Non-prescription sale of antibiotics in pharmacies across Puducherry, India

Background: Despite being illegal, non-prescription sales of antibiotics in India continue to be a major contributor to antibiotic abuse, which fosters antibiotic resistance.Methods: Two trained actors simulated symptoms of acute gastroenteritis (AGE) and upper respiratory tract infections (URTI) in 60 pharmacies each randomly selected in the Union Territory of Pondicherry, India. The ease of obtaining antibiotics, any additional enquiries made by the pharmacies, and any additional advise given were noted.Results: Only 33/120 pharmacies (27.5%) declined to dispense antibiotics without prescription; all 33 were attached to a hospital or nursing home. The most frequently dispensed antibiotics for AGE and URTI were ciprofloxacin (41.4%) and coamoxiclav (41.3%) respectively. Out of the 87 pharmacies which dispensed antibiotics without prescription, the presence of additional symptoms and previous drug allergy were enquired by 20 (22.9%) and 9 (10.3%) pharmacies respectively. While over half of the pharmacies gave instructions regarding dose, duration and frequency of antibiotic consumption, none of the pharmacies provided information regarding adverse reaction profile of antibiotics. Non-pharmacological measures for symptomatic improvement were advised by 24/120 pharmacies (20%).Conclusions: Non-prescription sales of antibiotics are unacceptably high in Pondicherry. Stricter implementation of the law and public awareness of the perils of inappropriate antibiotic usage are the need of the hour

Operational Challenges in Diagnosing Multi-Drug Resistant TB and Initiating Treatment in Andhra Pradesh, India

Revised National TB Control Programme (RNTCP), Andhra Pradesh, India. There is limited information on whether MDR-TB suspects are identified, undergo diagnostic assessment and are initiated on treatment according to the programme guidelines.To assess i) using the programme definition, the number and proportion of MDR-TB suspects in a large cohort of TB patients on first-line treatment under RNTCP ii) the proportion of these MDR-TB suspects who underwent diagnosis for MDR-TB and iii) the number and proportion of those diagnosed as MDR-TB who were successfully initiated on treatment.A retrospective cohort analysis, by reviewing RNTCP records and reports, was conducted in four districts of Andhra Pradesh, India, among patients registered for first line treatment during October 2008 to December 2009.Among 23,999 TB patients registered for treatment there were 559 (2%) MDR-TB suspects (according to programme definition) of which 307 (55%) underwent diagnosis and amongst these 169 (55%) were found to be MDR-TB. Of the MDR-TB patients, 112 (66%) were successfully initiated on treatment. Amongst those eligible for MDR-TB services, significant proportions are lost during the diagnostic and treatment initiation pathway due to a variety of operational challenges. The programme needs to urgently address these challenges for effective delivery and utilisation of the MDR-TB services

NF-kappaB p65-Dependent Transactivation of miRNA Genes following Cryptosporidium parvum Infection Stimulates Epithelial Cell Immune Responses

Cryptosporidium parvum is a protozoan parasite that infects the gastrointestinal epithelium and causes diarrheal disease worldwide. Innate epithelial immune responses are key mediators of the host's defense to C. parvum. MicroRNAs (miRNAs) regulate gene expression at the posttranscriptional level and are involved in regulation of both innate and adaptive immune responses. Using an in vitro model of human cryptosporidiosis, we analyzed C. parvum-induced miRNA expression in biliary epithelial cells (i.e., cholangiocytes). Our results demonstrated differential alterations in the mature miRNA expression profile in cholangiocytes following C. parvum infection or lipopolysaccharide stimulation. Database analysis of C. parvum-upregulated miRNAs revealed potential NF-κB binding sites in the promoter elements of a subset of miRNA genes. We demonstrated that mir-125b-1, mir-21, mir-30b, and mir-23b-27b-24-1 cluster genes were transactivated through promoter binding of the NF-κB p65 subunit following C. parvum infection. In contrast, C. parvum transactivated mir-30c and mir-16 genes in cholangiocytes in a p65-independent manner. Importantly, functional inhibition of selected p65-dependent miRNAs in cholangiocytes increased C. parvum burden. Thus, we have identified a panel of miRNAs regulated through promoter binding of the NF-κB p65 subunit in human cholangiocytes in response to C. parvum infection, a process that may be relevant to the regulation of epithelial anti-microbial defense in general

Combinatorial Effect of Non-Steroidal Anti-inflammatory Drugs and NF-κB Inhibitors in Ovarian Cancer Therapy

Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda-7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda-7/IL-24 by small interfering RNA abrogates apoptosis. mda-7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD) 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda-7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Advances in modeling transport phenomena in material-extrusion additivemanufacturing: Coupling momentum, heat, and mass transfer

Material-extrusion (MatEx) additive manufacturing involves layer-by-layer assembly ofextruded material onto a printer bed and has found applications in rapid prototyping.Both material and machining limitations lead to poor mechanical properties of printedparts. Such problems may be addressed via an improved understanding of thecomplex transport processes and multiphysics associated with the MatEx process.Thereby, this review paper describes the current (last 5 years) state of the art modelingapproaches based on momentum, heat and mass transfer that are employed in aneffort to achieve this understanding. We describe how specific details regardingpolymer chain orientation, viscoelastic behavior and crystallization are often neglectedand demonstrate that there is a key need to couple the transport phenomena. Such acombined modeling approach can expand MatEx applicability to broader applicationspace, thus we present prospective avenues to provide more comprehensive modelingand therefore new insights into enhancing MatEx performanc

Genetic Basis of Myocarditis: Myth or Reality?

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Non-prescription sale of antibiotics in pharmacies across Puducherry, India

Background: Despite being illegal, non-prescription sales of antibiotics in India continue to be a major contributor to antibiotic abuse, which fosters antibiotic resistance.Methods: Two trained actors simulated symptoms of acute gastroenteritis (AGE) and upper respiratory tract infections (URTI) in 60 pharmacies each randomly selected in the Union Territory of Pondicherry, India. The ease of obtaining antibiotics, any additional enquiries made by the pharmacies, and any additional advise given were noted.Results: Only 33/120 pharmacies (27.5%) declined to dispense antibiotics without prescription; all 33 were attached to a hospital or nursing home. The most frequently dispensed antibiotics for AGE and URTI were ciprofloxacin (41.4%) and coamoxiclav (41.3%) respectively. Out of the 87 pharmacies which dispensed antibiotics without prescription, the presence of additional symptoms and previous drug allergy were enquired by 20 (22.9%) and 9 (10.3%) pharmacies respectively. While over half of the pharmacies gave instructions regarding dose, duration and frequency of antibiotic consumption, none of the pharmacies provided information regarding adverse reaction profile of antibiotics. Non-pharmacological measures for symptomatic improvement were advised by 24/120 pharmacies (20%).Conclusions: Non-prescription sales of antibiotics are unacceptably high in Pondicherry. Stricter implementation of the law and public awareness of the perils of inappropriate antibiotic usage are the need of the hour

Degradation Of Metal Oxide Surge Arresters Under Simulated Natural Conditions

The degradation of metal oxide surge arresters (MOSA) under continous operating voltage (C. 0. V), with time, is a well-known fact. But the contribution of transient overvoltages in the form of lightning surges, switching surges etc. against which the arrester is used as a protection device, to the arrester degradation has not been studied much. The simulation of a situation, wherein the arrester is kept uder C.O.V and different surges are applied on it, is somewhat complex. A method for simulation of field operating conditions of an arrester in the laboratory is presented in this paper. Results of two separate degradation studies on different samples under A.C, and D.C excitations with superimposed transient stresses 9 are given. A comparison of observed data with calculated ones is also made