Cage-lid hanging behavior as a translationally relevant measure of pain in mice.

The development of new analgesic drugs has been hampered by the inability to translate preclinical findings to humans. This failure is due in part to the weak connection between commonly used pain outcome measures in rodents and the clinical symptoms of chronic pain. Most rodent studies rely on the use of experimenter-evoked measures of pain and assess behavior under ethologically unnatural conditions, which limits the translational potential of preclinical research.

Ten kilohertz SCS for Treatment of Chronic Upper Extremity Pain (UEP): Results from Prospective Observational Study.

Background: Chronic upper extremity pain (UEP) has complex etiologies and is often disabling. It has been shown that 10 kHz SCS can provide paresthesia-free and durable pain relief in multiple pain types and improve the quality of life of patients.

Objective: To gain additional evidence on the safety and effectiveness of 10 kHz SCS for the treatment of chronic UEP.

Pain relief and opioid usage in upper limb and neck pain patients after 10-kHz spinal cord stimulation treatment: subanalysis of USA studies.

It is argued that chronic pain patients who reduce/eliminate their opioids may have compromised pain relief. This study therefore aimed to analyze if reduced opioid consumption associated with 10-kHz spinal cord stimulation adversely affected pain relief. analysis was performed on data from two prospective studies in subjects with upper limbs and neck pain conducted in USA.

Community-based delivery of HIV treatment in Zambia: costs and outcomes.

Objective: The aim is to determine the total annual cost per patient treated and total cost per patient retained on antiretroviral therapy in Zambia in conventional care in facilities and across community-based differentiated service delivery (DSD) models.

Design: Economic evaluation was conducted using retrospective electronic record review.Twenty healthcare facilities (13 with DSD models and 7 as comparison sites) in six of Zambia's 10 provinces were considered.

Beyond the tubule: pathological variants of , encoding the megalin receptor, result in glomerular loss and early progressive chronic kidney disease.

Pathogenic variants in the gene, encoding the multiligand receptor megalin, cause a rare autosomal recessive syndrome: Donnai-Barrow/Facio-Oculo-Acoustico-Renal (DB/FOAR) syndrome. Because of the rarity of the syndrome, the long-term consequences of the tubulopathy on human renal health have been difficult to ascertain, and the human clinical condition has hitherto been characterized as a benign tubular condition with asymptomatic low-molecular-weight proteinuria. We investigated renal function and morphology in a murine model of DB/FOAR syndrome and in patients with DB/FOAR.

Role of diversity-generating retroelements for regulatory pathway tuning in cyanobacteria.

Background: Cyanobacteria maintain extensive repertoires of regulatory genes that are vital for adaptation to environmental stress. Some cyanobacterial genomes have been noted to encode diversity-generating retroelements (DGRs), which promote protein hypervariation through localized retrohoming and codon rewriting in target genes. Past research has shown DGRs to mainly diversify proteins involved in cell-cell attachment or viral-host attachment within viral, bacterial, and archaeal lineages.

Treatment outcomes and costs of a simplified antiviral treatment strategy for hepatitis C among monoinfected and HIV and/or hepatitis B virus-co-infected patients in Myanmar.

Access to hepatitis C virus (HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL) ± weight-based ribavirin for 12 weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12 weeks after treatment.

The central nervous system and heart failure.

The view that chronic heart failure was exclusively a disease of the heart dominated the cardiovascular literature until relatively recently. However, over the last 40 years it has increasingly come to be seen as a multisystem disease. Aside from changes in the sympathetic and parasympathetic nervous systems and the renin-angiotensin-aldosterone system, adaptations to the lungs, muscles and gastrointestinal tract have been clearly documented.

Glucocorticoid receptor expression in multiple myeloma patients is a predictor of survival.

Multiple myeloma (MM) is a blood neoplasia characterized by abnormal proliferation of plasma cells. Various treatments such as stem cell transplant (SCT), proteasome inhibitors, immune-modulating drugs, monoclonal antibodies and selective inhibitors of nuclear export have been routinely used to treat MM. However, relapse and treatment resistance are common problems in MM patients.

Striated Preferentially Expressed Protein Kinase (SPEG)-Deficient Skeletal Muscles Display Fewer Satellite Cells with Reduced Proliferation and Delayed Differentiation.

Centronuclear myopathies (CNMs) are a subtype of congenital myopathies characterized by skeletal muscle weakness and an increase in the number of central myonuclei. SPEG (striated preferentially expressed protein kinase) has been identified as the sixth gene associated with CNM, and it has been shown that striated muscle-specific Speg-knockout (KO) mice have defective triad formation, abnormal excitation-contraction coupling, and calcium mishandling. The impact of SPEG deficiency on the survival and function of myogenic cells remains to be deciphered.

Activity of transgene-produced B-domain-deleted factor VIII in human plasma following AAV5 gene therapy.

Adeno-associated virus (AAV)-based gene therapies can restore endogenous factor VIII (FVIII) expression in hemophilia A (HA). AAV vectors typically use a B-domain-deleted FVIII transgene, such as human FVIII-SQ in valoctocogene roxaparvovec (AAV5-FVIII-SQ). Surprisingly, the activity of transgene-produced FVIII-SQ was between 1.

Economic evaluation of facility-based HIV self-testing among adult outpatients in Malawi.

Introduction: HIV self-testing (HIVST) in outpatient departments (OPD) is a promising strategy for HIV testing in Malawi, given high OPD patient volumes and substantial wait times. To evaluate the relative cost and expected impact of facility-based HIVST (FB-HIVST) at OPDs in Malawi for increasing HIV status awareness, we conducted an economic evaluation of an HIVST cluster-randomized controlled trial.

Methods: A cluster-randomized trial was conducted at 15 sites in Malawi from September 2017 to February 2018 with three arms: 1) Standard provider-initiated-testing-and-counselling (PITC); 2) Optimized PITC (additional provider training and job-aids) and 3) FB-HIVST (HIVST demonstration, distribution and kit use in OPD, private kit interpretation and optional HIV counselling).

Patient Perspectives of Quality of the Same-Day Antiretroviral Therapy Initiation Process in Gauteng Province, South Africa: Qualitative Dominant Mixed-Methods Analysis of the SLATE II Trial.

Background: HIV patients in South Africa continue to report operational barriers to starting antiretroviral therapy (ART). In the Simplified Algorithm for Treatment Eligibility (SLATE) II trial, same-day initiation (SDI) of ART increased the number of patients commencing ART and achieving HIV viral suppression by using a screening tool to distinguish between patients eligible for SDI and those requiring additional care before starting treatment. We conducted a mixed-methods evaluation to explore trial patients' perceptions and experiences of SDI.

Prevalence of TB symptoms, diagnosis and treatment among people living with HIV (PLHIV) not on ART presenting at outpatient clinics in South Africa and Kenya: baseline results from a clinical trial.

Objective: We used screening data and routine clinic records for intervention arm patients in the Simplified Algorithm for Treatment Eligibility (SLATE) trials to describe the prevalence of tuberculosis (TB) symptoms, diagnosis and treatment among people living with HIV (PLHIV), not on antiretroviral therapy (ART) and presenting at outpatient clinics in South Africa and Kenya. We compared the performance of the WHO four-symptom TB screening tool with a baseline Xpert test.

Setting: Outpatient HIV clinics in South Africa and Kenya.

Models of service delivery for optimizing a patient's first six months on antiretroviral therapy for HIV: an applied research agenda.

Differentiated models of service delivery (DSD models) for HIV treatment in sub-Saharan Africa were conceived as a way to manage rapidly expanding populations of experienced patients who are clinically "stable" on antiretroviral therapy (ART). Entry requirements for most models include at least six months on treatment and a suppressed viral load. These models thus systematically exclude newly-initiated patients, who instead experience the conventional model of care, which requires frequent, multiple clinic visits that impose costs on both providers and patients.

Pressure abnormalities in patients with Zenker's diverticulum using pharyngeal high-resolution manometry.

Objectives: Zenker's diverticulum is associated with reduced cricopharyngeal compliance and abnormal intrabolus pressure. However, it is unclear how the pharynx compensates for these deficits. Developments in manometric technology have improved our ability to capture pharyngeal pressure events.

A clinical algorithm for same-day HIV treatment initiation in settings with high TB symptom prevalence in South Africa: The SLATE II individually randomized clinical trial.

Background: Many countries encourage same-day initiation of antiretroviral therapy (ART), but evidence on eligibility for same-day initiation, how best to implement it, and its impact on outcomes remains scarce. Building on the Simplified Algorithm for Treatment Eligibility (SLATE) I trial, in which nearly half of participants were ineligible for same-day initiation mainly because of TB symptoms, the study evaluated the revised SLATE II algorithm, which allowed same-day initiation for patients with mild TB symptoms and other less serious reasons for delay.

Methods And Findings: SLATE II was a nonblinded, 1:1 individually randomized pragmatic trial at three primary healthcare clinics in Johannesburg, South Africa.

SUMOylation of E2F1 Regulates Expression of EZH2.

Elevated expression of EZH2, the enzymatic subunit of polycomb repressive complex 2 (PRC2), often occurs in cancer. EZH2 expression results in the silencing of genes that suppress tumor formation and metastasis through trimethylation of histone H3 at lysine 27 (H3K27me3) at their promoters. However, inhibitors of EZH2 enzymatic activity have not shown the expected efficacy against cancer in clinical trials, suggesting a need for other strategies to address EZH2 overexpression.

Intratumoral collagen signatures predict clinical outcomes in feline mammary carcinoma.

Breast cancer is the most common cause of cancer-related deaths in women worldwide. Identification of reliable prognostic indicators and therapeutic targets is critical for improving patient outcome. Cancer in companion animals often strongly resembles human cancers and a comparative approach to identify prognostic markers can improve clinical care across species.

Hypothesis: Pentoxifylline is a potential cytokine modulator therapeutic in COVID-19 patients.

We propose a new hypothesis that the established drug pentoxifylline deserves attention as a potential repurposed therapeutic for COVID-19. Pentoxifylline is an immunomodulator with anti-inflammatory properties. It is a nonselective phosphodiesterase inhibitor and through Adenosine A2A Receptor-mediated pathways reduces tumor necrosis factor alpha, interleukin 1, interleukin 6, and interferon gamma and may act to reduce tissue damage during the cytokine storm host response to SARS-CoV-2 infection.

Case report of surgical management of a locally invasive colostomy adenocarcinoma.

Introduction: This case report involves the presentation and management of a locally invasive adenocarcinoma at the site of a colostomy in a patient with multiple comorbidities and anatomic constraints.

Presentation Of Case: 63 year-old woman with a complicated medical and surgical history, including imperforate anus and permanent colostomy, who presented with a fungating mass at the site of her colostomy. Evaluation revealed a locally invasive adenocarcinoma requiring surgical management for symptom control and oncologic treatment.

Will differentiated care for stable HIV patients reduce healthcare systems costs?

Introduction: South Africa's National Department of Health launched the National Adherence Guidelines for Chronic Diseases in 2015. These guidelines include adherence clubs (AC) and decentralized medication delivery (DMD) as two differentiated models of care for stable HIV patients on antiretroviral therapy. While the adherence guidelines do not suggest that provider costs (costs to the healthcare system for medications, laboratory tests and visits to clinics or alternative locations) for stable patients in these differentiated models of care will be lower than conventional, clinic-based care, recent modelling exercises suggest that such differentiated models could substantially reduce provider costs.

The role of myeloid-derived suppressor cells in hematologic malignancies.

Purpose Of Review: This article focuses on the immunosuppressive impact of myeloid-derived suppressor cells (MDSCs) and the potential clinical implications in hematological malignancies.

Recent Findings: MDSCs play a critical role in the regulation of the immune response in cancer. They inhibit activation of adaptive immune response and as a result foster the growth of the malignancy.

Targeting microRNA in hematologic malignancies.

Purpose Of Review: MiRNAs are critical regulators for gene expression. Numerous studies have revealed how miRNAs contribute to the pathogenesis of hematologic malignancies.

Recent Findings: The identification of novel miRNA regulatory factors and pathways crucial for miRNA dysregulation has been linked to hematologic malignancies.