A Novel Technique for Detecting Depressive Disorder: A Speech Database-Based Approach.

Depression is the second most diagnosed disease in the world and is predicted to be the highest by the year 2030. Depressive disorder impacts both on mentally and physically, thus diagnosing this disorder in early stage is essential. Automatic Depression Detection (ADD) system via speech can greatly facilitate early-stage depression diagnosis. Development of such systems demands a standard balanced database. In this work, we present a novel labeled audio distress interview database. To our knowledge, this is the first depression database in Bengali language that contains audio responses from depressed and non-depressed subjects. Alongside this, we present a set of hand-crafted acoustic features that effectively detect depression mood using speech signals. Finally, we justify the quality of our developed database and the efficacy of the feature set in predicting depression using a baseline machine learning (ML) model. We believe that the annotated database will be a valuable resource for use by treating clinicians.Clinical Relevance-This research reports a new speech database in Bengali language for depression detection. This database can be used in healthcare by developing an automatic prediction model for depression detection.

Inflammation decreases keratin level in ulcerative colitis; inadequate restoration associates with increased risk of colitis-associated cancer.

BACKGROUND: Keratins are intermediate filament (IF) proteins, which form part of the epithelial cytoskeleton and which have been implicated pathology of inflammatory bowel diseases (IBD). METHODS: In this study biopsies were obtained from IBD patients grouped by disease duration and subtype into eight categories based on cancer risk and inflammatory status: quiescent recent onset (<5 years) UC (ROUC); UC with primary sclerosing cholangitis; quiescent long-standing pancolitis (20-40 years) (LSPC); active colitis and non-inflamed proximal colonic mucosa; pancolitis with dysplasia-both dysplastic lesions (DT) and distal rectal mucosa (DR); control group without pathology. Alterations in IF protein composition across the groups were determined by quantitative proteomics. Key protein changes were validated by western immunoblotting and immunohistochemical analysis. RESULT: Acute inflammation resulted in reduced K8, K18, K19 and VIM (all p<0.05) compared to controls and non inflamed mucosa; reduced levels of if- associated proteins were also seen in DT and DR. Increased levels of keratins in LSPC was noted relative to controls or ROUC (K8, K18, K19 and VIM, p<0.05). Multiple K8 forms were noted on immunoblotting, with K8 phosphorylation reduced in progressive disease along with an increase in VIM:K8 ratio. K8 levels and phosphorylation are reduced in acute inflammation but appear restored or elevated in subjects with clinical and endoscopic remission (LSPC) but not apparent in subjects with elevated risk of cancer. CONCLUSIONS: These data suggest that keratin regulation in remission may influence subsequent cancer risk.

Keratins in colorectal epithelial function and disease.

Keratins are the largest subgroup of intermediate filament proteins, which are an important constituent of the cellular cytoskeleton. The principally expressed keratins (K) of the intestinal epithelium are K8, K18 and K19. The specific keratin profile of a particular epithelium provides it with strength and integrity. In the colon, keratins have been shown to regulate electrolyte transport, likely by targeting ion transporters to their correct location in the colonocytes. Keratins are highly dynamic and are subject to post-translational modifications including phosphorylation, acetylation and glycosylation. These affect the filament dynamics and hence solubility of keratins and may contribute to protection against degradation. Keratin null mice (K8(-/-) ) develop colitis, and abnormal keratin mutations have been shown to be associated with inflammatory bowel disease (IBD). Abnormal expression of K7 and K20 has been noted in colitis-associated dysplasia and cancers. In sporadic colorectal cancers (CRCs) may be useful in predicting tumour prognosis; a low K20 expression is noted in CRCs with high microsatellite instability; and keratins have been noted as dysregulated in peri-adenomatous fields. Caspase-cleaved fragment of K18 (M30) in the serum of patients with CRC has been used as a marker of cancer load and to assess response to therapy. These data suggest an emerging importance of keratins in maintaining normal function of the gastrointestinal epithelium as well as being a marker of various colorectal diseases. This review will primarily focus on the biology of these proteins, physiological functions and alterations in IBD and CRCs.

An integrated workflow for extraction and solubilization of intermediate filaments from colorectal biopsies for proteomic analysis.

We report a technique for isolation and solubilization of intermediate filament (IF) proteins from colonic biopsies compatible with both gel electrophoresis and liquid chromatography "shotgun" proteomics using mass spectrometry (MS). This is important because changes in the IF proteome, particularly in keratin expression and modification, are noted in colonic mucosa of patients with colorectal cancer. Though keratins have traditionally been dissolved in high concentration of urea, the latter solvent precludes efficient proteolytic digestion by trypsin prior to gel-free LC-MS/MS approaches. The extraction of cytoskeletal proteins was initially evaluated using MCF-7 cancer cell lines using a published, differential detergent solubilization protocol. IF proteins were extracted from colonic biopsies using a combination of homogenization and sonication. Since comparable efficiency of solubilization was noted on the extracted IF from cell lines between urea and guanidine hydrochloride (GuHCl) in triethylammonium bicarbonate buffer, isolated proteins from endoscopic biopsies were solubilized in GuHCl. Using immunoblotting techniques, we successfully demonstrated isolation of keratins and preservation of posttranslational modifications (phosphorylation, acetylation). Dissolved proteins were tryptically digested and peptides analyzed by MS, showing the functionality of the workflow in shotgun proteomic applications, specifically compatibility of the workflow for isobaric tagging relative and absolute quantification based quantitation approaches.

Conversion (dissociative) symptoms as a presenting feature in early onset bipolar disorder: a case series.

We present three cases of early onset bipolar disorder where dissociative (conversion) symptoms preceded the onset of mania. This case series underscores the significance of dissociative/conversion symptoms as an early atypical presentation in juvenile bipolar disorder.

Cardiac dysfunction in portal hypertension among patients with cirrhosis and non-cirrhotic portal fibrosis.

BACKGROUND/AIMS: In cirrhosis, diastolic dysfunction of heart is well documented. Contribution of portal hypertension towards cardiac changes in cirrhosis is difficult to assess. We examined the patients of non-cirrhotic portal fibrosis who have portal hypertension without liver insufficiency to understand the contribution of portal hypertension in causing cardiac changes. METHODS: Cardiac function was studied in four groups of patients: normal controls, patients with non-cirrhotic portal fibrosis (having portal hypertension without liver dysfunction) and cirrhotics with and without ascites. Cardiac function was evaluated by echocardiography. Additional measurements of plasma renin activity and aldosterone levels were performed. RESULTS: Diastolic function as assessed by the ratio between E wave and A wave (E/A ratio), was significantly lower in patients with non-cirrhotic portal fibrosis (median 1.3) compared to normal controls (median 1.52). However, even lower values were observed in cirrhotics without ascites (median 1.05) and with ascites (median 0.94). There was a significant correlation (r=-0.75) between plasma aldosterone levels and the E/A ratio in cirrhotics. CONCLUSIONS: Diastolic dysfunction is not only present in cirrhosis but also in non-cirrhotic portal fibrosis. It indicates that portal hypertension is an important factor in the genesis of cardiac dysfunction.

Portal pressure response to losartan compared with propranolol in patients with cirrhosis.

OBJECTIVES: Losartan, an angiotensin II receptor blocker, has portal hypotensive effects. This study evaluates the effect of losartan on portal pressure after 14 days and compares it with that of propranolol. METHODS: A total of 39 individuals with cirrhosis were randomized into two groups of 19 and 20 patients each and were treated with losartan and propranolol, respectively. Hepatic venous pressure gradient was measured at baseline and on day 14 of therapy. Responders to therapy had hepatic venous pressure gradient reduction of >/=20% of baseline value. RESULTS: With losartan, 15 of 19 (78.94%) patients were responders and with propranolol, nine of 20 (45%) patients were responders (p < 0.05). Although the hepatic venous pressure gradient reduction (i.e., percentage from baseline) with losartan (26.74 +/- 21.7%) was higher than with propranolol (14.52 +/- 32%), the difference was not significant. The reduction in hepatic venous pressure gradient with losartan was contributed mainly by a significant drop of wedge hepatic venous pressure from 32.42 +/- 6.61 mm of Hg to 28.31 +/- 5.09 mm of Hg (p < 0.05) compared to that with propranolol, which was from 34.55 +/- 5.41 mm of Hg to 32.75 +/- 8.13 mm of Hg (p > 0.05). Responders among alcohol-abusing patients were significantly higher with losartan (81.8%) compared to those on propranolol (27.2%; p < 0.05). In the losartan group, all seven nonascitic cirrhotic individuals, as compared with two of five in the propranolol group, responded to the drugs. During the study, no significant side effects were observed in either group (who were not receiving diuretics) or in follow-up with diuretics. CONCLUSIONS: Losartan is as effective as propranolol in reducing portal pressure in cirrhotic patients who are not receiving diuretics. Losartan is also superior to propranolol for achieving target level hepatic venous gradient for prevention of variceal bleeding in nonascitic and alcohol-abusing cirrhotic patients.

Cloning and expression of Chlorobium vibrioforme uroporphyrinogen decarboxylase gene in a Salmonella heme auxotroph.

To study the post-uroporphyrin steps in heme and chlorophyll biosynthesis in Chlorobium, we attempted to clone the uroporphyrinogen decarboxylase ( hemE) gene. A Chlorobium genomic library was used to transform a restriction-minus Salmonella typhimurium strain. The recombinant DNA molecules were transduced into an auxotrophic Salmonella double mutant ( hemA(-) hemE(-)) by phage P22. Faster-growing colonies indicated complementation of the hemE mutation. Each clone was tested by backcross transduction of the mutant. Growth rates of the confirmed clones in LB medium were comparable to wild-type Salmonella. HPLC analysis of the substrate (uroporphyrinogen) and the product (coproporphyrinogen) of the decarboxylase activity was performed in one such clone. This clone showed an active hemE gene within a 4-kb insert.