Search

Background: Research on suicidality in low to middle-income countries is scarce. We addressed this issue by investigating suicidality in a cross-national college student samples from 11 predominantly low to middle-income majority Muslim countries., Methods: The sample consisted of 7427 college students (56% female) who reported to be affiliated with Islam. Data on self-construal, social support, negative life-events, acceptability of suicide, suicidal ideation, and suicide attempts were collected with self-administered questionnaires., Results: Acceptability of suicide and the experience of negative life-events were positively, and perceived social support was negatively associated with suicidal ideation. Interdependent self-construal was negatively related to the acceptability of suicide and positively associated with perceived social support, implying a negative indirect effect on suicidal ideation although its direct effect was positive. The number of negative life-events was the strongest positive predictor of ever attempting suicide. The interdependent self-construal moderated the association of negative life-events with suicide attempts., Limitations: Cross-sectional and self-report nature of the study were its major limitations. Participants may have suppressed their responses about suicide because of religious and legal reasons., Conclusion: Remarkable similarities across 11 country samples emerged in the linkages between cultural and interpersonal factors with suicidality. Our findings highlight the value of a nuanced approach to suicidality, that can recognize the differences in the processes associated with suicidal ideation and suicide attempts, as well as the need to consider the interplay of a broad range of personal, interpersonal, and cultural influences., (Copyright © 2021. Published by Elsevier B.V.)

Early childhood trauma can have adverse effects on brain development. This results in higher rates of mental health and medical problems in adults. Unfortunately, psychiatry trainees are not adequately trained in dealing with trauma survivors. Hence, we implemented an online trauma curriculum and assessed its efficacy. Socratic methods of teaching, flipped classroom approach, brainstorming, role play, and case-based discussions were utilized. Participants were able to exhibit good knowledge and clinical skills as assessed through summative assessment and communication skills assessment. This curriculum showed online training can help with clinical skill development along with improving knowledge when dealing with trauma survivors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: This study translated and validated the Urdu version of the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) and Brain Module (QLQ-BN20) amongst patients with primary brain tumors (PBT) in Pakistan, and assessed the correlation of QoL with resilience, depression, and anxiety., Methods: Translation of the EORTC QLQ-C30 and QLQ-BN20 was performed as per EORTC guidelines. A survey comprising of Urdu translations of EORTC QLQ-C30, QLQ-BN20, Wagnild and Young Resilience Scale (RS-14) and Hospital Anxiety and Depression Scale was administered to patients with PBT at a tertiary care hospital in Pakistan. Reliability (via Cronbach alpha), content validity index (CVI) scores, construct validity, and inter-scale correlations were assessed., Results: Our sample consisted of 250 patients with PBT, most commonly glioma (46.8%) and meningioma (21.2%). All patients were able to understand the Urdu translations. The Cronbach alphas for the QLQ-C30 and the QLQ-BN20 were 0.860 and 0.880, respectively. The CVI scores for clarity and relevance were high for both the EORTC QLQ-C30 (0.98 and 0.96, respectively) and the QLQ-BN20 tool (0.81 and 0.95, respectively). The global QoL domain (EORTC QLQ-C30) showed significant positive correlations with resilience (r = 0.422), and significant negative correlations with depression (r =  - 0.541) and anxiety (r =  - 0.502). Strong inter-scale correlations were observed between physical functioning and insomnia (r =  - 0.690) and role functioning and insomnia (r =  - 0.641)., Conclusion: Our study confirms the Urdu versions of the EORTC QLQ-C30 and QLQ-BN20 as valid clinical tools for the measurement of QoL in primary brain tumors patients within the cultural and socioeconomic context of Pakistan., (© 2021. The Author(s).)

Trauma is a major global health problem. Currently a trauma curriculum, from a psychological perspective, has not been uniformly incorporated in medical education. Nonetheless, professionals from various medical disciplines have an integral role in providing trauma care to survivors. The current COVID-19 pandemic only underscores the relevance and urgent need of this training, as studies show an uptick in mental health disorders due to this trauma. This article will present a discussion on the need for trauma curriculum for health care professionals, using information gained through trauma informed care workshops for healthcare personnel at Aga Khan University Hospital Pakistan., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: The study aimed to assess resilience and its associated factors in head and neck cancer patients, post-treatment in a low middle income country (LMIC) such as Pakistan., Methods: An analytical cross-sectional study was conducted from November 2019 to May 2020 among head and neck cancer patients aged at least 18 years at the largest private tertiary care hospital, in Karachi, Pakistan. Information regarding their resilience scores was collected through Wagnild and Young's Resilience scale that comprises of 14 items (RS-14). Moreover, depression and anxiety were also assessed via Hospital Anxiety and Depression Scale (HADS) and social support was assessed by Enriched Social Support Instrument (ESSI)., Results: The data was analyzed by linear regression modeling. Unadjusted and adjusted beta coefficients with 95% CI were reported. A total of 250 head and neck cancer patients were recruited, 79% of them were males. Mean age of the patients was 51.59 years with 93% having high social support and only 8% having severe depression and 3% having severe anxiety. After adjusting for the covariates in multivariable analysis resilience was associated with severe depression (- 17[- 20.98,-12.93]) or borderline depression (- 4[- 8.41,-0.39]), severe anxiety (- 11 [- 17.88,-4.18]), low social support (- 6[- 9.62,-1.71]), having family members of > 6 in the household (- 2[- 4.31,-0.29), smokeless tobacco users post- treatment (10[5.79, 14.45]), and those who underwent tracheotomy (- 4[- 7.67,-0.21]). There was a significant interaction between education and role in the family (decision maker)., Conclusion: In Pakistan, a South Asian LMIC, collectivist culture prevails, family ties are greatly promoted thus resilience and social support is highly prevalent in head and neck cancer patients resulting in lower prevalence of depression and anxiety. Our study highlights that higher resilience is prevalent among small families less than six members, as the welfare of the individual is prioritized over multiple needs of the family. Formal Education and role in household/decision making power are effect modifiers in our study, demonstrating its protective effect on the mental health of head and neck cancer patients. High resilience scores were reported among current smokeless tobacco users as compared to quitters post treatment. Resilience-building interventions should be formulated to aid head and neck cancer patients to cope with the disease and its sequel., (© 2021. The Author(s).)

Neuromodulation mediated by synaptically released endogenous transmitters acting in G-protein-coupled receptors (GPCRs) is slow primarily because of multistep downstream signaling. What is less well understood is the spatial and temporal kinetics of transmitter and receptor interaction. The present work uses the combination of the dopamine sensor, dLight, to detect the spatial release and diffusion of dopamine and a caged form of a D2-dopamine receptor antagonist, CyHQ-sulpiride, to rapidly block the D2 autoreceptors. Photoactivation of the CyHQ-sulpiride blocks receptors in milliseconds such that the time course of dopamine/receptor interaction is mapped onto the downstream signaling. The results show that highly localized release, but not dopamine diffusion, defines the time course of the functional interaction between dopamine and D2 autoreceptors, which determines downstream inhibition., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To explore healthcare provider's perspectives and experiences of the barriers and facilitators to treat and manage COVID-19 cases., Design and Setting: We conducted an exploratory qualitative study using a purposive sampling approach, at a private tertiary care teaching hospital in Karachi, Pakistan. Study data were analysed manually using the conventional content analysis technique., Participants: Key-informant interviews (KIIs) were conducted with senior management and hospital leadership and in-depth interviews (IDIs) were conducted with front-line healthcare providers., Results: A total of 31 interviews (KIIs=19; IDIs=12) were conducted, between April and May 2020. Three overarching themes emerged. The first was 'challenges faced by front-line healthcare providers working in COVID-19 wards. Healthcare workers experienced increased anxiety due to the fear of acquiring infection and transmitting it to their family members. They felt overwhelmed due to the exhaustive donning and doffing process, intense work and stigmatisation. The second theme was 'enablers supporting healthcare providers to deal with the COVID-19 pandemic'. Front liners pointed out several enabling factors that supported hospital staff including a safe hospital environment, adequate training, a strong system of information sharing and supportive management. The third theme was 'recommendations to support the healthcare workforce during the COVID-19 crisis'. Healthcare workers recommended measures to mitigate current challenges including providing risk allowance to front-line healthcare providers, preparing a backup health workforce, and establishing a platform to address the mental health needs of the healthcare providers., Conclusion: This study provides an initial evidence base of healthcare providers' experiences of managing patients with COVID-19 in the early stage of the pandemic and highlights measures needed to address the encountered challenges. It offers lessons for hospitals in low-income and middle-income countries to ensure a safe working environment for front-line workers in their fight against COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We report a photoactivatable agonist of the AMPA subtype of ionotropic glutamate receptors, TMP-CyHQ-AMPA, which was designed to study the fast excitatory transmission between neurons. Upon visible light excitation, TMP-CyHQ-AMPA quantitatively released AMPA in high quantum yield on an ultra-short timescale. Intriguingly, the photolyisis can be carried out using 2-photon excitation (2PE) with remarkable efficiency, giving a two-photon uncaging action cross section (δu) value of 1.71 GM. TMP-CyHQ-AMPA is soluble in pysiological buffer and no hydrolysis was detected in the absence of light. Molecular docking experiments indicated that the photocaging strategy abolishes the affinity of AMPA for the GluR2 receptor and no GABAergic effects (as commonly observed in caged glutamates) are expected. TMP-CyHQ-AMPA can be used to study glutamatergic neuronal transmission with exceptional spatial-temporal resolution in complex tissue preparations.

A dopamine D2 receptor mutation was recently identified in a family with a novel hyperkinetic movement disorder. Compared to the wild type D2 receptor, the novel allelic variant D2-I 212 F activates a Gα i1 β 1 γ 2 heterotrimer with higher potency and modestly enhanced basal activity in human embryonic kidney (HEK) 293 cells and has decreased capacity to recruit arrestin3. We now report that omitting overexpressed G protein-coupled receptor kinase-2 (GRK2) decreased the potency and efficacy of quinpirole for arrestin recruitment. The relative efficacy of quinpirole for arrestin recruitment to D2-I 212 F compared to D2-WT was considerably lower without overexpressed GRK2 than with added GRK2. D2-I 212 F exhibited higher basal activation of Gα oA than Gα i1 but little or no increase in the potency of quinpirole relative to D2-WT. Other signs of D2-I 212 F constitutive activity for G protein-mediated signaling, in addition to basal activation of Gα i/o , were enhanced basal inhibition of forskolin-stimulated cyclic AMP accumulation that was reversed by the inverse agonists sulpiride and spiperone and a ∼4-fold increase in the apparent affinity of D2-I 212 F for quinpirole, determined from competition binding assays. In mouse midbrain slices, inhibition of tonic current by the inverse agonist sulpiride in dopamine neurons expressing D2-I 212 F was consistent with our hypothesis of enhanced constitutive activity and sensitivity to dopamine relative to D2-WT. Molecular dynamics simulations with D2 receptor models suggested that an ionic lock between the cytoplasmic ends of the third and sixth α-helices that constrains many G protein-coupled receptors in an inactive conformation spontaneously breaks in D2-I 212 F. Overall, these results confirm that D2-I 212 F is a constitutively active and signaling-biased D2 receptor mutant and also suggest that the effect of the likely pathogenic variant in a given brain region will depend on the nature of G protein and GRK expression.

Objectives: This study assessed resilience in brain tumor patients at a tertiary care hospital in Pakistan (a lower middle-income country; LMIC) and explored its relationship with patients' sociodemographic factors, clinical characteristics, social support, and mental health., Methods: A cross-sectional survey was conducted amongst adult (≥18 years) patients with brain tumor at the Aga Khan University Hospital, Pakistan. Resilience was assessed by Wagnild and Young's Resilience Scale, and patients' psychosocial characteristics by the Hospital Anxiety and Depression Scale and the Enriched Social Support Instrument., Results: A total of 250 patients were included (mean age: 44 years; 68% males), with majority (97.6%) having high social support and only 4.4% and 2% having symptomatic depression and anxiety, respectively. On multivariable linear regression adjusted for covariates, lower resilience was associated with not being involved in household decision-making (Adjusted Beta Coefficient: 4.58 [95% Confidence Interval:-7.59, -1.56]), not currently working (-2.80 [-4.61, -0.99]), undergoing multiple neurosurgical interventions such as tumor biopsies or resections (-8.64 [-13.11, -4.16]), receiving chemotherapy (-5.17 [-9.51, -0.83]) or combination adjuvant therapy (-2.91 [-5.14, -0.67]), low social support (-7.77 [-13.73, 1.81]), mild depression (-13.00 [-17.00,-8.99]) or symptomatic depression (-19.79 [-24.69, -14.89]), and mild anxiety (-4.24 [-7.98, -0.50])., Conclusion: Our study highlights the function of familial/household role and working status in mediating resilience, and demonstrates the well-known protective effect of resilience for mental health in brain tumor patients in Pakistan, a South-Asian LMIC. These findings are of clinical relevance with regards to the development of culture-specific evidence-based resilience-building interventions that may help patients with brain tumors to cope with the psychological distress of cancer., (© 2021 John Wiley & Sons Ltd.)

Aims: Discontinuation or non-publication of trials may hinder scientific progress and violates the commitment made to research participants. We sought to identify the prevalence of discontinuation and non-publication of heart failure (HF) clinical trials., Methods and Results: We conducted a cross-sectional search of ClinicalTrials.gov to identify all completed and discontinued HF clinical trials. We limited our search to only include trials that were completed by 31 December 2017. Trials were investigated to identify reasons for discontinuation. Informative termination was defined as trial termination due to safety or efficacy concerns. Data pertaining to the trial phase, funding, intervention, enrolment, and trial completion date were extracted for each trial. A total of 572 trials were included. Of these, 21% (n = 118) were discontinued before completion. Patient accrual was the most frequently cited reason (n = 42; 36%) for trial discontinuation, followed by informative termination (n = 16; 14%) and funding (n = 14; 12%). Overall, 24 780 patients were enrolled in trials that were terminated. Of trials that were completed and not terminated, nearly one-third (n = 131/454; 29%) were not published. Seventy-nine (24%) trials were published within 12 months, 192 (59%) within 24 months, and 252 (78%) trials within 36 months., Conclusions: Discontinuation and non-publication of HF trials is common. This raises ethical concerns towards participants who volunteer for research and are exposed to potential risks, inconvenience, and discomfort without furthering scientific progress., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background : Children with disabilities are more likely to experience violence or injury at school and at home, but there is little evidence from Central Asia. Objective : To describe the prevalence of disability and associations with peer violence perpetration and victimization, depression, corporal punishment, school performance and school attendance, among middle school children in Pakistan and Afghanistan. Method : This is a secondary analysis of data gathered in the course of evaluations of interventions to prevent peer violence conducted in Pakistan and Afghanistan as part of the 'What Works to Prevent Violence against Women and Girls Global Programme'. In Pakistan, the research was conducted in 40 schools, and disability was assessed at midline in 1516 interviews with Grade 7s. In Afghanistan, the data were from the baseline study conducted in 11 schools with 770 children. Generalized Linear Mixed Modeling was used to assess associations with disability. Results : In Afghanistan, the prevalence of disability was much higher for girls (22.1%) than boys (12.9%), while in Pakistan 6.0% of boys and girls reported a disability. Peer violence victimization was strongly associated with disability in Afghanistan and marginally associated in Pakistan. In Pakistan, perpetration of peer violence was associated with disability. In both countries, disability was significantly associated with higher depression scores. Food insecurity was strongly associated with disability in Afghanistan. Conclusion : Disability is highly prevalent in Afghanistan and Pakistan schools and this is associated with a greater risk of experiencing and perpetrating peer violence. It is important to ensure that all children can benefit from school-based prevention interventions.

Background: Peer violence is common globally, but a little researched topic in low-and middle-income countries. This study presents the evaluation of a two-year randomized controlled trial of a structured play-based life-skills intervention implemented in schools in Hyderabad, Pakistan., Objective: To determine the impact of the intervention on school-based peer violence (victimization and perpetration) and depression among school children., Methods: 40 single-sex public schools were randomized into two study arms (20 per arm 10 of each sex). A total of 1752 grade 6 students (929 from intervention and 823 from control schools) were enrolled in the trial. The two-year intervention was a biweekly structured game led by a coach followed by critical reflection and discussion for 30 minutes. Primary outcomes (exposure to peer violence exhibited through victimization and perpetration and depression) were evaluated using generalized linear-mixed models., Results: Of the enrolled children (N = 1752) 91% provided data for analysis. There were significant decreases in self-reported peer violence victimization, perpetration and depression. For peer violence victimization, the reductions in the intervention and control arms were: 33.3% versus 27.8% for boys and 58.5% versus 21.3% for girls. For peer violence perpetration, the reductions were: 25.3% versus 11.1% for boys and 55.6% versus 27.6% for girls in the intervention and control arms, respectively. There were significant drops in mean depression scores (boys 7.2% versus 4.8% intervention and control and girls 9.5% versus 5.6% intervention and control)., Conclusion: A well-designed and implemented play-based life-skills intervention delivered in public schools in Pakistan is able to effect a significant reduction in peer violence.

Objective: The study investigated the associations of religiosity, religious coping and suicide acceptance to suicide ideation and attempts in 7427 young adults affiliating with Islam from 11 Muslim countries., Method: A self-administered questionnaire was used to collect the data. We used F and χ2 tests and correlation analyses to report descriptive statistics. Multi-group path models with (i) a zero-inflated Poisson distribution and, (ii) a Binomial distribution were used to model the number of occurrences of suicidal ideation, and occurrence of a suicide attempt, respectively., Results: Religiosity was negatively associated with acceptability of suicide, but it was positively related to punishment after death across the 11 countries. Religiosity was negatively associated with ever experiencing suicidal ideation, both directly and indirectly through its association with attitudes towards suicide, especially the belief in acceptability of suicide. Neither positive nor negative religious coping were related to suicidal ideation. However, religiosity was negatively related to suicide attempts among those who experienced suicidal ideation at least once. This association was mediated through the belief in acceptability of suicide and religious coping. Negative religious coping was positively associated with suicide attempts probably because it weakened the protective effects of religiosity., Conclusions: Findings from this study suggest that the effects of religiosity in the suicidal process operate through attitudes towards suicide. We therefore conclude that clinical assessment as well as research in suicidology may benefit from paying due attention to attitudes towards suicide., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: In Pakistan there is a dire need to explore the quality of life in infertile males and females and its undesirable psychological outcomes. This, study aimed to compare the quality of life (QoL) of males and females visiting an infertility centre for treatment and to assess its association with resilience, depression, and other socio-demographic factors., Methods: An Analytical Cross-Sectional study was conducted amongst infertile males and females at the Australian Concept Infertility Medical Centre (ACIMC), Karachi, Pakistan. The non-probability (purposive) sampling strategy was used to recruit the participants. The sample size was 668. Data was analysed using STATA version 12. FertiQoL tool, Beck II Depression Inventory Tool and Resilience Scale 14 (RS-14) were used for assessing the quality of life, depression and resilience respectively of infertile patients., Results: Total 668 infertile patients, 334 males and 334 females participated in the study. The mean age was 35.53 ± 6.72, among males, and 30.87 ± 6.12 among females. The mean resilience scores were significantly higher among males, (77.64 ± 8.56), as compared to females (76.19 ± 8.69) (95% CI; - 2.757, - 0.1347). However, a significantly higher proportion of females were depressed (13.8%) as compared to males (6%). The mean QoL scores for the general health domain, emotional domain, mind and body domain, and relational domain, and the total QoL were significantly higher in males as compared to females (p value< 0.001); however, QoL for the social domain was not significantly different in both the groups. On multivariable linear regression resilience and depression among males had a significant association with QoL, after adjusting for the covariates educational status, monthly income, and number of friends. Similar association was observed among females after adjusting for the covariate monthly income only., Conclusion: Fertility related QoL of men and women has a significant association with no formal education, number of friends, income, depression and resilience. Therefore, health care professionals in the field of infertility must be adequately trained to respond to the needs of individuals going through these psychological problems.

Objective: The study aimed to assess the need of mental wellbeing services for post graduate medical (PGME) trainees working at the Aga Khan University Hospital in Karachi, Pakistan., Methods: A cross-sectional study was conducted among all PGME trainees working at Aga Khan University Hospital in Karachi, Pakistan. The study questionnaire was developed by the team of investigators. The data collection was done through online survey from April 2019 to May 2019 and it was analyzed using descriptive and inferential analyses., Results: Out of total 623 PGME trainees, 334 trainees completed the online survey (response rate of 53.61%). A total of 292 participants (87.4%) perceived a need for mental health services. The major stressors identified were increase work hours (77.8%), excessive workload (75.1%), and difficulty balancing between work and personal life (72.8%). The perceived obstacles of utilizing mental services included lack of protected time (69.8%), fear of consequences (36.8%), lack of confidentiality (36.5%), and stigma (32.9%). The study participants indicated various suggestions to reduce their stressors such as separate relaxation space in hospital (91.3%), appreciation gestures like encouraging emails (65%), mentoring programs (43.4%), and regular surveys about resident needs (39.8%)., Conclusion: It is evident that innovative strategies to address trainees' mental health needs, looking at limitations of developing countries like Pakistan with large population and limited resources, need to be explored., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© International Association of Medical Science Educators 2020.)

The COVID-19 pandemic has overwhelmed hospitals all over the world. To reduce the risk of transmission of COVID-19 and meet the increasing mental health demands due to this trauma, psychiatry outpatient services have gone online in various countries. We describe steps taken at a tertiary care hospital in Karachi, Pakistan, to start these services during this pandemic. We also discuss the obstacles faced. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Stress-induced changes to the dendritic architecture of neurons have been demonstrated in numerous mammalian and invertebrate systems. Remodeling of dendrites varies tremendously among neuron types. During the stress-induced dauer stage of Caenorhabditis elegans, the IL2 neurons arborize to cover the anterior body wall. In contrast, the FLP neurons arborize to cover an identical receptive field during reproductive development. Using time-course imaging, we show that branching between these two neuron types is highly coordinated. Furthermore, we find that the IL2 and FLP arbors have a similar dendritic architecture and use an identical downstream effector complex to control branching; however, regulation of this complex differs between stress-induced IL2 branching and FLP branching during reproductive development. We demonstrate that the unfolded protein response (UPR) sensor IRE-1, required for localization of the complex in FLP branching, is dispensable for IL2 branching at standard cultivation temperatures. Exposure of ire-1 mutants to elevated temperatures results in defective IL2 branching, thereby demonstrating a previously unknown genotype by environment interaction within the UPR. We find that the FOXO homolog, DAF-16, is required cell-autonomously to control arborization during stress-induced arborization. Likewise, several aspects of the dauer formation pathway are necessary for the neuron to remodel, including the phosphatase PTEN/DAF-18 and Cytochrome P450/DAF-9. Finally, we find that the TOR associated protein, RAPTOR/DAF-15 regulates mutually exclusive branching of the IL2 and FLP dendrites. DAF-15 promotes IL2 branching during dauer and inhibits precocious FLP growth. Together, our results shed light on molecular processes that regulate stress-mediated remodeling of dendrites across neuron classes., Competing Interests: The authors have declared that no competing interests exist.

The chemosensory system of any animal relies on a vast array of detectors tuned to distinct chemical cues. Odorant receptors and the ion channels of the TRP family are all uniquely expressed in olfactory tissues in a species-specific manner. Great effort has been made to characterize the molecular and pharmacological properties of these proteins. Nevertheless, most of the natural ligands are highly hydrophobic molecules that are not amenable to controlled delivery. We sought to develop photoreleasable, biologically inactive odorants that could be delivered to the target receptor or ion channel and effectively activated by a short light pulse. Chemically distinct ligands eugenol, benzaldehyde, 2-phenethylamine, ethanethiol, butane-1-thiol, and 2,2-dimethylethane-1-thiol were modified by covalently attaching the photoremovable protecting group (8-cyano-7-hydroxyquinolin-2-yl)methyl (CyHQ). The CyHQ derivatives were shown to release the active odorant upon illumination with 365 and 405 nm light. We characterized their bioactivity by measuring activation of recombinant TRPV1 and TRPA1 ion channels expressed in HEK 293 cells and the electroolfactogram (EOG) response from intact mouse olfactory epithelium (OE). Illumination with 405 nm light was sufficient to robustly activate TRP channels within milliseconds of the light pulse. Photoactivation of channels was superior to activation by conventional bath application of the ligands. Photolysis of the CyHQ-protected odorants efficiently activated an EOG response in a dose-dependent manner with kinetics similar to that evoked by the vaporized odorant amyl acetate (AAc). We conclude that CyHQ-based, photoreleasable odorants can be successfully implemented in chemosensory research.

Kinetic analysis of dopamine receptor activation and inactivation and the study of dopamine-dependent signaling requires precise simulation of the presynaptic release of the neurotransmitter dopamine and tight temporal control over the release of dopamine receptor antagonists. The 8-cyano-7-hydroxyquinolinyl (CyHQ) photoremovable protecting group was conjugated to dopamine and the dopamine receptor antagonist sulpiride to generate "caged" versions of these neuromodulators (CyHQ- O -DA and CyHQ-sulpiride, respectively) that could release their payloads with 365 or 405 nm light or through 2-photon excitation (2PE) at 740 nm. These compounds are stable under physiological conditions in the dark, yet photolyze rapidly and cleanly to yield dopamine or sulpiride and the caging remnant CyHQ-OH. CyHQ- O -DA mediated the light activation of dopamine-1 (D1) receptors on the breast cancer cell line MDA-MB-231 in culture. In mouse brain slice from the substantia nigra pars compacta, localized flash photolysis of CyHQ- O -DA accurately mimicked the natural presynaptic release of dopamine and activation of dopamine-2 (D2) receptors, causing a robust, concentration-dependent, and repeatable G protein-coupled inwardly rectifying potassium channel-mediated outward current in whole-cell voltage clamp recordings that was amplified by cocaine and blocked by sulpiride. Photolysis of CyHQ-sulpiride rapidly blocked synaptic activity, enabling measurement of the unbinding rates of dopamine and quinpirole, a D2 receptor agonist. These tools will enable more detailed study of dopamine receptors, their interactions with other GPCRs, and the physiology of dopamine signaling in the brain.

Objective: To measure the psychological distress among the informal caregivers of disabled young adults with traumatic brain injuries (TBI) and to identify its associated factors., Methods: An analytical cross sectional study was conducted with 76 informal caregivers of young adults (19 - 50 years) with TBI, using admission records of one of the tertiary care hospitals in Karachi, Pakistan from 2015 to 2016. Data were collected using a structured questionnaire comprising a general demographic questionnaire and the General Health Questionnaire- 28. The effect of the predictors on the psychological distress was determined by applying multiple linear regression analysis., Results: The mean score of the psychological distress was found to be 23.5±14.28. The findings indicated that anxiety and insomnia, and social dysfunction were the most affected domains of psychological distress; whereas, depression was the least affected. Factors including the management of finances, number of children, patient's gender, and patient's level of disability and lack of socialization were positively associated with the level of distress. As reported by participants, religious beliefs served as a coping mechanism for most of them., Conclusions: The study showed a high level of distress among informal caregivers of young adults with TBI. For recognizing the psychological effects of TBI in patients and their informal caregivers, it is important to initiate and ensure the provision of psychological support to the patients and their families.

Abuse is associated with short and long term psychiatric consequences. There is a need to develop more culturally competent treatment, especially in the South Asian context. We present an account of our clinical experience with hospital-based therapeutic strategies that we found to be successful in a largely conservative, developing country., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Photoremovable protecting groups (PPGs) are powerful tools for physiological studies, harnessing light as an on/off switch to provide tight spatio-temporal control over the release of biological effectors through two-photon excitation (2PE) in tissue culture and whole-animal studies. We carried out a series of systematic structural modifications to the (8-cyano-7-hydroxyquinolin-2-yl)methyl (CyHQ) chromophore to conduct an SAR study with the aim of enhancing its photochemical properties, especially its two-photon uncaging action cross section (δ u ). The best results were obtained when substituents were added at the C4 position, which improved δ u for release of acetate up to 7-fold, while retaining all the other excellent properties of the CyHQ PPG, including high quantum yield (Φ u ), low susceptibility to spontaneous hydrolysis in the dark, and good aqueous solubility. Hammett correlation analysis suggested that photolysis efficiency is favored by electron-rich substituents at C4, giving important insights into the mechanism of the photolysis reaction. The four best CyHQ derivatives were used to mediate the efficient release of homopiperonylic acid in high yield under simulated physiological conditions. Our efforts have led to the development of 2PE-sensitive PPGs with remarkable δ u values (up to 2.64 GM), excellent quantum yields (up to 0.88), and high-yielding effector release (up to 92%).

Background: Deliberate self-harm is not only a major global public health problem but also an important index of psychological distress and a risk factor for suicide., Aims: We aimed to determine the psychosocial risk factors for deliberate self-harm in patients aged ≥ 16 years presenting to tertiary care hospitals in Kabul, Afghanistan., Methods: A matched case-control study was conducted from February 2015 to May 2015. We recruited 185 cases (patients with deliberate self-harm) and 555 age- and sex-matched controls (patients with general medical conditions) from 4 tertiary care hospitals in Kabul. We developed a questionnaire to record the sociodemographic characteristics of the participants, history of domestic violence, drug abuse and details about the act of deliberate self-harm, including the methods used. To assess depression and anxiety, we used the WHO self-reporting questionnaire (SRQ-20). Matched odds ratios with 95% confidence interval using conditional logistic regression were used to determine statistically significant associations between psychosocial factors and deliberate self-harm., Results: Family conflicts, domestic violence, interpersonal arguments and living in extended families were found to be significantly associated with deliberate self-harm., Conclusions: In Afghanistan, deliberate self-harm appears to be predominately related to interpersonal problems and family conflicts. About two-thirds of females and more than half of males scored positive for depression, yet none were receiving treatment for this. These findings have important policy implications for mental health and suicide prevention programmes in the country., (Copyright © World Health Organization (WHO) 2019. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Background: Cancer is a devastating disease and has detrimental effects on the quality of life (QoL) of cancer survivors and interferes with their treatment compliance. The aim of the study is to assess resilience and QoL among cancer survivors and to evaluate the important factors affecting their resilience and QoL, with respect to the Pakistani cultural context., Method and Analysis: A cross-sectional study will be conducted at a tertiary care hospital in Karachi, Pakistan. A minimum sample size of 250 head and neck cancers and 250 brain tumour survivors with 10% inflation for non-response rate will be required. The SD of QoL and resilience will range from 16.5 to 40.8 for head and neck cancer, and 12.7 to 34.1 for brain tumour, at 5% level of significance, with 2.5 precision. QoL will be assessed by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-H&N35 and EORTC QLQ-BN20 and resilience will be evaluated by Wagnild and Young's 14-item scale. Mean±SD will be reported for resilience and QoL scores. Unadjusted and adjusted β-coefficients, with 95% CI, will be reported by using multiple linear regression analysis. Correlation analysis will also be performed using Pearson or Spearman rank correlation coefficients. A p value of <0.05 will be considered significant., Ethics and Dissemination: Ethical approval has been obtained from the Aga Khan University Pakistan's Ethical Review Committee. Written informed consent will be taken from the participants by trained research assistants. A trained psychologist will provide on-spot counselling to the participants and those identified with severe depression will be referred to a psychiatrist. The study materials will be kept under lock and key and the electronic data base will be password protected and will only be accessed by the research team. The study findings will be disseminated through publications conferences and workshops and research briefs., Trial Registration Number: Clinicaltrials.gov registry (NCT03466762)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Sortilin is a multifunctional neuronal receptor involved in sorting of neurotrophic factors and apoptosis signaling. So far, structural characterization of sortilin and its endogenous ligands has been limited to crystallographic studies of sortilin in complex with the neuropeptide neurotensin. Here, we use hydrogen/deuterium exchange mass spectrometry to investigate the conformational response of sortilin to binding biological ligands including the peptides neurotensin and the sortilin propeptide and the proteins progranulin and pro-nerve growth factor-β. The results show that the ligands use two binding sites inside the cavity of the β-propeller of sortilin. However, ligands have distinct differences in their conformational impact on the receptor. Interestingly, the protein ligands induce conformational stabilization in a remote membrane-proximal domain, hinting at an unknown conformational link between the ligand binding region and this membrane-proximal region of sortilin. Our findings improve our structural understanding of sortilin and how it mediates diverse ligand-dependent functions important in neurobiology., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The direct release of dialkylanilines was achieved by controlling the outcome of a photorearrangement reaction promoted by the (8-cyano-7-hydroxyquinolin-2-yl)methyl (CyHQ) photoremovable protecting group. The substrate scope was investigated to obtain structure-activity relationships and to propose a reaction mechanism. Introducing a methyl substituent at the 2-methyl position of the CyHQ core enabled the bypass of the photorearrangement and significantly improved the aniline release efficiency. We successfully applied the strategy to the photoactivation of mifepristone (RU-486), an antiprogestin drug that is also used to induce the LexPR gene expression system in zebrafish and the gene-switch regulatory system based on the pGL-VP chimeric regulator in mammals.

There is a scarcity of research on suicidal phenomena in the Muslim world. Therefore, this study aimed at investigating the self-reported prevalence of suicidal thoughts, attempts and motives in 12 Muslim countries. A total of 8417 (54.4% women) university students were surveyed by means of a self-report questionnaire. Overall, 22% of the participants reported suicidal ideation and 8.6% reported attempting suicide. The odds of suicidal thoughts were elevated in Azerbaijan, Indonesia and Saudi Arabia, while reduced ORs were recorded in Egypt, Jordan, Lebanon and Malaysia. While odds of suicide attempts were high in Azerbaijan, Palestine and Saudi Arabia reduced odds ratios (OR) were detected in Indonesia, Iran, Jordan, Lebanon, Malaysia and Tunisia. Taking drugs and using a sharp instrument were the two most frequently used methods to attempt suicide. Only 32.7% of attempts required medical attention. Escape motives were endorsed more than social motives by participants who attempted suicide. Suicidal behaviors were more frequent in women than in men. Compered to men, fewer attempts by women required medical attention. Moreover, our results show that making suicide illegal does not reduce the frequency of suicidal behavior. Results from this comparative study show that suicidal thoughts and attempts are frequent events in young adults in countries where religious scripture explicitly prohibit suicide and the frequencies of nonfatal suicidal behavior show large variation in nations adhering to the same religion.

Background: In Pakistan, there is high prevalence of mental health disorders, but mental health services to address these are not well developed. To provide effective mental health services, the World Health Organization emphasizes the integration of mental health into primary health care (PHC)., Objectives: This study aimed to assess the views of key stakeholders about integration of mental health into PHC in Karachi, Pakistan., Methods: A qualitative, exploratory study was conducted between June and September 2013 among 15 decision-making (from the Department of Health) and implementation-level stakeholders (mental health and public health professionals and primary care staff) from both the public and private sectors. Face-to-face, in-depth interviews were conducted using a semi-structured interview guide. Data were collected until theoretical saturation was achieved and conventional content analysis was carried out., Results: Although there was general support among all the stakeholders for integration of mental health services within PHC, there were also a number of reservations. First was the perceived lack of support within the system in terms of resource allocation and acceptance from the community. Second was the lack of human resources in the field of mental health. In addition, resistance at the PHC level is likely as staff are already burdened with other preventive care services., Conclusions: The study suggests that strong political commitment, adequate human and financial resources, and strong advocacy are needed for the integration of mental health into PHC in Pakistan., (Copyright © World Health Organization (WHO) 2018. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Objective: To observe inpatient satisfaction at different public sector hospitals of Karachi, Pakistan., Methods: A cross sectional study was carried out during 2010-2012 in four major public sector hospitals of Karachi. A total of 710 patients completed the study. Responses were gathered in a self-structured questionnaire that comprised of four dimensions of satisfaction with doctor, staff, administration and treatment. Average Score of each dimension was taken and compared using one way analysis of variance., Result: Satisfaction with doctors, staff and administration of provincial and federal hospitals were comparatively similar (P > 0.05). However, satisfaction with treatment significantly differed in all four hospitals (P < 0.0001). Highest satisfaction with treatment was observed among inpatients of hospital running by medical institute (P < 0.0001). Comparison with respect to different departments revealed significant difference for treatment satisfaction of medicine and surgery units. Patients who were admitted from emergency mode acquired lowest satisfaction in all aspects., Conclusion: Response of inpatients from public sector hospitals showed satisfaction with healthcare personnel and related administration. However, treatment dimension needs to be improved to get more satisfaction.

Background: Depression and peer violence are global issues impacting youth. We are presenting baseline data as part of a cluster randomized control trial underway, on adolescent depression, and associated factors among boys and girls in schools., Method: Cluster randomized control trial is underway for measuring the effectiveness of school-based play intervention program of the NGO Right to Play, in a sample of 1752 grade 6 youth in 40 public schools of Hyderabad, Pakistan. Students responded to Child Depression Inventory (CDI-2), the Peer Victimization Scale (PVS), the Peer Perpetration Scale (PPS), and investigator-driven seven-item School Performance Scale., Results: We report baseline assessments to examine the prevalence of depressive symptoms, and associated occurrence of peer perpetration and victimization. Boys report significantly more depressive symptoms as well as perpetration and victimization compared to girls (p ≤ .0001). Our analysis indicates that among boys, depression was found associated with greater age, food insecurity, poorer school performance and working for money, as well as being beaten at home and witnessing beating of their mother by their father or other relatives. Among girls, depression was associated with a younger age, greater food insecurity and poorer school performance. Depression was also associated with a great likelihood of engagement in peer violence, experience of punishment at home, and witnessing their father fighting with other men or beating their mother., Conclusions: Engagement in violent behaviors, exposure to violent acts and poverty surfaces as detrimental to mental health in youth age groups, suggesting strong measures to address youth violence, and poverty reduction for positive mental health outcomes in school age children., (© 2017 Association for Child and Adolescent Mental Health.)

Representative tertiary amines were linked to the 8-cyano-7-hydroxyquinolinyl (CyHQ) photoremovable protecting group (PPG) to create photoactivatable forms suitable for use in studying cell physiology. The photoactivation of tamoxifen and 4-hydroxytamoxifen, which can be used to activate Cre recombinase and CRISPR-Cas9 gene editing, demonstrated that highly efficient release of bioactive molecules could be achieved through one- and two-photon excitation (1PE and 2PE). CyHQ-protected anilines underwent a photoaza-Claisen rearrangement instead of releasing amines. Time-resolved spectroscopic studies revealed that photorelease of the tertiary amines was extremely fast, occurring from a singlet excited state of CyHQ on the 70 ps time scale.

Background: Emergency medical service (EMS) personnel who work to provide emergency medical care at the scene and during transportation are exposed to various kinds of stressors and are particularly susceptible to developing stress-reactions. This study assesses symptoms of post-traumatic stress disorder and its predictors among the personnel of a selected EMS in Karachi, Pakistan., Methods: Data were gathered from 518 personnel working in an EMS setting from February to May 2014. Participants were screened for post-traumatic stress symptoms using the Impact of Event Scale-Revised (IES-R). Demographic and work-related characteristics, coping styles and the social support systems of the participants were assessed. Linear regression was used on the IES-R to identify predictors of post-traumatic stress symptoms., Results: The mean score of the IES-R was 23.9 ± 12.1. EMS personnel with a dysfunctional coping style (β = 0.67 CI 0.39 - 0.95), anxiety, and depression (β = 0.64 CI 0.52 - 0.75) were more likely to have increased severity of post-traumatic stress symptoms. Age was found to have an inverse relationship with stress symptoms (β = -0.17 CI 0.33 - -0.023), indicating the susceptibility of younger EMS personnel to stress., Conclusion: The EMS personnel in this setting were found to have a moderate level of post-traumatic stress symptoms. The significant predictors of post-traumatic stress symptoms in this EMS population were age, coping style, and levels of anxiety and depression. These predicting factors can be a potential avenue for interventions to improve the mental health of these frontline workers.

Background: The purpose of the study was to explore the association between post-traumatic stress disorder (PTSD) and work performance of emergency medical services personnel in Karachi, Pakistan., Methods: Emergency medical service personnel were screened for potential PTSD using Impact of Event Scale-Revised (IES-R). Work performance was assessed on the basis of five variables: number of late arrivals to work, number of days absent, number of days sick, adherence to protocol, and patient satisfaction over a period of 3 months. In order to model outcomes like the number of late arrivals to work, days absent and days late, negative binomial regression was applied, whereas logistic regression was applied for adherence to protocol and linear for patient satisfaction scores., Results: Mean scores of PTSD were 24.0±12.2. No association was found between PTSD and work performance measures: number of late arrivals to work ( RR adj 0.99; 0.98-1.00), days absent ( RR adj 0.98; 0.96-0.99), days sick ( RR adj 0.99; 0.98-1.00), adherence to protocol ( OR adj 1.01; 0.99-1.04) and patient satisfaction ( β 0.001%-0.03%) after adjusting for years of formal schooling, living status, coping mechanism, social support, working hours, years of experience and anxiety or depression., Conclusion: No statistically significant association was found between PTSD and work performance amongst EMS personnel in Karachi, Pakistan., Competing Interests: Conflicts of interest: Funders have no role in study design, conduct or analysis of the study. Authors are responsible solely for the content and writing of paper.

Background: Two thirds of the global mortality of stroke is borne by low and middle income countries (LMICs). Pakistan is the world's sixth most populous country with a stroke-vulnerable population and is without a single dedicated chronic care center. In order to provide evidence for a viable solution responsive to this health care gap, and leveraging the existing >70% mobile phone density, we thought it rational to test the effectiveness of a mobile phone-based video intervention of short 5-minute movies to educate and support stroke survivors and their primary caregivers., Methods: Movies4Stroke will be a randomized control, outcome assessor blinded, parallel group, single center superiority trial. Participants with an acute stroke, medically stable, with mild to moderate disability and having a stable primary caregiver will be included. After obtaining informed consent the stroke survivor-caregiver dyad will be randomized. Intervention participants will have the movie program software installed in their phone, desktop, or Android device which will allow them to receive, view and repeat 5-minute videos on stroke-related topics at admission, discharge and first and third months after enrollment. The control arm will receive standard of care at an internationally accredited center with defined protocols. The primary outcome measure is medication adherence as ascertained by a locally validated Morisky Medication Adherence Scale and control of major risk factors such as blood pressure, blood sugar and blood cholesterol at 12 months post discharge. Secondary outcome measures are post-stroke complications and mortality, caregiver knowledge and change in functional outcomes after acute stroke at 1, 3, 6, 9 and 12 months. Movies4Stroke is designed to enroll 300 participant dyads after inflating 10% to incorporate attrition and non-compliance and has been powered at 95% to detect a 15% difference between intervention and usual care arm. Analysis will be done by the intention-to-treat principle., Discussion: Movies4Stroke is a randomized trial testing an application aimed at supporting caregivers and stroke survivors in a LMIC with no rehabilitation or chronic support systems., Trial Registration: NCT02202330 (28 January 2015).

The generation of common and stereochemically rich medium-sized benzo-fused sultams via complementary pairing of heretofore-unknown (o-fluoroaryl)sulfonyl aziridine building blocks with an array of amino alcohols/amines in a modular one-pot, sequential protocol using an aziridine ring opening and intramolecular nucleophilic aromatic substitution is reported. The strategy employs a variety of amino alcohols/amines and proceeds with 6 + 4/6 + 5 and 6 + 1 cycloetherification pathways in a highly chemo- and regioselective fashion to obtain skeletally and structurally diverse, polycyclic, 10- to 11- and 7-membered benzo-fused sultams for broad-scale screening.

Background: There were no instrument exists in South Asia to assess resilience. Thus, this study assessed the validity and reliability of the Urdu version of Wagnild and Young's long and short Resilience Scales., Methods: Study was carried out in two urban squatter settlements of Karachi, Pakistan. Resilience Scales were validated against the depression, anxiety, and life satisfaction scales among 20- to 40-year-old married women. Sample size for validity and reliability were 636 and 319., Results: Moderate negative correlation with the depression and anxiety and moderate positive significant correlation with life satisfaction were found with both scales. The test-retest correlation were .54 and .49, respectively. Internal consistency were found acceptable. Concurrent validity were .729 and .813., Conclusions: Study found a valid and reliable resilience scale in Urdu language.

Rare Caenorhabditis elegans males arise when sex chromosome non-disjunction occurs during meiosis in self-fertilizing hermaphrodites. Non-disjunction is a relatively rare event, and males are typically observed at a frequency of less than one in five hundred wild-type animals. Males are required for genetic crosses and phenotypic analysis, yet current methods to generate large numbers of males can be cumbersome. Here, we identify RNAi reagents (dsRNA-expressing bacteria) with improved effectiveness for eliciting males. Specifically, we used RNAi to systematically reduce the expression of over two hundred genes with meiotic chromosome segregation functions, and we identified a set of RNAi reagents that robustly and reproducibly elicited male progeny., (Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

A one-pot, sequential protocol is reported that involves complementary ambiphile pairing (CAP) of a vinyl sulfonamide with a variety of unprotected amino acids via aza-Michael addition and subsequent intramolecular amidation. The method generates diverse, sp(3)-rich mono- and bicyclic acyl sultams in a highly scalable manner. Modular pairing of stereochemically rich building blocks allows quick access to all possible isomers. Extension to include one-pot, sequential 3-, 4-, and 5-multicomponent protocols is also discussed.

All blood bank services, especially those of developing countries, face a major shortfall of blood donations due to lack of voluntary blood donors. Our study aims to evaluate the acceptability of Short Message Service based interventions towards becoming voluntary blood donors among medical university students of Karachi, Pakistan. Methods. A total of 350 medical students were approached in medical universities of Karachi, Pakistan, using a nonprobability convenient sampling technique. Data collectors administered a self-made questionnaire to each participant using an interview based format. All data was recorded and analyzed on SPSS 16. Results. 350 participants, having a mean age of 21.47 ± 1.36, were included in our study with 30.6% (107/350) being males and 69.4% (243/350) being females. 93.4% (327/350) of participants agreed that donating blood was healthy, but only 26% had donated blood in the past with 79.1% donating voluntarily. 65.7% (230/350) of the participants agreed to take part in Short Message Service based behavioral interventions to become voluntary blood donors with 69.7% (244/350) also agreeing that Short Message Service reminders will promote them to donate blood more often. Conclusion. With university students willing to become voluntary blood donors, Pakistani blood banks can carry out Short Message Service based interventions to encourage them to donate blood.

Background: Facebook is a social networking service launched in February 2004, owned and operated by Facebook, Inc. As of June 2012, Facebook reports more than 1 billion active users. Objective of study was to evaluate the effect of Facebook on the social life, health and behavior of medical students., Methodology: It was a cross sectional, observational and questionnaire based study conducted in Dow University OF Health Sciences during the period of January 2012 to November 2012. We attempted to interview all the participants who could be approached during the period of the study. Participants were MBBS students, while all students of other courses and programs were taken as exclusion criteria. Approximately 1050 questionnaires were distributed to participants. Fifty questionnaires were rejected due to incomplete answers, yielding 1000 usable responses for an approximate 95% response rate. Informed verbal consent was taken from each participant. Study was ethically approved by Institutional Review Board of Dow University of Health Sciences. All the data was entered and analyzed through SPSS 19., Result: Out of total 1000 participants, males were 400 (40%) and females were 600 (60%). Participants were in the age group of 18-25 years with a mean age of 20.08 years. Most of the participants were using Facebook daily (N = 640, 64%) for around 3-4 hours (N = 401, 40.1%). Majority of them (N = 359, 35.9%) believed that they were equally active on Facebook and in real life while few believed their social life became worse after start using Facebook (N = 372, 37.2%). Most of the participants admitted that they were considered as shy in real world (N = 390, 39.0%) while in the world of Facebook they were considered as fun loving by their friends (N = 603, 60.3%). A large number of participants (N = 715, 75%) complained of mood swings., Conclusion: Youngsters are willing to compromise their health, social life, studies for the sake of fun and entertainment or whatever satisfaction they get after using Facebook. What we observed in our study was that although majority of our subjects showed multiple signs of Facebook addiction, they don't realize it and if even they realize it they don't want to quit Facebook and even if they want to quit, they can't. Our observance concluded that majority of the users are highly addicted.

Objective: Significant neurodevelopmental sequelae are known to occur after acute bacterial meningitis (ABM). This study determined the burden of such sequelae in Pakistani children aged <5 years to guide policies for Haemophilus influenzae type b (Hib) and pneumococcal vaccination., Study Design: Cases of ABM were recruited from hospital-based surveillance and assigned to 1 of 3 etiologic groups (Hib, Streptococcus pneumoniae, or unknown etiology). Two age-matched controls were recruited for each case. Six months after enrollment, each case underwent neurologic history and examination, neurodevelopmental evaluation, and neurophysiological hearing test. Controls were assessed in parallel., Results: Of 188 cases, 64 (34%) died. Mortality among subgroups were 7 (27%), 14 (28%), and 43 (39%) for Hib, Streptococcus pneumoniae, and unknown etiology, respectively. Eighty cases and 160 controls completed the assessments. Sequelae among cases included developmental delay (37%), motor deficit (31%), hearing impairment (18.5%), epilepsy (14%), and vision impairment (14%). Sequelae were higher after pneumococcal meningitis (19, 73%) compared with Hib meningitis (8, 53%). Compared with controls, cases were at significantly higher risk for all sequelae (P < .0001)., Conclusions: ABM causes a substantial long-term burden of poor neurodevelopmental outcomes. Hib and pneumococcal vaccines are very effective interventions to prevent meningitis and its disabling sequelae., (Copyright © 2013. Published by Mosby, Inc.)

Pakistan ranks 125th out of 169 countries on the Gender Development Index and has high prevalence rates of Violence against Women (VAW). Contributing factors toward gender based violence at the micro, meso and macro levels include the acceptability of violence amongst both men and women, internalization of deservability, economic disempowerment, lack of formal education, joint family systems, entrenched patriarchal norms and values, and a lack of awareness of legal and other support systems. These factors have a long-lasting impact on the health of women and children. The gender disparities in the experience of women seeking health care in Pakistan are well-recognized and documented. In the past, common government policy responses to these disparities have included developing the role of community health workers (CHWs) and lady health visitors (LHVs). Despite being commendable initiatives, these too have been unsuccessful in addressing these multi-faceted disparities. Within this complex scenario, new interventions to address VAW and its impact on health in Pakistan include Group Counselling, Economic Skills Building, Health-Based Microfinance, and Family-Based models that increase male involvement, especially at the primary health care level. The purpose of this article is to outline key contributing factors to VAW, explore tested and new interventions, and highlight the opportunities that exist in implementing them.

Organisms used as model genomics systems are maintained as isogenic strains, yet evidence of sequence differences between independently maintained wild-type stocks has been substantiated by whole-genome resequencing data and strain-specific phenotypes. Sequence differences may arise from replication errors, transposon mobilization, meiotic gene conversion, or environmental or chemical assault on the genome. Low frequency alleles or mutations with modest effects on phenotypes can contribute to natural variation, and it has proven possible for such sequences to become fixed by adapted evolutionary enrichment and identified by resequencing. Our objective was to identify and analyze single locus genetic defects leading to RNAi resistance in isogenic strains of Caenorhabditis elegans. In so doing, we uncovered a mutation that arose de novo in an existing strain, which initially frustrated our phenotypic analysis. We also report experimental, environmental, and genetic conditions that can complicate phenotypic analysis of RNAi pathway defects. These observations highlight the potential for unanticipated mutations, coupled with genetic and environmental phenomena, to enhance or suppress the effects of known mutations and cause variation between wild-type strains.

In a developing country such as Pakistan, where illiteracy, poverty, gender differences, and health issues are prevalent, violence against women is a commonly observed phenomenon. The rising incidences of abuse among women indicate a need to introduce evidence-based community-derived interventions for meeting Millennium Developmental Goals by 2015. This article discusses the application of counseling, economic skills building, and microcredit programs as practical and effective interventions to improve the health outcomes of abused women and, therefore, improving maternal and child health in the Pakistani society., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The construction of two libraries of triazole-containing isothiazolidine 1,1-dioxides is reported utilizing either a one-pot click/aza-Michael or click/OACC esterification protocol. One core dihydroisothiazole 1,1-dioxide scaffold was prepared rapidly on multigram scale via ring-closing metathesis (RCM) and was subjected to a one-pot multicomponent click/aza-Michael protocol with an array of amines and azides for the generation of a 180-member triazole-containing isothiazolidine 1,1-dioxide library. Alternatively, three daughter scaffolds were generated via the aza-Michael of three amino alcohols, followed by a one-pot, multicomponent click/esterification protocol utilizing a ring-opening metathesis polymerization (ROMP)-derived coupling reagent, oligomeric alkyl carbodiimide (OACC) to generate a 41-member library of triazole-containing isothiazole 1,1-dioxides.