Health research priorities in Pakistan: A Child Health and Nutrition Research Initiative (CHNRI) exercise.

Background: The National Health Vision of Pakistan 2016-2025 is to provide affordable health services through a resilient and responsive health system for achieving health-related Sustainable Development Goals (SDGs) and universal health coverage (UHC) targets. Through this study, we wanted to identify the research priorities at the national level that would help to provide the necessary evidence for achieving this vision through essential package of health services (EPHS). Methods: We followed World Health Organization (WHO) guidance for undertaking research priority-setting exercises and the Child Health and Nutrition Research Initiative (CHNRI) methodology in conducting this national exercise. The proposed research options for the next three to five years were identified in five thematic research areas: communicable diseases; non-communicable diseases (NCDs) and injuries; reproductive, maternal, newborn, child, and adolescent health (RMNCAH); mental health; and health systems and services. We assessed these research options against five priority-setting criteria: feasibility, public health importance, sustainability, equity, and community involvement. Results: Forty-three experts proposed 272 research ideas, which were consolidated into a list of 155 research options and sent back to the experts for scoring. The top 10 research priorities in each of the five research areas were identified based on the weighted research priority scores (wRPS) rankings. Tuberculosis and antimicrobial resistance; NCD screening and prevention; maternal and neonatal mortality; mental health of children, adolescents, and youth; and human resource management were the issues that were most frequently reflected in the list of research priorities. Most research priorities aimed to identify barriers to the implementation of interventions. Conclusions: Through this exercise, we identified the top 50 national health research priorities, which also have a strong correlation with EPHS interventions. To realise the findings of this exercise, funding agencies should establish funding mechanisms to support the undertaking of the identified research priorities, and academic researchers should actually utilise them in future studies. Such activities could hopefully contribute to achieving the national health goals.

Phosphorus High-rate application through band placement improved cotton productivity under arid climate.

The plant-available soil phosphorus rate and methods for applying phosphatic fertilizer and soil P-fixation capacity are critical factors for lower cotton productivity in Southern Punjab, Pakistan. Hence, a two-year study was conducted in Central Cotton Research Institute (CCRI), Multan, Pakistan, to examine the effects of various P rates and application methods on cotton crop output during the growing seasons of 2014 and 2015. Phosphorus was applied in four rates (0, 40, 80, and 120 kg ha-1 P2O5) using broadcast, band application, and fertigation methods. Results indicated that the impact of P rates was statistically significant on plant height, the number of nodes, monopodial and sympodial branches, leaf area index, harvest index, and seed cotton yield. The greater P application (120 kg P2O5 ha-1) had a better effect on cotton productivity than the lower application rates (0, 40, and 80 kg P2O5 ha-1). The band application responded better on nodes plant-1, sympodial branches plant-1, boll weight, leaf area index, lint yield, and harvest during the growing season 2015. Therefore, by adopting the band application coupled with 120 kg P2O5 ha-1 rather than the conventional method of broadcast, productivity of cotton crops could be increased.

Biochemical and Oxidative Biomarkers in Preeclampsia.

OBJECTIVE: To determine the biochemical and oxidative stress parameters as biomarkers in preeclampsia. STUDY DESIGN: Cross-sectional analytical study. Place and Duration of the Study: Departments of Obstetrics / Gynaecology and Biochemistry, Quaid-e-Azam Medical College, Bahawalpur, Pakistan, from September 2022 to February 2023. METHODOLOGY: Women with preeclampsia were selected based on blood pressure exceeding 140/90 mmHg and proteinuria levels exceeding 300 mg/24 hours or showing a +1 on a dipstick test. Normotensive pregnant women were selected as controls. Venous blood was taken and centrifuged, and routine biochemical methods were used to estimate serum lipid profile levels and minerals. The estimation of oxidative stress enzymes was carried out manually using special chemicals. Student's t-test and Pearson's correlation were applied to analyse the result. RESULTS: The study included 228 subjects: 114 preeclampsia patients and 114 normal pregnant women as controls. The mean systolic blood pressure was measured at 166.25 mmHg and the diastolic blood pressure was 92.80 mmHg (p <0.001). All lipid profile estimations showed notable abnormalities, but the mean level of triglycerides (TGs) (214.90 ± 15.59 mg/dl) in preeclamptic patients was significantly elevated (p <0.05). In terms of minerals, all were deranged but magnesium (1.37 ± 0.35 mg/dl) and calcium (7.55 ± 0.45 mg/dl) were significantly decreased (p <0.05). All oxidative enzyme levels were increased (p <0.05) but malondialdehyde (MDA) with a mean level of 2.58 ± 0.40 nmol/ml was significantly elevated. The Pearson's correlation of these parameters with blood pressure also showed a positive association. CONCLUSION:  Total cholesterol triglyceride in the lipid profile, calcium and magnesium in minerals, and MDA in oxidative parameters were markedly deranged and exhibited significant associations with the severity of the disease, so could be used as disease biomarkers of preeclampsia. KEY WORDS: Preeclampsia, Gestational hypertension, Proteinuria, Lipid profile, Minerals, Oxidative stress.

In vivo biological screening of extract and bioactive compound from Ficus benghalensis L. and their in silico molecular docking analysis.

BACKGROUND: Ficus benghalensis has been used by local health care practitioners to treat pain, inflammation, rheumatism, and other health issues. OBJECTIVE: In this study, the crude extract and diverse fractions, along with the isolated compound of F. benghalensis were examined for their roles as muscle relaxants, analgesics, and sedatives. METHODS: The extract and isolated compound 1 were screened for muscle-relaxant, analgesic, and sedative actions. The acetic acid-mediated writhing model was utilized for analgesic assessment, the muscle relaxant potential was quantified through traction and inclined plan tests, and the open field test was applied for sedative effects. RESULTS: The extract/fractions (25, 50, and 100 mg/kg) and isolated compounds (2.5, 5, 10, and 20 mg/kg) were tested at various doses. A profound (p< 0.001) reduce in the acetic acid-mediated writhing model was observed against carpachromene (64.44%), followed by ethyl acetate (60.67%) and methanol (58.42%) fractions. A marked (p< 0.001) muscle relaxant activity was noticed against the isolated compound (71.09%), followed by ethyl acetate (66.98%) and methanol (67.10%) fractions. Regarding the sedative effect, a significant action was noted against the isolated compound (71.09%), followed by ethyl acetate (66.98%) and methanol (67.10%) fractions. Furthermore, the binding modes of the isolated compounds were explored using molecular docking. The molecular docking study revealed that the isolated compound possessed good binding affinity for COX2 and GABA. Our isolated compound may possess inhibitory activity against COX2 and GABA receptors. CONCLUSION: The extract and isolated compounds of Ficus benghalensis can be used as analgesics, muscle relaxants, and sedatives. However, detailed molecular and functional analyses are essential to ascertain their function as muscle relaxants, analgesics, and sedatives.

Advances in MXene-based technologies for the remediation of toxic phenols: A comprehensive review.

The pressing global issue of organic pollutants, particularly phenolic compounds derived primarily from industrial wastes, poses a significant threat to the environment. Although progress has been made in the development of low-cost materials for phenolic compound removal, their effectiveness remains limited. Thus, there is an urgent need for novel technologies to comprehensively address this issue. In this context, MXenes, known for their exceptional physicochemical properties, have emerged as highly promising candidates for the remediation of phenolic pollutants. This review aims to provide a comprehensive and critical evaluation of MXene-based technologies for the removal of phenolic pollutants, focusing on the following key aspects: (1) The classification and categorization of phenolic pollutants, highlighting their adverse environmental impacts, and emphasizing the crucial need for their removal. (2) An in-depth discussion on the synthesis methods and properties of MXene-based composites, emphasizing their suitability for environmental remediation. (3) A detailed analysis of MXene-based adsorption, catalysis, photocatalysis, and hybrid processes, showcasing current advancements in MXene modification and functionalization to enhance removal efficiency. (4) A thorough examination of the removal mechanisms and stability of MXene-based technologies, elucidating their operating conditions and stability in pollutant removal scenarios. (5) Finally, this review concludes by outlining future challenges and opportunities for MXene-based technologies in water treatment, facilitating their potential applications. This comprehensive review provides valuable insights and innovative ideas for the development of versatile MXene-based technologies tailored to combat water pollution effectively.

Timing of development of osteoradionecrosis post head and neck radiotherapy: does a safe time interval exist for dental extraction?

INTRODUCTION: Risk factors for developing osteoradionecrosis (ORN) are well known, but less is known about factors influencing the interval between radiotherapy and the onset of ORN. Also, it is unknown whether there is any specific period post-radiotherapy with a reduced probability of ORN when irradiated teeth require extraction. PURPOSE: The primary aim of this study was to identify factors influencing the interval in developing ORN in the following subgroups of patients: (1) patients who spontaneously developed ORN, (2) surgical-intervention-related ORN with a particular focus on patients after mandibulectomy. The secondary aim was to attempt to identify a possible time for safer dental intervention after primary treatment. MATERIALS AND METHODS: The authors retrospectively analysed 1608 head and neck cancer (HNC) patients treated in a single centre. Time intervals were measured from the end of radiotherapy to the development of ORN and further analysed in the subgroups listed above. RESULTS: In all, 141 patients (8.8%) developed intra-oral ORN. Median time from radiotherapy to ORN development in the whole cohort was 9 months. Median interval for spontaneous ORN was 8 months, 6.5 months for intervention-related ORN, and 15 months for patients post-mandibulectomy. In patients who required dental extraction preradiotherapy, median interval of ORN onset was 5 months. CONCLUSION: In our study, a slightly higher proportion of patients with intervention developed ORN earlier in comparison with spontaneous ORN. The period from 12-18 months after radiotherapy was identified as having the highest probability of developing ORN in patients after mandibulectomy. A time for safer dental intervention after primary treatment was not identified.

An Oxalato-Bridged Cu(II)-Based 1D Polymer Chain: Synthesis, Structure, and Adsorption of Organic Dyes.

In the current research, we prepared a polymeric framework, {[Cu(C2O4)(C10H8N2)]·H2O·0.67(CH3OH)]}n (1) (where C2O4 = oxalic acid; C10H8N2 = 2,2-bipyridine), and explored this compound for adsorption of methylene blue (MB) and methyl orange (MO). The crystal structure of the compound consists of a Cu(ox)(bpy) unit connected via oxalate to form a 1D polymeric chain. This polymeric chain has adsorption capacities of 194.0 and 167.3 mg/g for MB and MO, respectively. The removal rate is estimated to be 77.6% and 66.9% for MB and MO, respectively. The plausible mechanisms for adsorption are electrostatic, π-π interaction, and OH-π interaction for dye stickiness. The adsorbent surface exhibits a negative charge that produces the electrostatic interaction, resulting in excellent adsorption efficiency at pH 7 and 8. The pseudo-first-order kinetic model is selected for the adsorption of MB and MO on the adsorbent. The reported compound has remarkable efficiency for sorption of organic dyes and can be useful in wastewater treatment.

Healthcare consumers' perceptions of incentive-linked prescribing: A scoping review.

Incentive-linked prescribing (ILP) is considered a controversial practice universally. If incentivised, physicians may prioritise meeting pharmaceutical sales targets through prescriptions, rather than considering patients' health and wellbeing. Despite the potential harms of ILP to patients and important stakeholders in the healthcare system, healthcare consumers (HCCs) which include patients and the general public often have far less awareness about the practice of pharmaceutical incentivisation of physicians. We conducted a scoping review to explore what existing research says about HCCs' perceptions of the financial relationship between physicians and pharmaceutical companies. To conduct this scoping review, we followed Arksey and O'Malley's five-stage framework: identifying research questions, identifying relevant studies, selecting eligible studies, data charting, and collating, summarising, and reporting results. We also used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses' extension for scoping reviews (PRISMA-ScR), as a guide to organise the information in this review. Quantitative and qualitative studies with patients and the general public, published in the English language were identified through searches of Scopus, Medline (OVID), EMBASE (OVID), and Google Scholar. Three themes emerged through the analysis of the 13 eligible studies: understanding of incentivisation, perceptions of hazards linked to ILP, and HCCs' suggestions to address it. We found documentation that HCCs exhibited a range of knowledge from good to insufficient about the pharmaceutical incentivisation of physicians. HCCs perceived several hazards linked to ILP such as a lack of trust in physicians and the healthcare system, the prescribing of unnecessary medications, and the negative effect on physicians' reputations in society. In addition to strong regulatory controls, it is critical that physicians self-regulate their behaviour, and publicly disclose if they have any financial ties with pharmaceutical companies. Doing so can contribute to trust between patients and physicians, an important part of patient-focused care and a contributor to user confidence in the wider health system.

Recapitulation of Peste des Petits Ruminants (PPR) Prevalence in Small Ruminant Populations of Pakistan from 2004 to 2023: A Systematic Review and Meta-Analysis.

Peste des petits ruminants (PPR) is an extremely transmissible viral disease caused by the PPR virus that impacts domestic small ruminants, namely sheep and goats. This study aimed to employ a methodical approach to evaluate the regional occurrence of PPR in small ruminants in Pakistan and the contributing factors that influence its prevalence. A thorough search was performed in various databases to identify published research articles between January 2004 and August 2023 on PPR in small ruminants in Pakistan. Articles were chosen based on specific inclusion and exclusion criteria. A total of 25 articles were selected from 1275 studies gathered from different databases. The overall pooled prevalence in Pakistan was calculated to be 51% (95% CI: 42-60), with heterogeneity I2 = 100%, τ2 = 0.0495, and p = 0. The data were summarized based on the division into five regions: Punjab, Baluchistan, KPK, Sindh, and GB and AJK. Among these, the pooled prevalence of PPR in Sindh was 61% (95% CI: 46-75), I2 = 100%, τ2 = 0.0485, and p = 0, while in KPK, it was 44% (95% CI: 26-63), I2 = 99%, τ2 = 0.0506, and p < 0.01. However, the prevalence of PPR in Baluchistan and Punjab was almost the same. Raising awareness, proper surveillance, and application of appropriate quarantine measures interprovincially and across borders must be maintained to contain the disease.

Comparative Transcriptome and sRNAome Analysis Suggest Coordinated Citrus Immune Responses against Huanglongbing Disease.

Citrus Huanglongbing (HLB), caused by the phloem-inhibiting bacterium Candidatus Liberibacter asiaticus (CLas), is the most devastating citrus disease, intimidating citrus production worldwide. Although commercially cultivated citrus cultivars are vulnerable to CLas infection, HLB-tolerant attributes have, however, been observed in certain citrus varieties, suggesting a possible pathway for identifying innate defense regulators that mitigate HLB. By adopting transcriptome and small RNAome analysis, the current study compares the responses of HLB-tolerant lemon (Citrus limon L.) with HLB-susceptible Shatangju mandarin (Citrus reticulata Blanco cv. Shatangju) against CLas infection. Transcriptome analysis revealed significant differences in gene expression between lemon and Shatangju. A total of 1751 and 3076 significantly differentially expressed genes were identified in Shatangju and lemon, respectively. Specifically, CLas infected lemon tissues demonstrated higher expressions of genes involved in antioxidant enzyme activity, protein phosphorylation, carbohydrate, cell wall, and lipid metabolism than Shatangju. Wet-lab experiments further validated these findings, demonstrating increased antioxidant enzyme activity in lemon: APX (35%), SOD (30%), and CAT (64%) than Shatangju. Conversely, Shatangju plants exhibited higher levels of oxidative stress markers like H2O2 (44.5%) and MDA content (65.2%), alongside pronounced ion leakage (11.85%), than lemon. Moreover, microscopic investigations revealed that CLas infected Shatangju phloem exhibits significantly more starch and callose accumulation than lemon. Furthermore, comparative sRNA profiles revealed the potential defensive regulators for HLB tolerance. In Shatangju, increased expression of csi-miR166 suppresses the expression of disease-resistant proteins, leading to inadequate defense against CLas. Conversely, reduced expression of csi-miR166 in lemon plants enables them to combat HLB by activating disease-resistance proteins. The above findings indicate that when infected with CLas, lemon exhibits stronger antioxidative activity and higher expression of disease-resistant genes, contributing to its enhanced tolerance to HLB. In contrast, Shatangju shows lower antioxidative activity, reduced expression of disease-resistant genes, significant ion leakage, and extensive callose deposition, possibly related to damage to plant cell structure and blockage of phloem sieve tubes, thereby promoting the development of HLB symptoms.

Effectiveness of functional ingredients to enhance gill disease in Atlantic salmon (Salmo salar, L.).

The development and application of functional feed ingredients represents a great opportunity to advance fish growth and health, boost the immune system, and induce physiological benefits beyond those provided by traditional feeds. In the present study, we looked at the feasibility of in vitro methods for screening the qualities of functional feed ingredients using the fish cell line RTgill-W1, which has never been used in fish nutrition, and the culture of Paramoeba perurans. Five functional feed ingredients (arginine, ß-glucan, vitamin C, and two phytogenic feed additives) were selected to investigate their effects on cell viability and reactive oxygen species production. Three of the selected ingredients (arginine and two phytogenic feed additives) were additionally tested to assess their potential amoebicidal activity. As these functional ingredients are the core of a commercially available feed (Protec Gill, Skretting AS), their beneficial effects were further assessed in a field trial in fish affected by complex gill disease. Here, the analyzed parameters included the evaluation of macroscopic and histopathological gill conditions, pathogen detections, and analyses of plasma parameters. RTgill-W1 cell line assays were a good tool for screening functional ingredients and provided information about the optimal ingredient concentration ranges, which can be helpful for adjusting the concentrations in future feed diets. Through the culture of P. perurans, the tested ingredients showed a clear amoebicidal activity, suggesting that their inclusions in dietary supplements could be a viable way to prevent microbial infections. A three-week period of feeding Protec Gill slowed the disease progression, by reducing the pathogen load and significantly improving gill tissue conditions, as revealed by histological evaluation. The use of diets containing selected functional ingredients may be a feasible strategy for preventing or mitigating the increasingly common gill diseases, particularly in cases of complex gill disease, as documented in this study.

In vivo analgesic, anti-inflammatory, sedative, muscle relaxant activities, and docking studies of 3',4',7,8-tetrahydroxy-3-methoxyflavone isolated from Pistacia chinensis.

Background: Pistacia chinensis is extensively employed in traditional medicine. This study aimed to isolate and evaluate the therapeutic effects of 3'4'78-tetrahydroxy-3-methoxyflavone from P. chinensis crude extract. Materials and Methods: The study utilized column chromatography for isolation. The plant extract and its isolated compound were assessed for in vivo analgesic (hot plate model), anti-inflammatory (carrageenan-induced paw edema), sedative (open field model), and muscle relaxing properties (inclined plane and traction test). Results: In the thermal-induced analgesic model, a significant analgesic effect was observed for the extract (25, 50, and 100 mg/kg) and the isolated compound (2.5, 5, 10, and 15 mg/kg) at higher doses. The extract (100 mg/kg) significantly prolonged latency time (21.98 seconds) after 120 minutes of administration. The isolated compound elevated the latency time (20.03 seconds) after 30 minutes, remaining significant up to 120 minutes with a latency time of 24.11 seconds. The anti-inflammatory effect showed a reduction in inflammatory reactions by 50.23% (extract) and 67.09% (compound) after the fifth hour of treatment. Both samples demonstrated significant sedative effects, with the extract hindering movement by 54.11 lines crossed compared to the negative control (180.99 lines). The isolated compound reduced the number of lines crossed to 15.23±SEM compared to the negative control. Both samples were also significant muscle relaxants. Docking studies indicated that the compound's therapeutic effect is due to inhibiting COX and nociceptive pathways. Conclusion: The isolated compound from Pistacia chinensis exhibits significant analgesic, anti-inflammatory, sedative, and muscle relaxing properties, with potential therapeutic applications by inhibiting COX and nociceptive pathways.

Synthesis, molecular docking evaluation for LOX and COX-2 inhibition and determination of in-vivo analgesic potentials of aurone derivatives.

In the current study, seven (7) aurone derivatives (ADs) were synthesized and employed to in-vitro LOX and COX-2 assays, in-vivo models of acetic acid-induced mice writhing, formalin-induced mice paw licking and tail immersion test to evaluate their analgesic potential at the doses of 10 mg and 20 mg/kg body weight. Molecular docking was performed to know the active binding site at both LOX and COX-2 as compared to standard drugs. Among the ADs, 2-(3,4-dimethoxybenzylidene)benzofuran-3(2H)-one (WE-4)possessed optimal LOX and COX-2 inhibitory strength (IC50=0.30 µM and 0.22 µM) as compared to standard (ZileutonIC50 = 0.08 µM, CelecoxibIC50 = 0.05 µM). Similarly in various pain models compound WE-4 showed significantly (p < 0.05) highest percent analgesic potency as compared to control at a dose of 20 mg/kg i.e. 77.60 % analgesic effect in acetic acid model, 49.97 % (in Phase-1) and 70.93 % (inPhase-2) analgesic effect in formalin pain model and 74.71 % analgesic response in tail immersion model. By the administration of Naloxone, the tail flicking latencies were reversed (antagonized) in all treatments. The WE-4 (at 10 mg/kg and 20 mg/kg) was antagonized after 90 min from 11.23 ± 0.93 and 13.41 ± 1.21 to 5.30 ± 0.48 and 4.80 ± 0.61 respectively as compared to standard Tramadol (from 17.74 ± 1.33 to 3.70 ± 0.48), showing the opiodergic receptor involvement. The molecular docking study of ADs revealed that WE-4 had a higher affinity for LOX and COX-2 with docking scores of -4.324 and -5.843 respectively. As a whole, among the tested ADs, compound WE-4 demonstrated excellent analgesic effects that may have been caused by inhibiting the LOX and COX-2 pathways.

Estimation of instantaneous peak flows in Canadian rivers: an evaluation of conventional, nonlinear regression, and machine learning methods.

Instantaneous peak flows (IPFs) are often required to derive design values for sizing various hydraulic structures, such as culverts, bridges, and small dams/levees, in addition to informing several water resources management-related activities. Compared to mean daily flows (MDFs), which represent averaged flows over a period of 24 h, information on IPFs is often missing or unavailable in instrumental records. In this study, conventional methods for estimating IPFs from MDFs are evaluated and new methods based on the nonlinear regression framework and machine learning architectures are proposed and evaluated using streamflow records from all Canadian hydrometric stations with natural and regulated flow regimes. Based on a robust model selection criterion, it was found that multiple methods are suitable for estimating IPFs from MDFs, which precludes the idea of a single universal method. The performance of machine learning-based methods was also found reasonable compared to conventional and regression-based methods. To build on the strengths of individual methods, the fusion modeling concept from the machine learning area was invoked to synthesize outputs of multiple methods. The study findings are expected to be useful to the climate change adaptation community, which currently heavily relies on MDFs simulated by hydrologic models.

Efficacy of massage versus massage with post isometric relaxation in temporomandibular disorders: a randomized controlled trial.

BACKGROUND: Temporomandibular joint disorder (TMD) is a common condition affecting the masticatory muscles and joint mobility. OBJECTIVES: The primary objective was to compare the effects of massage therapy alone and massage therapy combined with post-isometric relaxation exercises in patients with TMD for pain and maximal mouth opening. DESIGN: Assessor-blinded randomized controlled trial. SETTING: Sir Ganga Ram Hospital, Chaudhry Muhammad Akram Dental Hospital, Lahore Medical and Dental Hospital. SUBJECTS: Temporomandibular joint disorder patients. INTERVENTION: Group A (n = 23) received conventional treatment including massage and therapeutic exercises consecutively for 2 weeks. Group B (n = 23) received post-isometric relaxation technique along with conventional treatment for consecutive 2 weeks. MAIN MEASURES: The main outcome measures were pain and maximal mouth opening. Pain was measured using the Visual Analogue Scale (VAS) and maximal mouth opening (MMO) was measured using the TheraBite Scale. RESULTS: Both groups demonstrated significant improvements in pain and MMO scores post-treatment. However, Group B (massage with post-isometric relaxation exercises) showed significantly better outcomes compared to Group A (massage alone). There was a statistically significant difference in post-treatment pain scores (P = 0.000) and MMO scores (P = 0.000) between the two groups. CONCLUSION: The results suggest that massage therapy combined with post-isometric relaxation is more effective than massage therapy alone in managing pain and improving mouth opening in TMD patients. The study provides evidence supporting the use of these therapies in TMD management. TRIAL REGISTRY NUMBER: NCT05810831. Date of registration/First submission: 15 March 2023.

Barriers to sexual health care for sexually diverse Muslim men: a scoping review.

Sexually diverse Muslim men (SDMM) are seen to present later and with more advanced symptoms of HIV and other sexually transmitted infections (STIs). The limited access to sexual healthcare services is attributed to the stigma associated with their multiple intersecting identities. We conducted a scoping review to synthesise research on barriers impeding SDMM's access to sexual health care. We used Arksey and O'Malley's five-stage framework as the methodology for the review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses' extension for scoping reviews, was used as a guide for the presentation of the results. Searches conducted in EBSCOhost, Scopus, MEDLINE, Embase, CINAHL, Global Health, and Google Scholar yielded 1382 results, of which 18 studies were deemed eligible for this review. Bronfenbrenner's socioecological model was employed as a framework to analyse the studies. Through analysing the eligible studies, we identified factors operating at three different levels that can impede SDMM's access to sexual health care. Limited awareness and low-perceived risk of HIV/STIs, coupled with the fear of sexual identity disclosure might act as individual-level barriers to sexually diverse Muslim men's access to sexual health care. The experiences of discrimination within clinical settings were presented as a healthcare system-related issue discouraging SDMM from revisiting those services. Heteronormative and religious ideologies, homophobic government programs, and poverty might manifest in the more intimate domains of healthcare delivery, creating hostile spaces for SDMM. Intensive research and advocacy efforts are required to improve SDMM's access to sexual health care, which can reduce their risk of HIV/STIs.

A novel variant in the FLNB gene associated with spondylocarpotarsal synostosis syndrome.

OBJECTIVES: Genetic disorders involved in skeleton system arise due to the disturbance in skeletal development, growth and homeostasis. Filamin B is an actin binding protein which is large dimeric protein which cross link actin cytoskeleton filaments into dynamic structure. A single nucleotide changes in the FLNB gene causes spondylocarpotarsal synostosis syndrome, a rare bone disorder due to which the fusion of carpels and tarsals synostosis occurred along with fused vertebrae. In the current study we investigated a family residing in north-western areas of Pakistan. METHODS: The whole exome sequencing of proband was performed followed by Sanger sequencing of all family members of the subject to validate the variant segregation within the family. Bioinformatics tools were utilized to assess the pathogenicity of the variant. RESULTS: Whole Exome Sequencing revealed a novel variant (NM_001457: c.209C>T and p.Pro70Leu) in the FLNB gene which was homozygous missense mutation in the FLNB gene. The variant was further validated and visualized by Sanger sequencing and protein structure studies respectively as mentioned before. CONCLUSIONS: The findings have highlighted the importance of the molecular diagnosis in SCT (spondylocarpotarsal synostosis syndrome) for genetic risk counselling in consanguineous families.

Corrigendum: A metagenomic analysis of mosquito virome collected from different animal farms at Yunnan-Myanmar border of China.

[This corrects the article DOI: 10.3389/fmicb.2020.591478.].

The inhibitory effects of endophytic metabolites on glycated proteins under non-communicable disease conditions: A review.

Protein glycation in human body is closely linked to the onset/progression of diabetes associated complications. These glycated proteins are commonly known as advanced glycation end products (AGEs). Recent literature has also highlighted the involvement of AGEs in other non-communicable diseases (NCDs) such as cardiovascular, cancer, and Alzheimer's diseases and explored the impact of plant metabolites on AGEs formation. However, the significance of endophytic metabolites against AGEs has recently garnered attention but has not been thoroughly summarized thus far. Therefore, the objective of this review is to provide a comprehensive overview of the importance of endophytic metabolites in combating AGEs under NCDs conditions. Additionally, this review aims to elucidate the processes of AGEs formation, absorption, metabolism, and their harmful effects. Collectively, endophytic metabolites play a crucial role in modulating signaling pathways and enhancing the digestibility properties of gut microbiota (GM) by targeting on AGEs/RAGE (receptor for AGEs) axis. Furthermore, these metabolites exhibit anti-AGEs activities similar to those derived from host plants, but at a lower cost and higher production rate. The use of endophytes as a source of such metabolites offers a risk-free and sustainable approach that holds substantial potential for the treatment and management of NCDs.

"Caught in Each Other's Traps": Factors Perpetuating Incentive-Linked Prescribing Deals Between Physicians and the Pharmaceutical Industry.

BACKGROUND: Despite known adverse impacts on patients and health systems, "incentive-linked prescribing," which describes the prescribing of medicines that result in personal benefits for the prescriber, remains a widespread and hidden impediment to quality of healthcare. We investigated factors perpetuating incentive-linked prescribing among primary care physicians in for-profit practices (referred to as private doctors - PDs), using Pakistan as a case study. METHODS: Our mixed-methods study synthesised insights from a survey of 419 systematically sampled PDs and 68 semi-structured interviews with PDs (n=28), pharmaceutical sales representatives (SRs) (n=12), and provincial and national policy actors (n=28). For the survey, we built a verified database of all registered PDs within Karachi, Pakistan's most populous city, administered an electronic questionnaire in-person and descriptively analysed the data. Semi-structured interviews incorporated a vignette-based exercise and data was analysed using an interpretive approach. RESULTS: Our survey showed that 90% of PDs met pharmaceutical SRs weekly. Three interlinked factors perpetuating incentive-linked prescribing we identified were: gaps in understanding of conflicts of interest and loss of values among doctors; financial pressures on doctors operating in a (largely) privately financed health-system, exacerbated by competition with unqualified healthcare providers; and aggressive incentivisation by pharmaceutical companies, linked to low political will to regulate an over-saturated pharmaceutical market. CONCLUSION: Regular interactions between pharmaceutical companies and PDs are normalised in our study setting. Progress on regulating these is hindered by the substantial role of incentive-linked prescribing in the financial success of physicians and pharmaceutical industry employees. A first step towards addressing the entrenchment of incentive-linked prescribing may be to reduce opposition to restrictions on incentivisation of physicians from stakeholders within the pharmaceutical industry, physicians themselves, and policy-makers concerned about curtailing growth of the pharmaceutical industry.