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Natural disasters create immense challenges for young children by exposing them to a high degree of adversity. Interventions designed to build resilience in the aftermath of a natural disaster may help buffer the negative consequences of these adverse experiences. In this article, we report the results of our quasi-experimental evaluations of two interventions designed by Save the Children to improve children's developmental outcomes and parental engagement during a critical period. These interventions provided resources across eco-developmental levels to young survivors of the 2015 earthquake in Nepal's Sindhupalchok district by targeting children's families, teachers, and communities. The first was a caregiver-focused intervention aimed at improving parents' and caregivers' ability to provide early stimulation and responsive, positive caregiving for children ages 0-3; the other was a facilitator-focused intervention at an early childhood development (ECD) center that aimed to improve the quality of learning environments, family engagement, and psychosocial supports for children ages 3-6. We found that the interventions had a mixed impact. The age 0-3 components had no detectable effect on developmental outcomes, whereas the age 3-6 components had a positive impact on children's early learning and development, particularly their pre-academic skills. Neither intervention improved parental engagement. We highlight the challenges of implementing family-focused interventions in emergency contexts and the importance of the delivery agents in ECD programs. Despite the null effects for the 0-3 group, these evaluations demonstrate that bolstering the quality of early learning environments and the skills of ECD facilitators can have a meaningful impact on child-level outcomes, even in postdisaster and emergency settings.

Abstract Introduction Patients presenting with a thyroid nodule, if malignant, may call for removal. A good screening tool with high diagnostic value for preoperative evaluation is preferred. Through real-time visualization of the needle to aspirate from the suspicious site, ultrasonography-guided fine-needle aspiration cytology could be an excellent screening tool. Materials and method A cross-sectional descriptive study was conducted at Ganesh Man Singh Memorial Academy of Ear Nose Throat–Head and Neck Studies, Kathmandu, Nepal, from September 2018 to November 2019. We included 59 subjects of 15–72 years meeting the inclusion criteria. All study participants underwent preoperative ultrasonography-guided fine-needle aspiration cytological evaluation of thyroid nodule, which was correlated with their histopathological findings to determine diagnostic values. Result The sensitivity, specificity, and accuracy of ultrasonography-guided fine-needle aspiration cytology of thyroid nodule was 96.96%, 61.53%, and 81.35%, respectively. On stratification according to size, high sensitivity of 100% was observed in evaluating lesions of size 4 cm. There was a good inter-rater agreement between findings of ultrasonography-guided fine-needle aspiration cytology and histopathology with a kappa coefficient of 0.607. Conclusion Ultrasonography-guided fine needle aspiration cytology is a reliable procedure to evaluate thyroid lesions with high diagnostic value. It is an excellent tool for evaluating small, non-palpable nodules.

Given the escalating environmental temperature and a considerable progress in meat production capacity, broiler chickens are more sensitive to heat stress than before. The detrimental influences of heat stress include diminished feed intake and reduced average daily gain, low feed efficiency, impaired immune response, deterioration of meat quality, and disturbed gastrointestinal microflora. Generation of free radicals, reactive oxygen species, and their combined action on cell membrane leads to damage in the cell membrane integrity and alters the metabolic function of the body resulting in various physiological abnormalities. There have been numerous studies on cost-effective strategies to mitigate the harmful effect of heat stress. The use of various dietary antioxidants, vitamins, minerals, flavonoids, and probiotics, alone or in combination, has led to promising results on the growth performance of broiler chickens, thereby decreasing the unexpected losses incurred due to heat stress. This article aims to review the scientific evidence concerning the various harmful consequences of heat stress in broiler chicken, with emphasis on meat quality, carcass traits, and growth performance. We also discuss some mitigation strategies in the next section.

Abstract Background Umbrella clinical trials in precision oncology are designed to tailor therapies to the specific genetic changes within a tumor. Little is known about the risk/benefit ratio for umbrella clinical trials. The aim of our systematic review with meta-analysis was to evaluate the efficacy and safety profiles in cancer umbrella trials testing targeted drugs or a combination of targeted therapy with chemotherapy. Methods Our study was prospectively registered in PROSPERO (CRD42020171494). We searched Embase and PubMed for cancer umbrella trials testing targeted agents or a combination of targeted therapies with chemotherapy. We included solid tumor studies published between 1 January 2006 and 7 October 2019. We measured the risk using drug-related grade 3 or higher adverse events (AEs), and the benefit by objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). When possible, data were meta-analyzed. Results Of the 6207 records identified, we included 31 sub-trials or arms of nine umbrella trials (N = 1637). The pooled overall ORR was 17.7% (95% confidence interval [CI] 9.5–25.9). The ORR for targeted therapies in the experimental arms was significantly lower than the ORR for a combination of targeted therapy drugs with chemotherapy: 13.3% vs 39.0%; p = 0.005. The median PFS was 2.4 months (95% CI 1.9–2.9), and the median OS was 7.1 months (95% CI 6.1–8.4). The overall drug-related death rate (drug-related grade 5 AEs rate) was 0.8% (95% CI 0.3–1.4), and the average drug-related grade 3/4 AE rate per person was 0.45 (95% CI 0.40–0.50). Conclusions Our findings suggest that, on average, one in five cancer patients in umbrella trials published between 1 January 2006 and 7 October 2019 responded to a given therapy, while one in 125 died due to drug toxicity. Our findings do not support the expectation of increased patient benefit in cancer umbrella trials. Further studies should investigate whether umbrella trial design and the precision oncology approach improve patient outcomes.

Background: Acid sensitivity can be altered in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis helps clear gastro-esophageal refluxate and residual ingested food bolus. Objectives: The aim of this study was to investigate the associations among acid sensitivity, esophageal mucosal integrity, chemical clearance, and secondary peristalsis before and after esophageal acid infusion. Design: This was an investigator-initiated, prospective, cross-sectional study. Methods: Adult reflux patients underwent high resolution manometry and 24 h impedance-pH monitoring off acid suppression to identify GERD phenotypes, including non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Secondary peristalsis was assessed using five rapid 20 mL air injections into the esophagus before and after infusion of hydrochloric acid (0.1 N) into the mid-esophagus. Conventional acid infusion parameters recorded included lag time, intensity rating, and sensitivity score. Chemical clearance was evaluated using the post-reflux swallow-induced peristaltic wave (PSPW), and mucosal integrity was assessed by the mean nocturnal baseline impedance (MNBI) derived from impedance-pH monitoring. Results: A total of 88 patients (age 21–64 years, 62.5% women) completed the study including 12 patients with NERD, 45 with RH, and 31 with FH. There was no significant difference in acid infusion parameters between patients with NERD, RH, and FH. Upon acid infusion, patients who exhibited successful secondary peristalsis had longer lag time, higher MNBI, and shorter bolus contact time than those without secondary peristalsis. Meanwhile, patients with intact PSPW demonstrated significantly higher intensity ratings in response to acid perfusion and higher MNBI than those with impaired PSPW. The lag time correlated positively with MNBI ( r = 0.285; p = 0.007). Conclusion: In conclusion, the protective effect of esophageal secondary peristalsis and chemical clearance on esophageal mucosal integrity was demonstrated. Concerning acid sensitivity, longer lag time in patients with intact secondary peristalsis may be attributed to better esophageal mucosal integrity, while stronger intensity ratings may have a greater tendency to induce PSPW and protect esophageal mucosal integrity.

Drug-resistant tuberculosis (DRTB) is a growing concern worldwide. The poor rate of service delivery exacerbates the severity, leading to an increase in community transmission, which is further amplified by stigma. Health care workers (HCWs) are at the forefront lines of service delivery; their efforts are suspected of resulting in stigmatization, negatively impacting patient-centered care. However, little is known about DRTB-related stigma among these HCWs, and interventions are limited. Our scoping review is significant because it provides an overview of the DRTB stigma confronting HCWs and informs subsequent stigma-reduction initiatives. Utilizing Arksey and O’Malley framework, we exhaustively searched electronic databases for relevant English-language studies published from 2010 to 2022, identifying the drivers and facilitators of DRTB-related stigma among HCWs from high-TB and -DRTB burden countries, and compiling recommendations that could reduce DRTB stigma. From 443 de-duplicated papers, 11 articles on HCWs’ DRTB-related stigma were reviewed and synthesized. Fear was mentioned across included articles as a stigma driver. Other reported stigma drivers identified included feelings of discrimination, isolation, danger, lack of support, shame, and stress. Poor infection control (IC) was the leading stigma facilitator. Other stigma facilitators identified were differing IC interpretations, workforce culture, and workplace inequality facilitating to stigmatization of HCWs. Three key recommendations identified were addressing infection control issues; increase the competence of healthcare workers; and provide psychosocial assistance, emphasizing HCW safety during DRTB activities. DRTB stigma among HCWs is multifaceted, largely driven by fear and facilitated by varying implementation or interpretations of policies within the workplace. Making HCWs feel safe while conducting DRTB activities is a priority issue that should be addressed by improving IC, training and psychosocial support. More studies investigating country-specific and multilevel DRTB-related stigma among HCWs are required to inform the development of an effective stigma intervention strategy.

Agriculture has been a cornerstone of human civilization for thousands of years, providing food and other essential resources to sustain our societies. However, as we enter the 21st century, we face unprecedented challenges that threaten the very foundations of our agricultural systems. Climate change, resource depletion, and population growth are just a few of the issues that demand urgent attention from policymakers and practitioners alike. Further, the growing population, climate change, the recent COVID-19 pandemic, the Ukraine-Russia war, and the depreciation of national currencies have disrupted the global food supply chain and increased food prices and food insecurity in many countries, including Nepal. The Nepalese agriculture sector alone contributed employment opportunities for more than 60 % of the population with a 23.9% share in total value added of the national economy (Ministry of Finance, 2022). Though the majority of farmers in Nepal are engaged in the agriculture sector, there is still a dominance of traditional and subsistence agriculture and the country's agricultural production is not enough to feed its population. The continued rise in import bills and volume of food products in recent years has been a major challenge for the country. Addressing these constraints warrants consortia of efforts from the government, nonprofits, and private sectors to promote sustainable and regenerative agricultural concepts and practices that align with local farm attributes and the agroecological environment. With the above mentioned issue, Policy Research Institute, the publisher of NPPR, collaborated with Association of Nepalese Agricultural Professionals of Americas (NAPA) for the utilization of expert knowledge for public policy making and policy discussion. PRI is open to collaborating with any professional and intellectual society for policy issues. Thereof, a two-day (January 6-7, 2023) virtual symposium on "Agricultural Policies and Practices in Nepal: Pathways for Transformation" was jointly organized by the PRI and NAPA with the aim to discuss and synthesize structural, policy intervention-related procedural, and local barriers and issues inherent to inadequate agricultural growth in Nepal and recommend transformative and pragmatic policies, programs, and practices feasible at local, regional, and national levels. The other symposium collaborators were the Ministry of Agriculture and Livestock Development (MoALD), Nepal Agricultural Research Council (NARC), Agriculture and Forestry University (AFU), Institute of Agriculture and Animal Sciences (IAAS, Tribhuvan University), Nepal Agricultural Cooperative Central Federation Ltd. (NACCFL), and Society of Agricultural Scientists-Nepal (SAS-Nepal). The 38 papers presented at the symposium brought together over 500 researchers, policymakers, and practitioners from around the world. The symposium highlighted the importance of innovative policies and practices that can help transform agriculture and ensure its sustainability for future generations. The symposium was organized and facilitated in four thematic areas. The Agriculture Policy theme highlighted an analysis of current agricultural policies, laws, and regulations that have hindered the production and marketing of farm products, land use policies, transformative agriculture for the viable and circular economy, promoting cooperative farming, farm diversity, and sustainability including internationally successful policy practices suitable for Nepal. The Agricultural Research, Education, and Extension theme included diverse subject matters. These were genetic improvement of crops and livestock for diverse agro-climatic zones; technology innovations and dissemination; science-based knowledge and extension practices; climate-smart and organic agriculture; agri-business and entrepreneurship; commercial agriculture; and integration of agricultural research, education, and extension. Similarly, the Technology and Infrastructure Development theme focused on varied avenues of innovative technology (such as UAV, GIS, and Remote Sensing), farm mechanization, and smart and efficient irrigation practices to optimize costs of production, labor, fertilizer shortages, and monitoring of plant and soil health Finally, the Governance theme underpinned coherence and discordance between the policy frameworks and governing structures/mechanisms of three levels of government and opportunities for realignment for agricultural transformation as well as a local governance framework for agricultural service delivery at a municipality level. Finally, the symposium highlighted the importance of partnerships and collaborations in driving transformational change. The papers discussed the potential of public-private partnerships, multi-stakeholder platforms, and other forms of collaboration to leverage resources, share knowledge, and scale up innovative solutions. This special issue received 20 papers for publication consideration, however, after the review process, it is able to manage 12 papers for publication. These papers provide a rich and diverse set of insights into the pathways for transforming agriculture. They offer both practical guidance and theoretical frameworks for policymakers and practitioners seeking to navigate the complex challenges facing agriculture today. We hope this special issue will inspire further research and action towards a more sustainable and equitable agricultural future. We thank all the authors who contributed to this special issue and the reviewers who provided their valuable feedback. We also extend our appreciation to the symposium organizers and collaborators. Finally, we encourage additional authors/presenters to submit their papers in the NPPR’s Regular Issue, which will be published in September 2023.

BackgroundGiven the profound impact of tuberculosis (TB) on immunity and given murine studies suggesting that infections may influence immunity across generations, we hypothesize that parental TB might impact health and disease in future offspring.ObjectiveThis study investigated the impact of maternal and paternal TB on offspring asthma and respiratory symptoms.MethodsWe included data from the third follow-up of the Respiratory Health in Northern Europe study (RHINE). Information on own asthma status, asthma-like symptoms and other respiratory symptoms, as well as information about parental TB and asthma, were collected using standardized questionnaires. The associations between parental TB and RHINE participants' asthma and respiratory symptoms were analyzed using multiple logistic regression, with adjustment for parental education, smoking habits and asthma.ResultsOf 8,323 study participants, 227 (2.7%) reported only paternal TB, 282 (3.4%) only maternal TB, and 33 (0.4%) reported that both parents had TB. We found a higher risk of asthma (aOR: 1.29, 95% CI: 1.05–1.57) in offspring with a history of parental TB as compared to offspring without parental TB., Parental TB was significantly associated with allergic asthma in offspring (aOR: 1.58, 95% CI: 1.29–2.05), while no significant association between parental TB and asthma without allergy (aOR: 1.00, 95% CI: 0.76–1.32) in offspring was observed.ConclusionResults from this study indicate that parental TB might be a risk factor for offspring's asthma and respiratory symptoms. We raise the hypothesis that the immunological impact of infections might be transmitted to influence offspring phenotype in humans.

The use of steel fillers enhances the flexural behaviour of mortar and concrete. However, it makes it more difficult to disperse them uniformly and coat them firmly in the mortar/concrete with the conventional mixing method while using them at higher content. In this method, steel fillers are generally mixed after the mixing of mortar with a full part of water. In the high ductile mortar mixing method, the viscous mortar was first prepared with the first part of the water and then the steel fillers were mixed. Its workability was increased in the final stage of mixing with the second part of the water. The mixture proportion of the base mortar was similar to that used for the production of the permanent formwork (W/C = 30% and W = 206 kg/m3). The content of steel filler (0, 1.5%, and 2.5%) was by volume of the mortar and it was used as part of the sand. The distribution and coating condition of steel filler was better in the second mixing method. It was made possible due to the strong kneading and lapping action within the viscous mortar. The flexural strength was increased by 28.7% with less variation. It was a 241% increase from that of plain mortar and only a 165% increase was with the conventional mixing method. The high ductile mortar mixing method enhanced the flexural strength, deflection, rigidity, flexural performance, and fracture energy of steel filler mortar more than that of the conventional mixing method. This result contributes to reducing the thickness of permanent steel filler mortar formwork as well as of other structures enabling easier transportation and erection work. Moreover, it also helps to reduce the overall cost of the steel filler mortar structures.

Background Tuberculosis (TB) infection induces profound local and systemic, immunological and inflammatory changes that could influence the development of other respiratory diseases; however, the association between TB and asthma is only partly understood. Our objective was to study the association of TB with asthma and respiratory symptoms in a Nordic–Baltic population-based study. Methods We included data from the Respiratory Health in Northern Europe (RHINE) study, in which information on general characteristics, TB infection, asthma and asthma-like symptoms were collected using standardised postal questionnaires. Asthma was defined based on asthma medication usage and/or asthma attacks 12 months prior to the study, and/or by a report of ≥three out of five respiratory symptoms in the last 12 months. Allergic/nonallergic asthma were defined as asthma with/without nasal allergy. The associations of TB with asthma outcomes were analysed using logistic regressions with adjustments for age, sex, smoking, body mass index and parental education. Results We included 8379 study participants aged 50–75 years, 61 of whom reported having had TB. In adjusted analyses, participants with a history of TB had higher odds of asthma (OR 1.99, 95% CI 1.13–3.47). The associations were consistent for nonallergic asthma (OR 2.17, 95% CI 1.16–4.07), but not for allergic asthma (OR 1.20, 95% CI 0.53–2.71). Conclusion We found that in a large Northern European population-based cohort, persons with a history of TB infection more frequently had asthma and asthma symptoms. We speculate that this may reflect long-term effects of TB, including direct damage to the airways and lungs, as well as inflammatory responses.

Midbrain and striatal dopamine signals have been extremely well characterized over the past several decades, yet novel dopamine signals and functions in reward learning and motivation continue to emerge. A similar characterization of real-time sub-second dopamine signals in areas outside of the striatum has been limited. Recent advances in fluorescent sensor technology and fiber photometry permit the measurement of dopamine binding correlates, which can divulge basic functions of dopamine signaling in non-striatal dopamine terminal regions, like the dorsal bed nucleus of the stria terminalis (dBNST). Here, we record GRABDA signals in the dBNST during a Pavlovian lever autoshaping task. We observe greater Pavlovian cue-evoked dBNST GRABDA signals in sign-tracking (ST) compared to goal-tracking/intermediate (GT/INT) rats and the magnitude of cue-evoked dBNST GRABDA signals decreases immediately following reinforcer-specific satiety. When we deliver unexpected rewards or omit expected rewards, we find that dBNST dopamine signals encode bidirectional reward prediction errors in GT/INT rats, but only positive prediction errors in ST rats. Since sign- and goal-tracking approach strategies are associated with distinct drug relapse vulnerabilities, we examined the effects of experimenter-administered fentanyl on dBNST dopamine associative encoding. Systemic fentanyl injections do not disrupt cue discrimination but generally potentiate dBNST dopamine signals. These results reveal multiple dBNST dopamine correlates of learning and motivation that depend on the Pavlovian approach strategy employed.

Abstract Schizencephaly, an extremely rare anomaly of the cortex, is characterized by abnormal clefts in the cerebral cortex. Very often, this condition is diagnosed early in the childhood period but few instances exist in literature where schizencephaly‐associated seizures and hemiparesis have presented later in life too. Here, we report a rare case scenario of a lady in her late 30s who initially presented to us with obstetric concerns wherein schizencephaly remained an incidental finding despite the significantly large cortical cleft along with lobar holoprosencephaly and lissencephaly.

Intro: Ross River virus (RRV) is a multi-vector, multi-host pathogen, responsible for most notifications of human arboviral infections in Australia. Despite regular outbreaks, the most important vectors and hosts that drive transmission cycles are not known. Recent studies have shown that whilst marsupials are competent reservoirs of RRV, there is potential for placental mammals and birds to contribute to transmission dynamics, although their role in maintaining the virus is still unclear. We aimed to use mosquitoes and their blood meals as the sampling tool for exploring vector‐host dynamics and RRV epidemiology. Methods: We combined mosquito surveys with molecular and serological assays to investigate transmission pathways across five urban sites in Brisbane, Australia. We identified host origins of mosquito blood meals through amplification and sequencing of the Cytochrome b gene. In addition, mosquito blood meals were assessed for the presence of antibodies to RRV using a micro- plaque reduction neutralisation test (mPRNT). Findings: A total of 480 blood-fed mosquitoes were collected from March 2021 to May 2022. These included mainly Culex annulirostris (68.7%) and Cx. orbostiensis (9.4%). Blood meals of 307 mosquitoes were identified mainly as humans (52%) and cattle (6.8%). RRV seroprevalence was 71% in 21 samples from cattle and 52% in 253 samples of human origin. Discussion: Relatively high RRV seroprevalence in humans indicates high rates of exposure. The high proportion of human blood in mosquito blood meals may reflect host availability in the study area. It also contrasts with previous Australian studies in which humans represented a relatively small proportion of meals. Conclusion: Our results show that mosquitoes may be used to derive species- specific information on vectors, reservoirs and pathogen exposure, which can help identify potential transmission pathways. It also provides a novel, non- invasive method of estimating seroprevalence in both humans and wildlife.

PURPOSEMany countries face a significant shortage of medical oncologists. To mitigate this problem, some countries, including Canada, have established training programs for general practitioners in oncology (GPOs), which train family physicians (FPs) in the fundamentals of cancer care. This type of GPO training model may be useful in other countries facing similar challenges. Therefore, Canadian GPOs were surveyed to learn from their experiences and inform the development of similar programs in other countries.METHODSA survey was designed and administered to Canadian GPOs to understand the methods and outcomes of GPO training and practice in the Canadian context. The survey was active from July 2021 to April 2022. Participants were recruited through personal and provincial networks and an email list provided by the Canadian GPO network.RESULTSThe survey received 37 responses for an estimated response rate of 18%. Although only 38% of respondents indicated that family medicine training sufficiently prepared them to care for patients with cancer, 90% indicated that GPO training did. Clinics with oncologists were found to be the most effective mode of learning, followed by small group learning and online education. Critical knowledge domains and skills most relevant for GPO training were identified as the treatment of side effects, symptom management, palliative care, and breaking bad news.CONCLUSIONParticipants in this survey felt that a dedicated GPO training program offered value beyond family medicine residency in preparing providers to adequately care for patients with cancer. GPO training can be done effectively through virtual and hybrid content delivery. Critical knowledge domains and skills identified as the most important in this survey may be valuable for other groups and nations implementing similar training programs to increase their oncology workforce.

Thrombotic microangiopathy is a pathological condition comprised of microvascular thrombosis involving any body organ leading to thrombocytopenia, coombs-negative hemolytic anemia, and end-organ damage. The clinical presentation of the case shows typical hemolytic uremic syndrome, however, lab reports show atypical hemolytic uremic syndrome (low C3). Pain abdomen and loose stool with some signs of dehydration were initial presentations. Early initiation of renal replacement therapy and management of dehydration was done. Simple diarrhea can also manifest as acute kidney injury with the hemolytic uremic syndrome. Hence we should keep hemolytic uremic syndrome as the differential diagnosis of diarrhea. Irrespective of lab parameters, early management in line with the typical hemolytic uremic syndrome should be done for better outcomes.

Immediate implant placement is an approach to immediately insert a dental implant into newly created extraction socket following tooth extraction. Since osseointegration is one of the major factors for implant success, placing an immediate implant in between mesial and distal roots acts as natural surgical template and bone formation around the implant from extraction socket acts or gives better osseointegration. We reported 4 cases, in which nobel technique was used. It was used in mandibular first and second molars where we do immediate implants in case of a tooth beyond repair and in case of leftover roots. Here in the case of only root involvement, we have drilled and prepared osteotomy in between the mesial and distal root while in the case of the whole tooth, we have to section the crown first, then drill. Thus, better osseointegration with good amount of soft tissue formation above the implant was achieved.

Parbati Thapa,1 Bhuvan KC,1,2 Shaun Wen Huey Lee,1 Juman Abdulelah Dujaili,1 Sudesh Gyawali,3 Mohamed Izham Mohamed Ibrahim,4 Alian A Alrasheedy5 1School of Pharmacy, Monash University Malaysia, Subang Jaya, Selangor, Malaysia; 2College of Public Health, Medical, and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia; 3Department of Pharmacology, Manipal College of Medical Sciences, Pokhara, Nepal; 4Department of Clinical Pharmacy and Practice, College of Pharmacy, QU Health, Qatar University, Doha, Qatar; 5Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraidah, Qassim, Saudi ArabiaCorrespondence: Bhuvan KC, School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Subang Jaya, Selangor, 47500, Malaysia, Email kcbhuvan@gmail.com Alian A Alrasheedy, Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraidah, Qassim, Saudi Arabia, Email aarshiedy@qu.edu.saBackground: Pain is a public health problem and affects millions of people globally. Effective pain management is possible through comprehensive pain management guidelines, adequate facilities, and trained healthcare professionals. Therefore, this study aims to analyze the healthcare professionals’ knowledge, attitude, and practice regarding pain management in Western Nepal.Methods: A cross-sectional study was carried out in hospitals of Pokhara, Nepal. Healthcare professionals, including doctors, pharmacists, and nurses, were enrolled. Tools for the study were “The Knowledge and Attitudes Survey Regarding Pain (KASRP)” and a validated practice-based questionnaire. Frequencies and descriptive statistics were used to describe the outcomes. Kruskal–Wallis H-test and Mann-Whitney U-test were used to analyze the association between the mean rank of KASRP score and sample characteristics. A p-value of < 0.05 was considered significant for all statistical tests.Results: A total of 336 healthcare professionals were enrolled in this study (108 medical doctors, 150 nurses, and 78 pharmacists). The mean KASRP scores (% ± SD) obtained by doctors, pharmacists, and nurses were 58.48± 8.98, 53.01± 7.80, and 52.26± 6.39, respectively. A significant difference was found between the KASRP score and sample characteristics (p< 0.001). The pain assessment tool is used by 96 (29%) healthcare professionals every time they meet the patients. Doctors and nurses used it more frequently as compared to pharmacists. Many of the pharmacists, 40 (51%), reported that they counsel the patients on the prescribed medicine (analgesics, NSAIDs, and opioids) every time. As only few participants had already attended a training on pain management, most healthcare professionals, 110 (33%), agreed and 198 (59%) strongly agreed that training related to pain management is needed in NepalConclusion: Adequate training and support are required to enhance the knowledge, attitude and ultimately better practice for healthcare professionals regarding pain management in Nepal.Keywords: pain management, knowledge, attitude, practice, healthcare professionals, Nepal

Given the importance of snow on different land and atmospheric processes, accurate representation of seasonal snow evolution, including distribution and melt volume, is highly imperative to any water resources development trajectories. The limitation of reliable snowmelt estimation in mountainous regions is, however, further exacerbated by data scarcity. This study attempts to develop relatively simple extended degree-day snow models driven by freely available snow-cover images. This approach offers relative simplicity and a plausible alternative to data-intensive models, as well as in situ measurements, and has a wide range of applicability, allowing for immediate verification with point measurements. The methodology employs readily available MODIS composite images to calibrate the snowmelt models on spatial snow distribution in contrast to the traditional snow-water-equivalent-based calibration. The spatial distribution of snow-cover is simulated using different extended degree-day models with parameters calibrated against individual MODIS snow-cover images for cloud-free days or a set of images representing a period within the snow season. The study was carried out in Baden-Württemberg (Germany) and in Switzerland. The simulated snow-cover data show very good agreement with MODIS snow-cover distribution, and the calibrated parameters exhibit relative stability across the time domain. Furthermore, different thresholds that demarcate snow and no-snow pixels for both observed and simulated snow cover were analyzed to evaluate these thresholds' influence on the model performance and identified for the study regions. The melt data from these calibrated snow models were used as standalone inputs to a modified Hydrologiska Byråns Vattenbalansavdelning (HBV) without the snow component in all the study catchments to assess the performance of the melt outputs in comparison to a calibrated standard HBV model. The results show an overall increase in Nash–Sutcliffe efficiency (NSE) performance and a reduction in uncertainty in terms of model performance. This can be attributed to the reduction in the number of parameters available for calibration in the modified HBV and an added reliability of the snow accumulation and melt processes inherent in the MODIS calibrated snow model output. This paper highlights that the calibration using readily available images used in this method allows for a flexible regional calibration of snow-cover distribution in mountainous areas with reasonably accurate precipitation and temperature data and globally available inputs. Likewise, the study concludes that simpler specific alterations to processes contributing to snowmelt can contribute to reliably identify the snow distribution and bring about improvements in hydrological simulations, owing to better representation of the snow processes in snow-dominated regimes.

Abstract Background Activity Scale for Kids (ASK) is self reported, widely used tool to measure the physical disability in children aged 5–15 years. It has two versions; ASK-performance version and ASK-capability version, both with excellent psychometric properties in English and other translated languages. However, the tool is not available in Nepali. The aim of our study is to translate, culturally adapt and validate the tool in the context of the Nepali population. Methods A standard translation guideline was used to translate both the versions of ASK tool into the Nepali language. One hundred and two participants were assessed to establish the reliability and validity of the tool. Internal consistency and test retest reliability was established using cronbach’s alpha and intra class correlation coefficient. Validity was established by three methods; ceiling and floor effects, group discriminations, and comparing the results of ASK with the Nepali version of KINDL. Results The mean age of the sample participants were 12.74 years (SD 2.2). The internal consistency and test retest reliability for both the Nepali versions of ASK was significant at 0.98 and 0.94 respectively. The tool had a negligible ceiling effect (

Background: In this study, we compared and contrasted design characteristics, results, and publications of randomized controlled trials (RCTs) in gastrointestinal (GI), lung, and breast cancer. Methods: A PUBMED search identified phase III RCTs of anticancer therapy in GI, lung, and breast cancer published globally during the period 2014–2017. Descriptive statistics, chi-square tests, and the Kruskal–Wallis test were used to compare RCT design, results, and output across the cancer sites. Results: A total of 352 RCTs were conducted on GI (36%), lung (29%), and breast (35%) cancer. Surrogate endpoints were used in 55% of trials; this was most common in breast trials (72%) compared to GI (47%) and lung trials (43%, p < 0.001). Breast trials more often met their primary endpoint (54%) than GI (41%) and lung trials (41%) (p = 0.024). When graded with the ESMO-MCBS, lung cancer trials (50%, 15/30) were more likely to meet the threshold for substantial benefit. GI trials were published in journals with a substantially lower impact factor (IF; median IF 13) than lung (median IF 21) and breast cancer trials (median IF 21) (p = 0.038). Conclusions: Important differences in RCT design and output exist between the three major cancer sites. Use of surrogate endpoints and the magnitude of benefit associated with new treatments vary substantially across cancer sites.

The occurrence of amoeba, Naegleria fowleri, in sediment samples from Lake Pontchartrain in Louisiana was investigated. This amoeba is pathogenic and can cause primary amoebic meningoencephalitis. In this study, quantitative polymerase chain reaction methods were used to test for the prevalence of Naegleria fowleri, HF183, and E. coli. N. fowleri was detected in 51.25% of our sediment samples. Illumina sequencing of sediment samples revealed ten different phyla, with Cyanobacteria being the most predominant at sites that generally presented with the highest median N. fowleri concentrations. N. fowleri was however strongly negatively correlated with HF183 (r = −0.859, p < 0.001). Whenever sediment E. coli concentrations were below 1.54 Log GC/g, there was only a 37.5% chance that N. fowleri would be detected in the same sample. When sediment E. coli concentrations exceeded 2.77 Log GC/g, the chances of detecting N. fowleri in the same sample increased to 90%, potentially suggesting predatory activity by the amoeba. The effect of temperature was observed to be different in relation to observed N. fowleri concentrations and detection rates. Although sediment samples collected during periods of higher temperatures had significantly lower mean N. fowleri concentrations (2.7 Log GC/g) compared to those collected at lower temperatures (3.7 Log GC/g, t(39) = 4.167, p < 0.001), higher N. fowleri detection rates in the overall samples were observed at higher temperatures (>19.1 °C) than at lower temperatures (

Aged care staff and doctors frequently highlight consumers' role in antibiotic treatment decisions. However, few studies include consumers. This study aimed to investigate consumer perspectives on antibiotic use in residential aged care. A search across 6 online databases yielded 3,373 studies, with 5 meeting inclusion criteria. Participant quotes, themes, statistical analyses, and authors' interpretive summaries in the included studies were inductively coded and refined to generate themes. Three themes emerged: perception of benefits and risks of antibiotics, perceived role in antibiotic treatment decision-making, and information-communication needs. Consumers held positive attitudes toward antibiotics, did not associate antibiotics with the exclusive treatment of bacterial infections, and had limited awareness of potential risks, such as antibiotic resistance. Studies showed diverse perceptions regarding residents' and their families' involvement in antibiotic treatment decision-making with some residents actively seeking antibiotics and others trusting doctors to decide. Studies also described consumer need for effective provider-consumer communication and information sharing that was affected by contextual barriers such as motivation, preferences, available information resources, and provider attitudes. Limited literature is available on consumer perspectives on antibiotic use in aged care. The review highlights that consumer needs are more complex than simply wanting an antibiotic. Antimicrobial stewardship programs should target consumer awareness, beliefs, and provider-consumer communication to enhance antibiotic use in aged care. • Consumer perspectives on antibiotic use in aged care are underexplored. • Limited consumer knowledge of antibiotics and antibiotic resistance is a concern. • Consumers generally trust health care providers in antibiotic treatment decisions. • Effective provider-consumer communication is crucial for better antibiotic use in aged care. [ABSTRACT FROM AUTHOR]

We present an annotation scheme for classifying differences in the outputs of syntactic constituency parsers when a gold standard is unavailable or undesired, as in the case of texts written by nonnative speakers of English. We discuss its automated implementation and the results of a case study that uses the scheme to choose a parser best suited to a downstream task that processes nonnative written text.

This article discusses the use of appropriate medium of instruction in multilingual classroom contexts, which is one of the most debated issues in education around the world. It first briefly overviews mother tongue education in relation to English language teaching in Nepal. Then, presenting a case study from Nepal, it offers theoretical insights about the use of mother tongue for higher education in general. Given that the issue of language of instruction is less often questioned in higher education around the world, it calls for such a discussion by drawing insights from the use of English, a foreign language, as the medium of instruction at different levels of education in Nepal.

Abstract Background Amyotrophic lateral sclerosis (ALS) is a devasting neurodegenerative disorder for which no successful therapeutics are available. Valproic acid (VPA), a monocarboxylate derivative, is a known antiepileptic drug and a histone deacetylase inhibitor. Methods To investigate whether monocarboxylate transporter 1 (MCT1) and sodium-coupled MCT1 (SMCT1) are altered in ALS cell and mouse models, a cellular uptake study, quantitative real time polymerase chain reaction and western blot parameters were used. Similarly, whether VPA provides a neuroprotective effect in the wild-type (WT; hSOD1WT) and ALS mutant-type (MT; hSOD1G93A) NSC-34 motor neuron-like cell lines was determined through the cell viability assay. Results [3H]VPA uptake was dependent on time, pH, sodium and concentration, and the uptake rate was significantly lower in the MT cell line than the WT cell line. Interestingly, two VPA transport systems were expressed, and the VPA uptake was modulated by SMCT substrates/inhibitors in both cell lines. Furthermore, MCT1 and SMCT1 expression was significantly lower in motor neurons of ALS (G93A) model mice than in those of WT mice. Notably, VPA ameliorated glutamate- and hydrogen peroxide-induced neurotoxicity in both the WT and MT ALS cell lines. Conclusions Together, the current findings demonstrate that VPA exhibits a neuroprotective effect regardless of the dysfunction of an MCT in ALS, which could help develop useful therapeutic strategies for ALS.

The use of fibre in concrete enhances its flexural behaviour and ductility. Different types of synthetic fibres are developed and replaced steel fibre to solve the corrosion of steel. Polyvinyl alcohol (PVA) is one of the synthetic fibres used in cementitious fibre composites. The High Ductile Mortar (HDM) was developed using PVA fibres. This paper assesses the effect of sand types and mixing procedures on the (PVA) fibre-reinforced high ductile mortar (HDM) in monotonic and cyclic loadings. Two different types of sands (crushed and river) and mixing methods were used for the comparison of the properties of HDM. The Pre-mixed mortar method refers to the mixing of PVA fibres in the pre-mixed mortar. And, pre-mixed paste method refers to the mixing of PVA fibres in a pre-mixed paste and the mixing of PVA mortar with the addition of sand. The pre-mixed mortar method gave a better flexural performance of the HDM than the pre-mixed paste method. The pre-mixed mortar method with crusher sand enhanced the flexural strength in the cyclic loading (11.8 MPa) than in the monotonic loading (10.3 MPa). It was the same for the case of river sand (11.4 MPa). Overall, the pre-mixed mortar method using river (finer) sand is better to enhance the strength, deflection, strain hardening, fracture energy, and toughness. The coarser sand is better for rigidity and fatigue flexural strength.

A workforce trained in the development and delivery of equitable surgical care is critical in reducing the global burden of surgical disease. Academic global surgery aims to address the present inequities through collaborative partnerships that foster research, education, advocacy and training to support and increase the surgical capacity in settings with limited resources. Barriers include a deficiency of resources, personnel, equipment, and funding, a lack of communication, and geographical challenges. Multi–level partnerships remain fundamental; these types of partnerships include a wide range of trainees, professionals, institutions, and nations, yet care must be taken to avoid falling into the trap of surgical “voluntourism” and undermining the expertise and practice of long–standing frontline providers. Academic global surgery has the benefit of developing a community of surgeons who possess the tools needed to collaborate on individual, institutional, and international levels to address inequities in surgery that are spread variously across the globe. However, challenges for surgeons pursuing a career in global surgery include balancing clinical responsibilities while integrating global surgery as a career during training. This is due in part to the lack of mentorship, research time, grant funding, support to attend conferences, and a limitation of resources, all of which are significantly more pronounced for surgeons from low–resource countries.

Abstract An 83‐year‐old‐male patient presented with obstructive jaundice, whose imagings were consistent with the cholangiocarcinoma of the distal common bile duct. The tumor markers were within normal limits. IgG4 level was raised; therefore, IgG4‐sclerosing cholangitis was made as the provisional diagnosis. Steroid therapy was started to which he responded well.

Pomelo, Citrus maxima, peel was chemically modified with lime water and then loaded with Fe(III) to develop anion exchange sites for effective sequestration of As(V) from water. Biosorbent characterizations were done by using FTIR, SEM, XRD, EDX, and Boehm's titration. The batch biosorption studies were carried out at various pHs using modified and non-modified biosorbents and optimum biosorption of As(V) occurred at acidic pH (3.0–5.0) for both the biosorbents. A kinetic study showed a fast biosorption rate and obtained results fitted well with the pseudo-second-order (PSO) model. When isotherm data were modeled using the Langmuir and Freundlich isotherm models, the Langmuir isotherm model fit the data better and produced maximal As(V) biosorption capacities of 0.72 ± 03, 0.86 ± 06, and 0.95 ± 05 mmol/g at temperatures 293± 1K, 298± 1K and 303± 1K, respectively. Desorptionof As(V) was effective using 0.1 M NaOH in batch mode. Negative values of ΔG° for all temperatures with positive ΔH° confirmed the spontaneous and endothermic nature of As(V) biosorption. The existence of co-existing chloride (Cl−), nitrate (NO3−), sodium (Na+), and calcium (Ca2+) showed insignificant interference whereas a high concentration of sulphate (SO42−) and phosphate (PO43−) significantly lowered As(V) biosorption percentage. Arsenic concentrations in actual arsenic polluted groundwater could be reduced to the WHO drinking water standard (10 μg/L) by using only 1 g/L of investigated Fe(III)-SPP. The dynamic biosorption of As(V) in a fixed bed system showed that Fe(III)-SPP was effective also in continuous mode and different design parameters for fixed bed system were determined using Thomas, Adams-Bohart, BDST, and Yoon-Nelson models. Therefore, from all of these results it is suggested that Fe(III)-SPP investigated in this study can be a potential, low cost and environmentally benign biosorbent material for an effective removal of trace amounts of arsenic from polluted water.

The global burden of non-communicable diseases (NCDs) has led to an increased mobilization of community health workers (CHWs) in the prevention and management of NCDs, particularly in resource-poor settings. However, little is known about the experiences of CHWs as they navigate the complex social context while proving home-based NCD management. This study aims to explore the experiences of female community health volunteers (FCHVs) in a community-based pilot project in western Nepal, specially regarding the social challenges they face while delivering basic type 2 diabetes (T2D) services. Using a qualitative phenomenological approach, the study conducted two focus group discussions and nine in-depth interviews with a total of 14 and 9 FCHVs, respectively. Social Capital theory was employed to understand the sociological aspects. The findings shed light on the challenges encountered by FCHVs in expanding their social networks, building trust, and fostering reciprocity among T2D intervention recepients. Notably, social trust was a significant challenge, compounded by power dynamics related to gender and socioeconomic status. FCHVs managed to overcome these challenges through their perseverance, self-motivation, and leaveraging their strong bonding and linking social capital. The recognition they received from the community played a crucial role in sustaining their motivation. The study highlights the importance of FCHVs' strong social capital, supported by available resources and personal motivation, in overcoming social obstacles. It is imperative for community health interventions to anticipate challenges across various elements of social capital to ensure the long-term retention and motivation of CHWs. Establishing appropriate support systems that address personal motivating factors and the strengthen social capital is essential.

BackgroundDrug-resistant tuberculosis (DRTB) is an increasing threat to human health and economic security worldwide. Exacerbating the severity of DRTB is the low rate of service delivery, leading to increased community transmission of the disease, further amplified by stigma. Health workers are on the front line of service delivery; their efforts in all areas of disease control are suspected of having resulted in stigmatization, impacting patient-centered care. As a growing concern, attention to addressing the DRTB stigma confronting health workers is required. However, little is known about stigma among health workers delivering services to patients with DRTB. This scoping review will provide an overview that could help inform appropriate responses toward stigma-reduction interventions for these health workers. ObjectiveThis scoping review protocol articulates a methodology that will examine the facets of DRTB-related stigma confronting health workers in high TB- and DRTB-burdened countries. This scoping review will (1) summarize stigma barriers and facilitators contributing to stigmatization among health workers delivering services to patients with DRTB, (2) identify the most common stigma barrier and facilitator, and (3) summarize the stigma-reduction intervention recommendations in the studies. MethodsGuided by Arksey and O’Malley’s framework and the recommendations of Munn et al, we will conduct a scoping review of relevant literature providing evidence of DRTB-related stigma among health workers from countries with a high burden of tuberculosis (TB) and DRTB. We will search published articles written in English from 2010 onward in electronic databases using Medical Subject Headings and keywords. Our search will apply a 3-step search strategy and use software tools to manage references and facilitate the entire scoping review process. The findings of our review will be presented following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews checklist. Our study is registered with Open Science Framework Registries. ResultsThis scoping review is part of a bigger project that will critically investigate stigma among health workers delivering services to patients resistant to TB medications. This study began in November 2021 and is expected to finish in 2023. The study has retrieved 593 abstracts out of 12,138 articles searched since February 2022 from the identified databases. The findings of this study will be published in a peer-reviewed journal. ConclusionsThis review will provide an outline of the aspects of DRTB-related stigma confronting health workers. The findings of this review could help inform appropriate responses toward stigma-reduction interventions for these health workers. This is significant because interventions addressing related TB (and DRTB) stigma in the workplace are lacking. International Registered Report Identifier (IRRID)DERR1-10.2196/43084

Purpose. Evidence suggests that choroid is thinner in myopes as compared to nonmyopes. However, choroidal thickness varies with the refractive error, age, axial length, and ethnicity. The purpose of this study was to determine the subfoveal choroidal thickness (SFCT) in high myopic Nepalese subjects and to investigate its association with the mean spherical equivalent refractive error (MSE), axial length, and age. Methods. Ninety-two eyes of 92 high myopic subjects (MSE ≤ −6 diopters) and 83 eyes of 83 emmetropic subjects (MSE: 0.00 Diopters) were included in the study. SFCT was assessed using spectral domain optical coherence tomography, and the axial length was measured using partial coherence interferometry. SFCT was measured manually using the inbuilt tool within the imaging software. Results. SFCT in the high myopic subjects was significantly thinner (mean ± SD: 224.17 ± 68.91 μm) as compared to the emmetropic subjects (353.24 ± 65.63 μm) (mean difference, 127.76 ± 130.80 μm, and p

Diabetes is a major health problem worldwide, which is increasing day by day. Since ancient times, medicinal plants have been a key source of medicinal agents, and many of them have been authorized as strong medications or drug candidates. This study evaluated the antioxidant, α-glucosidase, and α-amylase inhibition activities of Erythropalum scandens Blume. The plant revealed the significant antioxidant and in vitro antidiabetic activity. The crude methanolic extract reported the highest antioxidant activity with an IC50 of 59.35 ± 5.47 μg/mL, followed by its dichloromethane (DCM) and ethyl acetate (EA) fractions with an IC50 of 66.45 ± 2.46 μg/mL and 80.46 ± 2.69 μg/mL, respectively, as compared to the standard quercetin’s IC50 value of 6.29 ± 1.02 μg/mL. Among the crude extract and its fractions, the EA fraction disclosed the significant inhibiting activity against α-glucosidase and α-amylase with an IC50 value of 17.92 ± 0.88 μg/mL and 44.51 ± 0.12 μg/mL, respectively. This research work has scientifically validated the traditional use of this plant.

The prevalence of stroke increases each year and while mortality from stroke has decreased, the prevalence of comorbidities such as anxiety, depression and fatigue affects as many as 75% of stroke survivors. The aetiology of post-stroke fatigue is not clear, although it has been shown to be interrelated with comorbidities such as stress and depression. Due to the interconnected nature of these comorbidities, it is important to improve the specificity of diagnosis and identify novel therapeutic targets to improve the quality of life for stroke survivors. The investigation of molecular biomarkers associated with post-stroke stress, fatigue, and depression may shed light on the relationships between comorbidities and also contribute to the development of novel diagnostics and therapies. Several biomarkers have been identified for stress, depression, and fatigue, some of which are specific to stroke survivors. However, there remain several gaps in understanding, particularly in relation to the physiological mechanisms underlying these side effects and molecular biomarkers associated with post-stroke fatigue. The aim of this scoping review protocol is to outline the methodologies that will be used to provide a comprehensive understanding of the current literature on biomarkers associated with post-stroke fatigue, stress, and depression, informing future research questions.

The adenosquamous carcinoma of the gallbladder is a rare variant accounting for only 1-4% of all primary gallbladder carcinoma. Regardless of the histological types, all gallbladder carcinomas have silent and rapid progression resulting in delayed diagnosis and poor prognosis. Even with medical and/or surgical interventions, the median survival of patients with adenosquamous carcinoma, one of the histological variants, is less than a year. However, we present a case of adenosquamous carcinoma with an unusually better prognosis. A 70-year-old female patient, after being diagnosed with gallbladder carcinoma was suggested for surgical resection but was lost to follow-up since then. Two years later, the patient presented and was managed with extended cholecystectomy. The slow progression and non-recurrence of the tumour during follow-up for two years after the surgery indicates a better prognosis in this case.

Summary: Background: Spontaneous regression of advanced solid tumors is infrequent but may occur. Quantifying response rates from placebo in cancer drug trials may provide important information for physicians, patients, and regulators. We aimed to provide a pooled placebo response rate from drug trials in advanced solid tumors. Methods: We pooled the overall response rate (ORR), complete response rate (CR) and partial response rates (PR) in the placebo arm of placebo-controlled randomized controlled trials (RCTs) of cancer drugs for advanced solid tumors published during 2015–2021 using random-effects model. Findings: 45 phase 3 RCTs including 5684 patients on placebo met our inclusion criteria and formed the study cohort. The pooled overall ORR, CR and PR rates in the placebo arm were 1% (95% CI, 0%–2%), 0% (95% CI, 0%–0%), and 1% (95% CI, 0%–2%) respectively. Higher placebo responses were observed in prostate cancer and sarcoma trials. Interpretation: Overall, 1% patients with advanced solid tumors can expect to achieve some response even in absence of treatment. However, complete regression without treatment is extremely rare, almost zero percent. This information will be helpful to patients in their decisions, as well as regulators in evaluating cancer drugs’ efficacy based on response rates alone. Funding: None.