In vivo genotoxic effect of arsenic trioxide in mice using comet assay

Although arsenic has been the subject of toxicological research, acute in vivo genotoxic studies using relevant animal models and uniform methodology are lacking. Hence, the present study aims to study DNA damage caused by arsenic trioxide in mice in in vivo using alkaline single cell gel electrophoresis (Comet) assay. Mice were administered orally 0,0.13,0.27,0.54,1.08,2.15,4.3 and 6.45 mg/kg body weight of arsenic trioxide dissolved in distilled water. The samples of whole blood were collected at 24,48,72 h, first and second week post-treatment and the assay was carried out to determine DNA damage as represented by comet tail-length. All the doses induced significant increase in comet tail-length at 24 h post-treatment (P<0.05) showing a clear dose dependent increase from 0.13 to 2.15 mg/kg b.wt. and a dose dependent decrease in higher doses (4.3-6.45 mg/kg b.wt). At 48 h post-treatment all the doses showed a significant increase (P<0.05) in comet tail-length when compared to 24 h post-treatment. A gradual decrease in the comet tail-length was observed for all the doses from 72 h post-treatment onwards indicating a gradual repair in DNA damage. This indicates a non-linear dose and time response between DNA damage and different doses of arsenic trioxide at different time-intervals. A significant increase in comet tail-length at all the doses clearly gives evidence that arsenic trioxide cause DNA damage effectively. The study indicates that the alkaline comet assay is a reliable and effective method to detect DNA damage caused by metals.     

Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design

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Highlights? Quantitative fitness landscapes were extracted from viral sequence databases ? We developed a landscape for HIV Gag by using a model from statistical physics ? Predictions show good agreement with new in vitro and existing clinical data     

Individualized decision-making for older men with prostate cancer: balancing cancer control with treatment consequences across the clinical spectrum

Prostate cancer (PCa) is the most prevalent non-skin cancer among men and is the second leading cause of cancer death in men. PCa has an increased incidence and prevalence in older men. Age-associated incidence is on the rise due to increased screening in the older population. This has led to a sharp rise in the detection of early stage PCa. Given the indolent nature of many prostatic malignancies, a large proportion of older men with PCa will ultimately die from other causes. As a result, physicians and patients are faced with the challenge of identifying optimal treatment strategies for localized PCa, biochemically recurrent PCa and later-stage PCa. Age-related changes can impact tolerance of hormonal therapy and chemotherapy in men with metastatic disease and shift the risk-benefit ratio of these treatments. Tools such as the Comprehensive Geriatric Assessment (CGA) can help estimate remaining life expectancy and can help predict treatment-related morbidity and mortality in older men. Application of CGA in older men with PCa is important to help individualize and optimize treatment strategies. Research that integrates multidisciplinary and multidimensional assessment of PCa and the patient's overall health status is needed.     

Antinociceptive, antidiarrheal, and neuropharmacological activities of Barringtonia acutangula

Context: Barringtonia acutangula (L.) Gaertn. (Lecythidaceae) has been used in folk medicine in the treatment of arthralgia, chest pain, dysmenorrhea, inflammation, hemorrhoids, diarrhea, and also in psychological disorders. Objective: To investigate the antinociceptive, antidiarrheal, and neuropharmacological effect of the methanol extract of B. acutangula leaves and seeds in mice. Materials and methods: The extracts (200 and 400 mg/kg; p.o.) were tested for antinociceptive activity by acetic acid-induced writhing, hot plate and tail immersion models; castor oil- and magnesium sulphate-induced diarrheal models were used to evaluate antidiarrheal activity whereas hole cross and open field models were employed for testing neuropharmacological activity. Results: Both extracts exhibited significant antinociceptive effect (p < 0.001) in acetic acid and heat induced pain models in a dose-dependent manner. The extracts prolonged the latency period to the thermal stimuli in both hot plate and tail immersion test. The extracts also showed significant inhibition of defecation (p < 0.001, 0.01) in both diarrheal models. Again, the spontaneous motor activity was decreased (p < 0.001) by the extracts in both hole cross and open field test. Discussion and conclusion: The results of this study suggest that the methanol extracts of B. acutangula leaves and seeds possess good antinociceptive, antidiarrheal, and central nervous system (CNS) depressant activities. This study validates the use of this plant in traditional medicine.     

Three-dimensional bioprinting in ophthalmic care

Three-dimensional (3D) bioprinting is widely used in ophthalmic clinic, including in diagnosis, surgery, prosthetics, medications, drug development and delivery, and medical education. Articles published in 2011–2022 into bioinks, printing technologies, and bioprinting applications in ophthalmology were reviewed and the strengths and limitations of bioprinting in ophthalmology highlighted. The review highlighted the trade-offs of printing technologies and bioinks in respect to, among others, material type cost, throughput, gelation technique, cell density, cell viability, resolution, and printing speed. There is already widespread ophthalmological application of bioprinting outside clinical settings, including in educational modelling, retinal imaging/visualization techniques and drug design/testing. In clinical settings, bioprinting has already found application in pre-operatory planning. Even so, the findings showed that even with its immense promise, actual translation to clinical applications remains distant, but relatively closer for the corneal (except stromal) tissues, epithelium, endothelium, and conjunctiva, than it was for the retina. This review similarly reflected on the critical on the technical, practical, ethical, and cost barrier to rapid progress of bioprinting in ophthalmology, including accessibility to the most sophisticated bioprinting technologies, choice, and suitability of bioinks, tissue viability and storage conditions. The extant research is encouraging, but more work is clearly required for the push towards clinical translation of research.     

Sinus node dysfunction during transcatheter assessment and stent correction of sinus venosus atrial septal defects

Covered stent correction of a superior sinus venosus atrial septal defect is increasingly performed as an alternative to surgical repair. While sinus node dysfunction requiring pacemaker implantation may be required after surgical repair, this has not been previously reported after covered stent implantation. We reviewed the experience in two interventional centers. Balloon inflation in the superior vena cava was used to confirm the anomalous pulmonary vein drainage would be unobstructed after stent implantation. During balloon testing in 62 consecutive patients, we assessed gradients across the pulmonary vein to left atrium while monitoring the rhythm. We observed the outcomes after covered stent correction in 51 patients. In a single patient, significant bradycardia and pauses developed on repeat balloon testing and the procedure was abandoned without stent implantation. In another patient, there was no sign of sinus node dysfunction during balloon testing but several hours after stent implantation, the patient became symptomatic from sinus bradycardia and pauses and had a pacemaker implanted 3 days later. Over a year later there are some signs of improvement in sinus node function. While sinus node dysfunction has not been described previously during balloon testing or after stent implantation, this report demonstrates for the first time that it may occur. Larger registries are therefore required to monitor for this uncommon complication.