Acetaminophen influences musculoskeletal signaling but not adaptations to endurance exercise training.

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% incline for 2 min at 15 cm/s, 2 min at 20 cm/s, and 26 min at 25 cm/s. A human equivalent dose of ACE was administered (379 mg/kg body weight) in drinking water and adjusted each week based on body weight. Food, water intake, and body weight were measured daily. At the beginning of week 6, animals in the exercise group completed a maximal treadmill test. At the end of week 6, rats were euthanized, and muscle cross-sectional area (CSA), fiber type, and signaling pathways were measured. Additionally, three-point bending and microcomputer tomography were measured in the femur. Follow-up experiments in human primary muscle cells were used to explore supra-physiological effects of ACE. Data were analyzed using a two-way ANOVA for treatment (ACE or placebo) and condition (exercise or non-exercise) for all animal outcomes. Data for cell culture experiments were analyzed via ANOVA. If omnibus significance was found in either ANOVA, a post hoc analysis was completed, and a Tukey's adjustment was used. ACE did not alter body weight, water intake, food intake, or treadmill performance (p > .05). There was a treatment-by-condition effect for Young's Modulus where placebo exercise was significantly lower than placebo control (p < .05). There was no treatment by condition effects for microCT measures, muscle CSA, fiber type, or mRNA expression. Phosphorylated-AMPK was significantly increased with exercise (p < .05) and this was attenuated with ACE treatment. Furthermore, phospho-4EBP1 was depressed in the exercise group compared to the control (p < .05) and increased in the ACE control and ACE exercise group compared to placebo exercise (p < .05). A low dose of ACE did not influence chronic musculoskeletal adaptations in exercising rodents but acutely attenuated AMPK phosphorylation and 4EBP1 dephosphorylation post-exercise.

Multiple palisaded encapsulated neuromas presenting as cobblestoned plaques over palms and oral cavity.

Palisaded encapsulated neuroma (PEN) is a benign circumscribed nerve sheath tumor usually seen as a solitary painless papule on the face in middle-aged adults. We report a 22-year-old male with multiple adolescent-onset PENs distributed extensively, including the oral cavity and palms, contrary to the typical presentations. The lesions formed cobblestoned plaques and were confirmed through a skin biopsy, showing characteristic nodules of wavy spindle cells forming interlacing fascicles with interspersed clefts, and positive staining for specific markers, including markers for axons and perineurium. Notably, this case deviates from the usual presentation, shedding light on atypical manifestations of PEN in a young individual without any features suggestive of a neurocutaneous syndrome or multiple endocrine neoplasia syndrome.

Glucose uptake by GLUT1 in photoreceptors is essential for outer segment renewal and rod photoreceptor survival.

Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced glucose supply underlies photoreceptor cell death in inherited retinal degeneration and age-related retinal disease. We have previously shown that restricting glucose transport into the outer retina by conditional deletion of Slc2a1 encoding GLUT1 resulted in photoreceptor loss and impaired OS renewal. However, retinal neurons, glia, and the retinal pigment epithelium play specialized, synergistic roles in metabolite supply and exchange, and the cell-specific map of glucose uptake and utilization in the retina is incomplete. In these studies, we conditionally deleted Slc2a1 in a pan-retinal or rod-specific manner to better understand how glucose is utilized in the retina. Using non-invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic deletion of Slc2a1 from retinal neurons and Müller glia results in reduced OS growth and progressive rod but not cone photoreceptor cell death. Rhodopsin levels were severely decreased even at postnatal day 20 when OS length was relatively normal. Arrestin levels were not changed suggesting that glucose uptake is required to synthesize membrane glycoproteins. Rod-specific deletion of Slc2a1 resulted in similar changes in OS length and rod photoreceptor cell death. These studies demonstrate that glucose is an essential carbon source for rod photoreceptor cell OS maintenance and viability.

Unwinding the potentials of vitamin C in COVID-19 and other diseases: An updated review.

Background: The discovery of vitamin C (ascorbic acid) is related to the ancient history of persistent research on the origins of the haemorrhagic disease scurvy. Vitamin C is an important nutrient that aids in a variety of biological and physiological processes. Scientists have been researching the function of vitamin C in the prevention and ailment of sepsis and pneumonia for decades. This has created a potential platform for applying these results to individuals suffering from severe coronavirus infection (COVID-19). Vitamin C's ability to activate and enhance the immune system makes it a promising treatment in the present COVID-19 pandemic. Vitamin C also aids in the activation of vitamin B, the production of certain neurotransmitters, and the transformation of cholesterol into bile acids. Hence, vitamin C is used for the treatment of many diseases. Aim: This review highlights the Vitamin C investigations that are performed by various researchers on patients with COVID 19 infection, the clinical studies and their observations. The authors have additionally updated information on the significance of vitamin C insufficiency, as well as its relevance and involvement in diseases such as cancer, wound healing, iron deficiency anaemia, atherosclerosis and neurodegenerative disorders. Here, we discuss them with the references. Methods: The method used in order to perform literature search was done using SciFinder, PubMed and ScienceDirect. Results: There is a potential role of vitamin C in various diseases including neurodegenerative disorders, COVID-19 and other diseases and the results are highlighted in the review with the help of clinical and preclinical data. Conclusion: More research on vitamin C and the undergoing clinical trials might prove a potential role of vitamin C in protecting the population from current COVID-19 pandemic.

Durability of left bundle branch area pacing.

BACKGROUND: Left bundle branch area pacing (LBBAP) is a form of conduction system pacing. Long-term data on the safety and performance of LBBAP 1 year postdevice implantation has not been well described. METHODS AND RESULTS: Sixty-five patients (49% females) who received LBBAP for bradycardia indications using the SelectSecure 3830 lead (Medtronic) were retrospectively evaluated. Clinical variables were examined. Lead parameters were obtained at implant and during regular follow-up. Mean age of patients was 75.7 ± 10.1 years with left ventricular ejection fraction 59.8 ± 10.4%. Indications for pacing were atrioventricular block 55%, sinus node dysfunction 19%, tachy-brady syndrome 15%, atrioventricular node ablation 8%, and bail out cardiac resynchronization therapy 3%. Mean baseline QRS measured 120 ± 38 ms, paced QRS duration was 138 ± 22ms. Paced QRS narrowed by 24 ms in those with pre-existing left bundle branch block (BBB), increased by 1 ms in those with pre-existing right BBB, and increased by 42 ms in those with no BBB. LBBAP threshold at implant was 0.521 ± 0.153 V at 0.4 ms, and increased to 0.654 ± 0.186 V at 3 months (+26%), 0.707 ± 0.186 V at 6 months (+36%), and 0.772 ± 0.220 V at 12 months (+48%). Patients with left BBB showed the maximum benefit with QRS narrowing 24 ms. Pacing impedance remained unchanged with no procedure-related complications. CONCLUSION: LBBAP is a durable form of conduction system pacing with pacing thresholds remaining relatively stable over 12 months post device implantation. Patients with left BBB display the narrowest paced QRS.

Safety and efficacy of left atrial appendage closure using an epicardial suture snaring device: Systematic review and current status.

INTRODUCTION: The LARIAT epicardial suture snaring device has been fraught with technical challenges and procedural complications. Over time, technique modification and improved operator experience have helped overcome many of these challenges. METHODS AND RESULTS: Studies reporting left atrial appendage epicardial closure over a 12-year period from 2009 to 2020 were evaluated. The primary efficacy outcome evaluated was left atrial appendage closure with residual flow ≤1 mm. Safety outcomes evaluated were periprocedural and long term complications after device placement. Nine studies consisting of 1430 patients were included in this analysis, of which 1386 (97%) underwent successful device placement. The mean age was 69.3 years, with a mean CHADS2 -VASC score of 3.78. Primary efficacy end point was achieved in 95.8% patients immediately after device placement, and in 92.8% patients on long term follow-up. Early procedural complications consisted of pericardial effusion 5.6%, cardiac perforation 2.7%, pericarditis 2.6%, and need for open heart surgery 1.5%. Long term complications consisted of all-cause mortality 2.3%, stroke 1.5%, and left atrial appendage thrombus 2.3%. Reduced complications were noted using micropuncture needles (2.20% vs. 10.14%; p < .0001), a longer duration pericardial drainage, and use of anti-inflammatory medications (1.58% vs. 8.4%). Oral anticoagulation use decreased from 44.7% to 22.9% post device implantation, and to 8.5% on last clinical follow up. CONCLUSIONS: The LARIAT device is effective in epicardial closure of the left atrial appendage. Improvement in device techniques such as use of micropuncture needle, prophylactic colchicine, and maintenance of a pericardial drain have helped improve safety over time.

An unusual variant of lichen nitidus: Generalized follicular spinous with perifollicular granulomas.

Several unusual variants of lichen nitidus are described in the literature. Spinous follicular lichen nitidus with perifollicular granulomas is one such variant characterized by generalized follicular as well as nonfollicular keratotic papules, which show perifollicular granulomas on histopathology as well as a lichenoid granulomatous tissue reaction typical of lichen nitidus. Owing to its atypical clinical and histopathologic manifestations, it raises several clinical possibilities and can be a diagnostic challenge. We report this rare variant of lichen nitidus in a 19-year-old female, and discuss its clinical and histopathological differential diagnosis.

Court evidence via video conferencing by doctors: Savings of time, money and energy.

Background: . Doctors are called to courts to give evidence as experts. This is time-consuming and impedes routine patient care. The court ordered the state to instal a video conferencing system for the benefit of doctors in hospitals for this purpose. We aimed to quantify the costs and benefits of the video conferencing system for doctors to give evidence as expert witness in courts. Methods: . We analysed the tele-evidence system at our institution from the societal point of view examining whether the arrangements were positive for the taxpayers and second from the point of view of a cost-break-even analysis. Results: . Over a period of 1 year, 482 tele-evidences were recorded from our site. Most of the doctors appearing for court evidence were males (84%) and the majority were in government health services (84.4%). These expert witnesses included specialists (83.8%), followed by super-specialists (10.4%) and non-specialists (5.8%). The subject experts who were called the most were radiologists (19.5%), forensic experts (18.3%), surgeons (18.0%), orthopaedic surgeons (12.4%) and neurosurgeons (6.6%). Average savings per tele-evidence were ₹2620; 181 km of travel was prevented and 4 hours and 12 minutes of time was saved. Conclusions: . Given our limited resources, video conferencing saves costs, time and travel.

Re-Operative Pancreaticoduodenectomy: Challenges and Outcomes.

BACKGROUND: Tata Memorial Centre (TMC) is a high-volume centre for pancreatic tumour resections. We found a continually increasing referral of pancreatic tumours for re-evaluation for surgery, after an initial unsuccessful attempt at resection. AIM: To evaluate reasons of initial in-operability, the feasibility of re-operative pancreatico-duodenectomy (R-PD) and short- and long-term outcomes after R-PD. METHODS: Data was collected from a prospective database of GI and hepato-pancreato-biliary service, TMC, Mumbai from January 2008 to December 2016. RESULTS: Forty patients with periampullary/pancreatic head tumours were referred to us after exploration. Thirty were planned for re-exploration, of whom 25 patients underwent successful R-PD, either upfront (n = 12) or after neo-adjuvant therapy (n = 13). Twenty were adenocarcinomas, 5 had other histologies. Majority of the patients were deemed inoperable in view of suspected vascular involvement at the time of initial surgery (68%). R0 resection was achieved in 90% of adenocarcinoma cases (n = 18). Postoperative major morbidity was 20% and mortality was 4% (n = 1). The estimated 1-, 2- and 5-year survival for those with adenocarcinoma was 83, 71.2, and 29.9% respectively. CONCLUSION: R-PD is safe and should be performed in experienced centres and can achieve long-term outcomes, comparable to conventional PD. The most common reason for denying resection at initial surgery was suspected or perceived vascular involvement.