Assessment of tuberculosis drug efficacy using preclinical animal models and in vitro predictive techniques.

Tuberculosis (TB) killed approximately 1.3 million people in 2022 and remains a leading cause of death from the bacteria Mycobacterium tuberculosis (M.tb); this number of deaths was surpassed only by COVID-19, caused by the SARS-CoV-2 virus.

Enhanced D614G and Omicron Variants Antibody Persistence in Infants at 2 Months of Age Following Maternal mRNA Booster Vaccination During Pregnancy or Postpartum.

Background: Following maternal COVID-19 vaccination, the persistence of antibodies in sera and breast milk for mothers and infants is not well characterized. We sought to describe the persistence of antibodies through 2 months after delivery in maternal and infant serum and breast milk following maternal COVID-19 mRNA vaccination and to examine differences by receipt of booster dose during pregnancy or postpartum.

Methods: This is a prospective cohort study with enrollment from July 2021 to January 2022 at 9 US academic sites.

The chosen few: isolates for IMPAc-TB.

The three programs that make up the Immune Mechanisms of Protection Against Centers (IMPAc-TB) had to prioritize and select strains to be leveraged for this work. The CASCADE team based at Seattle Children's Research Institute are leveraging M.tb H37Rv, M.

Teosinte Pollen Drive guides maize diversification and domestication by RNAi.

Selfish genetic elements contribute to hybrid incompatibility and bias or 'drive' their own transmission. Chromosomal drive typically functions in asymmetric female meiosis, whereas gene drive is normally post-meiotic and typically found in males. Here, using single-molecule and single-pollen genome sequencing, we describe Teosinte Pollen Drive, an instance of gene drive in hybrids between maize (Zea mays ssp.

Protective interplay: diminishes SARS-CoV-2 severity through innate immune priming.

At the beginning of the COVID-19 pandemic those with underlying chronic lung conditions, including tuberculosis (TB), were hypothesized to be at higher risk of severe COVID-19 disease. However, there is inconclusive clinical and preclinical data to confirm the specific risk SARS-CoV-2 poses for the millions of individuals infected with (M.tb).

Effects of Cardiopulmonary Rehabilitation on Cardiorespiratory Fitness and Clinical Symptom Burden in Long COVID: Results From the COVID-Rehab Randomized Controlled Trial.

Objective: The aim of the study is to investigate the effectiveness of an 8-wk cardiopulmonary rehabilitation program on cardiorespiratory fitness (VO 2 peak) and key cardiopulmonary exercise test measures, quality of life, and symptom burden in individuals with long COVID.

Design: Forty individuals with long COVID (mean age 53 ± 11 yrs), were randomized into two groups: (1) rehabilitation group: center-based individualized clinical rehabilitation program (8 wks, 3 sessions per week of aerobic and resistance exercises, and daily inspiratory muscle training) and (2) control group: individuals maintained their daily habits during an 8-wk period.

Results: There was a significant difference between groups in mean VO 2 peak improvement ( P = 0.

A Novel Use of a Not So "EZ-Blocker" For Lung Isolation During a Direct Transaortic Transcatheter Aortic Valve Replacement.

Alternate access transcatheter aortic valve replacement presents unique challenges for anesthesiologists, including the possible need for lung isolation while working with space constraints around the patient's airway. Troubleshooting lung isolation in these cases can be challenging, requiring quick thinking and adaptability while maintaining patient safety. We present a case of direct transaortic transcatheter aortic valve replacement with an endobronchial blocker ("EZ-blocker") used for lung isolation that required a novel use of the "EZ-blocker" to achieve adequate lung isolation.

Chromatin remodeling of histone H3 variants by DDM1 underlies epigenetic inheritance of DNA methylation.

Nucleosomes block access to DNA methyltransferase, unless they are remodeled by DECREASE in DNA METHYLATION 1 (DDM1), a Snf2-like master regulator of epigenetic inheritance. We show that DDM1 promotes replacement of histone variant H3.3 by H3.

guides maize diversification and domestication by RNAi.

Meiotic drivers subvert Mendelian expectations by manipulating reproductive development to bias their own transmission. Chromosomal drive typically functions in asymmetric female meiosis, while gene drive is normally postmeiotic and typically found in males. Using single molecule and single-pollen genome sequencing, we describe , an instance of gene drive in hybrids between maize () and teosinte (), that depends on RNA interference (RNAi).

Chromatin remodeling of histone H3 variants underlies epigenetic inheritance of DNA methylation.

Epigenetic inheritance refers to the faithful replication of DNA methylation and histone modification independent of DNA sequence. Nucleosomes block access to DNA methyltransferases, unless they are remodeled by DECREASE IN DNA METHYLATION1 (DDM1 ), a Snf2-like master regulator of epigenetic inheritance. We show that DDM1 activity results in replacement of the transcriptional histone variant H3.

A localizing nanocarrier formulation enables multi-target immune responses to multivalent replicating RNA with limited systemic inflammation.

RNA vaccines possess significant clinical promise in counteracting human diseases caused by infectious or cancerous threats. Self-amplifying replicon RNA (repRNA) has been thought to offer the potential for enhanced potency and dose sparing. However, repRNA is a potent trigger of innate immune responses in vivo, which can cause reduced transgene expression and dose-limiting reactogenicity, as highlighted by recent clinical trials.

Preparation Strategies of the Anti-Mycobacterial Drug Bedaquiline for Intrapulmonary Routes of Administration.

() has infected one-quarter of the world's population and led to the deaths of 1.6 million individuals in 2021 according to estimates from the World Health Organization. The rise in prevalence of multidrug-resistant and extensively drug-resistant strains coupled with insufficient therapies to treat such strains has motivated the development of more effective treatments and/or delivery modalities.

Evaluation of repRNA vaccine for induction and in utero transfer of maternal antibodies in a pregnant rabbit model.

Mother-to-child transmission is a major route for infections in newborns. Vaccination in mothers to leverage the maternal immune system is a promising approach to vertically transfer protective immunity. During infectious disease outbreaks, such as the 2016 Zika virus (ZIKV) outbreak, rapid availability of vaccines can prove critical in reducing widespread disease burden.

Cardiorespiratory Fitness Moderates the Age-Related Association Between Executive Functioning and Mobility: Evidence From Remote Assessments.

Background And Objectives: In older adults, executive functions are important for daily-life function and mobility. Evidence suggests that the relationship between cognition and mobility is dynamic and could vary according to individual factors, but whether cardiorespiratory fitness reduces the age-related increase of interdependence between mobility and cognition remains unexplored.

Research Design And Methods: One hundred eighty-nine participants (aged 50-87) were divided into 3 groups according to their age: middle-aged (MA; <65), young older adults (YOA; 65-74), and old older adults (OOA; ≥75).

Characterizing in vivo loss of virulence of an HN878 Mycobacterium tuberculosis isolate from a genetic duplication event.

The increase of global cases of drug resistant (DR) Mycobacterium tuberculosis (M.tb) is a serious problem for the tuberculosis research community and the goals to END TB by 2030. Due to the need for advancing and screening next generation therapeutics and vaccines, we aimed to design preclinical DR models of Beijing lineage M.

Mastering the Relationship between the Body and the Brain? The Case of a Female Master Athlete.

Background: Physical inactivity significantly increases risk of cardiovascular diseases, which are highly prevalent in aging. Conversely, higher levels of physical activity in aging have been associated with benefits for physical and cognitive health and is hypothesized to prevent and reduce development of cardiovascular risk factors. However, those older adults with the highest activity levels (i.

COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn (DMID 21-0004).

Importance: COVID-19 vaccination is recommended during pregnancy for the protection of the mother. Little is known about the immune response to booster vaccinations during pregnancy.

Objective: To measure immune responses to COVID-19 primary and booster mRNA vaccination during pregnancy and transplacental antibody transfer to the newborn.

Cardiopulmonary Rehabilitation in Long-COVID-19 Patients with Persistent Breathlessness and Fatigue: The COVID-Rehab Study.

(1) Background: Cardiopulmonary and brain functions are frequently impaired after COVID-19 infection. Exercise rehabilitation could have a major impact on the healing process of patients affected by long COVID-19. (2) Methods: The COVID-Rehab study will investigate the effectiveness of an eight-week cardiopulmonary rehabilitation program on cardiorespiratory fitness (V˙Omax) in long-COVID-19 individuals.

Triazolopyrimidines Target Aerobic Respiration in Mycobacterium tuberculosis.

We previously identified a series of triazolopyrimidines with antitubercular activity. We determined that Mycobacterium tuberculosis strains with mutations in QcrB, a subunit of the cytochrome supercomplex, were resistant. A cytochrome oxidase deletion strain was more sensitive to this series.

Videoconference version of the Montreal Cognitive Assessment: normative data for Quebec-French people aged 50 years and older.

Background: The COVID-19 pandemic forced health professionals to rapidly develop and implement telepractice and remote assessments. Recent reviews appear to confirm the validity of a wide range of neuropsychological tests for teleneuropsychology and among these, the Montreal Cognitive Assessment (MoCA), a cognitive screening test widely used in clinical settings. The normative data specific to the context of videoconference administration is essential, particularly that consider sociodemographic characteristics.