A novel assessment of potentially toxic elements (PTEs) in water and sediment samples from the Indus River, Pakistan: An ecological risk assessment approach.

Pakistan, a country with limited water resources and highly vulnerable to the adverse effects of climate change, faces numerous challenges in managing its water supply. In this sense, this study assessed potentially toxic elements (PTEs) in the surface water and sediments of Pakistan's Indus River and its tributaries. Key water quality parameters such as pH, electrical conductivity (EC), and total dissolved solids (TDS) were determined, with respective average values of 7.1, 40 µS/cm, and 208 mg L-1. The concentrations of Cd, Cr, Cu, Ni, and Zn in surface water samples averaged 26 µg L-1, 0.9 µg L-1, 1.4 µg L-1, 22 µg L-1, and 2.1 µg L-1, respectively. The general sediment PTE profile was Ni > Cd > Zn > Cu > Cr. Certain PTE levels exceeded recommended thresholds, indicating the establishment of environmental pollution. Calculated geo-accumulation index values suggested moderate to heavy pollution levels in sediment, with PERI (404) values reinforcing the ecological risk posed by elevated PTE concentrations. Furthermore, significant correlations were observed between specific PTE pairs in both water and sediment samples. This study contributes with novel insights into the distribution and ecological implications of PTE contamination in the Indus River and its tributaries, paving the way for ecological risk management efforts.

Nivolumab and Ipilimumab Acting as Tormentors of Advanced Tumors by Unleashing Immune Cells and Associated Collateral Damage.

Combining immune checkpoint inhibitors, specifically nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4), holds substantial promise in revolutionizing cancer treatment. This review explores the transformative impact of these combinations, emphasizing their potential for enhancing therapeutic outcomes across various cancers. Immune checkpoint proteins, such as PD1 and CTLA4, play a pivotal role in modulating immune responses. Blocking these checkpoints unleashes anticancer activity, and the synergy observed when combining multiple checkpoint inhibitors underscores their potential for enhanced efficacy. Nivolumab and ipilimumab harness the host's immune system to target cancer cells, presenting a powerful approach to prevent tumor development. Despite their efficacy, immune checkpoint inhibitors are accompanied by a distinct set of adverse effects, particularly immune-related adverse effects affecting various organs. Understanding these challenges is crucial for optimizing treatment strategies and ensuring patient well-being. Ongoing clinical trials are actively exploring the combination of checkpoint inhibitory therapies, aiming to decipher their synergistic effects and efficacy against diverse cancer types. This review discusses the mechanisms, adverse effects, and various clinical trials involving nivolumab and ipilimumab across different cancers, emphasizing their transformative impact on cancer treatment.

A protein-miRNA biomic analysis approach to explore neuroprotective potential of nobiletin in human neural progenitor cells (hNPCs).

Chemical-induced neurotoxicity is increasingly recognized to accelerate the development of neurodegenerative disorders (NDs), which pose an increasing health burden to society. Attempts are being made to develop drugs that can cross the blood-brain barrier and have minimal or no side effects. Nobiletin (NOB), a polymethoxylated flavonoid with anti-oxidative and anti-inflammatory effects, has been demonstrated to be a promising compound to treat a variety of NDs. Here, we investigated the potential role of NOB in sodium arsenate (NA)-induced deregulated miRNAs and target proteins in human neural progenitor cells (hNPCs). The proteomics and microRNA (miRNA) profiling was done for different groups, namely, unexposed control, NA-exposed, NA + NOB, and NOB groups. Following the correlation analysis between deregulated miRNAs and target proteins, RT-PCR analysis was used to validate the selected genes. The proteomic analysis showed that significantly deregulated proteins were associated with neurodegeneration pathways, response to oxidative stress, RNA processing, DNA repair, and apoptotic process following exposure to NA. The OpenArray analysis confirmed that NA exposure significantly altered miRNAs that regulate P53 signaling, Wnt signaling, cell death, and cell cycle pathways. The RT-PCR validation studies concur with proteomic data as marker genes associated with autophagy and apoptosis (HO-1, SQSTM1, LC-3, Cas3, Apaf1, HSP70, and SNCA1) were altered following NA exposure. It was observed that the treatment of NOB significantly restored the deregulated miRNAs and proteins to their basal levels. Hence, it may be considered one of its neuroprotective mechanisms. Together, the findings are promising to demonstrate the potential applicability of NOB as a neuroprotectant against chemical-induced neurotoxicity.

Human amniotic epithelial cells (HAECS); a potential cell type for the hepatic disorders.

OBJECTIVE: To isolate a homogenous population of human amniotic epithelial cells (hAECs) from the amniotic membrane of the human placenta and differentiate them into hepatic-like cells with the help of small molecules. METHODS: hAECs were isolated by using the enzymatic digestion method and characterized for the presence of specific stem cell markers. In-vitro, hepatic differentiation of hAECs was carried out by using a combination of small molecules. Differentiated cells were observed under a live cell imaging microscope for morphological changes followed by gene and protein expression analysis by qPCR and immunocytochemistry respectively. RESULTS: The isolated hAECs attained characteristic cuboid epithelial shape and express stem cells marker. The hepatic differentiation method was optimized based on soluble chemical compounds supplied in the culture medium. The differentiated hAECs phenotypically acquire hepatic-like cell features and expressed hepatic markers as well as hepatic protein albumin at immature levels. CONCLUSIONS: The isolated population of hAECs is highly proliferative. Moreover, hepatic markers expression in the isolated hAECs makes them an exclusive source for the treatment of chronic liver diseases.

Understanding the Mechanisms of Change in the Supportive and Respectful Maternity Care Intervention in Sindh, Pakistan: Provider Perspectives.

INTRODUCTION: We conducted this qualitative investigation to explore the mechanisms of change in providing respectful care resulting from the supportive and respectful maternity care intervention (S-RMC) in Sindh, Pakistan. METHODS: We applied the principles of realist evaluation methodology with a descriptive explanatory research design. We conducted in-depth interviews with 36 maternity care providers at secondary-level public health facilities where S-RMC was implemented for 6 months. The S-RMC broad components included capacity-building of maternity teams and systemic changes for improvements in governance and accountability within public health facilities. Data were analyzed using a deductive content analysis approach. RESULTS: We identified mechanisms of change, categorized by the S-RMC components: (1) S-RMC training: insight into women's feelings and rights, realization of the value that nonclinical staff can play, understanding of team coordination, orientation in psychosocial components of maternity care; (2) assessment of women's psychosocial vulnerabilities: identification of women's differential needs beyond routine care to provide woman-centered care; (3) psychosocial support: effective engagement with women and within maternity teams and the customization of woman- and companion-focused care; (4) care coordination: improved coordination among clinical and nonclinical staff to provide personalized care and psychosocial support and proper handover to ensure continuity of care; (5) assessment of quality of care: identification of service gaps from women's feedback; and (6) performance review and accountability: monthly performance review meetings to establish team member communication, systematic awareness of the maternity team's performance and challenges, and implementation of collective corrective actions. CONCLUSION: Our findings pointed to S-RMC working along multiple pathways-and concertedly with various health system components-to enable positive processes and behavioral change in maternity teams.

Elucidating the effects of heavy metals contamination on vital organ of fish and migratory birds found at fresh water ecosystem.

Heavy metal pollution in aquatic environments threatens marine life and lowers the quality of freshwater supplies. This research aimed to quantify the heavy metal concentration in fish, avian tissue, and water of the Mangla reservoir. Concentrations of heavy metals such as Cu, Cd, Cr, and Pb were determined in five vital organs of six species of fishes (Cirrhinus cirrhosis, Catla catla, Hypophthalmichthys molitrix, Wallagu attu, Cyprinus carpio, Sperata seenghala) and five species of migratory birds (Anas strepera, Aythya ferina, Anas platyrhynchos, Anas crecca, Anas clypeata) and water of Mangla dam. Heavy metal concentration was observed with AAS' help after the samples' complete chemical digestion. The average concentration of these metals in water samples was higher than the mean values in fish and birds. Heavy metals damaged fish and birds in the same order: Cd > Cu > Cr > Pb. The results of this research will hopefully prompt further consideration on the dangers of heavy metal contamination in freshwater ecosystem.

In Vitro Biofilm-Mediated Biodegradation of Pesticides and Dye-Contaminated Effluents Using Bacterial Biofilms.

Overuse of pesticides in agricultural soil and dye-polluted effluents severely contaminates the environment and is toxic to animals and humans making their removal from the environment essential. The present study aimed to assess the biodegradation of pesticides (cypermethrin (CYP) and imidacloprid (IMI)), and dyes (malachite green (MG) and Congo red (CR)) using biofilms of bacteria isolated from pesticide-contaminated soil and dye effluents. Biofilms of indigenous bacteria, i.e., Bacillus thuringiensis 2A (OP554568), Enterobacter hormaechei 4A (OP723332), Bacillus sp. 5A (OP586601), and Bacillus cereus 6B (OP586602) individually and in mixed culture were tested against CYP and IMI. Biofilms of indigenous bacteria i.e., Lysinibacillus sphaericus AF1 (OP589134), Bacillus sp. CF3 (OP589135) and Bacillus sp. DF4 (OP589136) individually and in mixed culture were tested for their ability to degrade dyes. The biofilm of a mixed culture of B. thuringiensis + Bacillus sp. (P7) showed 46.2% degradation of CYP compared to the biofilm of a mixed culture of B. thuringiensis + E. hormaechei + Bacillus sp. + B. cereus (P11), which showed significantly high degradation (70.0%) of IMI. Regarding dye biodegradation, a mixed culture biofilm of Bacillus sp. + Bacillus sp. (D6) showed 86.76% degradation of MG, which was significantly high compared to a mixed culture biofilm of L. sphaericus + Bacillus sp. (D4) that degraded only 30.78% of CR. UV-VIS spectroscopy revealed major peaks at 224 nm, 263 nm, 581 nm and 436 nm for CYP, IMI, MG and CR, respectively, which completely disappeared after treatment with bacterial biofilms. Fourier transform infrared (FTIR) analysis showed the appearance of new peaks in degraded metabolites and disappearance of a peak in the control spectrum after biofilm treatment. Thin layer chromatography (TLC) analysis also confirmed the degradation of CYP, IMI, MG and CR into several metabolites compared to the control. The present study demonstrates the biodegradation potential of biofilm-forming bacteria isolated from pesticide-polluted soil and dye effluents against pesticides and dyes. This is the first report demonstrating biofilm-mediated bio-degradation of CYP, IMI, MG and CR utilizing soil and effluent bacterial flora from Multan and Sheikhupura, Punjab, Pakistan.

Zinc Foliar Application Mitigates Cadmium-Induced Growth Inhibition and Enhances Wheat Growth, Chlorophyll Contents, and Yield.

Cadmium (Cd) is a toxic heavy metal that significantly threatens plants and the environment. Its toxicity in plants can result in various adverse effects, including reduced growth, altered metabolism, and cell damage. Cadmium can also interfere with nutrient uptake, particularly zinc (Zn), leading to Zn deficiency and further exacerbating Cd toxicity. On the other hand, foliar application of zinc might be a useful strategy to mitigate cadmium (Cd) toxicity in plants. Hence, a pot experiment was conducted with three replications. The wheat plants were treated with various concentrations of Zn as a foliar spray (control, 0.1, 0.2, 0.4, and 0.5%) in Cd-spiked soil in pots. The results showed that foliar use of Zn at 0.4 or 0.5% resulted in higher plant height, grain yield, and dry matter yield than the control group. Using Zn as foliar spray enriched shoot and grain Zn content while reducing Cd content in the shoot and grain. The leaf's electrolyte leakage (EL) decreased by 15.4, 29.8, 40.7, and 45.9% in the Zn 0.1%, Zn 0.2%, Zn 0.4%, and Zn 0.5% treatments, respectively, compared to the control treatment. Regarding superoxide dismutase (SOD) activity, Zn 0.5% treatment showed a decrease of 42.9% over control. Specifically, the Zn 0.1% showed a 27.2%, Zn 0.2% showed a 56.8%, Zn 0.4% showed a 91.1%, and Zn 0.5% showed a 133.7% increase in total chlorophyll content than control. Based on the results, it is recommended that 0.4% Zn solution may be used for foliar application for enhancing crop productivity and Zn concentration in plants under high Cd stress. Additionally, continued research on the mechanisms of cadmium uptake, transport, and detoxification in plants may lead to the identification of new targets for intervention.

Reconnaissance Survey of Organic Contaminants of Emerging Concern in the Kabul and Swat Rivers of Pakistan.

The Swat and Kabul rivers of northern Pakistan are within an important regional watershed that supports river-based livelihoods and is impacted by untreated effluent discharges and municipal solid waste. Evidence indicates that fish populations are decreasing in these rivers. One potential cause of poor aquatic health is pollution; therefore, we investigated the presence of contaminants of emerging concern (CECs) in the river systems. Water samples were collected in the Kabul River (n = 9) and Swat River (n = 10) during seasons of high (summer 2018) and low (winter 2019) river flow. Agrochemicals, pharmaceuticals, plasticizers, chemicals in personal care products, and hormones were quantified via liquid chromatography high-resolution mass spectrometry. In the Swat River, caffeine (18-8452 ng/L), N,N-diethyl-meta-toluamide (DEET; 16-56 ng/L), and plasticizers (13-7379 ng/L) were detected at all sites during both seasons, while butachlor (16-98 ng/L) was detected only during high flow. In the Kabul River, caffeine (12-2081 ng/L) and several plasticizers (91-722 ng/L) were detected at all sites during both seasons, while DEET (up to 97 ng/L) was detected only during high flow. During low flow, pharmaceuticals (analgesics and nonsteroidal anti-inflammatory drugs) were quantified in both rivers (up to 823 ng/L), with detection frequencies from 70% to 100% and 0% to 78% in the Swat and Kabul Rivers, respectively. Intermittent-use and natural seasonal processes (increased runoff and dilution from rainfall and snowmelt) yielded higher agrochemical concentrations and lower concentrations of continuous-use compounds (e.g., caffeine) during high flow. The present study provides the first insight into CEC concentrations in the Swat River, additional insight into the Kabul River stressors, and, overall, contaminant risks to aquatic life. Environ Toxicol Chem 2023;42:2599-2613. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Parasite Diversity in a Freshwater Ecosystem.

Parasites are a significant component of biodiversity. They negatively affect fish appearance, growth, and reproduction. In this study, the prevalence of infection, diversity, and mean intensity of parasites were examined in 9 freshwater fish species (45 samples per fish species). Ecto-parasites were examined on the skin, gills, and fins with a hand lens. Wet mounts were prepared using mucosal scrapings from all the external and internal organs of the sampled fish. Microscopy, muscle compression, and the pepsin-HCL artificial digestion technique were also performed. In this study, 26 species of parasites were identified including three taxa belonging to 9 species of protozoan parasites, 11 treamtodes, and 6 monogenean parasites. The identified protozoan parasites were Entamoeba histolitica, Chilodonella sp., Coccidia sp., Costia sp., Cryptobia sp., Ichthyopthiris-multifilis, Microsporidia, Piscinoodinium sp., and Ichthyobodo necator. The identified trematode parasites were Fasciola gigantica, Echinostoma revolutum, Fasciola hepatica, Haplorchis pumilio, Brachylaima cribbi, Echinostoma cinetorchis, Neascus sp., Deropegus sp., Trematode Soldier, Centrocestus formosanus, and Clinostomum marginatum. The identified monogenean parasites were Dactylogyrus limipopoensis, Dactylogyrus anchoratus, Dactylogyrus myersi, Dactylogyrus vastator, Gyrodactylus salaris, and Ancyrocephalus. The diversity of parasites was maximum at the Okara site. The host's organs that were targeted for parasitic infection included the intestine, liver, gills, fins, skin, and kidneys. The majority of the parasites were identified in Labeo rohita followed by Hypophthalmichthys molitrix, Ctenopharyngodon idella, Oreochromis niloticus, Cyprinus carpio, and Wallagu attu. Two species appeared to be resistant species because none of the parasites were observed in Notopterus notopterus or Sperata seenghala. This study also concluded that the prevalence of parasites increased with increasing length, size, and age of fish.

Evaluating the Efficacy of Activated Carbon in Minimizing the Risk of Heavy Metals Contamination in Spinach for Safe Consumption.

Toxicity induced by heavy metals is a major concern in agriculture as it decreases crops' growth and yield and leads to the deterioration of food quality. Recently, activated carbon has been identified as a possible solution. It can potentially improve crop nutrition and immobilize heavy metals in soil. That is why a glasshouse trial was conducted to investigate the effects of sugarcane bagasse-derived biochar on spinach growth and the availability of cadmium (Cd) and chromium (Cr) in artificially contaminated soil. The soil was placed in pots and contaminated with Cd and Cr at a rate of 10 mg kg-1. Biochar was added to the soil at concentrations of 0 (control), 0 (contaminated control), 100, 150, and 200 g, and 10-day-old nursery spinach plants were transplanted to the pots. The results showed that applying 200 g of biochar significantly increased shoot weight (235 g), soil pH, electrical conductivity, and organic matter. The highest levels of Cd (27.71 mg kg-1) and Cr (20.44 mg kg-1) were observed in the contaminated control pots, while the lowest levels of Cd (16.80 mg kg-1) and Cr (9.80 mg kg-1) were found in pots treated with 200 g of biochar (2%). Similarly, the highest levels of Cd (35.80 mg kg-1) and Cr (40.24 mg kg-1) in the roots were found in the contaminated control pots, while the lowest levels of Cd (19.26 mg kg-1) and Cr (21.34 mg kg-1) were observed in pots treated with 200 g of biochar. Biochar application at a rate of 2% can immobilize Cd and Cr in the soil and improve chlorophyll contents, carotenoids, photosynthetic rate, transpiration rate, and stomatal conductance in spinach in Cd- and Cr-contaminated soils. Further long-term field studies will be necessary to determine the feasibility of applying biochar as an organic amendment for enhancing spinach growth and reducing Cd and Cr bioavailability in contaminated soil.

Effect of the SPRING home visits intervention on early child development and growth in rural India and Pakistan: parallel cluster randomised controlled trials.

Introduction: Almost 250 million children fail to achieve their full growth or developmental potential, trapping them in a cycle of continuing disadvantage. Strong evidence exists that parent-focussed face to face interventions can improve developmental outcomes; the challenge is delivering these on a wide scale. SPRING (Sustainable Programme Incorporating Nutrition and Games) aimed to address this by developing a feasible affordable programme of monthly home visits by community-based workers (CWs) and testing two different delivery models at scale in a programmatic setting. In Pakistan, SPRING was embedded into existing monthly home visits of Lady Health Workers (LHWs). In India, it was delivered by a civil society/non-governmental organisation (CSO/NGO) that trained a new cadre of CWs. Methods: The SPRING interventions were evaluated through parallel cluster randomised trials. In Pakistan, clusters were 20 Union Councils (UCs), and in India, the catchment areas of 24 health sub-centres. Trial participants were mother-baby dyads of live born babies recruited through surveillance systems of 2 monthly home visits. Primary outcomes were BSID-III composite scores for psychomotor, cognitive and language development plus height for age z-score (HAZ), assessed at 18 months of age. Analyses were by intention to treat. Results: 1,443 children in India were assessed at age 18 months and 1,016 in Pakistan. There was no impact in either setting on ECD outcomes or growth. The percentage of children in the SPRING intervention group who were receiving diets at 12 months of age that met the WHO minimum acceptable criteria was 35% higher in India (95% CI: 4-75%, p = 0.023) and 45% higher in Pakistan (95% CI: 15-83%, p = 0.002) compared to children in the control groups. Discussion: The lack of impact is explained by shortcomings in implementation factors. Important lessons were learnt. Integrating additional tasks into the already overloaded workload of CWs is unlikely to be successful without additional resources and re-organisation of their goals to include the new tasks. The NGO model is the most likely for scale-up as few countries have established infrastructures like the LHW programme. It will require careful attention to the establishment of strong administrative and management systems to support its implementation.

Occurrence and Bioaccumulation Patterns of Per- and Polyfluoroalkyl Substances (PFAS) in the Marine Environment.

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic compounds used in commercial applications, household products, and industrial processes. The concern around the environmental persistence, bioaccumulation and toxicity of this vast contaminant class continues to rise. We conducted a review of the scientific literature to compare patterns of PFAS bioaccumulation in marine organisms and identify compounds of potential concern. PFAS occurrence data in seawater, sediments, and several marine taxa was analyzed from studies published between the years 2000 and 2020. Taxonomic and tissue-specific differences indicated elevated levels in protein-rich tissues and in air-breathing organisms compared to those that respire in water. Long-chain perfluoroalkyl carboxylic acids, particularly perfluoroundecanoic acid, were detected at high concentrations across several taxa and across temporal studies indicating their persistence and bioaccumulative potential. Perfluorooctanesulfonic acid was elevated in various tissue types across taxa. Precursors and replacement PFAS were detected in several marine organisms. Identification of these trends across habitats and taxa can be applied towards biomonitoring efforts, determination of high-risk taxa, and criteria development. This review also highlights challenges related to PFAS biomonitoring including (i) effects of environmental and biological variables, (ii) evaluation of protein binding sites and affinities, and (iii) biotransformation of precursors.

Promoting Supportive and Respectful Maternity Care in Public Health Facilities in Sindh, Pakistan: A Theory-Informed Health System Intervention.

BACKGROUND: Disrespect, abuse, discrimination, and lack of emotional support characterize intrapartum care in the health systems of many low- and middle-income countries. Although the World Health Organization (WHO) provides frameworks and guidelines to address this issue, no operational model exists that effectively incorporates WHO intrapartum care guidelines into routine public health services. We aimed to develop and pilot-test a theory-driven, service-delivery intervention package linking dignified care with perinatal mental health to promote psychosocially supportive and respectful maternity care (S-RMC) in public health facilities in Sindh, Pakistan. METHODS: Using a mixed-method, pre-post design, the study was implemented in 6 secondary-level public health facilities in 2 rural districts of Southern Sindh, Pakistan. Its development was guided by the COM-B framework and informed by a literature review, formative research, and consultative sessions with implementers. The intervention was implemented in March-September 2021 and compared women's experiences of S-RMC during childbirth at baseline (n=313) and endline (n=314). We used descriptive statistics and linear regression techniques for analysis. RESULTS: A substantial reduction was observed in the cumulative level of overall mistreatment from baseline to endline, yielding a relative change of 50% (P<.001). Similar change was evident across different types of mistreatment: physical abuse (75%), verbal abuse (72%), ineffective communication (60%), nonconfidential care (78%), health system conditions and constraints (25%), noninclusive care (28%), lack of supportive care (52%), and stigma and discrimination (82%). Furthermore, we observed a significant reduction in the proportion of women experiencing symptoms of anxiety and depression before and after the intervention. CONCLUSION: This intervention built the capacity of maternity teams while improving accountability, health information systems, and governance measures. Given its promise to promote supportive and respectful childbirth in public health facilities, a large-scale effectiveness evaluation across diverse settings is warranted.

Psychosocial support during childbirth: Development and adaptation of WHO's Mental Health Gap Action Programme (mhGAP) for maternity care settings.

INTRODUCTION: Poor psychosocial support and lack of respectful care for women during childbirth are commonplace in health facilities in low- and middle-income countries. While WHO recommends providing supportive care to pregnant women, there is a scarcity of material for building the capacity of maternity staff to provide systematic and inclusive psychosocial support to women in the intrapartum phase, and prevent work stress and burnout in maternity teams. To address this need we adapted WHO's mhGAP for maternity staff to provide psychosocial support in labour room settings in Pakistan. Mental Health Gap Action Programme (mhGAP) is an evidence-based guidance which provides psychosocial support in resource-limited health care settings. This paper aims to describe the adaptation of mhGAP to develop psychosocial support capacity building materials for maternity staff to provide support to maternity patients, and also to staff, in the labour room context. METHODS: Adaptation was conducted within the Human-Centered-Design framework in three phases: inspiration, ideation, and implementation feasibility. In inspiration, a review of national-level maternity service-delivery documents and in-depth interviews of maternity staff were conducted. Ideation involved a multidisciplinary team to develop capacity-building materials by adapting mhGAP. This phase was iterative and included cycles of pretesting, deliberations, and revision of materials. In implementation feasibility, materials were tested via the training of 98 maternity staff and exploring system feasibility via post-training visits to health facilities. RESULTS: Inspiration phase identified gaps in policy directives and implementation and formative study identified limited understanding and skills of staff to assess patients' psychosocial needs and provide appropriate support. Also, it became evident that staff themselves needed psychosocial support. In ideation, team developed capacity-building materials comprising two modules: one dedicated to conceptual understanding, the other to implementing psychosocial support in collaboration with maternity staff. In implementation feasibility, staff found the materials relevant and feasible for the labour room setting. Finally, users and experts endorsed usefulness of the materials. CONCLUSION: Our work in developing psychosocial-support training materials for maternity staff extends the utility of mhGAP to maternity care settings. These materials can be used for capacity-building of maternity staff and their effectiveness can be assessed in diverse maternity care settings.

Facile approach for nanoconfinement of multilayer graphene oxide with polyether polyurethane sponge as biological carrier for the establishment of microalgal-bacterial bioreactor.

Physically precise and mechanically robust biocarrier is basic and urgent requirement of algal-bacterial wastewater treatment plants for homogenously biofilm growth. Herein, a highly efficient graphene oxide (GO) coordinated polyether polyurethane (PP) sponge was synthesized through GO incorporation into PP sponge to improve the GO coating, followed by UV-light treatment for industrial application. The resulted sponge showed remarkable physiochemical characteristics, excellent thermal (>0.02 Wm-1 K-1) and mechanical (>363.3 KPa) stability. To test the potential of sponge in real world scenarios, the activated sludge from real wastewater treatment plant was utilized. Interestingly, the GO-PP sponge enhanced the electron transfer between microorganisms and promoted the standardized microorganism's growth and biofilm formation (22.7 mg/d per gram sponge, 172.1 mg/g), providing the feasibility to accomplish a symbiotic system within specifically design upgraded algal-bacterial reactor. Furthermore, the continuous flow process by utilizing GO-PP sponge in algal-bacterial reactor demonstrated the effectiveness in treating low concentration antibiotic wastewater, presenting 86.7 % removal rate and >85 % after 20 cycles. Overall, this work illustrates an applicable strategy to develop a sophisticated modified pathway for the next-generation biological-based applications.

Emerging Mechanisms of Skeletal Muscle Homeostasis and Cachexia: The SUMO Perspective.

Mobility is an intrinsic feature of the animal kingdom that stimulates evolutionary processes and determines the biological success of animals. Skeletal muscle is the primary driver of voluntary movements. Besides, skeletal muscles have an immense impact on regulating glucose, amino acid, and lipid homeostasis. Muscle atrophy/wasting conditions are accompanied by a drastic effect on muscle function and disrupt steady-state muscle physiology. Cachexia is a complex multifactorial muscle wasting syndrome characterized by extreme loss of skeletal muscle mass, resulting in a dramatic decrease in life quality and reported mortality in more than 30% of patients with advanced cancers. The lack of directed treatments to prevent or relieve muscle loss indicates our inadequate knowledge of molecular mechanisms involved in muscle cell organization and the molecular etiology of cancer-induced cachexia (CIC). This review highlights the latest knowledge of regulatory mechanisms involved in maintaining muscle function and their deregulation in wasting syndromes, particularly in cachexia. Recently, protein posttranslational modification by the small ubiquitin-like modifier (SUMO) has emerged as a key regulatory mechanism of protein function with implications for different aspects of cell physiology and diseases. We also review an atypical association of SUMO-mediated pathways in this context and deliberate on potential treatment strategies to alleviate muscle atrophy.

A Novel Homozygous Nonsense Variant in the DYM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family.

(1) Background: Dyggve-Melchior-Clausen Syndrome is a skeletal dysplasia caused by a defect in the DYM gene (OMIM number 607461). Pathogenic variants in the gene have been reported to cause Dyggve-Melchior-Clausen (DMC; OMIM 223800) dysplasia and Smith-McCort (SMC; OMIM 607326) dysplasia. (2) Methods: In the present study, large consanguineous families with five affected individuals with osteochondrodysplasia phenotypes were recruited. The family members were analyzed by polymerase chain reaction for homozygosity mapping using highly polymorphic microsatellite markers. Subsequent to linkage analysis, the coding exons and exon intron border of the DYM gene were amplified. The amplified products were then sent for Sanger sequencing. The structural effect of the pathogenic variant was analyzed by different bioinformatics tools. (3) Results: Homozygosity mapping revealed a 9 Mb homozygous region on chromosome 18q21.1 harboring DYM shared by all available affected individuals. Sanger sequencing of the coding exons and exon intron borders of the DYM gene revealed a novel homozygous nonsense variant [DYM (NM_017653.6):c.1205T>A, p.(Leu402Ter)] in affected individuals. All the available unaffected individuals were either heterozygous or wild type for the identified variant. The identified mutation results in loss of protein stability and weekend interactions with other proteins making them pathogenic (4) Conclusions: This is the second nonsense mutation reported in a Pakistani population causing DMC. The study presented would be helpful in prenatal screening, genetic counseling, and carrier testing of other members in the Pakistani community.

Applying the COM-B Model to Understand the Drivers of Mistreatment During Childbirth: A Qualitative Enquiry Among Maternity Care Staff.

INTRODUCTION: Respectful maternity care (RMC) during childbirth is an integral component of quality of care. However, women's experiences of mistreatment are prevalent in many low- and middle-income countries. This is a complex phenomenon that has not been well explored from a behavioral science perspective. We aimed to understand the behavioral drivers of mistreatment during childbirth among maternity care staff at public health facilities in the Sindh province of Pakistan. METHODS: Applying the COM-B (capability-opportunity-motivation that leads to behavior change) model, we conducted semistructured in-depth interviews among clinical and nonclinical staff in public health facilities in Thatta and Sujawal, Sindh, Pakistan. Data were analyzed using thematic deductive analysis, and findings were synthesized using the COM-B model. RESULTS: We identified several behavioral drivers of mistreatment during childbirth: (1) institutional guidelines on RMC and training opportunities were absent, resulting in a lack of providers' knowledge and skills; (2) facilities lacked the infrastructure to maintain patient privacy and confidentiality and did not permit males as birth companions; (3) lack of provider performance monitoring system and patient feedback mechanism contributed to providers not feeling appreciated or recognized. Staff bias against patients from lower castes contributed to patient abuse and mistreatment. The perspectives of clinical and nonclinical staff overlapped regarding potential drivers of mistreatment during childbirth. CONCLUSIONS: Addressing mistreatment during childbirth requires improving the knowledge and capacity of maternity staff on RMC and psychosocial support to enhance their understanding of RMC. At the health facility level, governance and accountability mechanisms in routine supervision and monitoring of staff need to be improved. Patients' feedback should be incorporated for continuous improvement in providing maternity care services that meet patients' preferences and needs.