli may not be maladaptive providing that once a stimulus is attended to, there is not an overestimation that something negative might subsequently occur. Unless increased attention toward threat was also associated with anticipation of an aversive event, then we might not expect any return of fear to occur. As The research to date also lacks an analysis of any possible interactive effects of attentional biases with diagnosis on treatment outcome. Most studies include a broad range of anxiety disorders and lack the sample size to investigate whether the effects of attentional biases on treatment outcome are specific to a given anxiety diagnosis or whether the effects are transdiagnostic. There is evidence to suggest that there is some specificity in the direction and latency of attentional biases between anxiety disorders  and so wwhy individual differences in attentional biases can influence treatment outcome. There must be a move away from reaction time measures to more robust measurement techniques that allow for direct, online, measurement of overt and covert attention before and during exposures. Eye-tracking methodology could provide such a measure of overt attention and neuroimaging might be used to assess covert attention. Pre-treatment fixation data could be used to predict subsequent treatment response in the same way that Dot Probe data has to-date. This could be coupled with neuroimaging data to assess whether the relationship between overt attention toward or away from threat and treatment outcome is in turn related to neural patterns of covert threat engagement. We might also measure fixation and neural activity during exposures. From this it would be possible to relate pre-treatment attention biases to actual visual behavior and covert engagement during exposure and to relate these variables to fear within- and between- sessions as well as overall clinical response at post-treatment and follow-up. This would make it possible to test whether people with an attention bias show better treatment response than people with no attention bias because they spend more time processing exposure stimuli rather than to distractors in the environment, contexts or safe stimulus features.Nevertheless, research must now directly examine, through experimental and clinical investigation, In order to further improve already efficacious treatments, it is important that there is now a move within clinical psychology from a broad perspective where treatment modalities compete against one another for superiority, to one in which we consider which treatments work best for whom and why. It is important that we now consider how the individual differences that underlie disorder interact with existing treatments in order to better understand the mechanisms by which these treatments work. This knowledge can be used to not only guide the prescription of treatment but also to enhance some element of treatment. More specifically, it is also important that there is a move away from considering biases in attention – and no doubt cognitive biases in general – as universally negative, and a move toward considering them from a functional perspective where they can be positive in certain situations where enhanced threat processing and reduced peripheral processing is required.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Here we present a new method for predicting cellular growth rate, termed SUMEX, which does not require any empirical variables apart from a metabolic network  and the growth medium. SUMEX is calculated by maximizing the SUM of molar EXchange fluxes (hence SUMEX) in a genome-scale metabolic model. SUMEX successfully predicts relative microbial growth rates across species, environments, and genetic conditions, outperforming traditional cellular objectives . The success of SUMEX suggests that the ability of a cell to catabolize substrates and produce a strong proton gradient enables fast cell growth. Easily applicable heuristics for predicting growth rate, such as what we demonstrate with SUMEX, may contribute to numerous medical and biotechnological goals, ranging from the engineering of faster-growing industrial strains, modeling of mixed ecological communities, and the inhibition of cancer growth.Growth rate has long been considered one of the most valuable phenotypes that can be measured in cells. Aside from being highly accessible and informative in laboratory cultures, maximal growth rate is often a prime determinant of cellular fitness, and predicting phenotypes that underlie fitness is key to both understanding and manipulating life. Despite this, current methods for predicting microbial fitness typically focus on  In the data-rich landscape of present-day biology, large-scale network-based models are being increasingly tapped to make sense of the deluge of available data. Towards this end, genome-scale metabolic models (GEMs) have proven highly successful rate. Recently, several works have incorporated large-scale data along with metabolic reconstructions into multi-system models, which include processes such as transcription, translation, growth rate dependence of the production of biomass constituents, and often vast numbers of empirical or approximated parameters rate data, which makes them impractical for predicting growth rates in circumstances in which such rate information cannot be systematically measured. This is inevitable, as without some rate information being added, GEMs are typically suited for predicting not growth rates but growth yields.Metabolic phenotypes in GEMs are typically computed by a linear optimization method termed Flux Balance Analysis (FBA), in which a biomass objective is optimized while various network-defined constraints are upheld. Non-biomass objectives have also been tried, with varying powers of prediction yield (units of [g biomass produced]/[g substrate consumed]) is different from growth rate (units of 1/[hour]), although they are related by the substrate uptake rates of an organism growing at steady state . Prediction of yield using GEMs applies most rigorously to highly defined conditions such as in a chemostat in which one nutrient is limiting, and it is unclear how broadly applicable the ‘maximization of yield’ principle actually is rate could be determined using genome-scale properties of GEMs that do not necessitate the arduous measurement of substrate uptake rates Growth In this study we explore novel large-scale methods to predict variability in growth rates from GEMs grown on rich or defined media, and in some cases with gene knockouts. We focus on environments in which cells are expected to be optimizing their growth rate, such as maximal listed growth rates for species in rich media, or careful growth rate measurements of isogenic cultures in early exponential phase of batch growth. Our approach was inspired by an article by Vieira-Silva and Rocha Vieira Silva and Rocha, we explore a new class of metabolic objectives, related to maximizing the total metabolic secretion of a cell, which predict relative growth rate directly from GEMs. We focus on exchange fluxes because they are the missing gap between growth yield , and because there is an observed strong positive correlation between cellular surface-to-volume ratio and growth rate, as well as additional evidence suggesting that cell surface metabolism exerts most of the control of a cell over growth rate SUM of EXchange fluxes’), while setting a nominal lower bound on biomass production in order to ensure that some flux runs through biomass-producing pathways .SUMEX has a clear intuitive linkage to the concept of a cell's ability to do catabolism. A high SUMEX value indicates that a cell is capable of breaking down a small number of moles of its collective substrates  into a much larger number of moles of product , and a low SUMEX value indicates that the capacity of a cell to break down substrates in this manner is low see . Since SSUMEX represents a simple heuristic to maximizing catabolic activity of a cell, focusing exclusively on exchange reactions, and still ensuring a nominal production of biomass  (see Table S2 in Escherichia coli wild type (WT) and knockout (KO) strains evolved for growth on a number of minimal media (ds57) in vitro in the early exponential phase of batch cultures of 6 organisms on 3 defined media (ds18) . This suggests that in rich media and when looking across a large range of organisms, both the growth rate and yield depend greatly on the capacity of an organism to take up many substrates – an observation supported by the relatively strong correlation between “count of uptake exchange reactions” and growth rate, as well as by the strong observed correlation between SUMEX and biomass yield, in ds66 . This is despite previously noted strong correlations between GEM-predicted biomass yields and growth rates in ds57 when accounting for experimentally measured glucose uptake rates ds66 see . DespiteE. coliE. coli grown on 24 minimal media (henceforth: ds24), and achieved equivalent results to the state of the art  gradient Interestingly, the removal of proton exchange from the SUMEX objective reduced the correlation of SUMEX with growth rate more than removal of any other component  and 57 organisms that can respire (ds66r). We found that the correlation of SUMEX with growth rate is stronger among only the respirers than among all organisms in ds66 see , that SULactobacillus plantarum, which has been shown to respire if provided heme and menaquinone When we remove a borderline case from the set of obligate fermenters , which is a confounding factor in any attempt to produce parameter-less metrics in GEMs. Therefore, in order to ensure that the results seen for SUMEX are not simply due to the particular bounds we chose, we performed a sensitivity analysis. This test revealed that the correlation of SUMEX with growth rate is highly robust even up to 50% (or more) random variations imposed across all uptake (or secretion) bounds; we furthermore found that biomass is significantly less robust than SUMEX in 2 of the 3 datasets see .The sensitivity of biomass to the bounds prompted us to try a follow-up analysis, in which we summed (but did not maximize) the mean allowed values of exchange fluxes given a constraint of optimal biomass. We did this only for models with randomly chosen uptake bounds that cause maximum biomass to correlate significantly with growth rate, which, in the absence of reliable full-organism exchange flux data, we assumed would be closer to the true exchange flux values than totally random bounds. This ‘sum of exchange’ (SUMofEX) variant on SUMEX also correlated significantly with growth rate in nearly every case, indicating that, if the exchange fluxes are known for an organism, merely summing them might be able to give an accurate value for growth rate  their GEMs were available from SEED and published in E. coli model was used E. coli SEED model was used. Table S2 in Unless otherwise noted, analyses were done on genome-scale metabolic reconstructions (GEMs) as obtained from SEED in silico environments consistent with the known media, in which all exchange metabolites for a given species were available at a fixed rate of −50.0 (with output bounds of 1000). A sensitivity analysis was done to determine if these bounds affected the performance of SUMEX, and SUMEX was found to be robust to random changes in the bounds  are negative valued, while exchanges denoting exit of a metabolite from the cell (output/secretion) are positive valued. Therefore, maximizing the total exchange flux (i.e. the SUMEX metric) would denote maximizing the output at the expense of the input (output exchanges – input exchanges). A full mathematical description of SUMEX is provided in For simulation of maximal proton production (PMAX) e.g., in , we incrOptimizations were done using the cplex tomlab optimization tool in a matlab environment. The free Gnu solver (GLPK) was checked in a few cases and returned identical results to the cplex solver, and could thus be easily exchanged. Most of the analyses were run using a standard desktop computer; a few were run in a computing cluster or on a high-powered linux machine. Sample Matlab code to run SUMEX is provided in in vitro experiments to measure the growth rates of a number of organisms Click here for additional data file.File S2Supplementary raw data files, and Table S2 (containing details on organisms in ds66).(XLSX)Click here for additional data file.Materials S1Zipped file containing matlab code to run SUMEX (read README.txt after unzipping).(ZIP)Click here for additional data file.


Jason Block and S. V. Subramanian explore avenues for improving the health of Americans through reducing dietary inequalities and look at whether concern over "food deserts" has been taken too far. Most Americans fail to meet recommendations for diet quality, with disparities evident by race/ethnicity, socioeconomic status, and use of nutrition assistance programs.The evidence supporting the elimination of food deserts as a strategy to reduce disparities in diet quality is weak.More use of evidence-based policies to improve diet quality and reduce disparities in the United States is needed, specifically for school- and child care-based interventions, useful population educational strategies, changes to nutrition assistance programs, and taxation of unhealthy foods such as sugar-sweetened beverages.Scientific interest in dietary patterns and the relationship between diet and disease has persisted for centuries . During Poor diet quality is strongly patterned by socioeconomic status (SES). In a recent US study examining trends in dietary quality from 1999 to 2010, lower-income individuals consumed lower-quality foods, as measured by the Alternate Healthy Eating Index 2010 score, than higher-income individuals . NotablyIn this essay, we discuss the specific role of physical access to food and the extent to which eliminating food deserts can improve dietary quality and decrease economic and racial/ethnic disparities in dietary quality. While a variety of factors contribute to income disparities in dietary quality, considerable attention has been focused on poor physical access to healthy foods leading to “food deserts.” The White House Task Force on Childhood Obesity explicitly considered the existence of “food deserts”  and at least one-third of tract residents live more than 1 mile away  from a supermarket or large grocery store .Food deserts refer to low-income geographic areas that lack access to a supermarket or large grocery store. Eliminating food deserts could improve diet either by providing access to healthy foods for individuals seeking those foods but with prior poor access or by generating demand within communities that had limited exposure to healthy foods. In contrast, living near fast-food restaurants might lead to poor diet quality because of enhanced access to the foods sold there; restricting access to these locations might improve diet by making this food less available. It has been shown that while area poverty was not an independent predictor of access to fast food restaurants, predominantly black neighborhoods had closer access to fast food restaurants . MeanwhiFour quasi-experimental studies have found similar results. One study examined the effect of a new supermarket in a Philadelphia food desert . After oEven if proximity to healthy food establishments were beneficial to health, can “healthy” food establishments be easily defined? While supermarkets typically devote more shelf space to fruits and vegetables than other food stores, unhealthy snack foods still dominate their shelves. One study in southern Louisiana and Los Angeles found that supermarkets had one-half to three-quarters more unhealthy snacks than fruit and vegetables in their stores; convenience stores and drug stores had 90% more of these unhealthy snacks than fruits and vegetables . SupermaPeople may not shop within their own neighborhoods even when a supermarket is present –31. In oWith unhealthy dietary consumption so prevalent, initiatives that focus on a narrow, at-risk population such as those living in food deserts without cars (less than 1% of the US population) are likely to be less effective than alternate interventions that help families make better decisions regardless of where they live and which food establishments are near their homes. Rather than assuming that “if we build it, they will come”  and eat Research on effective population-level strategies to improve diet remains limited. More evidence is needed to determine which interventions are best for specific populations, including low-income and minority populations that bear a greater burden of diet-related diseases. Here we discuss several feasible strategies that have the potential to lower disparities in diet quality more than eliminating food deserts.Interventions in child care centers across both the US and Australia have demonstrated beneficial effects on diet, physical activity, screen time, and even body weight –37. For School nutrition programs also might have some effect on the diets of children . BecauseThe provision of easily accessible information at the point of sale could help consumers better understand the health consequences of their purchases in restaurants and food stores. Calorie menu labeling in chain food establishments, which will be implemented across the US in 2016, is a start, though evidence of effectiveness is rather limited at this point ,43. ReviIncentivizing healthy food purchases, or disincentivizing unhealthy purchases, in food assistance programs could decrease disparities in diet quality. In 2009, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) made changes to encourage purchases of healthier foods, including adding more fruits and vegetables to the food packages the program financed. This change led retailers to stock more healthy foods  and was The benefit of healthy food subsidies is generally modest and may be amplified in the SNAP population if SNAP vouchers could not be used for unhealthy foods such as sugar-sweetened beverages. Simulation studies have found that banning the use of SNAP dollars for sugar-sweetened beverages could be cost effective  and could modestly reduce rates of diabetes, cardiovascular disease, and obesity with an expected 15% decline in calories from sugar-sweetened beverages ,55. ThesAs with investigations of changes to the WIC ,46–49, sTaxing unhealthy foods such as sugar-sweetened beverages (SSBs) may have important benefits for dietary quality ,53. BaseAddressing disparities in dietary quality may have important payoffs for the health of the population: we should promote policies and programs to support these changes while studying their effectiveness. These strategies do not preclude the elimination of food deserts but rather build a necessary infrastructure to promote healthy food consumption, in any neighborhood. Many reasons, such as economic and social justice, exist to support such initiatives and to remedy the lack of healthy food availability in low-income communities. We just should not expect the reduction of food deserts to have much impact on the prevailing health crisis of our time. We need to focus our efforts on initiatives more likely to improve dietary quality and decrease disparities.


Aedes aegypti[We compliment the team of investigators from Saudi Arabia and Malaysia for their meticulous update on the incidence of dengue in Saudi Arabia as well as the population control of the vector mosquito, s aegypti. In our Aedes aegypti is a day biter, but will bite at night if there is sufficient artificial lighting. Aedes aegypti usually bites at the ankles of humans[Aedes albopictus is a very aggressive daytime biter, with peaks during early morning or late afternoon. Both are container-inhabiting species that lay eggs in clean water-containing receptacles in and around the home environment.The vector responsible for dengue virus in Saudi Arabia, Aedes af humans. Aedes aDuring the initial phase of illness, a patient is viremic with circulating viral RNA and non-structural protein NS1 antigen. Later the viral RNA and NS1 antigen disappear with a coincident appearance of antibody, although NS1 antigen may be detectable in a few patients for a small number of days after defervescence. If any Generally, anti-mosquito measures are practiced at night when repellents, insecticides, or mosquito nets are used. Even after nocturnal caretaking, one could still be exposed to bites from the Aedes group of mosquito.The natives and expatriates to Saudi Arabia should bAedes group of mosquitoes. Prominent public personalities like film stars and sports personalities should wear such clothes during their appearances in public. School children should avoid use of shorts or skirts in the school. Local governments may offer subsidy to ensure reduced cost of such clothesAs a final suggestion, fashion designers in Saudi Arabia should be urged to create formal and informal clothing for both sexes which would protect against mosquito bites and that are also suited to local customs in each region. Although Saudi males wear long white clothing and females would cover themselves wearing black clothing while outdoors, such dress would not be worn inside the house when informal dress would be used as a rule rather than an exception. Consequently, informal attire for indoor usage during day-time would protect individuals from the bites of The authors declare that they have no competing interests.Both authors contributed to, read and approved the final version of the manuscript.


The liver is the most injured organ in abdominal trauma. Currently, the treatmentin most cases is non-operative, but surgery may be necessary in severe abdominaltrauma with blunt liver damage, especially those that cause uncontrollablebleeding. Despite the damage control approaches in order to achieve hemodynamicstability, many patients develop hypovolemic shock, acute liver failure, multipleorgan failure and death. In this context, liver transplantation appears as thelifesaving last resource Analyze the use of liver transplantation as a treatment option for severe livertrauma. Were reviewed 14 articles in the PubMed, Medline and Lilacs databases, selectedbetween 2008-2014 and 10 for this study. Were identified 46 cases undergoing liver transplant after liver trauma; the maintrauma mechanism was closed/blunt abdominal trauma in 83%, and severe trauma(>grade IV) in 81 %. The transplant can be done, in this context, performingone-stage procedure (damaged organ removed with immediate transplantation), usedin 72% of cases. When the two-stage approach is performed, end-to-side temporaryportacaval shunt is provided, until new organ becomes available to betransplanted. If two different periods are considered - from 1980 to 2000 and from2000 to 2014 - the survival rate increased significantly, from 48% to 76%, whilethe mortality decreased from 52% to 24%.  Despite with quite restricted indications, liver transplantation in hepaticinjury is a therapeutic modality viable and feasible today, and can be used incases when other therapeutic modalities in short and long term, do not provide thepatient survival chances. The main causes of death following severe hepatic trauma areuncontrollable bleeding due to vascular and liver laceration injury and acute liverfailure. Both conditions can be treated by selected cases of liver transplantation;however, indications are still well restricted,,,In cases of severe liver injury (TSAA grade>IV) mortality rates rise to about 46-80%,and liver transplantation should be considered in cases where all other therapies havefailed to achieve hemodynamic stability, making it imperative to adopt damage controlmeasures in order to promote temporary hemostasis until an organ becomes available fortransplantation 3,7,1,,,,,The indications for liver transplantation due to trauma more described in the literatureare: uncontrollable continuous bleeding after damage control operation; extensivecomplex liver lacerations not amenable to surgical correction; extensive lesions of theportal vein, hepatic vein or bile duct that cannot be repaired by surgery; progressiveliver failure due to trauma, and hepatic necrosis. In these patients, often the livertransplant is the last therapeutic alternative; however, not all patients are candidatesfor transplant and that choice should be conducted carefully and individually.Situations such as severe sepsis, multiple organ failure, other serious injuriesassociated may contraindicate the transplant2,,There are two types of procedures described in the literature: transplantation in oneand two steps. The in one, is the immediate removal of the native liver with subsequentimplantation of a new organ. During the procedure performed in two stages there will bea temporary vascular portocaval shunt type to allow the patient to wait for a new bodyand avoid congestion in mesenteric splanchnic systemThe objective of this study was to analyze the use of liver transplantation as atreatment option for severe liver trauma.Survey was conducted in the Pubmed, Medline and Lilacs, between 2008-2014 correlatingliver trauma and liver transplantation headings. Was found 14 related articles, of which10 were selected for theme analysis.After making systematic literature review of the literature was identified total of 46case reports of patients undergoing liver transplant after liver trauma; closed/blunttrauma had a higher prevalence with total of 83%, as well as severe trauma . Whilethe main indication, statistically significant for the technique in two steps was acuteliver failure with 77% , early transplant on within 72 h, since this therapy isrecommended in acute cases, as discussed above. Conversely, patients undergoingtransplantation in one step, in addition to cover the majority of transplant patients(n=33) had a greater number of late transplantation (n=12), since this is the techniqueof choice for elective procedures and chronic complications when a compatible donor waspreviously chosen,,,Regarding retransplantation were identified a total of 11 cases in which the main causeswere of cholestasis and repeated cholangitis due to ischemic lesions of the bile duct,hepatic artery thrombosis, primary graft failure, and late failure of the transplantedorgan by diabetesCurrent survival after transplantation for liver trauma is about 76% while two decadesago was around 48%. Sepsis is still the main cause of mortality after transplantation(50%), despite a significant drop in the total number of cases over the past 10 years.This increase in survival rates may be attributed to the fact that 20 years ago thesigns were smaller and less frequentThe patients submitted to the standard procedure in one step survival rate is around70%, while with the two steps is 54%. Such data are justified by the selection of caseswhere every mode has been indicated. The cases undergoing treatment in two steps usuallyend up being more severe cases that end up presenting progressive organ failure andtherefore have a worse prognosis, increasing with it the mortalityAnother important factor is the transplantation in patients who develop liver necrosisin the days following the trauma; necrotic liver has been seen as toxic agent leading toincreased hemodynamic instability. Therefore, total hepatectomy followed bytransplantation in two steps is also indicated in these patients. However, the ethicalimplications of this approach are key, leaving the post-trauma liver transplantation asthe only solution, which is, however, entirely dependent on the availability of aadequate donorThe ethical issue also includes the context of patients received grafts from livingdonors. Because of the many implications and repercussions that this theme will bring,not being the focus of this study, was identified only one report from a living donorfor a patient who received the right lobe of his brother. They were not identified inthe review other casesWith the increase in the number of organ donors, as well as transplants performed in thelast decade, today is considered even in cases of trauma such as early as possibleapproach with the procedure in one step with significant increase in survival,In this context, liver failure is a challenge that requires urgent livertransplantation, since it leads to worsening of the clinical condition and hemodynamicstability, leading to complications such as cerebral edema and increased intracranialpressure, which can lead to irreversible brain damage to the patient. Thus, wasdeveloped an extracorporeal liver support system, that controls these complications,helping to keep patients stable until a suitable donor was found for the viable andavailable for transplantation. The methods used for extracorporeal support can beclassified between biological and non-biological. The bioartificial system uses primaryporcine hepatocytes or processed human hepatocytes that are housed within a bioreactorthrough which blood is pumped into the extracorporeal circuit. The difficulty of findinga compatible donor quickly, coupled with the inability to maintain stable patient inanhepatic stage for long periods of time, they become a major problem in the managementof these patients. Thus, it appears as support therapy an alternative, by increasing thesurvival time where the transplant precocioulycannot be performedDespite not having been found in the present review any study that uses this type as thedevice bridge method for patients who have their organs removed as a result of thetrauma extent and therefore were subjected to the use of this type of device, it mayhave relevant role in increasing survival during anhepatic phase, as well as the waitingtime on the list and may allow patients who previouly could not afford to wait forlonger times in the list, are likely to be transplanted.Liver transplantation, despite having very limited information on the stage of hepaticinjury, is therapeutic modality viable and feasible on these days and can be used incases where surgical treatment as well as other therapeutic modalities, do not offer thepatient chances of survival to short and long term.


The integration of gene delivery technologies with electrospun nanofibers is a versatile strategy to increase the potential of gene therapy as a key platform technology that can be readily utilized for numerous biomedical applications, including cancer therapy, stem cell therapy, and tissue engineering. As a spatial template for gene delivery, electrospun nanofibers possess highly advantageous characteristics, such as their ease of production, their ECM-analogue nature, the broad range of choices for materials, the feasibility of producing structures with varied physical and chemical properties, and their large surface-to-volume ratios. Thus, electrospun fiber-mediated gene delivery exhibits a great capacity to modulate the spatial and temporal release kinetics of gene vectors and enhance gene delivery efficiency. This review discusses the powerful characteristics of electrospun nanofibers, which can function as spatial interfaces capable of promoting controlled and efficient gene delivery.The online version of this article (doi:10.1186/1754-1611-8-30) contains supplementary material, which is available to authorized users. Gene delivery has emerged as a powerful platform technology for a variety of biomedical applications, including tissue engineering, cancer therapy, and stem cell therapy. Altering genetic information through exogenous stimulation of target cells can accomplish numerous intended goals, such as differentiation of the targets cells into specialized cell types –3, activUsing the full potential of gene delivery in numerous biomedical applications requires a series of toolkits that can help to overcome the limitations associated with gene delivery technologies, the first necessary step prior to employing gene delivery in applications is the selection of suitable gene delivery vehicles, which can be categorized into viral or non-viral vectors, depending on the target applications or cell types. The engineering of versatile gene delivery carriers, which can specifically target clinically valuable cell types , can avoid immune system effects or toxicities, and can safely pass through complicated intracellular steps to reach the nucleus, is one of the most critical tasks in gene delivery –13. HoweIn this review, we primarily focus on the strategy that combines gene delivery with electrospun nanofibers as one strategy among all of the interdisciplinary approaches of gene delivery with biomaterials, which have been typically employed as tissue engineering scaffolds –19, micrElectrospinning is a versatile method for fabricating ultrafine polymeric nanofibrous structures through electrostatic interactions Figure . DepositOwing to these multiple merits, highly porous fibrous structures have recently been employed as powerful templates for delivering genes of interest for various purposes  in a spatially or temporally regulated manner –26. Non-To ensure that electrospun fibers can be used as gene delivery templates, the lack of harmful effects of two major processing features on the bioactivities of gene vectors must be confirmed; the processing typically includes direct contact between gene vectors and organic solvents and exposure to a high electric voltage. No systematic studies have been performed to thoroughly investigate the detrimental effects of the electrospinning processes on the activities of gene vectors. However, no substantial loss of the capabilities of gene vectors as a result of the relatively harsh electrospinning processes has been observed in many previous studies , 48, 58.Combining gene delivery with engineered polymeric biomaterials has been regarded as an indispensable strategy to increase delivery efficiencies and modulate gene delivery kinetics in a spatial and temporal manner. Genes delivered via a classic method  diffuse freely within the body and thus suffer from the regulation of gene delivery rates or the localization of gene expression within a designated region , 14. In The high porosity of electrospun nanofibers can facilitate increased cellular contacts with well-distributed gene vectors within or over large surface areas, thereby allowing more opportunities to internalize gene vectors across the cellular membrane. Furthermore, the pores of electrospun nanofibers are typically produced with interconnected open structures, which can improve the cellular penetration into fibrous interiors and increase the gene vector loading capacities, thereby increasing in the gene delivery efficiencies . For exaOwing to the ease of tuning structural variations of electrospun nanofibers, the capability of these fibers to mediate controlled and sustained gene delivery has been recognized as the most representative feature of electrospun nanofibers compared with other existing polymeric gene delivery templates. It is well known that variations in polymer degradation through hydrolysis and alterations of diffusion routes through porous structures have been key design parameters that can vary the release kinetics of biomolecules encapsulated within or adsorbed on polymeric templates . In addiThe encapsulation of gene vectors within electrospun nanofibers for subsequent diffusion through porous routes can result in the sustained release of gene vectors, as well as controlled delivery via manipulations of the physical or chemical properties of the fibrous structures. Gene vectors can be incorporated within the inner space of fibrous structures, as illustrated in Figure The release profiles of gene vectors within the inner space of nanofibers were readily regulated using environmental factors that can degrade polymer matrices Figure B. It is Another key factor that can modulate the release modes of gene vectors encapsulated within nanofibers is the inclusion of additives within fibers Figure C and 2D.Altering the compositions of polymeric materials comprising nanofibers can be an additional option to tailor the release profiles of gene vectors, as well as the delivery efficiencies. The copolymerization of ethyl ethylene phosphate (EEP) with caprolactone facilitated the incorporation of gene vector elements into the inner space of nanofibers and resulted in a sustained release of siRNA complexes that exceeded 40 days . The co-A notable structural feature of the electrospinning process is its capability to produce a core-sheath structure within individual fibers, where multiple biomolecules at each layer can be designed to diffuse out sequentially Figure . The eleThe presence of porogens in the shell layers can facilitate the sustained and controlled release of gene vectors incorporated in the core layers and can also extend the duration of gene delivery Figure E. The prThe variations in the PEG contents in the shell layers demonstrated the distinctive controlled release profiles of viral vectors that were encapsulated within the core layers. The release rates of adenoviral (Ad) vectors encapsulated within co-axially produced PCL fibers were dependent on the PEG concentrations in the shell layers . As the The core-sheath fibrous structures can provide multiple physical spaces for separately delivering dual factors, which possess individual roles Figure F. Co-axiAn alternative approach capable of delivering gene vectors from electrospun nanofibers is to immobilize gene vectors onto the surfaces of completed nanofibrous structures; this technique is termed substrate-mediated delivery. This approach can block any attempts to expose gene vectors to both organic solvents and a high electric field because the gene vectors are adsorbed on the surface of fibrous constructs in the last step after the manipulation of the fibrous constructs is completely finished. Thus, the relatively harsh processing steps could have no harmful effects on the bioactivities of gene vectors. Importantly, this delivery method can place gene vectors in close proximity to the desired location within the cellular microenvironment and can extend the residence time of the gene vectors within the boundary layers; thus, this method can overcome mass transfer limitations to deliver the genes of interest to target cells , 75. IncThe most representative method of immobilizing gene vectors on electrospun fibers is non-specific random adsorption, which is typically accomplished using van der Waals, hydrophobic, and electrostatic interactions between gene vectors and the fiber surfaces Figure A 7, 13,,13, 79. Producing multiple DNA layers on fibrous surfaces was proposed as a means to increase gene delivery Figure C 45, 4646, 76. LElectrospun nanofiber-mediated gene delivery approaches using naked plasmid DNA typically require additional process, such as condensing the plasmid DNA to further increase the delivery efficiencies; the delivery capability for naked plasmid DNA is substantially lower than that for viral vectors. Different methods were employed to decrease the size of plasmid DNA upon electrospinning: i) solvent-induced condensation , 80, ii)The chemical modification of fibrous surfaces is an efficient way to adhere gene vectors onto fibrous interfaces, through increasing the specificity of the fibers for the gene vectors Figure D 77, 7878, 88. MOne of the key unique characteristics of electrospinning compared with other fabrication tools is that it can readily produce uni-axially aligned or patterned fibrous structures Figure . The uniThe modification of either fibrous surfaces or gene vectors can allow spatially patterned or localized gene delivery on the fibrous matrices, and these matrices can possibly be used for patterned tissue regeneration –97. CovaOwing to both their versatile capabilities that can be used to coordinate the release profiles of gene vectors and their ECM-analogue nature Figure , gene vein vitro[in vivo[In addition to the ability of electrospun fibers to precisely mimic bone ECM, these fibers have large surface-to-volume ratios, allowing vascularization across the newly produced tissues within fibrous structures; these features provide strong rationales for the use of nanofibers as a guide to regenerate bone tissues . Bone moin vitro and in vo[in vivo. The suso[in vivo, ultimato[in vivo. Additioo[in vivo. As prevo[in vivo. Thus, co[in vivo.Figure 6ex vivo stem cell transplantation [Skin tissue engineering has emerged as a powerful means to promote wound healing, a sophisticated cellular process that can be achieved by coordinating hemostasis, inflammation, epithelialization, angiogenesis, and collagen synthesis –106. Impantation  with eleBoth endothelial cell lining and smooth muscle cell layers on the luminal surface of vessel architectures have been regarded as crucial design factors to explore in vascular tissue engineering , 108. AdEmploying neural stem cells, which have the capabilities of self-renewal as well as neuronal differentiation, and providing patterned physical guidance along with biochemical cues  have been regarded as pivotal factors to induce neural regeneration , 111. Thin situ gene transfection in mouse embryonic stem cells [Electrospun fibers have been recently employed in a stem cell study or a cancer therapy approach in addition to their use in tissue engineering applications. Fei et al. fabricated a nanofiber-based sandwich electroporation (NSE) device capable of em cells . Unlike em cells . A plasmGene therapy has demonstrated increasing promise for treating a variety of human diseases, including inherited or acquired disorders, infectious diseases, tissue loss, and organ failure. The development of highly efficient gene delivery systems that can deliver a gene of interest safely to particular target cells has been always regarded as a large hurdle that must be cleared for the further advancement of gene delivery technologies. Electrospun fibers have highly advantageous characteristics, including ease of production, an ECM-analogue nature, a broad range of choices for materials, the feasibility of producing structures with varied physical and chemical properties, and large surface-to-volume ratios. Because of these characteristics, electrospun nanofibers have recently been highlighted as versatile and powerful templates that can be applied to numerous biomedical fields. Therefore, the integration of gene delivery with electrospun nanofibers is a highly promising strategy to improve gene delivery for a broad range of applications.For further innovation of approaches that combine gene delivery and electrospun nanofibers, there are several critical challenges, especially improving the structural aspects of electrospun nanofibers. Electrospinning typically produces flat two-dimensional sheet-like meshes, which may not fully represent the three-dimensional extracellular environments in the body. These structural characteristics may limit the ease of application of electrospun nanofibers to many biomedical fields. Numerous studies have created three-dimensional electrospun nanofibers, typically by modifying collectors or by utilizing an extra apparatus . Additio


Stresses provoked by adverse living conditions are inherent to a changing environment (climate change and anthropogenic influence) and they are basic factors that limit plant development and yields. Agriculture always struggled with this problem. The survey of non-toxic, natural, active substances useful in protection, and stimulation of plants growing under suboptimal and even harmful conditions, as well as searching for the most effective methods for their application, will direct our activities toward sustainable development and harmony with nature. It seems highly probable that boosting natural plant defense strategies by applying biostimulators will help to solve an old problem of poor yield in plant cultivation, by provoking their better growth and development even under suboptimal environmental conditions. This work is a concise review of such substances and methods of their application to plants. Different intensity and duration of a negative stimulus generate stress, which triggers specific or non-specific reaction. The former usually appears when a stressor focuses on a particular target, the latter when reactions to different stressors are similar. Since plants being rooted cannot escape from a harmful environment, they evolved other defense strategies including (i) ability to avoid stress  are limited due to the inability to effectively use the biological potential of the cultivated variety. In the face of a difficult task of preventing damage caused by harmful organisms or abiotic stresses in field crops, the plant production and protection should be based on stimulation of their growth and development with simultaneous reduction of hazards presented to humans and environment as well as with securing safe high quality agricultural products (it implies strong limitation of toxic pesticides and herbicides). Application of biostimulators seems to be the best means to appease an urgent need for alternative organic methods based on new biologically active, environmentally friendly, and safe substances.Table 1).Plant biostimulators – phytostimulators – are various non-toxic substances mostly of natural origin that improve and stimulate plant life processes differentially than fertilizers or phytohormones. Their influence on plants is not the consequence of their direct ability to regulate metabolism and their action could be multidirectional. The crucial point is that biostimulators in contrast to bioregulators and hormones improve plant metabolic processes without changing their natural pathway  activity in maize leaves  treated with Moringa oleifera extract  content. Over-production of these reactive compounds not followed by their neutralization, disturbs redox homeostasis and induces oxidative stress, which is a well known secondary effect of all biotic and abiotic stresses. Thus, on the one hand antioxidant activity is very desirable in stressed plant cells, on the other hand, it is worth to remembering ROS and free radicals could be also formed naturally as products of biochemical reactions involved in normal metabolic functions  and they also play important signaling functions in plants, thus they cannot be eliminated but only restricted.ortho- and para-nitrophenolates with sodium 5-nitroguaiacolate, are easily metabolized by plants into other phenolics which are involved in mitochondrial energy generating processes. Their action results also in low cytoplasm viscosity, which fosters translocation of all biosynthesis products. Moreover, diphenols are specific inhibitors of auxin oxidases so indirectly they have positive influence on this important phytohormone activity.Phenolic compounds, as effective antioxidants at low concentrations, influence lots of biochemical and physiological processes in plants . ComponeVicia faba root meristematic cells against copper stress (Cu2+). The surprisingly good effect of ATH influence was observed even after Cu2+ treatment. This may suggest that ATH not only significantly limits, but heals cytological disturbances caused by Cu2+ as well. Generally, ATH applied before and during Cu2+ stress protected root meristems against toxic heavy metal activity preventing genetic damage. The mechanisms of their action still need elucidation. Evidence suggests that polyphenols including flavonoids  can act in one or more ways: (i) modulating activation of metabolic mutagens, (ii) by stimulating antioxidant and/or detoxification enzymes, (iii) directly scavenging free radicals [(ii) and (iii) limit secondary oxidative stress therefore inhibit lipoprotein and lipid peroxidation], (iv) forming strong ligand complexes with ions of transition metals, such as Fe, Cu, and Mo . The phenomenon of DNA structure stabilization by ATH is also widely discussed in literature  embryo during seed germination. The majority of additional proteins were (i) energy metabolism enzymes, (ii) proteins involved in proteome plasticity via improving protein synthesis, folding, destination and storage, and – most importantly – (iii) defense, anti-stresses, and detoxifying proteins. This explains why the seeds hydroprimed with melatonin and the seedlings grown from them were stronger in comparison to the non-treated ones, and so quickly and efficiently adapted to changing environmental conditions. They were a priori prepared to cope with potential harmful conditions. These results partially explain how melatonin acts in plant stress defense and why various plant species rich in melatonin have shown higher capacity for stress tolerance  non-toxic, safe for animals and environment; (ii) easily and actively taken up by plants from environment; (iii) of natural origin or easily synthesized in laboratories; (iv) not expensive; (v) dissolved in different solvents: water, alcohols but also lipids – that facilitates the use of various application methods; (vi) easily penetrating cell compartments, (vii) it must improve plant resistance to adverse conditions and help generate tolerance to stresses.Many scientists as well as breeders consider new biostimulator searching and application as the most prospective and promising method to produce ecological crops, to protect the environment, and to support safety-food production.MP: work concept, the manuscript revising, and final approval of the version to be published. KS: drafting of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Research on pornography and its association with HIV-related sexual behaviours is limited in India. This study aims to examine the prevalence and correlates of viewing pornographic videos and examine its associations with HIV-related sexual risk behaviours among male migrant workers in India.Data were drawn from a cross-sectional survey conducted in 2007–08 across 21 districts in four states of India. Respondents included 11,219 male migrants aged 18 years or older, who had migrated to at least two places in the past two years for work. Bivariate and multivariate methods were used to examine the association between viewing pornography and HIV-related sexual risk behaviours.Two-fifths (40%) of the migrants had viewed pornographic videos in one month prior to the survey. Migrants aged 25–29 years, literate, unmarried and away from native village for more than five years were more likely to view pornography than their counterparts. Migrants who viewed pornographic videos were more likely to engage in paid  and unpaid sex , report inconsistent condom use in paid sex  and experience STI-like symptoms  than their counterparts.The findings regarding migrants' exposure to pornography and its linkage with high HIV risk behaviour suggest that the HIV prevention programmes for migrants need to be more innovative to communicate on the negative-effects of viewing pornography. More importantly, programmes need to find alternative ways to engage migrants in infotainment activities during their leisure time in an effort to reduce their exposure to pornographic videos as well as risky sexual behaviours. Recent evidence from India and elsewhere suggests that male migrants are at an increased risk of HIV infection Empirical research suggests that in conjunction with the above mentioned socio-cultural factors, there could be various other environmental and psycho-social factors that could influence individual attitudes and behaviour. Empirical research among adolescents and adults from the general population suggests that exposure to pornographic material influences an individual's sexual risk behaviour. A review of empirical research suggests that exposure to pornography influences sexual attitudes, moral values, and sexual activity individuals As male migrants are vulnerable to HIV risk Data for this study were drawn from a cross-sectional survey conducted in 2007–08 across 21 districts in four states of southern  and western (Maharashtra) India, identified as high epidemic states by the Indian National AIDS Control Organisation prior to the year 2005 A total of 11,635 eligible male migrant workers satisfied the inclusion criteria- age 18 years or older, having migrated to at least two places in the past two years for work- were selected for the cross-sectional survey. Of these, 145 (1.2%) men refused to be interviewed, and 271 (2.3%) men did not complete their interview and were thus excluded from the analyses, providing our final sample size of 11,219.Data were obtained through face-to-face interviews conducted in private locations close to the respondent's residence or workplace. Verbal consent was obtained from all respondents before being interviewed. Verbal consent was sought for two reasons: first, large proportions of male migrants were expected to be illiterates and cannot read and sign the consent form; second, no personal identifier or biological data were collected. The interviewers read the complete script of the consent form in to the respondent and explained if there was any doubt about any aspects of survey. For each respondent, a separate consent form was used and those who consented to be interviewed were asked to give their thumb impression on the consent form. Ethical approval for the study was obtained from the institutional review boards of the Population Council and the University of Manitoba, Canada.Respondents who had viewed either adult movies with sex content or blue films (using compact discs or shown in video parlours) in the one month prior to the survey were categorised as having exposure to pornographic videos (coded as 1); else considered as no exposure to pornographic videos (coded as 0). In this study, this variable was first used as a dependant variable to understand the predictors of viewing pornographic videos and then as an independent variable to examine the effect of viewing pornographic videos on HIV-related sexual risk behaviours.HIV-related sexual risk behaviours in the study were measured using the following indicators: paid sex (sex with a sex worker) and unpaid sex , engagement in anal/oral sex, inconsistent condom use, experience of STI-related symptoms and alcohol consumption prior to sex.All respondents were asked a question with dichotomous response categories  to examine whether they had sex with a sex worker in the 12 months prior to survey. A similar question was asked to examine if respondents had sex with a non-sex worker other than spouse (hereinafter referred to as non-sex worker) in the 12 months prior to survey to assess unpaid sex. Questions were also asked on the type of sex acts they engaged in the last time they had sex with these partners. Individuals who reported either engaging in anal or oral sex were considered to have engaged in anal/oral sex in the last sex. Inconsistent condom use was assessed separately for sex workers and non-sex workers. For each type of partners, respondents were asked about frequency of condom use  during sex in the past 12 months. Individuals who had “always” used condoms in the last 12 months were coded as 0 (consistent condom users) and the rest were coded as 1 (inconsistent condom users).The survey also collected information on self-reported STI symptoms. Participants were defined as having STI-like symptoms if they reported any of the following in the past 12 months: genital ulcers; swelling in groin area; itching in genital area; or frequent painful urination. To examine alcohol consumption prior to sex, a question with dichotomous response categories was asked to those who ever had sex.Data collected included the socio-demographic characteristics of migrants, including age, highest level of education completed, marital status including cohabitation status with spouse, income, ability to save money, living arrangement, and frequency of return to the native place (origin). These variables were used as independent variables while predicting the likelihood of exposure to pornographic videos and as covariates while predicting the risk associated with the exposure to pornographic videos for different HIV-related sexual risk behaviours.Univariate, bivariate and multivariate analyses were performed. Univariate analysis was used to describe the profile of the study population. Bivariate analysis was used to present the prevalence of exposure to pornographic materials by socio-demographic characteristics. A series of multiple logistic regression models were generated; first to examine the predictors of viewing pornographic videos and second to examine the effect of viewing pornographic videos on HIV-related sexual risk behaviours. In the first logistic regression analysis, viewing pornographic videos was considered as the dependent variable and socio-demographic characteristics of migrants were considered as independent variables. In the rest of the logistic regressions, viewing pornographic videos was the key independent variable whereas socio-demographic factors were used as covariates and indicators of HIV-related sexual risk behaviours were considered as dependent variables. Results were presented in the form of percentages, adjusted odds ratios (AOR) and their corresponding 95% confidence interval (CI). All the analyses were carried out using STATA version 12.1 .th) or above education. About half (51%) were currently unmarried and one-quarter (25%) of them were married and staying with their spouse. About one-third (34%) reported staying away from home overnight for work.Two-fifths (40%) of the migrants had viewed pornographic videos in the one month prior to the survey. The associations between viewing pornographic videos and HIV-related sexual risk behaviours are presented in The issue of pornography has received a great deal of attention among researchers over the years, both in developed and developing countries. In developed countries ample information is available on pornography and the pathways by which it affects sexual behaviour; however, such research is limited in India. To the best of our knowledge, this is the first study in its entirety to examine the prevalence of viewing pornography among male migrant workers in India. This study found that two-fifths of migrants had exposure to pornographic videos in the one month prior to survey, which is a little higher than one of the previous study among young males The study observed that male migrants aged 25–29 years were more likely to view pornographic videos as compared to their younger and older counterparts. This is contrary to studies in developed countries, which suggest that younger males, particularly adolescents were more likely to be view pornography. There could have been a possible under-reporting among younger migrants as viewing pornography is not socially accepted in India. Future research is required to confirm this finding. Moreover, migrant who were unmarried were more likely to view pornographic videos as compared to married ones. Interestingly, more than 90% of unmarried migrants were aged below 30 years. The study also found that the duration of migration is positively associated with exposure to pornographic videos. This finding supports previous research on how long-duration migration keeps migrant men away from their families for long periods of time; and the living arrangements and peer dynamics in such instances make them engage in risky leisure activities such as gambling, visiting bars or pubs, visiting brothels and watching pornographic videos The study findings shows that viewing pornographic videos can increase the likelihood of engaging in HIV risk behaviours among male migrants. Migrants who had viewed pornographic videos in the past one month were more likely to report paid sex  and unpaid sex  and reported practicing risk sexual practices such as anal and/or oral sex than others. Past research from developed countries has also suggested that exposure to pornography is associated with increased acceptance of premarital and extramarital sex including paid sex The study finding revealed an interesting pattern in condom use behaviour. Inconsistent condom use by migrants is relatively higher in unpaid sexual relationships than in paid sex. Further, inconsistent condom use with female sex workers was higher among those who viewed pornography as compared to those who did not. However, a reverse relationship was observed with regard to inconsistent condom use in unpaid sex. The increasing proportion of migrants reporting inconsistent condom use with female sex workers reflects the influence of exposure to pornographic videos. In most of the pornographic videos, condoms are rarely used, which could have influenced the behaviour of individuals who are exposed to these This study also found that migrants who had viewed pornographic videos consumed alcohol prior to sex. Consumption of alcohol prior to sex is a well-recognised factor that can increase HIV risk multiple times. Empirical research has linked alcohol consumption prior to sex to increased HIV risk behaviour. Based on findings from this study, one can suggest that individuals may be adopting such behaviour due to their exposure to pornography. Pornographic videos, where alcohol is usually shown to be a stimulator before sex, could have guided a certain section of migrants to practice such behaviour in their sexual life as well. A significantly higher proportion of male migrants reported experience of STI-like symptoms in the 12 months prior to the survey, similar to findings from other studies examining the effect of pornography on STIs Although the study findings offer new insights in a little-researched area in India, these findings should be viewed in light of certain limitations. First, data were collected in a cross-sectional survey and hence, while associations between exposure to pornographic videos and HIV-related sexual risk factors are evident, the cause-effect relationship between them is difficult to establish. Second, the indicators used in this study relied on self-reports and there could be a chance of social desirability bias in reporting. The potential for social desirability influences were minimised by assuring participant confidentiality and conducting interviews in private locations without any other person's presence. Significant rates of high risk sexual behaviour were reported by participants, which suggest that they were generally honest in their responses. Third, our measure of exposure to pornography was associated with increased sexual risk behaviour; however, more detailed measures assessing pornography exposure are needed to fully explain this line of research. Future research studies should examine other dimensions of exposure to pornography, such as time spent viewing pornography, frequency of exposure, reasons for exposure, context of use, and norms and attitudes towards gender and sex. Fourth, we measured exposure to pornography only if respondents had watched adult movies or blue films. However, there could be several other types of pornographic materials, such as magazines, internet and books, which were not considered in this study. Fifth, the survey did not collect information on sexual attitudes and beliefs and therefore, we could not examine how viewing pornography influences migrants' attitudes and beliefs. We recommend that future research should collect these information along with behaviour data to draw more meaningful conclusions. Finally, this study was conducted among male migrants and hence, the findings may not be generalised to the general population in India. More research is required among the general population to establish if the findings of this study holds true. Nevertheless, the study findings are important from the point of view of India's HIV prevention programme.Despite these study limitations, the findings of this study have several important programmatic implications. Even though pornography is illegal in India, the study findings reveal that a significant proportion of migrants have access to pornographic movies, and those exposed to pornographic videos have higher sexual risk behaviours. These results suggest the need for designing specific communication messages that focus on the need for safe sex in all relationships even though they are not shown in pornographic videos. Communication materials should also include the messages on negative temptations that can come post-pornography viewing, and its linkages with risky behaviours including consumption of alcohol prior to sex, and visits to sex workers, and unsafe sex. It may also be helpful to create infotainment activities for migrants, so that in their leisure time, they can get themselves engaged in these activities and get educated as well as entertained. Moreover, HIV prevention programmes while discussing issues of pornography should prioritise migrants who are middle aged, educated, currently unmarried, and staying away from native place for longer duration.In conclusion, this is the first study to provide evidence on the relationship between exposure to pornography and HIV-related sexual risk behaviours among male migrants in India. Two in five male migrants have viewed pornography. The study demonstrates a positive relationship between viewing pornography and extra- and pre-marital sex. Also, the study notes that inconsistent condom use with paid partners is higher among migrants viewing pornography than their counterparts. Findings of this study suggest that there is a need for HIV prevention education addressing issues related to the negative effects of viewing pornography.


Sir,We would like to present an idiopathic sigmoid colon perforation revealed with a rare manifestation of pneumoscrotum. A forty two days old boy was referred to us because of agitation, progressive abdominal distention and swollen scrotum . There w On physical examination, the infant had tachycardia and tachypnea. His abdomen had distention but was soft and lax, and his scrotum had swelling with red skin that led us into a consideration of strangulated inguinal hernia. Portable CXR was normal but plain abdominal x-ray three hours later revealed bowel distention, specially in the distal colon, with free intra-peritoneal gas (Rigler's sign). A small An urgent ultrasound of the scrotum revealed only reverberation artefact, consistent with gas. Both testes were normal. An exploratory laparotomy was done through midline incision. The peritoneum was grossly contaminated and there was perforation of the descending and sigmoid colon on the antimesenteric side . Rest of the large and small bowel was normal and there were not any vesiculation or ulceration and the mucosal surfaces were intact. The mucosal biopsy specimen from the edge of perforation had a normal appearance under light microscopy, and there were not any characteristic CMV inclusions or HSV cytopathic changes. However, we had not immunohistochemistry, FISH, and PCR in our center to detect latent infection. Also multiple distal biopsies revealed normal ganglion cells and Hirschprung's disease was excluded. The incidence of spontaneous colonic perforation is extremely rare. As in one study, it was reported only ten cases, seven of ten in very-low-birth-weight (VLBW) infants and three of ten in term or near-term neonates (one with Hirschsprung disease and the two cases without clear etiology during 10 years (2000-2009), there are few reported pneumoscrotum due to procedural or pathologic processes[4]. We think that our patient was the first case which reported spontaneous colonic perforation with unknown etiology, which presented with pneumoscrotum during the last decades. Since 1912 (the first reported case) [5]. Endoscopic (upper and lower) and laparoscopic procedures were the second and third most common causes, respectively Therefore, as mentioned above, the finding of gas in the scrotal sac may be an early sign of a life-threatening condition like visceral perforation or may represent an incidental finding associated with more benign conditions like laparoscopic procedures.[9], this case presentation reminds us that eventhough pneumoscrotum is a benign, rare condition, its mere presence should signal the possibility of a severe, life-threatening disease process within the peritoneum like bowel perforation or retroperitoneum like pancreatic or renal abscess.  In conclusion, although a combination of free abdominal gas and distended abdomen usually make the diagnosis evident and surgical intervention should be the rule


Childhood maltreatment has been shown to increase the risk of a range of psychiatric disorders including substance use disorders (SUDs) and is associated with the onset, course and severity of illness. We review the evidence for alterations in brain structure and neurocognitive processing in individuals who have experienced childhood maltreatment, focusing specifically on changes related to reward processing, executive functioning and affect processing. Changes in these neurocognitive systems have been documented in adults presenting with SUDs, who are typically characterized by heightened subcortico-striatal responses to salient stimuli and impairments in fronto-cingulate regulation. Maltreatment-specific effects in these processing domains may account for the particularly severe clinical presentation of SUDs in adults with histories of maltreatment in childhood. The findings are considered in relation to the theory of latent vulnerability, which contends that alterations in these neurocognitive systems may reflect calibration to early risk environments that in turn increases the risk of developing of SUDs later in life. Childhood maltreatment, including physical and emotional neglect, has been identified as a major risk factor for a variety of negative outcomes spanning the domain of mental and physical health as well as economic attainment . SpecifiThe theory of latent vulnerability has been proposed to account for the link between maltreatment and psychiatric disorder ••. AccorThis notion of latent vulnerability provides a helpful framework within which to study substance use disorders (SUDs), one of the most robust psychiatric disorders associated with childhood maltreatment ••, 7. SUThe ability to seek out stimuli that have incentive salience such as appetitive cues (e.g. food and sex) or social rewards (e.g. smiles and praise) governs most motivational behaviour in animals and humans. The neural systems underlying reward processing and motivational behaviour include the ventral striatum , the anterior cingulate cortex (ACC), the medial prefrontal cortex ) and the amygdala, jointly forming the mesocorticolimbic reward circuitry. Alterations in the reward system can interfere with an individual’s ability to goal-direct their behaviour and decision-making, and reduced or altered reward processing is a hallmark feature of maltreatment-related psychopathology such as major depression, PTSD and especially substance abuse –16. IndeThere is an established relationship between stress and altered reward sensitivity in the animal literature showing that chronically stressed animals show a reduced behavioural motivation to obtain appetitive food cues, suggesting hyposensitivity to reward following stress . The fewCollectively, these findings suggest that stress-related alterations in the subjective and neural processing of reward anticipation may follow experiences of childhood maltreatment, with important implications for decision-making and the ability to initiate goal-directed actions. While these changes may potentiate the development of SUDs later in development, the evidence at the current time is preliminary in nature. Next, we review studies that have explicitly investigated reward function in individuals presenting with SUDs with and without experiences of childhood maltreatment.It is now well established that individuals who abuse substances are characterized by altered brain functioning in the reward system, specifically within the fronto-striatal and fronto-limbic pathways, consistent with behavioural evidence of altered motivational behaviour and impulsivity in response to drug-related cues . SpecifiThe role of developmental timing of adversity was highlighted in a recent longitudinal study with young adult males by Casement and colleagues . The autThree main conclusions may be drawn from the extant literature. First, maltreatment in childhood is associated with behavioural changes as well as alterations in the brain structure and function that are consistent with altered reward processing. Second, maltreatment-related changes in reward processing are remarkably consistent with those reported in adults presenting with SUDs, typically showing blunted responses to natural rewards. Finally, recent studies have reported maltreatment-specific effects on reward processing, which may account for the particularly severe clinical presentation of SUDs in adults with histories of maltreatment in childhood. Important limitations of the studies discussed above include the uniform use of monetary reward cues to index the reward system along with the frequent investigation of all-male samples with a heterogeneous range of early adverse experiences. An important task for future research will be to extend the investigation of reward processing to include female samples as well as other forms of reward, in particular social reward.Deficits in executive functioning and cognitive control associated with childhood maltreatment are important to consider in the study of SUDs given that impairments in impulse control and behavioural inhibition have consistently been identified as predictors for SUDs , 32. SpeThere is now robust evidence that executive functioning deficits characterize children and adolescents who have experienced childhood abuse and neglect, including in relation to working memory, cognitive control and emotion regulation ••, 37–40Structural MRI studies investigating adults who experienced maltreatment as children frequently report smaller prefrontal grey matter volumes, specifically in the dorsolateral and medial prefrontal cortex involved in cognitive control and emotion regulation, respectively , 44. SimTo date, only a small number of studies have directly investigated the functional neural correlates underlying cognitive and emotional control in individuals with maltreatment experiences. In a study of adult women with childhood experiences of sexual and physical abuse, Cromheeke and colleagues  investigCollectively, these preliminary findings point to medium- and long-term influences of maltreatment experiences on emotion regulation and cognitive control of emotion. While research into the structural correlates of executive functioning and emotion regulation have reported robust alterations in prefrontal cortical architecture, functional brain imaging studies of these domains of functioning in maltreated individuals remains relatively sparse. It is noteworthy that the same brain regions associated with emotional and cognitive control in maltreated populations overlap with those identified as potential predictors of SUDs.The study of affect processing in childhood maltreatment has increasing relevance in the understanding of the development of SUDs, since limited, but increasing evidence points towards alterations in affect-related processing including the perception, experience and regulation of emotions in SUDs . ChildhoMedial temporal lobe structures such as the amygdala play a key role in the neural processes underlying salience detection, the ability to process negative information and learn stimulus-outcome associations. Findings of structural alterations in amygdala volume in individuals who experienced childhood maltreatment have been mixed, some suggesting no differences in amygdala volume in children with maltreatment-related PTSD relative to non-maltreated peers and others suggesting increased amygdala volumes in previously institutionalized adoptees , 62. TheBy contrast, there is an emerging consensus that childhood maltreatment has a significant impact on amygdala functioning. Several fMRI studies conducted with children who have experienced maltreatment have now reported a heightened amygdala response to angry faces relative to non-maltreated peers , 64–66 .To date, only few studies have investigated affect processing in individuals with SUDs with a history of childhood maltreatment, which is surprising given the anxiolytic potential of some substances to blunt affective reactivity, particularly to threat . Indeed,Findings from fMRI studies investigating affect processing in children with a history of childhood maltreatment and individuals with SUDs have demonstrated both behavioural hypervigilance and heightened amygdala reactivity to threat-related cues. Preliminary evidence from individuals with SUDs and a history of childhood maltreatment points towards similar processes by which conditioned stimulus associations may influence the salience of drug-related stimuli and the degree of the arousal response. Importantly, considering the anxiolytic effects of alcohol on anxiety levels and amygdala reactivity, sustained drug abuse in maltreated individuals could be understood in part as a way of reducing negative affect and heightened arousal, consistent with a self-medication account .The review of the present literature demonstrates a growing empirical basis to infer a link between the experience of childhood maltreatment and an elevated risk of developing SUDs later in life. Such a putative link may be mediated by alterations in those neurocognitive systems implicated in reward processing, cognitive control and affect processing given that these systems are atypical both in those who have experienced maltreatment in childhood and in those who present with SUDs. It has been suggested that calibration of each of these systems may embed a degree of latent vulnerability, increasing the risk of future psychopathology, including SUDs. We speculate that heightened subcortical and striatal activity to salient cues along with altered capacities for affect regulation and reasoning in maltreated individuals may increase risk for SUDs in three possible ways: first, by altering the balance and strength of responses to drug and natural reward cues, enhancing the former while attenuating the latter; second, by compromising the ability of the individual to regulate their emotional and behavioural responses increasing the likelihood of substance abuse initiation; and third, by increasing the likelihood of self-medication as a result of maltreatment-related increases in internal aversive states combined with impairments in regulatory control.However, a number of limitations constrain inferences that can be made in this regard. Firstly, most of the evidence reviewed here is cross-sectional making it difficult to disentangle the effects of childhood maltreatment and SUD on brain structure and function. While only longitudinal studies can help inform causal inferences, recent studies have suggested that childhood maltreatment has independent effects on brain structure above and beyond SUD ••, 74. FIn a similar vein, any comprehensive account linking maltreatment and SUDs needs to consider possible genetic factors, given that SUD is highly heritable . While