Daily Remote Ischaemic Preconditioning for Intermittent Claudication: A Sham Controlled Randomised Trial.

Objective: Remote ischaemic preconditioning (RIPC) is a promising non-invasive strategy in which brief episodes of ischaemia and reperfusion can increase skeletal muscle resistance to ischaemia and improve mobility. This study aimed to determine whether 28 consecutive days of RIPC improved intermittent claudication (IC) symptoms compared with sham intervention.

Methods: This single centre, parallel, randomised, sham controlled, double blind trial was conducted from January 2022 to April 2023 in outpatient settings.

CNTN4 modulates neural elongation through interplay with APP.

The neuronal cell adhesion molecule contactin-4 () is genetically associated with autism spectrum disorder (ASD) and other psychiatric disorders. -deficient mouse models have previously shown that CNTN4 plays important roles in axon guidance and synaptic plasticity in the hippocampus. However, the pathogenesis and functional role of CNTN4 in the cortex has not yet been investigated.

Lateral Extra-articular Tenodesis Augmentation of Anterior Cruciate Ligament Reconstruction Is Most Commonly Indicated for Pivot Shift of Grade 2 or Greater and for Revision Anterior Cruciate Ligament Reconstruction.

Purpose: To determine the most common indications for lateral extra-articular tenodesis (LET) augmentation of anterior cruciate ligament reconstruction (ACLR).

Methods: A systematic review of the literature was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched PubMed, Embase, Web of Science, and Cochrane Database of Systematic Reviews from 2000 to the present (June 2022).

Lung-to-Heart Nano-in-Micro Peptide Promotes Cardiac Recovery in a Pig Model of Chronic Heart Failure.

Background: The lack of disease-modifying drugs is one of the major unmet needs in patients with heart failure (HF). Peptides are highly selective molecules with the potential to act directly on cardiomyocytes. However, a strategy for effective delivery of therapeutics to the heart is lacking.

Review of Intra-Articular Use of Antibiotics and Antiseptic Irrigation and Their Systematic Association with Chondrolysis.

Introduction: Intra-articular antibiotics have been proposed as a treatment for septic arthritis to allow for high local concentrations without subjecting a patient to the toxicity/side effects of systemic therapy. However, there is concern for chondrotoxicity with intra-articular use of these solutions in high concentrations. The purpose of this systematic review was to evaluate the intra-articular use of antibiotics and antiseptic solutions, and to determine their association with chondrolysis following or administration.

Effect of a prediction tool and communication skills training on communication of treatment outcomes: a multicenter stepped wedge clinical trial (the SOURCE trial).

Background: For cancer patients to effectively engage in decision making, they require comprehensive and understandable information regarding treatment options and their associated outcomes. We developed an online prediction tool and supporting communication skills training to assist healthcare providers (HCPs) in this complex task. This study aims to assess the impact of this combined intervention (prediction tool and training) on the communication practices of HCPs when discussing treatment options.

The α-(1,3)-glucan synthase gene agsE impacts the secretome of Aspergillus niger.

Aspergillus niger is widely used as a cell factory for the industrial production of enzymes. Previously, it was shown that deletion of α-1-3 glucan synthase genes results in smaller micro-colonies in liquid cultures of Aspergillus nidulans. Also, it has been shown that small wild-type Aspergillus niger micro-colonies secrete more protein than large mirco-colonies.

Time to reimbursement of novel anticancer drugs in Europe: a case study of seven European countries.

Background: Time to reimbursement (TTR) of new anticancer medicines differs between countries and contributes to unequal access. We aimed to investigate TTR of new anticancer medicines and explore factors influencing the reimbursement process in seven high-income European countries.

Materials And Methods: We carried out a retrospective case study of anticancer medicines with European Union Market Access (EU-MA) and a positive Committee for Medicinal Products for Human Use opinion from 2016 until 2021 with subsequent national reimbursement approval (NRA).

Access to medicines for rare diseases: A European regulatory roadmap for academia.

: Novel or repurposed medicines for rare diseases often emerge from fundamental research or empirical findings in academia. However, researchers may be insufficiently aware of the possibilities and requirements to bring novel medicinal treatment options to the patient. This paper aims to provide an easily applicable, comprehensive roadmap designed for academic researchers to make medicines for rare diseases available for patients by addressing the relevant regulatory frameworks, including marketing authorization and alternative routes.

Heterogeneity in Spore Aggregation and Germination Results in Different Sized, Cooperative Microcolonies in an Aspergillus niger Culture.

The fungus Aspergillus niger is among the most abundant fungi in the world and is widely used as a cell factory for protein and metabolite production. This fungus forms asexual spores called conidia that are used for dispersal. Notably, part of the spores and germlings aggregate in an aqueous environment.

Inorganic nitrate supplementation may improve diastolic function and the O cost of exercise in cancer survivors: a pilot study.

In non-cancer populations, inorganic dietary nitrate (NO) supplementation is associated with enhanced cardiorespiratory function but remains untested in patients with a history of cancer. Therefore, this pilot study sought to determine if oral NO supplementation, as a supportive care strategy, increases left ventricular (LV) function and exercise performance in survivors of cancer treated with anticancer therapy while simultaneously evaluating the feasibility of the methods and procedures required for future large-scale randomized trials. Two cohorts of patients with a history of cancer treated with anticancer chemotherapy were recruited.

Painful lower limb nodules as first symptom of resectable pancreatic acinar cell cancer: a case report.

Background: Pancreatic panniculitis is characterized by subcutaneous fat necrosis and is a rare presentation of an underlying pancreatic disease, appearing in approximately 2-3% of all patients with a pancreatic disease. The nodules usually involve the lower extremities. Pancreatic panniculitis is commonly associated with acute or chronic pancreatitis, and occasionally with pancreatic cancer, especially acinar cell carcinoma.

Sbk2, a Newly Discovered Atrium-Enriched Regulator of Sarcomere Integrity.

Background: Heart development relies on tight spatiotemporal control of cardiac gene expression. Genes involved in this intricate process have been identified using animals and pluripotent stem cell-based models of cardio(myo)genesis. Recently, the repertoire of cardiomyocyte differentiation models has been expanded with iAM-1, a monoclonal line of conditionally immortalized neonatal rat atrial myocytes (NRAMs), which allows toggling between proliferative and differentiated (ie, excitable and contractile) phenotypes in a synchronized and homogenous manner.

Genetic characterization of populations in the Marquesas Archipelago in the context of the Austronesian expansion.

Our exploration of the genetic constitution of Nuku Hiva (n = 51), Hiva Oa (n = 28) and Tahuata (n = 8) of the Marquesas Archipelago based on the analyses of genome-wide autosomal markers as well as high-resolution genotyping of paternal and maternal lineages provides us with information on the origins and settlement of these islands at the fringe of the Austronesian expansion. One widespread theme that emerges from this study is the genetic uniformity and relative isolation exhibited by the Marquesas and Society populations. This genetic homogeneity within East Polynesia groups is reflected in their limited average heterozygosity, uniformity of constituents in the Structure analyses, reiteration of complete mtDNA sequences, marked separation from Asian and other Oceanic populations in the PC analyses, limited differentiation in the PCAs and large number of IBD segments in common.

Optimal effectiveness of heart failure management - an umbrella review of meta-analyses examining the effectiveness of interventions to reduce (re)hospitalizations in heart failure.

Heart failure (HF) is a major health concern, which accounts for 1-2% of all hospital admissions. Nevertheless, there remains a knowledge gap concerning which interventions contribute to effective prevention of HF (re)hospitalization. Therefore, this umbrella review aims to systematically review meta-analyses that examined the effectiveness of interventions in reducing HF-related (re)hospitalization in HFrEF patients.

Ribociclib Induces Broad Chemotherapy Resistance and EGFR Dependency in ESR1 Wildtype and Mutant Breast Cancer.

While endocrine therapy is highly effective for the treatment of oestrogen receptor-α (ERα)-positive breast cancer, a significant number of patients will eventually experience disease progression and develop treatment-resistant, metastatic cancer. The majority of resistant tumours remain dependent on ERα-action, with activating gene mutations occurring in 15-40% of advanced cancers. Therefore, there is an urgent need to discover novel effective therapies that can eradicate cancer cells with aberrant ERα and to understand the cellular response underlying their action.

Multistep mechanism of G-quadruplex resolution during DNA replication.

G-quadruplex (or G4) structures form in guanine-rich DNA sequences and threaten genome stability when not properly resolved. G4 unwinding occurs during S phase via an unknown mechanism. Using Xenopus egg extracts, we define a three-step G4 unwinding mechanism that acts during DNA replication.

In-hospital Heart Rate Reduction With Beta Blockers and Ivabradine Early After Recovery in Patients With Acute Decompensated Heart Failure Reduces Short-Term Mortality and Rehospitalization.

In the past years, heart rate (HR) has emerged as a highly relevant modifiable risk factor for heart failure (HF) patients. However, most of the clinical trials so far evaluated the role of HR in stable chronic HF cohorts. The aim of this multi-center, prospective observational study was to assess the association between HR and therapy with HR modulators (beta blockers, ivabradine, or a combination of ivabradine and beta blockers) at hospital discharge with patients' cardiovascular mortality and re-hospitalization at 6 months in acutely decompensated HF patients.

Non-invasive CMR-Based Quantification of Myocardial Power and Efficiency Under Stress and Ischemic Conditions in Landrace Pigs.

Myocardial efficiency should be maintained stable under light-to-moderate stress conditions, but ischemia puts the myocardium at risk for impaired functionality. Additionally, the measurement of such efficiency typically requires invasive heart catheterization and exposure to ionizing radiation. In this work, we aimed to non-invasively assess myocardial power and the resulting efficiency during pharmacological stress testing and ischemia induction.

Proteomics and Phosphoproteomics Profiling of Drug-Addicted BRAFi-Resistant Melanoma Cells.

Acquired resistance to MAPK inhibitors limits the clinical efficacy in melanoma treatment. We and others have recently shown that BRAF inhibitor (BRAFi)-resistant melanoma cells can develop a dependency on the therapeutic drugs to which they have acquired resistance, creating a vulnerability for these cells that can potentially be exploited in cancer treatment. In drug-addicted melanoma cells, it was shown that this induction of cell death was preceded by a specific ERK2-dependent phenotype switch; however, the underlying molecular mechanisms are largely lacking.

The Ami and Yami aborigines of Taiwan and their genetic relationship to East Asian and Pacific populations.

This article reports on the genetic characteristics of the Ami and Yami, two aboriginal populations of Taiwan. Y-SNP and mtDNA markers as well as autosomal SNPs were utilized to investigate the phylogenetic relationships to groups from MSEA (mainland Southeast Asia), ISEA (island Southeast Asia), and Oceania. Both the Ami and Yami have limited genetic diversity, with the Yami having even less diversity than the Ami.