jaenisch

Mutations in the methyl-DNA-binding protein MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT). How MECP2 contributes to transcriptional regulation in normal and disease states is unresolved; it has been reported to be an activator and a repressor. We describe here the first integrated CUT&Tag, transcriptome, and proteome analyses using human neurons with wild-type (WT) and mutant MECP2 molecules. MECP2 occupies CpG-rich promoter-proximal regions in over four thousand genes in human neurons, including a plethora of autism risk genes, together with RNA polymerase II (RNA Pol II)...

Observational data provide invaluable real-world information in medicine, but certain methodological considerations are required to derive causal estimates. In this systematic review, we evaluated the methodology and reporting quality of individual-level patient data meta-analyses (IPD-MAs) conducted with non-randomized exposures, published in 2009, 2014, and 2019 that sought to estimate a causal relationship in medicine. We screened over 16,000 titles and abstracts, reviewed 45 full-text articles out of the 167 deemed potentially eligible, and included 29 into the analysis...

No abstract text is available yet for this article.

INTRODUCTION: Protocols for obtaíníng the maxímum threshold pressure have been applied wíth límited precision to evaluate ínspiratory muscle endurance. In thís sense, new protocols are needed to allow more relíable measurements. The purpose of the present study was to compare a new incremental ramp load protocol for the evaluation of ínspíratory muscle endurance wíth the most used protocol in healthy indíviduals. METHODS: This was a prospective cross-sectional study carried out ín a síngle center...

The 2015-17 Zika virus (ZIKV) epidemic in the Americas subsided faster than expected and evolving population immunity was postulated to be the main reason. Herd immunization is suggested to occur around 60-70% seroprevalence, depending on demographic density and climate suitability. However, herd immunity was only documented for a few cities in South America, meaning a substantial portion of the population might still be vulnerable to a future Zika virus outbreak. The aim of our study was to determine the vulnerability of populations to ZIKV by comparing the environmental suitability of ZIKV transmission to the observed seroprevalence, based on published studies...

OBJECTIVES: To compare the effects of passive recovery (PR), active recovery (AR), and recovery through self-massage with the aid of foam rolling (FRR) on pain and physical capacity in healthy volunteers after a resistance exercise (RE) session. METHODS: The sample of this randomized crossover trial comprised 37 physically healthy men who underwent three sessions of RE (squat, leg press, and leg extension), involving four sets of 10 repetitions with 80% of 10MR, with an interval of seven days between sessions...

This short communication is an effort to describe and elucidate the trajectory of the modern historical concept of "One Health." It is dedicated to the many integrated approaches of health closely related to One Health, while also recognizing the contribution and origination of One Health perspectives/notions from those that have led the way and spearheaded this movement while considering Indigenous cultures across the world. The effects of synergies of those involved in building these integrative approaches are potentially bigger and better lasting than the sum of the individual players...

Developing effective vaccines against viral infections have significant impacts on development, prosperity and well-being of human populations. Thus, successful vaccines such as smallpox and polio vaccines, have promoted global societal well-being. In contrast, ineffective vaccines may fuel arguments that retard scientific progress. We aim to stimulate a multilevel discussion on how to develop effective vaccines against recent and future pandemics by focusing on acquired immunodeficiency syndrome (AIDS), coronavirus disease (COVID) and other viral infections...

Bat-borne viruses have attracted considerable research, especially in relation to the Covid-19 pandemic. Although bats can carry multiple zoonotic viruses that are lethal to many mammalian species, they appear to be asymptomatic to viral infection despite the high viral loads contained in their bodies. There are several differences between bats and other mammals. One of the major differences between bats and other mammals is the bats' ability to fly, which is believed to have induced evolutionary changes. It may have also favoured them as suitable hosts for viruses...

Biological augmentation of bony defects in weight-bearing areas of both the acetabulum and the femur remains challenging. The calcium-silicate-based ceramic Baghdadite is a very interesting material to be used in the field of revision total hip arthroplasty for the treatment of bony defects in weight-bearing and non-weight-bearing areas alike. The aim of this study was to investigate the biocompatibility of Baghdadite utilizing an osteoblast-like, human osteosarcoma cell line (MG-63) and the human monocytic leukemia-derived cell line (THP-1)...

A complete knockout of a single key pluripotency gene may drastically affect embryonic stem cell function and epigenetic reprogramming. In contrast, elimination of only one allele of a single pluripotency gene is mostly considered harmless to the cell. To understand whether complex haploinsufficiency exists in pluripotent cells, we simultaneously eliminated a single allele in different combinations of two pluripotency genes (i.e., Nanog+/- ;Sall4+/- , Nanog+/- ;Utf1+/- , Nanog+/- ;Esrrb+/- and Sox2+/- ;Sall4+/- )...

We present a framework for a federated, virtual biorepository system (VBS) with locally collected and managed specimens, as a 'global public good' model based on principles of equitable access and benefit sharing. The VBS is intended to facilitate timely access to biological specimens and associated data for outbreak-prone infectious diseases to accelerate the development and evaluation of diagnostics, assess vaccine efficacy, and to support surveillance and research needs. The VBS is aimed to be aligned with the WHO BioHub and other specimen sharing efforts as a force multiplier to meet the needs of strengthening global tools for countering epidemics...

Total hip arthroplasty (THA) is commonly performed using off-the-shelf implants. In the case of a severe mismatch between the anatomy of the proximal femur and the geometry of the stem, the use of custom-made stems might become necessary. The goal of this study was to investigate the precision of the implantation of custom-made stems of one manufacturer (CTX stem, AQ Implants) and to determine risk factors for malpositioning. All patients receiving a custom-made CTX stem between 2014 and 2020 at six high-volume academic centers were retrospectively recruited...

The planning and implantation of a customized partial pelvis replacement places high demands on both the surgeon and the entire team (engineer, assistants, surgical team). Thanks to careful preoperative planning and meticulous perioperative execution, customized partial pelvic replacement represents a complex but reliable procedure for defect reconstruction even with highly complex acetabular bone defects or after multiple previous surgeries.

Observational data provide invaluable real-world information in medicine, but certain methodological considerations are required to derive causal estimates. In this systematic review, we evaluated the methodology and reporting quality of individual-level patient data meta-analyses (IPD-MAs) published in 2009, 2014, and 2019 that sought to estimate a causal relationship in medicine. We screened over 16,000 titles and abstracts, reviewed 45 full-text articles out of the 167 deemed potentially eligible, and included 29 into the analysis...

Parkinson's disease (PD) is characterized by the aggregation of α-synuclein into Lewy bodies and Lewy neurites in the brain. Microglia-driven neuroinflammation may contribute to neuronal death in PD, however the exact role of microglia remains unclear and has been understudied. The A53T mutation in the gene coding for α-synuclein has been linked to early-onset PD, and exposure to A53T-mutant human α-synuclein increases the potential for inflammation of murine microglia. To date, its effect has not been studied in human microglia...

COVID-19 has impacted billions of people since 2019 and unfolded a major healthcare crisis. With an increasing number of deaths and the emergence of more transmissible variants, it is crucial to better understand the biology of the disease-causing virus, the SARS-CoV-2. Peripheral neuropathies appeared as a specific COVID-19 symptom occurring at later stages of the disease. In order to understand the impact of SARS-CoV-2 on the peripheral nervous system, we generated human sensory neurons from induced pluripotent stem cells that we infected with the SARS-CoV-2 strain WA1/2020 and the variants delta and omicron...

Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), nearly 20% of hospitalized patients are at risk for thromboembolic events 1 . This prothrombotic state is considered a key factor in the increased risk of stroke, which has been observed clinically during both acute infection and long after symptoms have cleared 2 . Here we developed a model of SARS-CoV-2 infection using human-induced pluripotent stem cell-derived endothelial cells, pericytes, and smooth muscle cells to recapitulate the vascular pathology associated with SARS-CoV-2 exposure...

INTRODUCTION: People with type 2 diabetes mellitus present multiple complications and comorbidities, such as peripheral autonomic neuropathies and reduced peripheral force and functional capacity. Inspiratory muscle training is a widely used intervention with numerous benefits for various disorders. The present study aimed to conduct a systematic review to identify inspiratory muscle training effects on functional capacity, autonomic function, and glycemic indexes in patients with type 2 diabetes mellitus...

BACKGROUND: The four Dengue viruses (DENV) serotypes were re-introduced in Brazil's Northeast region in a couple of decades, between 1980's and 2010's, where the DENV1 was the first detected serotype and DENV4 the latest. Zika (ZIKV) and Chikungunya (CHIKV) viruses were introduced in Recife around 2014 and led to large outbreaks in 2015 and 2016, respectively. However, the true extent of the ZIKV and CHIKV outbreaks, as well as the risk factors associated with exposure to these viruses remain vague...