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Science-related populism regressing in the COVID-19 crisis: Any screen survey with the Exercise human population both before and after the actual Coronavirus herpes outbreak.
OBJECTIVE Biventricular assist device (BVAD) implantation is the treatment of choice in patients with severe biventricular heart failure and cardiogenic shock. Our team has developed a miniaturized continuous flow, double-ended centrifugal pump intended for total artificial heart implant (CFTAH). The purpose of this initial in vivo study was to demonstrate that the scaled-down CFTAH (P-CFTAH) can be appropriate for BVAD support. METHODS The P-CFTAH was implanted in four acute lambs (average weight, 41.5 ± 2.8 kg) through a median sternotomy. The cannulation was performed through the left and right atria, and cannulae length adjustment was performed for atrial and ventricular cannulation. The BVAD system was tested at three pump speeds (3000, 4500 and 6000 rpm). RESULTS The BVAD performed very well for both atrial and ventricular cannulation within the 3000 - 6000 rpm range. Stable hemodynamics were maintained after implantation of the P-CFTAH. The self-regulating performance of the system in vivo was demonstrated by the left (LAP) and right (RAP) pressure difference (LAP-RAP) falling predominantly within the range of - 5 to 10 mm Hg with variation, in addition to in vitro assessment of left and right heart failure conditions. Left and right pump flows and total flow increased as the BVAD speed was increased. CONCLUSIONS This initial in vivo testing of the BVAD system demonstrated satisfactory device performance and self-regulation for biventricular heart failure support over a wide range of conditions. The BVAD system keeps the atrial pressure difference within bounds and maintains acceptable cardiac output over a wide range of hemodynamic conditions. The stereotypical spread of pathological protein inclusions and clinicopathological heterogeneity are well described in neurodegenerative diseases. Accumulating evidence suggests that the former can be attributed to consecutive cell-to-cell transmission of pathological proteins between anatomically connected brain regions, while the latter has been hypothesized to result from the spread of conformationally distinct pathological protein aggregates, or strains. These emerging concepts have dramatically changed our understanding of neurodegenerative diseases. In this review, we first summarize the background and recent findings underpinning these concepts with a focus on two major pathological proteins tau and α-synuclein. We then discuss their clinical implications for tauopathies and synucleinopathies and propose a working hypothesis for future research. Permanent damage to the salivary glands and resulting hyposalivation and xerostomia have a substantial impact on patient health, quality of life, and healthcare costs. Currently, patients rely on lifelong treatments that alleviate the symptoms, but no long-term restorative solutions exist. Recent advances in adult stem cell enrichment and transplantation, bioengineering, and gene transfer have proved successful in rescuing salivary gland function in a number of animal models that reflect human diseases and that result in hyposalivation and xerostomia. By overcoming the limitations of stem cell transplants and better understanding the mechanisms of cellular plasticity in the adult salivary gland, such studies provide encouraging evidence that a regenerative strategy for patients will be available in the near future. Keratinocytes and skin immune cells are actively metabolizing nutrients present in their microenvironment. This is particularly important in common chronic inflammatory skin diseases such as psoriasis and atopic dermatitis, characterized by hyperproliferation of keratinocytes and expansion of inflammatory cells, thus suggesting increased cell nutritional requirements. Proliferating inflammatory cells and keratinocytes express high levels of glucose transporter (GLUT)1, l-type amino acid transporter (LAT)1, and cationic amino acid transporters (CATs). Main metabolic regulators such as hypoxia-inducible factor (HIF)-1α, MYC, and mechanistic target of rapamycin (mTOR) control immune cell activation, proliferation, and cytokine release. Here, we provide an updated perspective regarding the potential role of nutrient transporters and metabolic pathways that could be common to immune cells and keratinocytes, to control psoriasis and atopic dermatitis. Background & Aims Fewer data exist on neuro-mental development after fetal exposure to telbivudine. We investigated the developmental consequences of infants from mothers that received telbivudine treatment for chronic hepatitis B (CHB). Methods CHB mothers with high viral load at gestational week 28 were assigned to receive either telbivudine (LdT) or usual care without antiviral therapy, based on the mothers' preference. Their infants were followed for 52 weeks to assess physical and neuro-metal development with Gesell Developmental Schedule tools. Developmental consequences were compared between the two groups. Results Among 258 mothers enrolled, 159 and 99 in the telbivudine-treated and the non-treated group, respectively. The mean duration of telbivudine therapy for the treatment group was 12.31 ± 1.02 weeks. When compared to the control group, infants at the treated-group at the age of 52 weeks had similar neuro-mental development outcomes regarding Gesell Developmental Schedule scores for gross motor (p = 0.55), fine motor (p = 0.31), adaptive (p = 0.10), linguistic (p = 0.97), and personal social (p = 0.52) domains; their physical parameters were also comparable, which included mean height (77.83±3.31 vs. 77.55±3.03 cm; p=0.51) and mean body weight (and 10.59±1.14 vs.10.57±1.19 kg; p=0.89). However, the vertical transmission rates were slightly higher in the control group (3.19% [3/94] vs. 0% [0/150]; p=0.056). Multivariate logistic regression suggested that telbivudine did not associated with negative developmental consequences. Conclusions The developmental consequences of prenatal telbivudine exposure were comparable to those without the exposure in one year observation. Etomoxir cell line We now know that Telbivudine therapy is safe for hepatitis B mothers during pregnancy; ClincialTrials.gov number, NCT02301650. BACKGROUND & AIMS Treatment of older patients (more than 60 years) with ulcerative colitis (UC) can be a challenge, because they might be more vulnerable to adverse events (AEs). We determined the effects of age on the safety and efficacy of anti-tumor necrosis factor (TNF) therapy in a pooled analysis of data from randomized trials. METHODS We obtained individual patient-level data from 4 trials of anti-TNF therapy for patients with UC from the Yale Open Data Access Project. Participants were assigned to groups of older age (60 years or older) and younger age (younger than 60 years). The primary outcome was difference in serious AEs (SAEs), defined as death, life-threatening event, hospitalization, and/or significant disability. Secondary outcomes were severe infections, non-severe infections, neoplasms, and achievement of clinical remission, defined by trial investigators as Mayo score ≤ 2 with no sub-score >1 at the end of induction or maintenance therapy. A random effects logistic regression model was fit in maintaining remission (odds risk ratio, 0.49; 95% CI, 0.18-1.33). CONCLUSIONS In a pooled analysis of data from randomized trials, we found that older patients with UC have an increased baseline increased risk of SAEs, but no increase in risk can be attributed to anti-TNF therapy in older vs younger patients. BACKGROUND Patients eligible and referred for lung cancer screening (LCS) may not complete the visit. We aimed to identify differences in demographic, clinical, and socioeconomic characteristics between LCS participants and LCS-eligible nonparticipants and determine potential reasons for nonparticipation. MATERIALS AND METHODS LCS-eligible patients referred between April 2015 and August 2016 were divided into participants and nonparticipants. Retrospective data were collected. A telephone survey was conducted in a subset of nonparticipants to identify reasons for not participating and assess their understanding of the benefits and harms of LCS. RESULTS We identified 542 participants and 276 LCS-eligible nonparticipants. Female sex, lower pack-years, active smoking, the absence of a history of chronic obstructive pulmonary disease, coronary artery disease, or liver disease, and chronic kidney disease or a history of malignancy were associated with not participating. One hundred nonparticipants completed the telephone survey-29% were unaware of the appointment; 19% had concerns about the distance from the screening site and 14% with insurance coverage; 10% had fear of the imaging result; and 10% felt the computed tomography scan was unnecessary. Eighteen percent knew the benefit of LCS, and 69% were not aware of any screening harms. CONCLUSIONS LCS-eligible nonparticipants are more likely to be female, active smokers, have fewer total pack-years of smoking, chronic kidney disease, a history of prior malignancy, and not have chronic obstructive pulmonary disease, coronary artery disease, or liver disease. Targeted education about the benefits and harms of LCS, verification of insurance coverage, and providing convenient screening locations may improve participation. Alzheimer's disease (AD) is the most common cause of dementia, characterised by advanced cognitive and memory deterioration with no effective treatments available. Previous in vitro and in vivo studies suggest that paeoniflorin (PF), a major bioactive constituent of Radix Paeoniae, might possess anti-dementia properties; however, the underlying mechanism remains unclear. The aim of the current study was to determine the therapeutic effects of PF in a transgenic mouse model of AD and to identify its mechanism. Transgenic mice with five familial AD mutations (5XFAD) were used in this study. We showed that 28 days of PF (5 mg/kg, ip) treatment significantly decreased the escape latency and path length in the Morris water maze test and increased the alternation rate in the T-maze test, compared to the vehicle treatment group. In addition, PF treatment significantly alleviated amyloid β plaque burden, inhibited astrocyte activation, and decreased IL-1β and TNF-α expression in the brain of 5XFAD mice. However, the anti-cognitive deficits, anti-amyloidogenic, and anti-inflammatory effects of PF were abolished by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.3 mg/kg), an adenosine A1 receptor (A1R) antagonist. In conclusion, our results suggest that PF might act as a potential therapeutic agent for AD via activation of adenosine A1R. Pathologic intracellular inclusions formed from polymers of misfolded α-synuclein (αsyn) protein define a group of neurodegenerative diseases termed synucleinopathies which includes Parkinson's disease (PD). Prion-like recruitment of endogenous cellular αsyn has been demonstrated to occur in animal models of synucleinopathy, whereby misfolded αsyn can induce further pathologic αsyn inclusions to form through a prion-like mechanism. It has been suggested that misfolded αsyn may assume differing conformations which lead to varied clinical and pathological manifestations of disease; this phenomenon bears similarities to that of prion strains whereby the same misfolded protein can produce unique diseases. It is unclear what factors influence the development of unique αsyn strains, however post-translational modifications (PTMs) such as phosphorylation and truncation that are present in misfolded αsyn in disease may play a role due to their modulation of biochemical and structural αsyn properties. Herein, we investigate the prion-like properties of misfolded αsyn polymers containing either phosphomimetic (S129E) αsyn, 5 different major carboxy (C)-truncated forms of αsyn (1-115, 1-119, 1-122, 1-125, and 1-129 αsyn), or a mixture of these PTM containing αsyn forms compared to full-length (FL) αsyn in HEK293T cells and M83 transgenic mice overexpressing A53T αsyn.
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