Evaluation of a school-based sexual abuse prevention program for female children with intellectual disabilities in rural Pakistan- A feasibility study.

BACKGROUND: Child sexual abuse is one of the most pervasive threats to children's wellbeing worldwide. Globally, around 7% to 19% of children have been estimated to be a victim of child sexual abuse. In Pakistan, around 18 thousand instances of child sexual abuse were reported in the last five years. AIMS: Current study aimed to evaluate the preliminary effect, acceptability and feasibility of a sexual abuse prevention program for children with intellectual disabilities, in a rural public school of Pakistan. METHOD: A non-randomized (pre-post) evaluation of the acceptability, feasibility and impact of the adapted sexual abuse prevention program on a range of knowledge and skills-based outcomes of 15 female children with mild intellectual disability was undertaken. Participants were exposed to a 5-session based program incorporating common sexual abuse prevention concepts, e.g. knowledge of private body parts, body ownership, discriminating between safe and threatening situations, refusing to sexual lures, escaping the situation and reporting the potential offender. Structured assessments were conducted with children before and after intervention delivery. RESULTS: The school-based sexual abuse prevention program was shown to be acceptable, feasible and efficacious in improving sexual abuse prevention knowledge and skills of female children with a mild intellectual disability enrolled in a public school of rural Pakistan. CONCLUSIONS: The program offers a promising framework for school-based sexual abuse prevention in Pakistan.

All hands on deck: Adipocytes lept-in to drive nerve regeneration.

The glial metabolic state instructs nerve regeneration. In this issue of Cell Metabolism, Sundaram, Schütza, Schröter, et al. demonstrate that nerve injury induces adipocytes-glia signaling via leptin, thereby modulating glial metabolism and driving nerve regeneration.

A developmental pathway for epithelial-to-motoneuron transformation in C. elegans.

Motoneurons and motoneuron-like pancreatic ß cells arise from radial glia and ductal cells, respectively, both tube-lining progenitors that share molecular regulators. To uncover programs underlying motoneuron formation, we studied a similar, cell-division-independent transformation of the C. elegans tube-lining Y cell into the PDA motoneuron. We find that lin-12/Notch acts through ngn-1/Ngn and its regulator hlh-16/Olig to control transformation timing. lin-12 loss blocks transformation, while lin-12(gf) promotes precocious PDA formation. Early basal expression of ngn-1/Ngn and hlh-16/Olig depends on sem-4/Sall and egl-5/Hox. Later, coincident with Y cell morphological changes, ngn-1/Ngn expression is upregulated in a sem-4/Sall and egl-5/Hox-dependent but hlh-16/Olig-independent manner. Subsequently, Y cell retrograde extension forms an anchored process priming PDA axon extension. Extension requires ngn-1-dependent expression of the cytoskeleton organizers UNC-119, UNC-44/ANK, and UNC-33/CRMP, which also activate PDA terminal-gene expression. Our findings uncover cell-division-independent regulatory events leading to motoneuron generation, suggesting a conserved pathway for epithelial-to-motoneuron/motoneuron-like cell differentiation.

Evaluating the impact of a common elements-based intervention to improve maternal psychological well-being and mother-infant interaction in rural Pakistan: study protocol for a randomised controlled trial.

INTRODUCTION: Millions of children in low resource settings are at high risk of poor development due to factors such as under nutrition, inadequate stimulation and maternal depression. Evidence-based interventions to address these risk factors exist, but often as a separate and overlapping package. The current study aims to evaluate the effectiveness of a common elements-based intervention to improve mother-infant interaction at 12 months post-partum. METHOD AND ANALYSIS: A two-arm, single-blinded, individual randomised controlled trial is being carried out in the community settings of the rural subdistrict of Gujar Khan in Rawalpindi, Pakistan. 250 pregnant women in third trimester with distress (Self-Reporting Questionnaire, cut-off score >9) have been randomised on 1:1 allocation ratio into intervention (n=125) and treatment-as-usual arms (n=125). The participants in the intervention arm will receive 15 individual sessions of intervention on a monthly basis by non-specialist facilitators. The intervention involves components of early stimulation, learning through play, responsive feeding, guided discovery using pictures, behavioural activation and problem solving. The primary outcome is caregiver-infant interaction at 12 months postpartum. The secondary outcomes include maternal psychological well-being, quality of life, social support and empowerment. Infant secondary outcomes include growth, nutrition and development. The data will be collected at baseline, 6 and 12 months postpartum. A qualitative process evaluation will be conducted to inform the feasibility of intervention delivery. ETHICS: Ethics approval for the present study was obtained from the Human Development Research Foundation Institutional Review Board, Islamabad Pakistan. DISSEMINATION: If proven effective, the study will contribute to scale-up care for maternal and child mental health in low resource settings, globally. The findings of the present study will be published in peer-reviewed journals and presented at conferences and community forums. TRIAL REGISTRATION NUMBER: NCT04252807.

TULIP study: Trail of Lurasidone in bipolar disorder in Pakistan.

BACKGROUND: This study examined usefulness and efficiency of Lurasidone in appraisal with the placebo as for the treatment of Bipolar Disorders. METHODS: Seven treatment centers in Pakistan were selected for the purpose of starting a six week-long control trial (randomized and double-blind placebo). 76 subjects, already diagnosed with Bipolar I or II based on DSM 5 diagnosis, were selected after randomization. Patients were allocated in one of the two groups. Primary efficacy of the drug was measured using Young Mania Rating Scale. Positive response of the drug was defined as 50% reduction in symptoms from the baseline/13 point less than the baseline score on Young Mania Rating Scale. Efficacy and safety of the drug was assessed using variety of markers such as administering extra-pyramidal symptoms rating scale, adverse side effects reported, electrocardiograms, body weight, vital signs changes, and laboratory investigations. RESULTS: Patients treated with Lurasidone showed enhanced improvement in their overall health and symptoms manifestation in comparison to patients who were given placebo. Lurasidone treated patients showed a better response to the drug (66%), in comparison with the placebo treated patients (42%). LIMITATIONS: Study was conducted on small scale due to complexity. CONCLUSION: Patients treated with Lurasidone showed reduction in bipolar symptoms and tolerate the drug well.

Pandemic anxiety and its correlates among young doctors working frontline in Pakistan.

BACKGROUND: The study explores the challenges and threats young doctors in Pakistan working frontline toward the pandemic face, and how it translates into their personal and social lives. METHODS: Thirteen resident doctors working frontline with COVID-19 cases were approached and interviewed in-depth until the point of data saturation. Interpretative phenomenological analysis was used as a method for analysis. RESULTS: Four themes emerged in the analysis: pandemic anxiety, organizational lack of readiness for change, impact on interpersonal relationships, and commitment to service. Young doctors experienced psychological distress, and emotional vulnerability due to the challenges and concerns faced by them in the wake of COVID-19. Shortage and excessive reuse of personal protective equipment, direct exposure to the disease, concern for personal safety, fear and apprehension of being a probable disease carrier for families, physical distancing from loved ones, long working hours, and increased organizational responsibility altered the quality of life for doctors working frontline toward pandemic in COVID wards. Doctors who received appreciation and support by families reported improved filial bonds. CONCLUSION: The adverse effect on psychological health, personal and social life, and increased professional demands have been some of the major challenges and threats faced by young doctors working frontline toward the pandemic. However, unconditional love and support from family and community has proven to reduce pandemic anxiety among doctors. Furthermore, the sense of compassion and the satisfaction in service to community has kept doctors devoted to fight against pandemic 2020.

EFF-1 fusogen promotes phagosome sealing during cell process clearance in Caenorhabditis elegans.

Phagocytosis of dying cells is critical in development and immunity1-3. Although proteins for recognition and engulfment of cellular debris following cell death are known4,5, proteins that directly mediate phagosome sealing are uncharacterized. Furthermore, whether all phagocytic targets are cleared using the same machinery is unclear. Degeneration of morphologically complex cells, such as neurons, glia and melanocytes, produces phagocytic targets of various shapes and sizes located in different microenvironments6,7. Thus, such cells offer unique settings to explore engulfment programme mechanisms and specificity. Here, we report that dismantling and clearance of a morphologically complex Caenorhabditis elegans epithelial cell requires separate cell soma, proximal and distal process programmes. Similar compartment-specific events govern the elimination of a C. elegans neuron. Although canonical engulfment proteins drive cell soma clearance, these are not required for process removal. We find that EFF-1, a protein previously implicated in cell-cell fusion 8 , specifically promotes distal process phagocytosis. EFF-1 localizes to phagocyte pseudopod tips and acts exoplasmically to drive phagosome sealing. eff-1 mutations result in phagocytosis arrest with unsealed phagosomes. Our studies suggest universal mechanisms for dismantling morphologically complex cells and uncover a phagosome-sealing component that promotes cell process clearance.

Medications for Children: A Survey of Community Pharmacists.

BACKGROUND: Seamless and safe discharge of children from hospital requires successful collaboration with community pharmacists, for whom pediatrics is often a small part of their practice. OBJECTIVES: The purpose of this study was to understand community pharmacists' comfort level and confidence in providing care for children. METHODS: We conducted a self-administered online survey of community pharmacists in Ontario, Canada. Respondents rated their comfort and confidence on a scale of 1 to 7 in each of 3 scenarios: oral morphine, prednisone, and amoxicillin. We also evaluated the relationship between participants' comfort level and demographics. RESULTS: We included 622 responses (377 completed and 245 partially completed surveys). A total of 182 participants (48%) were female, 271 participants (72%) had children of their own, and they had practiced pharmacy for a median (interquartile range) of 19 (5-28) years. The percentage of respondents who were comfortable (5-7 on a 7-point scale) with filling the prescriptions as written was 64% for morphine, 58% for prednisone, and 61% for amoxicillin and was not different among the scenarios. Having children was associated with increased comfort (p = 0.02), whereas other demographic variables were not. Compared to the amoxicillin scenario, pharmacists reported being significantly more likely to choose another course of action for prednisone (p = 0.01) but not for morphine (p = 0.25). Although 428 pharmacists (70%) agreed that they maintained adequate knowledge of pediatric topics, 558 (91%) were interested in more education. CONCLUSIONS: Variability exists in the confidence and comfort levels of community pharmacists when dealing with children, and many are not comfortable with the common prescriptions in this survey.

Cell-Specific Transcriptional Profiling of Ciliated Sensory Neurons Reveals Regulators of Behavior and Extracellular Vesicle Biogenesis.

Cilia and extracellular vesicles (EVs) are signaling organelles [1]. Cilia act as cellular sensory antennae, with defects resulting in human ciliopathies. Cilia both release and bind to EVs [1]. EVs are sub-micron-sized particles released by cells and function in both short- and long-range intercellular communication. In C. elegans and mammals, the autosomal dominant polycystic kidney disease (ADPKD) gene products polycystin-1 and polycystin-2 localize to both cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation [2]. A fundamental understanding of EV biology and the relationship between the polycystins, cilia, and EVs is lacking. To define properties of a ciliated EV-releasing cell, we performed RNA-seq on 27 GFP-labeled EV-releasing neurons (EVNs) isolated from adult C. elegans. We identified 335 significantly overrepresented genes, of which 61 were validated by GFP reporters. The EVN transcriptional profile uncovered new pathways controlling EV biogenesis and polycystin signaling and also identified EV cargo, which included an antimicrobial peptide and ASIC channel. Tumor-necrosis-associated factor (TRAF) homologs trf-1 and trf-2 and the p38 mitogen-activated protein kinase (MAPK) pmk-1 acted in polycystin-signaling pathways controlling male mating behaviors. pmk-1 was also required for EV biogenesis, independent of the innate immunity MAPK signaling cascade. This first high-resolution transcriptome profile of a subtype of ciliated sensory neurons isolated from adult animals reveals the functional components of an EVN.

Dauer-specific dendrite arborization in C. elegans is regulated by KPC-1/Furin.

BACKGROUND: Dendrites often display remarkably complex and diverse morphologies that are influenced by developmental and environmental cues. Neuroplasticity in response to adverse environmental conditions entails both hypertrophy and resorption of dendrites. How dendrites rapidly alter morphology in response to unfavorable environmental conditions is unclear. The nematode Caenorhabditis elegans enters into a stress-resistant dauer larval stage in response to an adverse environment. RESULTS: Here we show that the IL2 bipolar sensory neurons undergo dendrite arborization and axon remodeling during dauer development. When dauer larvae are returned to favorable environmental conditions, animals resume reproductive development and IL2 dendritic branches retract, leaving behind remnant branches in postdauer L4 and adult animals. The C. elegans furin homolog KPC-1 is required for dauer IL2 dendritic arborization and dauer-specific nictation behavior. KPC-1 is also necessary for dendritic arborization of PVD and FLP sensory neurons. In mammals, furin is essential, ubiquitously expressed, and associated with numerous pathologies, including neurodegenerative diseases. While broadly expressed in C. elegans neurons and epithelia, KPC-1 acts cell autonomously in IL2 neurons to regulate dauer-specific dendritic arborization and nictation. CONCLUSIONS: Neuroplasticity of the C. elegans IL2 sensory neurons provides a paradigm to study stress-induced and reversible dendritic branching, and the role of environmental and developmental cues in this process. The newly discovered role of KPC-1 in dendrite morphogenesis provides insight into the function of proprotein convertases in nervous system development.