The surgical success rate was significantly higher in eyes with PEG than it was in those with POAG.The use of inappropriate methods for estimating the effects of covariates in survival data with frailty leads to erroneous conclusions in medical research. This study evaluated the performance of 13 survival regression models in assessing the factors associated with the timing of complications in implant-supported dental restorations in a Swedish cohort. Data were obtained from randomly selected cohort (n = 596) of Swedish patients provided with dental restorations supported in 2003. Patients were evaluated over 9 years of implant loss, peri-implantitis or technical complications. Best Model was identified using goodness, AIC and BIC. The loglikelihood, the AIC and BIC were consistently lower in flexible parametric model with frailty (df = 2) than other models. Adjusted hazard of implant complications was 45% (adjusted Hazard Ratio (aHR) = 1.449; 95% Confidence Interval (CI) 1.153-1.821, p = 0.001) higher among patients with periodontitis. While controlling for other variables, the hazard of implant complications was about 5 times (aHR = 4.641; 95% CI 2.911-7.401, p less then 0.001) and 2 times (aHR = 2.338; 95% CI 1.553-3.519, p less then 0.001) higher among patients with full- and partial-jaw restorations than those with single crowns. Flexible parametric survival model with frailty are the most suitable for modelling implant complications among the studied patients. After the elimination of leprosy in 1995, there were 10-30 newly detected leprosy cases every year in Zhejiang Province, and the epidemiological characteristics of the newly detected leprosy cases have changed. While most of the newly detected cases came from other provinces in China, not Zhejiang, it brought a new challenge for leprosy prevention and control in post- elimination era in Zhejiang, China. This study was aimed to understand the temporal-spatial distribution characteristics of newly detected leprosy cases, and provide the scientific rationales for the development of leprosy control strategy. Data on the demographic of Zhejiang Province from 2011 to 2019 were obtained from the China Information System for Disease Control and Prevention, and the epidemiological data on leprosy cases newly detected in Zhejiang Province from 2011 to 2019 were obtained from the LEPROSY MANAGEMANT INFORMATION SYSTEM IN CHINA (LEPMIS), and temporal-spatial distributions were described. The geographic information sys, and it is also necessary to strengthen the early detection and standard management of the leprosy cases in floating population in Zhejiang. A few scattered cases still can be seen in post-elimination era, and there was a spatial clustering of the newly detected leprosy cases in Zhejiang Province. Most of the cases in Zhejiang Province were from other high epidemic provinces in China, which brought a new challenge for leprosy control and prevention in post- elimination era in Zhejiang, and it is also necessary to strengthen the early detection and standard management of the leprosy cases in floating population in Zhejiang. Tick-borne encephalitis (TBE) is the most important tick-borne viral disease in Eurasia and causes disease in humans and in a number of animals, among them dogs and horses. There is still no good correlation between tick numbers, weather conditions and human cases. There is the hypothesis that co-feeding due to simultaneous occurrence of larvae and nymphs may be a factor for the increased transmission of the virus in nature and for human disease. Based on long-term data from a natural TBEV focus, phylogenetic results and meteorological data we sought to challenge this hypothesis. Ticks from an identified TBE natural focus were sampled monthly from 04/2009 to 12/2018. Ticks were identified and pooled. Pools were tested by RT-qPCR. Positive pools were confirmed by virus isolation and/or sequencing of additional genes (E gene, NS2 gene). Temperature data such as the decadal (10-day) mean daily maximum air temperature (DMDMAT) were obtained from a nearby weather station and statistical correlations between tiaintenance of transmission cycle of TBEV in nature is not supported by our findings. There was no particular correlation between DMDMAT dynamics in spring and/or autumn and the MIR of nymphs or adult ticks detected. However, there was a positive correlation between the number of nymphs and the number of reported human TBE cases in the following months, but not in the following year. The hypothesis of the importance of co-feeding of larvae and nymphs for the maintenance of transmission cycle of TBEV in nature is not supported by our findings.Hospitals in Kenya continue to use the Febrile Antigen Brucella Agglutination Test (FBAT) to diagnose brucellosis, despite reports showing its inadequacy. This study generated hospital-based evidence on the performance and cost-effectiveness of the FBAT, compared to the Rose Bengal Test (RBT).Twelve hospitals in western Kenya stored patient serum samples that were tested for brucellosis using the FBAT, and these were later re-tested using the RBT. Data on the running time and cost of the FBAT, and the treatment prescribed for brucellosis, were collected. The cost-effectiveness of the two tests, defined as the cost in US Dollars ($) per Disability Adjusted Life Year (DALY) averted, was determined, and a basic sensitivity analysis was run to identify the most influential parameters. Over a 6-month period, 180 patient serum samples that were tested with FBAT at the hospitals were later re-tested with RBT at the field laboratory. Of these 24 (13.3%) and 3 (1.7%) tested positive with FBAT and RBT, respectively. The agreement between the FBAT and RBT was slight (Kappa = 0.12). Treatment prescribed following FBAT positivity varied between hospitals, and only one hospital prescribed a standardized therapy regimen. The mean $/DALY averted when using the FBAT and RBT were $2,065 (95% CI $481-$6,736) and $304 (95% CI $126-$604), respectively. Brucellosis prevalence was the most influential parameter in the cost-effectiveness of both tests. https://www.selleckchem.com/products/curzerene.html Extrapolation to the national level suggested that an estimated $338,891 (95% CI $47,000-$1,149,000) per year is currently spent unnecessarily treating those falsely testing positive by FBAT. These findings highlight the potential for misdiagnosis using the FBAT. Furthermore, the RBT is cost-effective, and could be considered as the mainstay screening test for human brucellosis in this setting. Lastly, the treatment regimens must be harmonized to ensure the appropriate use of antibiotics for treatment.

Physician burnout is endemic across medical education and has numerous deleterious effects. Given the prevalence and negative effects of burnout, there is an urgent need to understand how residents experience and cope with stress and develop explanatory models that inform the development of more effective interventions. Using a qualitative, constructivist approach informed by grounded theory, the authors conducted semistructured interviews from March to April 2019, in which psychiatry residents were asked about their experiences of stress and how they coped. First- through fourth-year trainees at Zucker Hillside Hospital at Northwell Health, Glen Oaks, New York, were invited. Two authors independently and inductively coded deidentified transcripts. https://www.selleckchem.com/products/lusutrombopag.html A constant comparative approach was used to analyze data and support construction of themes. Theoretic sufficiency was observed after 14 interviews. The authors constructed an explanatory model for how residents cope with stress and whether they tended towardating spaces that promote peer connection and providing training in addressing conflict, and facilitating engagement in meaning-making activities. These findings provide guidance for how residency programs may help residents cope with stress and move away from burnout toward wholehearted engagement. Strategies may include reducing barriers to self-care and to accessing help early in training, creating spaces that promote peer connection and providing training in addressing conflict, and facilitating engagement in meaning-making activities.This article is the sixth in a series on the biological basis of child health. It provides an overview of the development of the skeletal system before and after birth, and outlines the potential congenital anomalies that may occur. The article explains the structure and function of the bones before describing the role of the joints, tendons and ligaments. It also outlines the presentation and management of some of the common orthopaedic conditions seen in infants and children, including fractures, osteogenesis imperfecta, scoliosis, juvenile idiopathic arthritis, developmental dysplasia of the hip and achondroplasia.Hypertrophic scar (HS) is a severe fibrotic skin disease. It has always been a major problem in clinical treatment, mainly because its pathogenesis has not been well understood. The roles of bacterial contamination and prolonged wound inflammation were considered significant. IL-10 is a potent anti-inflammatory cytokine and plays a pivotal role in wound healing and scar formation. Here, we investigate whether IL-10 alleviates lipopolysaccharide (LPS)-induced inflammatory response and skin scarring and explore the possible mechanism of scar formation. Our results showed that the expression of TLR4 and pp65 was higher in HS and HS-derived fibroblasts (HSFs) than their counterpart normal skin (NS) and NS-derived fibroblasts (NSFs). LPS could up-regulate the expression of TLR4, pp65, Col I, Col III and α-SMA in NSFs, but IL-10 could down-regulate their expression in both HSFs and LPS-induced NSFs. Blocking IL-10 receptor (IL-10R) or the phosphorylation of STAT3, their expression was up-regulated. In addition, in vitro and in vivo models results showed that IL-10 could alleviate LPS-induced fibroblast-populated collagen lattice (FPCL) contraction and scar formation. Therefore, IL-10 alleviates LPS-induced skin scarring via IL-10R/STAT3 axis regulating TLR4/NF-κB pathway in dermal fibroblasts by reducing ECM proteins deposition and the conversion of fibroblasts to myofibroblasts. Our results indicate that IL-10 can alleviate the LPS-induced harmful effect on wound healing, reduce scar contracture, scar formation and skin fibrosis. Therefore, the down-regulation of inflammation may lead to a suitable scar outcome and be a better option for improving scar quality. Adolescents with single ventricle congenital heart disease (SVHD) show functional deficits, particularly in memory and mood regulation. Hippocampi are key brain structures that regulate mood and memory; however, their tissue integrity in SVHD is unclear. Our study aim is to evaluate hippocampal volumes and their associations with memory, anxiety, and mood scores in adolescents with SVHD compared to healthy controls. We collected brain magnetic resonance imaging data from 25 SVHD (age 15.9±1.2years; 15 male) and 38 controls (16.0±1.1years; 19 male) and assessed memory (Wide Range Assessment of Memory and Learning 2, WRAML2), anxiety (Beck Anxiety Inventory, BAI), and mood (Patient Health Questionnaire 9, PHQ-9) functions. Both left and right hippocampi were outlined and global volumes, as well as three-dimensional surfaces were compared between groups using ANCOVA and associations with cognitive and behavioral scores with partial correlations (covariates age and total brain volume). The SVHD group showed4, subiculum, and dentate gyrus), which are associated with memory deficits. The findings indicate the need to explore ways to improve memory to optimize academic achievement and ability for self-care in the condition.Temperature-induced change in reactivity of the frequently used ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([C4 C1 im]BF4 ) is presented as a prerequisite for the rational screening of reaction courses in material synthesis. [C4 C1 im]BF4 becomes active with oxidic precursor compounds in reduction reaction at ϑ≥200 °C, even without the addition of an external reducing agent. The reaction mechanism of forming red amorphous selenium from SeO2 is investigated as a model system and can be described similarly to the Riley oxidation. The reactive species but-1-ene, which is formed during the decomposition of [C4 C1 im]BF4 , reacts with SeO2 and form but-3-en-2-one, water, and selenium. Elucidation of the mechanism was achieved by thermoanalytical investigations. The monotropic phase transition of selenium was analyzed by the differential scanning calorimetry. Beyond, the suitability of the single source oxide precursor Bi2 Se3 O9 for the synthesis of Bi2 Se3 particles was confirmed. Identification, characterization of formed solids succeeded by using light microscopy, XRD, SEM, and EDX.

003). Conclusions These findings add to the growing literature on the applicability of DBT skills-training to heterogeneous psychological conditions, particularly when patients' challenges reflect underlying difficulties with emotion regulation.Although the relationship between both need frustration and, particularly, need satisfaction and different motivational regulations for exercise has been widely examined in the literature, little is known about the co-occurrence of both need satisfaction and need frustration in the exercise context. Grounded in self-determination theory, the present study aimed to examine the effects of both need satisfaction and frustration on motivational regulations for exercise, by applying a response surface analysis approach. In total, 477 regular exercisers aged 18-54 years participated in this study. The interaction between needs (high on both need satisfaction and frustration) displayed a positive and significant association with amotivation, integrated regulation, and intrinsic motivation. Considering the direction of the discrepancy (high vs. low levels of need satisfaction and frustration) related to the behavioral regulations, results showed that higher need satisfaction relative to need frustration was associated with more self-determined regulations of motivation. Contrarily, higher need satisfaction relative to need frustration was associated with lower scores on amotivation, external, introjected, and identified regulation. Overall, these findings extend previous literature, suggesting that need satisfaction and frustration are distinct factors that can be experienced simultaneously in individuals during exercise and that different degrees of both needs have different associations with behavioral regulations. To determine whether the revised 2018 ATS/ERS/JRS/ALAT radiological criteria for usual interstitial pneumonia (UIP) provide better diagnostic agreement compared to the 2011 guidelines. Cohort for this cross-sectional study (single center, nonacademic) was recruited from a multidisciplinary team discussion (MDD) from July 2010 until November 2018, with clinical suspicion of fibrosing interstitial lung disease ( = 325). Exclusion criteria were technical HRCT issues, known connective tissue disease (rheumatoid arthritis, systemic sclerosis, poly-or dermatomyositis), exposure to pulmonary toxins or lack of working diagnosis after MDD. Four readers with varying degrees in HRCT interpretation independently categorized 192 HRCTs, according to both the previous and current ATS/ERS/JRS/ALAT radiological criteria. An inter-rater variability analysis (Gwet's second-order agreement coefficient, AC2) was performed. The resulting Gwet's AC2 for the 2011 and 2018 ATS/ERS/JRS/ALAT radiological criteria is 0.62 (±0.05)ter-rater agreement among radiologist is moderate for both classification systems, without a significantly higher degree of agreement when applying the revised radiological criteria. - In 2018, a revision of the 2011 ATS/ERS/JRS/ALAT radiological criteria for UIP was published, part of diagnostic guidelines for idiopathic pulmonary fibrosis.- The inter-rater agreement among radiologist is moderate for both classification systems, without a significantly higher degree of agreement when applying the revised radiological criteria.Substantial racial disparities accounted for 66% of non-Hispanic Black mothers initiating breastfeeding in 2015 compared with 83% of non-Hispanic white mothers and 87% of Hispanic mothers in Tennessee. Created in 2015, Breastfeeding Sisters That Are Receiving Support (BSTARS) uses key partnerships at monthly meetings that promote supportive environments with topics around breastfeeding education, support, and women's health issues. https://www.selleckchem.com/products/tdi-011536.html The BSTARS group helps rebuild the culture surrounding the health equity of Black women and women of color and their families by offering informational and emotional support, facilitate positive changes, and heal historical trauma. BSTARS addresses barriers to breastfeeding support for Black women and women of color, including lack of support from the mother's partner, family, or health care provider, generational myths, unawareness of public health programs to support breastfeeding, educational gaps, and embarrassment. This program incorporates critical partnerships, including health care providers, birth workers, and other supporters, into the organization to offer comprehensive support for the mother's continuity of care. The environment and educational support for breastfeeding and women's health issues are addressed under the lens of health equity and eliminating barriers experienced by the mother's color, or socioeconomic status. A mother's socioeconomic status often unjustly hinders her from receiving the lactation and social support needed for healthier outcomes. In 2019, the breastfeeding initiation rate in Tennessee increased to 71.3% among non-Hispanic Blacks. BSTARS has reached >500 families since its inception. BSTARS focuses their specific intervention on all facets of the family dyad, through teaching the importance of breastfeeding and breast milk now and sustainable for the future.How can people wisely navigate social conflict? Two preregistered longitudinal experiments (Study 1 Canadian adults; Study 2 American and Canadian adults; total N = 555) tested whether encouraging distanced (i.e., third-person) self-reflection would help promote wisdom. Both experiments measured wise reasoning (i.e., intellectual humility, open-mindedness about how situations could unfold, consideration of and attempts to integrate diverse viewpoints) about challenging interpersonal events. In a month-long experiment (Study 1), participants used either a third- or first-person perspective in diary reflections on each day's most significant experience. Compared with preintervention assessments, assessments made after the intervention revealed that participants reflecting in the third person showed a significant increase in wise reasoning about interpersonal challenges. These effects were statistically accounted for by shifts in diary-based reflections toward a broader self-focus. A week-long experiment (Study 2) replicated the third-person self-reflection effect on wise reasoning (vs.

Objectives A phase III, 24-weeks Chinese clinical trial demonstrated that efficacy and safety outcomes of treatments with 40 mg/0.8 ml HS016 (n = 416) or adalimumab (n = 232) for active ankylosing spondylitis (AS) patients was comparable. https://www.selleckchem.com/products/gusacitinib.html In the present study, a subanalysis of the clinical trial was conducted to determine whether also individual efficacy indicators were comparable between HS016 and adalimumab. Methods The individual efficacy indicators total and nocturnal back pain, global assessment of disease activity, swollen joint count, Maastricht AS Enthesitis Score, Bath AS Disease Activity Index, Bath AS Functional Index, Bath AS Metrology Index and chest expansion, were assessed at baseline and every 2 weeks during the treatment period. Results This subanalysis revealed no significant difference between the patient groups treated with HS016 or adalimumab for any individual efficacy indicator investigated at any time point (all p > 0.05) beside faster total back pain score improvements in the adalimumab group on week 10, 12 and 22, which became equal at week 24. Among these indicators, chest expansion showed a significant increase at each time point compared with baseline, whereas all other efficacy indicators showed significant decreases compared with baseline at each time point (all p less then 0.05). All efficacy indicators had increased or decreased rapidly by week 2, and the values continued to increase/decrease up to week 12, with subsequent smaller changes thereafter up to week 24 of treatment. Conclusion The response trajectory of most individual efficacy indicators was comparable between HS016 and adalimumab at each time point during the 24 weeks of the trial. Clinical Trial Registration http//www.chictr.org.cn/showproj.aspx?proj=37910, identifier [ChiCTR1900022520].Cardamonin (CD), a naturally occurring chalcone derived from the Alpinia species, has been shown to exert antioxidant and anti-inflammatory activity, but its role in the prevention of acetaminophen- (APAP-) induced hepatotoxicity remains elusive. The objective of this study was to determine the protective effects of CD against APAP-induced acute liver injury (ALI) and the underlying mechanisms. Wild-type or transcription factor nuclear factor erythroid 2-related factor 2- (NFE2L2-) deficient mice were treated with CD (50 or 100 mg/kg, i.p.) or vehicle for 24 h. Subsequently, these mice were challenged with APAP (400 mg/kg, i.p.) for 6 h. Liver and blood samples were collected to evaluate liver injury and protein abundance. Treatment with CD significantly reduced APAP-induced hepatotoxicity. Furthermore, CD effectively reduced APAP-induced inflammation by inhibiting high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), and NOD-like receptor protein 3 (NLRP3) signaling. In addition, CD induced activation of sequestosome 1 (p62) and NFE2L2 signaling and facilitated autophagy. By applying autophagy inhibitor 3-methyladenine (3-MA; 20 mg/kg, i.p.), further mechanistic exploration revealed that NFE2L2 deficiency promoted autophagic activity induced by CD treatment, which was conducive to the hepatoprotective effect of CD against APAP-induced hepatoxicity in NFE2L2-/- mice. Overall, data suggest that CD has hepatoprotective effect against APAP-induced ALI, which might contribute to the activation of NFE2L2 and autophagy.The pandemic of COVID-19, caused by SARS-CoV-2, has recently overwhelmed medical centers and paralyzed economies. The unparalleled public distress caused by this pandemic mandated an urgent quest for an effective approach to manage or treat this disease. Due to their well-established anti-infectious and anti-inflammatory properties, quinine derivatives have been sought as potential therapies for COVID-19. Indeed, these molecules were originally employed in the treatment and prophylaxis of malaria, and later in the management of various autoimmune rheumatic and dermatologic diseases. Initially, some promising results for the use of hydroxychloroquine (HCQ) in treating COVID-19 patients were reported by a few in vitro and in vivo studies. However, current evidence is not yet sufficiently solid to warrant its use as a therapy for this disease. Additionally, the therapeutic effects of HCQ are not without many side effects, which range from mild gastrointestinal effects to life-threatening cardiovascular and neurological effects. In this review, we explore the controversy associated with the repurposing of HCQ to manage or treat COVID-19, and we discuss the cellular and molecular mechanisms of action of HCQ.Eicosanoids represent a family of active biolipids derived from arachidonic acid primarily through the action of cytosolic phospholipase A2-α. Three major downstream pathways have been defined the cyclooxygenase (COX) pathway which produces prostaglandins and thromboxanes; the 5-lipoxygenase pathway (5-LO), which produces leukotrienes, lipoxins and hydroxyeicosatetraenoic acids, and the cytochrome P450 pathway which produces epoxygenated fatty acids. In general, these lipid mediators are released and act in an autocrine or paracrine fashion through binding to cell surface receptors. The pattern of eicosanoid production is cell specific, and is determined by cell-specific expression of downstream synthases. Increased eicosanoid production is associated with inflammation and a panel of specific inhibitors have been developed designated non-steroidal anti-inflammatory drugs. In cancer, eicosanoids are produced both by tumor cells as well as cells of the tumor microenvironment. Earlier studies demonstrated that ping the tumor microenvironment. While the role of PGE2 will be discussed, data implicating other eicosanoids, especially products produced through the lipoxygenase and cytochrome P450 pathway will be examined. The existence of small molecular inhibitors and activators of eicosanoid pathways such as specific receptor blockers make them attractive candidates for therapeutic trials, especially in combination with novel immunotherapies such as immune checkpoint inhibitors.Elaphuri Davidiani Cornu (EDC) is the natural shedding horn of Elaphurus davidiauus Millne-Edwards that was used by people in ancient China for maintaining physical and mental health. We evaluated the antidepressant effect of EDC using depression-like animal models and explored possible mechanisms in mouse primary astrocyte cultures. We found that aqueous extracts of EDC significantly improved depression-like behavior in a mouse model of depression. The extracts enhanced expression of nerve growth factor and brain-derived neurotrophic factor neurotrophic factors in mouse prefrontal cortex and hippocampus tissues. In the mouse primary astrocyte cultures, the EDC aqueous extracts significantly increased the neurotrophic factor expression both at the transcriptional and protein levels. EDC extracts might exhibit these functions by regulating matrix metalloprotein-9 of the nerve growth factor and brain-derived neurotrophic factor metabolic pathways and might enhance expression of neurotrophic factors via the cAMP- and ERK-dependent pathways.

Brain-derived neurotrophic factor (BDNF) plays a role in synaptic plasticity and neuroprotection. BDNF has well-established pro-survival effects, whereas its precursor protein, proBDNF, induces apoptosis. Thus, it has been suggested that the proBDNF/BDNF ratio could be an indicator of neuronal health. Access to neurons is, understandably, limited. Because of their similarities, platelets have been put forward as a non-invasive biomarker of neuronal health; indeed, they store large quantities of BDNF and can release it into circulation upon activation, similarly to neurons. However, whether platelets also express the precursor proBDNF protein remains unknown. We therefore sought to characterize proBDNF levels in human platelets and plasma. The presence of proBDNF was assessed by immunoblotting, cell fractionation, flow cytometry, and confocal microscopy in washed platelets from 10 healthy volunteers. Platelets from 20 independent healthy volunteers were activated with several classical agonists and the release of BDNF and proBDNF into plasma was quantified by ELISA. Platelets expressed detectable levels of proBDNF (21±13 fmol/250x10 platelets). ProBDNF expression was mainly localized in the intracellular compartment. The proBDNF to BDNF molar ratio was ~15 in platelets and 101 in plasma. In stark contrast to the release of BDNF during platelet activation, intraplatelet and plasma concentrations of proBDNF remained stable following stimulation with classical platelet agonists, consistent with non-granular expression. Platelets express both the mature and the precursor form of BDNF. Whether the intraplatelet proBDNF to BDNF ratio could be used as a non-invasive biomarker of cognitive health warrants further investigation. Platelets express both the mature and the precursor form of BDNF. Whether the intraplatelet proBDNF to BDNF ratio could be used as a non-invasive biomarker of cognitive health warrants further investigation.Membranous nephropathy (MN) is a rare autoimmune kidney disease. Most autoimmune diseases are associated with a pro-inflammatory Th17-immune response, but little is known about immune dysregulation in MN. In China, MN was associated with exposure to fine air particulate matter (PM2.5) that could act as a danger signal and redirect immune response toward the Th2 or Th17 pathway. We aimed to analyze the cytokine profile of MN patients and to study the possible environmental factors involved in this immune reorientation, as well as the consequences on the prognosis of the disease. In this prospective study, 59 MN patients filled a comprehensive lifestyle questionnaire. https://www.selleckchem.com/products/ldc7559.html Peripheral blood cells from MN patients were stimulated in vitro to measure the cytokines produced in supernatant. Cytokine profiles of MN patients were compared to 28 healthy donors and analyzed regarding individual PM2.5 exposure. Compared to healthy donors, MN patients had higher serum levels of Th17 and Th2 cytokines IL-17A (62 pg/ml [IQR, 16-rgeting dysregulated cytokine balance could be considered for these patients at high risk of relapse.Human telomerase reverse transcriptase (hTERT) is a target antigen for cancer immunotherapy in patients with non-small cell lung cancer (NSCLC). We have tested a novel hTERT vaccine, UV1, designed to give high population coverage. UV1 is composed of three synthetic long peptides containing multiple epitopes identified by epitope spreading data from long-term survivors from previous hTERT vaccination trials. Eighteen non-HLA-typed patients with stage III/IV NSCLC with no evidence of progression after prior treatments, were enrolled in a phase I dose-escalation study of UV1 vaccination with GM-CSF as adjuvant, evaluating safety, immune response, and long-term clinical outcome. Treatment with UV1 was well tolerated with no serious adverse events observed. Seventeen patients were evaluable for tumor response; 15 patients had stable disease as best response. The median progression free survival (PFS) was 10.7 months, and the median overall survival (OS) was 28.2 months. The OS at 4 years was 39% (7/18). Five patients are alive (median survival 5.6 years), and none of these are known to have received checkpoint therapy after vaccination. UV1 induced specific T-cell responses in the majority (67%) of patients. Immune responses were dynamic and long lasting. Both immune response (IR) and OS were dose related. More patients in the highest UV1 dosage group (700 μg) developed IRs compared to the other groups, and the IRs were stronger and occurred earlier. Patients in this group had a 4-year OS of 83%. The safety and clinical outcome data favor 700 μg as the preferred UV1 dose in this patient population. These results provide a rationale for further clinical studies in NSCLC with UV1 vaccination in combination with immune checkpoint blockade. https//www.clinicaltrials.gov, identifier NCT0178909. https//www.clinicaltrials.gov, identifier NCT0178909.B cell-activating factor (BAFF) production is increased in septic patients. However, the specific role of BAFF in sepsis remains unknown. This study was designed to investigate the expression and function of BAFF in an experimental endotoxemia model and to identify the potential mechanisms. We established an endotoxemia mouse (6-8 weeks, 20-22 g) model by administering 30 mg/kg lipopolysaccharide (LPS). BAFF levels in the circulating system and organ tissues were measured 4 and 8 h after LPS injection. Survival rates in the endotoxemia mice were monitored for 72 h after BAFF blockade. The effects of BAFF blockade on systemic and local inflammation, organ injuries, and intestinal barrier function were also evaluated 4 h after LPS treatment. BAFF production was systemically and locally elevated after LPS challenge. BAFF blockade improved the survival rate, systemic inflammation, and multi-organ injuries. Moreover, BAFF blockade attenuated both intestinal inflammation and impaired intestinal permeability. BAFF blockade upregulated ZO-1 and occludin protein levels via the NF-κB/MLCK/MLC signaling pathway. These results suggested that BAFF blockade protects against lethal endotoxemia at least partially by alleviating inflammation, multi-organ injuries, and improving intestinal barrier function and provides a novel focus for further research on sepsis and experimental evidence for clinical therapy.

Infertility caused by reproductive pathologies plays a significant role in animal breeding and could result in massive economic losses to livestock owners. Hence, this study was designed to allocate various pathological lesions in the female reproductive tract of she-camels ( ) slaughtered in Egypt and isolate the causative agents associated with those pathologies. A total of 500 genitalia of adult nonpregnant she-camels aged between 6 and 15 years old were collected from three slaughterhouses at the Giza Governorate, Egypt, from August 2017 to August 2019. The uterus, cervix, and vagina were examined pathologically and microbiologically. The uteri of 152 cases (30.4%), cervices of 24 cases (4.8%), and vaginae of 20 cases (4.2%) showed pathological abnormalities. https://www.selleckchem.com/products/5-chloro-2-deoxyuridine.html The uterine inflammatory lesions were detected in 119 cases (23.8%), and the non-inflammatory lesions were detected in 58 cases (11.6%). Pathological changes of the cervix comprised 4.8%, whereas vaginal abnormalities represented 4%. The totalt to the environment and, consequently, human. In addition, attention should be paid toward the possibility of infected she-camels to transmit such infections to farm animals in contact. This study aimed to inspect the occurrence of ( ) in falcons from the central area of Saudi Arabia. Blood samples from 100 falcons species, including 55 , 22 , 13 and 10 , were collected from November 2018 to April 2019 and examined for by microscopic examination and nested PCR, targeting a cytochrome b ( ) gene. The prevalence was 1% by microscopic examination. The prevalence rate of was 1% by the microscopic method and 3% by PCR. Only was infected. In the sequence and phylogenetic analyses, the two sequences were 100% identical and closely related to the Lithuanian isolate with 99.35% identity. This study presents the first report of molecular detection and characterization of in from the Kingdom of Saudi Arabia. This study presents the first report of molecular detection and characterization of H. tinnunculai in F. cherrug from the Kingdom of Saudi Arabia. In recent years, lead (Pb) has arisen as a foremost contaminant due to overpopulation, rapid industrialization, and expansion that could contaminate the human food chain. However, the correlation between the environmental contamination of Pb and its spatial transfer to the dairy products is still unmapped. In this paper, we intend to evaluate the concentration of environmental Pb and its spatial distribution in dairy feed and products in Narayangonj, a highly polluted district of Bangladesh. A total of 125 samples of soil, water, forage, and milk were collected from five upazilas (Narayangonj Sadar, Bondor, Rupgonj, Araihazar, and Sonargoan) of Narayangonj. The samples were digested by acid digestion, and Pb was detected by flame atomic absorption spectrophotometer and graphite furnace atomic absorption spectrometer. The bioconcentration factor of the samples was also calculated. In this study, 25% of the soil, 20% of the water, 5% of the forage, and 2% of the milk samples contained Pb at a variable levapted to cease the residue to the human food chain. The study of an embryosis is crucial in genetics for breed improvement and reproduction in livestock, identifying the causes of infertility, and stem cell application. Meanwhile, the problem of nucleic acid denaturation observed during embryo development is yet to be resolved. This study was set out to analyze the nucleic acid denaturation during the development of embryos. Using an fertilization-embryo in porcine, the cell development and apoptosis were evaluated by adding rapamycin by concentration to the TCM-199 containing 10% FBS or 10% porcine follicle fluid (pFF). Real-time PCR, zymography, DNA fragment, Western blot, and immunofluorescence analysis were also carried out to determine the development rate of inner cell mass in the fertilization-embryo. The findings indicated that the addition of rapamycin to the 10% pFF group during maturation led to an increase in the rates of cleavage and blastocyst development and the expression of active matrix metallopeptidase (MMP-9), while nucleic acid denaturation was suppressed. In other words, the addition of rapamycin was found to increase the expression of MMP-2 in the inner cell mass and trophoblast, while it inhibited apoptosis. The addition of rapamycin influences the regulation of apoptosis and MMPs, and based on this, it is presumed to have a positive effect on blastocyst development. The addition of rapamycin influences the regulation of apoptosis and MMPs, and based on this, it is presumed to have a positive effect on blastocyst development. The aim of this research is to investigate the relationship level of oxytocin released and the tactile stimulation of the cervix in Holstein cattle from the northwestern arid regions in México. The cervixes of 10 Holstein Friesian dairy cows in mid-lactation were manually stimulated for 60 sec. Oxytocin released in the blood was analyzed before and after stimulation. The enzyme-linked immunosorbent assay was used in the analysis to make oxytocin detectable by spectrometry techniques and by converting the luminescence absorbance of each sample into pg per mol. The study revealed that tactile stimulation of the cervix increased oxytocin levels. The highest increase in oxytocin level was 10,940.8222 pg/mol, while the lowest increase in oxytocin level was 1,830.94254 pg/mol. Besides, the milk production by tactile stimulation of the cervix had a higher milk yield and a value of 9.4 × 10 ( < 0.05) in comparison to the monthly average without tactile stimulation. Tactile stimulation of the cervix activates the Ferguson reflex and increases the oxytocin released in the blood and increases the milk released from the alveolar glands. Tactile stimulation of the cervix activates the Ferguson reflex and increases the oxytocin released in the blood and increases the milk released from the alveolar glands. Selenium (Se), as the form of selenite, is commonly supplemented in poultry diet, which has low bioavailability and high toxicity. Here, we compared the effects of the supplementation of the diet with Se nanoparticles (nano-Se) on the growth, sexual behavior, and reproductive performance (gonad size, sperm quality traits, and plasma testosterone levels for males and egg production for females) of Japanese quail ( ). Quail chicks ( = 300) aging 14 days were divided into three groups Group 1 (basal diet and Se at 0.2 mg/kg ration), Group 2 (basal diet and nano-Se at 0.2 mg/kg ration), and Group 3 (basal diet and nano-Se at 0.1 mg/kg ration). Several parameters relating to body weight and egg were measured. Sexual behaviors of the birds were observed by continuous visual scanning. The sperm viability, sperm morphology, and concentration of spermatozoa were determined after staining and microscopic examination. The plasma testosterone levels were determined by indirect enzyme immunoassay assay. The Se concentrations in the testicular, ovarian, and ration samples were measured by flame emission atomic absorption spectrophotometer.

This was followed by misdiagnosis/delayed diagnosis (n = 47), and failure of informed consent (n = 34). The highest number of malpractice claims with a total of 53 cases was from 1991 to 2000. The highest mean amount per payment was in the past decade (2011-2020) with a mean of $3,841,052.68. https://www.selleckchem.com/products/sodium-hydroxide.html Conclusions and Relevance Over the past century, improper performance/procedure, delayed/misdiagnosis, and failure of informed consent were the most common reasons for litigations related to facial nerve paralysis.Type 1 diabetes occurs as a consequence of progressive autoimmune destruction of beta cells. A potential treatment for this disease should address the immune attack on beta cells and their preservation/regeneration. The objective of this study was to elucidate whether the immunomodulatory synthetic oligonucleotide IMT504 was able to ameliorate diabetes in NOD mice and to provide further understanding of its mechanism of action. We found that IMT504 restores glucose homeostasis in a diabetes mouse model similar to human type 1 diabetes, by regulating expression of immune modulatory factors and improving beta cell function. IMT504 treatment markedly improved fasting glycemia, insulinemia, and homeostatic model assessment of beta cell function (HOMA-Beta cell) index. Moreover, this treatment increased islet number and decreased apoptosis, insulitis, and CD45+ pancreas-infiltrating leukocytes. In a long-term treatment, we observed improvement of glucose metabolism up to 9 days after IMT504 cessation and increased survival after 15 days of the last IMT504 injection. We postulate that interleukin (IL)-12B (p40), possibly acting as a homodimer, and Galectin-3 (Gal-3) may function as mediators of this immunomodulatory action. Overall, these results validate the therapeutic activity of IMT504 as a promising drug for type 1 diabetes and suggest possible downstream mediators of its immunomodulatory effect.Background This study aims to consolidate all available articles on this topic and evaluate MSA effectiveness in the management of gastroesophageal reflux disease (GERD). Matherials and Methods We conducted an electronic systematic search using MEDLINE databases (PubMed), EMBASE, and Web of Science. An electronic systematic search of articles comparing preoperative and postoperative health-related quality of life (GERD-HRQL) scores in patients who underwent MSA placement for management of GERD following bariatric surgery was performed. Three retrospective studies totaling 33 patients met the inclusion criteria and were included in this meta-analysis. Results The pooled mean difference in change from preoperative GERD-HRQL score was 17.5 (95% CrI; -22.88 to -12.20) and it was statistically significant. The between-study variability is 3.621 (95% HPD; 1.39 4.99) with low heterogeneity (I2 = 15%; 95% HPD; 2.1 26.2%). Conclusions MSA for refractory GERD following bariatric surgery appears feasible. Prospective randomized controlled with standardized surgical technique and objective follow-up evaluation is needed to better assess short- and long-term efficacy.Objective The effectiveness and feasibility of the primary closure after laparoscopic common bile duct exploration (LCBDE) have been well demonstrated, however, the incidence of postoperative bile leakage after LCBDE remains high. The current study aimed at investigating whether our new suturing method could reduce the risk of bile leakage after LCBDE. Materials and Methods This retrospective study included 81 patients who underwent primary two-layered closure or traditional primary closure of the common bile duct (CBD) after LCBDE, and the related clinical data were compared and analyzed. Results The primary two-layered closure group had a lower rate of bile leakage compared with the traditional primary closure group (P  less then  .05). There were no significant differences in additional parameters, such as operative time, estimated blood loss, postoperative stay duration, time to drain removal, postoperative pancreatitis, stone recurrence, and overall morbidity. No patients developed bile duct stenosis during the follow-up period. Conclusions Primary two-layered closure of CBD can reduce the postoperative bile leakage after LCBDE. Moreover, it is a safe and effective therapeutic option for patients with choledocholithiasis.Background Incisional hernias are a common complication of abdominal surgery (10%-35%) and are notorious for recurrence. Laparoscopic incisional hernia repair (LIHR) was first performed in 1991 and is reported to have lower recurrence rates. Few studies to date have assessed quality of life (QoL) resulting from a repair. The purpose of this observational study was to present a 12-year experience performing LIHR, with a focus on the impact on QoL. Methods All adult patients undergoing elective LIHR performed by a single surgeon, whether primary or recurrent, were included in the study. The data collection was performed prospectively between 2007 and 2019 to include demographic details, intraoperative findings and postoperative short- and longterm outcomes. We used the Carolinas Comfort Scale (CCS) to assess QoL following surgery. Results Ninety-seven patients were included in the study. Patients had a median age of 57 years, body mass index of 32 kg/m2, 35% were male and 88% were American Society of Anesthesiologists (ASA) class I or II. The duration of surgery was 90 minutes*. Nineteen percent of patients had complications during or after surgery; 1 (1%) had recurrence. length of stay in hospital was 1* (0-12) days and long-term follow-up period was 42* (2-140) months after surgery. Time of return to daily activities was 14* (1-365) days. Eighty-six percent of patients rated their experience undergoing LIHR as "Excellent" or "Good". Regarding QoL after surgery, scores on the CCS indicated that 82% of patients had minimal or no discomfort following surgery, and only 1% had significant discomfort. *Presented as median. Conclusions The technique for LIHR displayed in this study is safe and effective. There was an acceptable rate of complications, with a low recurrence rate. Patients were highly satisfied and had a good QoL after the procedure. Research Registry ID Number researchregistry6056.

Nonobstetric surgery during pregnancy should be avoided if possible, but when surgery is required, an obstetrician should be part of the perioperative team. In general, preoperative assessment is similar regardless of whether a woman is pregnant, but cardiovascular, pulmonary, hematologic, and renal changes of pregnancy can increase surgical risk and must be taken into account. Special management considerations include pregnancy-associated laboratory changes, timing of surgery, anesthesia choice, intubation precautions, patient positioning, preoperative blood typing, intraoperative fetal monitoring, and venous thromboembolism prophylaxis.Relationships between µ-opioid receptor (MOR) efficacy and effects of mitragynine and 7-hydroxymitragynine are not fully established. We assessed in vitro binding affinity and efficacy and discriminative stimulus effects together with antinociception in rats. The binding affinities of mitragynine and 7-hydroxymitragynine at MOR (Ki values 77.9 and 709 nM, respectively) were higher than their binding affinities at κ-opioid receptor (KOR) or δ-opioid receptor (DOR). [35S]guanosine 5'-O-[γ-thio]triphosphate stimulation at MOR demonstrated that mitragynine was an antagonist, whereas 7-hydroxymitragynine was a partial agonist (Emax = 41.3%). In separate groups of rats discriminating either morphine (3.2 mg/kg) or mitragynine (32 mg/kg), mitragynine produced a maximum of 72.3% morphine-lever responding, and morphine produced a maximum of 65.4% mitragynine-lever responding. Other MOR agonists produced high percentages of drug-lever responding in the morphine and mitragynine discrimination assays 7-hydroxymitragyninefinity than mitragynine and is an MOR partial agonist. In rats, intraperitoneal mitragynine exhibits a complex pharmacology including MOR agonism; 7-hydroxymitragynine has higher MOR potency and efficacy than mitragynine. These results are consistent with 7-hydroxymitragynine being a highly selective MOR agonist and with mitragynine having a complex pharmacology that combines low efficacy MOR agonism with activity at nonopioid receptors.Currently available tocolytics are ineffective at significantly delaying preterm birth. This is due in part to our failure to better understand the mechanisms that drive spontaneous preterm labor (sPTL). Cyclic nucleotides are not the primary contributors to myometrial quiescence, but instead nitric oxide (NO)-mediated protein S-nitrosation (SNO) is integral to the relaxation of the tissue. Connexin-43 (Cx43), a myometrial "contractile-associated protein" that functions as either a gap junction channel or an hemichannel (HC), was the focus of this study. https://www.selleckchem.com/products/pterostilbene.html Protein analysis determined that Cx43 is downregulated in sPTL myometrium. Furthermore, Cx43 is S-nitrosated by NO, which correlates with an increase of phosphorylated Cx43 at serine 368 (Cx43-pS368 -gap junction inhibition) as well as an increase in the HC open-state probability (quiescence). Pharmacologic inhibition of Cx43 with 18β-glycyrrhetinic acid (18β-GA) exhibits a negative inotropic effect on the myometrium in a dose-dependent manner, as does adminia novel approach to tocolysis that leverages maladjusted pathways in women who experience sPTL.Understanding genome organization requires integration of DNA sequence and three-dimensional spatial context; however, existing genome-wide methods lack either base pair sequence resolution or direct spatial localization. Here, we describe in situ genome sequencing (IGS), a method for simultaneously sequencing and imaging genomes within intact biological samples. We applied IGS to human fibroblasts and early mouse embryos, spatially localizing thousands of genomic loci in individual nuclei. Using these data, we characterized parent-specific changes in genome structure across embryonic stages, revealed single-cell chromatin domains in zygotes, and uncovered epigenetic memory of global chromosome positioning within individual embryos. These results demonstrate how IGS can directly connect sequence and structure across length scales from single base pairs to whole organisms.Granulomatosis with polyangiitis is an antineutrophil cytoplasmic antibody-associated vasculitis that primarily affects small vessels. The disease typically affects the respiratory tract and kidneys but has also been known to involve the gastrointestinal tract, genitourinary tract, thyroid, and liver. Cardiac involvement is rare. Coronary artery aneurysms (CAAs) are an extremely uncommon finding, with only 1 reported case in an adult patient and no pediatric cases reported to date. Here, we report the unique case of a child with granulomatosis with polyangiitis who initially presented with fever of unknown origin and pulmonary and renal symptoms with no cardiac complaints. An echocardiogram revealed severe bilateral fusiform CAAs. Because of the high risk of mortality posed by the severity of her renal and cardiac disease, the patient was managed with intensive induction immunosuppression with steroids, rituximab, and cyclophosphamide. She is maintained on steroids, rituximab, aspirin, and warfarin with improved renal function but no change in her CAAs. Artificial intelligence algorithms have the potential to become an important diagnostic tool to optimize stroke workflow. Viz LVO is a medical product leveraging a convolutional neural network designed to detect large-vessel occlusions on CTA scans and notify the treatment team within minutes via a dedicated mobile application. We aimed to evaluate the detection accuracy of the Viz LVO in real clinical practice at a comprehensive stroke center. Viz LVO was installed for this study in a comprehensive stroke center. All consecutive head and neck CTAs performed from January 2018 to March 2019 were scanned by the algorithm for detection of large-vessel occlusions. The system results were compared with the formal reports of senior neuroradiologists used as ground truth for the presence of a large-vessel occlusion. A total of 1167 CTAs were included in the study. Of these, 404 were stroke protocols. Seventy-five (6.4%) patients had a large-vessel occlusion as ground truth; 61 were detected by the system. Sensitivity was 0.

Thus, the result also suggests the evolution of binding sites is spatially cooperative. The proposed method as an effective tool of considering evolutionary information can be widely used for the nucleic acid-/protein-binding site prediction and functional motif finding.During the 18th century, debates about what constituted the sublime flourished in Europe, and particularly in Germany. These debates were nourished by two different visions The Kantian concept supposed that the sublime is supra-sensible and rooted in reason (Logos) rather than in the object, thus provoking a mental state of tension between nature and art; Edmund Burke's concept, on the other hand, conceived of the sublime as a bodily immersive experience, which we here define as "sensitive" sublime. In summary, Burke's view of the sublime is rooted in the senses and not in the power of reason, unlike Kant's. This was to disrupt the mainstream ideas of that time, unconsciously anticipating some of the recent neuroaesthetic acquisitions regarding the central role played by the sensory apparatus in the experience of beauty and of the sublime. Insects rely on their sense of smell to locate food and hosts, find mates and select sites for laying eggs. Use of volatile compounds, such as essential oils (EOs), to repel insect pests and disrupt their olfaction-driven behaviors has great practical significance in integrated pest management. However, our knowledge on the olfaction-based mechanisms of EO repellency is quite limited. We evaluated the repellency of peppermint oil and nine plant EO components in Drosophila melanogaster, a model insect for olfaction study, and D. suzukii, a major fruit crop pest. All nine volatiles, menthone, (-)-menthol, menthyl acetate, (R)-(+)-limonene, nerol, (+)-fenchone, (-)-α-thujone, camphor, norcamphor and peppermint oil, elicited repellency in D. melanogaster in a dose-dependent manner. Most of the compounds, except camphor, also elicited repellency in D. suzukii. Menthone, (R)-(+)-limonene and (+)-fenchone were the most potent repellents against D. suzukii. Repellency was reduced or abolished in two D. melanogaster mutants of the odorant receptor co-receptor (Orco), indicating that the observed repellency is odorant receptor (Or)-mediated. Repellency by peppermint oil, menthone, (R)-(+)-limonene, (-)-α-thujone and norcamphor also involves Or-independent mechanism(s). Single sensillum recording from both species revealed that common and distinct Ors and olfactory receptor neurons were activated by these compounds. The tested plant EO components evoke repellency by activating multiple Ors in both Drosophila species. Our study provides a foundation for further elucidation of the mechanism of EOs repellency and species-specific olfactory adaptations. © 2021 Society of Chemical Industry. The tested plant EO components evoke repellency by activating multiple Ors in both Drosophila species. Our study provides a foundation for further elucidation of the mechanism of EOs repellency and species-specific olfactory adaptations. © 2021 Society of Chemical Industry. Circadian rhythm controls complicated physiological activities in organisms. Circadian clock genes have been related to tumour progression, but its role in glioma is unknown. Therefore, we explored the relationship between dysregulated circadian clock genes and glioma progression. Samples were divided into different groups based on circadian clock gene expression in training dataset (n=672) and we verified the results in other four validating datasets (n=1570). The GO and GSEA enrichment analysis were conducted to explore potential mechanism of how circadian clock genes affected glioma progression. The single-cell RNA-Seq analysis was conducted to verified previous results. The immune landscape was evaluated by the ssGSEA and CIBERSORT algorithm. Cell proliferation and viability were confirmed by the CCK8 assay, colony-forming assay and flow cytometry. The cluster and risk model based on circadian clock gene expression can predict survival outcome. Samples were scoring by the least absolute shrinkage and selection operator regression analysis, and high scoring tumour was associated with worse survival outcome. Samples in high-risk group manifested higher activation of immune pathway and cell cycle. Tumour immune landscape suggested high-risk tumour infiltrated more immunocytes and more sensitivity to immunotherapy. Interfering TIMELESS expression affected circadian clock gene expression, inhibited tumour cell proliferation and arrested cell cycle at the G0/G1 phase. Dysregulated circadian clock gene expression can affect glioma progression by affecting tumour immune landscape and cell cycle. The risk model can predict glioma survival outcome, and this model can also be applied to pan-cancer. Dysregulated circadian clock gene expression can affect glioma progression by affecting tumour immune landscape and cell cycle. The risk model can predict glioma survival outcome, and this model can also be applied to pan-cancer. To determine the relationship between multiple medications and falls. This case-control and case-crossover study was carried out at Kudanzaka Hospital in Chiyoda, Tokyo, Japan. A total of 325 patients who experienced their first falls when hospitalized between January 2016 and November 2018, and 1285 controls matched by sex, age and clinical departments were included in this study. Hospitalization duration and fall risk score were adjusted for in the analyses. In the case-control study, multivariable logistic regression showed that increasing the intake of oral medications was not significantly associated with the incidence of falls (odds ratio 1.02, 95% confidence interval 0.998-1.049). In contrast, drugs prescribed with special caution in accordance with the Elderly Oral Medication Guidelines were significantly associated with falls (odds ratio 1.17, 95% confidence interval 1.09-1.26). A similar pattern was observed in the case-crossover analysis. Among the drugs to be prescribed with special caution according to the guidelines, atypical antipsychotics, non-benzodiazepine hypnotics and magnesium oxide were significantly associated with the risk of falls. The drugs to be prescribed with special caution according to the guidelines were associated with an increased fall risk. The risk of falls in hospitalized older people due to multiple medications varies among medications. https://www.selleckchem.com/products/omaveloxolone-rta-408.html Geriatr Gerontol Int ••; •• ••-•• Geriatr Gerontol Int 2021; •• ••-••. The drugs to be prescribed with special caution according to the guidelines were associated with an increased fall risk. The risk of falls in hospitalized older people due to multiple medications varies among medications. Geriatr Gerontol Int ••; •• ••-•• Geriatr Gerontol Int 2021; •• ••-••.