Effect of single versus grouped culture of human cumulus-oocyte complexes in PCOS women treated with biphasic in vitro maturation: A sibling oocyte pilot study.

Purpose: This study investigated the differences in the maturation rate of single versus grouped cumulus-oocyte complexes (COCs) culture methods for capacitation in vitro maturation (CAPA-IVM) in women with polycystic ovary syndrome (PCOS). Methods: This study was performed at My Duc Phu Nhuan Hospital, Vietnam from October 1, 2020 to October 24, 2021. Women aged 18-37 years with a diagnosis of PCOS were recruited. COCs from each woman were randomly divided into two groups: single or grouped culture during CAPA-IVM culture. The primary outcome was the maturation rate. Results: A total of 322 COCs from 15 eligible women included were randomly assigned to the two study groups. The maturation rate was comparable between the single and grouped culture groups (61.3% vs. 64.8%; p = 0.56). There were no significant differences in the number of 2-pronuclei fertilized oocytes, number of day-3 embryos, and number of good-quality embryos in the two culture method groups. In the single culture group, COCs morphology was associated with the day-3 embryo formation rate but not the maturation rate. Conclusions: Comparable oocyte maturation and embryology outcomes between single and grouped COCs culture utilizing sibling COCs derived from women with PCOS suggest the feasibility of both methods for CAPA-IVM culture.

Health literacy mediates the relationships of cognitive and physical functions with health-related quality of life in older adults.

Background: Declining cognitive function (CF) and physical function (PF) relate to poorer health-related quality of life (HRQoL) in older adults. As health literacy (HL) facilitates health information utilization, it may mediate links between functionality and HRQoL appraisals. This study examined HL as an intermediary between joint CF and PF contributions and HRQoL in Hong Kong older adults. Methods: 490 older adults aged 50-80 years completed assessments from March to July 2021. Health Literacy Survey Questionnaire Short Form 12 questions (HLS-SF12), Montreal Cognitive Assessment (MoCA), Senior Fitness Test (SFT) and 12-Item Short-Form Health Survey version 2 (SF-12v2) were used to assess HL, CF, PF and HRQoL, respectively. Path analysis tested a model with HL mediating CF/PF predictors and HRQoL outcome. Results: Results for direct effects indicated that CF significantly associated with PF (ß = 0.115, SE = 0.012, p < 0.001), PF significantly connected to HL (ß = 0.101, SE = 0.022, p < 0.001), and HL significantly related to HRQoL (ß = 0.457, SE = 0.049, p < 0.001). Meanwhile, PF significantly linked to HRQoL directly (ß = 0.156, SE = 0.025, p < 0.001) as well as indirectly (ß = 0.046, 95% CI [0.028, 0.067]). Significant mediating effect of HL was found on the relationship of PF and HRQoL. Conclusion: Findings confirm CF and PF joint impacts on HL and HRQoL in older adults, elucidating HL's mediating role in translating functionality levels into HRQoL. Fostering enduring health knowledge access may thus buffer effects of age-related declines on well-being. Results can inform interventions leveraging this pathway to promote resilient trajectories.

Down Syndrome Patients with Congenital Portosystemic Shunts: A Case Report and Review.

Introduction: Down syndrome is due to trisomy 21 and is characterized by intellectual disability, dysmorphic facial features, congenital malformations, and gastrointestinal abnormalities. There is an increased appreciation of congenital portosystemic shunts in Down syndrome patients. Congenital portosystemic shunts have been associated with many defects in body systems, including cardiac, metabolic, and neurological. Case Presentation: Herein, we describe a portosystemic shunt in a Down syndrome patient that resulted in hyperammonemia with altered mental status and choreiform movements. Computed tomography angiography of the abdomen and pelvis identified a connection between the right portal vein and inferior vena cava. An 18 mm Amplatzer PFO closure device was placed within the congenital shunt, significantly improving symptoms. The patient has no sequelae from the related shunt or the device at the 2-year follow-up. We extensively reviewed the literature and identified cases of portosystemic shunts in Down syndrome patients. Shunts can either be extrahepatic or intrahepatic and are classified by vasculature connections. Conclusion: From our literature review and case presentation, we identify other conditions in patients, including cardiac and gastrointestinal defects. We then review the available treatment options, whether observation or surgical, depending on the patient's clinical picture.

Brain-Derived Neurotrophic Factor (BDNF) and Translocator Protein (TSPO) as Diagnostic Biomarkers for Acute Ischemic Stroke.

Brain-derived neurotrophic factor (BDNF) interacts with tropomyosin-related kinase B (TrkB) to promote neuronal growth, survival, differentiation, neurotransmitter release, and synaptic plasticity. The translocator protein (TSPO) is known to be found in arterial plaques, which are a symptom of atherosclerosis and a contributory cause of ischemic stroke. This study aims to determine the diagnostic accuracy of plasma BDNF and TSPO levels in discriminating new-onset acute ischemic stroke (AIS) patients from individuals without acute ischemic stroke. A total of 90 AIS patients (61% male, with a mean age of 67.7 ± 12.88) were recruited consecutively in a stroke unit, and each patient was paired with two age- and gender-matched controls. The sensitivity, specificity, and area of the curve between high plasma BDNF and TSPO and having AIS was determined using receiver operating characteristic curves. Furthermore, compared to the controls, AIS patients exhibited significantly higher levels of BDNF and TSPO, blood pressure, HbA1c, and white blood cells, as well as higher creatinine levels. The plasma levels of BDNF and TSPO can significantly discriminate AIS patients from healthy individuals (AUC 0.76 and 0.89, respectively). However, combining the two biomarkers provided little improvement in AUC (0.90). It may be possible to use elevated levels of TSPO as a diagnostic biomarker in patients with acute ischemic stroke upon admission.

Association between Hypertension and Stroke Recurrence as Modified by Pro-oxidant-Antioxidant Balance: A Multi-Center Study.

BACKGROUND: Hypertension and oxidative stress are involved in the pathophysiological mechanism of stroke. We aimed to investigate the modification impact of the pro-oxidant-anti-oxidant balance (PAB) on the association between hypertension and stroke recurrence (SR). METHODS: A cross-sectional design was conducted from December 2019 to December 2020 in 951 stroke patients in six hospitals across Vietnam. Hypertension was defined using antihypertensive medication or systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg. PAB was estimated using weighting methods based on smoking, drinking, and overweight/obesity with pro-oxidant capacity, diet quality, fruit intake, vegetable intake, and physical activity with antioxidant capacity. The higher PAB scores indicated a beneficial balance shifting toward antioxidant dominance. SR was diagnosed by neurologists. Moreover, sociodemographic and health conditions were included as covariates. Multiple logistic regression analyses were used to explore the associations and interactions. RESULTS: The hypertension and SR proportions were 72.8% and 17.5%, respectively. hypertension was associated with an increased SR likelihood (odds ratio (OR) = 1.93; p = 0.004), whereas a higher PAB score was associated with a lowered SR likelihood (OR = 0.87; p = 0.003). Moreover, hypertension interacting with every one-point increment of PAB was associated with a lowered SR likelihood (OR = 0.83; p = 0.022). CONCLUSIONS: The harmful impact of hypertension on SR could be alleviated by PAB. The interplay of health behaviors should be highlighted in the intervention strategies for stroke prevention.

Thyroid Peroxidase Antibodies in Infertile Women with Polycystic Ovary Syndrome.

To compare the rate of positive thyroid peroxidase antibodies (TPO Ab) between women with different polycystic ovary syndrome (PCOS) phenotypes and women without PCOS. This is a retrospective cohort study. Women with PCOS at My Duc Hospital between June 1, 2020, and March 27, 2021, were matched with non-PCOS women by age. TPO Ab (cut-off: 34 IU/mL) and thyroid-stimulating hormone (TSH) levels were measured as markers of Hashimoto thyroiditis and thyroid function, respectively. One thousand eight hundred eight infertile women were included, 904 with PCOS (mean age 29.0 ± 3.58 years) and 904 without PCOS (29.1 ± 3.4 years; controls). Women with PCOS had a higher body mass index (22.8 ± 3.84 vs. 19.9 ± 2.23 kg/m2, p < 0.001), but most were not overweight/obese. Rates of positive TPO Ab in women with versus without PCOS were 8.2% and 8.4%, respectively (p = 0.932). Rates of positive TPO Ab in patients with PCOS phenotype A, B, C, or D were not statistically different (7.5%, 2.9%, 20.0%, and 7.8%, respectively). Median TSH concentrations were similar in the PCOS and control groups (1.84 mIU/L vs. 1.78 mIU/L, respectively; p = 0.194). Based on a linear regression model, there was no correlation between either BMI or the estradiol to progesterone ratio and TPO Ab status. In a large population of infertile women with PCOS who were mostly lean patients, rates of positive TPO Ab across all four PCOS phenotypes did not differ significantly from those in women without PCOS. These findings did not support the hypothesis that PCOS is a risk factor for Hashimoto thyroiditis.

Darrach vs. Sauve-Kapandji: A Comprehensive Meta-Analysis of Surgical Outcomes in Distal Radioulnar Joint (DRUJ) Dysfunction.

Introduction: Optimal treatment of chronic distal radioulnar joint (DRUJ) arthritis and instability remains unresolved in the literature. Specifically, no systematic comparison of two common options, Sauve-Kapandji (SK) and Darrach's, is available. Methods: A meta-analysis was performed utilizing the PUBMED and EMBASE databases and yielded a total of 47 available studies. Objective outcomes, such as wrist range of motion (ROM), forearm ROM, grip strength, and subjective outcomes, including pain and rate of return to work, were recorded. Statistical analysis was done using t test and chi-square test. Results: For both the SK and Darrach's procedures, forearm ROM was significantly better postoperatively in both pronation (p = 0.0001 for both groups) and supination (p = 0.0001 for both groups). Wrist flexion decreased in the SK group (p = 0.0007), but no difference was found for wrist extension (p = 0.09). The Darrach's group showed a significance improvement in wrist extension (p = 0.0001). Grip strength was improved in the SK group (p < 0.0001), but not in the Darrach's group (p = 0.7831). No difference existed between the SK and Darrach's groups in proportion of patients who were pain-free. The SK group had higher numbers of patients return to work (p = 0.0057). There was not enough data from the studies to make any meaningful analysis in term of treatment failure and complications. Conclusions: Overall, both the SK and Darrach's procedures helped improve pain, wrist ROM, and forearm ROM in patient with chronic DRUJ disorders. The SK procedure can have advantages over the Darrach's procedures in terms of grip strength and rate of return to work. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-023-00826-5.

Development of children born to women with twin pregnancies treated with cervical pessary or vaginal progesterone: Follow-up of a randomized controlled trial.

INTRODUCTION: Preterm birth is the most common cause of neonatal morbidity and mortality. Women with twin pregnancies and a short cervical length are at high risk for preterm birth. Vaginal progesterone and cervical pessary have been proposed as potential strategies to reduce preterm birth in this high-risk population. Therefore, we aimed to compare the effectiveness of cervical pessary and vaginal progesterone in improving developmental outcomes of children born to women with twin pregnancies and mid-trimester short cervical length. MATERIAL AND METHODS: This was a follow-up study (NCT04295187) of all children at 24 months of age, born from women treated with cervical pessary or progesterone to prevent preterm birth in a randomized controlled trial (NCT02623881). We used a validated Vietnamese version of Ages & Stages Third Edition Questionnaires (ASQ-3) and a red flag questionnaire. In surviving children, we compared the mean ASQ-3 scores, abnormal ASQ-3 scores, the number of children with any abnormal ASQ-3 scores and red flag signs between the two groups. We reported the composite outcome of perinatal death or survival with any abnormal ASQ-3 score in offspring. These outcomes were also calculated in a subgroup of women with a cervical length ≤28 mm (<25th percentile). RESULTS: In the original randomized controlled trial, we randomized 300 women to pessary or progesterone. After counting the number of perinatal deaths and lost to follow-up, 82.8% parents in the pessary group and 82.5% parents in progesterone group returned the questionnaire. The mean ASQ-3 scores of the five skills and red flag signs did not differ significantly between the two groups. However, the percentage of children having abnormal ASQ-3 scores in fine motor skills was significantly lower in the progesterone group (6.1% vs 1.3%, P = 0.01). There were no significant differences in the composite outcome of perinatal death or survival with any abnormal ASQ-3 score in unselected women and in those with cervical length ≤28 mm. CONCLUSIONS: Cervical pessary and vaginal progesterone may have comparable effects on developmental outcomes in children at ≥24 months of age, born to women with twin pregnancies and short cervical length. However, this finding could be likely due to a lack of study power.

Discovery of Orally Bioavailable FGFR2/FGFR3 Dual Inhibitors via Structure-Guided Scaffold Repurposing Approach.

Fibroblast growth factor receptors (FGFRs) are transmembrane receptor tyrosine kinases that regulate multiple physiological processes. Aberrant activation of FGFR2 and FGFR3 has been linked to the pathogenesis of many tumor types, including cholangiocarcinoma and bladder cancer. Current therapies targeting the FGFR2/3 pathway exploiting small-molecule kinase inhibitors are associated with adverse events due to undesirable inhibition of FGFR1 and FGFR4. Isoform-specific FGFR2 and FGFR3 inhibitors that spare FGFR1 and FGFR4 could offer a favorable toxicity profile and improved therapeutic window to current treatments. Herein we disclose the discovery of dual FGFR2/FGFR3 inhibitors exploiting scaffold repurposing of a previously reported ALK2 tool compound. Structure-based drug design and structure-activity relationship studies were employed to identify selective and orally bioavailable inhibitors with equipotent activity toward wild-type kinases and a clinically observed gatekeeper mutant.

Potent and Selective Biaryl Amide Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1).

Herein we report the discovery of a novel biaryl amide series as selective inhibitors of hematopoietic protein kinase 1 (HPK1). Structure-activity relationship development, aided by molecular modeling, identified indazole 5b as a core for further exploration because of its outstanding enzymatic and cellular potency coupled with encouraging kinome selectivity. Late-stage manipulation of the right-hand aryl and amine moieties surmounted issues of selectivity over TRKA, MAP4K2, and STK4 as well as generating compounds with balanced in vitro ADME profiles and promising pharmacokinetics.

Fear of COVID-19, healthy eating behaviors, and health-related behavior changes as associated with anxiety and depression among medical students: An online survey.

Background: Medical students' health and wellbeing are highly concerned during the COVID-19 pandemic. This study examined the impacts of fear of COVID-19 (FCoV-19S), healthy eating behavior, and health-related behavior changes on anxiety and depression. Methods: We conducted an online survey at 8 medical universities in Vietnam from 7th April to 31st May 2020. Data of 5,765 medical students were collected regarding demographic characteristics, FCoV-19S, health-related behaviors, healthy eating score (HES), anxiety, and depression. Logistic regression analyses were used to explore associations. Results: A lower likelihood of anxiety and depression were found in students with a higher HES score (OR = 0.98; 95%CI = 0.96, 0.99; p = 0.042; OR = 0.98; 95%CI = 0.96, 0.99; p = 0.021), and in those unchanged or more physical activities during the pandemic (OR = 0.54; 95%CI = 0.44, 0.66; p < 0.001; OR = 0.44; 95%CI = 0.37, 0.52; p < 0.001) as compared to those with none/less physical activity, respectively. A higher likelihood of anxiety and depression were reported in students with a higher FCoV-19S score (OR = 1.09; 95%CI = 1.07, 1.12; p < 0.001; OR = 1.06; 95%CI = 1.04, 1.08; p < 0.001), and those smoked unchanged/more during the pandemic (OR = 6.67; 95%CI = 4.71, 9.43; p < 0.001; OR = 6.77; 95%CI = 4.89, 9.38; p < 0.001) as compared to those stopped/less smoke, respectively. In addition, male students had a lower likelihood of anxiety (OR = 0.79; 95%CI = 0.65, 0.98; p = 0.029) compared to female ones. Conclusions: During the pandemic, FCoV-19S and cigarette smoking had adverse impacts on medical students' psychological health. Conversely, staying physically active and having healthy eating behaviors could potentially prevent medical students from anxiety and depressive symptoms.

Body mass index, body fat percentage, and visceral fat as mediators in the association between health literacy and hypertension among residents living in rural and suburban areas.

Background: Hypertension is a major cause of death and disability worldwide. Enhancing health literacy (HL) may help to alleviate the risk of hypertension and its burden. However, evidence on the association between HL and hypertension and potential mechanisms remain to be explored. Objectives: This study examined the association between HL and hypertension; and explored whether body mass index (BMI), body fat percentage (PBF), and visceral fat (VF) were mediators of this association in people who resided in rural and suburban areas in Vietnam. Methods: A cross-sectional survey was conducted from 1st July to 31st December 2019, involving 1655 residents and exploring participants' sociodemographic characteristics, HL, health-related behaviors, comorbidities, body composition, and blood pressure (BP). People with systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg or using antihypertensive medication were classified as having hypertension. Multiple logistic regression and mediation analyses were used to explore associations. Results: The hypertension prevalence was 41.9% (694/1,655). In adjusted models, a higher HL score was associated with a lower hypertension likelihood (OR = 0.96; 95%CI = 0.95-0.97; p < 0.001). Factors associated with a higher odd of hypertension were overweight/obese (OR = 1.69; 95%CI = 1.24-2.29; p = 0.001), high PBF (OR = 2.35; 95%CI = 1.85-2.99; p < 0.001), and high VF (OR = 2.27; 95%CI = 1.63-3.16; p < 0.001). Notably, PBF significantly mediated the association between HL and hypertension (indirect effect, OR = 0.99; 95%CI = 0.98-0.99; p = 0.009; percent mediated = 8.56%). The mediating roles of BMI and VF were not found. Conclusion: The prevalence of hypertension was relatively high. People with better HL were less likely to have hypertension. The association between HL and hypertension was partially explained by PBF. Strategic approaches are required to improve people's HL and body fat which further help to manage hypertension in rural and suburban areas.

COVID-19-related fear, stress and depression in school principals: impacts of symptoms like COVID-19, information confusion, health-related activity limitations, working hours, sense of coherence and health literacy.

BACKGROUND: School principals have been reported to have a higher prevalence of burnout and psychological problems than their colleagues. During the pandemic, extra workload and pressure from unprecedented situations potentially cause fear, stress and depression. Therefore, we aimed to explore associated factors of stress, fear of COVID-19 (F-CoV-19S) and depressive symptoms among school principals. METHODS: A cross-sectional online survey was conducted in Taiwan from 23 June to 16 July 2021. Data of 413 school principals were collected, including socio-demographic factors, COVID-19-related factors, work-related information, health status, sense of coherence (SoC), health literacy (HL), F-CoV-19S, stress and depression. Multiple linear and logistic regression models were utilized to explore associations. RESULTS: School principals with symptoms like COVID-19 (S-COVID-19-S), or with health-related activity limitations had a higher score of stress (B = 0.92; p = .039) (B = 1.52; p < .001) and a higher depression likelihood (OR = 3.38; p < .001) (OR = 3.06; p < .001), whereas those with a better SoC had a lower stress score (B = -1.39; p < .001) and a lower depression likelihood (OR = 0.76; p = .020). School principals confusing about COVID-19-related information had a higher score of stress (B = 2.47; p < .001) and fear (B = 3.77; p < .001). The longer working time was associated with a higher fear score (B = 1.69; p = .006). Additionally, school principals with a higher HL score had a lower stress score (B = -1.76; p < .001), a lower fear score (B = -1.85; p < .001) and a lower depression likelihood (OR = 0.53; p = .043). CONCLUSIONS: Health-related activity limitations, S-COVID-19-S, COVID-19-related information confusion and longer working hours were positively associated with at least one mental health problem (e.g. stress, fear and depression), whereas better SoC and HL showed the benefits to mitigate fear, stress and depressive symptoms in school principals. Our study provides evidence for appropriate strategies to improve principals' mental health during the pandemic.Key messages:School principals with health-related activity limitations or with symptoms like COVID-19 were more likely to be stressed and depressed.Higher levels of stress and fear were observed in school principals who confused about COVID-19-related information, and who had longer working time than before the pandemic.Better sense of coherence and higher health literacy could potentially mitigate the fear, stress and depressive symptoms in school principals.

The Marine-Derived Macrolactone Mandelalide A Is an Indirect Activator of AMPK.

The mandelalides are complex macrolactone natural products with distinct macrocycle motifs and a bioactivity profile that is heavily influenced by compound glycosylation. Mandelalides A and B are direct inhibitors of mitochondrial ATP synthase (complex V) and therefore more toxic to mammalian cells with an oxidative metabolic phenotype. To provide further insight into the pharmacology of the mandelalides, we studied the AMP-activated protein kinase (AMPK) energy stress pathway and report that mandelalide A is an indirect activator of AMPK. Wild-type mouse embryonic fibroblasts (MEFs) and representative human non-small cell lung cancer (NSCLC) cells showed statistically significant increases in phospho-AMPK (Thr172) and phospho-ACC (Ser79) in response to mandelalide A. Mandelalide L, which also harbors an A-type macrocycle, induced similar increases in phospho-AMPK (Thr172) and phospho-ACC (Ser79) in U87-MG glioblastoma cells. In contrast, MEFs co-treated with an AMPK inhibitor (dorsomorphin), AMPKα-null MEFs, or NSCLC cells lacking liver kinase B1 (LKB1) lacked this activity. Mandelalide A was significantly more cytotoxic to AMPKα-null MEFs than wild-type cells, suggesting that AMPK activation serves as a protective response to mandelalide-induced depletion of cellular ATP. However, LKB1 status alone was not predictive of the antiproliferative effects of mandelalide A against NSCLC cells. When EGFR status was considered, erlotinib and mandelalide A showed strong cytotoxic synergy in combination against erlotinib-resistant 11-18 NSCLC cells but not against erlotinib-sensitive PC-9 cells. Finally, prolonged exposures rendered mandelalide A, a potent and efficacious cytotoxin, against a panel of human glioblastoma cell types regardless of the underlying metabolic phenotype of the cell. These results add biological relevance to the mandelalide series and provide the basis for their further pre-clinical evaluation as ATP synthase inhibitors and secondary activators of AMPK.

Development of children born after in vitro maturation with a prematuration step versus natural conception: a prospective cohort study.

PURPOSE: IVM preceded by a prematuration step (capacitation [CAPA]-IVM) improves the acquisition of oocyte developmental competence and can enhance embryo quality. There is currently no follow-up data on babies born from CAPA-IVM. This study investigated developmental outcomes in children born after CAPA-IVM versus natural conception. METHODS: This prospective cohort study was conducted at a fertility clinic in Vietnam in August/September 2019. Children born after CAPA-IVM were propensity score-matched with those born after natural conception. All parents were asked to complete the Developmental Red Flags and Ages & Stages Third Edition (ASQ-3) questionnaires. RESULTS: A total of 46 parents (23 in each group) of 55 babies (31 CAPA-IVM and 24 natural conception) were included in the study. Baseline characteristics, including mother's age and body mass index, gestational age at delivery, and birth weight, were comparable. The mean age of children at the end of follow-up was 15 months. The overall proportion of children with any abnormal ASQ-3 score was 6.5% in the CAPA-IVM group and 20.8% in the natural conception group (p = 0.24). The proportion of children with a developmental red flag did not differ significantly between the CAPA-IVM and natural conception groups (9.7% vs. 4.2%; p = 0.80). CONCLUSIONS: The use of CAPA-IVM did not have any significant impact on childhood physical and mental development compared with children born as a result of natural conception.

Psychometric Properties of the Short-Form Geriatric Depression Scale (GDS-SF) and Its Associated Factors among the Elderly in Bangladesh.

Background: This study aimed to (1) evaluate the psychometric properties of a Comprehensive Short-Form Geriatric Depression Scale (GDS-SF) and (2) examine the associated factors of GDS-SF among the elderly. Methods: A cross-sectional study was conducted from November 2019 to April 2020 in Dhaka City Corporation, Bangladesh. Data of 377 elderly were collected, including socio-demographic characteristics, social supports, comorbidities, sleep behaviours, and depression (as measured by the GDS-SF). We used the principal component analysis, correlation analysis, and logistic regression analysis to validate GDS-SF, and explore its associations. Results: The GDS-SF was reliable and homogeneous with Cronbach's alpha = 0.836, and McDonald's Omega = 0.841, with no floor/ceiling effects. The questionnaire demonstrated a good construct validity with item-scale convergent validity and KMO measure of sampling adequacy (0.869 for the total sample, 0.838 for the community subsample, and 0.851 for the slum subsample). In the multivariate model, older people had a higher likelihood of moderate and severe depression (OR, 1.06; 95% CI, 1.00, 1.12; p = 0.048). The likelihood of having moderate and severe depression was lower in men (OR, 0.48; 95% CI, 0.28, 0.85; p = 0.011) and those satisfied with their children's support (OR, 0.17; 95% CI, 0.08, 0.35; p < 0.001), compared with their counterparts, respectively. Conclusions: The GDS-SF is a reliable and valid survey tool for evaluating depression in Bangladeshi older adults. Age, gender, and satisfaction with children's support were predictors of depression.

Discovery of Novel Pyrazolopyrimidines as Potent, Selective, and Orally Bioavailable Inhibitors of ALK2.

Activin receptor-like kinase 2 (ALK2) is a transmembrane kinase receptor that mediates the signaling of the members of the TGF-ß superfamily. The aberrant activation of ALK2 has been linked to the rare genetic disorder fibrodysplasia ossificans progressiva (FOP) and diffuse intrinsic pontine glioma (DIPG) that are associated with severely reduced life expectancy in pediatric patients. ALK2 has also been shown to play an essential role in iron metabolism by regulating hepcidin levels and affecting anemia of chronic disease. Thus, selective inhibition of ALK2 has emerged as a promising strategy for the treatment of multiple disorders. Herein, we report the discovery of a novel pyrazolopyrimidines series as highly potent, selective, and orally bioavailable inhibitors of ALK2. Structure-based drug design and systematic structure-activity relationship studies were employed to identify potent inhibitors displaying high selectivity against other ALK subtypes with good pharmacokinetic profiles.

Negative Impact of Comorbidity on Health-Related Quality of Life Among Patients With Stroke as Modified by Good Diet Quality.

Background: Comorbidity, along with aging, affects stroke-induced health-related quality of life (HRQoL). We examined the potential role of diet quality in modifying the association between comorbidity and HRQoL in patients with stroke. Methods: A cross-sectional study was conducted on 951 patients with stroke from December 2019 to December 2020 across Vietnam. Comorbidity was assessed using the Charlson Comorbidity Index (CCI) items and classified into two groups (none vs. one or more). Diet quality was evaluated using the Dietary Approaches to Stop Hypertension Quality (DASH-Q) questionnaire, and HRQoL was measured using the RAND-36, with a higher score indicating better diet quality or HRQoL, respectively. Besides, socio-demographics, health-related behaviors (e.g., physical activity, smoking, and drinking), disability (using WHODAS 2.0), and health literacy were also assessed. Linear regression analysis was utilized to explore the associations and interactions. Results: The proportion of patients with stroke aged ≥65 years and having comorbidity were 53.7 and 49.9%, respectively. The HRQoL scores were 44.4 ± 17.4. The diet quality was associated with higher HRQoL score (regression coefficient, B, 0.14; (95% confidence interval, 95% CI, 0.04, 0.23; p = 0.004), whereas comorbidity was associated with lower HRQoL score (B, -7.36; 95% CI, -9.50, -5.23; p < 0.001). In interaction analysis, compared to patients without comorbidity and having the lowest DASH-Q score, those with comorbidity and higher DASH-Q score had a higher HRQoL score (B, 0.21; 95% CI, 0.03, 0.39; p = 0.021). Conclusion: The findings showed that good diet quality could modify the adverse impact of comorbidity on HRQoL in patients with stroke. Diet quality should be considered as a strategic intervention to improve the HRQoL of patients with stroke, especially those with comorbidity, and to promote healthier aging.