Stent grafts are utilized to treat and exclude visceral arterial aneurysms while preserving flow through the vessel. Stent-associated thrombocytopenia is a rare complication not typically seen with modern stents. The following case describes the clinical presentation of stent kinking and consumptive coagulopathy. Stent-associated microangiopathic hemolytic anemia was inferred from protracted workup and exclusion of alternative diagnoses. Despite the risk of arterial puncture in the setting of profound thrombocytopenia, the patient was successfully treated with stent embolization with near immediate rebound in platelet count. This case report documents the presentation of rare stent-associated thrombocytopenia leading to challenging diagnostic evaluation and necessitating high-risk intervention.Although retirement age is increasing in aging societies, its impact on individuals and communities is unclear. This study examined how age moderates the linkage between transition into retirement and participation in productive and non-productive social activities after retirement, using a nationwide longitudinal survey with a probability sample of Japanese aged 60 and over (n = 3,493). Multinomial logistic regression analyses were performed to predict changes in volunteering and hobbies/learning during 3-5 years of follow-up and their participation level at the follow-up. The significant interactions between change in work status (remained working as reference, full/partial retirement, remained not-working) and age at baseline showed that fully retired persons were more likely to increase these activities than remained workers only when they retired by their early seventies. Thus it is important to encourage engagement in social activities before retirement and remove psychological and environmental barriers that hinder starting new activities at old age. Commercial truck drivers (CTDs) are significantly affected by shoulder injuries; however, little is known about the unique mechanisms of injury (MOIs), specific injuries, or possible preventive measures among this group of workers. This study characterized the MOIs, musculoskeletal disorders (MSDs), and factors associated with MSDs of the shoulder among a group of CTDs. A retrospective medical record review was conducted of CTDs between 21 and 65 years of age who were seen for MSDs of the shoulder between 2007 and 2015. A total of 130 CTDs were included, who were aged 21 to 65 years. Commercial truck drivers were most often injured during a fall (35%) or while using chains, tarps, or straps (31%). The two most common MSDs were unspecified sprains/strains (58%) and rotator cuff tears (24%). #link# Age was found to be associated with all MSDs ( .001) and an increased risk of developing rotator cuff tears ( .005). Seventy-four percent of CTDs who experienced a rotator cuff tear were 46 years of age or older. This study highlights the course of the injury in terms of diagnostics such as magnetic resonance imaging (MRI) and referral for surgery and describes the occupational activities associated with CTDs. These findings can inform employer injury prevention programs, patient and health care provider education, and future interventional research. This study highlights the course of the injury in terms of diagnostics such as magnetic resonance imaging (MRI) and referral for surgery and describes the occupational activities associated with CTDs. These findings can inform employer injury prevention programs, patient and health care provider education, and future interventional research. Burnout is a common phenomenon among health care providers known to adversely affect their mental health and clinical acumen. As mindfulness has been shown to diminish burnout with large-scale interventions, our aim was to assess whether smaller, on-shift activities aimed at increasing mindfulness could decrease burnout among staff in a pediatric emergency department (PED). Prior to the implementation of a series of mindfulness-based activities, a diverse cohort of PED staff including nurses, physicians, nurse practitioners, technicians, and administrative personnel completed electronic preintervention surveys about their demographics, personal mindfulness engagement, and individual baseline burnout level using the Maslach Burnout Inventory (MBI). Trained nurses and physicians served as champions who coordinated on-shift mindfulness activities, and burnout levels were subsequently reassessed using a postintervention survey. Among 83 eligible staff, 75 completed the preintervention and 69 completed the pantly reduce burnout levels. Hospital leadership should consider dedicating resources to more intensive mindfulness activities to combat amplified burnout levels among emergency department staff. Effective management of health emergencies is an important strategy to improve health worldwide. One way to manage health emergencies is to build and sustain national capacities. The Ebola epidemic of 2014 to 2015 resulted in greater infection prevention and control (IPC) capacity in Liberia, but few studies have investigated if and how that capacity was sustained. The purpose of this study was to examine the maintenance of IPC capacity in Liberia after Ebola. For this case study, data were collected via direct observation of nurse practice, semistructured interviews, and document collection. Data were collected in two counties in Liberia. Data were analyzed using directed content and general thematic analysis using codes generated from the theoretical framework, which describes an organization's intangible occupational health resources. Thirty-seven nurses from 12 facilities participated. Ebola was a seminal event in the development of safety capital in Liberia, particularly regarding nurse knowledgent by donor countries in personal protective equipment, access to water, and clinician training.Iliac artery aneurysms (IAA) are associated frequently with abdominal aortic (AAA) and other degenerative large-vessel aneurysms. Concurrent fistulization of the aortoiliac tree into the gastrointestinal tract (GIT) and bladder is exceptionally rare. https://www.selleckchem.com/products/arry-380-ont-380.html report a unique case of concurrent ilio-enteric and ilio-vesical fistula arising from a large aorto-iliac aneurysm.

In addition, electrochemical measurements demonstrated that the coating application does not increase the susceptibility of medical-grade stainless steel to corrosion. In vitro cell testing using all cell types with which such coatings come into contact in the body (osteoblasts, chondrocytes, and mesenchymal stem cells (MSCs)) showed very good biocompatibility towards all of the mentioned cells. It further confirmed that the coatings promoted MSCs osteogenic differentiation, which is the desired mode of action for orthopedic implants.The level of spatial accessibility is directly related to how street networks are connected. Connected or so-called "permeable" network systems encourage walking, cycling, and riding public transit. Fast urbanization during the recent decades in the world metropolises has created separated urban areas. Gated-style apartment complexes have led this segregation more obviously with their inaccessible internal networks. Opening the internal network of apartment complexes and redesigning the pedestrian paths among apartment buildings will significantly mitigate these networks' adverse effects on network permeability and increase spatial accessibility. This paper analyzes how such an opening design proposal for apartment complexes can change spatial accessibility using the case study of Mapo-gu, Seoul, Korea. It simulates three types of street networks and compares the results of accessibility in three conditions (1) the internal networks of apartment complexes are not used by outsiders; (2) the internal networks of apartment complexes are open to outsiders with its existing entrances and path; and (3) the internal networks of sites are opened and redesigned by the Voronoi diagram method, which generates the optimal shortest path. An urban network analysis tool, Rhinoceros three-dimensional software, and Grashopper3D visual programming language have been used for the study results, which shows that a policy change in opening the intra-network of apartment complexes is likely to make the city more permeable. In addition, this study suggests extra modification on the pedestrian path for a higher level of accessibility in neighborhoods.The design of high-performance nanocomposites with improved mechanical, thermal or optical properties compared to starting polymers has generated special interest due to their use in a wide range of targeted applications. In the present work, polymer nanocomposites composed of polyurethane elastomers based on polycaprolactone or polycaprolactone/poly(ethylene glycol) soft segments and titanium dioxide (TiO2) nanoparticles as an inorganic filler were prepared and characterized. Initially, the surface of TiO2 nanoparticles was modified with (3-iodopropyl) trimethoxysilane as a coupling agent, and thereafter, the tertiary amine groups from polyurethane hard segments were quaternized with the silane-modified TiO2 nanoparticles in order to ensure covalent binding of the nanoparticles on the polymeric chains. In the preparation of polymer nanocomposites, two quaternization degrees were taken into account (1/1 and 1/0.5 molar ratios), and the resulting nanocomposite coatings were characterized by various methods (Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, contact angle, thermogravimetric analysis, dynamic mechanical thermal analysis). The mechanical parameters of the samples evaluated by tensile testing confirm the elastomeric character of the polyurethanes and of the corresponding composites, indicating the obtaining of highly flexible materials. The absorbance/transmittance measurements of PU/TiO2 thin films in the wavelength range of 200-700 nm show that these partially block UV-A radiation and all UV-B radiation from sunlight and could possibly be used as UV-protective elastomeric coatings.Electromagnetic tracking is a safe, reliable, and cost-effective method to track medical instruments in image-guided surgical navigation. However, https://www.selleckchem.com/products/ml141.html and magnetic field distortions heavily impact the accuracy of tracked position and orientation. The use of redundant magnetic sensors can help to map and mitigate for patient movements and magnetic field distortions within the tracking region. We propose a planar inductive sensor design, printed on PCB and embedded into medical patches. The main advantage is the high repeatability and the cost benefit of using mass PCB manufacturing processes. The article presents new operative formulas for electromagnetic tracking of planar coils on the centimetre scale. The full magnetic analytical model is based on the mutual inductance between coils which can be approximated as being composed by straight conductive filaments. The full model is used to perform accurate system simulations and to assess the accuracy of faster simplified magnetic models, which are necessary to achieve real-time tracking in medical applications.Every woman needs to know about the importance of the function of pelvic-floor muscles and pelvic organ prolapse prevention, especially pregnant women because parity and labor are the factors which have the biggest influence on having pelvic organ prolapse in the future. In this article, we searched for methods of training and rehabilitation in prepartum and postpartum periods and their effectiveness. The search for publications in English was made in two databases during the period from August 2020 to October 2020 in Cochrane Library and PubMed. 77 articles were left in total after selection-9 systematic reviews and 68 clinical trials. Existing full-text papers were reviewed after this selection. Unfinished randomized clinical trials, those which were designed as strategies for national health systems, and those which were not pelvic-floor muscle-training-specified were excluded after this step. Most trials were high to moderate overall risk of bias. #link# Many of reviews had low quality of evidence. Despite clinical heterogeneity among the clinical trials, pelvic-floor muscle training shows promising results. Most of the studies demonstrate the positive effect of pelvic-floor muscle training in prepartum and postpartum periods on pelvic-floor dysfunction prevention, in particular in urinary incontinence symptoms. However more high-quality, standardized, long-follow-up-period studies are needed.

Consequently, our data support that the repertoire of actionable mutations present in every osteosarcoma cell is largely limited to cell cycle G1 mutations. Since they occur in mutually exclusive combinations favoring either CDK2 or CDK4/6 pathway activation, we propose a new genomically-based algorithm to direct patients to correct clinical trial options. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland. The Illness Identity model posits that self-stigma reduces hope and self-esteem among persons with severe mental illnesses, impacting a range of outcomes. The "insight paradox" anticipates that the negative effects of self-stigma are amplified by insight. This study tested these predictions using both cluster and path analyses. A total of 117 participants meeting the criteria for schizophrenia-spectrum disorders completed measures of self-stigma, self-esteem, hopelessness, insight, social functioning, coping, and symptoms. Cluster analysis supported the insight paradox; persons with low self-stigma/high insight had fewer psychiatric symptoms and better interpersonal functioning than persons with high self-stigma/low insight. #link# Path analysis did not support the insight paradox, but indicated that self-stigma and insight impact different outcomes. Findings suggest that support for the predictions of the Illness Identity model and insight paradox are supported may depend on analytic method. Finding suggest that the benefits of self-stigma reduction may be constrained by insight. Finding suggest that the benefits of self-stigma reduction may be constrained by insight.In humans, IL-8 (CXCL8) is a key chemokine for chemotaxis of polymorphonuclear leukocytes and monocytes/macrophages when acting on CXCR1 and CXCR2. CXCL8 activity on neutrophils includes chemotaxis and eliciting the extrusion of neutrophil extracellular traps (NETs). In this study, we show that concentrations of IL-8 that induce NETosis surpass in at least one order of magnitude those required to elicit chemoattraction in human neutrophils. IL-8-induced NETosis was less dependent on G-proteins than migration, while extracellular Ca+2 chelation similarly inhibited both processes. Reactive oxygen species (ROS) were more important for NETosis than for chemotaxis as evidenced by neutralization with N-acetyl -cysteine. Interestingly, selective blockade with anti-CXCR1 mAb inhibited NETosis much more readily than chemotaxis, while pharmacological inhibition of both CXCR1 and CXCR2, or selective inhibition for CXCR2 alone, similarly inhibited both functions. Together, these results propose a model according to which low concentrations of IL-8 in a gradient attract neutrophils to the inflammatory foci, while high receptor-saturating concentrations of IL-8 give rise to NETosis once leukocytes reach the core of the inflammatory insult.Violence committed by individuals with severe mental disorders has become a growing focus of interest among physicians, law enforcement officials, and the general population. Homicide involving relatives, specially parricide, matricide, and filicide, despite the relatively low incidence of these crimes, may be enigmatic, so forensic psychiatrist are frequently called on the courts to answer questions about insanity and criminal responsibility. The current study aims to describe Brazilian cases of parricide, matricide, and filicide associated with presence of major mental disorders and personality disorders, discussing the assessment of criminal responsibility in each case. The case series described were specifically related to people with mental illness, as bipolar disorder, schizophrenia, and borderline personality with comorbidity of drug abuse. Two of them were considered not guilty by reason of insanity, and the other one was considered partially criminally responsible, according to Brazilian Law and Forensic Psychiatric Reports of the cases. The justice determined compulsory psychiatric treatment for all of them. The question of criminal responsibility of individuals with mental disorders is challenging for criminal justice, psychiatry, and society. Adequate treatment is mandatory to prevent crimes involving mental disorders, as shown in literature. The verification of criminal responsibility is essential for persons' adequate referral in any system of criminal law, thus protecting human rights and referring those who need psychiatric treatment.Drug addiction is a devastating disorder with a huge economic and social burden for modern society. Although an individual may slip into drug abuse throughout his/her life, adolescents are at higher risk, but, so far, only a few studies have attempted to elucidate the underlying cellular and molecular bases of such vulnerability. Indeed, preclinical evidence indicates that psychostimulants and adolescence interact and contribute to promoting a dysfunctional brain. In this review, we have focused our attention primarily on changes in neuroplasticity brought about by cocaine, taking into account that there is much less evidence from exposure to cocaine in adolescence, compared with that from adults. This review clearly shows that exposure to cocaine during adolescence, acute or chronic, as well as contingent or non-contingent, confers a vulnerable endophenotype, primarily, by causing changes in neuroplasticity. Given the close relationship between drug abuse and psychiatric disorders, we also discuss the translational implications providing an interpretative framework for clinical studies involving addictive as well as affective or psychotic behaviours. Using two intensive longitudinal data sets with different timescales (90minutes, daily), we examined emotion network density, a metric of emotional inflexibility, as a predictor of clinical-level anxiety and depression. Mobile-based intensive longitudinal assessments. 119 participants (61 anxious and depressed, 58 healthy controls) completed ecological momentary assessment (EMA) to rate a variety of negative (NE) and positive emotions (PE) 9 times per day for 8days using a mobile phone application. 169 participants (97 anxious and depressed and 72 healthy controls) completed an online daily diary on their NE and PE for 50days. Multilevel vector autoregressive models were run to compute NE and PE network densities in each data set. In the EMA data set, both NE and PE network densities significantly predicted participants' diagnostic status above and beyond demographics and the mean and standard deviation of NE and PE. https://www.selleckchem.com/products/brm-brg1-atp-inhibitor-1.html and lower PE network density were associated with anxiety and depression diagnoses.

The homobimetallic Au(i)2 complex and precursor pro-ligand displayed no antibacterial activity up to 256 μg mL-1, whereas the homobimetallic Ag(i)2 was active against all Gram-positive and Gram-negative bacterial strains tested (MIC = 8-32 μg mL-1). Interestingly, both Au(i)-Ag(i) heterobimetallic complexes displayed similar broad-spectrum activity (MIC = 4-32 μg mL-1) to the Ag(i)2 homobimetallic complex.The constitutions of five metabolites formed during co-metabolic, anaerobic degradation of diethyl ether by the denitrifying betaproteobacterium Aromatoleum sp. strain HxN1 were elucidated by comparison of mass spectrometric and gas chromatographic data with those of synthetic reference standards. Furthermore, the absolute configurations of two stereogenic centers in the metabolites were established. Based on these results a degradation pathway for diethyl ether by Aromatoleum sp. HxN1 analogous to that of n-hexane is proposed. Synthesis of both enantiomers of methyl (E)-4-ethoxy-2-pentenoate was accomplished by etherification of ethyl (R)- or (S)-lactate, followed by hydrolysis of the ester group and reduction to furnish 2-ethoxy-1-propanol. The primary alcohol was converted by a Swern oxidation followed by a Horner-Wadsworth-Emmons reaction to methyl (E)-4-ethoxy-2-pentenoate that was finally hydrogenated to methyl 4-ethoxypentanoate. https://www.selleckchem.com/products/akti-1-2.html (S)-4-ethoxy-3-oxopentanoate was prepared by conversion of (S)-2-ethoxypropanoyl chloride with Meldrum's acid. Reduction of the resulting β-oxoester with NaBH4 or baker's yeast gave both diastereoisomers of methyl 4-ethoxy-3-hydroxypentanoate. The stereocenter at C-3 of the main diastereoisomer produced with baker's yeast was determined by Mosher ester analysis to be (R)-configurated. Dimethyl 2-(1-ethoxyethyl)succinate was prepared by Michael addition of nitroethane to diethyl maleate, followed by conjugate addition of sodium ethanolate, hydrolysis and esterification with diazomethane.It is known that double-stranded DNA (dsDNA) turns into a liquid crystalline phase by the addition of a high concentration of polymer with salt. SYBR Green I (SG) is a well-known sensitive fluorescent stain for dsDNA, and is intercalated in liquid crystalline DNA. Formation of the liquid crystalline dsDNA-SG complex has been confirmed by CD spectral measurements, fluorescence spectral measurements and confocal fluorescence microscopy. SG in dsDNA was also used as a singlet oxygen generator. We conducted photoirradiation experiments using three kinds of 42-mer oligonucleotides with SG. The amount of guanine decomposition by selective irradiation of SG was analyzed using HPLC after digestion of dsDNA in each sample solution. We found that singlet oxygen produced in liquid crystalline DNA promoted guanine damage much more efficiently than in homogeneous solution.Current control of pathogenic bacteria at all biomaterial interfaces is poorly attuned to a broad range of disease-causing pathogens. Leading antimicrobial surface functionalization strategies with antimicrobial peptides (AMPs), defensins, have not shown their promised efficacy. One of the main problems is the lack of stability and swift clearance from the surface. Surface nanotopography bearing sharp protrusions is a non-chemical solution that is intrinsically stable and long-lasting. #link# Previously, the geometrically ordered arrays of nanotipped spines repelled or rapidly ruptured bacteria that come into contact. The killing properties so far work on cocci and rod-like bacteria, but there is no validation of the efficacy of protrusional surfaces on pathogenic bacteria with different sizes and morphologies, thus broadening the utility of such surfaces to cover increasingly more disease entities. Here, we report a synthetic analogue of nanotipped spines with a pyramidal shape that show great effectiveness on species of bacteria with strongly contrasting shapes and sizes. To highlight this phenomenon in the field of dental applications where selective bacterial control is vital to the clinical success of biomaterial functions, we modified the poly(methyl)-methacrylate (PMMA) texture and tested it against Streptococcus mutans, Enterococcus faecalis, Porphyromonas gingivalis, and Fusobacterium nucleatum. These nanopyramids performed effectively at levels well above those of normal and roughened PMMA biomaterials for dentistry and a model material for general use in medicine and disease transmission in hospital environments. Ifosfamide, a widely prescribed antineoplasic agent, is frequently associated with kidney dysfunction. Its nephrotoxicity is well documented in children, but data are lacking in adult patients. The aim of this retrospective study was to describe the clinical, biological and histological characteristics of ifosfamide nephrotoxicity. We report 34 patients (median age 41 years) admitted in six French nephrology departments for kidney failure and/or tubular dysfunction. Fifteen patients (44.1%) received cisplatin as part of their chemotherapy. In 6 patients (17.7%), ifosfamide nephrotoxicity was revealed by a proximal tubular dysfunction (PTD), in 5 patients (14.4%) by an acute kidney injury (AKI), in 6 patients (17.7%) by a chronic kidney disease (CKD) and in 17 patients (49.7%) by an association of PTD and AKI. Fourteen renal biopsies (41.2%) were performed and revealed acute tubular necrosis (85.7%), vacuolation (78.6%) and nuclear atypias (71.4%) of renal epithelial cells, interstitial inflammation (71.itial inflammation (71.4%) and fibrosis (57.1%). Electron microscopy showed mitochondrial enlargement and dysmorphic changes suggestive of mitochondrial toxicity. Ten patients (29.4%) progressed to Stage 5 CKD, six (17.6%) required haemodialysis and six patients died during a median follow-up period of 31 months. Risk factors for Stage 5 CKD were age and cisplatin co-administration. Acute kidney injury (AKI) can affect hospitalized patients with coronavirus disease 2019 (COVID-19), with estimates ranging between 0.5% and 40%. We performed a systematic review and meta-analysis of studies reporting incidence, mortality and risk factors for AKI in hospitalized COVID-19 patients. We systematically searched 11 electronic databases until 29 May 2020 for studies in English reporting original data on AKI and kidney replacement therapy (KRT) in hospitalized COVID-19 patients. Incidences of AKI and KRT and risk ratios for mortality associated with AKI were pooled using generalized linear mixed and random-effects models. Potential risk factors for AKI were assessed using meta-regression. Incidences were stratified by geographic location and disease severity. A total of 3042 articles were identified, of which 142 studies were included, with 49048 hospitalized COVID-19 patients including 5152 AKI events. The risk of bias of included studies was generally low. The pooled incidence of AKI was 28.

Patients diagnosed in 1978-1982 have a mean survival time of 62.3 (52.0, 72.6) months, while those diagnosed in 2008-2012 have mean survival time of 99.4 (96.4, 102.4) months. There is no significant difference in survival time between T4D patients and patients with other T staging and extent of disease coding consistent with clinical IBC presentation. IBC survival has increased over four decades. Despite the improvement in survival for all racial groups, a persistent survival disparity that has not narrowed over two decades remains between white and black patients. https://www.selleckchem.com/products/pf-477736.html has increased over four decades. Despite the improvement in survival for all racial groups, a persistent survival disparity that has not narrowed over two decades remains between white and black patients.Vitrification of embryos has been known as the most efficient cryopreservation method in assisted reproductive technology clinics. Vitrification of preimplantation embryo might be associated with altered gene expression profile and biochemical changes of vitrified embryos. Stringent regulation of gene expression in early embryonic stages is very critical for normal development. In the present study, we investigated the effect of vitrification on the canonical miRNA biogenesis pathway, and also the expression of developmental related miRNAs, in 8-cell and blastocyst mouse embryos. Although the expression pattern of the miRNA biogenesis pathway genes differed between 8-cell and blastocyst mouse embryos, vitrification did not affect the expression level of these genes in preimplantation embryos. The expression levels of miR-21 and let-7a were significantly decreased in vitrified 8-cell embryos and fresh blastocysts when compared with fresh 8-cell embryos. The expression of Stat3 was significantly reduced in blastocysts after vitrification. The alteration in the expression pattern of miRNAs, due to their mode of action, can affect broad downstream key developmental signaling pathways. #link# Therefore, the blastocyst stage is the preferred point for embryo vitrification as they are less susceptible to cryo-damages regarding the stability of miRNAs related to the developmental and implantation competence of embryo.The safety of the tissue transplant recipient is a top priority for tissue banks, and the emergence of the new coronavirus SARS-CoV-2 has raised significant concerns about the risks of releasing tissue for clinical use. In the present study, we conducted a literature review about the potential infectivity of SARS-CoV-2 in different biological tissues and the influence of various tissue processing and sterilization procedures on viral inactivation. The search revealed that SARS-CoV-2 binds to the human angiotensin-converting enzyme receptor to penetrate human cells. These receptors are present in skin cells, musculoskeletal tissue, amniotic membranes, cardiovascular tissue and ocular tissues, including the cornea. In general, we found that coronaviruses are stable at low temperatures, and inactivated upon exposure to extreme heat and pH. Notably, gamma irradiation, which has already been employed to inactivate SARS and MERS, could be useful for sterilizing skin, amnion and musculoskeletal tissues against SARS-CoV-2. We conclude that due to the limited information about the effects of physical and chemical tissue processing methods on viral neutralization, rigorous donor screening is still essential for tissue transplant recipient safety.Ivabradine and its metabolite both demonstrate heart rate-reducing effect (If current inhibitors) and undergo CYP3A4 metabolism. The purpose of this study was to develop a joint parent-metabolite physiologically based pharmacokinetic (PBPK)/pharmacodynamic (PD) model to predict the PK and PD of ivabradine and its metabolite following intravenous (i.v.) or oral administration (alone or co-administered with CYP3A4 inhibitors). Firstly, a parent-metabolite disposition model was developed and optimised using individual plasma concentration-time data following i.v. administration of ivabradine or metabolite within a Bayesian framework. Secondly, the model was extended and combined with a mechanistic intestinal model to account for oral absorption and drug-drug interactions (DDIs) with CYP3A4 inhibitors (ketoconazole, grapefruit juice). Lastly, a PD model was linked to the PBPK model to relate parent and metabolite PK to heart rate (HR) reduction. The disposition model described successfully parent-metabolite PK following i.v. administration. Following integration of a gut model, the PBPK model adequately predicted plasma concentration profiles and the DDI risk (92% and 85% of predicted AUC+inhibitor/AUCcontrol and Cmax+inhibitor/Cmaxcontrol for ivabradine and metabolite within the prediction limits). Ivabradine-metabolite PBPK model was linked to PD by using the simulated unbound parent-metabolite concentrations in the heart. This approach successfully predicted the effects of both entities on HR (observed vs predicted - 7.7/- 5.9 bpm and - 15.8/- 14.0 bpm, control and ketoconazole group, respectively). This study provides a framework for PBPK/PD modelling of a parent-metabolite and can be scaled to other populations or used for investigation of untested scenarios (e.g. evaluation of DDI risk in special populations). To synthesize reported long-term outcomes in patients undergoing tracheostomy after severe acute brain injury (SABI). We systematically searched PubMed, EMBASE, and Cochrane Library for studies in English, German, and Spanish between 1990 and 2019, reporting outcomes in patients with SABI who underwent tracheostomy. We adhered to the preferred reporting items for systematic reviews and meta-analyses guidelines and the meta-analyses of observational studies in epidemiology guidelines. We excluded studies reporting on less than 10 patients, mixed populations with other neurological diseases, or studies assessing highly select subgroups defined by age or procedures. Data were extracted independently by two investigators. Results were pooled using random effects modeling. The primary outcome was long-term functional outcome (mRS or GOS) at 6-12months. Secondary outcomes included hospital and long-term mortality, decannulation rates, and discharge home rates. Of 1405 studies identified, 61 underwent full manuscript review and 19 studies comprising 35,362 patients from 10 countries were included in the meta-analysis.

We compared COVID-19 risk management, fear of infection and fear of transmission of infection among frontline employees working within eldercare, hospital/rehabilitation, psychiatry, childcare and ambulance service and explored if group differences in fear of infection and transmission could be explained by differences in risk management. https://www.selleckchem.com/products/ei1.html investigated the association of risk management with fear of infection and fear of transmission of infection among eldercare personnel. We used cross-sectional questionnaire data collected by the Danish labour union, FOA . Data were collected 5½ weeks after the first case of COVID-19 was registered in Denmark. Data for the first aim included 2623 participants. #link# Data for the second aim included 1680 participants. All independent variables were mutually adjusted and also adjusted for sex, age, job title and region. Fear of infection (49%) and fear of transmitting infection from work to the private sphere (68%) was most frequent in ambulance service. Fear of transmitting infection during work was most frequent in the eldercare (55%). Not all differences in fear of infection and transmission between the five areas of work were explained by differences in risk management. Among eldercare personnel, self-reported exposure to infection and lack of access to test was most consistently associated with fear of infection and fear of transmission, whereas lack of access to personal protective equipment was solely associated with fear of transmission. We have illustrated differences and similarities in COVID-19 risk management within five areas of work and provide new insights into factors associated with eldercare workers' fear of infection and fear of transmission of infection. We have illustrated differences and similarities in COVID-19 risk management within five areas of work and provide new insights into factors associated with eldercare workers' fear of infection and fear of transmission of infection.The popliteal sciatic nerve block is routinely used for anesthesia and analgesia during foot and ankle surgery. This article reviews our current understanding of the anatomy of the sciatic nerve and discusses how fascial tissue layers associated with the nerve may affect block outcomes . The anatomy of the sciatic nerve is more complex than previously described. The tibial and common peroneal nerves within the sciatic nerve trunk appear to be centrally separated by the Compton-Cruveilhier septum and encompassed by their own paraneural sheaths. This unique internal architecture of the sciatic nerve appears to promote proximal spread of local anesthetic to the internal aspect of the sciatic nerve trunk after a subparaneural injection at or below the divergence of the tibial and common peroneal nerves.Insect metamorphosis originated around the middle Devonian, associated with the innovation of the final molt; this occurs after histolysis of the prothoracic gland (PG; which produces the molting hormone) in the first days of adulthood. We previously hypothesized that transcription factor E93 is crucial in the emergence of metamorphosis, because it triggers metamorphosis in extant insects. This work on the cockroach Blattella germanica reveals that E93 also plays a crucial role in the histolysis of PG, which fits the above hypothesis. Previous studies have shown that the transcription factor FTZ-F1 is essential for PG histolysis. We have found that FTZ-F1 depletion towards the end of the final nymphal instar downregulates the expression of E93, whereas E93-depleted nymphs molt to adults that retain a functional PG. Interestingly, these adults are able to molt again, which is exceptional in insects. The study of insects able to molt again in the adult stage may reveal clues about how nymphal epidermal cells definitively become adult cells, and whether it is possible to reverse this process.Macrophages reprogram their metabolism to promote appropriate responses. Proresolving macrophages primarily use fatty acid oxidation as an energy source. Metabolites generated during the catabolism of fatty acids aid in the resolution of inflammation and tissue repair, but the regulatory mechanisms that control lipid metabolism in macrophages are not fully elucidated. Lipin-1, a phosphatidic acid phosphatase that has transcriptional coregulator activity, regulates lipid metabolism in a variety of cells. In this current study, we show that lipin-1 is required for increased oxidative phosphorylation in IL-4 stimulated mouse (Mus musculus) macrophages. We also show that the transcriptional coregulatory function of lipin-1 is required for β-oxidation in response to palmitate (free fatty acid) and apoptotic cell (human) stimulation. Mouse bone marrow-derived macrophages lacking lipin-1 have a reduction in critical TCA cycle metabolites following IL-4 stimulation, suggesting a break in the TCA cycle that is supportive of lipid synthesis rather than lipid catabolism. Together, our data demonstrate that lipin-1 regulates cellular metabolism in macrophages in response to proresolving stimuli and highlights the importance of aligning macrophage metabolism with macrophage phenotype.Obesity and nonalcoholic fatty liver disease (NAFLD) affect expression and function of cytochrome P450 genes (P450s). The increased expression of inflammatory cytokines is a major driver of the downregulation of P450 expression in NAFLD. Decrease in P450 expression could potentially lead to drug-drug interaction, inefficient pharmacological effect of a drug, or hepatotoxicity. An epigenetic modifier, histone 3 lysine 9 methyl transferase enzyme (G9a), known to increase histone 3 lysine 9 methylation, is downregulated in diet-induced obesity animal models. In a liver-specific G9a knockout animal model, expression of P450s was downregulated. Currently, the role of G9a in regulation of P450s in steatosis is unknown. Our hypothesis is that in steatosis G9a plays a role in downregulation of P450 expression. In this study, we used HepaRG cells to induce steatosis using a combination of free fatty acids oleic acid and palmitic acid. The G9a was knocked down and overexpressed using small interfering RNA and adenovirus mediated approaches, respectively.

Children who were diagnosed with type 1 diabetes had increased school absenteeism 4 months before diagnosis. To compare effects of the dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin with those of a sulfonylurea on renal physiology in metformin-treated patients with type 2 diabetes mellitus (T2DM). In this double-blind randomized trial, 46 overweight T2DM patients without renal impairment received once-daily linagliptin (5 mg) or glimepiride (1 mg) for 8 weeks. Fasting glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric acid clearances. Fractional excretions, urinary damage markers, and circulating DPP-4 substrates (among others, glucagon-like peptide 1 and stromal cell-derived factor-1α [SDF-1α]) were measured. HbA reductions were similar with linagliptin (-0.45 ± 0.09%) and glimepiride (-0.65 ± 0.10%) after 8 weeks ( = 0.101). Linagliptin versus glimepiride did not affect GFR, ERPF, estimated intrarenal hemodynamics, or damage markers. #link# Only linagliptin increased fractional excretion (FE) of sodium (FE ) and potassium, without affecting FE of lithium. Linagliptin-induced change in FE correlated with SDF-1α ( = 0.660) but not with other DPP-4 substrates. Linagliptin does not affect fasting renal hemodynamics compared with glimepiride in T2DM patients. DPP-4 inhibition promotes modest natriuresis, possibly mediated by SDF-1α, likely distal to the macula densa. Linagliptin does not affect fasting renal hemodynamics compared with glimepiride in T2DM patients. DPP-4 inhibition promotes modest natriuresis, possibly mediated by SDF-1α, likely distal to the macula densa.Outside sleep laboratory settings, peripheral arterial tonometry (PAT, eg, WatchPat) represents a validated modality for diagnosing obstructive sleep apnea (OSA). We have shown before that the accuracy of home sleep apnea testing by WatchPat 200 devices in diagnosing OSA is suboptimal (50%-70%). In order to improve its diagnostic performance, we built several models that predict the main functional parameter of polysomnography (PSG), Apnea Hypopnea Index (AHI). Participants were recruited in our Sleep Center and underwent concurrent in-laboratory PSG and PAT recordings. https://www.selleckchem.com/products/t0070907.html were then developed to predict AHI by using robust functional parameters from PAT-based testing, in concert with available demographic and anthropometric data, and their performance was confirmed in a random validation subgroup of the cohort. Five hundred synchronous PSG and WatchPat sets were analyzed. Mean diagnostic accuracy of PAT was improved to 67%, 81% and 85% in mild, moderate-severe or no OSA, respectively, by several models that included participants' age, gender, neck circumference, body mass index and the number of 4% desaturations/hour. WatchPat had an overall accuracy of 85.7% and a positive predictive value of 87.3% in diagnosing OSA (by predicted AHI above 5). In this large cohort of patients with high pretest probability of OSA, we built several models based on 4% oxygen desaturations, neck circumference, body mass index and several other variables. These simple models can be used at the point-of-care, in order to improve the diagnostic accuracy of the PAT-based testing, thus ameliorating the high rates of misclassification for OSA presence or disease severity. Detailed data on the characteristics and outcomes of patients with COVID-19 in sub-Saharan Africa are limited. We determined the clinical characteristics and treatment outcomes of patients diagnosed with COVID-19 in Uganda. As of the 16 May 2020, a total of 203 cases had been confirmed. We report on the first 56 patients; 29 received hydroxychloroquine (HCQ) and 27 did not. Endpoints included admission to intensive care, mechanical ventilation or death during hospitalisation. The median age was 34.2 years; 67.9% were male; and 14.6% were <18 years. Up 57.1% of the patients were asymptomatic. The most common symptoms were fever (21.4%), cough (19.6%), rhinorrhea (16.1%), headache (12.5%), muscle ache (7.1%) and fatigue (7.1%). Rates of comorbidities were 10.7% (pre-existing hypertension), 10.7% (diabetes) and 7.1% (HIV), Body Mass Index (BMI) of ≥30 36.6%. 37.0% had a blood pressure (BP) of >130/90 mm Hg, and 27.8% had BP of >140/90 mm Hg. Laboratory derangements were leucopenia (10.6%), lymphopenia (11.1%) and thrombocytopenia (26.3%). Abnormal chest X-ray was observed in 14.3%. No patients reached the primary endpoint. Time to clinical recovery was shorter among patients who received HCQ, but this difference did not reach statistical significance. Most of the patients with COVID-19 presented with mild disease and exhibited a clinical trajectory not similar to other countries. Outcomes did not differ by HCQ treatment status in line with other concluded studies on the benefit of using HCQ in the treatment of COVID-19. Most of the patients with COVID-19 presented with mild disease and exhibited a clinical trajectory not similar to other countries. Outcomes did not differ by HCQ treatment status in line with other concluded studies on the benefit of using HCQ in the treatment of COVID-19. Relieving gastrointestinal (GI) symptoms was identified as a 'top ten' priority by our James Lind Alliance Priority Setting Partnership in cystic fibrosis (CF). We conducted an online survey to find out more about the effect of GI symptoms in CF. We co-produced an online survey distributed to the CF community via web-based platforms. The survey consisted of open and closed questions designed to help us learn more about the effects of GI symptoms for people with CF (pwCF). We analysed the data using descriptive statistics and thematic analysis. We promoted the survey via social media and web-based platforms which allowed respondents from any country to take part. Our participants came from the CF community, including adults and children with CF, parents and close family of pwCF and healthcare professionals (HCPs) working with pwCF. There were 276 respondents 90 (33%) pwCF, 79 (29%) family, 107 (39%) HCPs. The most commonly reported symptoms by lay respondents were stomach cramps/pain, bloating and a 'combination of symptoms'.

strate any differences in fibrinolysis between the two TXA dosing regimens and placebo. Diagnostic test, level III. Diagnostic test, level III. Balanced resuscitation strategies have led to increased utilization of plasma. Fresh frozen plasma that is thawed and never used is a large source of blood component wastage. Thawed plasma (TP) and can only be stored for 5 days. Liquid plasma (LP) has never been frozen and can be stored for 26 days. Due to longer storage duration, we hypothesized that using LP would result in decreased waste and cost savings compared with TP. We performed a retrospective review of all trauma patients at our Level I trauma center in the years 2015 to 2016. We compared 2015 when only TP was used to 2016 when both TP and LP were used. All plasma units ordered for trauma patients were tracked until the time of transfusion or wastage. Wastage rates were compared between years and plasma type. There were 5,789 trauma patients admitted to our institution from 2015 to 2016. There were 4,107 plasma units ordered with 487 (11.9%) units wasted. During 2015, 2,021 total units of plasma were ordered with 273 (13.5%) units wasted whi This longitudinal case series provides valuable long-term data on the safety and efficacy of iStent inject with concomitant cataract surgery. Patients experienced significant and durable reductions in both intraocular pressure (IOP) and medication burden through 3 years postoperative. The purpose of this study was to examine the 3-year effectiveness and safety of iStent inject second-generation trabecular micro-bypass stent implantation with concomitant phacoemulsification cataract surgery in eyes with various glaucoma subtypes and severities. This was a single-center consecutive case series. Three-year outcomes included mean IOP and medications, the proportions of eyes with IOP ≤18, ≤15, and ≤12 mm Hg, and success (absence of secondary glaucoma interventions). Safety included best-corrected visual acuity (BCVA), cup-to-disc ratio, visual field (VF) mean deviation, retinal nerve fiber layer (RNFL), and ganglion cell-inner plexiform layer (GCIPL) thickness, and adverse events. A total of 124 eyes with ugh 3 years after iStent inject implantation with cataract surgery in a real-world clinical population with mild-to-severe glaucoma, along with favorable safety including stable BCVA, VF, and RNFL and GCIPL thickness. Significant and sustained IOP and medication reductions were achieved through 3 years after iStent inject implantation with cataract surgery in a real-world clinical population with mild-to-severe glaucoma, along with favorable safety including stable BCVA, VF, and RNFL and GCIPL thickness.A healthy corneal endothelium is required for corneal clarity. Both the glaucoma disease state and its various forms of treatment can have adverse effects on the corneal endothelium. Both the presence of glaucoma and the magnitude of intraocular pressure elevation are related to endothelial cell loss (ECL). #link# Topical medical therapy, laser procedures, and both traditional surgeries-trabeculectomy and tube-shunts-and newer minimally invasive glaucoma surgeries have variable effects on ECL. This review will summarize the reported effects of glaucoma and its treatment on ECL. Concerns for corneal endothelial cell health should be part of the decision-making process when planning glaucoma therapy for lowering intraocular pressure, with added caution in case of planned device implantation in eyes with preexisting ECL and low endothelial cell density at high risk for corneal endothelial decompensation. Given the increasing usage of total ankle arthroplasty (TAA), a better understanding of the reasons leading to implant revision and the factors that might influence those indications is necessary to identify at-risk patients. Using a single-design three-component ankle prosthesis, we asked (1) What is the cumulative incidence of implant revision at 5 and 10 years? (2) What are the indications for implant revision in our population? (3) What factors are associated with an increased likelihood of implant revision during the time frame in question? Between 2003 and 2017, primary TAA using a single-design three-component ankle implant was performed by or under the supervision of the implant designer in 1006 patients (1074 ankles) aged between 17 and 88 years to treat end-stage ankle osteoarthritis. No other TAA systems were used during the study period at the investigators' institution. In 68 patients with bilateral surgery, only the first TAA was considered. Of the patients treated with the study implant, , deep infection (9% [11 of 121]), and technical error (7% [9 of 121]). Ankles with a major hindfoot deformity before TAA were more likely to undergo revision than ankles with a minor deformity (hazard ratio 1.9 [95% CI 1.2 to 3.0]; p = 0.007) or neutral alignment (HR 2.5 [95% CI 1.5 to 4.4]; p = 0.001). https://www.selleckchem.com/ increased revision probability compared with a varus deformity (HR 2.1 [95% CI 1.4 to 3.4]; p = 0.001). Instability was a more common reason for implant revision after TAA with this three-component design than previously reported. All causes inducing either a varus or valgus hindfoot deformity must be meticulously addressed during TAA to prevent revision of this implant. Future studies from surgeons/institutions not involved in this implant design are needed to confirm these findings and to further investigate why a substantial number of patients had pain of unknown cause prompting revision. Level III, therapeutic study. Level III, therapeutic study. There is increasing interest in the development of statistical models that can be used to estimate risk of adverse patient outcomes after joint arthroplasty. Competing risk approaches have been recommended to estimate risk of longer-term revision, which is often likely to be precluded by the competing risk of death. However, a common approach is to ignore the competing risk by treating death as a censoring event and using standard survival models such as Cox regression. It is well-known that this approach can overestimate the event risk for population-level estimates, but the impact on the estimation of a patient's individualized risk after joint arthroplasty has not been explored. We performed this study to (1) determine whether using a competing risk or noncompeting risk method affects the accuracy of predictive models for joint arthroplasty revision and (2) determine the magnitude of difference that using a competing risks versus noncompeting risks approach will make to predicted risks for individual patients.

Breast cancer is the most common malignancy for women. Accurate prediction of breast cancer and its pathological stages is important for treatment decision-making. Although many studies have focused on discovering circulating biomarkers of breast cancer, no such biomarkers have been reported for different stages of this disease. In this study, we identified blood protein biomarkers for each stage of breast cancer by analyzing transcriptome and proteome data from patients. Analysis of the TCGA transcriptome datasets revealed that a large number of genes were differentially expressed in tumor samples of each stage of breast cancer compared with adjacent normal tissues. Blood-secretory proteins encoded by these genes were then predicted by bioinformatics programs. Furthermore, iTRAQ-based proteomic analysis was conducted for plasma samples of breast cancer patients with different stages. A portion of predicted blood-secretory proteins could be detected and verified differentially expressed. Finally, several proteins were chosen as potential blood protein biomarkers for different stages of breast cancer due to their consistent expression patterns at both mRNA and protein levels. Overall, our data provide new insights into diagnosis and classification of breast cancer as well as selection of optimal treatments. SIGNIFICANCE We identified blood protein biomarkers for each stage of breast cancer by analyzing tissue-based transcriptome and blood-based proteome data from patients. To our knowledge, this is the first time to try to identify blood protein biomarkers for different stages of breast cancer via these integrative analyses. Our data may provide new insights into diagnosis and classification of breast cancer as well as selection of optimal treatment. Human and animal research has long documented the negative effects of early traumatic events on long-term development and socioemotional behavior. Yet, how and where the body stores these memories remains unclear. Current theories propose that the brain stores such memory in the subcortical limbic system. However, a clear theory of change with testable hypothesis has yet to emerge. In this paper, we review the classical Pavlovian conditioning learning tradition, along with its functional variant. Then, we review calming cycle theory, which builds upon the idea that mother/infant learning is distinct from other types of learning, requiring a new set of assumptions in light of functional Pavlovian conditioning. Calming cycle theory states that learning of behaviors associated with subcortical autonomic physiology is separate and distinct from learning of behaviors associated with cortical physiology. Mother/infant autonomic learning starts in the uterine environment via functional Pavlovian co-conditioninnomic nervous systems. These reflexes are preserved transnatally as autonomic socioemotional reflexes (ASRs), which can be used to monitor mother-infant relational health. The functional Pavlovian co-conditioning mechanism can be exploited to change the physiological/behavioral reflex response. The theory provides a well established learning mechanism, a theory of change and a method of change, along with a set of hypotheses with which to test the theory. We present evidence from a randomized controlled trial with prematurely born infants and their mothers that supports calming cycle theory. Subcutaneous immunoglobulin (SCIg) administered through infusion pump has been reported as effective in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients. In this study we evaluate an alternative technique of SCIg administration, based on the delivery of lower volumes administered daily using manual push technique (MPT) in 10 CIDP patients. In this randomized, controlled, two-arm, crossover clinical trial, CIDP patients were randomly assigned 11 to receive SCIg either by MPT or pumps for 4 consecutive months with crossover to the other. The primary objective was to assess whether MPT had the same effectiveness as pumps. #link# The secondary objectives were to assess whether MPT resulted in greater plasma IgG levels and improved quality of life (QoL). Ten patients (mean age = 48.3) were enrolled. No significant changes were observed in the efficacy parameters (INCAT, MRC, R-ODS, and GS scales). A positive mean variation of 5.4 % in plasma IgG levels in the group treated with MPT was observed at the end of MPT periods. Treatment interference, which is one of the dimensions of the Life Quality Index, showed a significant improvement in the MPT periods. In CIDP patients, the MPT technique was as effective as pump infusion, allowed comparable, slightly increases plasma IgG levels, and also improved the QoL. In CIDP patients, the MPT technique was as effective as pump infusion, allowed comparable, slightly increases plasma IgG levels, and also improved the QoL.Artisanal vegetable fermentations are regaining popularity in industrialized countries, but they could be prone to contamination with foodborne pathogens. By simulating home or small-scale restaurant fermentations, we evaluated the microbiological safety of spontaneous carrot juice fermentations. Raw carrot juice was spiked with Listeria monocytogenes, Salmonella enterica subsp. enterica Typhimurium and Escherichia coli O157H7, and the microbial dynamics were followed throughout the entire fermentation process by cultivation and amplicon sequencing. In addition, the behavior of these pathogens was also monitored after addition of raw cucumber juice and storage under refrigerated conditions to mimic post-contamination issues. Although the numbers of the pathogens increased during the first phase of the fermentation, the pathogens were not able to persist throughout the fermentation. Their numbers fell below the detection limit after 8 days of fermentation at 20 °C. https://www.selleckchem.com/products/CI-1040-(PD184352).html using amplicon sequencing also showed that there was no major impact on the general microbial dynamics of the spontaneous carrot juice fermentation. This indicates that the artisanal carrot juice fermentation is a robust process which resists the persistence of pathogens. More caution is needed however when mixing the final fermented product with a raw juice. When simulating pathogen post-contamination, both Salmonella enterica and Escherichia coli were able to survive in the refrigerated fermented juice up to 10 days after the fermentation. Listeria monocytogenes was detected up to 8 days in the refrigerated juice. Pasteurization of the raw juice before adding it to the fermented product is thus recommended.

Migrant health has been the subject of various international agreements in recent years. In parallel, there has been a growth in academic research in this area. However, this increase in focus at international level has not necessarily strengthened the capacity to drive evidence-informed national policy and action in many low- and middle-income countries. The Migration Health South Asia (MiHSA) network aims to challenge some of the barriers to progress in the region. Examples include the bias towards institutions in high-income countries for research funding and agenda-setting and the overall lack of policy-focused research in the region. MiHSA will engage researchers, funders and policy-makers in collectively identifying the most pressing, yet feasible, research questions that could help strengthen migrant and refugee health relevant to the region's national contexts. In addition, policies and provisions for different migrant populations in the region will be reviewed from the health and rights perspectives, to identify opportunities to strategically align research agendas with the questions being asked by policy-makers. The convergence of migration policy with other areas such as health and labour at global level has created a growing imperative for policy-makers in the region to engage in cross-sector dialogue to align priorities and coordinate responses. Such responses must go beyond narrow public health interventions and embrace rights-based approaches to address the complex patterns of migration in the region, as well as migrants' precarity, vulnerabilities and agency.Sex workers have been one of the marginalized groups that have been particularly affected by India's stringent lockdown in response to the coronavirus disease 2019 (COVID-19) pandemic. The sudden loss of livelihood and lack of access to health care and social protection intensified the vulnerabilities of sex workers, especially those living with HIV. In https://www.selleckchem.com/products/t0070907.html , Ashodaya Samithi, an organization of more than 6000 sex workers, launched an innovative programme of assistance in four districts in Karnataka. Since access to antiretroviral therapy (ART) was immediately disrupted, Ashodaya adapted its HIV outreach programme to form an alternative, community-led system of distributing ART at discreet, private sites. WhatsApp messaging was used to distribute information on accessing government social benefits made available in response to the COVID-19 pandemic. Other assistance included advisory messages posted in WhatsApp groups to raise awareness, dispel myths and mitigate violence, and regular, discreet phone check-ins to follow up on the well-being of members. The lessons learnt from these activities represent an important opportunity to consider more sustainable approaches to the health of marginalized populations that can enable community organizations to be better prepared to respond to other public health crises as they emerge.The Government of Thailand was prompt to launch social and economic measures to mitigate the effects on the general population following lockdown measures to counter coronavirus disease 2019 (COVID-19). However, sex workers were one of the vulnerable groups who were unable to access state support. A rapid survey of sex workers in Thailand showed that almost all had become unemployed and lost their income as a consequence of the lockdown, restrictions on international flights into the country and the closure of entertainment venues. Most were unable to cover the costs of food and shelter for themselves and their dependents. COVID-19 had also disrupted testing and treatment for sexually transmitted infections and HIV services for sex workers. As in other countries, community-based organizations were essential to providing an immediate, short-term COVID-19 response for sex workers. Also as in other countries, the pandemic has demonstrated that many people's health and well-being depends on very fragile foundations. This presents a clear opportunity to build back better by committing to a longer-term vision for the overall societal inclusion of sex workers. Thailand should advocate for decriminalization of sex work and ensure sex workers are entitled to equal labour rights and inclusion in the government social protection programme. Progress in innovative government initiatives aimed at ending HIV stigma and discrimination show how structural change can come about through harnessing community-based organizations. In turn, HIV services for sex workers need to expand and incorporate targeted interventions to reduce sex workers' occupational susceptibility to COVID-19.Almost half of the deaths worldwide caused by tuberculosis in 2018 occurred in the World Health Organization (WHO) South-East Asia Region, home to around a quarter of the global population. Maintaining robust progress in this region is therefore essential if the global goal of ending the tuberculosis epidemic is to be realized. Substantial gains have been made in the region, but the threat to health worldwide posed by the coronavirus disease 2019 (COVID-19) pandemic includes not only the direct effects of the pandemic but also the potential eclipsing of the global tuberculosis emergency. The results of modelling studies present stark warnings of a reversal of years of progress and a significant resurgence in deaths from tuberculosis. The COVID-19 pandemic has had variable impacts in the WHO South-East Asia Region to date, but in the countries most affected there has been targeted diversion and repurposing of tuberculosis services, health-care workers and diagnostic equipment. The combined effects of COVID-19, containment measures and fragmentation of tuberculosis services have resulted in delays in diagnosis or non-diagnosis and disruption in treatment resulting in increased morbidity, mortality, transmission and drug resistance. Countries of the region have made attempts to ensure continuity of services and civil society and nongovernmental organizations have instituted a range of innovative mechanisms to support national programmes. #link# However, a comprehensive approach - including scaling up successful initiatives, empowering community leadership, harnessing digital tools, and implementing easily accessible cash transfers and nutrition support - will be critical to success. As COVID-19 recedes, countries will need "catch-up plans" to deploy supplementary measures to address the increased tuberculosis burden. Urgent, targeted and agile responses have the potential to mitigate and reverse the impact of the COVID-19 pandemic on tuberculosis in South-East Asia.