Exposure to an enriched environment promotes dendritic remodelling in hippocampal neurons affected by endogenous depression

Neuronal plasticity is enhanced in an enriched environment (EE) with more sensory and social interaction. In an animal model of endogenous depression, we have previously shown that EE has positive effects on spatial memory and hippocampus synaptic plasticity. However, nothing is known about how EE influences dendritic remodelling in hippocampal neurons affected by endogenous depression. In depressed rats, the impact of EE on hippocampus neuronal morphology was examined. Neonatal clomipramine exposure from postnatal days (PND) 8-21 days induced endogenous depression. The depressed-like rats were exposed to an enriched environment for two weeks in adulthood. Brains were then collected, stained with a modified Golgi-cox technique and, the hippocampal CA1 dendritic arborisation was evaluated using the Neurolucida software. Depression resulted in the atrophy of CA1 hippocampal neurons. The number of branching points and the overall number of dendritic intersections were reduced in depressed rats,. Exposure to an enriched environment significantly increased dendritic branching and the total number of dendritic intersections in hippocampal CA1 pyramidal neurons. The hippocampal pyramidal neuronal morphology of depressed rats improved after exposure to environmental enrichment. Neuronal plasticity and the development of novel therapeutic strategy will be improved by a greater understanding of how the environment affects neuronal morphology in depressed states

Angiomatosis in the Head and Neck—3 Case Reports

Angiomatosis is a diffuse vascular lesion which involves a large segment of the body in a contiguous fashion involving multiple tissues (e.g. subcutis, muscle, bone, adipose tissue etc.) in different planes. Such lesions usually present in the first two decades of life with female predilection and are commonly seen in lower extremities. It clinically mimics hemangioma or vascular malformation and its surgical removal is difficult because of its infiltrative nature and thus has high recurrence rate (90%). Therefore a precise histopathological diagnosis of angiomatosis is important to achieve a curative resection. Histopathologically it consists of proliferating blood vessels of varying caliber, infiltrating into the soft tissues. Proliferating capillaries are seen within or adjacent to major vessels. Few cases are reported in head and neck region. This article highlights three unusual cases of angiomatosis reported as benign lesions, in rare sites such as the malar region (predominantly infiltrating the adipose tissue), within the masseter (predominantly infiltrating the muscle) and in the mandible (infiltrating the bone). Histopathological differential diagnosis is also discussed

Comparing the spatio-temporal variability of remotely sensed oceanographic parameters between the Arabian Sea and Bay of Bengal throughout a decade

The spatio-temporal variability of sea-surface temperature (SST), photosynthetically active radiation (PAR), chlorophyll-a (Chl-a), particulate organic carbon (POC) and particulate inorganic carbon (PIC) was evaluated in the Arabian Sea (ABS) and Bay of Bengal (BoB), from July 2002 to November 2014 by means of remotely sensed monthly composite Aqua MODIS level-3 data having a spatial resolution of 4.63 km. Throughout the time period under consideration, the surface waters of ABS (27.76 ± 1.12°C) were slightly cooler than BoB (28.93 ± 0.76°C); this was observed during all the seasons. On the contrary, the availability of PAR was higher in ABS (45.76 ± 3.41 mol m-2 d-1) compared to BoB (41.75 ± 3.75 mol m-2 d-1), and its spatial dynamics in the two basins was mainly regulated by cloud cover and turbidity of the water column. The magnitude and variability of Chl-a concentration were substantially higher in ABS (0.487 ± 0.984 mg m-3), compared to BoB (0.187 ± 0.243 mg m-3), and spatially higher values were observed near the coastal waters. Both POC and PIC exhibited higher magnitudes in ABS compared to BoB; however, the difference was substantially high in case of POC. None of the parameters showed any significant temporal trend during the 12-year span, except PIC, which exhibited a significant decreasing trend in ABS

Recognizing recurrent neural networks (rRNN): Bayesian inference for recurrent neural networks

Recurrent neural networks (RNNs) are widely used in computational neuroscience and machine learning applications. In an RNN, each neuron computes its output as a nonlinear function of its integrated input. While the importance of RNNs, especially as models of brain processing, is undisputed, it is also widely acknowledged that the computations in standard RNN models may be an over-simplification of what real neuronal networks compute. Here, we suggest that the RNN approach may be made both neurobiologically more plausible and computationally more powerful by its fusion with Bayesian inference techniques for nonlinear dynamical systems. In this scheme, we use an RNN as a generative model of dynamic input caused by the environment, e.g. of speech or kinematics. Given this generative RNN model, we derive Bayesian update equations that can decode its output. Critically, these updates define a 'recognizing RNN' (rRNN), in which neurons compute and exchange prediction and prediction error messages. The rRNN has several desirable features that a conventional RNN does not have, for example, fast decoding of dynamic stimuli and robustness to initial conditions and noise. Furthermore, it implements a predictive coding scheme for dynamic inputs. We suggest that the Bayesian inversion of recurrent neural networks may be useful both as a model of brain function and as a machine learning tool. We illustrate the use of the rRNN by an application to the online decoding (i.e. recognition) of human kinematics

Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues

Defining the pharmacological target(s) of currently used drugs and developing new analogues with greater potency are both important aspects of the search for agents that are effective against drug-sensitive and drug-resistant Mycobacterium tuberculosis. Thiacetazone (TAC) is an anti-tubercular drug that was formerly used in conjunction with isoniazid, but removed from the antitubercular chemotherapeutic arsenal due to toxic side effects. However, several recent studies have linked the mechanisms of action of TAC to mycolic acid metabolism and TAC-derived analogues have shown increased potency against M. tuberculosis. To obtain new insights into the molecular mechanisms of TAC resistance, we isolated and analyzed 10 mutants of M. tuberculosis that were highly resistant to TAC. One strain was found to be mutated in the methyltransferase MmaA4 at Gly101, consistent with its lack of oxygenated mycolic acids. All remaining strains harbored missense mutations in either HadA (at Cys61) or HadC (at Val85, Lys157 or Thr123), which are components of the bhydroxyacyl-ACP dehydratase complex that participates in the mycolic acid elongation step. Separately, a library of 31 new TAC analogues was synthesized and evaluated against M. tuberculosis. Two of these compounds, 15 and 16, exhibited minimal inhibitory concentrations 10-fold lower than the parental molecule, and inhibited mycolic acid biosynthesis in a dose-dependent manner. Moreover, overexpression of HadAB HadBC or HadABC in M. tuberculosis led to high level resistance to these compounds, demonstrating that their mode of action is similar to that of TAC. In summary, this study uncovered new mutations associated with TAC resistance and also demonstrated that simple structural optimization of the TAC scaffold was possible and may lead to a new generation of TAC-derived drug candidates for the potential treatment of tuberculosis as mycolic acid inhibitors

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Translational Medicine - doing it backwards

In recent years the concept of "translational medicine" has been advanced in an attempt to catalyze the medical applications of basic biomedical research. However, there has been little discussion about the readiness of scientists themselves to respond to what we believe is a required new approach to scientific discovery if this new concept is to bear fruit. The present paradigm of hypothesis-driven research poorly suits the needs of biomedical research unless efforts are spent in identifying clinically relevant hypotheses. The dominant funding system favors hypotheses born from model systems and not humans, bypassing the Baconian principle of relevant observations and experimentation before hypotheses. Here, we argue that that this attitude has born two unfortunate results: lack of sufficient rigor in selecting hypotheses relevant to human disease and limitations of most clinical studies to certain outcome parameters rather than expanding knowledge of human pathophysiology; an illogical approach to translational medicine. If we wish to remain true to our responsibility and duty of performing research relevant to human disease, we must begin to think about fundamental new approaches