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Introduction: Estimating Neonatal Abstinence Syndrome (NAS) and prenatal substance exposure rates in Medicaid can help target program efforts to improve access to services., Methods: The data for this study was extracted from the 2016-2020 Transformed Medicaid Statistical Information System (T-MSIS) Analytic Files (TAF) Research Identifiable Files (RIF) and included infants born between January 1, 2016 and December 31, 2020 with a either a NAS diagnosis or prenatal substance exposure., Results: Between 2016 and 2020, the estimated national rate of NAS experienced a 18% decline, while the estimated national rate of prenatal substance exposure experienced a 3.6% increase. At the state level in 2020, the NAS rate ranged from 3.2 per 1000 births (Hawaii) to 68.0 per 1000 births (West Virginia). Between 2016 and 2020, 28 states experienced a decline in NAS births and 20 states had an increase in NAS rates. In 2020, the lowest prenatal substance exposure rate was observed in New Jersey (9.9 per 1000 births) and the highest in West Virginia (88.1 per 1000 births). Between 2016 and 2020, 38 states experienced an increase in the rate of prenatal substance exposure and 10 states experienced a decline., Discussion: Estimated rate of NAS has declined nationally, but rate of prenatal substance exposure has increased, with considerable state-level variation. The reported increase in prenatal substance exposure in the majority of US states (38) suggest that substances other than opioids are influencing this trend. Medicaid-led initiatives can be used to identify women with substance use and connect them to services., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Safe levels of heavy metals in the surface water and sediment of the eastern Bay of Bengal coast have not been universally established. Current study characterized heavy metals such as arsenic (As), chromium (Cr), cadmium (Cd) and lead (Pb) in surface water and sediments of the most important fishing resource at the eastern Bay of Bengal coast, Bangladesh. Both water and sediment samples were analyzed using inductively coupled plasma mass spectrometer. Considering both of the seasons, the mean concentrations of Cr, As, Cd, and Pb in water samples were 33.25, 8.14, 0.48, and 21.14 μg/L, respectively and in sediment were 30.47, 4.48, 0.20, and 19.98 mg/kg, respectively. Heavy metals concentration in water samples surpassed the acceptable limits of usable water quality, indicating that water from this water resource is not safe for drinking, cooking, bathing, and any other uses. Enrichment factors also directed minor enrichment of heavy metals in sediment of the coast. Other indexes for ecological risk assessment such as pollution load index (PLI), contamination factor (CF), geoaccumulation index (I geo ), modified contamination degree (mC d ), and potential ecological risk index (PERI) also indicated that sediment of the coastal watershed was low contamination. In-depth inventorying of heavy metals in both water and sediment of the study area are required to determine ecosystem health for holistic risk assessment and management., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

One of the central regulators of cell growth, proliferation, and metabolism is the mammalian target of rapamycin, mTOR, which exists in two structurally and functionally different complexes: mTORC1 and mTORC2; unlike m TORC2, mTORC1 is activated in response to the sufficiency of nutrients and is inhibited by rapamycin. mTOR complexes have critical roles not only in protein synthesis, gene transcription regulation, proliferation, tumor metabolism, but also in the regulation of the programmed cell death mechanisms such as autophagy and apoptosis. Autophagy is a conserved catabolic mechanism in which damaged molecules are recycled in response to nutrient starvation. Emerging evidence indicates that the mTOR signaling pathway is frequently activated in tumors. In addition, dysregulation of autophagy was associated with the development of a variety of human diseases, such as cancer and aging. Since mTOR can inhibit the induction of the autophagic process from the early stages of autophagosome formation to the late stage of lysosome degradation, the use of mTOR inhibitors to regulate autophagy could be considered a potential therapeutic option. The present review sheds light on the mTOR and autophagy signaling pathways and the mechanisms of regulation of mTOR-autophagy., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cardiovascular disease remains a leading cause of morbidity and mortality in the United States (US). Although high-quality data are accessible in the US for cardiovascular research, digital literacy (DL) has not been explored as a potential factor influencing cardiovascular mortality, although the Social Vulnerability Index (SVI) has been used previously as a variable in predictive modeling. Utilizing a large language model, ChatGPT4, we investigated the variability in CVD-specific mortality that could be explained by DL and SVI using regression modeling. We fitted two models to calculate the crude and adjusted CVD mortality rates. Mortality data using ICD-10 codes were retrieved from CDC WONDER, and the geographic level data was retrieved from the US Department of Agriculture. Both datasets were merged using the Federal Information Processing Standards code. The initial exploration involved data from 1999 through 2020 ( n = 65,791; 99.98% complete for all US Counties) for crude cardiovascular mortality (CCM). Age-adjusted cardiovascular mortality (ACM) had data for 2020 ( n = 3118 rows; 99% complete for all US Counties), with the inclusion of SVI and DL in the model (a composite of literacy and internet access). By leveraging on the advanced capabilities of ChatGPT4 and linear regression, we successfully highlighted the importance of incorporating the SVI and DL in predicting adjusted cardiovascular mortality. Our findings imply that just incorporating internet availability in the regression model may not be sufficient without incorporating significant variables, such as DL and SVI, to predict ACM. Further, our approach could enable future researchers to consider DL and SVI as key variables to study other health outcomes of public-health importance, which could inform future clinical practices and policies.

Objectives: To compare the outcomes of bipolar Transurethral Enucleation Resection of the Prostate (TUERP) and simple retropubic prostatectomy in patients with prostate volumes larger than 80 cc., Patients and Methods: A prospective randomized study included all patients amenable to surgeries for benign prostate hyperplasia (BPH) with prostate size over 80 cc at a tertiary care hospital between January 2020 to February 2022. Bipolar TUERP and Retropubic open prostatectomy techniques were compared regarding patients' demographics, intraoperative parameters, outcomes, and peri-operative complications., Results: Ninety patients were included in our study and randomly assigned to bipolar TUERP (Group 1 = 45 patients) and retropubic open prostatectomy (Group 2 = 45 patients). The TUERP group demonstrated significantly lower operative time (77 ± 11 minutes vs. 99 ± 14 minutes, p < 0.001), hemoglobin drop (median = 1.1 vs. 2.5, p < 0.001), and resected tissue weight (71 ± 6.6 cc vs. 84.5 ± 10.6 cc, p < 0.001). Postoperatively, the TUERP group demonstrated significantly lower catheter time (median = 2 vs. 7 days, p < 0.001) and less hospital stay. IPSS, Qmax, and patient satisfaction were better in the TUERP group within six months of surgery. We reported 90-day complications after TUERP in 13.3% of patients compared to 17.8% after retropubic prostatectomy, with a statistically insignificant difference. Urethral stricture predominated after TUERP, while blood transfusion dominated in retropubic prostatectomy., Conclusions: The present study found that TUERP had equivalent efficacy and safety to open retropubic prostatectomy for patients with BPH and prostate volumes > 80 ml.

In the modern world, plastic trash has been recognized as a global issue, and studies on microplastics (MPs) in the marine and inland environments have previously been conducted. Marine ecosystems act as a bio-diverse ecosystem where coral reefs contribute to make a sound living of the coastal people by gathering natural resources. The current study indicates that MPs and heavy metals (HMs) accumulation to biofilm and organic matter through sedimentation, precipitation, adsorption, and desorption that may have potential effect on growth and development of coral reefs in the marine ecosystems. However, the knowledge of distribution, impact, mechanism, degradation, and association mechanisms between MPs and HMs in the natural environment may open a new window for conducting analytical research from an ecological viewpoint. The current study thus summarizes the types of marine samples with the analytical techniques, polymers of MPs, and their impact on corals and other marine biota. This study also identifies existing knowledge gaps and recommends fresh lines of inquiry in light of recent developments in MPs and HMs research on the marine ecosystems. Overall, the present study suggests a sustainable intervention for reducing MPs and HMs from the marine ecosystems by demonstrating their existence in water, sediment, fish, corals, and other biota, and their impending ecotoxicological impacts on the environment and human health. The impacts of MPs and HMs on coral reefs are critically assessed in this study in light of the most recent scientific knowledge, existing laws, and new suggestions to minimize their contamination in the marine ecosystems., 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., (© 2023 The Author(s).)

Background: Low-intensity shockwave therapy for erectile dysfunction is emerging as a promising treatment option., Aim: This randomized sham-controlled crossover trial assessed the efficacy of low-intensity shockwave therapy in the treatment of erectile dysfunction., Methods: Thirty-three participants with organic erectile dysfunction were enrolled and randomized to shockwave therapy (n = 17) or sham (n = 16). The sham group was allowed to cross over to receive shockwave therapy after 1 month., Outcomes: Primary outcomes were the changes in Sexual Health Inventory for Men (SHIM) score and Erection Hardness Score at 1 month following shockwave therapy vs sham, and secondary outcomes were erectile function measurements at 1, 3, and 6 months following shockwave therapy., Results: At 1 month, mean SHIM scores were significantly increased in the shockwave therapy arm as compared with the sham arm (+3.0 vs -0.7, P  = .024). Participants at 6 months posttreatment (n = 33) showed a mean increase of 5.5 points vs baseline ( P  < .001), with 20 (54.6%) having an increase ≥5. Of the 25 men with an initial Erection Hardness Score <3, 68% improved to a score ≥3 at 6 months. When compared with baseline, the entire cohort demonstrated significant increases in erectile function outcomes at 1, 3, and 6 months after treatment., Clinical Implications: In this randomized sham-controlled crossover trial, we showed that 54.6% of participants with organic erectile dysfunction met the minimal clinically important difference in SHIM scores after treatment with low-intensity shockwave therapy., Strengths and Limitations: Strengths of this study include a sham-controlled group that crossed over to treatment. Limitations include a modest sample size at a single institution., Conclusions: Low-intensity shockwave therapy improves erectile function in men with erectile dysfunction as compared with sham treatment, which persists even 6 months after treatment., Clinical Trial Registration: ClinicalTrials.gov NCT04434352., Competing Interests: None declared., (© Published by Oxford University Press on behalf of The International Society of Sexual Medicine 2023.)

Environmental stresses, including the salt and heavy metals contaminated sites, signify a threat to sustainable crop production. The existence of these stresses has increased in recent years due to human-induced climate change. In view of this, several remediation strategies including nanotechnology have been studied to find more effective approaches for sustaining the environment. Nanoparticles, due to unique physiochemical properties; i.e. high mobility, reactivity, high surface area, and particle morphology, have shown a promising solution to promote sustainable agriculture. Crop plants easily take up nanoparticles, which can penetrate into the cells to play essential roles in growth and metabolic events. In addition, different iron- and carbon-based nanocompositions enhance the removal of metals from the contaminated sites and water; these nanoparticles activate the functional groups that potentially target specific molecules of the metal pollutants to obtain efficient remediation. This review article emphasises the recent advancement in the application of nanotechnology for the remediation of contaminated soils with metal pollutants and mitigating different abiotic stresses. Different implementation barriers are also discussed. Furthermore, we reported the opportunities and research directions to promote sustainable development based on the application of nanotechnology.

Utilizing carbon quantum dots (CQDs) as biomaterials for delivering small substances has gained significant attention in recent research. However, the interactions and mechanisms of action of CQDs on plants have received relatively little focus. Herein, we investigated the transportation of CQDs into various organs of Arabidopsis thaliana (L.) Heynh. via the vessel system, leading to the epigenetic inheritance of Argonaute family genes. Our findings reveal that CQDs may interact with microRNAs (miRNAs), leading to the repression of post-transcriptional regulation of target genes in the cytoplasm. Transcriptome and quantitative PCR analyses demonstrated consistent gene expression levels in offspring. Moreover, microscopic observations illustrated rapid CQD localization on cell membranes and nuclei, with increased nuclear entry at higher concentrations. Notably, our study identified an alternative regulatory microRNA, microRNA172D, for the Argonaute family genes through methylation analysis, shedding light on the connection between CQDs and microRNAs.

Glycosphingolipids (GSLs) are products of lipid glycosylation that have been implicated in the development of cardiovascular diseases. In diabetes, the adipocyte microenvironment is characterized by hyperglycemia and inflammation, resulting in high levels of GSLs. Therefore, we sought to assess the GSL content in extracellular vesicles derived from the adipose tissues (adiposomes) of obese-diabetic (OB-T2D) subjects and their impact on endothelial cell function. To this end, endothelial cells were exposed to adiposomes isolated from OB-T2D versus healthy subjects. Cells were assessed for caveolar integrity and related signaling, such as Src-kinase and caveolin-1 (cav-1) phosphorylation, and functional pathways, such as endothelial nitric oxide synthase (eNOS) activity. Compared with adiposomes from healthy subjects, OB-T2D adiposomes had higher levels of GSLs, especially LacCer and GM3; they promoted cav-1 phosphorylation coupled to an obvious loss of endothelial surface caveolae and induced eNOS-uncoupling, peroxynitrite generation, and cav-1 nitrosylation. These effects were abolished by Src kinase inhibition and were not observed in GSL-depleted adiposomes. At the functional levels, OB-T2D adiposomes reduced nitric oxide production, shear response, and albumin intake in endothelial cells and impaired flow-induced dilation in healthy arterioles. In conclusion, OB-T2D adiposomes carried a detrimental GSL cargo that disturbed endothelial caveolae and the associated signaling.

Triple-negative breast cancer (TNBC), as one of the most aggressive forms of breast cancer, is characterized by a poor prognosis and a very low rate of disease-free and overall survival. In recent years, immunotherapeutic approaches targeting T cell checkpoint molecules, such as cytotoxic lymphocyte antigen-4 (CTLA-4), programmed death1 (PD-1) or its ligand, programmed death ligand 1 (PD-L1), have shown great potential and have been used to treat various cancers as single therapies or in combination with other modalities. However, despite this remarkable progress, patients with TNBC have shown a low response rate to this approach, commonly developing resistance to immune checkpoint blockade, leading to treatment failure. Extracellular acidosis within the tumor microenvironment (also known as the Warburg effect) is one of the factors preventing immune cells from mounting effective responses and contributing to immunotherapy treatment failure. Therefore, reducing tumor acidity is important for increasing cancer immunotherapy effectiveness and this has yet to be realized in the TNBC environment. In this study, the oral administration of sodium bicarbonate (NaHCO 3 ) enhanced the antitumor effect of anti-PD-L1 antibody treatment, as demonstrated by generated antitumor immunity, tumor growth inhibition and enhanced survival in 4T1-Luc breast cancer model. Here, we show that NaHCO 3 increased extracellular pH (pH e ) in tumor tissues in vivo, an effect that was accompanied by an increase in T cell infiltration, T cell activation and IFN-γ, IL2 and IL12p40 mRNA expression in tumor tissues, as well as an increase in T cell activation in tumor-draining lymph nodes. Interestingly, these changes were further enhanced in response to combined NaHCO 3 + anti-PD-L1 therapy. In addition, the acidic extracellular conditions caused a significant increase in PD-L1 expression in vitro. Taken together, these results indicate that alkalizing therapy holds potential as a new tumor microenvironment immunomodulator and we hypothesize that NaHCO 3 can enhance the antitumor effects of anti-PD-L1 breast cancer therapy. The combination of these treatments may have an exceptional impact on future TNBC immunotherapeutic approaches by providing a powerful personalized medicine paradigm. Therefore, our findings have a great translational potential for improving outcomes in TNBC patients.

The Chinese plum ( Prunus salicina L.) is a fruit tree belonging to the Rosaceae family, native to south-eastern China and widely cultivated throughout the world. Fruit sugar metabolism and color change is an important physiological behavior that directly determines flavor and aroma. Our study analyzed six stages of fruit growth and development using RNA-seq, yielding a total of 14,973 DEGs, and further evaluation of key DEGs revealed a focus on sugar metabolism, flavonoid biosynthesis, carotenoid biosynthesis, and photosynthesis. Using GO and KEGG to enrich differential genes in the pathway, we selected 107 differential genes and obtained 49 significant differential genes related to glucose metabolism. The results of the correlation analyses indicated that two genes of the SWEET family, evm.TU.Chr1.3663 ( PsSWEET9 ) and evm.TU.Chr4.676 ( PsSWEET2 ), could be closely related to the composition of soluble sugars, which was also confirmed in the ethylene treatment experiments. In addition, analysis of the TOP 20 pathways between different growth stages and the green stage, as well as transient overexpression in chili, suggested that capsanthin/capsorubin synthase (PsCCS) of the carotenoid biosynthetic pathway contributed to the color change of plum fruit. These findings provide an insight into the molecular mechanisms involved in the ripening and color change of plum fruit.

The color of the chili fruit is an important factor that determines the quality of the chili, as red chilies are more popular among consumers. The accumulation of capsanthin is the main cause of reddening of the chili fruit. Capsanthin is an important metabolite in carotenoid metabolism, and its production level is closely linked to the expression of the genes for capsanthin/capsorubin synthase ( CCS ) and carotenoid hydroxylase ( CrtZ ). We reported for the first time that the synthesis of capsanthin in chili was enhanced by using a geminivirus (Bean Yellow Dwarf Virus). By expressing heterologous β-carotenoid hydroxylase ( CrtZ ) and β-carotenoid ketolase ( CrtW ) using codon optimization, the transcription level of the CCS gene and endogenous CrtZ was directly increased. This leads to the accumulation of a huge amount of capsanthin in a very short period of time. Our results provide a platform for the rapid enhancement of endogenous CCS activity and capsanthin production using geminivirus in plants.

Background: Inter-pregnancy interval has been identified as a potentially modifiable risk factor to improve perinatal outcomes. We examined the WHO recommended interval of at least 24 months after a livebirth to next pregnancy, and its recommendation of waiting for at least 6 months after a pregnancy loss to improve subsequent pregnancy outcomes. We aimed to estimate the association between inter-pregnancy interval and perinatal mortality using the Demographic and Health Survey reproductive and contraceptive calendar., Methods: For this population-based analysis, we extracted data for pregnancies with gestational age and pregnancy outcomes from 113 publicly available Demographic and Health Surveys conducted between 2000 and 2022 in 46 countries that included a reproductive or contraceptive calendar module. The primary outcome was perinatal mortality (stillbirth and early neonatal death) while the inter-pregnancy interval was the exposure of interest, grouped into categories of less than 6 months, 6-11 months, 12-17 months, 18-23 months, and 24-59 months. The analysis was stratified by preceding pregnancy outcome (livebirths, stillbirths, or abortions). The Kaplan-Meier method and Cox proportional hazard model were used to calculate the cumulative probability of perinatal mortality and the hazard ratios (HRs)., Findings: The analysis sample comprised of 692 402 pregnancies contributed by 570 145 women with a mean age of 28·4 years (SD 5·96). The overall HR of perinatal death was 2·72 (95% CI 2·52-2·93) times higher for an inter-pregnancy interval of less than 6 months compared with the WHO recommended optimal waiting time of 18-23 months following a livebirth. Overall HRs followed a context-related pattern, with the highest ratio of 2·95 (95% CI 2·67-3·25) in sub-Saharan Africa and the lowest of 1·98 (1·47-2·66) in north Africa, west Asia, and Europe. Inter-pregnancy intervals of less than 3 months, 6 months, and 12 months following stillbirth or abortion (spontaneous or induced) do not pose a higher risk for perinatal death in subsequent pregnancy., Interpretation: Our study reaffirms the WHO recommendation on optimal interval between the last livebirth and the next pregnancy of at least 24 months and avoiding pregnancy before 18 months. However, our analysis does not support the WHO recommendation of delaying the next pregnancy for at least 6 months after a pregnancy loss for improved perinatal survival., Funding: None., Competing Interests: Declaration of interests MMA and SB are staff members of WHO, and IHS is affiliated with Harvard T H Chan School of Public Health. The authors alone are responsible for the views expressed in this publication, and they do not necessarily represent the decisions, policy, or views of WHO or Harvard University. The country names used do not imply the expression of any opinion whatsoever on the part of WHO or Harvard University concerning the legal status of any country, territory, city or area, or of its authorities., (Copyright © 2023 World Health Organization. Published by Elsevier Ltd. All rights reserved. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background and objective Non-adherence to psychotropic medication can aggravate an individual's illness, diminish treatment efficacy, or make patients less responsive to future therapeutic interventions. There are several scales available to measure non-adherence to medications. In this study, we aimed to measure psychotropic medication adherence and its associated factors among schizophrenic outpatients in Saudi Arabia. Methodology A cross-sectional study was conducted with a view to measuring psychotropic medication adherence and its associated factors. The Medication Adherence Rating Scale (MARS) and the Drug Attitude Inventory-10 (DAI-10) were translated into Arabic, and their internal consistency was measured. The adjusted odds ratios (AOR) were calculated using logistic regression in the IBM SPSS Statistics software version 23 (IBM Corp., Armonk, NY). Results Spearman's rho correlation indicated a negative association between DAI-10 and MARS scores (r = -0.579; p<0.05). The Arabic version of MARS was more reliable than DAI-10, as evidenced by Cronbach's alpha value. Of note, 60.20% (n = 59) of the sample demonstrated high adherence levels. The adherence level based on MARS scoring remained unaffected (p>0.05) in terms of gender, age, employment, marital status, educational level, income level, and duration of sickness. These results were obtained by using the multivariate logistic regression model; 89% of respondents reported not using psychiatric drugs given by someone else, despite the adherence rate not affecting this number. Conclusion The rate of non-adherence to psychotropic treatment was found to be high in our cohort. Hence, it is imperative to develop comprehensive intervention methods targeting the causes of non-adherence to psychiatric medication., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ali et al.)

Introduction: Plastic is extensively used in everyday life, particularly for food and beverage containers. The inappropriate use of these containers may lead to the leaching of various chemicals from plastic, such as bisphenol A, phthalate, and styrene, which cause numerous adverse health effects. This study aimed to assess the knowledge, attitudes, and practices toward using plastic for food and drinks among a sample of the Egyptian population., Materials and Methods: A questionnaire was designed based on scientific literature to assess sociodemographic data, knowledge, attitudes, and practices toward the use of plastic for food and drinks. A total of 639 participants were recruited by employing the convenience sampling technique., Results: More than half of the participants (347, 54%) had poor knowledge scores. Personal experiences, social media, and web pages represented the most common knowledge sources. A comparison between plastic-related knowledge scores and the studied sociodemographic characteristics revealed statistically significant differences in age, gender, education, marital status, residence, working, and socioeconomic standard. A good attitude was reported by the majority (515, 80.6%) of participants. The majority (493, 77.2%) were occasional and frequent plastic users and the practice scores were significantly associated with age, education, residence, and socioeconomic standard. Higher educational level, gender (women), and rural residence were predictors of good participants knowledge, while lower socioeconomic status and urban residence were predictors of bad participants practice in a multivariate logistic regression analysis., Conclusion: The observed unsatisfactory knowledge and practice scores vs. the high attitude indicates a knowledge gap that can help direct future improvements. We call for public awareness programs about safe plastic use and the related health hazards of plastic chemicals. We also stress upon the urgent need for a collaboration between health authorities and the plastic and food industry to guarantee that information about proper plastic use is conveyed to consumers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hassan, El Desouky, Salem, Abdelsabour, Abdelmoneim, Elsaieed and Ali.)

Mycobacterium tuberculosis complex has an impact on public health and is responsible for over one million deaths per year. Substantial numbers of people infected with M. tuberculosis can develop tuberculosis lymphadenitis; however, there is a limited study in Adama, Ethiopia. The aim of this study was to determine the magnitude of Tuberculosis lymphadenitis, its predictors, and rifampicin-resistance gene-positive M. tuberculosis. A total of 291 patients with enlarged lymph nodes were recruited from May 2022 to August 30 at Adama Comprehensive Specialized Hospital Medical College (ACSHMC). GeneXpert, Ziehl-Neelsen staining, and cytology were used for the diagnosis of TB lymphadenitis from the Fine Needle Aspirate (FNA) specimen. Rifampicin-resistant gene was detected using GeneXpert. For data entry and analysis, Epi Data version 3.0 and SPSS version 25 were used respectively. A binary logistic regression model was used to identify predictors of TB lymphadenitis. A p < 0.05 with a 95% confidence interval (CI) was taken as a cut point to determine the significant association between dependent and independent variables. The prevalence of TB lymphadenitis using GeneXpert, Ziehl-Neelsen staining, and cytology were 138 (47.4%) (95% CI 41.70-53.10), 100 (34.4%) (95% CI 28.94-39.85), and 123 (42.3%) (95% CI 36.63-47.00) respectively. Nine (3.1%) participants were infected with rifampicin-resistant gene-positive M. tuberculosis. Out of the total M. tuberculosis detected by GeneXpert (n = 138), 9 (6.5%) were positive for rifampicin resistance-gene. Participants with a chronic cough had 2 times odds of developing TB lymphadenitis (AOR: 2.001, 95% CI 1.142-3.508). Close to half of patients with enlarged lymph nodes were positive for M. tuberculosis by the GeneXpert method in the study area. Chronic cough was significantly associated with TB lymphadenitis. Rifampicin-resistant gene-positive M. tuberculosis was relatively prevalent among patients with enlarged lymph node in the study area., (© 2023. The Author(s).)

Background: Hydrogen is a promising source of alternative energy. Fermentative production is more feasible because of its high hydrogen generation rate, simple operating conditions, and utilization of various organic wastes as substrates. The most significant constraint for biohydrogen production is supplying it at a low cost with fewer impurities., Results: Leaf biomass of Calotropis procera was used as a feedstock for a dark fermentative production of hydrogen by Bacillus coagulans AH1 (MN923076). The optimum operation conditions for biohydrogen production were 5.0% substrate concentrationand pH 9.0, at 35 °C. In which the biohydrogen yield was 3.231 mmol H 2 /g dry biomass without any pretreatments of the biomass. A freshwater microalga Oscillatroia sp was used for upgrading of the produced biohydrogen. It sequestrated 97 and 99% % of CO 2 from the gas mixture when it was cultivated in BG11 and BG11-N media, respectively After upgrading process, the residual microalgal cells exhibited 0.21mg/mL of biomass yield,high content of chlorophyll-a (4.8 µg/mL) and carotenoid (11.1 µg/mL). In addition to Oscillatroia sp residual biomass showed a lipid yield (7.5-8.7%) on the tested media., Conclusion: Bacillus coagulans AH1 is a promising tool for biohydrogen production avoiding the drawbacks of biomass pretreatment. Oscillatroia sp is encouraged as a potent tool for upgrading and purification of biohydrogen. These findings led to the development of a multiproduct biorefinery with zero waste that is more economically sustainable., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The first protein-binding allosteric RNA-cleaving DNAzyme (RCD) obtained by direct in vitro selection against eosinophil peroxidase (EPX), a validated marker for airway eosinophilia, is described. The RCD has nanomolar affinity for EPX, shows high selectivity against related peroxidases and other eosinophil proteins, and is resistant to degradation by mammalian nucleases. An optimized RCD was used to develop both fluorescence and lateral flow assays, which were evaluated using 38 minimally processed patient sputum samples (23 non-eosinophilic, 15 eosinophilic), producing a clinical sensitivity of 100 % and specificity of 96 %. This RCD-based lateral flow assay should allow for rapid evaluation of airway eosinophilia as an aid for guiding asthma therapy., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Cutaneous leishmaniasis (CL) is a vector-borne protozoal disease. Antimonial drugs remain the first-line treatment for CL despite the widespread drug resistance and high incidence of side effects. The present study aimed to compare the efficacy and safety of traditional intralesional sodium stibogluconate (SSG) alone and its combinations with trichloroacetic acid (TCA) 50% and fractional carbon dioxide (CO 2 ) laser for the treatment of CL., Materials and Methods: An interventional study was carried out on 25 CL patients. In each patient, three lesions were assigned to treatment either by SSG alone (GI), SSG plus TCA 50% (GII), or SSG plus fractional CO 2 laser (GIII). The overall clinical improvement and changes in the sizes of lesions and scars were assessed and compared among the three groups., Results: GIII patients had significantly lower treatment sessions as compared to GI patients (3.6 ± 1.29 versus 4.04 ± 2.11, P = 0.042). Moreover, GII and GIII patients had significantly shorter healing times when compared with GI (3.63 ± 1.35 and 3.46 ± 1.25, respectively, versus 4.0 ± 2.15 weeks, P = 0.019). Also, it was shown that GIII patients had significantly lower scar scores (1.40 ± 1.52) when compared with GI (3.00 ± 0.0) and GII (2.80 ± 1.10), P = 0.017., Conclusions: Intralesional SSG with TCA 50% is more effective than SSG alone and is comparable to SSG and fractional CO 2 combination in the treatment of CL with better safety profile and patient satisfaction., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Dermatology.)

Background: In the female population, pelvic organ prolapse is a common problem that lowers people's quality of life in terms of their health. Depending on the severity of the prolapse and the symptoms, there are many treatment options. Simple observation, vaginal pessaries, or surgical management are all possible treatments. Reconstructive pelvic surgery with or without mesh augmentation and obliterative surgery are two surgical treatments that are available. Due to the contentious concerns surrounding the use of mesh and the rising demand for uterine preservation, surgical practices are currently shifting., Methods: Just two cases are included in this study due to the rarity of this condition. In this study, I introduce a new technique to the literature (Mostafa Maged sling technique) which will be challenging. This technique depends on round ligaments and ovarian ligament to hitch up the whole uterus., Results: There were no difficulties following the procedure. None of the patients required blood transfusions, and there were no signs of dehiscence or incision infection. Non-steroidal antiinflammatory medications were administered to both patients as analgesia. On the first postoperative day, the foley catheters were removed from both patients., Conclusion: A simple and new manueuver is applied in the literature to treat the uterine prolapse. It is easy to learn and easy to perform. We need further studies to compare different techniques including Mostafa Maged sling operation to manage uterine prolapse., (© 2023 Mostafa Maged Ali.)

3-monochloropropane-1,2-diol esters (3-MCPDEs) and glycidyl esters (GEs) are food contaminants and have arisen continuous attention due to their toxicity, especially towards infants. Current risk assessment of these contaminants was mostly employing deterministic approaches, lacking quantitative characterization of the likelihood, incidence, or severity of the risks involved. Herein, 3-MCPDE and GE levels in 46 representative infant formulas (IFs) from Chinese market were determined by GC-MS/MS. Then, combining the occurrence data and consumption data from China National Food Consumption Survey, the Monte Carlo simulation-based probabilistic model for risk assessment of 3-MCPDEs and GEs in IFs from Chinese market was established. The results showed that all P90 (90th percentiles) hazard quotient values were below 1, demonstrating 3-MCPDEs didn't pose health risks to most populations aged 0-36 months old. However, for 0-12 months old groups, P10 (10th percentiles) margin of exposure values were all below 25000, indicating GEs may pose potential risks to 10% of this group. Uncertainty analysis revealed that the probabilistic model had considered uncertainties of model input and distribution, and realized refined assessment. This study is the first report on probabilistic assessment of 3-MCPDEs and GEs in IFs, which also provided references for the formulation of related regulatory limits in China., Competing Interests: Declaration of competing interest 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., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: Hepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors., Methods: An open forum for HCC-experienced health care workers from Africa and the rest of the world was held in October 2021. Participants completed a survey to help assess the real-life access to screening, diagnoses, and treatment in the North and Southern Africa (NS), East and West Africa (EW), Central Africa (C), and the rest of the world., Results: Of 461 participants from all relevant subspecialties, 372 were from Africa. Most African participants provided hepatitis B vaccination and treatment for hepatitis B and C. More than half of the participants use serum alpha-fetoprotein and ultrasound for surveillance. Only 20% reported using image-guided diagnostic liver biopsy. The Barcelona Clinic Liver Cancer is the most used staging system (52%). Liver transplant is available for only 28% of NS and 3% EW. C reported a significantly lower availability of resection. Availability of local therapy ranged from 94% in NS to 62% in C. Sorafenib is the most commonly used systemic therapy (66%). Only 12.9% reported access to other medications including immune checkpoint inhibitors. Besides 42% access to regorafenib in NS, second-line treatments were not provided., Conclusion: Similarities and differences in the care for patients with HCC in Africa are reported. This reconfirms the major gaps in access and availability especially in C and marginally less so in EW. This is a call for concerted multidisciplinary efforts to achieve and sustain a reduction in incidence and mortality from HCC in Africa.

Tobacco products are widely recognized as a major contributor to death. Cigarette smoke contains several toxic chemicals including heavy metals particulate causing high health risks. However, limited information has been available on the health risks associated with the heavy metals in cigarettes commonly sold in the Bangladeshi market. This study evaluated the concentrations and potential health risks posed by ten concerned heavy metals in ten widely consumed cigarette brands in Bangladesh using an atomic absorption spectrometer. The concentration (mg/kg) ranges of heavy metals Pb, Cd, Cr, As, Co, Ni, Mn, Fe, Cu, and Zn vary between 0.46-1.05, 0.55-1.03, 0.80-1.2, 0.22-0.40, 0.46-0.78, 2.59-3.03, 436.8-762.7, 115.8-184.4, 146.6-217.7, and 34.0-42.7, respectively. We assume that the heavy metals content among cigarette brands is varied due to the differences in the source of tobacco they use for cigarette preparation. The carcinogenic risks posed by heavy metals follow the order of Cr > Co > Cd > As > Ni > Pb, while the non-carcinogenic risks for Cu, Zn, Fe, and Mn were greater than unity (HQ > 1), except for Fe. The existence of toxic heavy metals in cigarette tobacco may thus introduce noticeable non-carcinogenic and carcinogenic health impacts accompanying inhalation exposure. This study provides the first comprehensive report so far on heavy metal concentration and associated health risks in branded cigarettes commonly sold in Bangladesh. Hence, this data and the information provided can serve as a baseline as well as a reference for future research and have potential implications for policy and legislation in Bangladesh., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In 2014, the European Academy of Allergy and Clinical Immunology published prevalence estimates for food allergy (FA) and food sensitization (FS) to the so-called eight big food allergens (i.e. cow's milk, egg, wheat, soy, peanut, tree nuts, fish and shellfish) in Europe for studies published between 2000 and 2012. The current work provides 10-year updated prevalence estimates for these food allergens. A protocol was registered on PROSPERO before starting the research (reference number CRD42021266657). Six databases were searched for studies published 2012-2021, added to studies published up to 2012, resulting in a total of 93 studies. Most studies were graded as at moderate risk of bias. The overall pooled estimates for all age groups of self-reported lifetime prevalence were as follows: cow's milk (5.7%, 95% confidence interval 4.4-6.9), egg (2.4%, 1.8-3.0), wheat (1.6%, 0.9-2.3), soy (0.5%, 0.3-0.7), peanut (1.5%, 1.0-2.1), tree nuts (0.9%, 0.6-1.2), fish (1.4%, 0.8-2.0) and shellfish (0.4%, 0.3-0.6). The point prevalence of food challenge-verified allergy were as follows: cow's milk (0.3%, 0.1-0.5), egg (0.8%, 0.5-1.2), wheat (0.1%, 0.01-0.2), soy (0.3%, 0.1-0.4), peanut (0.1%, 0.0-0.2), tree nuts (0.04%, 0.02-0.1), fish (0.02%, 0.0-0.1) and shellfish (0.1%, 0.0-0.2). With some exceptions, the prevalence of allergy to common foods did not substantially change during the last decade; variations by European regions were observed., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Invisible microplastics (MP) have become a significant problem worldwide in recent years. Although many studies have highlighted the sources, effects, and fate of MPs pollution on various ecosystems in developed countries, there is limited information on MPs in the marine ecosystem along the northeastern coast of the Bay of Bengal (BoB). Coastal ecosystems along the BoB coasts are critical to a biodiverse ecology that supports human survival and resource extraction. However, the multi-environmental hotspots, ecotoxicity effects, transport mechanisms, fates, and intervention measures to control MP pollution initiatives along the BoB coasts have received little attention. Therefore, this review aims to highlight the multi-environmental hotspots, ecotoxicity effects, sources, fates, and intervention measures of MP in the northeastern BoB to understand how MP spreads in the nearshore marine ecosystem. This study critically evaluates the hotspots and ecotoxic effects of pollution from MP on the coastal multi-environment, e.g., soil, sediment, salt, water, and fish, as well as current intervention measures and additional mitigation recommendations. This study identified the northeastern part of the BoB as a hotspot for MP. In addition, the transport mechanisms and fate of MP in different environmental compartments are highlighted, as are research gaps and potential future research areas. Research on the ecotoxic effects of MP on BoB marine ecosystems must be a top priority, given the increasing use of plastics and the presence of significant marine products worldwide. The knowledge gained from this study would inform decision-makers and stakeholders in a way that could reduce the impact of the legacy of micro- and nanoplastics in the area. This study also proposes structural and non-structural measures to mitigate the effects of MPs and promote sustainable management., Competing Interests: Declaration of competing interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Podoconiosis is one of the neglected tropical diseases (NTD) with the greatest potential for elimination. Despite its public health importance, podoconiosis is a poorly understood disease which led to a widespread misconception about its cause, prevention, and treatment. Even though the exact global burden is still to be measured, it is estimated that at least 4 million people are affected with podoconiosis worldwide, of which more than 1.5 million people are in Ethiopia. The objective of this study was to identify the determinants of podoconiosis in Bensa District, Sidama Regional State, Ethiopia., Methodology/principal Findings: A community-based unmatched case-control study was used to identify the determinants of podoconiosis. The sample size was estimated using the double population proportion formula. An interviewer-administered structured questionnaire was used for data collection. Blood specimens collected from cases were tested by Filariasis Test Strip to exclude lymphatic filariasis. Data were checked for completeness, coded and entered into Epi-data Version 4.6, and exported to the SPSS version 22 software. Variables with a p<0.2 in the bivariate analysis were further analyzed using multivariable binary logistic regression. Multivariable logistic regression analysis was used to examine determinants that could be associated with podoconiosis with a 95% confidence interval. A total of 459 (153 cases and 306 controls) participants were included with a response rate of 100%. Factors such as the age of participant [AOR = 0.34, 95% CI (0.13-0.87)], being female [AOR = 2.90, 95% CI (1.40-6.10)], age at which shoe wearing started [AOR = 0.7, 95% CI (0.03-0.16)], not wearing shoe daily [AOR = 2.26, 95% CI (1.05-4.86)], wearing hard plastic shoe [AOR = 3.38, 95% CI (1.31-10.89)], and family history with a similar disease (leg swelling) [AOR = 10.2, 95% CI (3.97-26.37)] were significantly associated with the occurrence of podoconiosis., Conclusions/significance: The age of the participants, gender, the age at which shoe wearing started, type of shoe the participants' wear, frequency of shoe wearing, traveling barefoot, and family history with similar disease (leg swelling) were significantly associated with the occurrence of podoconiosis. Sidama regional health bureau along with non-governmental organizations working on the neglected tropical disease should plan modalities on awareness creation and comprehensive health education on shoe wearing and foot hygiene., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hailu 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.)

Background: While learning and practicing on actual patients is a major mode of teaching clinical skills, concerns about patient safety, unavailability, and lack of standardization have led to the development of simulation for medical education. Simulation-based teaching is affected by challenges such as lack of protected time for faculty, inexperienced learners, and the number of students per group. These have led to the integration of various eLearning formats in the curriculum. The hybridized format changes the traditional clinical skills teaching into the flipped classroom. This study aims to measure the effectiveness of hybridizing video-based learning with simulation for flipping the clinical skills teaching of fourth-year medical students at the Department of Paediatrics and Child Health at Aga Khan University, Pakistan., Methods: The study employed a mixed-methods design. Fourth-year medical students of the batch 2020-21 (n = 100) consented to participate in the study. The quantitative component focuses on identifying the effect of the intervention on the perceived self-efficacy of medical students (batch 2020-21) relevant to the clinical skill. Along with this, the performance of the intervention batch of 2020-21 on the end of clerkship objective structured clinical exam (OSCE) was compared with the previous batch of 2019-20, taught using simulation alone. Focused group discussions (FGDs) were used to explore the experiences of medical students (batch 2020-21) about the intervention. Quantitative data underwent descriptive and inferential analysis using Stata v16 while qualitative data underwent content analysis using NVivo software., Results: Hybridization of video-based learning with simulation significantly improved self-efficacy scores for all examinations (cardiovascular, respiratory, neurological, and abdomen) with p-value < 0.05. OSCE scores of the intervention group were significantly higher on the neurological and abdominal stations as compared to the previous batch (p-value < 0.05). In addition, the overall structure of the intervention was appreciated by all the students, who stated it allowed reinforcement of basic concepts, retention, and further insight into clinical applications., Conclusion: The hybridization of video-based learning with simulation facilitated in creation of better opportunities for medical students to revive their prior knowledge, apply core concepts for the problem and engage in clinical reasoning., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Breast cancer has become the most common cancer in the US and worldwide. While advances in early detection and treatment have resulted in a 40% reduction in breast cancer mortality, this reduction has not been achieved uniformly among racial groups. A large percentage of non-metastatic breast cancer mortality is related to the cardiovascular effects of breast cancer therapies. These effects appear to be more prevalent among patients from historically marginalized racial/ethnic backgrounds, such as African American and Hispanic individuals. Anthracyclines, particularly doxorubicin and daunorubicin, are the first-line treatments for breast cancer patients. However, their use is limited by their dose-dependent and cumulative cardiotoxicity, manifested by cardiomyopathy, ischemic heart disease, arrhythmias, hypertension, thromboembolic disorders, and heart failure. Cardiotoxicity risk factors, such as genetic predisposition and preexisting obesity, diabetes, hypertension, and heart diseases, are more prevalent in racial/ethnic minorities and undoubtedly contribute to the risk. Yet, beyond these risk factors, racial/ethnic minorities also face unique challenges that contribute to disparities in the emerging field of cardio-oncology, including socioeconomic factors, food insecurity, and the inability to access healthcare providers, among others. The current review will address genetic, clinical, and social determinants that potentially contribute to this disparity.

Study Objectives: The treatment of obstructive sleep apnea is often impeded by intolerance of positive airway pressure therapy, which is frequently attributed to the inability to breathe through the nose. Providers caring for patients with sleep apnea need a working knowledge of nasal passage disease and available treatments to better manage this common comorbidity., Methods: This review examines the literature connecting rhinosinusitis to adverse sleep and sleep apnea outcomes. It explores the different types of nasal and sinus diseases a sleep apnea provider might encounter, focusing on the medications used to treat them and indications for referral to otolaryngology., Results: Chronic rhinosinusitis can be either allergic or nonallergic. Both types can interfere with sleep and sleep apnea therapy. The successful management of chronic rhinosinusitis can improve positive airway pressure tolerance and adherence. A wide range of over-the-counter and prescription pharmacotherapy is available, with data supporting intranasal over oral treatment. Surgical treatment for chronic rhinosinusitis in obstructive sleep apnea addresses nasal obstruction, often with inferior turbinate reduction and septoplasty., Conclusions: Sleep specialists should have a working knowledge of the available options to treat chronic rhinosinusitis. These options are often safe, effective, and readily accessible. Otolaryngologists and allergists/immunologists provide additional treatment options for more complicated patients. Providing treatment for chronic rhinosinusitis should be included as part of comprehensive sleep apnea care., Citation: Ali MM, Ellison M, Iweala OI, Spector AR. A sleep clinician's guide to runny noses: evaluation and management of chronic rhinosinusitis to improve sleep apnea care in adults. J Clin Sleep Med . 2023;19(8):1545-1552., (© 2023 American Academy of Sleep Medicine.)

Soluble sugars and organic acids are the most abundant components in ripe fruits, and they play critical roles in the development of fruit flavor and taste. In this study, loquat trees were sprayed with 0.1, 0.2 and 0.3% zinc sulphate. The contents of soluble sugars and organic acids were determined using HPLC-RID and UPLC-MS, respectively. The activities of key enzymes involved in sugar-acid metabolism were measured and expression profiling of related genes was done using RT-qPCR. The results revealed that 0.1% zinc sulphate was a promising treatment among other Zn applications with respect to the increased levels of soluble sugars and decreased acid contents in loquats. Correlation analysis showed that the enzymes i.e., SPS, SS, FK, and HK were may be involved in the regulation of fructose and glucose metabolism in the fruit pulp of loquat. While, the activity of NADP-ME showed negative and NAD-MDH showed a positive correlation with malic acid content. Meanwhile, EjSPS1-4, EjSS2-4, EjHK1-3, and EjFK1-6 may play an important role in soluble sugar metabolism in the pulp of loquat fruits. Similarly, EjPEPC2, EjPEPC3, EjNAD-MDH1, EjNAD-MDH3-5, EjNAD-MDH6 and EjNAD-MDH13 may have a vital contribution to malic acid biosynthesis in loquat fruits. This study provides new insights for future elucidation of key mechanisms regulating soluble sugars and malic acid biosynthesis in loquats., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Youming Hou and Faxing Chen reports financial support was provided by Fujian Agriculture and Forestry University., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Vancomycin-resistant Staphylococcus aureus (VRSA) is a zoonotic life-threatening pathogen. Vancomycin exhibits anti-bacterial activity by inhibiting peptidoglycan synthesis by binding to the D-ala-D-ala terminus of the peptidoglycan. But in VRSA, D-ala-D-ala is replaced by D-ala-D-lactate due to the presence of vanA, vanB or vanD genes. This study was intended to identify the molecular prevalence of VRSA in 768 bovine milk samples, risk factor association, antibiogram profile and bioinformatics analysis of VRSA by targeting vanB gene. Out of a total of 248 S. aureus isolates from mastitic milk samples, the phenotypic and genotypic prevalence of VRSA was estimated to be 17.74% and 10.89%, respectively. Farm-level risk factors including use of improper milking technique, lack of milker's care during milking, unhygienic conditions during milking and no dry cow therapy were found to be significantly associated (p < 0.05). Anti-microbial susceptibility testing of VRSA isolates exhibited the highest resistance to oxytetracycline, followed by oxacillin and Trimethoprim+sulfamethoxazole. The current study sequences showed more resemblance with reported sequences from Iraq (MN747834) and Egypt (MK095504, MK087830), which belong to vanB gene from S. aureus as compared to sequences from other countries, which belong to vanB gene from the genus Enterococcus. The Genetic Algorithm for Recombination Detection (GARD) found 234 potential breakpoints, translating into a search room of 123,883,305 models with up to 4 breakpoints. The phylogenetic motif profiling method discovered evolutionarily conserved residues across target genes' homologous protein sequences. These residues were discovered to be conserved in drug-resistant target proteins over the evolutionary process and may play a key role in their function. The current study revealed a molecular prevalence of VRSA in dairy animals, along with molecular analysis of vancomycin resistance in S. aureus by targeting the vanB gene using standard bioinformatics tools. The occurrence of VRSA in animals requires serious attention because this pathogen has zoonotic potential, so it can become a greater risk to consumer health., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Cutaneous squamous cell carcinoma (cSCC) is a fast-increasing cancer with metastatic potential. Extracellular vesicles (EVs) are small membrane-bound vesicles that play important roles in intercellular communication, particularly in the tumor microenvironment (TME). Here we report that cSCC cells secrete an increased number of EVs relative to normal human epidermal keratinocytes (NHEKs) and that interfering with the capacity of cSCC to secrete EVs inhibits tumor growth in vivo in a xenograft model of human cSCC. Transcriptome analysis of tumor xenografts by RNA-sequencing enabling the simultaneous quantification of both the human and the mouse transcripts revealed that impaired EV-production of cSCC cells prominently altered the phenotype of stromal cells, in particular genes related to extracellular matrix (ECM)-formation and epithelial-mesenchymal transition (EMT). In line with these results, co-culturing of human dermal fibroblasts (HDFs) with cSCC cells, but not with normal keratinocytes in vitro resulted in acquisition of cancer-associated fibroblast (CAF) phenotype. Interestingly, EVs derived from metastatic cSCC cells, but not primary cSCCs or NHEKs, were efficient in converting HDFs to CAFs. Multiplex bead-based flow cytometry assay and mass-spectrometry (MS)-based proteomic analyses revealed the heterogenous cargo of cSCC-derived EVs and that especially EVs derived from metastatic cSCCs carry proteins associated with EV-biogenesis, EMT, and cell migration. Mechanistically, EVs from metastatic cSCC cells result in the activation of TGFβ signaling in HDFs. Altogether, our study suggests that cSCC-derived EVs mediate cancer-stroma communication, in particular the conversion of fibroblasts to CAFs, which eventually contribute to cSCC progression., (© 2023. The Author(s).)

Mental health is a major concern for all classes of people, but especially physicians in the present world. A challenging task is to identify the significant risk factors that are responsible for depression among physicians. To address this issue, the study aimed to build a machine learning-based predictive model that will be capable of predicting depression levels and finding associated risk factors. A raw dataset was collected to conduct this study and preprocessed as necessary. Then, the dataset was divided into 10 sub-datasets to determine the best possible set of attributes to predict depression. Seven different classification algorithms, KNN, DT, LGBM, GB, RF, ETC, and StackDPP, were applied to all the sub-datasets. StackDPP is a stacking-based ensemble classifier, which is proposed in this study. It was found that StackDPP outperformed on all the datasets. The findings indicate that the StackDPP with the sub-dataset with all the attributes gained the highest accuracy (0.962581), and the top 20 attributes were enough to gain 0.96129 accuracy by StackDPP, which was close to the performance of the dataset with all the attributes. In addition, risk factors were analyzed in this study to reveal the most significant risk factors that are responsible for depression among physicians. The findings of the study indicate that the proposed model is highly capable of predicting the level of depression, along with finding the most significant risk factors. The study will enable mental health professionals and psychiatrists to decide on treatment and therapy for physicians by analyzing the depression level and finding the most significant risk factors.

The investigation of the micellization of a mixture of cetylpyridinium bromide (CPB) and levofloxacin hemihydrate (LFH) was carried out by a conductivity technique in aqueous and aq. additive mixtures, including NaCl, NaOAc, NaBenz, 4-ABA, and urea. The aggregation behavior of the CPB + LFH mixture was studied considering the variation in additive contents and the change in experimental temperature. The micelle formation of the CPB + LFH mixture was examined from the breakpoint observed in the specific conductivity versus surfactant concentration plots. Different micellar characteristics, such as the critical micelle concentration (CMC) and the extent of counter ion bound ( β ), were evaluated for the CPB + LFH mixture. The CMC and β were found to undergo a change with the types of solvents, composition of solvents, and working temperatures. The Δ G 0 m values of the CPB + LFH system in aqueous and aq. additive solutions were found to be negative, which denotes a spontaneous aggregation phenomenon of the CPB + LFH system. The changes in Δ H 0 m and Δ S 0 m for the CPB + LFH mixture were also detected with the alteration in the solvent nature and solution temperature. The Δ H 0 m and Δ S 0 m values obtained for the association of the CPB + LFH mixture reveal that the characteristic interaction forces may possibly be ion-dipole, dipole-dipole, and hydrophobic between CPB and LFH. The thermodynamics of transfer and Δ H 0 m -Δ S 0 m compensation variables were also determined. All the parameters computed in the present investigation are illustrated with proper logic., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Alternative and modified therapeutic approaches are key elements in culminating antibiotic resistance. To this end, an experimental trial was conducted to determine the cytotoxicity and antibacterial potential of composites of magnesium oxide (MgO) nanoparticles and antibiotics stabilized in sodium alginate gel against multi-drug-resistant Staphylococcus aureus isolated from a houbara bustard. The characterization of preparations was carried out using X-ray diffraction (XRD), scanning transmissible electron microscopy (STEM), and Fourier-transform infrared spectroscopy (FTIR). The preparations used in this trial consisted of gel-stabilized MgO nanoparticles (MG), gel-stabilized tylosin (GT), gel-stabilized ampicillin (GA), gel-stabilized cefoxitin (GC), gel-stabilized MgO and tylosin (GMT), gel-stabilized MgO and cefoxitin (GMC), and gel-stabilized MgO and ampicillin (GMA). The study presents composites that cause a lesser extent of damage to DNA while significantly enhancing mitotic indices/phases compared to the other single component preparations with respect to the positive control (methyl methanesulphonate). It was also noted that there was a non-significant difference ( p > 0.05) between the concentrations of composites and the negative control in the toxicity trial. Studying in parallel trials showed an increased prevalence, potential risk factors, and antibiotic resistance in S. aureus . The composites in a well diffusion trial showed the highest percentage increase in the zone of inhibition in the case of GT (58.42%), followed by GMT (46.15%), GC (40.65%), GMC (40%), GMA (28.72%), and GA (21.75%) compared to the antibiotics alone. A broth microdilution assay showed the lowest minimum inhibitory concentration (MIC) in the case of GMA (9.766 ± 00 µg/mL), followed by that of GT (13.02 ± 5.64 µg/mL), GMC (19.53 ± 0.00 µg/mL), GA (26.04 ± 11.28 µg/mL), GMT (26.04 ± 11.28 µg/mL), MG (39.06 ± 0.00 µg/mL), and GC (39.06 ± 0.00 µg/mL). The study thus concludes the effective tackling of multiple-drug-resistant S. aureus with sodium-alginate-stabilized MgO nanoparticles and antibiotics, whereas toxicity proved to be negligible for these composites.

Importance: In April 2021, the US Department of Health and Human Services (HHS) released practice guidelines exempting educational requirements to obtain a Drug Addiction Treatment Act (DATA) waiver to treat up to 30 patients with opioid use disorder with buprenorphine., Objective: To compare demographic and practice characteristics of clinicians who received traditional DATA waivers before and after release of the education-exempted HHS practice guidelines and those who were approved under the guidelines., Design, Setting, and Participants: This survey study was conducted electronically from February 1 to March 1, 2022. Eligible survey recipients were US clinicians who obtained an initial DATA waiver between April 2020 and November 2021., Exposure: DATA waiver approval pathway., Main Outcome and Measures: The outcomes were clinician demographic and practice characteristics, buprenorphine prescribing barriers, and strategies to treat patients with opioid use disorder, measured using χ2 tests and z tests to assess for differences among the waivered groups., Results: Of 23 218 eligible clinicians, 4519 (19.5%) responded to the survey. This analysis was limited to 2736 respondents with a 30-patient limit at the time of survey administration who identified their DATA waiver approval pathway. Among these respondents, 1365 (49.9%; female, 831 [61.9%]; male, 512 [38.1%]) received their DATA waiver prior to the education-exempted practice guidelines (prior DATA waiver), 550 (20.1%; female, 343 [63.4%]; male, 198 [36.6%]) received their waiver after guidelines were released but met education requirements (concurrent DATA waiver), and 821 (30.0%; female, 396 [49.2%]; male, 409 [50.8%]) received the waiver under the education-exempted guidelines (practice guidelines). Among practice guidelines clinicians, 500 (60.9%) reported that traditional DATA waiver educational requirements were a reason for not previously obtaining a waiver. Demographic and practice characteristics differed by waiver approval type. Across all groups, a large minority had not prescribed buprenorphine since obtaining a waiver (prior DATA waiver, 483 [35.7%]; concurrent DATA waiver, 226 [41.2%]; practice guidelines, 359 [44.3%]; P < .001). Clinicians who prescribed buprenorphine in the past 6 months reported treating few patients in an average month: 27 practice guidelines clinicians (6.0%) prescribed to 0 patients and 338 (75.1%) to 1 to 4 patients compared with 16 (2.2%) and 435 (59.9%) for prior and 11 (3.6%) and 166 (55.0%) for concurrent DATA waiver clinicians, respectively (P < .001). Across waiver types, clinicians reported multiple challenges to buprenorphine prescribing., Conclusions and Relevance: In this survey of DATA-waivered clinicians, clinician- and systems-level challenges that limit buprenorphine prescribing were observed, even among clinicians approved under the education-exempted guidelines pathway. The findings suggest that as implementation of legislation removing the DATA waiver begins, addressing these barriers could be essential to increasing buprenorphine access.

Exosomes are nanoscale, membrane-enclosed vesicles with contents similar to their parent cells, which are rich in potential biomarkers. Urine, as a noninvasive sampling body fluid, has the advantages of being simple to collect, stable in protein, diverse and not regulated by homeostatic mechanisms of the body, making it a favorable target for studying tumor biomarkers. In this report, the urinary exosomal proteome was analyzed and high-throughput downstream validation was performed using a supramolecular probe-based capture and in situ detection. The technology demonstrated the efficient enrichment of exosomes with a high concentration (5.5 × 10 10 particles/mL) and a high purity (2.607 × 10 10 particles/mg) of exosomes from urine samples. Proteomic analysis of urine samples from patients with hepatocellular carcinoma and healthy individuals combined with proteomic screening techniques revealed that 68 proteins were up-regulated in patients with hepatocellular carcinoma. As a proof-of-principle study, three of these differentially expressed proteins, including OLFM4, HDGF and GDF15, were validated using the supramolecular probe-based array (48 samples per batch). These findings demonstrate the great potential of this approach toward a liquid biopsy for the discovery and validation of biomarkers from urinary exosomes, and it can be extended to various biological samples with lower content of exosomes.

The early months of the COVID-19 pandemic saw a decline in psychotropic medication use; however, little is known about how this trend evolved as the pandemic progressed and how it varied across different payers in the United States. Using a national multi-payer pharmacy claims database and adopting a quasi-experimental research design, this study examines trends in psychotropic medication prescriptions dispensed from July 2018 - June 2022. The study finds that the number of patients with dispensed psychotropic medications and the number of psychotropic medications dispensed declined during the early months of the pandemic but experienced a statistically significant growth in later periods compared to the pre-pandemic rate. Average days supply of psychotropic medications dispensed increased significantly throughout the pandemic. Commercial insurance remained the primary payer for psychotropic medication during the pandemic, but there was a significant increase in the number of prescription fills covered under Medicaid. This implies that public insurance programs played an increasing role in financing psychotropic medication use during the COVID-19 pandemic., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier B.V.)

Introduction: Inguinal hernia is a common surgical condition in children. Conventionally, the open approach for inguinal hernia repair has been considered the gold standard. However, in the past two decades, laparoscopic inguinal hernia repair has gained popularity among paediatric surgeons as an alternative to the open approach. Apart from good cosmesis and shorter stay at hospital, laparoscopy offers clear-cut advantages of visualising contralateral site and simultaneous repair if it is patent. Many techniques for laparoscopic inguinal hernia repair have been proposed. In this retrospective observational study, we are comparing outcomes between proximal and distal disconnection of hernia sac., Materials and Methods: Ninety-five patients with inguinal hernia were studied in two groups. Group A included 50 patients in which hernia sac was disconnected from the peritoneal cuff proximal to deep inguinal ring (DIR). Group B included 45 patients in which hernia sac was disconnected distal to DIR. Various sociodemographic parameters and intraoperative findings were compared. Outcomes were analysed in terms of post-operative pain, duration of stay at the hospital and recurrences., Results: In group A, there were 46 males and four females with mean age of 4.01 years with standard deviation (SD) of 2.96. Group B included 37 males and eight females with mean age of 5.09 years with SD of 3.56. Excess post-operative pain was observed in 33 patients in Group A with proximal disconnection of hernia sac whereas it was seen in only three patients in Group B with distal disconnection of sac. The P was 0.001 which was highly significant. The duration of stay in the hospital was more in Group A (2.36 ± 1.22 days) as compared to Group B (1.8 ± 0.66 days) with a P of 0.0076 which was significant. Hernia recurrence was seen in four out of 50 patients in Group A (8%) as compared to no recurrence in Group B. However, the difference was not significant., Conclusion: The disconnection of hernia sac distal to DIR is associated with less post-operative pain and shorter duration of hospital stay. There is less recurrence seen in distal disconnection of hernia sac as compared to proximal disconnection; however, to achieve the level of significance, a large cohort study is required., Competing Interests: None