The strict regulation of HIF-1α by non-coding RNAs: new insight towards proliferation, metastasis, and therapeutic resistance strategies.

The hypoxic environment is prominently witnessed in most solid tumors and is associated with the promotion of cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, metabolic reprogramming, therapeutic resistance, and metastasis of tumor cells. All the effects are mediated by the expression of a transcription factor hypoxia-inducible factor-1α (HIF-1α). HIF-1α transcriptionally modulates the expression of genes responsible for all the aforementioned functions. The stability of HIF-1α is regulated by many proteins and non-coding RNAs (ncRNAs). In this article, we have critically discussed the crucial role of ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), Piwi-interacting RNAs (piRNAs), and transfer RNA (tRNA)-derived small RNAs (tsRNAs)] in the regulation of stability and expression of HIF-1α. We have comprehensively discussed the molecular mechanisms and relationship of HIF-1α with each type of ncRNA in either promotion or repression of human cancers and therapeutic resistance. We have also elaborated on ncRNAs that are in clinical examination for the treatment of cancers. Overall, the majority of aspects concerning the relationship between HIF-1α and ncRNAs have been discussed in this article.

Elucidating the role of EPPK1 in lung adenocarcinoma development.

BACKGROUND: We recently found that epiplakin 1 (EPPK1) alterations were present in 12% of lung adenocarcinoma (LUAD) cases and were associated with a poor prognosis in early-stage LUAD when combined with other molecular alterations. This study aimed to identify a probable crucial role for EPPK1 in cancer development. METHODS: EPPK1 mRNA and protein expression was analyzed with clinical variables. Normal bronchial epithelial cell lines were exposed to cigarette smoke for 16 weeks to determine whether EPPK1 protein expression was altered after exposure. Further, we used CRISPR-Cas9 to knock out (KO) EPPK1 in LUAD cell lines and observed how the cancer cells were altered functionally and genetically. RESULTS: EPPK1 protein expression was associated with smoking and poor prognosis in early-stage LUAD. Moreover, a consequential mesenchymal-to-epithelial transition was observed, subsequently resulting in diminished cell proliferation and invasion after EPPK1 KO. RNA sequencing revealed that EPPK1 KO induced downregulation of 11 oncogenes, 75 anti-apoptosis, and 22 angiogenesis genes while upregulating 8 tumor suppressors and 12 anti-cell growth genes. We also observed the downregulation of MYC and upregulation of p53 expression at both protein and RNA levels following EPPK1 KO. Gene ontology enrichment analysis of molecular functions highlighted the correlation of EPPK1 with the regulation of mesenchymal cell proliferation, mesenchymal differentiation, angiogenesis, and cell growth after EPPK1 KO. CONCLUSIONS: Our data suggest that EPPK1 is linked to smoking, epithelial to mesenchymal transition, and the regulation of cancer progression, indicating its potential as a therapeutic target for LUAD.

PLAAT1 deficiency alleviates high-fat diet-induced hepatic lipid accumulation in mice.

The phospholipase A and acyltransferase (PLAAT) family is composed of three isoforms in mice (PLAAT1, 3, and 5), all of which function as phospholipid-metabolizing enzymes exhibiting phospholipase A1 /A2 and acyltransferase activities. Plaat3-deficient (Plaat3-/- ) mice were previously reported to show lean phenotype and remarkable hepatic fat accumulation under high-fat diet (HFD) feeding, while Plaat1-/- mice have not been analyzed. In the present study, we generated Plaat1-/- mice and investigated the effects of PLAAT1 deficiency on HFD-induced obesity, hepatic lipid accumulation, and insulin resistance. After HFD treatment, PLAAT1 deficiency caused a lower body weight gain compared to wild-type mice. Plaat1-/- mice also showed reduced liver weight with negligible hepatic lipid accumulation. In accordance with these findings, PLAAT1 deficiency improved HFD-induced hepatic dysfunction and lipid metabolism disorders. Lipidomics analysis in the liver revealed that in Plaat1-/- mice, the levels of various glycerophospholipids tended to increase, while all classes of lysophospholipids examined tended to decrease, suggesting that PLAAT1 functions as phospholipase A1 /A2 in the liver. Interestingly, the HFD treatment of wild-type mice significantly increased the mRNA level of PLAAT1 in the liver. Furthermore, the deficiency did not appear to elevate the risk of insulin resistance in contrast to PLAAT3 deficiency. These results suggested that the suppression of PLAAT1 improves HFD-induced overweight and concomitant hepatic lipid accumulation.

Microproteins/micropeptides dysregulation contributes to cancer progression and development: A mechanistic review.

Microproteins, known as micropeptides, are small protein molecules encoded by short open reading frames. These recently identified molecules have been proven to be an essential part of the human proteome that participates in multiple processes, such as DNA repair, mitochondrial respiration, and regulating different signaling pathways. A growing body of studies has evidenced that microproteins exhibit dysregulated expression levels in various malignancies and contribute to tumor progression. It has been reported that microproteins interact with many proteins, such as enzymes (e.g., adenosine triphosphate synthase) and signal transducers (e.g., c-Jun), and regulate malignant cell metabolism, proliferation, and metastasis. Moreover, microproteins have been found to play a significant role in multidrug resistance in vitro and in vivo by their activity in DNA repair pathways. Considering that, this review intended to summarize the roles of microproteins in different aspects of tumorigenesis with diagnostic and therapeutic perspectives.

Association of medication clusters and subsequent labor market marginalization in refugee and Swedish-born young adults with common mental disorders in Sweden.

Little is known about the association between common mental disorders (CMD) and labor market integration among refugee and Swedish-born young adults. Socially disadvantaged patients such as refugees are more likely to discontinue their medication use prematurely. This study aimed to identify clusters of individuals with similar psychotropic medication patterns; and examine the relationship between cluster membership with labor market marginalization (LMM) in refugee and Swedish-born young adults with CMD. The study uses a longitudinal matched cohort aged 18-24 years with CMD diagnoses from Swedish registers covering 2006-2016. Dispensed psychotropic medications (antidepressants, antipsychotics, anxiolytics, sedative-hypnotics, mood stabilizers) were collected one year before and after CMD diagnosis. Clusters of patients with similar time courses of prescribed dosages were algorithmically identified. The association of cluster membership with subsequent LMM, (long-term sickness absence, SA, disability pension, DP, or long-term unemployment, UE) was assessed using Cox regression. Among 12,472 young adults with CMD, there were 13.9% with SA, 11.9% with DP, and 13.0% with UE during a mean follow-up of 4.1 years (SD 2.3 years). Six clusters of individuals were identified. A cluster with a sustained increase in all medication types yielded the highest hazard ratio (HR [95% CI]) 1.69 [1.34, 2.13] for SA and 2.63 [2.05, 3.38] for DP. The highest HRs of UE give a cluster with a concentrated peak in antidepressants at CMD diagnosis (HR 1.61[1.18, 2.18]). Refugees and Swedish-born showed similar associations between clusters and LMM. To prevent LMM, targeted support and early assessment of CMD treatment are needed for individuals with a sustained increase in psychotropic medication after CMD diagnosis and for refugees in high-risk clusters for UE characterized by a rapid lowering of treatment dosages, which could be an indicator for premature medication discontinuation.

Identifying postoperative cognitive dysfunction after elective coronary artery bypass graft surgery in a tertiary centre in Malaysia.

Postoperative cognitive dysfunction (POCD) is a significant concern, with incidences reported up to 70% following cardiac surgery. Therefore, we aim to evaluate the incidence of POCD after elective coronary artery bypass graft (CABG) surgery at our single centre over a one-year period from August 2021 to July 2022. We included 34 patients in the study and conducted serial cognitive assessments up to three months post-surgery. Interestingly, our findings indicated an absence of POCD among patients who underwent elective CABG. Reasons contributing to this outcome are multifactorial, which may include the patients' younger age, higher educational levels, lack of pre-existing neurological disorders, meticulous intraoperative cerebral saturation monitoring, and the duration of aortic crossclamp and cardiopulmonary bypass time.

Pharmacokinetic-Pharmacodynamic Determinants of Clinical Outcomes for Rifampin-Resistant Tuberculosis: A Multisite Prospective Cohort Study.

BACKGROUND: Rifampin-resistant and/or multidrug-resistant tuberculosis (RR/MDR-TB) treatment requires multiple drugs, and outcomes remain suboptimal. Some drugs are associated with improved outcome. It is unknown whether particular pharmacokinetic-pharmacodynamic relationships predict outcome. METHODS: Adults with pulmonary RR/MDR-TB in Tanzania, Bangladesh, and the Russian Federation receiving local regimens were enrolled from June 2016 to July 2018. Serum was collected after 2, 4, and 8 weeks for each drug's area under the concentration-time curve over 24 hours (AUC0-24). Quantitative susceptibility of the M. tuberculosis isolate was measured by minimum inhibitory concentrations (MICs). Individual drug AUC0-24/MIC targets were assessed by adjusted odds ratios (ORs) for favorable treatment outcome, and hazard ratios (HRs) for time to sputum culture conversion. K-means clustering algorithm separated the cohort of the most common multidrug regimen into 4 clusters by AUC0-24/MIC exposures. RESULTS: Among 290 patients, 62 (21%) experienced treatment failure, including 30 deaths. Moxifloxacin AUC0-24/MIC target of 58 was associated with favorable treatment outcome (OR, 3.75; 95% confidence interval, 1.21-11.56; P = .022); levofloxacin AUC0-24/MIC of 118.3, clofazimine AUC0-24/MIC of 50.5, and pyrazinamide AUC0-24 of 379 mg × h/L were associated with faster culture conversion (HR >1.0, P < .05). Other individual drug exposures were not predictive. Clustering by AUC0-24/MIC revealed that those with the lowest multidrug exposures had the slowest culture conversion. CONCLUSIONS: Amidst multidrug regimens for RR/MDR-TB, serum pharmacokinetics and M. tuberculosis MICs were variable, yet defined parameters to certain drugs-fluoroquinolones, pyrazinamide, clofazimine-were predictive and should be optimized to improve clinical outcome. CLINICAL TRIALS REGISTRATION: NCT03559582.

Overview of the role and action mechanism of microRNA-128 in viral infections.

Recently in vivo and in vitro studies have provided evidence establishing the significance of microRNAs (miRNAs) in both physiological and pathological conditions. In this regard, the role of miRNA-128 (miR-128) in health and diseases has been found, and its critical regulatory role in the context of some viral diseases has been recently identified. For instance, it has been found that miR-128 can serve as an antiviral mediator and significantly limit the replication and dissemination of human immunodeficiency virus type 1 (HIV-1). Besides, it has been noted that poliovirus receptor-related 4 (PVRL4) is post-transcriptionally regulated by miR-128, representing possible miRNA targets that can modulate measles virus infection. Of note, the downregulation of seminal exosomes eca-miR-128 is associated with the long-term persistence of Equine arteritis virus (EAV) in the reproductive tract, and this particular miRNA is a putative regulator of chemokine ligand 16 (C-X-C motif) as determined by target prediction analysis. In this review, the latest information on the role and action mechanism of miR-128 in viral infections will be summarized and discussed in detail.

Mesenchymal stem cell-released oncolytic virus: an innovative strategy for cancer treatment.

Oncolytic viruses (OVs) infect, multiply, and finally remove tumor cells selectively, causing no damage to normal cells in the process. Because of their specific features, such as, the ability to induce immunogenic cell death and to contain curative transgenes in their genomes, OVs have attracted attention as candidates to be utilized in cooperation with immunotherapies for cancer treatment. This treatment takes advantage of most tumor cells' inherent tendency to be infected by certain OVs and both innate and adaptive immune responses are elicited by OV infection and oncolysis. OVs can also modulate tumor microenvironment and boost anti-tumor immune responses. Mesenchymal stem cells (MSC) are gathering interest as promising anti-cancer treatments with the ability to address a wide range of cancers. MSCs exhibit tumor-trophic migration characteristics, allowing them to be used as delivery vehicles for successful, targeted treatment of isolated tumors and metastatic malignancies. Preclinical and clinical research were reviewed in this study to discuss using MSC-released OVs as a novel method for the treatment of cancer. Video Abstract.

Candida auris Blood stream infection- a descriptive study from Qatar.

BACKGROUND: Candida auris is an emerging yeast pathogen that can cause invasive infections, particularly candidemia, in healthcare settings. Candida auris is characterized by resistance to multiple classes of antifungal drugs and high mortality. OBJECTIVE: To describe the risk factors, clinical characteristics, antifungal susceptibility pattern and outcomes of Candida auris blood stream infection. METHODS: We conducted a retrospective review of electronic medical records of C. auris fungemia cases in the facilities under Hamad Medical corporation, Qatar from 1/11/2018 to 31/7/2021. Demographic data, risk factors, antibiogram and 30-day outcome are described. RESULTS: We identified 36 patients with C. auris fungemia. Most of the patients were in intensive care unit following severe COVID-19 pneumonia and had received steroids and broad-spectrum antibiotics. Most cases were central line related. Over 90% of isolates were non-susceptible to fluconazole, while amphotericin B resistance reached 85%. Factors associated with high mortality included initial SOFA score of 9 or above and absence of source control. CONCLUSION: Our study reveals a concerning 41.6% mortality rate within 30 days of C. auris candidemia. Furthermore, the prevalence of amphotericin B resistance in Qatar exceeds what has been reported in the literature necessitating further exploration. Echinocandins retains nearly 100% susceptibility and should be prioritized as the treatment of choice. These findings emphasize the need for vigilant monitoring and appropriate management strategies to combat C. auris infections and improve patient outcomes.

Vulnerable newborn types: analysis of subnational, population-based birth cohorts for 541 285 live births in 23 countries, 2000-2021.

OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.

Soluble receptor for advanced glycation end products (sRAGE) is associated with obesity rates: a systematic review and meta-analysis of cross-sectional study.

BACKGROUND: Several studies have highlighted the possible positive effects of soluble receptor for advanced glycation end products (sRAGE) against obesity. However, due to their inconsistent results, this systematic review and meta-analysis aimed to quantitatively evaluate and critically review the results of studies evaluating the relationship between sRAGE with obesity among adult population. METHODS: In the systematic search, the eligibility criteria were as follows: studies conducted with a cross-sectional design, included apparently healthy adults, adults with obesity, or obesity-related disorders, aged over 18 years, and evaluated the association between general or central obesity indices with sRAGE. RESULTS: Our systematic search in electronic databases, including PubMed, Scopus, and Embase up to 26 October, 2023 yielded a total of 21,612 articles. After removing duplicates, screening the titles and abstracts, and reading the full texts, 13 manuscripts were included in the final meta-analysis. According to our results, those at the highest category of circulating sRAGE concentration with median values of 934.92 pg/ml of sRAGE, had 1.9 kg/m2 lower body mass index (BMI) (WMD: -1.927; CI: -2.868, -0.986; P < 0.001) compared with those at the lowest category of sRAGE concentration with median values of 481.88 pg/ml. Also, being at the highest sRAGE category with the median values of 1302.3 pg/ml sRAGE, was accompanied with near 6 cm lower waist circumference (WC) (WMD: -5.602; CI: -8.820, -2.383; P < 0.001 with 86.4% heterogeneity of I2) compared with those at the lowest category of sRAGE concentration with median values of 500.525 pg/ml. Individuals with obesity had significantly lower circulating sRAGE concentrations (WMD: -135.105; CI: -256.491, -13.72; P = 0.029; with 79.5% heterogeneity of I2). According to the subgrouping and meta-regression results, country and baseline BMI were possible heterogeneity sources. According to Begg's and Egger's tests and funnel plots results, there was no publication bias. CONCLUSION: According to our results, higher circulating sRAGE concentrations was associated with lower BMI and WC among apparently healthy adults. Further randomized clinical trials are warranted for possible identification of causal associations.

Memory support training and lifestyle modifications to promote healthy aging in persons at risk for Alzheimer's disease: a digital application supported intervention (Brain Boosters).

BACKGROUND: Evidence-based interventions to protect against cognitive decline among older adults at risk for Alzheimer's disease and related dementias (ADRD) are urgently needed. Rehabilitation approaches to support memory and behavioral/lifestyle interventions are recognized as promising strategies for preserving or improving cognitive health, although few previous interventions have combined both approaches. This paper describes the protocol of the Brain Boosters intervention, which synergistically combines training in compensatory and healthy lifestyle behaviors and supports implementation and tracking of new behaviors with a digital application. METHODS: The study utilizes a single-site, single-blinded, randomized controlled design to compare a structured lifestyle and compensatory aid intervention to an education-only self-guided intervention. We plan to enroll 225 community-dwelling adults (25% from underrepresented groups) aged 65 + who endorse subjective cognitive decline (SCD) and low baseline levels of healthy lifestyle behaviors. Both interventions will be administered in group format, consisting of 15 two-hour classes that occur weekly for ten weeks and taper to bi-monthly and monthly, for an intervention duration of 6 months. Participants in both interventions will receive education about a variety of memory support strategies and healthy lifestyle behaviors, focusing on physical and cognitive activity and stress management. The structured intervention will also receive support in adopting new behaviors and tracking set goals aided by the Electronic Memory and Management Aid (EMMA) digital application. Primary outcomes include global cognition (composite of memory, attention, and executive function tests) and everyday function (Everyday Cognition Questionnaire). Data will be collected at baseline and outcome visits, at approximately 6, 12, and 18 months. Qualitative interviews, self-report surveys (e.g., indicators of self-determination, health literacy) and EMMA data metrics will also be used to identify what components of the intervention are most effective and for whom they work. DISCUSSION: Successful project completion will provide valuable information about how individuals with SCD respond to a compensation and preventative lifestyle intervention assisted by a digital application, including an understanding of factors that may impact outcomes, treatment uptake, and adherence. The work will also inform development, scaling, and personalization of future interventions that can delay disability in individuals at risk for ADRD. TRIAL REGISTRATION: ClinicalTrials.gov. (NCT05027789, posted 8/30/2021).

Effect of citrus-coconut electrolyte blend on growth performance, haemato-biochemical status, organs development and intestinal morphology of broiler chickens.

INTRODUCTION: In a bid to mitigate growing concerns regarding the use of antibiotics in food animals OBJECTIVES: This study determined the growth performance, haemato-biochemical status, organ development and intestinal morphology of Arbor Acre broiler chicken strain on oral administration of citrus-coconut electrolyte blend (CCEB) for 26 days. METHODS: One-hundred ninety-two chicks were brooded for 2 weeks and thereafter divided on a weight equalization basis into four groups (0, 5, 10 and 15 ml CCEB per litre of water) of six replicates each and eight birds per replicate. Phytochemical screening of CCEB was determined, while data collected for growth performance, organ proportions and intestinal morphology were subjected to a one-way analysis of variance. RESULTS: Phytochemical composition revealed the abundance of phenols (128.40 mg/100g) and tannins (78.10 mg/100g) in CCEB. All productive performance parameters measured were not significantly (p < 0.05) different across treatment means. However, significantly (p < 0.05) highest concentrations (134.47 and 66.48 mg/dl, respectively) for total cholesterol and high-density lipoprotein (HDL) and the lowest concentration (38.34 mg/dl) for low-density lipoprotein (LDL) were recorded in birds on 15 ml of CCEB/litre of water. Furthermore, a progressive reduction (p < 0.05) in the bursa of Fabricius was observed with increasing CCEB/litre of water. The supplementation of CCEB did not influence (p > 0.05) duodenal morphological parameters. CONCLUSION: The study concluded that 15 ml of CCEB/litre of water enhanced the production of HDL, reduced LDL, and improved immunity via the reduction of the bursa of Fabricius in broiler chickens.

Phyllanthus emblica (Amla) methanolic extract regulates multiple checkpoints in 15-lipoxygenase mediated inflammopathies: Computational simulation and in vitro evidence.

Amla (Phyllanthus emblica) has long been used in traditional folk medicine to prevent and cure a variety of inflammatory diseases. In this study, the antioxidant activity (DPPH scavenging and reducing power), anti-inflammatory activity (RBC Membrane Stabilization and 15-LOX inhibition), and anticoagulation activity (Serin protease inhibition and Prothrombin Time assays) of the methanolic extract of amla were conducted. Amla exhibited a substantial amount of phenolic content (TPC: 663.53 mg GAE/g) and flavonoid content (TFC: 418.89 mg GAE/g). A strong DPPH scavenging effect was observed with an IC50 of 311.31 µg/ml as compared to standard ascorbic acid with an IC50 of 130.53 µg/ml. In reducing power assay, the EC50 value of the extract was found to be 196.20 µg/ml compared to standard ascorbic acid (EC50 = 33.83 µg/ml). The IC50 value of the RBC membrane stabilization and 15-LOX assays was observed as 101.08 µg/ml (IC50 of 58.62 µg/ml for standard aspirin) and 195.98 µg/ml (IC50 of 19.62 µg/ml for standard quercetin), respectively. The extract also strongly inhibited serine protease (trypsin) activity with an IC50 of 505.81 µg/ml (IC50 of 295.44 µg/ml for standard quercetin). The blood coagulation time (PTT) was found to be 11.91 min for amla extract and 24.11 min for standard Warfarin. Thus, the findings of an in vitro study revealed that the methanolic extract of amla contains significant antioxidant, anti-inflammatory, and anticoagulation activity. Furthermore, in silico docking and simulation of reported phytochemicals of amla with human 15-LOXA and 15-LOXB were carried out to validate the anti-inflammatory activity of amla. In this analysis, epicatechin and catechin showed greater molecular interaction and were considerably stable throughout the 100 ns simulation with 15-lipoxygenase A (15-LOXA) and 15-lipoxygenase B (15-LOXB) respectively.

Roles of Endocannabinoids and Endocannabinoid-Like Molecules in Energy Homeostasis and Metabolic Regulation: A Nutritional Perspective.

The endocannabinoid system is involved in signal transduction in mammals. It comprises principally G protein-coupled cannabinoid receptors and their endogenous agonists, called endocannabinoids, as well as the enzymes and transporters responsible for the metabolism of endocannabinoids. Two arachidonic acid-containing lipid molecules, arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol, function as endocannabinoids. N-acylethanolamines and monoacylglycerols, in which the arachidonic acid chain is replaced with a saturated or monounsaturated fatty acid, are not directly involved in the endocannabinoid system but exhibit agonistic activities for other receptors. These endocannabinoid-like moleculesinclude palmitoylethanolamide, oleoylethanolamide (OEA), and 2-oleoylglycerol. Endocannabinoids stimulate feeding behavior and the anabolism of lipids and glucose, while OEA suppresses appetite. Both central and peripheral systems are included in these nutritional and metabolic contexts. Therefore, they have potential in the treatment and prevention of obesity. We outline the structure, metabolism, and biological activities of endocannabinoids and related molecules, and focus on their involvement in energy homeostasis and metabolic regulation.

Trajectories of antidepressant use and characteristics associated with trajectory groups among young refugees and their Swedish-born peers with diagnosed common mental disorders-findings from the REMAIN study.

PURPOSE: This study aimed to (1) identify the trajectories of prescribed antidepressants in refugee youth and matched Swedish-born peers diagnosed with common mental disorder (CMD) and (2) characterize the trajectories according to sociodemographic and medical factors. METHODS: The study population comprised 2,198 refugees and 12,199 Swedish-born individuals with both Swedish-born parents, aged 16-25 years in 2011, residing in Sweden and treated in specialised healthcare for CMD 2009-11. Group-based trajectory modelling was used to identify different trajectory groups of antidepressant use-based on annual defined daily dosages (DDDs). Multinomial logistic regression was applied to investigate the association of sociodemographic and medical characteristics with the identified trajectories. Nagelkerke pseudo-R2 values were estimated to evaluate the strength of these associations. RESULTS: Four trajectory groups of antidepressant use among young refugees were identified with following proportions and DDD levels in 2011: 'low constant' (88%, < 100), 'low increasing' (2%, ≈710), 'medium decreasing' (8%, ≈170) and 'high increasing' (2%, ≈860). Similar trajectories, however, with different proportions were identified in Swedish-born: 67%, 7%, 21% and 5%, respectively. The most influential factors discriminating the trajectory groups among refugees were 'duration of stay in Sweden' (R2 = 0.013), comorbid 'other mental disorders' (R2 = 0.009) and 'disability pension' (R2 = 0.007), while 'disability pension' (R2 = 0.017), comorbid 'other mental disorders' (R2 = 0.008) and 'educational level' (R2 = 0.008) were the most important determinants discriminating trajectory groups among Swedish-born youth. CONCLUSION: The lower use of antidepressants in refugees with CMDs compared to their Swedish-born counterparts warrants health literacy programs for refugees and training in transcultural psychiatry for healthcare professionals.

Disability-friendly healthcare at public health facilities in Bangladesh: a mixed-method study to explore the existing situation.

BACKGROUND: Several strategies and policies are being implemented in Bangladesh to address the healthcare needs of people with disabilities, who comprise about 10% of the country's total population. However, these measures are not adequate to provide accessible or friendly healthcare to the people with disabilities. This study aimed to explore the disability-friendliness of healthcare facilities, and the challenges of people with disabilities in terms of access to 1) information and communication, 2) access to infrastructure, and 3) providers' capacity in Bangladesh. METHODS: An explanatory sequential mixed-method study was conducted, including a cross-sectional survey of healthcare facilities, followed by structured-interview with people with disabilities and healthcare managers, and qualitative interviews among people with disabilities or their caregivers, healthcare providers (HCPs), policymakers, and community leaders. Data were collected from 150 public healthcare (primary-to-tertiary) facilities and from 300 people with disabilities in 16 districts across Bangladesh between January-December 2019. An observational checklist and structured questionnaires were used to assess the situation of healthcare facilities, and literature-guided guidelines were used for qualitative interviews. During analysis, the disability-friendliness of healthcare facilities were quantified through a scoring system, and thematic analysis of qualitative data was performed to identify the challenges of implementing disability-friendly healthcare (DFHC). RESULTS: The score for providing DFHC was low across all the four objectives in the healthcare facilities. The highest score (mean percentage) was observed in the infrastructure domain: 29.3 ± 20.5, followed by communication: 18.2 ± 4.8, and information: 14.6 ± 6.22, and the lowest (0.93 ± 7.1) score was for capacity of the HCPs to provide DFHC. Mean percentage scores for access to 13 infrastructure points were low, and extremely low scores were found in areas such as access to elevators (5.6 ± 5.0), ticket counters (7.3 ± 17.7) and toilets (10.6 ± 9.3). Furthermore, about 59.1% of people with disabilities expressed dissatisfaction regarding access to information and communication. The majority (98.2%) recommended that training of HCPs can improve the situation. CONCLUSION: This study revealed that most of the public health facilities in Bangladesh were not disability-friendly. Findings can inform development of a national disability-friendly policy with implementation guidelines.

Prevalence of and factors associated with insufficient physical activity among adolescents: evidence from a nationwide survey in Bangladesh.

The World Health Organization set a target of a 15% relative reduction in the prevalence of insufficient physical activity (IPA) by 2025 among adolescents and adults globally. In Bangladesh, there are no national estimates of the prevalence of IPA among adolescents. The aim of this study was to estimate the prevalence of and risk factors associated with IPA among adolescent girls and boys. Data for 4865 adolescent girls and 4907 adolescent boys, collected as a part of a National Nutrition Surveillance in 2018-19, were analysed for this study. A modified version of the Global Physical Activity Questionnaire (GPAQ) was used to collect physical activity data. The World Health Organization recommended cut-off points were used to estimate the prevalence of IPA. Bivariate and multivariable logistic regression was performed to identify factors associated with IPA. Prevalences of IPA among adolescent girls and boys were 50.3% and 29.0%, respectively, and the prevalence was significantly higher among early adolescents (10-14 years) than late adolescents (15-19 years) among both boys and girls. The IPA prevalence was highest among adolescents living in non-slum urban areas (girls: 77.7%; boys: 64.1%). For both boys and girls, younger age, non-slum urban residence, higher paternal education and increased television viewing time were significantly associated with IPA. Additionally, residing in slums was significantly associated with IPA only among the boys. Higher maternal education was associated with IPA only among the girls. This study identified several modifiable risk factors associated with IPA among adolescent boys and girls in Bangladesh. These factors should be addressed through comprehensive public health interventions to promote physical activity among adolescent girls and boys.

Spotlight on Exosomal Non-Coding RNAs in Breast Cancer: An In Silico Analysis to Identify Potential lncRNA/circRNA-miRNA-Target Axis.

Breast cancer (BC) has recently become the most common cancer type worldwide, with metastatic disease being the main reason for disease mortality. This has brought about strategies for early detection, especially the utilization of minimally invasive biomarkers found in various bodily fluids. Exosomes have been proposed as novel extracellular vesicles, readily detectable in bodily fluids, secreted from BC-cells or BC-tumor microenvironment cells, and capable of conferring cellular signals over long distances via various cargo molecules. This cargo is composed of different biomolecules, among which are the novel non-coding genome products, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and the recently discovered circular RNA (circRNA), all of which were found to be implicated in BC pathology. In this review, the diverse roles of the ncRNA cargo of BC-derived exosomes will be discussed, shedding light on their primarily oncogenic and additionally tumor suppressor roles at different levels of BC tumor progression, and drug sensitivity/resistance, along with presenting their diagnostic, prognostic, and predictive biomarker potential. Finally, benefiting from the miRNA sponging mechanism of action of lncRNAs and circRNAs, we established an experimentally validated breast cancer exosomal non-coding RNAs-regulated target gene axis from already published exosomal ncRNAs in BC. The resulting genes, pathways, gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis could be a starting point to better understand BC and may pave the way for the development of novel diagnostic and prognostic biomarkers and therapeutics.