Towards Clinical Application: Calcium Waves for In Vitro Qualitative Assessment of Propagated Primary Human Corneal Endothelial Cells.

Corneal endothelium cells (CECs) regulate corneal hydration between the leaky barrier of the corneal endothelium and the ionic pumps on the surface of CECs. As CECs do not regenerate, loss of CECs leads to poor vision and corneal blindness. Corneal transplant is the only treatment option; however, there is a severe shortage of donor corneas globally.

Hypertension in Adults With Diabetes in Southeast Asia: A Systematic Review.

Diabetes is one of the most pressing health issues in the Southeast Asian region, and hypertension has been commonly reported as a comorbidity in adults with diabetes. This systematic review aimed to synthesize evidence on the prevalence and management of hypertension in adults with diabetes in Southeast Asian countries. A literature search was conducted in Ovid MEDLINE and Embase Classic + Embase from database inception until March 15, 2024.

Serum lipidomic signatures in patients with varying histological severity of metabolic-dysfunction associated steatotic liver disease.

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a spectrum of pathologies ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Patients with metabolic associated steatohepatitis (MASH) with fibrosis are at greatest risk of liver and cardiovascular complications. To identify such at-risk MASLD patients, physicians are still reliant on invasive liver biopsies.

Esrra regulates Rplp1-mediated translation of lysosome proteins suppressed in metabolic dysfunction-associated steatohepatitis and reversed by alternate day fasting.

Objective: Currently, little is known about the mechanism(s) regulating global and specific protein translation during metabolic dysfunction-associated steatohepatitis (MASH; previously known as non-alcoholic steatohepatitis, NASH).

Methods: Unbiased label-free quantitative proteome, puromycin-labelling and polysome profiling were used to understand protein translation activity in vitro and in vivo.

Results: We observed a global decrease in protein translation during lipotoxicity in human primary hepatocytes, mouse hepatic AML12 cells, and livers from a dietary mouse model of MASH.

Potential therapeutic effects of peroxisome proliferator-activated receptors on corneal diseases.

The cornea is an avascular tissue in the eye that has multiple functions in the eye to maintain clear vision which can significantly impair one's vision when subjected to damage. Peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptor proteins comprising three different peroxisome proliferator-activated receptor (PPAR) isoforms, namely, PPAR alpha (α), PPAR gamma (γ), and PPAR delta (δ), have emerged as potential therapeutic targets for treating corneal diseases. In this review, we summarised the current literature on the therapeutic effects of PPAR agents on corneal diseases.

Type 1 Diabetes in Singapore: Self-Care Challenges, Diabetes Technology Awareness, Current Use, and Satisfaction, an Online Survey.

Introduction: To describe the self-care challenges, diabetes technology awareness, current use, and satisfaction among adults with type 1 diabetes and parents of children with type 1 diabetes in Singapore.

Methods: An anonymous online survey was administered between November 2020 and October 2021. Data are presented as mean (standard deviation) or count (percentages).

A meta-analysis of randomized controlled clinical trials for implications of acute treatment effects on glomerular filtration rate for long-term kidney protection.

Pharmacologic interventions to slow chronic kidney disease progression, such as ACE-inhibitors, angiotensin receptor blockers, or sodium glucose co-transporter 2 inhibitors, often produce acute treatment effects on glomerular filtration rate (GFR) that differ from their long-term chronic treatment effects. Observational studies assessing the implications of acute effects cannot distinguish acute effects from GFR changes unrelated to the treatment. Here, we performed meta-regression analysis of multiple trials to isolate acute effects to determine their long-term implications.

Dichotomous transactivation domains contribute to growth inhibitory and promotion functions of TAp73.

The transcription factor p73, a member of the p53 tumor-suppressor family, regulates cell death and also supports tumorigenesis, although the mechanistic basis for the dichotomous functions is poorly understood. We report here the identification of an alternate transactivation domain (TAD) located at the extreme carboxyl (C) terminus of TAp73β, a commonly expressed p73 isoform. Mutational disruption of this TAD significantly reduced TAp73β's transactivation activity, to a level observed when the amino (N)-TAD that is similar to p53's TAD, is mutated.

Counterproductive effects of anti-CD38 and checkpoint inhibitor for the treatment of NK/T cell lymphoma.

Introduction: Natural killer/T cell lymphoma (NKTL) is an aggressive malignancy associated with poor prognosis. This is largely due to limited treatment options, especially for relapsed patients. Immunotherapies like immune checkpoint inhibitors (ICI) and anti-CD38 therapies have shown promising but variable clinical efficacies.

Cascade testing for hereditary cancer in Singapore: how population genomics help guide clinical policy.

Hereditary Cancer makes up around 5-10% of all cancers. It is important to diagnose hereditary cancer in a timely fashion, as not only do patients require long-term care from a young age, but their relatives also require management. The main approach to capture at-risk relatives is cascade testing.

Endoplasmic reticulum stress enhances the expression of TLR3-induced TSLP by airway epithelium.

Thymic stromal lymphopoietin (TSLP) is an epithelial-derived pleiotropic cytokine that regulates T-helper 2 (Th2) immune responses in the lung and plays a major role in severe uncontrolled asthma. Emerging evidence suggests a role for endoplasmic reticulum (ER) stress in the pathogenesis of asthma. In this study, we determined if ER stress and the unfolded protein response (UPR) signaling are involved in TSLP induction in the airway epithelium.

Immunological signatures unveiled by integrative systems vaccinology characterization of dengue vaccination trials and natural infection.

Introduction: Dengue virus infection is a global health problem lacking specific therapy, requiring an improved understanding of DENV immunity and vaccine responses. Considering the recent emerging of new dengue vaccines, here we performed an integrative systems vaccinology characterization of molecular signatures triggered by the natural DENV infection (NDI) and attenuated dengue virus infection models (DVTs).

Methods And Results: We analyzed 955 samples of transcriptomic datasets of patients with NDI and attenuated dengue virus infection trials (DVT1, DVT2, and DVT3) using a systems vaccinology approach.

Therapeutic biomarkers in acute myeloid leukemia: functional and genomic approaches.

Acute myeloid leukemia (AML) is clinically and genetically a heterogeneous disease characterized by clonal expansion of abnormal hematopoietic progenitors. Genomic approaches to precision medicine have been implemented to direct targeted therapy for subgroups of AML patients, for instance, IDH inhibitors for mutated patients, and FLT3 inhibitors with mutated patients. While next generation sequencing for genetic mutations has improved treatment outcomes, only a fraction of AML patients benefit due to the low prevalence of actionable targets.

Bilobed Flap Coverage for the Reconstruction of Dorsal Soft Tissue Defect Over the Proximal Phalanx: A Case Report.

Soft tissue defects over the dorsal finger are common and may result from trauma, burns, or surgical management of infections and tumors. We present a case where a bilobed flap was used for the reconstruction of a soft tissue defect dorsal to the proximal phalanx of the ring finger and discuss the design of this flap. The defect was secondary to a collar button abscess of the right third webspace and the surgical debridement required to control the infection.

Health Care Challenges in the Management of Primary Aldosteronism in Southeast Asia.

Context: While guidelines have been formulated for the management of primary aldosteronism (PA), following these recommendations may be challenging in developing countries with limited health care access.

Objective: We aimed to assess the availability and affordability of health care resources for managing PA in the Association of Southeast Asian Nations (ASEAN) region, which includes low-middle-income countries.

Methods: We instituted a questionnaire-based survey to specialists managing PA, assessing the availability and affordability of investigations and treatment.

Estrogen receptor-related receptor (Esrra) induces ribosomal protein Rplp1-mediated adaptive hepatic translation during prolonged starvation.

Protein translation is an energy-intensive ribosome-driven process that is reduced during nutrient scarcity to conserve cellular resources. During prolonged starvation, cells selectively translate specific proteins to enhance their survival (adaptive translation); however, this process is poorly understood. Accordingly, we analyzed protein translation and mRNA transcription by multiple methods and to investigate adaptive hepatic translation during starvation.

Prolonged Hypokalemia and Delayed Diagnosis of Primary Aldosteronism: Clinical Course and Risk Factors.

Context: Primary aldosteronism (PA) is a common cause of hypertension (HT). However, diagnosis is often delayed, leading to poorer clinical outcomes. Hypokalemia with HT is characteristic of PA, and is an indication for screening.

Plasma Metanephrines Yield Fewer False-Positive Results Than Urine Metanephrines in Patients With Obstructive Sleep Apnea.

Context: Obstructive sleep apnea (OSA) is associated with increased nocturnal sympathetic activity. In OSA patients, elevations in metanephrines may lead to false-positive tests when evaluating for pheochromocytoma or paraganglioma (PPGL).

Objective: To evaluate whether morning plasma metanephrines would lead to fewer false-positive results than 24-hour urinary metanephrines in OSA patients.