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Introduction: Chronic kidney disease (CKD) is common cause of renal failure. It involves a progressive loss in the structure and function of the kidneys over the course of months, with or without decreased glomerular filtration rate (GFR). CKD can be diagnosed by its pathological abnormalities, changes in the levels of renal function markers in the blood or urine, or by imaging investigations (E.g. USG etc). Objectives: The purpose of our study is 1) To correlate renal echogenicity with serum creatinine in order to determine the significance of renal echogenicity for identifying the progression of chronic kidney disease (CKD) and for the sonographic grading of CKD, 2) To study association of blood pressure, renal cortical cysts and renal size with grade of chronic renal disease. Methods: This hospital based cross sectional study was carried out at National Kidney Centre, Banasthali Kathmandu. Two hundred patients above 20 years, diagnosed with CKD according to the guidelines of the National Kidney Foundation and referred for USG, were included in the study. Patients with kidney transplant, on dialysis, with liver disease and renal tumors were excluded. Ultrasound of kidneys was performed by senior consultant radiologist who was blind to the patients’ serum creatinine levels. The relationship between grade of CKD with serum creatinine, kidney size, blood pressure and cortical cysts were assessed. Statistical analysis was performed by Kruskal wallis test using SPSS version 17. P values less than 0.05 were considered statistically significant. Results: Mean serum creatinine was 1.7 mg/dl for Grade 1 (range: 1.1- 4.7 mg/dl, STD 0.44), 2.38 mg/dl for Grade 2 (range: 1.8-3.9 mg/dl STD 0.40), 4.18 mg/dl for Grade 3 (range: 2.6-6.0 mg/dl, STD 0.88), and 5.65 mg/dl for Grade 4 (range: 3.1-12 mg/dl, STD 2.0. Conclusion: Renal echogenicity and its grading correlates better with serum creatinine in CKD than other sonographic parameters. Hence, renal echogenicity is a better parameter than serum creatinine for estimating renal function in CKD, and has the added advantage of irreversibility.

Community health diagnosis is a comprehensive assessment of health status of the community in relation to its social, physical and biological environment. The purpose of community health diagnosis is to define existing problems, determine available resources and set priorities for planning, implementing and evaluation health action, by and for the community. A cross sectional descriptive study was done at Dhampus VDC from 1 Sept 2016 AD (16th Bhadra, 2073 BS) to 16 Sept 2016 AD (31st Bhadra, 2073). The data was collected by questionnaires, anthropometric measurements, interviews and secondary data. The community health diagnosis field visit gave us the opportunity to build our team spirit and taught us the arts of problem solving. It taught us the importance of correct conduct and building a good rapport with the people who were unfamiliar to us. J-GMC-N | Volume 11 | Issue 01 | January-June 2018, Page: 71-76

Community health diagnosis is a comprehensive assessment of health status of the community in relation to its social, physical and biological environment. The purpose of community health diagnosis is to define existing problems, determine available resources and set priorities for planning, implementing and evaluating health action, by and for the community. The community health diagnosis program began on 4th September 2015 and continued till 13th September 2015 in ward no 1 and 5 Rupakot VDC, Kaski, Nepal. The program was organized in following phases: data collection, data analysis, first community presentation, prioritization of need and planning of micro health project (MHP), implementation and evaluation of MHP, and final community presentation. On the basis of the observed and the felt needs of the community, we found the real needs and prioritized them as follows. For community: Proper water purification, information about common diseases, KAP on diseases, knowledge on TB and DOTS. For school-going children: Education on environmental sanitation, education on personal hygiene - teeth brushing and hand washing, adolescent health education. We launched micro health project (MHP) on these topics, conducting school-based as well as community-based programs. Journal of Gandaki Medical College Vol. 10, No. 1, 2017, Page: 59-62

Metastatic carcinoma to the testis is very rare.The incidence of secondary testicular tumors ranges from 0.02 to 2.5% among autopsies ingeneral. Despite the high incidence of prostatic adenocarcinoma and its ability for wide dissemination, metastatic cancer to the testis is a rare phenomenon of prostate carcinoma with only 80 cases reported in the literature.It is diagnosed in autopsies or incidentally, following therapeutic orchiectomies in moreadvanced stages of the disease.Ours is the very first case of prostatic carcinoma metastasizing to the testis, being reported from our country. We are reporting this case because of the rarity of metastasis of prostatic carcinoma to testis and for stressing the need for keeping in mind the possibility of metastatic carcinoma also while dealing with testicular tumors. In our case, unilateral testicular metastasis was detected incidentally after bilateral orchiectomy for hormonal management of metastatic prostatecarcinoma. The metastatic lesion was not identified in physical examination or in macroscopic dissection of the testis after surgery. Microscopy revealed an adenocarcinoma which, given the history of the patient and a positive immunohistochemical stain for PSA, was identified as metastatic prostatic adenocarcinoma.Journal of Pathology of Nepal (2015) Vol. 5, 784-786

Abstract Background Mesenchymal stem/stromal cells (MSCs) have attracted interest as a potential therapy given their anti-inflammatory and immunomodulatory properties. However, clinical trials using MSCs for acute respiratory distress syndrome (ARDS) have produced mixed and inconclusive data. In previous work, we performed a “head-to-head” comparison between different sources of MSCs and showed that each source had a unique genomic and proteomic “signature”. Method This study investigated which sources of MSC: bone marrow derived-MSCs (BM-MSCs), adipose tissue derived-MSCs (AD-MSCs) and umbilical cord derived-MSCs (UC-MSCs) would be the optimal candidate to be used as a therapy in an LPS-induced mouse model of ARDS. Immune cells assessment, tissue transcriptomics, animal survival, and endothelial-epithelial barrier assessment were used to evaluate their effects. Results When comparing the three most commonly used MSC sources, we found that UC-MSCs exhibited greater efficacy compared to other MSCs in improving animal survival, mitigating epithelial/endothelial damage, decreasing lung inflammation via reducing neutrophil infiltration, T cell proliferation, and M1 polarization. Bulk RNA sequencing of lung tissue also showed that UC-MSCs have the capability to downregulate extracellular trap formation, by the downregulation of key genes like Elane and Padi4. Notably, treatment with UC-MSCs demonstrated a significant reduction in Fc-γ R mediated phagocytosis, which has been associated with monocyte pyroptosis and intense inflammation in the context of COVID-19. Conclusion Our findings suggest that UC-MSCs are an optimal source of MSC to treat acute inflammatory conditions in the lungs, such as ARDS.

Post-harvest loss of fruits and vegetables, and health risks and environmental impact of current plastic packaging warrant new biodegradable packaging. To this end, cellulosic residue from agricultural processing byproducts is suitable due to its renewability and sustainability. Herein, soyhulls cellulosic residue was extracted, solubilized in ZnCl 2 solution, and crosslinked with calcium ions and glycerol to prepare biodegradable films. The film combination was optimized using Box Behnken Design and film properties were characterized. The optimized film is translucent and exhibits tensile strength, elongation at break, water vapor permeability, hydrophobicity, and IC50 of 6.3 ± 0.6 MPa, 30.2 ± 0.9%, 0.9 ± 0.3 × 10 -10  gm -1  s -1  Pa -1 , 72.6°, and 0.11 ± 0.1 g/mL, respectively. The water absorption kinetics follow the Peleg model and biodegrade within 25 days at 24% soil moisture. The film extends the shelf life of raspberries by 6 more days compared to polystyrene film. Overall, the value-added soyhull cellulosic films are advantageous in minimizing post-harvest loss and plastic-related issues, emphasizing the principles of the circular bioeconomy., Competing Interests: Declaration of competing interest We declare that we have no financial or personal relationships with others or organizations that can inappropriately influence our work. Both authors have directly participated in analyzing this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Gallstone disease (GSD) has a high prevalence in India. GSD presentation varies from being asymptomatic to severe complications. Laparoscopic cholecystectomy (LC) is the procedure of choice. Histopathological varies from chronic cholecystitis to carcinoma gall bladder (CaGB). Thick wall gall bladder (TWGB) is grey zone. Various parameters of GSD especially TWGB were evaluated to develop an approach to reduce perioperative complications and histopathological surprises., Patients and Methods: This study was conducted at the Department of Surgical Gastroenterology, Dr. RMLIMS, Lucknow. Data of all patients undergoing cholecystectomy between January 2015 and March 2023 were analysed retrospectively. Demographic profile, clinical presentation, blood investigations, radiological findings, operative findings and histopathology report were examined. Clinical and radiological features of difficult cholecystectomies, incidence and type of bile duct injury (BDI), presentation and outcomes of TWGB, incidence of incidental CaGB and its outcome, were evaluated and analysed., Results: A total of 5450 patients underwent cholecystectomy during the study period. GSD is common in females and 4 th decade. The laparoscopic to open conversion rate was 1.2%, the most common cause was unclear anatomy. The incidence of BDI in our series was 0.11% ( n = 6). The most common histopathological outcome was chronic cholecystitis followed by xanthogranulomatous cholecystitis. Incidence of incidental carcinoma gall in our series was 0.3% ( n = 16) with an overall survival of 68.75% at a mean follow-up of 19.4 months. TWGB workup includes contrast-enhanced computed tomography, intraoperative most have difficult cholecystectomy and had a higher rate of conversion, injury and incidental CaGB., Conclusion: Thorough pre-operative evaluation and using the suggested algorithm may decrease perioperative complications and histopathological surprises after LC., (Copyright © 2024 Journal of Minimal Access Surgery.)

Objectives: Patients with coronavirus disease 2019 (COVID-19) are at increased risk of opportunistic fungal infections. This study aims to identify fungal pathogens among COVID positive and negative patients, assess their antifungal susceptibility and evaluate biofilm forming ability of Candida spp. A cross-sectional study was conducted among sputum samples from 135 COVID positive and 101 COVID negative cases. Fungal pathogens were identified by conventional culture methods. Antifungal susceptibility test of Candida isolates was done by disc diffusion method and biofilm production by microtiter plate method., Results: The prevalence of fungal pathogens among COVID-positive and negative cases was 6.70% and 22.77% respectively. In COVID positive cases, Candida albicans (33.33%) was predominantly followed by Aspergillus flavus 2(22.22%) and Candida tropicalis, Mucor spp. and Aspergillus fumigatus. In COVID negative cases, Candida albicans (69.60%) prevailed followed by Trichosporon spp., Candida parapsilosis, Mucor and Alternaria. Age and gender were not associated with fungal infection. Most Candida spp. were susceptible to miconazole but resistant to ketoconazole. To the best of our knowledge, this study represents the first report from Nepal on critical and high priority fungal pathogens categorized by WHO. With fungal infections on the rise, enhanced clinical vigilanceand antifungal susceptibility testing are warranted., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in accordance with the Declaration of Helsiki. Ethical approval of this study was obtained from the Institutional Review Committee (IRC) of the Institute of Science and Technology, Tribhuvan University (Ref. No.: IRC-IOST-22–0052). At the time of enrolment, written informed consent was taken from the patients or their legal guardians on behalf of the patients in case of participants under 16 years of age. Participants, parents or guardians were assured about the non-disclosure of information collected from them and were also informed about the use of data for analysis and using the results for improving patient care activities as well as publication without disclosing the name or identity of cases. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Chronic wounds are often caused or exacerbated by microbial biofilms that are highly resistant to antimicrobial treatments and that prevent healing. This study compared the antimicrobial and antibiofilm activity of nine topical wound treatments, comprising gels with different concentrations of poloxamer 407 (20-26%) and different pH levels (4-6) and containing polyhexanide (PHMB) as an antimicrobial agent; the effects of pH on wound gels containing this agent have not been previously reported. The wound gel formulations were tested against six common wound-associated microbial pathogens: Staphylococcus aureus , S. epidermidis , Pseudomonas aeruginosa , Escherichia coli , Acinetobacter baumannii , and Candida albicans . Time-kill assays were used to assess antimicrobial activity against planktonic forms of each species, and a colony biofilm model was used to assess antibiofilm activity against existing biofilms as well as inhibition of new biofilm formation. Biofilm inhibition activity was also assessed in the presence of common wound dressing materials. Wound gels with higher pH levels exhibited stronger antimicrobial activity, while poloxamer 407 concentrations >20% negatively impacted antimicrobial activity. Wound gel formulations were identified that had antimicrobial, antibiofilm, and biofilm inhibition activity against all tested species in vitro . Biofilm inhibition activity was not affected by contact with common wound dressings. Further development of these wound gels may provide a valuable new option for the treatment and prevention of chronic wounds.

Background: Mesenchymal stem/stromal cells (MSCs) have attracted interest as a potential therapy given their anti-inflammatory and immunomodulatory properties. However, clinical trials using MSCs for acute respiratory distress syndrome (ARDS) have produced mixed and inconclusive data. In previous work, we performed a "head-to-head" comparison between different sources of MSCs and showed that each source had a unique genomic and proteomic "signature"., Method: This study investigated which sources of MSC: bone marrow derived-MSCs (BM-MSCs), adipose tissue derived-MSCs (AD-MSCs) and umbilical cord derived-MSCs (UC-MSCs)  would be the optimal candidate to be used as a therapy in an LPS-induced mouse model of ARDS. Immune cells assessment, tissue transcriptomics, animal survival, and endothelial-epithelial barrier assessment were used to evaluate their effects., Results: When comparing the three most commonly used MSC sources, we found that UC-MSCs exhibited greater efficacy compared to other MSCs in improving animal survival, mitigating epithelial/endothelial damage, decreasing lung inflammation via reducing neutrophil infiltration, T cell proliferation, and M1 polarization. Bulk RNA sequencing of lung tissue also showed that UC-MSCs have the capability to downregulate extracellular trap formation, by the downregulation of key genes like Elane and Padi4. Notably, treatment with UC-MSCs demonstrated a significant reduction in Fc-γ R mediated phagocytosis, which has been associated with monocyte pyroptosis and intense inflammation in the context of COVID-19., Conclusion: Our findings suggest that UC-MSCs are an optimal source of MSC to treat acute inflammatory conditions in the lungs, such as ARDS., (© 2024. The Author(s).)

Urbanization induces homogenization and changes the behavioural patterns of various bird species, thereby facilitating coexistence and prompting adaptations to disturbances in urban environments. However, there is limited research on the influence of how urbanization affects bird tolerance towards humans, especially in developing sub-tropical regions such as Nepal, which is undergoing rapid unplanned urbanization. This study identified the flight initiation distance (FID) as a proxy for assessing bird tolerance. We focused on evaluating the human tolerance levels of 33 bird species using their FIDs in urban and rural habitats within Kathmandu Valley, a rapidly urbanizing city in South Asia. We found higher tolerance in urban birds than in their rural conspecifics, which varies mainly with dietary guild and season. The positive impact on FID was associated with time of the day and body size, while a negative association was observed with flock size, mean population density of humans and interaction between body size and elevation. Our study highlights the increased tolerance level of birds in urban areas, probably owing to habituation, and emphasizes the imperative need to investigate the potential adverse effect on urban bird population owing to this increased tolerance level., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Cranial nerve palsies can be presenting signs of intracranial aneurysms. There is a classic pairing between an aneurysmal vessel and adjacent nerves leading to cranial neuropathy. Isolated abducens nerve palsy can be a localizing sign of an unruptured vertebrobasilar circulation aneurysm. Aneurysms involving Anterior Inferior Cerebellar Artery (AICA) and Posterior Inferior Cerebellar Artery (PICA) have been reported to be associated with abducens nerve palsy. The symptoms in unruptured aneurysms are due to the mass effect on adjacent neurovascular structures. Most of the abducens nerve palsy resolves following microsurgical clipping. Here, we present a rare case of an unruptured Posterior Cerebral Artery (PCA) aneurysm presenting with abducens nerve palsy and diplopia associated with contralateral hemianopsia which markedly improved following endovascular coil embolization.

While much attention has been given to methamphetamine's wake-promoting properties and the concept of using methamphetamine to increase energy, little is known about the ways people who use methamphetamine manage their use to pursue their functional goals or the challenges they encounter doing so. This qualitative study explores the experiences of people who used methamphetamine to manage wakefulness and reduce sleep as a means to achieve functional goals. We conducted a grounded theory analysis of 202 anonymous letters submitted to an online forum. Five themes emerged from this process: (1) Using methamphetamine to extend wakefulness and reduce the need for sleep; (2) Losing control over wakefulness and the need for sleep; (3) Managing wakefulness and the need for sleep while on methamphetamine; (4) Getting caught in a cycle of wakefulness and sleep; and (5) Sleep disruptions even after ceasing methamphetamine use. Participants believed methamphetamine was critical to meeting their functional goals, and they went to great lengths to try to manage the substance's ill effects. Thus, clients in treatment for methamphetamine use disorder may benefit from interventions addressing their underlying motivations and perceived associations between methamphetamine and meeting functional goals.

Background: Kidneys are at risk from drug-induced toxicity, with a significant proportion of acute kidney injury (AKI) linked to medications, particularly cisplatin. Existing cytoprotective drugs for cisplatin-AKI carry side effects, prompting a search for better biological therapies. Mesenchymal Stem Cells (MSCs) are under consideration given their regenerative properties, yet their clinical application has not achieved their full potential, mainly due to variability in the source of MSC tested. In addition, translating treatments from rodent models to humans remains challenging due to a lack of standardized dosing and understanding potential differential responses to cisplatin between animal strains., Method: In the current study, we performed a time-course analysis of the effect of cisplatin across different mouse strains and evaluated gender related differences to create a robust preclinical model that could then be used to explore the therapeutic efficacy of different sources of MSCs for their ability to reverse AKI., Result: Our data indicated that different mouse strains produce differential responses to the same cisplatin dosing regimen. Despite this, we did not observe any gender-related bias towards cisplatin nephrotoxicity. Furthermore, our time-course analysis identified that cisplatin-induced inflammation was driven by a strong CXCL1 response, which was used as a putative biomarker to evaluate the comparative therapeutic efficacy of different MSC sources in reversing AKI. Our data indicates that UC-MSCs have a stronger anti-inflammatory effect compared to BM-MSCs and AD-MSCs, which helped to ameliorate cisplatin-AKI., Conclusion: Overall, our data underscores the importance of using an optimized preclinical model of cisplatin-AKI to test different therapies. We identified CXCL1 as a potential biomarker of cisplatin-AKI and identified the superior efficacy of UC-MSCs in mitigating cisplatin-AKI., (© 2024. The Author(s).)

Newcastle disease (ND) is a highly contagious viral disease caused by the paramyxovirus, which is a single-stranded ribonucleic acid (RNA) virus. This study was conducted to investigate ND outbreaks in 10 vaccinated or non-vaccinated broiler farms, collectively housing 9840 birds of various ages in the Chitwan and Nawalpur districts of Nepal from July to December 2021. Clinically, the affected birds exhibited symptoms such as limb paralysis, greenish diarrhea (seven out of ten flocks), torticollis (two out of ten flocks), inappetence, and drowsiness (ten out of ten flocks). Birds that succumbed during the clinical course underwent a necropsy for gross pathology and samples were collected for the histopathology and molecular diagnosis. The gross and microscopic examination revealed hemorrhages in the proventriculus, erosions and ulcers in the small intestine, congestion, as well as sero-mucosal hemorrhages in the trachea of affected birds, which are typical of ND. Rapid test kits further confirmed the presence of the ND virus antigen while excluding the avian influenza virus. Furthermore, M gene-based real time polymerase chain reaction (RT-PCR) was performed in the pooled samples from the affected birds and the presence of a velogenic strain of the ND virus was identified. The phylogenetic analysis of the RT-PCR positive strain based on the partial F gene nucleotide sequence revealed these strains as genotype VII.2 (formerly VIIi). The findings highlight the occurrence of clinical ND outbreaks in farms despite adherence to recommended vaccination protocols in broiler flocks, underscoring the need for a regular comprehensive investigation involving in-depth examinations of available vaccines and genetic analyses.

Fingertip injuries, particularly those resulting from motorbike chain accidents, pose significant challenges due to their impact on daily life activities. This retrospective study conducted at B&B Hospital in Kathmandu from January 2018 to December 2022 aimed to explore the epidemiology and management of motorbike chain-related fingertip injuries. Among the 256 cases of fingertip injuries studied, 136 were attributed to motorbike chain accidents. Males comprised the majority of cases, and the index and middle fingers were the most frequently injured. Various surgical procedures were employed for treatment, with V-Y Plasty being the most common. These findings underscore the complexity of managing these injuries and highlight the importance of preventive measures and patient-centered care., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background:  Supratentorial intraventricular tumors, encompassing lateral and third ventricular tumors, are uncommon intracranial neoplasms, typically slow-growing and benign, manifesting symptoms only upon reaching a substantial size. This study aims to identify optimal surgical approaches, assess the prevalence and characteristics of these tumors, and evaluate postoperative outcomes among pediatric and adult age groups., Methods:  A retrospective comparative study at a tertiary care hospital from January 2014 to June 2020 included 165 patients (68 pediatrics, 97 adults) meeting inclusion criteria for intraventricular tumor management. Data covered demographic factors, clinical history, neurological assessments, neuroimaging, surgical approaches, histopathological diagnoses, immunohistochemical features, adjuvant therapies, follow-up status, postoperative complications, and morbidity/mortality., Results:  Ventricular tumor incidence showed male preponderance in both adults (M:F = 1.2:1) and pediatrics (M:F = 3:1). Lateral ventricles were the most common location. Pediatric cases exhibited more frequent calcifications on computed tomography scans (35.6% vs. 29.5%). Grade II and III tumors were more prevalent in adults within the lateral ventricle (27.1 and 1.9%) compared with pediatrics (6.5 and 8.4%). The third ventricle predominantly featured benign lesions, with pediatric patients experiencing significantly longer hospital stays (16.12 ± 21.94 days vs. 9.58 ± 6.21 days) ( p  = 0.006). Adults and pediatric patients showed a significant difference in high-grade lateral ventricle tumors ( p -value = 0.002*)., Conclusions:  Supratentorial ventricular tumors are relatively more prevalent in children than adults, presenting challenges due to size and bleeding risks. Surgical resection is the primary treatment, with a focus on the optimal approach for gross total excision to reduce recurrence risk., Competing Interests: No potential conflict of interest relevant to this article was reported., (Thieme. All rights reserved.)

Cardiovascular diseases (CVDs) account for nearly half of chronic kidney disease (CKD)-related deaths. Hypomagnesemia has been associated with various cardiovascular conditions and predicts a decline in renal function leading to end-stage renal disease (ESRD). The objective of this review is to delve into and discuss the significance of magnesium (Mg) in cardiovascular and renal functions, the clinical consequences of hypomagnesemia on CVD and CKD, and the benefits of Mg supplementation in managing CVD and CKD. This review is the result of an extensive search for pertinent articles in databases like PubMed, Medline, PubMed Central, and Google Scholar. Based on the literature search conducted in this review, we concluded that Mg protects against various CVDs and delays the progression of CKD. Mg can regulate pathways associated with inflammation, oxidative stress, and fibrosis. Therefore, maintaining slightly elevated Mg levels and timely Mg supplementation may benefit patients with CVD and CKD. There is a need for additional prospective randomized controlled trials to fully comprehend the therapeutic effects of Mg on CVD and CKD along with setting individualized target levels for serum Mg in such patients., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Panta et al.)

As opioid use-related behaviors continue at epidemic proportions, identifying the root causes of these behaviors is critical. Adverse childhood experiences (ACEs) are shown to be an important predictor of opioid initiation, opioid dependence, and lifetime opioid overdose. The purpose of this systematic review is to examine the association between ACEs and opioid use-related behaviors later in life and to discuss implications for policy, practice, and research regarding ACEs and opioids. Five databases (PubMed, PsycINFO, CINAHL, Medline, and Scopus) were used to identify studies investigating the association between ACEs and opioid use-related behaviors. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 20 studies out of the initial 428 met the inclusion criteria for this review. Among the included 20 studies, 15 focused on the relationship between ACEs and lifetime opioid use-related behaviors, and five focused on current opioid use-related behaviors. All studies found statistical associations between ACEs and lifetime or current opioid use-related behaviors. Five studies found a significant gradient effect; that is, as the number of ACEs increased, the risk of opioid use-related behaviors also increased. A significant dose-response relationship exists between ACEs and opioid use-related behaviors. Hence, it is essential for clinicians to screen for ACEs before prescribing opioid medications, for opioid treatment to incorporate trauma-informed methods, and for messaging around opioid use interventions to include information about ACEs. The current review points to a critical need to implement standardized ACE screening instruments in clinical and research settings., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Mesenchymal stem cells (MSCs) are a promising therapy to potentially treat diabetes given their potent anti-inflammatory and immune-modulatory properties. While these regenerative cells have shown considerable promise in cell culture, their clinical translation has been challenging. In part, this can be attributed to these cells not reaching the pancreas to exert their regenerative effects following conventional intravenous (IV) injection, with the majority of cells being trapped in the lungs in the pulmonary first-pass effect. In the present study, we will therefore examine whether direct delivery of MSCs to the pancreas via an intra-arterial (IA) injection can improve their therapeutic efficacy. Using a mouse model, in which repetitive low doses of STZ induced a gentle, but progressive, hyperglycemia, we tested bone marrow-derived MSCs (BM-MSCs) which we have shown are enriched with pro-angiogenic and immunomodulatory factors. In cell culture studies, BM-MSCs were shown to preserve islet viability and function following exposure to proinflammatory cytokines (IFN-γ, IL-1β, and TNF-α) through an increase in pAkt. When tested in our animal model, mice receiving IV BM-MSCs were not able to mitigate the effects of STZ, however those which received the same dose and batch of cells via IA injection were able to maintain basal and dynamic glycemic control, to similar levels as seen in healthy control animals, over 10 days. This study shows the importance of considering precision delivery approaches to ensure cell-based therapies reach their intended targets to enable them to exert their therapeutic effects., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Stem cell therapy is a promising alternative for inflammatory diseases and tissue injury treatment. Exogenous delivery of mesenchymal stem cells is associated with instant blood-mediated inflammatory reactions, mechanical stress during administration, and replicative senescence or change in phenotype during long-term culture in vitro. In this study, we aimed to mobilize endogenous hematopoietic stem cells (HSCs) using AMD-3100 and provide local immune suppression using FK506, an immunosuppressive drug, for the treatment of inflammatory bowel diseases., Methods: Reactive oxygen species (ROS)-responsive FK506-loaded thioketal microspheres were prepared by emulsification solvent-evaporation method. Thioketal vehicle based FK506 microspheres and AMD3100 were co-administered into male C57BL6/J mice with dextran sulfate sodium (DSS) induced colitis. The effect of FK506-loaded thioketal microspheres in colitis mice were evaluated using disease severity index, myeloperoxidase activity, histology, flow cytometry, and gene expression by qRT-PCR., Results: The delivery of AMD-3100 enhanced mobilization of HSCs from the bone marrow into the inflamed colon of mice. Furthermore, targeted oral delivery of FK506 in an inflamed colon inhibited the immune activation in the colon. In the DSS-induced colitis mouse model, the combination of AMD-3100 and FK506-loaded thioketal microspheres ameliorated the disease, decreased immune cell infiltration and activation, and improved body weight, colon length, and epithelial healing process., Conclusion: This study shows that the significant increase in the percentage of mobilized hematopoietic stem cells in the combination therapy of AMD and oral FK506 microspheres may contribute to a synergistic therapeutic effect. Thus, low-dose local delivery of FK506 combined with AMD3100 could be a promising alternative treatment for inflammatory bowel diseases., (© 2024. The Author(s).)

Introduction: Family planning (FP) is crucial for improving maternal and newborn health outcomes, promoting gender equality, and reducing poverty. Unmet FP needs persist globally, especially in South Asia and Sub-Saharan Africa leading to unintended pregnancies, unsafe abortions, and maternal fatalities. This study aims to identify the determinants of unmet needs for FP from a nationally representative survey., Methods: We analyzed the data of 11,180 currently married women from nationally representative Nepal Health Demographic Survey 2022. We conducted weighted analysis in R statistical software to account complex survey design and non-response rate. We conducted univariate and multivariable binary and multinomial logistic regression to assess association of unmet need for FP with independent variables including place of residence, province, ecological belt, ethnicity, religion, current age, participant's and husband's education, occupation, wealth quintile, parity, desire for child, and media exposure., Results: The total unmet FP need was 20.8% (95%CI: 19.7, 21.9) accounting 13.4% (95%CI: 12.5, 14.4) for unmet need for limiting and 7.4% (95%CI: 6.8, 8.0) for unmet for spacing. Lower odds of total unmet need for FP were present in 20-34 years and 35-49 years compared to <20 years, women belonging to Madhesi ethnic group (AOR: 0.78; 95%CI: 0.64, 0.95) compared to Brahmin/Chhetri, women from richest (AOR: 0.69; 95%CI: 0.56, 0.84), richer (AOR: 0.82; 95%CI: 0.68, 0.97) and middle wealth quintile (AOR: 0.82; 95%CI:0.70, 0.98) groups compared poorest wealth quintile group and women belonging to rural area (AOR: 0.89; 95%CI: 0.80, 0.99) compared to urban area. Higher odds of unmet need for FP were present among women with basic (AOR: 1.34; 95%CI: 1.17, 1.54), and secondary level (AOR: 1.32; 95%CI: 1.12, 1.56) education compared to women without education, among women from Madhesh (AOR: 1.56; 95%CI: 1.22, 1.98), Gandaki (AOR: 2.11; 95%CI: 1.66, 2.68), Lumbini (AOR: 1.97; 95%CI: 1.61, 2.42) and Sudurpashchim province (AOR: 1.64; 95%CI: 1.27, 2.10) compared to Koshi province and among women whose husband education was basic level (AOR:1.37; 95%CI: 1.15, 1.63), or secondary level (AOR: 1.32; 95%CI: 1.09, 1.60) education., Conclusion: Nepal faces relatively high unmet FP needs across various socio-demographic strata. Addressing these needs requires targeted interventions focusing on age, ethnicity, religion, education, and socio-economic factors to ensure universal access to FP services., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 K. C. et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The COVID-19 pandemic has tested the resilience capacities of health systems worldwide and highlighted the need to understand the concept, pathways, and elements of resilience in different country contexts. In this study, we assessed the health system response to COVID-19 in Nepal and examined the processes of policy formulation, communication, and implementation at the three tiers of government, including the dynamic interactions between tiers. Nepal was experiencing the early stages of federalization reform when COVID-19 pandemic hit the country, and clarity in roles and capacity to implement functions were the prevailing challenges, especially among the subnational governments., Methods: We adopted a cross-sectional exploratory design, using mixed methods. We conducted a desk-based review of all policy documents introduced in response to COVID-19 from January to December 2020, and collected qualitative data through 22 key informant interviews at three tiers of government, during January-March 2021. Two municipalities were purposively selected for data collection in Lumbini province. Our analysis is based on a resilience framework that has been developed by our research project, ReBUILD for Resilience, which helps to understand pathways to health system resilience through absorption, adaptation and transformation., Results: In the newly established federal structure, the existing emergency response structure and plans were utilized, which were yet to be tested in the decentralized system. The federal government effectively led the policy formulation process, but with minimal engagement of sub-national governments. Local governments could not demonstrate resilience capacities due to the novelty of the federal system and their consequent lack of experience, confusion on roles, insufficient management capacity and governance structures at local level, which was further aggravated by the limited availability of human, technical and financial resources., Conclusions: The study findings emphasize the importance of strong and flexible governance structures and strengthened capacity of subnational governments to effectively manage pandemics. The study elaborates on the key areas and pathways that contribute to the resilience capacities of health systems from the experience of Nepal. We draw out lessons that can be applied to other fragile and shock-prone settings., (© 2024. The Author(s).)

Background: Cerebral computed tomography angiography (CTA) has revolutionized the diagnosis of neurovascular emergencies. Strategies to reduce radiation, a concern for cancer, involve tube voltage and current reduction but with increased noise and inferior image quality. Hence, the objective of the study was to evaluate the quality of images obtained through low-dose radiation and low-contrast volume CTA with an iterative reconstruction (IR) technique versus standard CTA without IR., Methods: This prospective trial involved 100 adults requiring cerebral CTA for cerebrovascular diseases. They were split into two groups: one with 120 kVp tube voltage and 80 mL contrast using filtered back projection, and the other with 80 kVp and 30 mL contrast with IR. Evaluation criteria included attenuation values, signal-to-noise ratio, contrast-to-noise ratio, and subjective assessments., Results: Compared to 120 kVp, 80 kVp showed higher vessel attenuation in the internal (272.91 ± 30.59 vs 405.52 ± 53.08; p < .001) and middle cerebral artery (247.55 ± 29.84 vs 372.55 ± 49.02; p < .001) regions. Brain parenchymal attenuation at the centrum semiovale was lower with 80 kVp (29.12 ± 1.87 vs 24.78 ± 2.94; p < .001), accompanied by higher noise. Signal-to-noise ratio ( p < .001) and contrast-to-noise ratio ( p < .05) were lower at 80 kVp. Image quality didn't significantly differ, and radiation exposure reduced significantly by 70% in the 80 kVp group, suggesting its diagnostic feasibility., Conclusions: The 80 kVp protocol for CTA of the cerebral vessels combined with lower contrast volume produces images with similar image quality with significant radiation effective dose and total iodine dose reduction. The 80 kVp protocol holds significant promise for replacing the standard 120 kVp protocol in cerebral CTA., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Health disparities associated with e-cigarette use are increasingly apparent among US adolescents. Perceptions of e-cigarette harm and addiction play an important role in understanding adolescents' e-cigarette use behavior. The objective of this systematic review is to examine racial/ethnic and socio-economic disparities in e-cigarette harm and addiction perceptions among US adolescents., Methods: We searched five databases to identify cross-sectional or longitudinal studies that focused on adolescents (≤ 18 years of age) who were ever, current, or never e-cigarettes users; we then examined how race/ethnicity and/or socio-economic status (SES) impacted e-cigarette harm and/or addiction perceptions. Two co-authors independently identified relevant studies, extracted data, and assessed the risk of bias., Results: Adhering to PRISMA guidelines, eight of 226 identified studies met the inclusion criteria. These eight studies examined either perceptions regarding absolute e-cigarette harm and/or addiction (i.e., assessing perception of only e-cigarette) or relative e-cigarette harm and/or addiction (i.e., comparative perceptions to traditional cigarettes) by race and ethnicity. Two of the eight studies assessed absolute harm and/or addiction perceptions of e-cigarettes by SES. Our results indicate that, compared to all other racial/ethnic groups, relative e-cigarette harm and addiction perceptions were lower among Non-Hispanic White adolescents; however, absolute e-cigarette harm perception was higher among these groups. No clear patterns of racial/ethnic differences in absolute e-cigarette addiction perceptions and SES differences in absolute e-cigarette harm perceptions were reported., Conclusion: More research is needed to explicitly assess perceptions of e-cigarette harm and addiction among US adolescents by race/ethnicity and SES to develop subgroup appropriate public health messaging., (© 2023. W. Montague Cobb-NMA Health Institute.)

Background and Aims: Autism spectrum disorder (ASD) is a neurodevelopmental condition that impacts the brain, characterized by challenges in social communication and interaction, often accompanied by repetitive behaviors or focused interests. This study sheds light on the prevalence of ASD within the Southeast Asian region., Methods: The study protocol was registered in PROSPERO (Registration No: CRD42023413915). Appropriate search terms and Boolean operators were employed to explore electronic databases for relevant articles. Data thus extracted were prepared in Excel and analyzed in Comprehensive Meta-Analysis Software. The effect measure utilized in the study was represented by the proportion, and the choice between a fixed or random-effect model depended on the observed heterogeneity. Visual feedback was provided through the use of forest plots and funnel plots., Results: A total of 14 studies were included in the qualitative and quantitative synthesis after screening the imported studies. The prevalence of ASD was six per 1000 population (proportion: 0.006; CI: 0.002-0.017; I 2 : 99.263%). Among the ASD cases, 64.4% (proportion: 0.644; CI: 0.590-0.693; I 2 : 9.937%) were males and 35.6% (proportion: 0.356; CI: 0.307-0.410; I 2 : 9.937%) were females., Conclusion: The prevalence of ASD in Southeast Asia was estimated to be six cases per 1000 individuals, with a higher prevalence among males. This study contributes to our understanding of ASD prevalence in the region, although it is essential to note certain limitations in estimating prevalence., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)