Cryptosporidiosis, a public health challenge: A combined 3D shape-based virtual screening, docking study, and molecular dynamics simulation approach to identify inhibitors with novel scaffolds for the treatment of cryptosporidiosis

Cryptosporidiosis is a neglected tropical disease caused by the protozoan parasite Cryptosporidium parvum. Limited therapeutic options, limitation in in vitro parasite culture, and lack of a reliable animal model of parasite for replication of in vivo life cycle and drug testing demand alternative methods for drug development. The in silico methods of drug discovery prove a crucial process in such conditions.Recent research reported a limited number of small molecules for drug development. Purine nucleotide biosynthesis in Cryptosporidium species is dependent on the IMPDH (CpIMPDH) enzyme, so distortion of parasite IMPDH has been pursued as a compelling strategy for curbing Cryptosporidium infection due to its different kinetics from the host enzyme. Our study's primary aim was to discover novel ligand molecules with noticeable activity against Cryptosporidium parvum IMPDH. For this purpose, we selected 18 previously discovered ligands to understand the interaction feature between ligand and receptor, and their shape and electronic features are employed as a template for shape-based virtual screening of the ZINC database (drug-like subset) search approach via Schrodinger-2019 (Maestro 11.9). The obtained hits were subsequently subjected to structure-based screening, quantum polarized ligand docking (QPLD), and molecular dynamics simulations to fetch potential small molecules with the highest binding affinity for CpIMPDH protein. Further ligand binding energy and pharmacokinetic analysis were also taken into consideration as filtering criteria for selecting the most promising drug-like compounds. On this experimentation analysis, three top-ranked (ZINC24855054, ZINC58171263, and ZINC08000072) molecules were found to have appropriate pharmacokinetic properties along with surpassing in silico inhibitory potential towards the CpIMPDH compared to known inhibitors. The molecular docking and molecular dynamics simulation analysis results satisfactorily confirmed the inhibitory action. Therefore, these new scaffolds deduced by the presented computational methodology could recommend lead molecules for designing promising anti-cryptosporidial drugs targeting CpIMPDH protein.

A prospective observational study to assess compliance and factors influencing compliance with antiepileptic drugs among patients with epilepsy

Background: The primary treatment for epilepsy is Antiepileptic drug (AED) therapy. Non-compliance to AEDs can result in break-through seizure, emergency department visits, hospitalizations, fractures, head injuries and increased mortality. Thus, compliance to AEDs is crucial to be studied. Objective is to study compliance and factors influencing compliance with AEDs among patients with epilepsy.Methods: This observational study was conducted in 105 patients with epilepsy on AED therapy in community in Ludhiana (Punjab) after approval from Institutional Ethics Committee. Demographic data and drug history was collected. Monthly follow up for 6 months was done by paying home visits and data regarding type, dose, frequency of administration of AED was recorded on a semi-structured performa. Pill count was done by recording number of pills dispensed and number of pills remaining with patient. Response to Morisky’s Medication Adherence Scale (MMAS) was also recorded. Results were correlated with patient demographics, type, frequency and number of AEDs.Results: Out of 105 patients, 65 were males and 40 were females. Fifty-four patients were non-compliant with both pill-count and MMAS. Non-compliance was high in first month and decreased gradually. Poly-therapy, lower socio-economic status and multiple dosing regimens were most commonly associated with non-compliance.Conclusions: Under-dosing was more common among non-compliers, which explains the high reporting of forgetfulness to take medicine in MMAS. Both pill count and MMAS are effective non-invasive tools to study compliance.

Post-Operative Pain and Convalescence in Comparison of Laparoscopic Ventral Hernia Repair Vs Open Ventral Hernia Repair

Background: Ventral hernia is defined as a fascial defectlocated to the abdominal wall. The laparoscopic repair ofIncisional and ventral hernia is fast becoming the standard ofcare.Objectives: To compare and evaluate the post-operative painand convalescence between two groups.Methods: Study was conducted on 30 cases of ventral herniaadmitted in Rajindra Hospital, Patiala. They were divided intotwo comparison groups (15 cases each). Group A: Openventral hernia repair; Group B: Laparoscopic ventral herniarepair.Results and Conclusions: Laparoscopic repair should be thepreferred method of repair of ventral hernia as it is associatedwith a shorter hospital stay, decreased post-operative pain,better cosmetic results decreased complication rate likerecurrence, and seroma formation, decreased mesh infectionrate, early ambulation period, better patient satisfaction andearly return to activities.

Neurocysticercosis as a probable risk factor for hippocampal sclerosis / Neurocisticercose como provável fator de risco para esclerose hipocampal

ABSTRACT Neurocysticercosis is one of the most common risk factors for epilepsy but its association with drug-resistant epilepsy remains uncertain. Conjectures of an association with drug-resistant epilepsy have been fueled by reports of an association between calcific neurocysticercosis lesions (CNL) and hippocampal sclerosis (HS) from specialized epilepsy centers in Taenia solium-endemic regions. The debate arising from these reports is whether the association is causal. Evidence for the association is not high quality but sufficiently persuasive to merit further investigation with longitudinal imaging studies in population-based samples from geographically-diverse regions. The other controversial point is the choice of a surgical approach for drug-resistant epilepsy associated with CNL-HS. Three approaches have been described: standard anteromesial temporal lobectomy, lesionectomy involving a CNL alone and lesionectomy with anteromesial temporal lobectomy (for dual pathology); reports of the latter two approaches are limited. Presurgical evaluation should consider possibilities of delineating the epileptogenic zone/s in accordance with all three approaches.

RESUMO A neurocisticercose é um dos mais comuns fatores de risco para a epilepsia, mas sua associação com a epilepsia resistente a medicamentos (DRE) permanece incerta. Conjecturas de uma associação com a DRE têm sido alimentadas por relatos de uma associação entre lesões de neurocisticercose calcária (CNL) e esclerose hipocampal (HS) de centros especializados em epilepsia em regiões endêmicas de Taenia solium. O debate que surge desses relatórios é se a associação é causal. Se bem as evidências para a associação não são de alta qualidade, são suficientemente persuasivas para merecer mais investigação com estudos longitudinais de imagens em amostras de base populacional de regiões geograficamente diversas. O outro ponto controverso é a escolha da abordagem cirúrgica para a DRE associada à CNL-HS. Três abordagens têm sido descritas: lobectomia temporal ântero-mesial padrão, lesionectomia envolvendo apenas CNL e lesionectomia com lobectomia temporal ântero-mesial (para patologia dupla); os relatórios das duas últimas abordagens são limitados. A avaliação pré-cirúrgica deve considerar as possibilidades de delinear a (s) zona (s) epileptogênica (s) de acordo com as três abordagens.

Knowledge, attitude, and practice of dental implants among dental postgraduates and practitioners in Davangere City, Karnataka: A cross-sectional study

Implant therapy has become an important part of treatment to restore function and esthetics in partially/completely edentulous patients. Inspite of the progress made in implant dentistry since its inception, there have been some loopholes in scientific based knowledge and established clinical experience amongst dental professionals and postgraduates.So,an analysis was performed of the real picture. Objectives: A study was conducted to assess and compare the knowledge, attitude and practice of dental implants among dental postgraduate students and dental practitioners (General and institutional)in Davangere City, Karnataka and to identify the variations in their knowledge, attitude and practice with respect to dentist's factors (years of experience, implant training and their specialization). Materials and Methods: A cross sectional questionnaire based survey was conducted using census approach with informed consent. A pretested, self administered questionnaire containing demographic details and knowledge ,attitude and practice based questions was distributed and collected back from the respondents. Responses were coded before and decoded after the analysis. Statistical analysis was performed using SPSS SoftwareV17.0. Results: The results were determined after the statistically analyzed and concluded that the knowledge was widespread among postgraduates and dental practitioners and variations existed amongst the subjects with respect to age, gender, years of experience, practice type, implant training and their specialization. It was also found that the attitude and practice towards implants and their evidence based knowledge about the same was variable.

Bacillus cereus causing intratumoral brain abscess.

We report a case of intratumoral brain abscess due to Bacillus cereus in an adult male patient, which was managed successfully with excision of lesion and piperacillin‑tazobactam for the duration of 5 weeks. To the best of our knowledge, this is a first case report of B. cereus infection leading to intratumoral brain abscess in a patient with a history of steroid administration by the intravenous route.

Immunohistochemical expression of Ets‑related gene‑transcriptional factor in adenocarcinoma prostate and its correlation with Gleason score.

Background: Prostate carcinoma is the second leading cause of cancer‑related deaths in males worldwide. The burden is expected to grow 1.7 million new cases and 499,000 new deaths by 2030. In developing countries such as India, prostate carcinoma will show an increase by 140% in the next few years. Although the diagnosis of prostate carcinoma can usually be made on histological features, now a days many immunohistochemical (IHC) markers are used to distinguish it from benign mimickers as well as in predicting prognosis and treatment. Out of these markers, Ets‑related gene (ERG product) is a proto‑oncogene which participates in chromosomal translocations and is frequently over expressed in prostate carcinoma which harbors ERG‑transmembrane protease, serine 2 fusion. Materials and Methods: Fifty cases of carcinoma prostate diagnosed in needle biopsies and prostatic chips, in the Department of Pathology of a tertiary care teaching hospital in Punjab, India, were included in the present study. The slides were observed under the light microscope, and Gleason scoring was done using the 2005 International Society of Urological Pathology modified Gleason system. IHC study for ERG expression was done on all the cases, for which anti‑ERG monoclonal rabbit clone antibody EP111 (Dako, Denmark) was used. Lymphocytes and endothelial cells were taken as in built positive controls for staining. The intensity of ERG positivity was scored as no staining (0), weak staining (+1), moderate staining (+2) and intense staining (+3). The H score was then calculated by multiplying the intensity of the stain with the percentage (0–100) of the cells showing that staining intensity. The H‑score has a range of 0–300. The relationship between IHC expression and clinico‑pathological parameters was compared and analyzed using Chi-square test. P < 0.05 was considered statistically significant. Results: Majority of patients included in the study were in the age group of 61–80 (84% of the total). When ERG expression was studied with age‑specific rates, it was not found to be statistically significant. The most common pattern noted in the present study was 4 + 3, constituting 36% of total, followed by 3 + 4 constituting 32%. Calculating the score, the majority of patients had a Gleason score of 5–8, constituting 76% of total. Out of the total fifty cases of prostate carcinoma, ERG was positive in 29 cases (58%) and negative in 21 cases (42%). Fourteen out of 21 (48%) of the ERG positive cases had an intensity score of 3. When the ERG intensity was correlated with the Gleason score group, it was seen that patients having Gleason score 7–8 showed ERG positivity in 19 out of 38 cases (50%), with 11/19 (57%) cases showing an ERG intensity score of 3. The Gleason score group 9–10 showed ERG positivity in 83% (10/12) cases, 20% (2/10) cases showing intensity score of 3. This correlation was found to be statistically significant. Conclusion: ERG immunostaining was performed in a small Indian cohort of prostate cancer patients, diagnosed in trucut biopsy specimens and prostatic chips. ERG expression was found in 58% patients. An increase in the ERG expression was observed with an increase in Gleason score. The intensity of ERG expression, however, decreased with an increasing Gleason score.

occurrence of blaNDM-1 & absence of blaKPC genes encoding carbapenem resistance in uropathogens from a tertiary care centre from north India.

Background & objectives: Carbapenem resistance mediated by carbapenemases is increasingly being reported worldwide. This study was conducted to know the occurrence of important carbapenem resistance encoding genes in gram-negative bacilli (GNB) causing complicated urinary tract infection (CUTI), and to look at the genetic diversity of these isolates. Methods: The study was carried out on 166 consecutive carbapenem resistant uropathogens (CRU) isolated from cases with CUTI during 2008 and 2012. Carbapenemase production was characterized phenotypically and polymerase chain reaction was used to detect blaVIM, blaIMP, blaKPC, and blaNDM-1. BOX- PCR was done on 80 randomly selected isolates for molecular typing. Results: The blaVIM gene was present in 34 (43.6%), blaIMP in five (6.4%) and none of the isolates from 2008 had blaNDM-1 or blaKPC genes. Among the isolates from 2012, blaNDM-1 gene was present in 47 (53.4%), blaVIM in 19 (24.4%), blaIMP in one (1.1%) and none had blaKPC. There were nine isolates during the two years which had multiple genes encoding carbapenemases; while 66 did not have any of the genes tested. Of the 80 isolates subjected to BOX-PCR, 58 could be used for analysis and showed, presence of multiple clusters of carbapenem resistant isolates and absence of a single dominant clone. Interpretation & conclusions: The blaNDM-1 gene was absent in our isolates obtained during 2008 but was present amongst Enterobacteriaceae isolated in 2012. The blaKPC gene was also not found. Nine isolates obtained during the two years had multiple genes encoding carbapenemases confirming the previous reports of emergence of GNB containing genes encoding multiple carbapenemases. Typing using BOX-PCR indicated that this emergence was not because of clonal expansion of a single strain, and multiple strains were circulating at a single point of time.

A case of extensive chromoblastomycosis from North India

A case of extensive chromoblastomycosis of the right leg and thigh with verruciform to nodular lesions evolving rapidly over five years duration is reported. The diagnosis was confirmed by visualizing pathognomonic pigmented muriform bodies with unique septate hyphae and mycological culture yielding Fonsecaea pedrosoi.

Phenobarbitone induced drug reaction with eosinophilia and systemic symptoms (DRESS): a case report.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a life threatening cutaneous drug reaction with visceral involvement and hematological abnormalities. Being a rare side effect, it is often under-reported and misdiagnosed. The fatal adverse drug reaction is associated most commonly with aromatic anti-epileptics phenytoin, carbamazepine and less frequently with phenobarbitone. Here, we report a case of phenobarbitone induced DRESS in a 1 year old male child. He succumbed to fulminant hepatic failure inspite of being put on steroids, hepatoprotectives, antibiotics and ventilatory support.

Mycoplasma genitalium: An emerging sexually transmitted pathogen.

Mycoplasma genitalium is a member of genital mycoplasmas, which is emerging as an important causative agent of sexually transmitted infections both in males and females. The advent of polymerase chain reaction and other molecular methods have made studies on M. genitalium more feasible, which is otherwise a difficult organism to isolate. Besides Chlamydia trachomatis, M. genitalium is now an important and established cause of non gonococcal urethritis (NGU) in men, more so in persistent and recurrent NGU. Multiple studies have also shown a positive association of M. genitalium with mucopurulent cervicitis and vaginal discharge in females as well. The evidences for M. genitalium pelvic inflammatory diseases and infertility are quite convincing and indicate that this organism has potential to cause ascending infection. Lack of clear association with M. genitalium has been reported for bacterial vaginosis and adverse pregnancy outcomes. Diagnosis of M. genitalium infections is performed exclusively using nucleic acid amplification tests (NAATs), owing to poor or slow growth of bacterium in culture. Although there are no guidelines available regarding treatment, macrolide group of antimicrobials appear to be more effective than tetracyclines. The present review provides an overview of the epidemiology, pathogenesis, clinical presentation and management of sexually transmitted infections due to M. genitalium.

High occurrence of blaCMY-1 AmpC lactamase producing Escherichia coli in cases of complicated urinary tract infection (UTI) from a tertiary health care centre in north India.

AmpC beta lactamase producing Gram-negative bacteria have emerged worldwide. It is important to distinguish plasmid mediated AmpC β lactamases from chromosomally mediated enzymes for surveillance, epidemiology and hospital infection control as plasmid mediated genes can spread to other organisms. Occurrence of blaCMY-1 AmpC β-lactamase, a plasmid mediated cephamycinase was studied in 100 consecutive isolates of Escherichia coli from cases of complicated urinary tract infection (UTI). Screening for AmpC production was done by modified Hodge test, three dimensional test and AmpC disk test. All isolates showing a positive result by 2 out of 3 tests were then tested for blaCMY-1 gene by PCR. Fifty nine isolates were positive for AmpC β lactamase production, 56.6 per cent were positive by PCR. Eight out of 13 isolates which were negative by EDTA disk method were positive by PCR, whereas none of the isolates negative by 3D and modified Hodge test was positive by PCR. Among admitted patients urinary catheterisation was the major risk factor followed by obstructive uropathy, three patients developed urosepsis. High occurrence of blaCMY-1 AmpC β-lactamase warrants health care workers to endorse good hospital practices.

Epidemiologic lessons: Chickenpox outbreak investigation in a rural community around Chandigarh, North India.

Purpose: Primary infection with Varicella Zoster virus (VZV) leads to Varicella or chickenpox. The epidemiology of Varicella has changed dramatically since the introduction of the Varicella vaccine in 1995. The routine childhood immunization in a few countries in the western world like Germany and the United States has reduced the incidence of the disease, associated complications, hospital admissions and deaths related to its complications. However, chickenpox outbreaks are common in naive unvaccinated communities in India. Materials and Methods: We report an outbreak of chickenpox that occurred in a village situated on the outskirts of Chandigarh city in North India in the winter of 2007. The outbreak was confirmed by the detection of VZV IgM by enzyme-linked immunosorbent assay (ELISA) on serum samples from the patients. In patients showing active lesions, Giemsa and indirect immunofluorescence was carried out on scrapings from vesicular lesions. Results: A total of 162 cases occurred in the present outbreak. The serum samples were collected from 20 patients, and all of them showed positive serology for VZV IgM antibodies while 19 showed a positive VZV IgG result by ELISA. The scrapings were collected from two patients showing active lesions, and both were positive by the Tzanck smear examination, and VZV antigen could be demonstrated by immunofluorescence. Conclusions: There is an urgent need to identify naive communities and unvaccinated individuals at risk. Also, there is a need for regular training programmes of health workers posted in peripheral centers so that highly contagious communicable diseases can be picked up in time and such outbreaks can be prevented.

Isaac's syndrome associated with myasthenia gravis and thymoma.

A 65-year-old male developed fatigable weakness of ocular and bulbar muscle and positive anti-acetyl cholinesterase antibodies suggesting the diagnosis of myasthenia gravis. His condition responded to anticholinesterase and immunotherapy. However, 18 months later, he developed painful paresthesiae, muscle cramps with hyperhiderosis, and was diagnosed as having Isaac's syndrome (neuromyotonia, continuous muscle fibre activity). Computed tomography of the chest revealed a thymic mass, which was confirmed after surgery and histopathology as thymic cell carcinoma. The co-occurrence of myasthenia gravis and continuous muscle fiber activity should prompt the consideration of the occurrence of these disorders as one of the paraneoplastic manifestations, most often due to a thymic neoplasm. Both these conditions respond to treatment of underlying thymoma. This case is a very rare presentation worth reporting.

Catheter-related candidemia caused by Candida lipolytica in a child with tubercular meningitis.

Candida lipolytica is weakly pathogenic yeast, which is rarely isolated from the blood. We recovered this species from repeated blood samples and in the central venous catheter in a debilitated pediatric patient of tubercular meningitis. Identity was established on the basis of colony morphology and sugar assimilation tests (ID 32C assimilation profile). The fungemia and associated fever subsided after the removal of catheter and amphotericin B therapy. The data suggest that though of low virulence and usually a contaminant, C. lipolytica is emerging yeast pathogen in cases of catheter-related candidemia. Pathogenicity is indicated by isolation from repeated samples as in our case. Intensive therapy is recommended in cases not resolving spontaneously or responding to removal of catheter alone.

Attitude towards Acquired Immune Deficiency Syndrome and its determining factors: A community survey in rural and slum areas in India.

This survey was conducted to find out attitude of persons living in villages and slum areas of Chandigarh towards Acquired Immune Deficiency Syndrome and evaluate its determining factors. Methods - Households were selected from 5 villages and 5 slum areas by stratified random sampling. Trained field workers studied 2992 persons. A specially designed performa was administered to assess awareness, knowledge, and attitude about Acquired Immune Deficiency Syndrome. Result - Only 26.6% of study population had heard of Acquired Immune Deficiency Syndrome. Positive attitude towards Acquired Immune Deficiency Syndrome patients’ movement in community, work, school and continuing friendship was found. Majority knew about four major routes of transmission and basic preventive measures. A negative correlation was found between knowledge & attitude scores. On stepwise regression analysis, sex, education and marital status contributed to the variance with attitude as dependent variable. Conclusion – Majority of subjects held positive attitudes towards Acquired Immune Deficiency Syndrome. Education and marital status determined attitudes.