Potential biomarkers and therapeutic targets for obsessive compulsive disorder: Evidences from clinical studies.

Obsessive compulsive disorder (OCD) is a prevalent behavioral disorder with a complex etiology. However, the underlying pathogenic molecular pathways and the associated risk factors are largely obscure. This has hindered both the identification of relevant prognostic biomarkers and the development of effective treatment strategies. Because of the diverse range of clinical manifestations, not all patients benefit from therapies currently practiced in the clinical setting. Nevertheless, several lines of evidence indicate that neurotrophic, neurotransmitter, and oxidative signaling are involved in the pathophysiology of OCD. Based upon evidences from clinical (and pre-clinical studies), the present review paper sets out to decipher the utilities of three parameters (i.e. brain-derived neurotrophic factor; BDNF, noradrenalin-synthesizing enzyme dopamine beta-hydroxylase; DBH; and oxidative damage marker malondialdehyde; MDA) as diagnostic peripheral biomarkers as well as bio-targets for therapeutic strategies. While the data indicates promising results, there is necessitation for future studies to further confirm and establish these. Further, based again on the available clinical data, we investigated the possibilities of exploiting the etiological links between disruptions in the sleep-wake cycle and insulin signaling, and OCD for the identification of potential anti-OCD ameliorative agents with the ability to elicit multimodal effects, including attenuation of the alterations in BDNF, noradrenergic and redox pathways. In this respect, agomelatine and metformin may represent particularly interesting candidates; however, further clinical studies are warranted to establish these as singular or complementary medications in OCD subjects.

Navigating to objects in the real world.

Semantic navigation is necessary to deploy mobile robots in uncontrolled environments such as homes or hospitals. Many learning-based approaches have been proposed in response to the lack of semantic understanding of the classical pipeline for spatial navigation, which builds a geometric map using depth sensors and plans to reach point goals. Broadly, end-to-end learning approaches reactively map sensor inputs to actions with deep neural networks, whereas modular learning approaches enrich the classical pipeline with learning-based semantic sensing and exploration. However, learned visual navigation policies have predominantly been evaluated in sim, with little known about what works on a robot. We present a large-scale empirical study of semantic visual navigation methods comparing representative methods with classical, modular, and end-to-end learning approaches across six homes with no prior experience, maps, or instrumentation. We found that modular learning works well in the real world, attaining a 90% success rate. In contrast, end-to-end learning does not, dropping from 77% sim to a 23% real-world success rate because of a large image domain gap between sim and reality. For practitioners, we show that modular learning is a reliable approach to navigate to objects: Modularity and abstraction in policy design enable sim-to-real transfer. For researchers, we identify two key issues that prevent today's simulators from being reliable evaluation benchmarks-a large sim-to-real gap in images and a disconnect between sim and real-world error modes-and propose concrete steps forward.

Rhino-Orbito-Cerebral Mycosis and COVID-19: From Bad to Worse?

Background: There has been an increase an alarming rise in invasive mycoses during COVID-19 pandemic, especially during the second wave. Aims: Compare the incidence of invasive mycoses in the last three years and study the risk factors, manifestations and outcomes of mycoses in the COVID era. Methodology: Multicentric study was conducted across 21 centres in a state of western India over 12-months. The clinico-radiological, laboratory and microbiological features, treatment and outcomes of patients were studied. We also analysed yearly incidence of rhino-orbito-cerebral mycosis. Results: There was more than five-times rise in the incidence of invasive mycoses compared to previous two-years. Of the 122 patients analysed, mucor, aspergillus and dual infection were seen in 86.9%, 4.1%, and 7.4% respectively. Fifty-nine percent had simultaneous mycosis and COVID-19 while rest had sequential infection. Common presenting features were headache (91%), facial pain (78.7%), diplopia (66.4%) and vison loss (56.6%). Rhino-orbito-sinusitis was present in 96.7%, meningitis in 6.6%, intracranial mass lesions in 15.6% and strokes in 14.8%. A total of 91.8% patients were diabetic, while 90.2% were treated with steroids during COVID-19 treatment. Mortality was 34.4%. Conclusion: Invasive fungal infections having high mortality and morbidity have increased burden on already overburdened healthcare system. Past illnesses, COVID-19 itself and its treatment and environmental factors seem responsible for the rise of fungal infection. Awareness and preventive strategies are the need of hours and larger studies are needed for better understanding of this deadly disease.

Modulatory effect of continuous theta burst stimulation in patients with essential tremor.

INTRODUCTION: We aimed to study the cortical and intracortical functions in patients of ET using transcranial magnetic stimulation (TMS) and to evaluate the effect of continuous theta burst stimulation (cTBS) on the tremor characteristics. METHODS: Ten ET and 20 healthy controls were included in the study. All the participants were evaluated with TMS with recording of resting motor threshold (RMT), central motor conduction time, contralateral silent period (cSP), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Subsequently only ET patients underwent cTBS of the motor cortex (M1) followed by repeat TMS. RESULTS: The mean age of the patients (46.5 ± 17.2 years) was comparable to healthy controls (55.4 ± 9.2 years; p = 0.16). There was a non-significant increase in RMT in ET patients (44 ± 12.5%) when compared to healthy controls (40.9 ± 6.9%; p = 0.48). There was a significant reduction of cSP in the ET group (102.03 ± 15.26 msec) compared to healthy controls (116.1 ± 15.2, p = 0.03). In addition, a significant reduction in ICF was observed in ET patients (0.9 ± 0.7) compared to healthy controls (1.8 ± 0.8, p = 0.01). Following cTBS there was a significant reduction in the tremor scores [FTMRS (Pre-cTBS: 29.3 ± 18.7, Post-cTBS: 25.3 ± 16.8; p < 0.001) and TETRAS (pre-cTBS: 34.4 ± 16.2, post-cTBS: 29.8 ± 12.1; p = 0.01)] and improvement (increase) of the duration of cSP (pre-cTBS: 102.03 ± 15.3 msec., post-cTBS: 119.4 ± 12.03 msec; p = 0.05). CONCLUSIONS: Patients with ET have GABAergic and glutaminergic dysfunction as demonstrated by reduced cSP and ICF. However, only the cSP improved following cTBS of M1 region, with a corresponding improvement of tremor severity suggesting the effect of cTBS on the cerebello-thalamo-cortical network.

Cerebrovascular Involvement in Mucormycosis in COVID-19 Pandemic.

BACKGROUND: Many countries have seen an unprecedented rise of cases of coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM). Cerebrovascular involvement in CAM has not been studied so far. We describe clinico-radiological manifestations of cerebrovascular complications observed in CAM. METHODS: In this multicentric retrospective observational study from India, patients with CAM who developed cerebrovascular involvement were studied. Their demographics, risk factors, clinical manifestations, imaging, laboratory profile and outcomes were noted. RESULTS: Out of 49 subjects with cerebrovascular involvement, 71.4% were males while average age was 52.9 years. Ischemic stroke was commonest (91.8%) followed by intracranial haemorrhage (6.1%) and subarachnoid haemorrhage (2%). The incidence of cerebrovascular complications in CAM was found to be 11.8% in one center. Cerebrovascular symptoms appeared a median of 8.3 days from the onset of mucormycosis. Commonest presentation of mucormycosis was rhino-orbito-cerebral syndrome in 98%. Diabetes mellitus was present in 81.7%. Forty percent developed stroke despite being on antiplatelet agent and/or heparin. Amongst subjects with ischemic strokes, location of stroke was unilateral anterior circulation (62.2%); bilateral anterior circulation (17.8%); posterior circulation (11.1%) and combined anterior and posterior circulation (8.9%). Vascular imaging revealed intracranial occlusion in 62.1%; extracranial occlusion in 3.4% and normal vessels in 34.5%. Mortality was 51% during hospital stay. CONCLUSIONS: Cerebrovascular involvement was seen in 11.8% patients of CAM. Angio-invasive nature of the fungus, prothrombotic state created by COVID-19, and diabetes were important causative factors. Subjects with CAM should be screened for involvement of the brain as well as its vessel. Antiplatelet agents/heparin did not seem to provide complete protection from this type of stroke.

Knowledge, Attitude, and Perceptions about Deep Brain Stimulation for Parkinson's Disease: Observations from a Single Indian Center.

OBJECTIVE: Willingness to undergo deep brain stimulation (DBS) among patients with Parkinson's disease (PD) and their overall satisfaction with the procedure is highly dependent upon expectations, which are based on the core concepts of knowledge, attitude and perceptions. The present study aims to evaluate these factors in patients and caregivers with PD from a single tertiary care hospital in India. METHODS: A structured questionnaire designed to assess the knowledge, attitude and perceptions about DBS in PD was administered to 400 patients with PD and their caregivers. RESULTS: A very small proportion of patients and caregivers were aware of DBS. Even those who claimed to be aware of DBS were inadequately informed and had incorrect knowledge, which led to wrong attitudes and perceptions. CONCLUSION: There are very significant knowledge gaps and misconceptions regarding DBS among patients with PD and caregivers. Adequate and appropriate education is necessary to clarify these misconceptions to avoid the development of unrealistic expectations and poor satisfaction.

Comparison of effectiveness of trihexyphenidyl and levodopa on motor symptoms in Parkinson's disease.

Despite anti-cholinergics being the oldest type of medication used for the treatment of Parkinson's disease (PD), the mechanism of action and exact benefit is unclear. This study compared the effectiveness of trihexyphenidyl (THP) and levodopa (LD) on motor symptoms in patients with PD. Patients with PD who are currently taking or had taken THP were recruited. UPDRS-III was done following overnight medication OFF state and 30 min, 60 min, 90 min, and 120 min after THP (4 mg). After a forty-eight-hour interval, UPDRS-III was assessed one hour after Levodopa/carbidopa (200/50 mg) in an overnight OFF state. Twenty patients with a mean age of 57.9 ± 7.8 years and mean duration of illness of 5.1 ± 3.6 years were recruited. UPDRS-III score reduction (%) with THP was maximum in the tremor sub-score (53.8 ± 22.8) and was significantly better compared to improvement in total-UPDRS-III (27.0 ± 14.7), bradykinesia-UPDRS-III (22.2 ± 27.2), rigidity-UPDRS-III (29.5 ± 28.0) and axial-UPDRS-III (8.1 ± 13.3) sub-score. In comparison, respective LD improvement was 67.1 ± 22.9 (tremor-UPDRS-III), 61.3 ± 14.4 (total-UPDRS-III), 67.9 ± 32.1 (bradykinesia-UPDRS-III), 65.3 ± 25.5 (rigidity-UPDRS-III) and 50.7 ± 16.0 (axial-UPDRS-III). Improvement (%) in tre-UPDRS-III post-THP was comparable to that of post-LD (53.8 ± 22.8 vs. 67.1 ± 22.9, p = 0.057). Those with same or better tremor response with THP had significantly milder baseline tremor severity than those who had better response with LD (tre-UPDRS-III-OFF, 10.0 ± 2.8 vs. 5.8 ± 4.0, p = 0.013). Both THP and LD showed significant improvement in UPDRS-III. With THP, the maximum degree of improvement was in the tremor sub-score and not significantly different to that obtained by LD. Those with better tremor response on THP had milder tremor severity.

The spectrum of malignancies presenting with neurological manifestations: A prospective observational study.

INTRODUCTION: A neurological consultation is needed in nearly 45% of patients suffering from cancer. The present study was planned to evaluate the clinical, radiological and histopathological spectrum of patients with an underlying malignancy and presenting with a neurological complaint. MATERIALS AND METHODS: We prospectively evaluated all patients provisionally diagnosed either with a primary or secondary malignancy of the brain on the basis of clinical, radiological and/or histopathological features. RESULTS: A total of 155 patients were enrolled from a total of 4893 admissions done from January 2015 to July 2016. The common presenting symptoms were headache, back pain and paraparesis. Around 26% of patients presented with an altered sensorium, 19.4% with seizures and 21% had at least one cranial nerve involvement. The most common site of involvement was the brain noted in 49.7% of patients. Primary malignancies constituted 78 cases (50.7%) while secondary malignancies included 77 cases (49.3%). Magnetic resonance imaging (MRI) revealed 92 (59.4%) intra-axial lesions and 59 (38.1%) extra-axial lesions, with five cases having both. The most common diagnoses were intra-cerebral metastases and glioblastoma (intra-axial), and vertebral metastases and meningioma (extra-axial). Histopathological confirmation was obtained in 59 patients (38.1%) with 12 primary and 47 secondary lesions. Ten (6.45%) patients had an unknown primary with secondary metastases. The three most common histopathologically confirmed diagnoses were adenocarcinoma lung, plasma cell dyscrasia and adenocarcinoma prostate. CONCLUSION: Primary neurological consultations with an unknown primary are common hence a high index of suspicion can prevent an inadvertent delay in the diagnosis and appropriate treatment of a malignant lesion. Developing a neuro-oncology register may help us in gaining more insight into such situations.

Visual Dialog.

We introduce the task of Visual Dialog, which requires an AI agent to hold a meaningful dialog with humans in natural, conversational language about visual content. Specifically, given an image, a dialog history, and a question about the image, the agent has to ground the question in image, infer context from history, and answer the question accurately. Visual Dialog is disentangled enough from a specific downstream task so as to serve as a general test of machine intelligence, while being sufficiently grounded in vision to allow objective evaluation of individual responses and benchmark progress. We develop a novel two-person real-time chat data-collection protocol to curate a large-scale Visual Dialog dataset (VisDial). VisDial v0.9 has been released and consists of dialog question-answer pairs from 10-round, human-human dialogs grounded in images from the COCO dataset.

Clinical Profile of Hypertensive Emergencies in an Intensive Care Unit.

AIMS AND OBJECTIVE: To study the prevalence of hypertensive emergencies in an ICU set up and to study the clinical presentation of hypertensive emergencies related to cardiovascular, neurological and renovascular system. METHODS: Type of Study: Cross-sectional, descriptive study. DURATION OF STUDY: Two years from 1st December 2011 till 30th November 2013. SAMPLE SIZE: 50 patients of hypertensive emergencies admitted to the intensive care unit of Dr. V.M. Govt. Medical College, Solapur were studied. Inclusion criteria All patients above 18 years of age. Systolic blood pressure > 180 mmHg Diastolic blood pressure > 120 mm Hg Exclusion criteria Pregnancy Patients with diabetes mellitus We classified as hypertensive emergencies all cases in which the increase in blood pressure was associated with one or more of the following types of acute or ongoing end-organ damage: hypertensive encephalopathy; stroke (cerebral infarction or intracerebral or subarachnoid hemorrhage, transient ischemic attack); acute pulmonary edema, left ventricular failure; acute myocardial infarction or unstable angina, progressive renal insufficiency features suggestive of retinopathy. All these conditions were diagnosed clinically or by approprriate diagnostic tests. CONCLUSIONS: most common presenting complaint in patients was breathlessness seen in 17 patients (34%), followed by neurological deficit in 14 patients (28%). Thirteen patients (26%) had complaints of headache, whereas 12 (24%) patients complained of chest pain on admission. Other symptoms included vomiting, giddiness, psychomotor agitation, and decreased urine output. Out of a total of 4076 admissions during the study period in the intensive care unit we had 50 cases of hypertensive emergencies with prevalence of 1.22% in our intensive care unit. Most common organ involvement was the retina followed by cardiovascular system, renal and then the central nervous system.

Cortical laminar necrosis in dengue encephalitis-a case report.

BACKGROUND: Dengue encephalitis is a rare neurological manifestation of dengue fever. Its clinical presentation is similar to other viral encephalitides and encephalopathy. No single specific finding on magnetic resonance imaging of dengue encephalitis has yet been documented. They are highly variable and atypical. CASE PRESENTATION: A 15-year boy presented with fever, the headache and altered sensorium of 12-day duration. On neurological examination, his Glasgow Coma Scale score was 10 (E3M4V3). There was no focal neurological deficit. Laboratory evaluation revealed leukopenia and marked thrombocytopenia. Dengue virus IgM antibody was positive both in serum and cerebrospinal fluid. Magnetic resonance imaging of the brain revealed signal changes in bilateral parietooccipital and left frontal regions (left hemisphere more involved than the right hemisphere). There was gyriform enhancement bilateral parietooccipital regions consistent with cortical laminar necrosis. Bilaterally diffuse subcortical white matter was also involved and subtle T2 hyperintensity involving both basal ganglia was noted. Gradient echo sequence revealed presence of hemorrhage in the subcortical white matter. Patient was treated conservatively and received platelet transfusion. Patient became fully conscious after 7 days. CONCLUSION: In a patient with highly suggestive dengue e\ephalitis, we describe an unusual magnetic resonance imaging finding. This report is possibly the first instance of cortical laminar necrosis in such a setting.

Empirical Minimum Bayes Risk Prediction.

When building vision systems that predict structured objects such as image segmentations or human poses, a crucial concern is performance under task-specific evaluation measures (e.g., Jaccard Index or Average Precision). An ongoing research challenge is to optimize predictions so as to maximize performance on such complex measures. In this work, we present a simple meta-algorithm that is surprisingly effective - Empirical Min Bayes Risk. EMBR takes as input a pre-trained model that would normally be the final product and learns three additional parameters so as to optimize performance on the complex instance-level high-order task-specific measure. We demonstrate EMBR in several domains, taking existing state-of-the-art algorithms and improving performance up to 8 percent, simply by learning three extra parameters. Our code is publicly available and the results presented in this paper can be replicated from our code-release.

Transcriptome-wide functional characterization reveals novel relationships among differentially expressed transcripts in developing soybean embryos.

BACKGROUND: Transcriptomics reveals the existence of transcripts of different coding potential and strand orientation. Alternative splicing (AS) can yield proteins with altered number and types of functional domains, suggesting the global occurrence of transcriptional and post-transcriptional events. Many biological processes, including seed maturation and desiccation, are regulated post-transcriptionally (e.g., by AS), leading to the production of more than one coding or noncoding sense transcript from a single locus. RESULTS: We present an integrated computational framework to predict isoform-specific functions of plant transcripts. This framework includes a novel plant-specific weighted support vector machine classifier called CodeWise, which predicts the coding potential of transcripts with over 96 % accuracy, and several other tools enabling global sequence similarity, functional domain, and co-expression network analyses. First, this framework was applied to all detected transcripts (103,106), out of which 13 % was predicted by CodeWise to be noncoding RNAs in developing soybean embryos. Second, to investigate the role of AS during soybean embryo development, a population of 2,938 alternatively spliced and differentially expressed splice variants was analyzed and mined with respect to timing of expression. Conserved domain analyses revealed that AS resulted in global changes in the number, types, and extent of truncation of functional domains in protein variants. Isoform-specific co-expression network analysis using ArrayMining and clustering analyses revealed specific sub-networks and potential interactions among the components of selected signaling pathways related to seed maturation and the acquisition of desiccation tolerance. These signaling pathways involved abscisic acid- and FUSCA3-related transcripts, several of which were classified as noncoding and/or antisense transcripts and were co-expressed with corresponding coding transcripts. Noncoding and antisense transcripts likely play important regulatory roles in seed maturation- and desiccation-related signaling in soybean. CONCLUSIONS: This work demonstrates how our integrated framework can be implemented to make experimentally testable predictions regarding the coding potential, co-expression, co-regulation, and function of transcripts and proteins related to a biological process of interest.