Predictive profiling of gram-negative antibiotics in CagA oncoprotein inactivation: a molecular dynamics simulation approach.

Gastric cancer (GC) is the fifth most prevalent form of cancer worldwide. CagA - positive Helicobacter pylori infects more than 60% of the human population. Moreover, chronic infection of CagA-positive H. pylori can directly affect GC incidence. In the current study, we have repurposed FDA-approved antibiotics that are viable alternatives to current regimens and can potentially be used as combination therapy against the CagA of H. pylori. The 100 FDA-approved gram negative antibiotics were screened against CagA protein using the AutoDock 4.2 tool. Further, top nine compounds were selected based on higher binding affinity with CagA. The trajectory analysis of MD simulations reflected that binding of these drugs with CagA stabilizes the system. Nonetheless, atomic density map and principal component analysis also support the notion of stable binding of antibiotics to the protein. The residues ASP96, GLN100, PRO184, and THR185 of compound cefpiramide, doxycycline, delafloxacin, metacycline, oxytetracycline, and ertapenem were involved in the binding with CagA protein. These residues are crucial for the CagA that aids in entry or pathogenesis of the bacterium. The screened FDA-approved antibiotics have a potential druggability to inhibit CagA and reduce the progression of H. pylori borne diseases.

Melanoma Is Skin Deep: A 3D Reconstruction Technique for Computerized Dermoscopic Skin Lesion Classification.

Melanoma mortality rates are the highest amongst skin cancer patients. Melanoma is life threating when it grows beyond the dermis of the skin. Hence, depth is an important factor to diagnose melanoma. This paper introduces a non-invasive computerized dermoscopy system that considers the estimated depth of skin lesions for diagnosis. A 3-D skin lesion reconstruction technique using the estimated depth obtained from regular dermoscopic images is presented. On basis of the 3-D reconstruction, depth and 3-D shape features are extracted. In addition to 3-D features, regular color, texture, and 2-D shape features are also extracted. Feature extraction is critical to achieve accurate results. Apart from melanoma, in-situ melanoma the proposed system is designed to diagnose basal cell carcinoma, blue nevus, dermatofibroma, haemangioma, seborrhoeic keratosis, and normal mole lesions. For experimental evaluations, the PH2, ISIC: Melanoma Project, and ATLAS dermoscopy data sets is considered. Different feature set combinations is considered and performance is evaluated. Significant performance improvement is reported the post inclusion of estimated depth and 3-D features. The good classification scores of sensitivity = 96%, specificity = 97% on PH2 data set and sensitivity = 98%, specificity = 99% on the ATLAS data set is achieved. Experiments conducted to estimate tumor depth from 3-D lesion reconstruction is presented. Experimental results achieved prove that the proposed computerized dermoscopy system is efficient and can be used to diagnose varied skin lesion dermoscopy images.

Aza-heterocyclic Receptors for Direct Electron Transfer Hemoglobin Biosensor.

Direct Electron Transfer biosensors, facilitating direct communication between the biomolecule of interest and electrode surface, are preferable compared to enzymatic and mediator based sensors. Although hemoglobin (Hb) contains four redox active iron centres, direct detection is not possible due to inaccessibility of iron centres and formation of dimers, blocking electron transfer. Through the coordination of iron with aza-heterocyclic receptors - pyridine and imidazole - we report a cost effective, highly sensitive and simple electrochemical Hb sensor using cyclic voltammetry and chronoamperometry. The receptor can be either in the form of liquid micro-droplet mixed with blood or dry chemistry embedded in paper membrane on top of screen printed carbon electrodes. We demonstrate excellent linearity and robustness against interference using clinical samples. A truly point of care technology is demonstrated by integrating disposable test strips with handheld reader, enabling finger prick to result in less than a minute.

Biomethanation under psychrophilic conditions: a review.

Anaerobic digestion of animal manure, sewage and other agricultural wastes at psychrophilic temperatures has not been explored as extensively as either mesophilic or thermophilic digestion, probably due to little anticipation of the development of economically attractive systems using this technology. This review article discusses psychrophilic anaerobic digestion studies reported by various researchers using different substrates. The effect of operational parameters such as type of substrate, size of inoculum, concentration of volatile fatty acids, hydraulic retention time and loading rate, on reduction of TS/VS, BOD/COD and biogas yield is discussed in detail.

Applications of pectinases in the commercial sector: a review.

Pectinases are one of the upcoming enzymes of fruit and textile industries. These enzymes break down complex polysaccharides of plant tissues into simpler molecules like galacturonic acids. The role of acidic pectinases in bringing down the cloudiness and bitterness of fruit juices is well established. Recently, there has been a good number of reports on the application of alkaline pectinases in the textile industry for the retting and degumming of fiber crops, production of good quality paper, fermentation of coffee and tea, oil extractions and treatment of pectic waste water. This review discusses various types of pectinases and their applications in the commercial sector.

Salmonella. typhi OMPs induced immunomodulation in peritoneal macrophages.

The immunomodulatory properties of outer membrane proteins (OMPs) from S. typhi Ty2 were studied in mouse model at 72 hr and 20 days post-infection. Inspite of reduction in the number of macrophages and their protein content observed in the immunized group vis-à-vis infected group, OMPs activated macrophages showed significant upregulation of NO. At 20 days post infection, the level remained almost the same suggesting the prolonged cytotoxic and cytostatic activity due to the long lasting effects of OMPs activated macrophages. Higher activity of SOD in these aged cells pointed out towards the protective efficacy of OMPs to keep the macrophages themselves away from the noxious effects of O2-. Lower level of acid phosphatase in the macrophages from immunized mice group indicated the involvement of oxygen dependent rather than oxygen independent killing process. The enhanced uptake of organisms and their killing could be related to the production of oxygen and nitrogen radicals in the OMPs immunized group.

Association between diarrheal duration and nutritional decline: implications for an empirically validated definition of persistent diarrhea.

In an empiric approach to develop the definition of persistent diarrhea, we evaluated the relationship between diarrheal duration and risk of ensuing clinically significant decline in nutritional status, in a cohort of 395 children < 24 mo. Weights were obtained at the onset of diarrhea (wt I) and after three months interval (wt II). The occurrence of an adverse outcome (AO) was defined as a decline of -- 5% in NCHS weight for age (% WFA) between weights I and II or death in this interval. The risk of AO was similar for episodes of / or > 7 days while it was substantially higher in episodes with > 14 days duration (45%) than for shorter duration episodes, relative risk (RR) = 2.5 (p < 0.001). Relative risk remained similar for duration thresholds of 21 (2.3) and 28 days (2.6). As episode durations greater than 14 days are associated with substantial elevation of the risk of clinically cogent sequelae, such episodes may be termed 'persistent' at least in terms of poor prognostic expectations.

Efficacy of massive dose oral gentamicin therapy in nonbloody persistent diarrhea with associated malnutrition.

Overgrowth of aerobic and anaerobic bacteria in the upper small intestine is a common finding in persistent diarrhea. We hypothesized that a large dose of broad spectrum, nonabsorbable oral antibiotic would hasten recovery from persistent diarrhea by eradicating aerobic bacterial overgrowth. Sixty-eight patients were randomly assigned to treatment with either oral gentamicin (n = 33) or placebo (n = 35) for a period of 6 days. The two groups were comparable in their clinical features, stool weights, duodenal and fecal microflora, during an initial 24 h observation period before randomization. The proportion of patients recovering within 6 days post-treatment was similar in the antibiotic (45.2%) and placebo (50%) groups. The stool weights in the two groups during 24-72, 72-120, and 120-168 h of the study did not differ significantly. The percent mean weight gain (g) at 168 h post-treatment in the antibiotic (1.0 +/- 5.1) and placebo (1.4 +/- 5.3) groups also did not differ significantly (p = 0.8). A similar proportion of antibiotic- (61.3%) and placebo- (60.7%) treated patients had started to gain weight by the last day of the study. We conclude that oral gentamicin was no more effective than placebo in reducing purge rates, in achieving earlier recovery from diarrhea, and in promoting the earlier onset of weight gain in this study.

Alanine-based oral rehydration solution: assessment of efficacy in acute noncholera diarrhea among children.

This randomized, double-blind trial determined whether adding 90 mmol/L of alanine with a reduction in glucose to 90 mmol/L (alanine ORS) improves the efficacy of the standard oral rehydration solution (WHO-ORS). One hundred twenty-nine males aged 3-48 months with weight for length greater than or equal to 70% of NCHS, diarrheal duration less than or equal to 96 h, and clinical signs of mild to moderate dehydration were randomly allocated to either treatment group. During 0-6 h of treatment, ORS was offered at 120 ml/kg for rehydration without food or water. Beyond 6 h, ORS was offered as a volume-to-volume replacement for stool losses and a mixed diet of uniform composition was offered in amounts standardized for body weight. The most frequently isolated pathogens in alanine ORS and WHO-ORS groups were rotavirus (42 and 48%, respectively) and enterotoxigenic Escherichia coli (15 and 12%, respectively). In the 0-6 h period when food was withheld, median urine output in ml/kg (8;5, p less than 0.05) and percentage decrease in total serum solids (9:7%, p = 0.06) was significantly greater in alanine ORS than in WHO-ORS; median ORS intake and stool output were marginally lower in the alanine group but the differences were statistically not significant. Between 0 h and recovery, although the median values for duration of diarrhea (56.5 and 65.0 h), ORS consumption (260 and 323 ml/kg), and stool output (188.4 and 216.3 g/kg) were lower in the alanine ORS group, these differences with the WHO-ORS group were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)