Search

Abstract Background Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a recently recognized inborn error of metabolism associated with steroid-resistant nephrotic syndrome as well as adrenal insufficiency and immunological, neurological, and skin manifestations. SPLIS is caused by inactivating mutations in SGPL1, encoding the pyridoxal 5’phosphate-dependent enzyme sphingosine-1-phosphate lyase, which catalyzes the final step of sphingolipid metabolism. Some SPLIS patients have undergone kidney transplantation, and others have been treated with vitamin B6 supplementation. In addition, targeted therapies including gene therapy are in preclinical development. In anticipation of clinical trials, it will be essential to characterize the full spectrum and natural history of SPLIS. We performed a retrospective analysis of 76 patients in whom the diagnosis of SPLIS was established in a proband with at least one suggestive finding and biallelic SGPL1 variants identified by molecular genetic testing. The main objective of the study was to identify factors influencing survival in SPLIS subjects. Results Overall survival at last report was 50%. Major influences on survival included: (1) age and organ involvement at first presentation; (2) receiving a kidney transplant, and (3) SGPL1 genotype. Among 48 SPLIS patients with nephropathy who had not received a kidney transplant, two clinical subgroups were distinguished. Of children diagnosed with SPLIS nephropathy before age one (n = 30), less than 30% were alive 2 years after diagnosis, and 17% were living at last report. Among those diagnosed at or after age one (n = 18), ~ 70% were alive 2 years after diagnosis, and 72% were living at time of last report. SPLIS patients homozygous for the SPL R222Q variant survived longer compared to patients with other genotypes. Kidney transplantation significantly extended survival outcomes. Conclusion Our results demonstrate that SPLIS is a phenotypically heterogeneous condition. We find that patients diagnosed with SPLIS nephropathy in the first year of life and patients presenting with prenatal findings represent two high-risk subgroups, whereas patients harboring the R222Q SGPL1 variant fare better than the rest. Time to progression from onset of proteinuria to end stage kidney disease varies from less than one month to five years, and kidney transplantation may be lifesaving.

Kiran Shahbaz,1 Alamgeer,1 Vibhu Paudyal,2 Maryam Zubair,3 Maryam Zahra Safdar,4 Momina Tahir,4 Laraib Akram,4 Salamat Ali4 1Department of Pharmacology, University College of Pharmacy, University of the Punjab Lahore, Pakistan; 2Institute of Clinical Sciences, University of Birmingham, Edgbaston Birmingham, UK; 3Faculty of Experimental Medicine Orebro University, Sweden; 4Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad, PakistanCorrespondence: Salamat Ali, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad, Pakistan, Tel +00-92-3004189052; +00-92-041-9201036, Email drsalamatali@gcuf.edu.pkBackground: Prevalence of psychological disorders among individuals with diabetes is significantly higher as compared to the general population.Aim: This study aimed to assess the prevalence and impact of psychological disorders on pharmacotherapy of diabetes patients.Methodology: This cross-sectional study was conducted at two primary care hospitals in Pakistan from April to June 2023. The nine-item Patient Health Care Questionnaire (PHQ-9) scale was used to assess depression in the study’s population, and its effects on pharmacotherapy of diabetes. Chi-square test was used to evaluate relationship between ordinal variables/categorical variables and depression whereas; Student’s t-test was used to assess the relationship between numerical variables with depression.Results: A total of 320 patients were assessed, comprising 120 (37.5%) males and 200 (62.5%) females, with a mean age of 52.5 (SD± 11.8) years. The average duration of diabetes is 7.0 (SD± 5.4). The average PHQ-9 score was 8.3 (SD± 5.5). Depression was found to be prevalent in 43.7% of the study population. Gender (female) (p-value 0.002), advanced age (p-value 0.002), lower income (p-value 0.001), education levels (p-value 0.001), longer duration of diabetes (p-value 0.001), poor diabetes control according to BSR value (p-value 0.001), usage of injectable insulin (p-value 0.005), and concomitant diseases (p-value 0.001) were found to be independently linked with depression. Significant association was observed between depression and treatment adherence (p-value 0.0025), number of missed doses (p-value 0.045), and difficulty in diabetes management (p-value 0.0015).Conclusion: Our study highlights significant prevalence of depression in study population and the prevalent depression negatively impacts on treatment adherence. It also revealed that depression complicates diabetes management resulting in poor medication adherence, poor diabetes control and diabetes related complications, making diabetes control more challenging and difficult.Keywords: psychological disorders, diabetes, pharmacotherapy, PHQ-9

Formal infectious disease surveillance in Ukraine has been disrupted by Russia’s 2022 invasion, leading to challenges with tracking and containing epidemics. To analyze the effects of the war on infectious disease epidemiology, we used open-source data from EPIWATCH, an artificial intelligence early-warning system. We analyzed patterns of infectious diseases and syndromes before (November 1, 2021–February 23, 2022) and during (February 24–July 31, 2022) the conflict. We compared case numbers for the most frequently reported diseases with numbers from formal sources and found increases in overall infectious disease reports and in case numbers of cholera, botulism, tuberculosis, HIV/AIDS, rabies, and salmonellosis during compared with before the invasion. During the conflict, although open-source intelligence captured case numbers for epidemics, such data (except for diphtheria) were unavailable/underestimated by formal surveillance. In the absence of formal surveillance during military conflicts, open-source data provide epidemic intelligence useful for infectious disease control.

Abstract Background Antenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks’ gestation. However, dosing remains unoptimized and lung benefits are highly variable. Current treatment regimens generate high-concentration, pulsatile fetal steroid exposures now associated with increased risk of childhood neurodevelopmental diseases. We hypothesized that damage-associated changes in the fetal hippocampal transcriptome would be independent of preterm lung function. Methods Date-mated ewes carrying a single fetus at 122 ± 2dGA (term = 150dGA) were randomized into 4 groups: (i) Saline Control Group, 4×2ml maternal saline intramuscular(IM) injections at 12hr intervals (n = 11); or (ii) Dex High Group, 2×12mg maternal IM dexamethasone phosphate injections at 12hr intervals followed by 2×2ml IM saline injections at 12hr intervals (n = 12; representing a clinical regimen used in Singapore); or (iii) Dex Low Group, 4×1.5mg maternal IM dexamethasone phosphate injections 12hr intervals (n = 12); or (iv) Beta-Acetate Group, 1×0.125mg/kg maternal IM betamethasone acetate injection followed by 3×2ml IM sterile normal saline injections 12hr intervals (n = 8). Lambs were surgically delivered 48hr after first maternal injection at 122–125dGA, ventilated for 30min to establish lung function, and euthanised for necropsy and tissue collection. Results Preterm lambs from the Dex Low and Beta-Acetate Groups had statistically and biologically significant lung function improvements (measured by gas exchange, lung compliance). Compared to the Saline Control Group, hippocampal transcriptomic data identified 879 differentially significant expressed genes (at least 1.5-fold change and FDR

Introduction: The aims of this systematic review and meta-analysis are to synthesise quality of life (QOL) of family caregivers of children and young adults with Down syndrome (DS) and determine factors affecting their QOL. Method: This review was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Key search terms were “quality of life”, “down syndrome” and “trisomy 21”. Meta-analysis using random effect model was conducted where feasible. All studies underwent qualitative synthesis. The study protocol was registered with PROSPERO (CRD42023413532). Results: Eighteen studies with 1956 caregivers were included. Of the 10 studies utilising the World Health Organization Quality of Life Instrument-Brief Version, 5 were included in the meta-analysis. Psychosocial domain had the highest score with mean (95% confidence interval [CI]) of 63.18 (39.10–87.25). Scores were poorer in physical, environmental and social domains: 59.36 (28.24–90.48), 59.82 (19.57–100.07) and 59.83 (44.24–75.41), respectively. Studies were heterogenous with I2 values ranging from 99–100% (P less than 0.01). The remaining 8 studies used 6 other instruments. Qualitative synthesis revealed that caregivers’ QOL was adversely affected by child-related factors, such as level of functional independence, developmental delay, presence of multiple comorbidities, impaired activities of daily living and poor sleep quality. Environmental factors that adversely affected caregivers’ QOL included number of children, housing and support from the family. Personal factors that affected caregivers’ QOL included age, being a single mother, low education and low income. Conclusion: QOL of caregivers of children with DS was lower than population reference data. Understanding the factors that influence family caregivers’ QOL is an essential step towards improving the QOL of caregivers and their children with DS.

Introduction: Down syndrome (DS) negatively impacts the well-being of affected individuals. This study aimed to summarise the evidence on quality of life (QOL) of children and young adults with DS using quantitative measures from caregivers’ perspective and identify factors that affected their QOL. Method: Database search was conducted on PubMed, Embase, Web of Science and CINAHL on 24 April 2024. Meta-analysis using random effects model was conducted where feasible. All studies underwent qualitative synthesis. The study protocol was registered with PROSPERO (CRD42023413532). Results: Seventeen studies involving 3038 children with DS using various QOL measures were included: Pediatric Quality of Life Inventory (PedsQL) (8 studies), KIDSCREEN (4 studies), KidsLife (2 studies), The Netherlands Organization for Applied Scientific Research Academic Medical Center Children’s QOL (2 studies) and Personal Outcome Scale (1 study). Meta-analysis on PedsQL studies compared scores between children with DS and typically developing (TD) children. Total scale score was lower in children with DS (mean 70.28, 95% confidence interval [CI] 64.31–76.24) compared to TD children (mean 88.17, 95% CI 80.50–95.83). All subdomains of PedsQL were also lower in children with DS. Within the domain of psychosocial health, children with DS had statistically significant lower social functioning (standardised mean difference -1.40, 95% CI -2.27 to -0.53) and school functioning (standardised mean difference -1.09, 95% CI -1.55 to -0.62) scores, but similar emotional functioning scores. Qualitative synthesis revealed poorer subdomain QOL compared to TD children, especially in social functioning and cognitive functioning. QOL worsened during adolescent years. Family variables (parental education and occupation) did not affect parental perception of children’s QOL. Children with DS who had higher intelligent quotient had better QOL. Conclusion: Children with DS have lower caregiver-reported QOL than TD children, especially in social functioning and school functioning subdomains.

Abstract In this paper, we apply stochastic differential equations with the Wiener process to investigate the soliton solutions of the Chaffee–Infante (CI) equation. The CI equation, a fundamental model in mathematical physics, explains concepts such as wave propagation and diffusion processes. Exact soliton solutions are obtained through the application of the modified extended tanh (MET) method. The obtained wave figures in 3D, 2D, and contour are highly localized and determine an individual frequency shift under the behavior of sharp peak, periodic wave, and singular soliton. The MET method shows to be a valuable analytical tool for obtaining soliton solutions, essential for understanding the dynamics of nonlinear wave phenomena. Numerical simulations enable us to explore soliton solutions in two and three dimensions, shedding light on their properties over time. Our results have wide applications in various domains, including stochastic processes and nonlinear dynamics, impacting advancements in physics, engineering, finance, biology, and beyond.

Abstract Water contaminated with arsenic presents serious health risks, necessitating effective and sustainable removal methods. This article proposes a method for removing arsenic from water by impregnating biochar with iron oxide (Fe2O3) from brown seaweed (Sargassum polycystum). After the seaweed biomass was pyrolyzed at 400 °C, iron oxide was added to the biochar to increase its adsorptive sites and surface functional groups, which allowed the binding of arsenic ions. Batch studies were conducted to maximize the effects of variables, including pH, contact time, arsenic concentration, and adsorbent dosage, on arsenic adsorption. The maximum arsenic adsorption efficiency of 96.7% was achieved under optimal conditions: pH 6, the adsorbent dosage of 100 mg, the initial arsenic concentration of 0.25 mg/L, and a contact time of 90 min. Langmuir and Freundlich’s isotherms favored the adsorption process, while the kinetics adhered to a pseudo-second-order model, indicating chemisorption as the controlling step. Column studies revealed complete saturation after 200 min, and the adsorption behavior fits both the Adams–Bohart and Thomas models, demonstrating the potential for large-scale application. The primary mechanism underlying the interaction between iron-modified biochar and arsenic ions is surface complexation, enhanced by increased surface area and porosity. This study highlights the significant contribution of iron-modified biochar derived from macroalgae as an effective and sustainable solution for arsenic removal from water.

Abstract Background Equine-assisted services (EAS) involves the use of horses within therapy, learning or horsemanship sessions and has been used with military veterans suffering from post-traumatic stress disorder (PTSD). This study systematically reviewed existing research on the use of EAS in the treatment of PTSD in military veterans and evaluated its effectiveness. Methods A systematic review was performed, in May 2023, with searches and data extraction carried out from three separate databases (PubMed, JSTOR and Science Direct) related to testing the effect of EAS on PTSD outcomes in veterans. A risk of bias assessment of included studies was conducted and meta-analysis of outcomes performed when two or more studies reported the same outcomes. Other effects of EAS on veterans’ health were also discussed. Results A total of 13 studies were identified based on our inclusion and exclusion criteria with 11 originating from the US and the remaining two from Australia and Israel. There were 344 participants amongst all of the studies with a mean age of 47 years and a male:female ratio of 19:6. Eight out of the 13 studies reported PTSD scores, as measured by either PTSD Checklist for DSM-5 (PCL-5) or PCL-Veteran/-Military versions (PCL-V/-M), and results suggested a reduction in PTSD score after EAS treatment of 22.6%. A meta-analysis confirmed that EAS favored a significantly lower PTSD score after treatment, with a mean difference of 12.46, 95% CI [9.03,15.88], p

Objective: The American Thyroid Association (ATA) Pediatric Guidelines recommend selective, prophylactic central neck dissection (pCND) for patients with papillary thyroid carcinoma (PTC) based on tumor focality, tumor size, and the surgeon’s experience. With the expansion of pre-surgical somatic oncogene testing and continued controversy over the benefits of pCND, oncogenic alteration data may provide an opportunity to stratify pCND. This study compared lymph node (LN) involvement in pediatric patients with PTC between tumors with low- and high-invasive-associated alterations to explore the potential utility of preoperative oncogenic alterations in the stratification of pCND. Methods: This is retrospective cohort study of pediatric patients who underwent somatic oncogene testing post thyroidectomy for PTC between July 2003 and July 2022. Results: Of 192 eligible PTC patients with postoperative somatic oncogene data, 19 tumors harbored somatic alterations associated with low-invasive disease (19/192, 10%), and 128 tumors harbored a BRAFV600E alteration (45/192, 23%) or an oncogenic fusion (83/192, 43%). Tumors with low-invasive alterations were less likely to present malignant preoperative cytology (2/18, 11%) than those with high-invasive alterations (97/124, 78%; P < 0.001). Twelve patients with low-invasive alterations had LNs dissected from the central neck (12/19, 63%) compared to 127 patients (127/128, 99%) with high-invasive alterations. LN metastasis was identified in two patients with low-invasive alterations (2/19, 11%) compared to 107 patients with high-invasive alterations (107/128, 84%; P < 0.001). Conclusion: Pediatric patients with low-invasive somatic oncogenic alterations are at low risk for metastasis to central neck LNs. Our findings suggest that preoperative knowledge of somatic oncogene alterations provides objective data to stratify pediatric patients who may not benefit from pCND.

The hybrid nanofluid (Hnf) flow with heat and mass transmission under the magnetic field and activation energy consequences across parallel double-rotating surfaces has been studied. In order to synthesize the Hnf, polymer/CNT matrix nanocomposites (MNCs) are dissolved in water. Polymer/CNT MNCs are highly efficient and have exceptional properties. These MNCs are helpful in various applications, from engineering to biomedical research, because of their incredible thermophysical properties. Keeping in view the significant uses of the polymer/CNT MNC hybrid nanofluid flow, we have formulated the fluid flow in the form of the system of PDEs (partial differential equations), which are reformed into the non-dimensional form of ODEs (ordinary differential equations) and then solved numerically through the Matlab package (bvp4c). The numerical outputs for velocity, heat and mass profiles are compared with another numerical approach ND-solve. It has been determined that the outputs are precisely correct and reliable. Furthermore, the fluid velocity drops with the influence of suction/injection, Reynold number, and polymer/CNT MNC. The increasing quantity of polymer/CNT MNC in water reduces the energy and mass profiles. The energy field enhances with the upshot of the heat source term, whereas the concentration field falloffs with the effect of Schmidt number.

Introduction: Because of wide heterogeneity in the epidemiology of heart failure among different populations, it is imperative to establish population-specific databases. Aims and Objectives: To describe the clinical profile, treatment patterns, and outcomes of heart failure patients admitted to our tertiary care hospital. Material and Methods: The study was a prospective observational study conducted over two years at our tertiary care hospital. It included patients admitted with acute and acute-on-chronic heart failure. Results: We recruited 264 patients. Mean age of the study population was 57.8 ± 15.14 years. Males were 157 (59.5%). Dilated cardiomyopathy was the most common cause followed by ischemic heart disease. Most common risk factors were hypertension, tobacco use, anemia, and diabetes. Heart failure with reduced ejection fraction was present in 154 (62%) patients. Acute de novo heart failure was present in 91 (34.5%) patients. The most common precipitant for heart failure exacerbation was infection, followed by ischemic causes and non-adherence to drugs. The mean duration of hospital stay was 7.5 ± 3.1 days. The in-hospital mortality was 8.7%, and cumulative six-month and one-year mortality was 23% and 28%, respectively. In multivariate analysis, renal failure, readmission, and not being on guideline-directed medical treatment were significant predictors of mortality. Conclusion: Our patients were younger, predominantly males, with dilated and ischemic cardiomyopathy as commonest etiology. Hypertension and tobacco smoking were most common risk factors, with infections as most common precipitants. Only one-third of patients were on guideline-directed medical therapy. The one-year mortality was 28% and was higher in those without guideline-directed medical therapy.

Summary . Background: Nocturnal enuresis (NE) is believed to be commoner in children with homozygous sickle cell disease (SCD-SS) than in those with normal haemoglobin. The reasons for this have not been established and its prevalence and pattern have not been adequately described in the tropics. Objective: To determine the prevalence and describe the pattern of nocturnal enuresis in children with SCD-SS in the Guinea Savannah region of Nigeria. Method: A cross-sectional case-controlled study was carried out on randomly selected steady state children with SCD-SS attending the Haematology Clinic of the Department of Paediatrics at Ahmadu Bello University Teaching Hospital, Zaria. A structured questionnaire was used to collect historical and clinical data from the patients. Age-dependent definition of NE was used in analyzing data. Results: One hundred and fifty (47.1 percent) of the 360 children with SCD-SS studied had NE. The rate was significantly higher than that obtained in control children. Whereas significantly more male than female control children had NE, the difference did not reach statistical significance in those with SCD-SS. Mariy home caregivers used potentially harmful methods in attempts to control NE. Socioeconomic factors and family history did not play significant role in the prevalence of NE. Conclusion: Nocturnal enuresis is commoner in children with SCD-SS than in otherwise normal children, even in the Guinea Savannah region of Nigeria. It is suggested that NE in SCD-SS may not be innocuous.

Abstract Ventilator-associated pneumonia (VAP) affects up to 20% of critically ill patients and induces significant antibiotic prescription pressure, accounting for half of all antibiotic use in the ICU. VAP significantly increases hospital length of stay and healthcare costs yet is also associated with long-term morbidity and mortality. The diagnosis of VAP continues to present challenges and pitfalls for the currently available clinical, radiological and microbiological diagnostic armamentarium. Biomarkers and artificial intelligence offer an innovative potential direction for ongoing future research. In this Review, we summarise the pathobiological heterogeneity and diagnostic challenges associated with VAP.

Abstract Methadone maintenance treatment for opioid dependent mothers is standard of care. Infants of methadone maintained opioid dependent (MMOD) mothers have better outcomes compared to infants of opioid dependent mothers without treatment. However, when compared to non-exposed infants, infants of MMOD mothers are associated with worse outcomes. We conducted a pilot study to examine genome wide differential DNA methylation using cord blood samples from sixteen term and near-term infants of MMOD and opioid naïve mothers, excluding Infants with chorioamnionitis. A total of 152 differentially methylated loci were identified at a difference > + 2,

Abstract Clematis graveolens Lindl., an indigenous climbing plant found in the Himalayan areas, is used by local communities for the treatment of neck tumors. The objective of this work is to examine the comprehensive metabolomic profile, antioxidant capability, in vitro and in silico anti-glioma effects on U-87 human glioma cell lines of the crude extract and fractions from C. graveolens. Liquid chromatography coupled with mass spectroscopy (LC–MS/MS) was used to establish detailed metabolite profiling of C. graveolens. The assessment of cell cytotoxicity was conducted using MTT cell viability assay on U-87 and BHK-21. Through molecular docking studies, the mode of inhibition and binding interaction between identified compounds and target proteins were also determined to evaluate the in vitro results. The use of LC–MS/MS-based global natural products social (GNPS) molecular networking analysis resulted in the identification of 27 compounds. The crude extract, ethyl acetate fraction, and chloroform fraction exhibited significant inhibitory activity against the U-87 cell lines, with IC50 values of 112.0, 138.1, and 142.7 µg/mL, respectively. The ethyl acetate fraction exhibited significant inhibitory concentration for 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity and the metal chelation activity with IC50 value of 39.50 µg/mL, 32.27 µg/mL, and 53.46 µg/mL, respectively. The crude extract showed maximum total phenolic, and total flavonoid concentration measuring 338.7 µg GAE/mg, and 177.04 µg QE/mg, respectively. The findings of this study indicate that C. graveolens consists of a diverse range of active phytoconstituents that possess antioxidant and anti-glioma properties.

Abstract Background As part of the fight against coronavirus disease, Nigeria received nearly 4 million doses of the COVID-19 vaccine via the COVID-19 Vaccines Global Access (COVAX) Facility, marking a historic step towards equitable global distribution of COVID-19 vaccines. Although evidence exists on COVID-19 hesitancy in Nigeria, yet, we are unaware of any study on the optimization of COVID-19 vaccination from the lenses of the mobile teams. Objective This study seeks to explore the perceptions and experiences of mobile teams in selected communities during the implementation of COVID-19 vaccination in Benue and Niger. Methods An exploratory approach was adopted, and the study was conducted in Niger and Benue states based on poor performance in COVID-19 vaccination. Focus Group Discussions (FDGs) were conducted among 12 mobile vaccination teams from 12 LGAs. The recorded discussions were transcribed and coded (inductively and deductively) using Dedoose software (v9.0). Four themes and seven sub-themes were generated from the participants’ responses. Results Seventy-two (72) health workers including vaccinators, validators, Electronic Management of Immunization Data (EMID) recorders, social mobilizers, and paper recorders participated in this study. Health workers’ perceptions and experiences were thematized using the health building blocks. The mobilization teams in Benue and Niger states perceived that their mobilization efforts contributed to improved coverage, increased accessibility, and reduced hesitancy among the community dwellers. Challenges reported by the teams were vaccine misconceptions, requests for incentives in exchange for vaccine uptake, poor network services, distance to communities, and vaccine stockout. Conclusion This study concluded that social mobilizers play key roles in vaccine uptake, especially at the community level. Their roles in creating awareness, sensitization, and bringing the vaccine closer to hard-to-reach communities contributed to the success attained in the fight against COVID-19 in both states.

Abstract Microtubule associated proteins (MAPs) are widely expressed in the central nervous system, and have established roles in cell proliferation, myelination, neurite formation, axon specification, outgrowth, dendrite, and synapse formation. We report eleven individuals from seven families harboring predicted pathogenic biallelic, de novo, and heterozygous variants in the NAV3 gene, which encodes the microtubule positive tip protein neuron navigator 3 (NAV3). All affected individuals have intellectual disability (ID), microcephaly, skeletal deformities, ocular anomalies, and behavioral issues. In mouse brain, Nav3 is expressed throughout the nervous system, with more prominent signatures in postmitotic, excitatory, inhibiting, and sensory neurons. When overexpressed in HEK293T and COS7 cells, pathogenic variants impaired NAV3 ability to stabilize microtubules. Further, knocking-down nav3 in zebrafish led to severe morphological defects, microcephaly, impaired neuronal growth, and behavioral impairment, which were rescued with co-injection of WT NAV3 mRNA and not by transcripts encoding the pathogenic variants. Our findings establish the role of NAV3 in neurodevelopmental disorders, and reveal its involvement in neuronal morphogenesis, and neuromuscular responses.

Abstract Background This study delves into the intricate landscape of oral cancer, a global concern with a high incidence in Asian countries. We focus on oral squamous cell carcinoma (OSCC), primarily driven by the consumption of betel nut and its derivatives. OSCC often arises from premalignant lesions like oral submucous fibrosis (OSF). In Pakistan, OSCC is prevalent among men due to various addictive substances, including smokeless tobacco and chewing materials. Mutations in tumor suppressor genes, such as TP53 and p21, play crucial roles in this malignancy’s development. We also explore the involvement of TUSC3 gene deletion in OSCC and OSF. Methods In this study we investigated demographics, TUSC3 gene expression, deletion analysis, and TP53 and p21 genetic alterations in OSCC and OSF patients (blood and tissue of 50 samples in each condition) who had tobacco derivates usage history. The association analysis was carried out mainly through PCR based genotyping. Results The study’s patient cohort (OSCC and OSF) displayed a wide age range from 13 to 65 years (Mean = 32.96 years). Both conditions were more prevalent in males, with a male-female ratio of approximately 2.5:1. Chewing habits analysis revealed high frequencies of gutka use in both OSF and OSCC patients. TUSC3 expression analysis in OSCC cell lines indicated significant downregulation. Genotyping showed no TUSC3 deletion in OSF cases, but a deletion rate of over 22% in OSCC tissue samples. Analysis supported a significant association of TUSC3 deletion with OSCC development but not with OSF. Polymorphism in p53 exon 4 and p21 (rs1801270) were significantly associated with both OSCC and OSF, adding to their pathogenesis. Our findings further revealed a strong correlation between TUSC3 deletion and the excessive use of tobacco and related products, shedding light on the genetic underpinnings of OSCC development. Conclusions Notably, our study provides a crucial insight into genetic aspects underlying OSCC and OSF in response of addictive consumption of areca nut, betel quid, and tobacco derivatives. A significant association between TUSC3 deletion and OSCC development, along with polymorphisms in TP53 and p21, underscores the importance of further research into the molecular mechanisms driving oral cancer progression for improved diagnosis and treatment outcomes.

Background: This study investigated the impact of COVID-19 on patients with sickle cell crisis (SCC) using National Inpatient Sample (NIS) data for the year 2020. Methods: A retrospective cohort analysis was conducted utilizing International Classification of Diseases (ICD-10) codes to identify adults who were admitted with a principal diagnosis of sickle cell crisis. The primary outcomes examined were inpatient mortality, while the secondary outcomes assessed included morbidity, hospital length of stay, and resource utilization. Analyses were conducted with STATA. Multivariate logistic and linear regression analyses were used to adjust for confounding variables. Results: Of 66,415 adult patients with a primary SCC diagnosis, 875 were identified with a secondary diagnosis of COVID-19 infection. Unadjusted mortality rate was higher for SCC patients with COVID-19 (2.28%) compared to those without (0.33%), with an adjusted odds ratio (aOR) of 8.49 (p = 0.001). They also showed increased odds of developing acute respiratory failure (aOR = 2.37, p = 0.003) and acute kidney injury requiring dialysis (aOR = 8.66, p = 0.034). Additionally, these patients had longer hospital stays by an adjusted mean of 3.30 days (p < 0.001) and incurred higher hospitalization charges by an adjusted mean of USD 35,578 (p = 0.005). Conclusions: The SCC patients with COVID-19 presented higher mortality rates, increased morbidity indicators, longer hospital stays, and substantial economic burdens.

Background and Objectives: “Synchronous videoconference telemedicine in neonatal office-practice” (SyNTOP) has been a routine practice in our center since the start of the COVID-19-related lockdown. We recently reported our experience with the “success” of this practice in terms of removing the need to visit the hospital over the next 48 h after the teleconsult. Methods: Secondary results of this retrospective descriptive study which analyzed 829 consults are presented in this manuscript. Data from electronic medical records of those who availed teleconsultation facility between March 2020 and April 2021 were retrieved. Relevant information about clinical presentation, findings from the video call, demographic information, decisions made by the clinician, and outcomes were collected. Best efforts were made to obtain follow-up information by the clinical team or guest–patient relations officers. Results: Fever (n = 118) and acute diarrheal disease (n = 58) were the common presenting complaints; most (80.5% and 95.5%, respectively) were resolved without physical examination; 265 developmental assessments were completed by video-facilitated checks. Fast-track vaccination visits where queries were resolved and bills paid online, were an innovation where well babies could avoid queues and possible exposure to crowds. One-fourths of SyNTOP were from outside the district, and 1.4% were from foreign countries. Conclusions: Teleconsults were successfully conducted in neonatal office practice for different health-care enquiries. Strategies such as fast-track vaccinations and online developmental follow-up assessments were performed by leveraging technology. We highlight the benefits of these innovations in our center with a view to enhance their uptake elsewhere. Such approaches have the potential to increase health equity and access to specialty health care.

Abstract Background Catheter ablation and antiarrhythmic drug therapy are utilized for rhythm control in atrial fibrillation (AF), but their comparative effectiveness, especially with contemporary treatment modalities, remains undefined. We conducted a systematic review and meta-analysis contrasting current ablation techniques against antiarrhythmic medications for AF. Methods We searched PubMed, SCOPUS, Cochrane CENTRAL, and Web of Science until November 2023 for randomized trials comparing AF catheter ablation with antiarrhythmics, against antiarrhythmic drug therapy alone, reporting outcomes for > 6 months. Four investigators extracted data and appraised risk of bias (ROB) with ROB 2 tool. Meta-analyses estimated pooled efficacy and safety outcomes using R software. Results Twelve trials (n = 3977) met the inclusion criteria. Catheter ablation was associated with lower AF recurrence (relative risk (RR) = 0.44, 95%CI (0.33, 0.59), P ˂ 0.0001) and hospitalizations (RR = 0.44, 95%CI (0.23, 0.82), P = 0.009) than antiarrhythmic medications. Catheter ablation also improved the physical quality of life component score (assessed by a 36-item Short Form survey) by 7.61 points (95%CI -0.70-15.92, P = 0.07); but, due to high heterogeneity, it was not statistically significant. Ablation was significantly associated with higher procedural-related complications [RR = 15.70, 95%CI (4.53, 54.38), P

Abstract Diabetic retinopathy (DR) is a multifactorial disease displaying vascular-associated pathologies, including vascular leakage and neovascularization, ultimately leading to visual impairment. However, animal models accurately reflecting these pathologies are lacking. Vascular endothelial growth factor A (VEGF-A) is an important factor in the development of micro- and macro-vascular pathology in DR. In this study, we evaluated the feasibility of using a cumate-inducible lentivirus (LV) mediated expression of vegf-a to understand DR pathology in vitro and in vivo. Retinal pigment epithelial cells (ARPE-19) were transduced with cumate-inducible LV expressing vegf-a, with subsequent analysis of vegf-a expression and its impact on cell proliferation, viability, motility, and permeability. Cumate tolerability in adult Wistar rat eyes was assessed as an initial step towards a potential DR animal model development, by administering cumate via intravitreal injections (IVT) and evaluating consequent effects by spectral domain optical coherence tomography (SD-OCT), flash electroretinography (fERG), ophthalmic examination (OE), and immunohistochemistry. Transduction of ARPE-19 cells with cumate-inducible LV resulted in ~ 2.5-fold increase in vegf-a mRNA and ~ threefold increase in VEGF-A protein secretion. Transduced cells displayed enhanced cell proliferation, viability, permeability, and migration in tube-like structures. However, IVT cumate injections led to apparent retinal toxicity, manifesting as retinal layer abnormalities, haemorrhage, vitreous opacities, and significant reductions in a- and b-wave amplitudes, along with increased microglial activation and reactive gliosis. In summary, while cumate-inducible LV-mediated vegf-a expression is valuable for in vitro mechanistic studies in cellular drug discovery, its use is not a feasible approach to model DR in in vivo studies due to cumate-induced retinal toxicity.

Abstract Background The economic crisis that began in 2008 has severely affected Southern (Greece, Italy, Portugal, Spain) Western European (SWE) countries of Western Europe (WE) and may have affected ongoing efforts to eliminate viral hepatitis. This study was conducted to investigate the impact of the economic crisis on the burden of HBV and HCV disease. Methods Global Burden of Diseases 2019 data were used to analyse the rates of epidemiological metrics of HBV and HCV acute and chronic infections in SWE and WE. Time series modelling was performed to quantify the impact of healthcare expenditure on the time trend of HBV and HCV disease burden in 2000–2019. Results Declining trends in incidence and prevalence rates of acute HBV (aHBV) and chronic HBV were observed in SWE and WE, with the pace of decline being slower in the post-austerity period (2010–2019) and mortality due to HBV stabilised in SWE. Acute HCV (aHCV) metrics and chronic HCV incidence and mortality showed a stable trend in SWE and WE, whereas the prevalence of chronic HCV showed an oscillating trend, decreasing in WE in 2010–2019 (p

Abstract During the last decade, nanotechnology has attained a significant place among the scientific community for the biosynthesis of plant‐based nanoparticles owing to its effective, safe, and eco‐friendly nature. Hence, keeping in view the significance of nanotechnology, the current study was conducted to develop, characterize (UV–visible spectroscopy, scanning electron microscopy, Fourier‐transform infrared spectroscopy, and energy‐dispersive X‐ray spectroscopy), and assess the antimicrobial (antibacterial and antifungal) properties of Peganum harmala L. Extract‐based Gold (Au) and Silver (Ag) nanoparticles (NPs). Characteristic absorption peaks at 420 and 540 nm revealed the formation of AgNPs and AuNPs, respectively. SEM images revealed that both silver and gold nanoparticles were oval and spherical with average size ranging from 42 to 72 and 12.6 to 35.7 nm, respectively. Similarly, FT‐IR spectra revealed that the functional groups such as hydroxyl, carboxyl, and polyphenolic groups of biomolecules present in the extract are possibly responsible for reducing metallic ions and the formation of nanoparticles. Likewise, the EDX analysis confirmed the presence of silver and gold in synthesized NPs. Furthermore, the AgNPs and AuNPs showed good antibacterial and antifungal activities. The maximum antibacterial and antifungal activity was noticed for P. harmala extract against Pseudomonas aeroginosa (21 mm) and Candida albicon (18 mm), respectively. Whereas, the maximum antibacterial and antifungal activities of synthesized AgNPs were observed against Salmonella typhi (25 mm) and Penicillium notatum (36 mm), respectively. Moreover, in the case of AuNPs, the highest antibacterial and antifungal activity of synthesized AuNPs was noticed against Escherichia coli (25 mm) and C. albicon (31 mm), respectively. Findings of this study revealed that P. harmala extract and biosynthesized NPs (silver and gold) possessed significant antibacterial and antifungal properties against different bacterial (Bacillus subtilis, Staphylococcus aureus, E. coli, P. aeroginosa, and S. typhi) and fungal (C. albicans, Aspergillus Niger, and P. notatum) strains. Further studies must be carried out to assess the probable mechanism of action associated with these antimicrobial properties.

Abstract Background & objective Despite their continued use, the effectiveness and safety of vasopressors in post-cardiac arrest patients remain controversial. This study examined the efficacy of various vasopressors in cardiac arrest patients in terms of clinical, morbidity, and mortality outcomes. Methods A comprehensive literature search was performed using online databases (MeSH terms: MEDLINE (Ovid), CENTRAL (Cochrane Library), Embase (Ovid), CINAHL, Scopus, and Google Scholar) from 1997 to 2023 for relevant English language studies. The primary outcomes of interest for this study included short-term survival leading to death, return of spontaneous circulation (ROSC), survival to hospital discharge, neurological outcomes, survival to hospital admission, myocardial infarction, and incidence of arrhythmias. Results In this meta-analysis, 26 studies, including 16 RCTs and ten non-RCTs, were evaluated. The focus was on the efficacy of epinephrine, vasopressin, methylprednisolone, dopamine, and their combinations in medical emergencies. Epinephrine treatment was associated with better odds of survival to hospital discharge (OR = 1.52, 95%CI [1.20, 1.94]; p

Abstract Background The European Union (EU) faces many health-related challenges. Burden of diseases information and the resulting trends over time are essential for health planning. This paper reports estimates of disease burden in the EU and individual 27 EU countries in 2019, and compares them with those in 2010. Methods We used the Global Burden of Disease 2019 study estimates and 95% uncertainty intervals for the whole EU and each country to evaluate age-standardised death, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) rates for Level 2 causes, as well as life expectancy and healthy life expectancy (HALE). Results In 2019, the age-standardised death and DALY rates in the EU were 465.8 deaths and 20,251.0 DALYs per 100,000 inhabitants, respectively. Between 2010 and 2019, there were significant decreases in age-standardised death and YLL rates across EU countries. However, YLD rates remained mainly unchanged. The largest decreases in age-standardised DALY rates were observed for “HIV/AIDS and sexually transmitted diseases” and “transport injuries” (each -19%). “Diabetes and kidney diseases” showed a significant increase for age-standardised DALY rates across the EU (3.5%). In addition, “mental disorders” showed an increasing age-standardised YLL rate (14.5%). Conclusions There was a clear trend towards improvement in the overall health status of the EU but with differences between countries. EU health policymakers need to address the burden of diseases, paying specific attention to causes such as mental disorders. There are many opportunities for mutual learning among otherwise similar countries with different patterns of disease.

Polystyrene microplastics (PS-MPs) are raising global concerns as they have tendency to induce adverse effects on organisms. Herbacetin (HBN) is a natural flavone that shows diverse biological activities. Therefore, the current study was designed to evaluate the curative role of HBN against PS-MPs provoked hepatic damage. Forty-eight rats were divided into 4 groups, control, PS-MPs-intoxicated (0.01 mg/kg), PS-MPs + HBN co-treated (0.01 mg/kg + 40 mg/kg) and HBN only treated (40 mg/kg) group. The experiment was conducted for 30 days. PS-MPs administration reduced the expressions of Nrf-2 as well as anti-oxidants genes and increased Keap-1 expression. It also lessened the activities of superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and heme oxygenase-1 (HO-1) and glutathione (GSH) level, while elevating the levels of MDA and ROS. Additionally, PS-MPs exposure augmented the levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine transaminase (ALT). Furthermore, there was an upsurge in the levels of inflammatory indices in PS-MPs treated group. PS-MPs also upregulated Caspase-3 and Bax expression whereas, decreased Bcl-2 expression. Nevertheless, HBN treatment recovered all the impairments due to its anti-apoptotic, anti-oxidant and anti-inflammatory and hepatoprotective nature. Therefore, it is deduced that HBN could be used as a potential therapeutic agent to counter PS-MPs induced hepatic toxicity.

The current research was planned to evaluate the ameliorative role of juglanin (Jug) against polyethylene microplastics (PEMP) prompted testicular impairments. 48 rats were allocated in 4 groups: control, PEMP exposed, Jug + PEMP co-administrated and Jug supplemented group. The activities of antioxidant enzyme, inflammatory markers level, hormonal level, the expressions of steroidogenic enzymes, pro-apoptotic and anti-apoptotic protein were assessed after the 56 days of the trial. PEMP intoxication significantly disturbed Nrf-2/Keap-1 pathway and the biochemical profile of rats. However, the administration of Jug markedly increased Nrf-2 and anti-oxidant enzymes expressions, besides decreased the Keap-1 expression. Jug administration also increased Catalase (CAT), super oxide dismutase (SOD) glutathione reductase (GPx), glutathione peroxidase (GSR) and Hemeoxygenase-1 (HO-1) activities. On the other hand, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were decreased following Jug administration. Moreover, Jug administration decreased the levels of inflammatory markers. Additionally, Jug administration increased luteinizing hormone (LH), testosterone, follicle-stimulating hormone (FSH) levels and steroidogenic enzymes expression including 17β-hydroxysteroid dehydrogenase (17β-HSD), steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) expressions. Jug administration decreased Caspase-3 and Bax expressions, while increasing Bcl-2 expression. Therefore, the current findings suggested that Jug can remarkably alleviate PEMP induced testicular damage due to its therapeutical potentials.

Polystyrene microplastics (PSMPs) are noxious environmental pollutants that pose a significant threat to vital body organs including the lungs. Robinetin (ROB) is a flavonoid which demonstrates various pharmacological potentials. This trial was designed to assess the protective ability of ROB to avert PSMPs provoked pulmonary toxicity in rats. Twenty-four rats were divided into four groups i.e., control, PSMPs (0.1 mg/kg), PSMPs (0.1 mg/kg) + ROB (30 mg/kg) and ROB (30 mg/kg) only supplemented group. PSMPs exposure led to a notable reduction in the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GSR) as well as GSH contents while causing a pronounced elevation in the concentration of MDA and ROS. Furthermore, PSMPs significantly augmented the levels of myeloperoxidase (MPO), macrophages, neutrophils, and lymphocytes in BALF. Moreover, the levels of IL-1β, TNF-α, NF-κB, IL-6 and COX-2 activities were increased following the PSMPs exposure. Nonetheless PSMPs remarkably decreased Bcl-2 levels, coupled with an escalation in Caspase-9, Caspase-3 and Bax levels. Despite this, severe histological alterations were observed in lungs tissues after PSMPs provision. Nevertheless, ROB provision markedly protected the lungs via regulating aforementioned dysregulations. This investigation validated the shielding strength of ROB to counteract PSMPs caused pulmonary toxicity.

In this paper, Bi2ZnxSe3-x with compositions x = 0 and x = 0.25 were synthesized using the melt technique at 850˚C. The crystal structures and surface morphologies of both the samples were investigated with X-ray diffraction (XRD), Raman spectroscopy and field emission scanning electron microscopy (FESEM), respectively. XRD spectra of both the bulk alloys of Bi2ZnxSe3-x (x = 0 and x = 0.25) revealed a polycrystalline nature with a hexagonal structure. UV-Vis absorbance spectra have shown that Zn doping increases the optical band gap while decreasing the absorbance edge. The activation energy (Ea) as calculated using Arrhenius plot revealed that Zn doping in place of Se results in a decrease in Ea. The variation in resistance with temperature highlights the prevalence of phonon-phonon and electron-phonon scattering as the dominant mechanisms. Topological insulators, due to their ability to suppress intrinsic electron backscattering, are viable recommendations for use as counter electrode materials in photovoltaic cells. This approach is poised to create a novel pathway for the future commercialization of flexible photovoltaic applications.

OBJECTIVES To assess the effectiveness of retro pyloric Roux-En-Y Hepaticojejunostomy in cases of choledochal cysts and bile duct injuries to reduce complications, such as delayed gastric emptying and acute cholangitis. METHODOLOGY This retrospective cohort study was conducted in the surgical C unit of Hayatabad Medical Complex, Peshawar (January 2019 - December 2022). This study included 37 patients treated for bile duct injuries and choledochal cysts. All patients had an ASA III or above, aged 5 to 36 years. Amongst the 35 patients, 21 patients underwent surgery for choledochal cysts, while 14 patients were treated for bile duct injuries. Patients with type 1choledochal cysts were admitted through OPD after getting diagnosed by ultrasound abdomen and, in some cases, MRCP. RESULTS Out of 36 patients, 23 (63.71%) presented with type I choledochal cysts, while 14 (40%) exhibited bile duct injuries (BDI). Among the 14 BDI cases, 57.14% underwent open cholecystectomy, 42.85% underwent laparoscopic cholecystectomy, and 5.71% received immediate repair during the primary surgery. Conversely, 8.57% of patients with CBD ligation underwent exploration on the 3rd postoperative day upon early detection of the injury. Among the patients diagnosed with BDI after the 7th postoperative day, 25.71% underwent delayed repair at three months. Postoperatively, patients were authorized for fluid consumption within 24-48 hours. Moreover, 4 (11.42%) patients developed a fever of approximately 100°F, managed with intravenous Paracetamol in 2 (5.71%) cases. Patients also presented with subsequent wound infections, which were treated on an outpatient basis through oral antibiotics and wound dressing. CONCLUSION The Retropyloric Roux-en-Y hepaticojejunostomy is a modified biliary reconstruction procedure with minimal morbidity and better outcomes than traditional methods. It reduces complications like delayed gastric emptying and acute cholangitis. We recommend its frequent use for biliary reconstruction when appropriate.

Industrial dye effluent causes significant risks to the environment. The present study was focused on photocatalytic degradation of the dye Direct Red 28 using a ternary composite of graphitic carbon nitride, TiO2, and polyorthoanisidine (g-C3N4/TiO2/POA), prepared by in-situ oxidative polymerization o-anisidine. The synthesized composite g-C3N4/TiO2/POA properties were characterized using different analytical techniques. X-ray diffraction (XRD) results revealed the prominent pattern of TiO2 and g-C3N4 in the composite peak at 2θ° while Fourier transform infrared (FTIR) results provided the confirmation peaks for g-C3N4/TiO2/POA and POA at 1,110 cm−1 and 1,084 cm−1 for C-O-C ether. Scanning electron microscopy (SEM) demonstrated an increase in the average size of the composite up to 428 nm. The energy-dispersive X-ray spectroscopy (EDX) spectrum provided the weight percentages of the C, O, and Ti in the composite were 8.5%, 45.69%, and 45.81%, respectively. The photocatalytic degradation of Direct Red 28 dye under UV irradiation using a composite showed that 86% Direct Red 28 dye was degraded by a 30 mg/L dose of g-C3N4/TiO2/POA in 240 min at pH 2. After four consecutive cycles, the utilized composite showed 79% degradation of Direct Red 28, demonstrating the stability and effectiveness of the g-C3N4/TiO2/POA photocatalyst. The high reusability and efficiency of the g-C3N4/TiO2/POA composite are due to increased light absorption range and reduced e−/h+ recombination rate in the presence of g-C3N4 and POA.

Abstract Background Otitis media (OM) is the most frequent and complex middle ear condition with multifactorial etiology including genetic predisposition. OM depicts a variable clinical spectrum, leading to speech, developmental delay, and hearing loss. Here, we report the clinical and genetic findings of chronic suppurative otitis media (CSOM) segregating in a six‐generation consanguineous Pakistani family PKOM08. Methods Clinical evaluations, including audio and tympanometry, were conducted to assess OM manifestation and their impact on hearing function. Exome sequencing was performed to identify potential genetic variants underlying CSOM in the study participants. Results Clinical evaluation of participating individuals revealed varying degrees of disease severity, with mild to moderate hearing loss. All the affected individuals had CSOM with no other apparent comorbidity. Whole exome followed by Sanger sequencing revealed two rare heterozygous variants [c.1867C>T, p.(Pro623Ser) and c.11015G>A, p.(Arg3672Gln)] of BSN gene in most of the affected individuals of family PKOM08. BSN encodes a scaffold bassoon protein involved in synaptic vesicle trafficking. The identified variants replaced evolutionary conserved amino acid residues in the encoded protein and are predicted to impact the ionic interactions in the secondary structure. Conclusion A deep intronic variant of BSN has been previously implicated in the etiology of childhood ear infections. Our study further supports a link between BSN‐impaired function and ear infection and CSOM in children.

Recent research has shown that there is a link between the trend of cardiovascular disease (CVD), chronic symptoms of SARS-CoV-2 (COVID-19), and medical nutrition therapy. Making positive changes to an individual’s lifestyle can help to reduce the symptoms that follow exposure to CVD and COVID-19. Sustainable nutrition and lifestyle changes can positively impact an individual’s health. Studies have considered the risk factors associated with the disease, medical history, the link between nutrition and peripheral vascular disease (PVD), symptom management, and the interrelationship between nutrition, COVID-19, and PVD. One study has demonstrated that Western Dietary intake can boost the innate immune system while suppressing humoral response, causing chronic inflammation and poor host defense against viruses. However, further investigation is needed to confirm. Patients with PVD and COVID-19 have experienced a reduction in side effects when prescribed a regimen of medical nutrition therapy, heart-healthy diets, and adequate physical activity before and after symptoms of both diseases appear. This approach has proven to be a protective factor during the combination of both illnesses. Our findings indicate that balanced diet and lifestyle are essential in supporting an optimal immune system that can reduce the risk of virus load in individuals at risk of infection and symptoms from COVID-19 and PVD.

IntroductionEndotracheal intubation is an uncommon procedure for children in the emergency department but can be technically difficult and cause significant adverse effects. Videolaryngoscopy (VL) offers improved first-pass success rates over direct laryngoscopy (DL) for both adults and children undergoing elective surgery. This systematic review was designed to evaluate current evidence regarding how the effectiveness and safety of VL compares to DL for intubation of children in emergency departments.MethodsFour databases (MEDLINE, Embase, CENTRAL and Web of Science) were searched on 11th May 2023 for studies comparing first-pass success of VL and DL for children undergoing intubation in the emergency department. Studies including adult patients or where intubation occurred outside of the emergency department were excluded. Quality assessment of included studies was carried out using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Meta-analysis was undertaken for first-pass success and adverse event rate.ResultsTen studies met the inclusion criteria representing 5,586 intubations. All included studies were observational. Significantly greater first-pass success rate was demonstrated with VL compared to DL (OR 1.64, 95% CI [1.21–2.21], p = 0.001). There was no significant difference in risk of adverse events between VL and DL (OR 0.79, 95% CI [0.52–1.20], p = 0.27). The overall risk of bias was moderate to serious for all included studies.ConclusionVL can offer improved first-pass success rates over DL for children intubated in the emergency department. However, the quality of current evidence is low and further randomised studies are required to clarify which patient groups may benefit most from use of VL.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=415039, Identifier CRD42023415039.

This systematic review seeks to improve the existing framework for developing students’ Computing Identity (CI) by integrating contemporary elements and identifying new dimensions. A meticulous selection of 31 articles followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol, ensuring a comprehensive and systematic approach. The findings highlight factors that influence students’ CI and also the constructs defining the frameworks for developing students’ CI. The identified existing constructs are competence/performance, interest, sense of belonging, and recognition in computing, with competence/performance being the most explored and recognition the least. The review proposes a new framework for developing students’ CI that includes the “social context” as it interweaves with existing constructs to shape the multifaceted process of CI formation. The findings underscore a research gap concerning the inclusion of diverse perspectives, which is essential for a richer understanding of CI. Additionally, the study emphasizes the potential to incorporate new elements to enhance the existing frameworks for developing students’ CI, along with its validation in diverse contexts.

Introduction: Antimicrobial resistance (AMR), a transboundary health issue, critically impacting low- and middle-income countries (LMICs) where 80% of antibiotics are used in the community, with 20–50% being inappropriate. Southeast-Asia, including Bangladesh, faces heightened AMR risk due to suboptimal healthcare standard and unregulated antibiotic sales. This study aimed to audit antibiotic dispensing patterns from community pharmacies, identifying factors influencing purchasing behaviors. Methods: A cross-sectional survey of 385 antibiotic customers and structured observations of 1000 pharmacy dispensing events were conducted in four urban and rural areas in Bangladesh. Descriptive analysis defined antibiotic use, while Poisson regression examined how patients' demographics and health symptoms influenced prescription behaviors. Results: Among 1000 observed medicine dispensing events, 25.9% were antibiotics. Commonly purchased antibiotics included macrolides (22.8%), third-generation-cephalosporins (20.8%), and second-generation-cephalosporins (16.9%). Following WHO-AWaRe classifications, 73.5% of antibiotics were categorized as Watch, and 23.1% as Access. From the survey, 56.6% antibiotics were purchased without a prescription from drug-sellers and informal healthcare providers, primarily for “non-severe” health-symptoms such as upper-respiratory-tract infections (37.4%), fever (31.7%), uncomplicated skin infections (20%), gastrointestinal-infections (11.2%), and urinary-tract infections (7.9%). The likelihood of presenting a prescription while purchasing antibiotics was 27% lower for individuals aged 6–59 compared to those ≤5 or ≥ 60. Lower-respiratory-tract infections and enteric-fever had higher prescription rates, with adjusted prevalence ratios of 1.78 (95% CI: 1.04, 3.03) and 1.87 (95% CI: 1.07, 3.29), respectively. After adjusting for confounders, sex, urban-rural locations, income, education, and number of health-symptoms exhibited no significant influence on prescription likelihood. Conclusion: This study underscores unregulated antibiotic sales without prescriptions, urging tailored interventions considering prevailing health-seeking practices in diverse healthcare settings in LMICs. Enforcing prescription-only regulations is hindered by easy access through community pharmacies and conflicts of interest. Future strategies should consider how stewardship impacts the financial interests of pharmacy personnel in settings lacking clear authority to ensure optimal compliance.

Owing to enhanced features of nanomaterials, various applications of such materials have been suggested in the thermal systems, heat exchanges, electronic cooling systems, coolant processes, energy production etc. Following to such motivated applications, the objective of current analysis is to presents the bioconvective double stratification flow of Sutterby nanofluid due to bidirectional moving surface. The thermal interpretation of problem is subject to utilization of radiative effects, activation energy and heat source. The observations for heat, mass and microorganism's assessment are performed by using the convective boundary conditions. Shooting numerical simulations are performed for modeled problem. It is noticed that heat transfer enhances due to thermal stratification parameter. An increment in mass transfer is subject to larger values of mass stratification Biot number. The claimed results offer significance in controlling the heating and cooling processes, thermal devices, energy generation, manufacturing developments, solar systems etc.

Polyethylene microplastics (PEMPs) are widely distributed in environment and exerts deleterious effects on animal as well as human health. Sakuranetin (SKN) is a natural flavonoid that manifests profound therapeutic potential. Albino rats (n = 24) were partitioned into 4 groups i.e., Control, PEMPs 1.5 mg/kg, PEMPs 1.5 mg/kg + SKN 10 mg/kg and SKN 10 mg/kg administered group. After 30 days of treatment, our results revealed that PEMPs exposure reduced nuclear factor erythroid 2–related factor 2 (Nrf-2) and antioxidant genes while enhancing the expression of kelch-like ECH-associated protein 1(Keap-1). Besides, PEMPs intoxication reduced the level of renal biomarkers i.e., creatinine clearance and increased the level of creatinine, urea, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Additionally, it lessened the activities of glutathione S-transferase (GST), superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT), glutathione peroxidase (GPx) and heme oxygenase-1 (HO-1) whereas the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were increased. Conversely, it increased the levels of nuclear factor-kappa B (NF-kB), tumor necrosis factor-alpha (TNF-a), interleukin-1beta (IL-1b) and IL-6 as well as escalated the activity of cyclooxygenase-2 (COX-2). Furthermore, the expression of bcl-2-associated X protein (Bax) and caspase-3 were elevated, while the expression of B-cell lymphoma 2 (Bcl-2) was lowered. However, SKN treatment significantly (P

STEM education for deaf students aims to engage and include intellectual and experiential learning other than normal classrooms. These programs improve students' critical thinking, problem-solving, creativity, and complex decision-making, which are essential for academic and life success. This study aims to explore several aspects of a STEM based workshop including problem solving skills, STEM skills, subject knowledge, and effectiveness of the workshop for a group of 27 deaf students. The workshop spanned five consecutive days and focused on problem-solving principles within the context of global warming. Moreover, in this study, the Creative Problem-solving approach developed by Osborn and Parnes was implemented to measure improvement of the constructs above, through a post questionnaire. Cronbach's alpha and McDonald's Omega coefficient exceeded .7 for each construct. The data obtained from the questionnaire demonstrated a random distribution of data according to the Shapiro-Wilk test performed (p

Abstract Background Malaria in pregnancy remains a major global public health problem. Intermittent prophylaxis treatment of malaria in pregnancy with Sulphadoxine-pyrimethamine and co-trimoxazole is efficacious for prevention of malaria in pregnancy HIV negative and positive women, respectively. However, uptake of the recommended doses of therapies has remained suboptimal in Uganda, majorly due to inadequate knowledge among pregnant women. Therefore, this study aimed to explore attitudes and perceptions towards developing an educational video for malaria preventive therapy. Methods We conducted an exploratory study with qualitative methods among pregnant women attending antenatal care at Kisenyi Health Center IV (KHCIV), health workers from KHCIV, and officials from the Ministry of Health. The study was conducted at KHCIV from October 2022 to March 2023. Focus group discussions (FGD) were conducted among purposively selected pregnant women and key informant interviews (KII) among health workers and Ministry of Health officials. Data were analyzed using inductive and deductive thematic methods in atlas ti.8. Results A total of five FGDs comprising of 7–10 pregnant women were conducted; and KIIs were conducted among four mid-wives, two obstetricians, and two Ministry of Health officials. Generally, all respondents mentioned a need for interventions to improve malaria preventive knowledge among pregnant women; were positive about developing an educative video for malaria preventive therapy in pregnancy; and suggested a short, concise, and edutaining video focusing both the benefits of taking and risks of not taking malaria preventive therapy. They proposed that women may be encouraged to view the video as soon as they conceive and throughout the pregnancy. It also was suggested that the video may be viewed on television sets in maternal and reproductive health clinics and homes, and on smart phones. Conclusion Pregnant women, health workers, and Ministry of Health officials were positive about the development of a short edutaining video on malaria preventive therapy that focuses on both benefits of taking and risks of not taking the malaria preventive therapy in pregnancy. This information guided the video development and therefore, in the development of health educative videos, client and stakeholder inputs may always be solicited.

Introduction: Pancytopenia in the peripheral smear and hypocellularity in the bone marrow characterise aplastic anaemia (AA). It is far less common in Western countries. The Asian continent has a greater prevalence rate. Aplastic anemia carries a high mortality rate if it is not treated. Hence early diagnosis and treatment is important to reduce the mortality rate. Only few Indian studies are conducted to assess the epidemiology of AA. Aims and Objectives: To evaluate clinical and pathological profile of patients with aplastic anemia. Materials and Methods: This cross sectional observational study was done over a period of 1.5years in department of medicine, St johns medical college, Bangalore. A detailed clinical history, physical examination and available previous investigations were recorded. Results: In our study aplastic anemia had bimodal peak in age distribution noted in groups of 21-30 & 51-60yrs .Male preponderance of 1.33:1 .Most common presenting complaint was Fatigue. Severe (37.6%) and Very severe aplastic anemia (37.6%) were more common.Most common 1st line agent was Cyclosporine and 2nd line agent was Danazol. Out the 35 only 4 (11.4%) showed Complete Response, 19 (54.3%) showed Partial Remission, 10 were transfusion dependent (28.6%) and 2 (5.8%) expired. Conclusion: ATG and Cyclosporine showed significant improvement in most parameters. Many patients in the study were unwilling for ATG and bone marrow transplantation due to the cost factor. Many are still requiring frequent transfusions, thus probing us to search for newer novel forms of treatment to reduce the cost of treatment and mortality in aplastic anemia patients.

This study refines a single-layer Feed-Forward Neural Network (FFNN) for the treatment of textile dye wastewater, concentrating on percentage decolorization (%DEC) and percentage chemical oxygen demand (%COD) reduction. The optimized neural network configuration comprises four input and one output neuron, fine-tuned based on the mean squared error (MSE). The training phase demonstrates a consistent MSE decline, reaching its lowest at epoch 209 for %DEC and epoch 34 for %COD, with corresponding MSEs of $1.799 \times 10^{-5}$ and $ 1.4 \times 10^{-3} $, respectively. The maximum absolute errors for %DEC and %COD were found to be $ 4.0787 $ and $ 2.4486 $, while the mean absolute errors were $ 0.4821 $ and $ 0.7256 $, respectively. In contrast to second-degree polynomial regression, the FFNN model exhibits enhanced predictive accuracy, as indicated by higher $ R^2 $ values of $ 0.99363 $ for %DEC and $ 0.99716 $ for %COD, and reduced error metrics.

Abstract Introduction Acute pancreatitis poses a significant health risk due to the potential for pancreatic necrosis and multi-organ failure. Fluid resuscitation has demonstrated positive effects; however, consensus on the ideal intravenous fluid type and infusion rate for optimal patient outcomes remains elusive. Methods A comprehensive literature search was conducted using PubMed, Embase, the Cochrane Library, Scopus, and Google Scholar for studies published between 2005 and January 2023. Reference lists of potential studies were manually searched to identify additional relevant articles. Randomized controlled trials and retrospective studies comparing high (≥ 20 ml/kg/h), moderate (≥ 10 to

Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate. Methods A library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone. Results After screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC. Conclusion Collectively, these findings suggest that domperidone serves as an effective “multi-target” inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC.

Abstract Background Parent-reported experience measures are part of pediatric Quality of Care (QoC) assessments. However, existing measures were not developed for use across multiple healthcare settings or throughout the illness trajectory of seriously ill children. Formative work involving in-depth interviews with parents of children with serious illnesses generated 66 draft items describing key QoC processes. Our present aim is to develop a comprehensive parent-reported experience measure of QoC for children with serious illnesses and evaluate its content validity and feasibility. Methods For evaluating content validity, we conducted a three-round Delphi expert panel review with 24 multi-disciplinary experts. Next, we pre-tested the items and instructions with 12 parents via cognitive interviews to refine clarity and understandability. Finally, we pilot-tested the full measure with 30 parents using self-administered online surveys to finalize the structure and content. Results The Delphi expert panel review reached consensus on 68 items. Pre-testing with parents of seriously ill children led to consolidation of some items. Pilot-testing supported feasibility of the measure, resulting in a comprehensive measure comprising 56 process assessment items, categorized under ten subthemes and four themes: (1) Professional qualities of healthcare workers, (2) Supporting parent-caregivers, (3) Collaborative and holistic care, and (4) Efficient healthcare structures and standards. We named this measure the PaRental Experience with care for Children with serIOUS illnesses (PRECIOUS). Conclusions PRECIOUS is the first comprehensive measure and has the potential to standardize assessment of QoC for seriously ill children from parental perspectives. PRECIOUS allows for QoC process evaluation across contexts (such as geographic location or care setting), different healthcare workers, and over the illness trajectory for children suffering from a range of serious illnesses.

The study of fluid dynamics in the context of flow across a rotating disk is highly important since it has extensive applications in multiple industries, as well as in engineering and scientific fields. The objective of our current research is to investigate the heat transfer in the vicinity of a Stagnation Point of a Maxwell nanofluid flow passing over a porous rotating disk. A rotating disc is a phenomenon where a circular arc is formed at every point on the disc as it rotates uniformly around an axis. The shear stress at the interface between the disc and the spinning fluid provides information about the amount of power required to overcome friction and move the disc and the heat transfer is influenced by the alterations in the flow field inside the region. The heat and mass movement are studied in the context of a chemical process. Firstly, convert the PDEs into ODEs, suitable self-similarity transformation is used. After applying transformations, for graphical purpose we have used the Bvp4c technique. A variety of graphs (2D, Contour, vector plots, and Stream lines) and tables depict the impact of active parameters on the fluid's capacity to transfer significance. Velocity outline decreases for the greater values of the Deborah number values. The temperature profile improved with an improvement in the Nb parameter, while the opposite trend we noticed on ϕ(ζ). The findings of this study will have advantages in various fields, including transportation operations, architectural design systems, increased oil recovery systems, and medicinal applications that utilize nanofluids.

Abstract Background SRO (Similar to RCD1) genes family is largely recognized for their importance in the growth, development, and in responding to environmental stresses. However, genome-wide identification and functional characterization of SRO genes from cotton species have not been reported so far. Results A total of 36 SRO genes were identified from four cotton species. Phylogenetic analysis divided these genes into three groups with distinct structure. Syntenic and chromosomal distribution analysis indicated uneven distribution of GaSRO, GrSRO, GhSRO, and GbSRO genes on A2, D5 genomes, Gh-At, Gh-Dt, Gb-At, and Gb-Dt subgenomes, respectively. Gene duplication analysis revealed the presence of six duplicated gene pairs among GhSRO genes. In promoter analysis, several elements responsive to the growth, development and hormones were found in GhSRO genes, implying gene induction during cotton growth and development. Several miRNAs responsive to plant growth and abiotic stress were predicted to target 12 GhSRO genes. Organ-specific expression profiling demonstrated the roles of GhSRO genes in one or more tissues. In addition, specific expression pattern of some GhSRO genes during ovule development depicted their involvement in these developmental processes. Conclusion The data presented in this report laid a foundation for understanding the classification and functions of SRO genes in cotton.