Bioluminescent Pseudomonas aeruginosa and Escherichia coli for whole-cell screening of antibacterial and adjuvant compounds.

Continued efforts to discover new antibacterial molecules are critical to achieve a robust pre-clinical pipeline for new antibiotics. Screening of compound or natural product extract libraries remains a widespread approach and can benefit from the development of whole cell assays that are robust, simple and versatile, and allow for high throughput testing of antibacterial activity. In this study, we created and validated two bioluminescent reporter strains for high-throughput screening, one in Pseudomonas aeruginosa, and another in a hyperporinated and efflux-deficient Escherichia coli.

The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.

Deficits in IL-2 signaling can precipitate autoimmunity by altering the function and survival of FoxP3+ regulatory T cells (Tregs) while high concentrations of IL-2 fuel inflammatory responses. Recently, we showed that the non-beta IL-2 SYNTHORIN molecule SAR444336 (SAR'336) can bypass the induction of autoimmune and inflammatory responses by increasing its reliance on IL-2 receptor α chain subunit (CD25) to provide a bona fide IL-2 signal selectively to Tregs, making it an attractive approach for the control of autoimmunity. In this report, we further demonstrate that SAR'336 can support non-beta IL-2 signaling in murine Tregs and limit NK and CD8+ T cells' proliferation and function.

Determinants of Positive Evolution of Symptoms in Children with Autism Spectrum Disorders (ASD) during the COVID-19 Lockdown in the Democratic Republic of Congo. (DRC).

Lockdown imposed by the COVID 19 pandemic increased the time families spent together at home. A negative impact of the lock-down on children with autism has been reported. Few studies described the positive impact of parents' presence on the severity of their children's autism symptoms during lockdown.

Arterial stiffness as a novel tool for the early prediction of preeclampsia: a perspective.

Preeclampsia is a leading complication of pregnancy that lacks accurate tools for its early prediction. Improved risk stratification tools early in pregnancy would enable more efficient allocation of limited healthcare resources while ensuring that pregnant women destined to develop preeclampsia receive appropriate care. This brief perspective highlights the current state of first-trimester preeclampsia prediction.

Four-Year Trajectories of Symptoms and Quality of Life in Individuals Hospitalized After Mild Traumatic Brain Injury.

Objectives: To (1) detect distinct trajectories of symptoms and quality of life (QoL) over the first 4 years after mild traumatic brain injury (mTBI); (2) assess the relationship between symptom trajectory membership and QoL trajectory membership; and (3) identify participant characteristics associated with QoL trajectory membership.

Design: Prospective longitudinal cohort study. Assessments occurred at 4, 8, 12, 24, 36, and 48 months after mTBI.

Cytokine priming enhances the antifibrotic effects of human adipose derived mesenchymal stromal cells conditioned medium.

Background: Fibrosis is a pathological scarring process characterized by persistent myofibroblast activation with excessive accumulation of extracellular matrix (ECM). Fibrotic disorders represent an increasing burden of disease-associated morbidity and mortality worldwide for which there are limited therapeutic options. Reversing fibrosis requires the elimination of myofibroblasts, remodeling of the ECM, and regeneration of functional tissue.

Vascular injury derived apoptotic exosome-like vesicles trigger autoimmunity.

According to a central tenet of classical immune theory, a healthy immune system must avoid self-reactive lymphocyte clones but we now know that B cells repertoire exhibit some level of autoreactivity. These autoreactive B cells are thought to rely on self-ligands for their clonal selection and survival. Here, we confirm that healthy mice exhibit self-reactive B cell clones that can be stimulated by agonists of toll-like receptor (TLR) 1/2, TLR4, TLR7 and TLR9 to secrete anti-LG3/perlecan.

A qualitative study exploring the perinatal experiences of social stress among first- and second-generation immigrant parents in Quebec, Canada.

Background: Perinatal psychological distress adversely impacts the well-being and social adjustment of parents and their children. Expectant parents who have migrated may be at higher risk for perinatal psychological distress due to various migration-specific stressors and healthcare service barriers. Limited studies have examined the perceived determinants of perinatal distress in immigrant parents, particularly men.

Multivariate analyses and machine learning link sex and age with antibody responses to SARS-CoV-2 and vaccination.

Prevention of negative COVID-19 infection outcomes is associated with the quality of antibody responses, whose variance by age and sex is poorly understood. Network approaches identified sex and age effects in antibody responses and neutralization potential of infection and vaccination throughout the COVID-19 pandemic. Neutralization values followed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific receptor binding immunoglobulin G (RIgG), spike immunoglobulin G (SIgG) and spike and receptor immunoglobulin G (S, and RIgA) levels based on COVID-19 status.

Reactive oxygen species in hypertension.

Hypertension is a leading risk factor for stroke, heart disease and chronic kidney disease. Multiple interacting factors and organ systems increase blood pressure and cause target-organ damage. Among the many molecular elements involved in the development of hypertension are reactive oxygen species (ROS), which influence cellular processes in systems that contribute to blood pressure elevation (such as the cardiovascular, renal, immune and central nervous systems, or the renin-angiotensin-aldosterone system).

Investigating the effect of cGRP78 vaccine against different cancer cells and its role in reducing melanoma metastasis.

Background And Purpose: Treatment of malignancies with chemotherapy and surgery is often associated with disease recurrence and metastasis. Immunotherapy improves cancer treatment by creating an active response against tumor antigens. Various cancer cells express a large amount of glucose-regulated protein 78 (GRP78) protein on their surface.

Patterns of Gestational Hypertension or Preeclampsia Across 2 Pregnancies in Relationship to Chronic Hypertension Development: A Retrospective Cohort Study.

Background: Gestational hypertension (GHTN) and preeclampsia are established risk indicators for chronic hypertension. While recurrence is associated with a greater risk, it is unclear whether there are differences in risk when these gestational complications occur for the first time in an earlier pregnancy versus first occurrence in a subsequent one. We hypothesized that the absence of recurrence reflects a transition toward a lower hypertension risk trajectory, whereas a new occurrence in a later pregnancy indicates a transition toward elevated risk.

Effects of combined radiotherapy with immune checkpoint blockade on immunological memory in luminal-like subtype murine bladder cancer model.

MIBC is a highly lethal disease, and the patient survival rate has not improved significantly over the last decades. UPPL is a cell line that can be used to recapitulate the luminal-like molecular subtype of bladder cancer and to discover effective treatments to be translated in patients. Here, we investigate the effects of combinational treatments of radiotherapy and immunotherapy in this recently characterized UPPL tumor-bearing mice.

Signatures of epigenetic, biological and mitotic age acceleration and telomere shortening are associated with arsenic-induced skin lesions.

Chronic arsenic exposure is a global health hazard significantly associated with the development of deleterious cutaneous changes and increased keratinocyte cancer risk. Although arsenic exposure is associated with broad-scale cellular and molecular changes, gaps exist in understanding how these changes impact the skin and facilitate malignant transformation. Recently developed epigenetic "clocks" can accurately predict chronological, biological and mitotic age, as well as telomere length, on the basis of tissue DNA methylation state.

HiChIP-Based Epigenomic Footprinting Identifies a Promoter Variant of UXS1 That Confers Genetic Susceptibility to Gastroesophageal Cancer.

Genome-wide association studies (GWAS) have identified more than a hundred single nucleotide variants (SNV) associated with the risk of gastroesophageal cancer (GEC). The majority of the identified SNVs map to noncoding regions of the genome. Uncovering the causal SNVs and genes they modulate could help improve GEC prevention and treatment.

Incident Diabetes in Women With Patterns of Gestational Diabetes Occurrences Across 2 Pregnancies.

Importance: Gestational diabetes is a type 2 diabetes risk indicator, and recurrence further augments risk. In women with a single occurrence across 2 pregnancies, it is unclear whether first- vs second-pregnancy gestational diabetes differ in terms of risk.

Objective: To compare the hazards of incident diabetes among those with gestational diabetes in the first, in the second, and in both pregnancies with women without gestational diabetes in either.

Enrollment, adherence and retention rates among musculoskeletal disorders rehabilitation practitioners in knowledge translation studies: a systematic review and meta-regression.

Background: Practitioners' enrollment, adherence, and retention rates influence estimates of effectiveness in knowledge translation (KT) studies and remain important concerns for implementation researchers. This review aimed to systematically summarize the current evidence on feasibility measures as gauged by enrollment, adherence, and retention rates in KT evaluation studies targeting rehabilitation practitioners treating musculoskeletal disorders (MSDs).

Methods: We searched five electronic databases from the inception to October 2022.

Surround masking reveals binocular adding and differencing channels.

Recent studies suggest that binocular adding S+ and differencing S- channels play an important role in binocular vision. To test for such a role in the context of binocular contrast detection and binocular summation, we employed a surround masking paradigm consisting of a central target disk surrounded by a mask annulus. All stimuli were horizontally oriented 0.

Clinical Accuracy of Serum Neurofilament Light to Differentiate Frontotemporal Dementia from Primary Psychiatric Disorders is Age-Dependent.

Background: Symptoms of behavioral variant frontotemporal dementia (bvFTD) overlap with primary psychiatric disorders (PPD) making diagnosis challenging. Serum neurofilament light (sNfL) is a candidate biomarker to distinguish bvFTD from PPD, but large-scale studies in PPD are lacking.

Objective: Determine factors that influence sNfL from a large database of PPD patients, and test its diagnostic accuracy.

Deciphering the developmental trajectory of tissue-resident Foxp3 regulatory T cells.

Foxp3 T cells have been at the focus of intense investigation for their recognized roles in preventing autoimmunity, facilitating tissue recuperation following injury, and orchestrating a tolerance to innocuous non-self-antigens. To perform these critical tasks, T cells undergo deep epigenetic, transcriptional, and post-transcriptional changes that allow them to adapt to conditions found in tissues both at steady-state and during inflammation. The path leading T cells to express these tissue-specialized phenotypes begins during thymic development, and is further driven by epigenetic and transcriptional modifications following TCR engagement and polarizing signals in the periphery.

Improving emotion perception in cochlear implant users: insights from machine learning analysis of EEG signals.

Background: Although cochlear implants can restore auditory inputs to deafferented auditory cortices, the quality of the sound signal transmitted to the brain is severely degraded, limiting functional outcomes in terms of speech perception and emotion perception. The latter deficit negatively impacts cochlear implant users' social integration and quality of life; however, emotion perception is not currently part of rehabilitation. Developing rehabilitation programs incorporating emotional cognition requires a deeper understanding of cochlear implant users' residual emotion perception abilities.

Introduction of a new recombinant vaccine based on GRP78 for breast cancer immunotherapy and evaluation in a mouse model.

Introduction: Breast cancer is one of the most prevalent malignancies in women. Several treatment options are available today, including surgery, chemotherapy, and radiotherapy. Immunotherapy, as a highly specific therapy, involves adaptive immune responses and immunological memory.

The impact of Foxp3 regulatory T-cells on CD8 T-cell dysfunction in tumour microenvironments and responses to immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have been a breakthrough in cancer therapy, inducing durable remissions in responding patients. However, they are associated with variable outcomes, spanning from disease hyperprogression to complete responses with the onset of immune-related adverse events. The consequences of checkpoint inhibition on Foxp3 regulatory T (T ) cells remain unclear but could provide key insights into these variable outcomes.