Fitness costs of Mycobacterium tuberculosis resistant to rifampicin is compensated by rapid Th2 polarization mediated by early and high IL-4 production during mice infection.

It was a general belief that drug resistance in Mycobacterium tuberculosis (Mtb) was associated with lesser virulence, particularly rifampicin resistance, which is usually produced by mutations in the RNA polymerase Beta subunit (RpoB). Interestingly, this kind of bacterial mutations affect gene transcription with significant effects on bacterial physiology and metabolism, affecting also the bacterial antigenic constitution that in consequence can produce diverse immune responses and disease outcome. In the present study, we show the results of the Mtb clinical isolate A96, which is resistant to rifampicin and when used to infect BALB/c mice showed hypervirulence, apparently by rapidly polarization of the Th2 immune response through early and high production of IL-4.

Mind the gap in kidney care: translating what we know into what we do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do.

Protective role of ABCC drug subfamily resistance transporters (ABCC1-7) in intestinal inflammation.

The ABCC subfamily contains thirteen members. Nine of these transporters are called multidrug resistance proteins (MRPs). The MRPs have been associated with developing ulcerative colitis (UC).

Bayesian polygenic risk estimation approach to nuclear families with discordant sib-pairs for myelomeningocele.

Myelomeningocele (MMC) is the most severe and disabling form of spina bifida with chronic health multisystem complications and social and economic family and health systems burden. In the present study, we aimed to investigate the genetic risk estimate for MMC in a cohort of 203 Mexican nuclear families with discordant siblings for the defect. Utilizing a custom Illumina array, we analyzed 656 single nucleotide polymorphisms (SNPs) of 395 candidate genes to identify a polygenic risk profile for MMC.

Association between a geriatric measure tool and adverse outcomes among older adults treated in an emergency department: a retrospective cohort study.

The COVID-19 pandemic provided an ideal scenario for studying the care of the elderly population, we implemented a tool named the Geriatric Measure (GM) tool to determine the severity and need for hospitalization. The objective of the study is to evaluate if the results of a brief Geriatric Measure tool are associated with mortality and other outcomes among older adults with COVID-19 treated in the emergency department. Retrospective observational cohort study.

Decellularization of human iliac artery: A vascular scaffold for peripheral repairs with human mesenchymal cells.

This work presents strong evidence supporting the use of decellularized human iliac arteries combined with adipose tissue-derived stem cells (hASCs) as a promising alternative for vascular tissue engineering, opening the path to future treatments for peripheral artery disease (PAD). PAD is a progressive condition with high rates of amputation and mortality due to ischemic damage and limited graft options. Traditional synthetic grafts often fail due to poor integration, while autologous grafts may be unsuitable for patients with compromised vascular health.

Design and evaluation of a multi-epitope HIV-1 vaccine based on human parvovirus virus-like particles.

The development of a protective HIV vaccine remains a challenge given the high antigenic diversity and mutational rate of the virus, which leads to viral escape and establishment of reservoirs in the host. Modern antigen design can guide immune responses towards conserved sites, consensus sequences or normally subdominant epitopes, thus enabling the development of broadly neutralizing antibodies and polyfunctional lymphocyte responses. Conventional epitope vaccines can often be impaired by low immunogenicity, a limitation that may be overcome by using a carrier system.

Scalable Bioreactor-based Suspension Approach to Generate Stem Cell-derived Islets From Healthy Donor-derived iPSCs.

Background: Induced pluripotent stem cells (iPSCs) offer the potential to generate autologous iPSC-derived islets (iPSC islets), however, remain limited by scalability and product safety.

Methods: Herein, we report stagewise characterization of cells generated following a bioreactor-based differentiation protocol. Cell characteristics were assessed using flow cytometry, quantitative reverse transcription polymerase chain reaction, patch clamping, functional assessment, and in vivo functional and immunohistochemistry evaluation.

Rifaximin-Alpha Increases Lactase Activity in Patients with Irritable Bowel Syndrome Without Constipation and Small Intestinal Bacterial Overgrowth.

Background: Irritable bowel syndrome symptoms are associated with diverse pathophysiological mechanisms including small intestinal bacterial overgrowth and food intolerance. Small intestinal bacterial overgrowth leads to the decreased activity of several digestive enzymes, including lactase.

Aims: To assess the efficacy of rifaximin-alpha on the symptoms and lactase activity of patients with irritable bowel syndrome without constipation.

Brain reserve in hepatic encephalopathy: Pathways of damage and preventive strategies through lifestyle and therapeutic interventions.

Brain reserve is an important concept to understand the variability of damage associated with brain-related diseases and includes the adaptation of cognitive processes to preserve brain function. A good cognitive reserve might delay the onset of clinical manifestations of neurodegenerative diseases as well as hepatic encephalopathy, improving the quality of life in patients with chronic liver diseases. By stimulating activities and maintaining overall health, individuals may be able to enhance their brain's resilience to age-related changes and pathology.

Impact of maternal protein restriction on the proteomic landscape of male rat lungs across the lifespan.

The developmental origins of healthy and disease (DOHaD) concept has demonstrated a higher rate of chronic diseases in the adult population of individuals whose mothers experienced severe maternal protein restriction (MPR). Using proteomic and in silico analyses, we investigated the lung proteomic profile of young and aged rats exposed to MPR during pregnancy and lactation. Our results demonstrated that MPR lead to structural and immune system pathways changes, and this outcome is coupled with a rise in the PI3k-AKT-mTOR signaling pathway, with increased MMP-2 activity, and CD8 expression in the early life, with long-term effects with aging.

Morphological changes in the fetal kidney induced by exposure to fluoride during pregnancy.

To determine if fluoride's established negative impact on adult kidney health begins during gestation, an intergenerational model of Wistar rats was exposed to two doses of fluoride (2.5 or 5.0 mg/kg/day via gavage) 20 days before mating and during gestation (20 days).

The association between breakfast frequency and diabetes incidence in middle-aged women: Results from the MTC study.

Background And Aims: Breakfast consumption could have a synchronizer role in chronobiological functions. Across observational studies, the assessment of breakfast frequency consumption is heterogeneous, therefore consensus on the relation between of weekly frequency of breakfast consumption and the risk of diabetes is unclear. We examined the relation between weekly breakfast frequency consumption and the incidence of diabetes in middle-age women.

Ketosis Suppression and Ageing (KetoSAge) Part 2: The Effect of Suppressing Ketosis on Biomarkers Associated with Ageing, HOMA-IR, Leptin, Osteocalcin, and GLP-1, in Healthy Females.

Metabolic dysfunctions are among the best documented hallmarks of ageing. Cardiovascular disease, Alzheimer's disease, cancer, type 2 diabetes mellitus, metabolic-dysfunction-associated steatosis liver disease, and fragility fractures are diseases of hyperinsulinaemia that reduce life and healthspan. We studied the effect of suppressing ketosis in 10 lean (BMI 20.

The evolving role of immune checkpoint inhibitors in cervical and endometrial cancer.

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the treatment landscape for numerous tumor types, including cervical and endometrial cancers. Multiple ICIs against programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) have demonstrated encouraging outcomes in controlled clinical studies for advanced cervical and endometrial cancers. For advanced cervical cancer, approved ICIs as second-line treatment include cemiplimab, nivolumab, and pembrolizumab as single agents.

Maternal protein restriction combined with postnatal sugar consumption alters liver proteomic profile and metabolic pathways in adult male offspring rats.

This study investigated the impact of maternal protein restriction (MPR) and early postnatal sugar consumption (SUG) on the liver health of adult male descendant rats. Male offspring of mothers fed a normal protein diet (NPD) or a low protein diet (LPD) were divided into four groups: Control (CTR), Sugar Control (CTR + SUG), LPD during gestation and lactation (GLLP), and LPD with sugar (GLLP + SUG). Sugar consumption (10% glucose diluted in water) began after weaning on day 21 (PND 21), and at 90 days (PND 90), rats were sacrificed for analysis.

Granulomatous Panniculitis as an Initial Manifestation of Sjögren Syndrome.

A 65-year-old woman presented with unexplained weight loss, recurrent fever, and a dermatosis with painful nodules on the extremities. Biopsies showed focal lobular panniculitis with neutrophilic microgranulomas. Comprehensive investigations ruled out infection and hematologic and solid organ neoplasms.