Comparison of RECIST and iRECIST criteria in patients with advanced lung cancer treated with nivolumab.

Background: Systemic therapy in lung cancer is mainstay of treatment as most patients present in advanced stages, with rising importance of new immunotherapy agents. Purpose: To compare the RECIST 1.1 and the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECISTs) criteria for response assessment in lung cancer patients on immunotherapy. To find the incidence of pseudoprogression and associated imaging patterns. Material and Methods: Retrospective study in 28 patients treated with immunotherapy for advanced metastatic NSCLC. End points were progression-free survival (PFS) and overall survival (OS). Response assessments were separately tabulated according to RECIST 1.1 and iRECIST and classified into dichotomous groups of responders and nonresponders. Agreement in assessments between RECIST 1.0 and iRECIST examined using Cohen kappa (κ) coefficient with 95% confidence intervals. Kaplan-Meier survival analysis was done for PFS and OS. Differences between RECIST 1.1 and iRECIST for both responder and nonresponder were evaluated by the log rank test, Breslow (Generalized Wilcoxon) test, and Tarone-Ware test. Results: Incidence of pseudoprogression was 7% (2/28). The RECIST1.1 and iRECIST were in disagreement in two patients. The agreement between RECIST and iRECIST was almost perfect. The PFS and the OS are significantly longer in duration for responders in comparison to nonresponders for both RECIST and iRECIST and the difference between two assessment criteria is not significant. Conclusion: Although iRECIST aims to monitor treatment more precisely than conventional response criteria, this must be weighed against how infrequent pseudoprogression is and the cost of this therapy, both financially and in the potential delay in changing to a more effective treatment.

Enhancing the shelf life of chevon Seekh Kabab using chitosan edible film and Cinnamomum zeylanicum essential oil.

Chevon Seekh Kabab is a popular meat product of India. However, due to high protein and moisture content it undergoes quick microbial spoilage and oxidative reactions leading to lower shelf life. The combination of chitosan edible film and cinnamon essential oil (CEO) was chosen to remediate this problem because of its antimicrobial and antioxidative effect. Control and chitosan edible film with CEO coated chevon Seekh Kabab samples were stored at 4 °C. The physicochemical (pH, TBARS, TVBN, moisture, colour), microbiological (APC, psychrophilic, coliform and Staphylococcal count) and sensory attributes were evaluated over a 30 days period. The maximum shelf life of 27 days was observed when 2% chitosan edible film with 0.3% CEO was coated over samples. A reduction in moisture, L* value, a* value and sensory scores along with an increase in pH, TVBN, TBARS, b* value and microbiological parameters were observed during the storage period. Reaction kinetics for the physicochemical and microbiological parameters was also established. The physicochemical, microbiological and sensory parameters were within prescribed limits till spoilage in the treated sample. This investigation may aid researchers working on scaling up of processing and preservation of Seekh Kabab.

Detailed Sub-study Analysis of the SECRAB Trial: Quality of Life, Cosmesis and Chemotherapy Dose Intensity.

AIMS: SECRAB was a prospective, open-label, multicentre, randomised phase III trial comparing synchronous to sequential chemoradiotherapy (CRT). Conducted in 48 UK centres, it recruited 2297 patients (1150 synchronous and 1146 sequential) between 2 July 1998 and 25 March 2004. SECRAB reported a positive therapeutic benefit of using adjuvant synchronous CRT in the management of breast cancer; 10-year local recurrence rates reduced from 7.1% to 4.6% (P = 0.012). The greatest benefit was seen in patients treated with anthracycline-cyclophosphamide, methotrexate, 5-fluorouracil (CMF) rather than CMF. The aim of its sub-studies reported here was to assess whether quality of life (QoL), cosmesis or chemotherapy dose intensity differed between the two CRT regimens. MATERIALS AND METHODS: The QoL sub-study used EORTC QLQ-C30, EORTC QLQ-BR23 and the Women's Health Questionnaire. Cosmesis was assessed: (i) by the treating clinician, (ii) by a validated independent consensus scoring method and (iii) from the patients' perspective by analysing four cosmesis-related QoL questions within the QLQ-BR23. Chemotherapy doses were captured from pharmacy records. The sub-studies were not formally powered; rather, the aim was that at least 300 patients (150 in each arm) were recruited and differences in QoL, cosmesis and dose intensity of chemotherapy assessed. The analysis, therefore, is exploratory in nature. RESULTS: No differences were observed in the change from baseline in QoL between the two arms assessed up to 2 years post-surgery (Global Health Status: -0.05; 95% confidence interval -2.16, 2.06; P = 0.963). No differences in cosmesis were observed (via independent and patient assessment) up to 5 years post-surgery. The percentage of patients receiving the optimal course-delivered dose intensity (≥85%) was not significantly different between the arms (synchronous 88% versus sequential 90%; P = 0.503). CONCLUSIONS: Synchronous CRT is tolerable, deliverable and significantly more effective than sequential, with no serious disadvantages identified when assessing 2-year QoL or 5-year cosmetic differences.

Enhanced depression detection from speech using Quantum Whale Optimization Algorithm for feature selection.

There is an urgent need to detect depression using a non-intrusive approach that is reliable and accurate. In this paper, a simple and efficient unimodal depression detection approach based on speech is proposed, which is non-invasive, cost-effective and computationally inexpensive. A set of spectral, temporal and spectro-temporal features is derived from the speech signal of healthy and depressed subjects. To select a minimal subset of the relevant and non-redundant speech features to detect depression, a two-phase approach based on the nature-inspired wrapper-based feature selection Quantum-based Whale Optimization Algorithm (QWOA) is proposed. Experiments are performed on the publicly available Distress Analysis Interview Corpus Wizard-of-Oz (DAICWOZ) dataset and compared with three established univariate filtering techniques for feature selection and four well-known evolutionary algorithms. The proposed model outperforms all the univariate filter feature selection techniques and the evolutionary algorithms. It has low computational complexity in comparison to traditional wrapper-based evolutionary methods. The performance of the proposed approach is superior in comparison to existing unimodal and multimodal automated depression detection models. The combination of spectral, temporal and spectro-temporal speech features gave the best result with the LDA classifier. The performance achieved with the proposed approach, in terms of F1-score for the depressed class and the non-depressed class and error is 0.846, 0.932 and 0.094 respectively. Statistical tests demonstrate that the acoustic features selected using the proposed approach are non-redundant and discriminatory. Statistical tests also establish that the performance of the proposed approach is significantly better than that of the traditional wrapper-based evolutionary methods.

Triploid genetic algorithm for convolutional neural network-based diagnosis of mild cognitive impairment.

The diagnosis of mild cognitive impairment (MCI), which is deemed a formative phase of dementia, may greatly assist clinicians in delaying its headway toward dementia. This article proposes a deep learning approach based on a triploid genetic algorithm, a proposed variant of genetic algorithms, for classifying MCI converts and non-converts using structural magnetic resonance imaging data. It also explores the effect of the choice of activation functions and that of the selection of hyper-parameters on the performance of the model. The proposed work is a step toward automated convolutional neural networks. The performance of the proposed method is measured in terms of accuracy and empirical studies exhibit the preeminence of our proposed method over the existing ones. The proposed model results in a maximum accuracy of 0.97961. Thus, it may contribute to the effective diagnosis of MCI and may prove important in clinical settings.

Natural infection of Delta mutant of SARS-CoV-2 in Asiatic lions of India.

The current pandemic caused by a novel coronavirus (SARS-CoV-2) has underlined the importance of emerging diseases of zoonotic importance. Along with human beings, several species of wild and pet animals have been demonstrated to be infected by SARS-CoV-2, both naturally and experimentally. In addition, with constant emergence of new variants, the species susceptibility might further change which warrants intensified screening efforts. India is a vast and second most populated country, with a habitat of a very diverse range of animal species. In this study we place on record of SARS-CoV-2 infections in three captive Asiatic lions. Detailed genomic characterization revealed involvement of Delta mutant (Pango lineage B.1.617.2) of SARS-CoV-2 at two different locations. Interestingly, no other feline species enclosed in the zoo/park were found infected. The epidemiological and molecular analysis will contribute to the understanding of the emerging mutants of SARS-CoV-2 in wild and domestic animals.

Development and application of a triplex-PCR assay for rapid detection of methicillin-resistant Staphylococcus aureus from pigs.

A triplex-PCR assay was developed and evaluated for rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) recovered from various biological samples of pig. Three sets of primers were designed to target mecA, 16S rRNA and nuc genes of MRSA. The specific amplification generated three bands on agarose gel, with sizes 280 bp for mecA, 654 bp for 16S rRNA and 481 bp for nuc, respectively. A potential advantage of the PCR assay is its sensitivity with a detection limit of 102  CFU per ml of bacteria. In all, 79 MRSA isolates recovered from various samples of pigs were subjected to the amplification by the triplex-PCR assay and all the isolates yielded three bands corresponding to the three genes under this study. No false-positive amplification was observed, indicating the high specificity of the developed triplex-PCR assay. This assay will be a useful and powerful method for differentiation of MRSA from methicillin-sensitive S. aureus, coagulase-negative methicillin-resistant staphylococci and coagulase-negative methicillin-sensitive staphylococci.

Jamun fruit (Syzgium cumini) skin extract based indicator for monitoring chicken patties quality during storage.

Natural plant pigment, anthocyanins have the capability to change its color with the change of its structure influenced by changing pH. This feature of anthocyanin has been harnessed to design a meat products quality indicator. In the present experiment anthocyanin rich Jamun fruit (Syzgium cumini) skin extract was used to develop quality indicator by immobilizing on filter paper strips with the purpose of application in chicken patties packets stored at refrigeration temperature (4 ± 1 °C). The indicator changed its color from violet to yellow due to changed pH in it when it was attached inside packet of chicken patties during storage, due to reaction with volatile basic compounds generated from meat. During storage for 21 days, various changes in quality attributes of chicken patties viz., pH, Total volatile basic nitrogen (TVBN), ammonia level, color value, sensory attributes and microbial evaluation were estimated. The pH decreased (P < 0.5) from 6.22 to 6.04. TVBN and ammonia and level increased significantly (P < 0.5) throughout storage. Redness, yellowness, hue and chroma value gradually changed during storage. Sensory scores also decreased significantly (P < 0.5). Microbial count also increased (P < 0.5) during this time. The experiment showed that, during storage, the color changing pattern of quality indicator was well correlated with the changes in quality attributes of chicken meat patties. Therefore, it is expected that the developed quality indicator can provide a convenient, non destructive, visual mean to monitor the meat products quality during refrigerated storage.

Rapid visual isothermal nucleic acid-based detection assay of Brucella species by polymerase spiral reaction.

AIM: The aim of this study was to develop polymerase spiral reaction (PSR) for rapid, sensitive and specific detection of Brucella sp. METHODS AND RESULTS: Polymerase spiral reaction assay was developed using specifically designed primers targeting the conserved multicopy IS711 gene of Brucella sp. The assay could be performed within 60 min at an isothermal temperature of 64°C. The lower limit of detection of PSR was 11·8 fg and conventional PCR was 1·18 pg of Brucella abortus genomic DNA. Thus, PSR was found to be 100-fold more sensitive than conventional PCR and was comparable to real-time PCR. The specificity of PSR was tested with other non-Brucella bacteria and also with some bacterial and viral pathogens causing abortions. The assay was found to be specific as it did not detect any putative pathogens other than Brucella sp. Fifty-six clinical samples suspected for brucellosis (aborted fetal stomach content) were screened with PSR to validate the applicability of the test to detect Brucella DNA. The same samples were also screened with conventional PCR and real-time PCR. Of 56 samples, 25 samples were found to be positive with both PSR as well as real-time PCR, whereas only 20 samples were found positive with conventional PCR. CONCLUSIONS: The results of this study indicated that the PSR assay is a simple, rapid, sensitive and specific method for the detection of Brucella sp. that may improve diagnostic potential in clinical laboratories or can be used at diagnostic laboratories with minimal infrastructure. SIGNIFICANCE AND IMPACT OF THE STUDY: The PSR assay, because of its simplicity and low cost, can be preferred to other molecular methods in the diagnosis of infectious diseases.

Experimental bovine rotavirus-A (RV-A)infection causes intestinal and extra-intestinal pathology in suckling mice.

We describe here the intestinal and extra-intestinal spread of the species A rotavirus (RV-A) and associated lesions thereof in Swiss albino suckling mice pups, inoculated with a bovine-origin RV-A strain. In total, 35 suckling pups were used, wherein 20 pups received cell culture isolated RV-A @ 160 µL (TCID50/ml, 5 × 106.5) per pup [oral 80 µL and intra peritoneal (IP) 80 µL] and served as an infected group, while 15 pups were kept in the control group and inoculated the same volume of phosphate buffered saline (PBS) of neutral pH orally and IP. Four pups from the infected group and 3 from control group were sacrificed at 3, 5, 7, 9 and 12 day post infection (DPI). Of note, infected pups exhibited signs of dullness and restlessness till 5DPI, but none showed diarrhea at any point of time. No appreciable gross lesions were evident in any of the organs, except for mild congestion of the small intestine and yellowish catarrhal smearing over the luminal surface. However, light microscopic lesions in hematoxylin and eosin (H&E) stained sections of jejunum and ileum revealed vacuolation and pyknosis of nuclei of the mature enterocytes, their lysis and detachment, constriction and detachment of villi, mild mononuclear cells (MNCs) infiltration in the lamina propria and mildcell depletion of Peyer's patches and mesenteric lymph nodes (MLN). The extra-intestinal lesions of the cellular degeneration and mild MNCs infiltration were identified in the liver and kidneys from 3 to 7 DPI, but no lesion was seen in the brain. Interstitial thickening with MNCs of lung parenchyma was visible from 3 to 7 DPI. The lesions in the intestine, lymphoid tissues and lungs resolved after 7 DPI. The presence of viral nucleic acid was seen in the intestinal contents from 3 to 5 DPI by using a RV-A specific reverse-transcription polymerase chain reaction (RT-PCR), while in the MLNs and the lungs it could be detected till 5 DPI by both the RT-PCR and direct fluorescent antigen test (dFAT). However, liver, spleen and brain were tested negative for the presence of RV-A by any of these tests. Nonetheless, the persistence of the RV-A was seen in the MLNs even after the absence of virus from the small intestines. Findings here conclusively indicates that heterologous host origin RV-A has an affinity not only to the intestine but also to extra-intestinal tissues like MLNs and lung tissues.

Relevant Feature Selection from a Combination of Spectral-Temporal and Spatial Features for Classification of Motor Imagery EEG.

This paper presents a novel algorithm (CVSTSCSP) for determining discriminative features from an optimal combination of temporal, spectral and spatial information for motor imagery brain computer interfaces. The proposed method involves four phases. In the first phase, EEG signal is segmented into overlapping time segments and bandpass filtered through frequency filter bank of variable size subbands. In the next phase, features are extracted from the segmented and filtered data using stationary common spatial pattern technique (SCSP) that can handle the non- stationarity and artifacts of EEG signal. The univariate feature selection method is used to obtain a relevant subset of features in the third phase. In the final phase, the classifier is used to build adecision model. In this paper, four univariate feature selection methods such as Euclidean distance, correlation, mutual information and Fisher discriminant ratio and two well-known classifiers (LDA and SVM) are investigated. The proposed method has been validated using the publicly available BCI competition IV dataset Ia and BCI Competition III dataset IVa. Experimental results demonstrate that the proposed method significantly outperforms the existing methods in terms of classification error. A reduction of 76.98%, 75.65%, 73.90% and 72.21% in classification error over both datasets and both classifiers can be observed using the proposed CVSTSCSP method in comparison to CSP, SBCSP, FBCSP and CVSCSP respectively.

A novel fuzzy rough selection of non-linearly extracted features for schizophrenia diagnosis using fMRI.

BACKGROUND AND OBJECTIVES: Schizophrenia is a severe brain disorder primarily diagnosed through externally observed behavioural symptoms due to the dearth of established clinical tests. Functional magnetic resonance imaging (fMRI) can capture the distortions caused by schizophrenia in the brain activation. Hence, it can be useful for developing a decision model that performs computer-aided diagnosis of schizophrenia. But, fMRI data is huge in dimension. Therefore dimension reduction is indispensable. It is additionally required to identify the discriminative brain regions. Hence, we aim to build an effective decision model that incorporates suitable dimension reduction and also identifies discriminative brain regions. METHODS: We propose a three-phase dimension reduction. First phase involves spatially-constrained fuzzy clustering of 3-dimensional spatial maps (obtained from general linear model and independent component analysis). In the second phase, non-linear features are extracted from each cluster using a generalized discriminant analysis. In the third phase, a novel fuzzy rough feature selection is proposed. The features obtained after the third phase are used for learning a decision model by the help of support vector machine classifier. This complete method is implemented within leave-one-out cross-validation on two balanced datasets (respectively acquired on 1.5Tesla and 3Tesla scanners). Both these datasets are created using Function Biomedical Informatics Research Network multisite data and contain fMRI data acquired during auditory oddball task performed by age-matched schizophrenia patients and healthy subjects. A permutation test is also carried out to ensure that no bias is involved in the learning. RESULTS: The results indicate that the proposed method achieves maximum classification accuracy of 97.1% and 98.0% for the two datasets respectively. The proposed method outperforms the state-of-the-art methods. The results of the permutation test show that p-values are lesser than the significance level i.e. 0.05. Therefore, the classifier has found a significant class structure and does not involve any bias. Further, discriminative brain regions are identified and are in agreement with the findings in related literature. CONCLUSION: The proposed method is able to derive suitable non-linear features and the related brain regions for effective computer-aided diagnosis. The fuzzy and rough set based approaches help in handling uncertainty and ambiguity in real data.

Long-term effect of presurgical nasoalveolar molding on growth of maxillary arch in unilateral cleft lip and palate: randomized controlled trial.

The objective of this study was to investigate the long-term effect of presurgical nasoalveolar molding (PNAM) on growth of the maxillary arch through early childhood until 6 years of age in complete unilateral cleft lip and palate (UCLP) patients presenting for PNAM at different ages. Complete UCLP patients who were treated at our centre were divided into two groups. The study group underwent PNAM and was further subdivided into three subgroups (PNAM initiated within 1 month, between 1 and 6 months, and between 6 and 12 months of age in subgroup I, II, and III, respectively). The control group did not undergo PNAM and was further subdivided into three subgroups. Patients were evaluated at T1 (first visit), T2 (before cheiloplasty), and T3 (at 6 years). Between T1and T2, the intersegment distance (ISD) reduced significantly in the study group but increased in the control group, whereas the intercanine width (ICW) in both the study and control groups did not show significant change. Between T2 and T3, ISD and ICW were reduced significantly in the control group due to arch collapse, whereas in the study group, ISD reduced slightly with ICW remaining almost similar to noncleft norms. We conclude that reduced ISD following PNAM improves arch symmetry and stability, and thus may prevent arch collapse in the long term.

Infant and Young Child Feeding Guidelines, 2016.

JUSTIFICATION: Shaping up the post-2015 development agenda is of crucial importance in the development process around the Globe as 2015 was the last year of milllionium development goals. It is the right time to asses our own progress vis-a-vis the Millennium Development Goals and these Guidelines are an attempt in that regard. PROCESS: The Infant and Young Child Feeding (IYCF) chapter of Indian Academy of Pediatrics invited a group of experts for National Consultative Meet for discussing and contributing on latest scientific advances and developments. Various partners from WHO, UNICEF, Ministry of Child Welfare Department, Ministry of Health and Family Welfare, Ministry of Chemical and Fertilizers of Govt of India, Human Milk Banking Association (of India), Indian Medico-Legal and Ethics Association (IMLEA), non-governmental organizations and academicians from various states of India contributed to these guidelines. The guidelines were finalized during the IYCNCON 2015 at New Delhi in August 2015. OBJECTIVES: To formulate, endorse, adopt and disseminate guidelines related to Infant and Young Child feeding from an Indian perspective (including human milk banking, infant feeding in the HIV situation, and micro-nutrients). RECOMMENDATIONS: Early initiation of breastfeeding within first hour of birth, exclusive breastfeeding for the first six months followed by continued breastfeeding for up to two years and beyond with appropriate complementary foods after completion of 6 months is the most appropriate feeding strategy. Micro-nutrient supplementation in infants, and adequate nutrition and anemia control for adolescent girls, pregnant and lactating mothers is advocated. Concepts and need for human milk banks in India has also been incorporated.

Acetylcholinesterase histochemistry (AChE)--A helpful technique in the diagnosis and in aiding the operative procedures of Hirschsprung disease.

BACKGROUND: Hirschsprung's disease (HD) is an anomaly characterized by the absence of myenteric and submucosal ganglion cells (GC) in the distal alimentary tract. Diagnosis of HD is made by the absence of GC and missing out on even a single ganglion cell can be very devastating. Acetylcholinesterase (AChE) histochemistry, done on frozen sections is said to be a very useful ancillary technique in the diagnosis and in aiding the operative procedures of HD. METHODS: To assess this, 73 samples from 42 suspected/known cases of HD were subjected to frozen section analysis with rapid haematoxylin and eosin, toluidin blue stain along with AChE histochemistry. The remnant sample was paraffin embedded for routine haematoxylin and eosin staining. RESULTS: On frozen section analysis, 33 samples showed absence of ganglion cells, AChE histochemistry showed a positive staining pattern in 17 samples and paraffin embedded routine, H&E stained sections showed absence of ganglion cells in 19 samples. Sensitivity and specificity of both tests ie frozen section rapid H&E/AChE histochemistry in the diagnosis of HD, were calculated taking paraffin embedded H&E stained sections as the gold standard. Sensitivity of frozen section rapid H&E in the diagnosis of HD is 57.57 % and specificity is 79.10 %. The p-value is <0.0001, which is significant. The sensitivity of AChE histochemistry in the diagnosis of HD is 90.47 % and specificity is 96.36 %. The p-value is <0.0001, which is significant. CONCLUSIONS: Acetylcholineesterase (AChE) histochemistry is a very useful ancillary technique in the diagnosis and in aiding the operative procedures of HD. It acts as a double check in the diagnosis of HD.

A combination of dual-tree discrete wavelet transform and minimum redundancy maximum relevance method for diagnosis of Alzheimer's disease.

In this paper, we propose a three-phased method for diagnosis of Alzheimer's disease using the structural magnetic resonance imaging (MRI). In first phase, gray matter tissue probability map is obtained from every brain MRI volume. Further, five regions of interest (ROIs) are extracted as per prior knowledge. In second phase, features are extracted from each ROI using 3D dual-tree discrete wavelet transform. In third phase, relevant features are selected using minimum redundancy maximum relevance features selection technique. The decision model is built with features so obtained, using a classifier. To evaluate the effectiveness of the proposed method, experiments are performed with four well-known classifiers on four data sets, built from a publicly available OASIS database. The performance is evaluated in terms of sensitivity, specificity and classification accuracy. It was observed that the proposed method outperforms existing methods in terms of all three performance measures. This is further validated with statistical tests.

Beam based alignment and its relevance in Indus-2.

Initially in the Indus-2 storage ring, the closed orbit distortion (COD) could be best corrected to 1.3 mm rms in the horizontal and 0.43 mm rms in the vertical plane. The strength of the corrector magnets required high values for COD correction. This revealed that offsets in COD readout by the beam position monitors (BPMs) played a role in not achieving a rms COD lower than the above value. Thus, the offset between the electrical center of BPMs and the magnetic center of the nearest quadrupole magnet could be estimated using the beam based alignment (BBA) method. It prefers that the quadrupole magnet is able to be controlled individually and active shunt power supply (ASPS) system was designed for this purpose that works efficiently. This paper describes the methodology of BBA, topology of ASPS and its performance, and COD minimization using the measured BPM offsets. After BBA, the COD could be reduced to 0.45 mm rms and 0.2 mm rms in horizontal and vertical planes, respectively.

Pattern of glomerular disease in Nepal: A single-center experience.

Glomerulonephritis (GN) is the most common cause of end-stage renal disease in Nepal. The aim of the present study is to determine the clinical presentation and histological pattern of GN with and without immunofluorescence (IF). It is a retrospective analysis of all GN patients with kidney biopsy at the Bir Hospital from January 2000 to April 2009. The clinical presentation, blood pressure, urine analysis, 24-h urinary protein, biochemistry, hemoglobin, antinuclear antibody, anti-ds DNA, light microscopy (LM) and IF findings of kidney biopsies were computed from hospital records. SPSS package was used for analysis. A total of 398 patients [LM 204 (51%) and LM plus IF 194 (49%] were analyzed. The mean age of the study patients was 28 ± 13.6 years (range 7-74); males comprised 52.8% and females 47.2% of the patients; 51% were between 16 and 30 years of age. The common clinical presentations included nephrotic syndrome (NS), seen in 69% of the patients, followed by acute nephritic syndrome, seen in 14.4% of the patients. Kidney biopsy without IF showed mesangial proliferative GN (MesPGN) in 21.1%, membranoproliferative GN (MPGN) in 18.6%, membranous nephropathy (MN) in 14.2%, minimal change disease (MCD) in 12.3% and focal and segmental glomerulosclerosis (FSGS) in 9.8% of the cases. With IF, MCD was seen in 23.2%, FSGS in 18%, MN in 11.9%, IgA nephropathy in 9.8%, MesPGN in 8.2%, MPGN in 4.1% and crescentic GN in 3.1% of the cases. Lupus nephritis in the cases GN was most common in young adults, with the majority presenting with NS. MCD and FSGS were the most common glomerular lesions; over-diagnosis of MesPGN and MPGN by LM could be due to exclusion of IgA nephropathy.

Pharmacophore modeling and docking studies on some nonpeptide-based caspase-3 inhibitors.

Neurodegenerative disorders are major consequences of excessive apoptosis caused by a proteolytic enzyme known as caspase-3. Therefore, caspase-3 inhibition has become a validated therapeutic approach for neurodegenerative disorders. We performed pharmacophore modeling on some synthetic derivatives of caspase-3 inhibitors (pyrrolo[3,4-c]quinoline-1,3-diones) using PHASE 3.0. This resulted in the common pharmacophore hypothesis AAHRR.6 which might be responsible for the biological activity: two aromatic rings (R) mainly in the quinoline nucleus, one hydrophobic (H) group (CH3), and two acceptor (A) groups (-C=O). After identifying a valid hypothesis, we also developed an atom-based 3D-QSAR model applying the PLS algorithm. The developed model was statistically robust (q² = 0.53; pred_r² = 0.80). Additionally, we have performed molecular docking studies, cross-validated our results, and gained a deeper insight into its molecular recognition process. Our developed model may serve as a query tool for future virtual screening and drug designing for this particular target.

Over-expression of gene encoding heat shock protein 70 from Mycobacterium tuberculosis and its evaluation as vaccine adjuvant.

BACKGROUND: Heat shock proteins (Hsps) are evolutionary ancient and highly conserved molecular chaperons found in prokaryotes as well as eukaryotes. Hsp70 is a predominant member of Hsp family. Microbial Hsp70s (mHsp70s) have acquired special significance in immunity since they have been shown to be potent activators of the innate immune system and generate specific immune responses against tumours and infectious agents. OBJECTIVES: The present study was aimed to clone express and purify recombinant Hsp70 from the Mycobacterium tuberculosis and characterise it immunologically. The study also aimed at determining the potential of recombinant M. tuberculosis heat shock protein (rMTB-Hsp70) as adjuvant or antigen carrier. MATERIALS AND METHODS: Cloning of M. tuberculosis heat shock protein (MTB-Hsp70) amplicon was carried out using the pGEMT-Easy vector although for expression, pProExHTb prokaryotic expression vector was used. Purification of recombinant Hsp70 was carried out by nickel-nitrilotriacetic acid (Ni-NTA) affinity chromatography. For immunological characterization and determining the adjuvant effect of MTB-Hsp70, BALB/c mice were used. The data obtained was statistically analysed. RESULTS: Hsp70 gene was cloned, sequenced and the sequence data were submitted to National Center for Biotechnology Information (NCBI). Recombinant MTB-Hsp70 was successfully over-expressed using the prokaryotic expression system and purified to homogeneity. The protein was found to be immunodominant. Significant adjuvant effect was produced by the rMTB-Hsp70 when inoculated with recombinant outer membrane protein 31; however, effect was less than the conventionally used the Freund's adjuvant. CONCLUSION: Protocol standardised can be followed for bulk production of rHsp70 in a cost-effective manner. Significant adjuvant effect was produced by rMTB-Hsp70; however, the effect was than Freund's adjuvant. Further, studies need to be carried out to explore its applicability as carrier of antigen.