Impact of darolutamide on local symptoms: pre-planned and post hoc analyses of the ARAMIS trial.

Objective: To assess, the effect of darolutamide (a structurally distinct androgen receptor inhibitor) on urinary and bowel symptoms, using data from the phase III ARAMIS trial (NCT02200614) that showed darolutamide significantly reduced the risk of metastasis and death versus placebo.

Patients And Methods: Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) were randomised 2:1 to darolutamide (n = 955) or placebo (n = 554). Local symptom control was assessed by first prostate cancer-related invasive procedures and post hoc analyses of time to deterioration in quality of life (QoL) using total urinary and bowel symptoms, and individual questions for these symptoms from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module subscales and Functional Assessment of Cancer Therapy-Prostate prostate cancer subscale.

American College of Rheumatology, American Academy of Dermatology, Rheumatologic Dermatology Society, and American Academy of Ophthalmology 2020 Joint Statement on Hydroxychloroquine Use With Respect to Retinal Toxicity.

Four major medical societies involved with hydroxychloroquine (HCQ) therapy concur on the need for common principles and cooperation to minimize the risk of ocular toxicity. At a daily dosage of ≤5 mg/kg/day actual body weight, the risk of retinal toxicity from HCQ is <2% for usage up to 10 years. Widespread adoption of more sensitive testing techniques, such as optical coherence tomography and automated visual fields, by eye care providers will allow the detection of early toxicity and thus preserve the patient's visual function.

New developments in our understanding of vitamin metabolism, action and treatment.

Although vitamin D has been reported to have pleiotropic effects including effects on the immune system and on cancer progression, the principal action of vitamin D is the maintenance of calcium and phosphate homeostasis. The importance of vitamin D in this process is emphasized by the consequences of vitamin D deficiency which includes rickets in children and osteomalacia in adults. Vitamin D deficiency has also been reported to increase the risk of falls and osteoporotic fractures.

T-wave alternans testing for ventricular arrhythmias.

T-wave alterans (TWA) measures alternate-beat fluctuations in the ECG T-wave, and has been used to predict the risk for life-threatening ventricular arrhythmias in various clinical populations. This work reviews the traditional literature linking repolarization alternans in cellular and tissue-level studies, with clinical studies that TWA can successfully add to existing clinical risk factors in predicting ventricular arrhythmias. We conclude by providing an evidence-based framework integrating TWA with other risk factors to stratify risk for sudden cardiac arrest.

Biventricular pacing attenuates T-wave alternans and T-wave amplitude compared to other pacing modes.

Background: The impact of altered ventricular activation, including biventricular (BV) pacing, on T-wave alternans (TWA) and arrhythmic substrates is unclear. We studied how differing ventricular activation sequence alters TWA; the interval from peak-to-end of the T-wave (TpTe) and T-wave amplitude during right (RV), left (LV), and biventricular (BV) pacing; and right atrial (RA) pacing in patients with preexisting conduction delay.

Methods And Results: We measured TWA during RA, RV, LV, and BV pacing in 33 patients receiving cardiac-resynchronization-therapy-defibrillators.

Basis for improved permeability barrier homeostasis induced by PPAR and LXR activators: liposensors stimulate lipid synthesis, lamellar body secretion, and post-secretory lipid processing.

Previously, we demonstrated that topical applications of peroxisome proliferator-activated receptors (PPARs) and liver X receptor (LXR) activators improve permeability barrier homeostasis. We showed further that stimulation of epidermal differentiation provides one mechanism that could account for such improvement. Here, we studied the effects of these agents on the lipid matrix of the stratum corneum.

Overexpression of rat heat shock protein 70 is associated with reduction of early mitochondrial cytochrome C release and subsequent DNA fragmentation after permanent focal ischemia.

Although protective effects of heat shock protein 70 (HSP70) overproduction after ischemic injury have been shown both in vitro and in vivo in neurons, the mechanisms are not fully understood. The hypothesis of this study is that transgenic mice overexpressing HSP70 (HSP70 Tg) show reduced mitochondrial cytochrome c release into cytosol and diminished apoptotic cell death after permanent focal ischemia in comparison to wild-type (Wt) mice. Permanent middle cerebral artery occlusion (pMCAO) was produced by intraluminal suture cannulation in HSP70 Tg and Wt mice.

Effect of suture size and carotid clip application upon blood flow and infarct volume after permanent and temporary middle cerebral artery occlusion in mice.

Problems with the intraluminal suture method for induction of focal cerebral ischemia in genetically altered mice include occurrence of subarachnoid hemorrhage (SAH) and variability of infarct volume. We hypothesized that use of 5-0 curved or 6-0 straight suture for carotid cannulation might decrease SAH and that the application of a microvascular clip to the common carotid artery (CCA) might decrease variability of infarct volume. The purpose of this study is to evaluate and explain the results of these technical modifications.

Mild hypothermia reduces zinc translocation, neuronal cell death, and mortality after transient global ischemia in mice.

The authors sought to determine whether Zn translocation associated with neuronal cell death occurs after transient global ischemia (TGI) in mice, as has been previously shown in rats, and to determine the effect of mild hypothermia on this reaction. To validate the TGI model, carbon-black injection and laser-Doppler flowmetry were compared in three strains of mice (C57BL/6, SV129, and HSP70 transgenic mice) to assess posterior communicating artery (PcomA) development and cortical perfusion. In C57BL/6 mice, optimal results were obtained when subjected to 20-minute TGI.

Summary of research issues in personal, interpersonal, and group dynamics.

People working on space missions, whether they are crewmembers or Mission Control personnel, must interact in groups. Consequently, it is important to consider interpersonal and group dynamic issues to assure that mission goals are accomplished. Simulation studies on Earth and anecdotal reports from space have described a number of such issues that include crew heterogeneity, culture and language variations, leadership roles, and personality differences.

Interpersonal and cultural issues involving crews and ground personnel during Shuttle/Mir space missions.

Background: Anecdotal reports from space and results from simulation studies on Earth suggest that interpersonal and cultural issues will have an impact on the interactions of crewmembers and mission control personnel during future long-duration space missions.

Methods: To evaluate this impact we studied 5 astronauts, 8 cosmonauts, and 42 American and 16 Russian mission control personnel who participated in the Shuttle/Mir space program. Subjects completed questions from the Profile of Mood States, the Group Environment Scale, and the Work Environment Scale on a weekly basis during the missions.

Quantitation of erbB-2 gene copy number in breast cancer by an improved polymerase chain reaction (PCR) technique, competitively differential PCR.

A new method of measuring gene copy number in small samples of DNA was used to measure amplification of the erbB-2 gene and a reference gene in breast cancers. The method, termed 'competitively differential polymerase chain reaction' (CD-PCR), combines the advantages of two other techniques for measuring amplification by PCR, namely differential PCR (D-PCR) and competitive PCR (C-PCR). The CD-PCR methodology was evaluated for sensitivity and specificity by comparing amplification measured by CD-PCR with that obtained by fluorescence in situ hybridization (FISH), C-PCR, and Southern blotting analysis.

Multiple sites of loss of heterozygosity on chromosome 8 in human breast cancer has differential correlation with clinical parameters.

Recent studies have shown that chromosome 8p21-22 is the main site of frequent loss of heterozygosity (LOH) in breast cancers. However, the detailed molecular analysis of chromosome 8 so far in breast cancer has been variable. Most of the literature pertaining to LOH in breast cancer is mainly on short arm of chromosome 8.