Rapamycin extends lifespan and attenuates age-related pathologies in mice when administered through diet at 14 parts per million (PPM). Recently, we reported that daily intraperitoneal injection of rapamycin at 8 mg/kg attenuates mitochondrial disease symptoms and progression in the Ndufs4 knockout mouse model of Leigh Syndrome. Although rapamycin is a widely used pharmaceutical agent dosage has not been rigorously examined and no dose-response profile has been established. Given these observations we sought to determine if increased doses of oral rapamycin would result in more robust impact on mTOR driven parameters. To test this hypothesis, we compared the effects of dietary rapamycin at doses ranging from 14 to 378 PPM on developmental weight in control and Ndufs4 knockout mice and on health and survival in the Ndufs4 knockout model. High dose rapamycin was well tolerated, dramatically reduced weight gain during development, and overcame gender differences. The highest oral dose, approximately 27-times the dose shown to extend murine lifespan, increased survival in Ndufs4 knockout mice similarly to daily rapamycin injection without observable adverse effects. These findings have broad implications for the effective use of rapamycin in murine studies and for the translational potential of rapamycin in the treatment of mitochondrial disease. This data, further supported by a comparison of available literature, suggests that 14 PPM dietary rapamycin is a sub-optimal dose for targeting mTOR systemically in mice. Our findings suggest that the role of mTOR in mammalian biology may be broadly underestimated when determined through treatment with rapamycin at commonly used doses.

BackgroundThough rickettsiosis is common in India, there is paucity of rickettsial retinitis (RR) reports from India. Moreover, rickettsial sub-types and their association with retinitis have not been studied. We are reporting a case series of presumed RR with their course of the disease, visual outcome, and association with rickettsial sub-type based on Weil-Felix test.FindingsThis is a retrospective study of 19 eyes of 10 patients presented to a single institution. Cases diagnosed with presumed RR were identified from our database from March 2006 to October 2014 and studied retrospectively for patient’s demography, clinical presentation, and treatment. Patients with history of fever, retinitis, and a positive Weil-Felix test and a negative chikungunya and dengue serology were diagnosed as presumed rickettsial uveitis. One patient was diagnosed to have epidemic typhus, and four were diagnosed to have Indian tick typhus. Nine patients had bilateral presentation. One patient had history of dog tick bite, and four patients had skin rashes. All the patients presented between 2 and 4 weeks after a fever.ConclusionsRetinitis on posterior pole with recent history of fever with or without skin rash and a positive Weil-Felix test may suggest a rickettsial etiology. Its ocular manifestation could be an immune response to recent systemic rickettsial infection. Indian tick typhus and epidemic typhus could be the common sub-types seen in our population. Although it has aggressive presentation, it has a good visual prognosis.

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Background: As citizens have been forced to stay home during coronavirus disease of 2019 (COVID-19) pandemic, the crisis created unique trends in the neurotrauma patterns with changes in mode, severity, and outcome of head injured patients. Methods: Details of neurotrauma admissions under the neurosurgery department at our institute since the onset of COVID-19 pandemic in the country were collected retrospectively and compared to the same period last year in terms of demographic profile, mode of injury, GCS at admission, severity of head injury, radiological diagnosis, management (surgical/conservative), and outcome. The patients were studied according to which phase of pandemic they were admitted in – “lockdown” period (March 25 to May 31, 2020) or “unlock” period (June 1 to September 15, 2020). Results: The number of head injuries decreased by 16.8% during the COVID-19 pandemic. Furthermore, during the lockdown period, the number of admissions was 2.7/week while it was 6.8/week during the “unlock” period. RTA was the mode of injury in 29.6% patients during the lockdown, while during the unlock period, it was 56.9% (P = 0.000). Mild and moderate head injuries decreased by 41% and severe head injuries increased by 156.25% during the COVID-19 pandemic (P = 0.000). The mortality among neurotrauma patients increased from 12.4% to 22.5% during the COVID-19 era (P = 0.009). Conclusion: We observed a decline in the number of head injury admissions during the pandemic, especially during the lockdown. At the same time, there was increase in the severity of head injuries and associated injuries, resulting in significantly higher mortality in our patients during the ongoing COVID-19 pandemic.

A case of prosthetic valve endocarditis caused by Cryptococcus neoformans var. neoformans is described. The infection followed closed mitral valvotomy and insertion of a valvular prosthesis. Infection was manifested 2 weeks after the operation. The diagnosis was based on direct demonstration of the yeast with characteristic morphology in clinical material, isolation from an arterial thrombus and detection of cryptococcal antigen in the serum. The patient's infection could not be resolved despite institution of antifungal therapy.

The menace of cryptococcosis has assumed global proportions over the years. The tropical climate of the Indian subcontinent offers a suitable environment for Cryptococcus neoformans, and the onslaught of the acquired immune deficiency syndrome (AIDS) pandemic since the early 1990s has substantially influenced the situation. Coupled with that are the advances in laboratory diagnostic techniques that have made accurate diagnosis increasingly available. These factors together have led to a sharp increase in the number of reported cases of cryptococcosis. This review attempts to present an overview of the status of cryptococcosis in India from its first description to the most recent times. The disease has been reported from almost all parts of the country. C. neoformans var. neoformans is predominantly found in clinical samples, while C. n. var. gattii infection has also been reported. An organ commonly involved is the central nervous system, among others. Both immunocompromised and apparently immunocompetent patients have been affected. Laboratory diagnosis is mostly by conventional methods, while effective therapeutic options are limited. Early diagnosis followed by institution of specific therapy, where possible, has effectively reduced mortality. Awareness of the disease and maintenance of a high index of clinical suspicion is required. An integrated approach to patient management with active interaction between the clinicians and the laboratory personnel would be highly beneficial. The wide variety of presentations of the disease seen in India suggests the possibility of occurrence of strain variation which needs to be investigated fully. Introduction of routine testing of antifungal susceptibility of clinical isolates is also important in order to obtain baseline data on susceptibility patterns and to predict in advance any shift in those patterns in the population. To maintain a high standard in all such endeavours, the establishment of an external quality control system is desirable.

In the present study, fungal sinusitis could be correctly diagnosed on CT with high accuracy. Thus, understanding the different CT findings of fungal sinusitis allows the radiologist to play a crucial role in the diagnosis and prompt treatment.

Background Acute‐on‐chronic liver failure (ACLF) is associated with a high short‐term mortality rate in the absence of liver transplantation. The role of therapeutic plasma exchange (TPE) in improving the outcomes of ACLF and acute decompensation (AD) is unclear. In this retrospective analysis, we aimed to determine the impact of TPE on mortality in patients with ACLF. Methods ACLF patients receiving TPE with standard medical treatment (SMT) were propensity score matched (PSM) with those receiving SMT alone (1:1) for sex, grades of ACLF, CLIF C ACLF scores, and the presence of hepatic encephalopathy. The primary outcomes assessed were mortality at 30 and 90 days. Survival analysis was performed using Kaplan Meier survival curves. Results A total of 1151 patients (ACLF n = 864 [75%], AD [without organ failure] n = 287 [25%]) were included. Of the patients with ACLF (n = 864), grade 1, 2, and 3 ACLF was present in 167 (19.3%), 325 (37.6%), and 372 (43.0%) patients, respectively. Thirty‐nine patients received TPE and SMT, and 1112 patients received only SMT. On PSM analysis, there were 38 patients in each group (SMT plus TPE vs SMT alone). In the matched cohort, the 30‐days mortality was lower in the TPE arm compared to SMT (21% vs 50%, P = .008), however, the 90‐day mortality was not significantly different between the two groups (36.8% vs 52.6%, P = .166); HR, 0.82 (0.44‐1.52), P = .549. Conclusion TPE improves short‐term survival in patients with ACLF, but has no significant impact on long‐term outcomes. Randomized control trials are needed to obtain a robust conclusion in this regard.