Congenital diarrhea and enteropathies (CoDEs) condition is a rare cause of chronic diarrhea in infants that can be challenging to diagnose. This article discusses key signs to recognize in considering a CoDEs diagnosis and provides an overview of the diagnostic process. We report a late preterm twin infant with intractable watery diarrhea starting shortly after birth.
View Article and Find Full Text PDFCancer remains a leading cause of death worldwide and although prognosis and survivorship after therapy have improved significantly, current cancer treatments have long-term health consequences. For decades telomerase-mediated telomere maintenance has been an attractive anti-cancer therapeutic target due to its abundance and role in telomere maintenance, pathogenesis, and growth in neoplasms. Telomere maintenance-specific cancer therapies, however, are marred by off-target side effects that must be addressed before they reach clinical practice.
View Article and Find Full Text PDFT cell engagers (TCEs) are becoming an integral class of biological therapeutic owing to their highly potent ability to eradicate cancer cells. Nevertheless, the widespread utility of classical CD3-targeted TCEs has been limited by narrow therapeutic index (TI) linked to systemic CD4+ T cell activation and aberrant cytokine release. One attractive approach to circumvent the systemic activation of pan CD3+ T cells and reduce the risk of cytokine release syndrome is to redirect specific subsets of T cells.
View Article and Find Full Text PDFThis study investigated the prognostic value of the chemokine C-C motif ligand 2 (CCL2) and its receptor C-C motif chemokine receptor 2 (CCR2) expression in locally advanced prostate cancer treated with radiotherapy and androgen deprivation using the 10-year outcome data from the TROG 03.04 RADAR clinical trial. CCL2 and CCR2 protein expression in prostate cancer biopsies at the time of diagnosis were quantified by immunohistochemistry and digital quantification.
View Article and Find Full Text PDFIncreasing chronic disease rates in regional Australian communities necessitates innovative models of healthcare. We evaluated the efficacy of an interprofessional chronic disease program, delivered within a regional student-led nursing and allied health clinic in Southern Queensland, Australia. Changes to anthropometric, aerobic fitness and strength, and quality of life outcomes were examined at four time points spanning 16 months: intake, program transition (4 months), 6 and 12 months (post-transition).
View Article and Find Full Text PDFBispecific antibodies represent an increasingly large fraction of biologics in therapeutic development due to their expanded scope in functional capabilities. Asymmetric monovalent bispecific IgGs (bsIgGs) have the additional advantage of maintaining a native antibody-like structure, which can provide favorable pharmacology and pharmacokinetic profiles. The production of correctly assembled asymmetric monovalent bsIgGs, however, is a complex engineering endeavor due to the propensity for non-cognate heavy and light chains to mis-pair.
View Article and Find Full Text PDFThe acute and long-term benefits of exercise on cardiovascular health are well established, yet the optimal mode of exercise training that improves arterial stiffness in women with high blood pressure remains unclear. The aim of this systematic review and meta-analysis was to assess the influence of aerobic and resistance training on arterial stiffness in women with high blood pressure. After an extensive search of four online databases, six randomized controlled trials met the inclusion criteria and were included in meta-analyses.
View Article and Find Full Text PDFCoconut water is used as an alternative to conventional sports drinks for hydration during endurance cycling; however, evidence supporting its use is limited. This study determined if drinking coconut water compared to a sports drink altered cycling performance and physiology. In a randomized crossover trial, 19 experienced male ( = 15) and female ( = 4) cyclists (age 30 ± 9 years, body mass 79 ± 11 kg, V̇O 55 ± 8 mL·kg·min) completed two experimental trials, consuming either a commercially available sports drink or iso-calorific coconut water during 90 min of sub-maximal cycling at 70% of their peak power output, followed by a simulated, variable gradient, 20 km time trial.
View Article and Find Full Text PDFKaposi sarcoma (KS) of the gastrointestinal (GI) tract in a patient with acquired immunodeficiency syndrome (AIDS) has not been reported in an adolescent outside of Africa. We present a 16-year homosexual old male with AIDS, cutaneous KS, pulmonary KS, and gastrointestinal KS (GI-KS) lesions. Eighty percent of patients with GI-KS are asymptomatic, but our patient presented with a month-long history of dysphagia, abdominal pain, and hematochezia.
View Article and Find Full Text PDFTraditional continuous training and high-intensity interval training (HIIT) can increase maximal oxygen uptake (V̇O). However, there is conflicting evidence regarding which form of training demonstrates the greatest improvements to V̇O, and data in women is sparse. We conducted a systematic review and meta-analyses to assess whether moderate to vigorous-intensity continuous training (MVICT) or HIIT was superior at improving V̇O in women.
View Article and Find Full Text PDFTelomerase preserves genomic integrity by maintaining and protecting the telomeres. Seminal findings from 1985 revealed the canonical role of telomerase and motivated investigations into potential therapeutic strategies to combat one of the hallmarks of ageing-telomere attrition. Since then, the field of telomere biology has rapidly expanded, with telomerase serving essential roles in cancer and cell development through its canonical function.
View Article and Find Full Text PDFPurpose: To validate published models for the risk estimate of grade ≥ 1 (G1+), grade ≥ 2 (G2+) and grade = 3 (G3) late rectal bleeding (LRB) after radical radiotherapy for prostate cancer in a large pooled population from three prospective trials.
Materials And Methods: The external validation population included patients from Europe, and Oceanian centres enrolled between 2003 and 2014. Patients received 3DCRT or IMRT at doses between 66-80 Gy.
Ageing causes a gradual deterioration of bodily functions and telomere degradation. Excessive telomere shortening leads to cellular senescence and decreases tissue vitality. Six proteins, called shelterin, protect telomere integrity and control telomere length through telomerase-dependent mechanisms.
View Article and Find Full Text PDFImportance: Radiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain.
Objective: To determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT).
Previous reports have shown that quantification of high tumour grade is of prognostic significance for patients with prostate cancer. In particular, percent Gleason pattern 4 (GP4) has been shown to predict outcome in several studies, although conflicting results have also been reported. A major issue with these studies is that they rely on surrogate markers of outcome rather than patient survival.
View Article and Find Full Text PDFProstate cancer (PCa) is the second most commonly diagnosed cancer in men, and bone is the most frequent site of metastasis. The tumor microenvironment (TME) impacts tumor growth and metastasis, yet the role of the TME in PCa metastasis to bone is not fully understood. We used a tissue-engineered xenograft approach in NOD-scid IL2Rγ (NSG) mice to incorporate two levels of humanization; the primary tumor and TME, and the secondary metastatic bone organ.
View Article and Find Full Text PDFThe proper management of a prolapsed rectal mass in a child or teenager is challenging. Given that the underlying etiology of a prolapsed rectal mass in this population is not always immediately clear, interdisciplinary assessment is often required. Juvenile polyps, more commonly presenting with bleeding than a prolapsed mass, can mimic the appearance of both hemorrhoids and the rectum itself - making a purely clinical diagnosis difficult.
View Article and Find Full Text PDFExercise training is one of the few therapeutic interventions that improves health span by delaying the onset of age-related diseases and preventing early death. The length of telomeres, the 5'-TTAGGG -3' tandem repeats at the ends of mammalian chromosomes, is one of the main indicators of biological age. Telomeres undergo shortening with each cellular division.
View Article and Find Full Text PDFExercise training seems to promote healthy biological ageing partly by inducing telomere maintenance, yet the molecular mechanisms are not fully understood. Recent studies have emphasised the importance of microRNAs (miRNAs) in ageing and their ability to mirror pathophysiological alterations associated with age-related diseases. We examined the association between aerobic fitness and leukocyte telomere length before determining the influence of vigorous exercise training on the regulation of leukocyte miRNA networks.
View Article and Find Full Text PDFTelomeres protect genomic stability and shortening is one of the hallmarks of ageing. Telomerase reverse transcriptase (TERT) is the major protein component of telomerase, which elongates telomeres. Given that short telomeres are linked to a host of chronic diseases and the therapeutic potential of telomerase-based therapies as treatments and a strategy to extend lifespan, lifestyle factors that increase TERT gene expression and telomerase activity could attenuate telomere attrition and contribute to healthy biological ageing.
View Article and Find Full Text PDFPurpose: Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist.
Methods: Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m once every 3 weeks for three cycles before RT and 20 mg/m once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors.