Role of Annexin 7 (ANXA7) as a Tumor Suppressor and a Regulator of Drug Resistance in Thyroid Cancer.

Thyroid cancer is the most common endocrine malignancy in the United States, with an overall favorable prognosis. However, some patients experience poor outcomes due to the development of resistance to conventional therapies. Genetic alterations, including mutations in BRAF, Met, and p53, play critical roles in thyroid cancer progression, with the BRAF V600E mutation detected in over 60% of cases.

Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission.

Cyclic nucleotide-dependent phosphodiesterases (PDEs) play essential roles in regulating the malaria parasite life cycle, suggesting that they may be promising antimalarial drug targets. PDE inhibitors are used safely to treat a range of noninfectious human disorders. Here, we report three subseries of fast-acting and potent PDEβ inhibitors that block asexual blood-stage parasite development and that are also active against human clinical isolates.

The effect of expiratory flow limitation on supine persistent hyperinflation in COPD: a prospective observational study.

Introduction: COPD is characterised by airflow obstruction, expiratory airway collapse and closure causing expiratory flow limitation (EFL) and hyperinflation. Supine posture may worsen ventilatory function in COPD, which may cause hyperinflation to persist and contribute to symptoms of orthopnoea and sleep disturbance. Our aim was to determine the impact of supine posture on hyperinflation, dynamic elastance and EFL in COPD and healthy subjects.

Property and Activity Refinement of Dihydroquinazolinone-3-carboxamides as Orally Efficacious Antimalarials that Target PfATP4.

To contribute to the global effort to develop new antimalarial therapies, we previously disclosed initial findings on the optimization of the dihydroquinazolinone-3-carboxamide class that targets PfATP4. Here we report on refining the aqueous solubility and metabolic stability to improve the pharmacokinetic profile and consequently in vivo efficacy. We show that the incorporation of heterocycle systems in the 8-position of the scaffold was found to provide the greatest attainable balance between parasite activity, aqueous solubility, and metabolic stability.

Treatment of type 2 diabetes and stress using neuro-emotional technique: case report.

This case report presents a novel, non-pharmacological treatment of Type 2 Diabetes in a 46-year-old male, demonstrating improvements in blood chemistry and psychometric markers after 8 treatments using a Mind-Body Intervention (MBI) called Neuro-Emotional Technique (NET). The patient presented with a diagnosis of Type 2 Diabetes (T2D), pain, psychosocial indicators of stress and anxiety, and a score of 4 on the ACE-Q (Adverse Childhood Experiences Questionnaire) that is consistent with a predisposition to chronic disease and autoimmune disorders. Glucose levels for this patient were above normal levels (typically between 10-15mmol/L where optimal range is between 4-10mmol/L) for at least two months prior to the 4-week NET intervention period, despite the standard use of conventional antidiabetic medications (insulin injections).

Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 spike protein.

SARS-CoV-2-contributes to sickness and death in COVID-19 patients partly by inducing a hyper-proinflammatory immune response in the host airway. This hyper-proinflammatory state involves activation of signaling by NFκB, and unexpectedly, ENaC, the epithelial sodium channel. Post-infection inflammation may also contribute to "Long COVID"/PASC.

Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1.

With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1).

Treatment of Hypothyroidism and Stress Using Neuro-Emotional Technique (NET): A Case Study.

Hypothyroidism is generally considered an autoimmune condition, and typical medical management involves taking levothyroxine (synthetic thyroid hormone) for life. This case report details the results of a mind-body intervention (MBI) called the Neuro-Emotional Technique (NET) used to treat a 28-year-old Caucasian female presenting with symptoms and bloodwork markers associated with two years of hypothyroidism and a long history of stress. The patient's medical doctor provided a diagnosis of hypothyroidism after blood tests showed that thyroid-stimulating hormone (TSH) levels were high at 6.

Generalizability of a Musculoskeletal Therapist Electronic Health Record for Modelling Outcomes to Work-Related Musculoskeletal Disorders.

Purpose: Electronic Health Records (EHRs) can contain vast amounts of clinical information that could be reused in modelling outcomes of work-related musculoskeletal disorders (WMSDs). Determining the generalizability of an EHR dataset is an important step in determining the appropriateness of its reuse. The study aims to describe the EHR dataset used by occupational musculoskeletal therapists and determine whether the EHR dataset is generalizable to the Australian workers' population and injury characteristics seen in workers' compensation claims.

Electronic Health Records for Predicting Outcomes to Work-Related Musculoskeletal Disorders: A Scoping Review.

Purpose: Through electronic health records (EHRs), musculoskeletal (MSK) therapists such as chiropractors and physical therapists, as well as occupational medicine physicians could collect data on many variables that can be traditionally challenging to collect in managing work-related musculoskeletal disorders (WMSDs). The review's objectives were to explore the extent of research using EHRs in predicting outcomes of WMSDs by MSK therapists.

Method: A systematic search was conducted in Medline, PubMed, CINAHL, and Embase.

Correlative cryo-soft X-ray tomography and cryo-structured illumination microscopy reveal changes to lysosomes in amyloid-β-treated neurons.

Protein misfolding is common to neurodegenerative diseases (NDs) including Alzheimer's disease (AD), which is partly characterized by the self-assembly and accumulation of amyloid-beta in the brain. Lysosomes are a critical component of the proteostasis network required to degrade and recycle material from outside and within the cell and impaired proteostatic mechanisms have been implicated in NDs. We have previously established that toxic amyloid-beta oligomers are endocytosed, accumulate in lysosomes, and disrupt the endo-lysosomal system in neurons.

Electronic Health Records Role in Predicting Outcomes to Work-Related Musculoskeletal Disorders: A Study Protocol.

Work-related musculoskeletal disorders are increasing in cost and time lost from work. Electronic health records have the potential to provide rich data to help inform and predict outcomes to WMSDs. The objective is to compare an EHR dataset from an occupational health service to comparative data, to help determine if the EHR dataset can be used in future studies to predict outcomes to care.

A Dominant-Negative Mutant of ANXA7 Impairs Calcium Signaling and Enhances the Proliferation of Prostate Cancer Cells by Downregulating the IP3 Receptor and the PI3K/mTOR Pathway.

Annexin A7/ANXA7 is a calcium-dependent membrane fusion protein with tumor suppressor gene (TSG) properties, which is located on chromosome 10q21 and is thought to function in the regulation of calcium homeostasis and tumorigenesis. However, whether the molecular mechanisms for tumor suppression are also involved in the calcium- and phospholipid-binding properties of ANXA7 remain to be elucidated. We hypothesized that the 4 C-terminal endonexin-fold repeats in ANXA7 (GX(X)GT), which are contained within each of the 4 annexin repeats with 70 amino acids, are responsible for both calcium- and GTP-dependent membrane fusion and the tumor suppressor function.

Digoxin and Standard-of-Care Therapy for Heart Failure Patients with COVID-19: Analysis of Data from the US Military Health System (MHS) Data Repository.

Background: Cardiac glycosides such as digoxin, digitoxin and ouabain are still used around the world to treat patients with chronic heart failure with reduced ejection fraction (HFrEF) and/or atrial fibrillation (AF). However, in the US, only digoxin is licensed for treating these illnesses, and the use of digoxin for this group of patients is increasingly being replaced in the US by a new standard of care with groups of more expensive drugs. However, ouabain and digitoxin, and less potently digoxin, have also recently been reported to inhibit SARS-CoV-2 virus penetration into human lung cells, thus blocking COVID-19 infection.

Proteogenomic analysis of lung adenocarcinoma reveals tumor heterogeneity, survival determinants, and therapeutically relevant pathways.

We present a deep proteogenomic profiling study of 87 lung adenocarcinoma (LUAD) tumors from the United States, integrating whole-genome sequencing, transcriptome sequencing, proteomics and phosphoproteomics by mass spectrometry, and reverse-phase protein arrays. We identify three subtypes from somatic genome signature analysis, including a transition-high subtype enriched with never smokers, a transversion-high subtype enriched with current smokers, and a structurally altered subtype enriched with former smokers, TP53 alterations, and genome-wide structural alterations. We show that within-tumor correlations of RNA and protein expression associate with tumor purity and immune cell profiles.

Circulating Cell-free DNA in Serum as a Marker for the Early Detection of Tumor Recurrence in Breast Cancer Patients.

Background/aim: Circulating cell-free DNA (cfDNA) isolated from serum by noninvasive procedures can serve as a potential biomarker for the early detection of many cancers. The aim of this study was to implement a simple, yet effective quantitative method for measuring the cfDNA in serum and to investigate the relationship between cfDNA and the occurrence of recurrence in breast cancer (BrCa) patients.

Patients And Methods: A total of 240 cases were selected, which comprised different subtypes of BrCa patients and control individuals.

Germline mutation landscape of DNA damage repair genes in African Americans with prostate cancer highlights potentially targetable RAD genes.

In prostate cancer, emerging data highlight the role of DNA damage repair genes (DDRGs) in aggressive forms of the disease. However, DDRG mutations in African American men are not yet fully defined. Here, we profile germline mutations in all known DDRGs (N = 276) using whole genome sequences from blood DNA of a matched cohort of patients with primary prostate cancer comprising of 300 African American and 300 European Ancestry prostate cancer patients, to determine whether the mutation status can enhance patient stratification for specific targeted therapies.

A descriptive study of sports chiropractors with an International Chiropractic Sport Science Practitioner qualification: a cross-sectional survey.

Background: This paper describes the education and case management profile of sports chiropractors with the Federation of International Sports Chiropractors (FICS) postgraduate qualification: International Chiropractic Sport Science Practitioner (ICSSP). The ICSSP is the predominant international sports chiropractic qualification.

Methods: A cross-sectional survey, carried out between 22/10/2014 and 22/12/2014,was utilized with a 39-item web-based survey examining practitioner, practice and clinical management characteristics, and was distributed via email to all sports chiropractors who held an ICSSP qualification (n = 240) in 2014.

Common cardiac medications potently inhibit ACE2 binding to the SARS-CoV-2 Spike, and block virus penetration and infectivity in human lung cells.

To initiate SARS-CoV-2 infection, the Receptor Binding Domain (RBD) on the viral spike protein must first bind to the host receptor ACE2 protein on pulmonary and other ACE2-expressing cells. We hypothesized that cardiac glycoside drugs might block the binding reaction between ACE2 and the Spike (S) protein, and thus block viral penetration into target cells. To test this hypothesis we developed a biochemical assay for ACE2:Spike binding, and tested cardiac glycosides as inhibitors of binding.