Persisters

Gastrulation is the first major differentiation process in animal embryos. However, the dynamics of human gastrulation remain mostly unknown owing to the ethical limitations. We studied the dynamics of the mesoderm and endoderm cell differentiation from human pluripotent stem cells for insight into the cellular dynamics of human gastrulation. Human pluripotent stem cells have properties similar to those of the epiblast, which gives rise to the three germ layers. The mesoderm and endoderm were induced with more than 75% purity from human induced pluripotent stem cells...

The existence of neural stem cells (NSCs) in the adult mammalian nervous system, although small in number and restricted to the sub-ventricular zone of the lateral ventricles, the dentate gyrus of the hippocampus, and the olfactory epithelium, is a gift of evolution for the adaptive brain function which requires persistent plastic changes of these regions. It is known that most adult NSCs are latent, showing long cell cycles. In the past decade, the concept of quiescent NSCs (qNSCs) has been widely accepted by researchers in the field, and great progress has been made in the biology of qNSCs...

In multiple sclerosis (MS), persisting disability can occur independent of relapse activity or development of new central nervous system (CNS) inflammatory lesions, termed chronic progression. This process occurs early and it is mostly driven by cells within the CNS. One promising strategy to control progression of MS is the inhibition of the enzyme Bruton's tyrosine kinase (BTK), which is centrally involved in the activation of both B cells and myeloid cells, such as macrophages and microglia. The benefit of BTK inhibition by evobrutinib was shown as we observed reduced pro-inflammatory activation of microglia when treating chronic experimental autoimmune encephalomyelitis (EAE) or following the adoptive transfer of activated T cells...

BACKGROUND: Sacubitril/valsartan (Sac/Val) is the first angiotensin receptor-neprilysin inhibitor indicated for symptomatic chronic heart failure (HF) with reduced ejection fraction (HFrEF). Given most patients with HF in Germany are managed by general practitioners, AURORA-HF investigated the baseline characteristics and 1‑year follow-up of patients starting Sac/Val in primary care in Germany. METHODS: This was a prospective, multicenter, observational study, with all treatment decisions independent of participation...

BACKGROUND: The addition of pembrolizumab (pembro) to neoadjuvant chemotherapy (NAC) is standard of care for the treatment of early triple-negative breast cancer (TNBC) after KEYNOTE-522 trial demonstrated improved pathologic complete response (pCR) rates with the combination. However, the optimal treatment strategy for TNBC remains uncertain as questions persist about which patients benefit from pembro and the best treatment schedule and regimen. We identified real-world clinical characteristics and treatment variables associated with response to NAC plus pembro...

Persistent air leaks in patients with pneumothorax can lead to significant morbidity. If a patient with persistent air leak is medically unfit for thoracic surgery, medical pleurodesis via chest tube or thoracoscopy is either an option. Thoracoscopy offers the advantage of visualizing the site of the air leak and enabling direct instillation of the pleurodesis agent or glue at that location. Autologous blood patch instillation via chest tube has been reported to be a cheap and very effective technique for the management of persistent air leaks...

IMPORTANCE: Catheter ablation is associated with reduced heart failure (HF) hospitalization and death in select patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). However, the benefit in patients with HF with preserved ejection fraction (HFpEF) is uncertain. OBJECTIVE: To investigate whether catheter ablation for AF is associated with reduced HF-related outcomes according to HF phenotype. DATA SOURCE: A systematic search of MEDLINE, Embase, and Cochrane Central was conducted among studies published from inception to September 2023...

Synbiotics combine the concepts of probiotics and prebiotics to synergistically enhance the health-associated effects of both components. Previously, we have shown that the intestinal persistence of inulin-utilizing L. plantarum Lp900 is significantly increased in rats fed an inulin-supplemented, high-calcium diet. Here we employed a competitive population dynamics approach to demonstrate that inulin and GOS can selectively enrich L. plantarum strains that utilize these substrates for growth during in vitro cultivation, but that such enrichment did not occur during intestinal transit in rats fed a GOS or inulin-supplemented diet...

A high systolic/diastolic (S/D) ratio of umbilical cord blood is a manifestation of intrauterine hypoxia. However, the clinical significance of a persistently decreased S/D ratio of umbilical cord blood has not been reported. We report eight cases of a persistently decreased S/D ratio of umbilical cord blood, with two cases of umbilical thrombus, five cases of excessive torsion, and one case of a true cord knot. Fetuses with a persistently decreased S/D ratio of umbilical cord blood may be at risk, and it may be an important indication of umbilical cord lesions...

Diabetes mellitus type 3 refers to diabetes secondary to an existing disease or condition of the exocrine pancreas and is an uncommon cause of diabetes occurring due to pancreatogenic pathology. It accounts for 15-20% of diabetic patients in Indian and Southeast Asian continents. This is case report of a rare case of type 3 diabetes mellitus (T3DM) presenting with diabetic ketoacidosis (DKA). The patient was admitted for DKA along with complaint of hyperglycemia, blood glucose of 405 mg/dl with HbA1c level of 13...

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When chemical pollutants enter the environment, they can undergo diverse transformation processes, forming a wide range of transformation products (TPs), some of them benign and others more harmful than their precursors. To date, the majority of TPs remain largely unrecognized and unregulated, particularly as TPs are generally not part of routine chemical risk or hazard assessment. Since many TPs formed from oxidative processes are more polar than their precursors, they may be especially relevant in the context of persistent, mobile, and toxic (PMT) and very persistent and very mobile (vPvM) substances, which are two new hazard classes that have recently been established on a European level...

UNLABELLED: The utilization of ATP within cells plays a fundamental role in cellular processes that are essential for the regulation of host-pathogen dynamics and the subsequent immune response. This study focuses on ATP-binding proteins to dissect the complex interplay between Staphylococcus aureus and human cells, particularly macrophages (THP-1) and keratinocytes (HaCaT), during an intracellular infection. A snapshot of the various protein activity and function is provided using a desthiobiotin-ATP probe, which targets ATP-interacting proteins...

Sarcopenia is a pathology resulting from a progressive and severe loss of muscle mass, strength, and function in the course of aging, which has deleterious consequences on quality of life. Among the most widespread studies on the issue are those focused on the effect of different types of physical exercise on patients with sarcopenia. This randomized controlled study aimed to compare the effects of a whole-body vibration exercise (WBV) session on the inflammatory parameters of non-sarcopenic (NSG, n=22) and sarcopenic elderly (SG, n=22)...

OBJECTIVE: To evaluate, using spatial analysis, the occurrence of American Cutaneous Leishmaniasis (ACL) and analyze its association with the municipal human development index (MHDI) and deforestation in the state of Amazonas, Brazil, from 2016 to 2020. METHODS: This ecological study, carried out from January 2016 to December 2020, included the 62 municipalities of the state of Amazonas. The incidence rate of ACL was determined in space and time. Using Multiple Linear Regression by Ordinary Least Squares (OLS) and Spatial Autoregressive Regression (SAR) models, the relationship between incidence rates and Human Development Index (HDI) and deforestation was analyzed...

BACKGROUND: Malaria is a major global public health issue with varying epidemiologies across countries. In Colombia, it is a priority endemic-epidemic event included in the national public health policy. However, evidence demonstrating nationwide variations in the disease behavior is limited. This study aimed to analyze changes in the levels and distribution of endemic-epidemic malaria transmission in the eco-epidemiological regions of Colombia from 1978 to 1999 and 2000 to 2021. METHODS: We conducted a comprehensive time-series study using official secondary data on malaria-associated morbidity and mortality in Colombia from 1978 to 2021...

This study aimed to examine the sociodemographic profile of sexual and gender minorities who regularly interact with children and investigate whether such frequent interactions are associated with healthcare factors. This cross-sectional study utilized data from the LGBT+ Health Survey in Brazil, conducted online and anonymously from August to November 2020 with 958 participants. Regular interaction with children was defined as living with children or engaging in bi-weekly face-to-face meetings with children residing in different households...

OBJECTIVE: To longitudinally assess domestic violence (DV) during the postpartum period, identifying types, patterns and determinants of DV, according to mothers' reports in Fortaleza, Brazil. METHODS: Data from the Iracema-COVID cohort study interviewed at home mothers who gave birth in the first wave of COVID-19, at 18 and 24 months after birth. Patterns of reported DV were classified as follows: no DV, interrupted DV, started DV and persistent DV. Adjusted multinomial logistic regressions were used to assess factors associated with persistent DV...

OBJECTIVE: The aim of this study was to analyze the spatiotemporal evolution of the incidence rates of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in the state of Paraná, Brazil. METHODS: An ecological study with an analytical component of time series analysis was conducted in the state of Paraná from 2007 to 2022. The data source was the Notifiable Diseases Information System. To study the trend, the Prais-Winsten generalized linear regression model was used by decomposing the time series, and for spatial analysis, the Moran's index was applied...

OBJECTIVES: To determine the predictors for chronic and/or persistent ITP among children with newly diagnosed ITP. METHODS: Ours was a mixed-design study (prospective: January 2020 to March 2022 and retrospective: January 2014 to December 2019), wherein we enrolled children, aged 1 month to 18 years presenting with newly diagnosed ITP. RESULTS: Of the 64 enrolled participants, 58 were followed up for atleast 1-year duration and 6 children were followed up for 3 to 12 months' duration...