Leveraging Lymphatic System Targeting in Systemic Lupus Erythematosus for Improved Clinical Outcomes.

The role of advanced drug delivery strategies in drug repositioning and minimizing drug attrition rates, when applied early in drug discovery, is poised to increase the translational impact of various therapeutic strategies in disease prevention and treatment. In this context, drug delivery to the lymphatic system is gaining prominence not only to improve the systemic bioavailability of various pharmaceutical drugs but also to target certain specific diseases associated with the lymphatic system. Although the role of the lymphatic system in lupus is known, very little is done to target drugs to yield improved clinical benefits. In this review, we discuss recent advances in drug delivery strategies to treat lupus, the various routes of drug administration leading to improved lymph node bioavailability, and the available technologies applied in other areas that can be adapted to lupus treatment. Moreover, this review also presents some recent findings that demonstrate the promise of lymphatic targeting in a preclinical setting, offering renewed hope for certain pharmaceutical drugs that are limited by efficacy in their conventional dosage forms. These findings underscore the potential and feasibility of such lymphatic drug-targeting approaches to enhance therapeutic efficacy in lupus and minimize off-target effects of the pharmaceutical drugs. SIGNIFICANCE STATEMENT: The World Health Organization estimates that there are currently 5 million humans living with some form of lupus. With limited success in lupus drug discovery, turning to effective delivery strategies with existing drug molecules, as well as those in the early stage of discovery, could lead to better clinical outcomes. After all, effective delivery strategies have been proven to improve treatment outcomes.

Melatonin activity and receptor expression in endometrial tissue and endometriosis.

STUDY QUESTION: Are melatonin receptors (melatonin receptor 1A (MR1A) and melatonin receptor 1B (MR1B)) expressed in human endometrium and endometriotic tissue, and does melatonin affect endometrial cell proliferation? SUMMARY ANSWER: Melatonin receptors are expressed in human eutopic endometrium, endometriomas and peritoneal lesions, although to different extents, and melatonin treatment attenuated estradiol-induced endometrial epithelial cell proliferation in culture. WHAT IS KNOWN ALREADY: Melatonin decreased endometriotic lesion volume in a rat model of endometriosis. Melatonin treatment reduced pain scores in and analgesic use by women with endometriosis. STUDY DESIGN, SIZE, DURATION: Basic science study using human endometrial tissue and an endometrial epithelial cell line. PARTICIPANTS/MATERIALS, SETTING, METHODS: Measurement of melatonin receptor expression (mRNA and protein) in women with surgically confirmed endometriosis (endometrioma (n = 20) or peritoneal lesion (n = 11) alone) and women without surgical evidence of endometriosis (control, n = 15). Collection of endometrial and endometriotic tissue samples, gynecologic history and demographic information. Quantification of estradiol (1.0 nM) and melatonin (0.1 nM-1.0 µM) ± estradiol-induced endometrial epithelial cell proliferation in cultures of endometrial epithelial cells (CRL-1671) following 24 and 48 hours of culture. MAIN RESULTS AND THE ROLE OF CHANCE: MR1A and MR1B were localized by immunohistochemistry in glandular epithelial cells of endometrial biopsies from women with and without endometriosis. Both receptors were expressed in eutopic and ectopic endometrial tissue. mRNA expression of MR1A and MR1B was significantly greater in peritoneal lesions than in either endometriomas or eutopic endometrium. However, protein expression of MR1A was decreased in peritoneal lesions compared to control eutopic endometrium, whereas MR1B expression did not differ between the groups. Melatonin (0.1 nM-1.0 µM) treatment inhibited estradiol (1.0 nM)-induced endometrial epithelial cell proliferation at 48 hours but not 24 hours of culture. LIMITATIONS, REASONS FOR CAUTION: Beneficial effects of melatonin seen in culture have yet to be comprehensively evaluated in women with endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that melatonin may be useful as an adjunct to current endometriosis treatments. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Canadian Institutes of Health Research (grant MOP142230 to W.G.F.). A.A.M. is supported by a resident research grant through the Physicians Services Incorporated Foundation. The authors have no conflicts of interest.

Circulating genotypes of Pneumocystis jirovecii and its clinical correlation in patients from a single tertiary center in India.

The present study was carried out with the objectives of genotyping Pneumocystis jirovecii at three distinct loci, to identify the single nucleotide polymorphisms (SNPs), and to study its clinical implications in patients with Pneumocystis pneumonia (PCP). Analysis of genetic diversity in P. jirovecii from immunocompromised patients was carried out by genotyping at three distinct loci encoding mitochondrial large subunit rRNA (mtLSU rRNA), cytochrome b (CYB), and superoxide dismutase (SOD) using polymerase chain reaction (PCR) assays followed by direct DNA sequencing. Of the 300 patients enrolled in the present study, 31 (10.33%) were positive for PCP by a specific mtLSU rRNA nested PCR assay, whereas only 15 P. jirovecii could be amplified at the other two loci (SOD and CYB). These positives were further subjected to sequence typing. Important genotypic combinations between four SNPs (mt85, SOD110, SOD215, and CYB838) and clinical outcomes could be observed in the present study, and mt85A, mt85T, and SOD110C/SOD215T were frequently associated with "negative follow-up". These SNPs were also noted to be relatively more prevalent amongst circulating genotypes in our study population. The present study is the first of its kind from the Indian subcontinent and demonstrated that potential SNPs of P. jirovecii may possibly be attributed to the clinical outcome of PCP episodes in terms of severity or fatality in different susceptible populations likely to develop PCP during their course of illness.

Impact of Buserelin Acetate or hCG Administration on the Day of First Artificial Insemination on Subsequent Luteal Profile and Conception Rate in Murrah Buffalo (Bubalus bubalis).

This study was designed to investigate the impact of buserelin acetate (BA) or human chorionic gonadotropin (hCG) administration on the day of first artificial insemination (AI) on subsequent luteal profile (diameter of corpus luteum (CL) and plasma progesterone) and conception rate in Murrah buffalo. The present experiment was carried out at two locations in 117 buffalo that were oestrus-synchronized using cloprostenol (500 µg) administered (i.m.) 11 days apart followed by AI during standing oestrus. Based on treatment (i.m.) at the time of AI, buffalo were randomly categorized (n = 39 in each group) into control (isotonic saline solution, 5 ml), dAI-BA (buserelin acetate, 20 µg) and dAI-hCG (hCG, 3000 IU) group. Out of these, 14 buffalo of each group were subjected to ovarian ultrasonography on the day of oestrus to monitor the preovulatory follicle and on days 5, 12, 16 and 21 post-ovulation to monitor CL diameter. On the day of each sonography, jugular vein blood samples were collected for the estimation of progesterone concentrations. All the buffalo (n = 117) were confirmed for pregnancy on day 40 post-ovulation. The conception rate was better (p < 0.05) in dAI-BA (51.3%) and dAI-hCG (66.7%) groups as compared to their control counterparts (30.8%). Furthermore, the buffalo of dAI-hCG group had improved (p < 0.05) luteal profile, whereas the buffalo of dAI-BA group failed (p > 0.05) to exhibit stimulatory impact of treatment on luteal profile when compared to control group. In brief, buserelin acetate or hCG treatment on the day of first AI leads to an increase in conception rate; however, an appreciable impact on post-ovulation luteal profile was observed only in hCG-treated Murrah buffalo.

Intricate Assessment and Evaluation of Effect of Bruxism on Long-term Survival and Failure of Dental Implants: A Comparative Study.

INTRODUCTION: Dental implants are one of the common lines of treatment used for the treatment of missing tooth. Various risk factors are responsible for the failure of the dental implants and occurrence of postoperative complications. Bruxism is one such factor responsible for the failure of the dental implants. The actual relation between bruxism and dental implants is a subject of long-term controversy. Hence, we carried out this retrospective analysis to assess the complications occurring in dental implants in patients with and without bruxism. MATERIALS AND METHODS: The present study included 1100 patients which were treated for rehabilitation by dental implant procedure at 21 dental offices of Ghaziabad (India) from 2004 to 2014. Analyzing the clinical records of the patients along with assessing the photographs of the patients was done for confirming the diagnosis of bruxism. Clinical re-evaluation of the patients, who came back for follow-up, was done to confirm the diagnosis of bruxism. Systemic questionnaires as used by previous workers were used to evaluate the patients about the self-conscience of the condition. Estimation of the mechanical complications was done only in those cases which occurred on the surfaces of the restoration of the dental implants. All the results were analyzed by Statistical Package for Social Sciences (SPSS) software. Student's t-test and Pearson's chi-square test were used to evaluate the level of significance. RESULTS: In both bruxer and non-bruxers, maximum number of dental implants was placed in anterior maxillary region. Significant difference was obtained while comparing the two groups for dimensions of the dental implants used. On comparing the total implant failed cases between bruxers and non-bruxers group, statistically significant result was obtained. Statistically significant difference was obtained while comparing the two study groups based on the health parameters, namely hypertension, diabetes, and smoking habit. CONCLUSION: Success of dental implant is significantly affected by bruxism. Special attention is required in such patients while doing treatment planning. CLINICAL SIGNIFICANCE: For the long-term clinical success and survival of dental implants in patients, special emphasis should be given on the patient's deleterious oral habits, such as bruxism as in long run, they influence the stability of dental implants.

Influence of protein tyrosine phosphatase gene (PTPN22) polymorphisms on rheumatic heart disease susceptibility in North Indian population.

This study was aimed to assess the association of Protein tyrosine phosphatase non-receptor22 (PTPN22) gene single nucleotide polymorphisms (SNPs) with rheumatic heart disease (RHD) susceptibility in 400 RHD patients and 300 controls. The PTPN22 polymorphisms (rs2476601, rs1217406 and rs3789609) were genotyped using Taqman probes (Applied Biosystems, Foster City, CA). Statistical analysis was performed by spss and haplotype analysis by snpstat. The frequencies of variant alleles were not different between controls and cases (rs2476601: 2.00% & 1.05%; rs1217406: 36.33% & 34.75%; and rs3789609: 38.17% & 40.00%, respectively]. However, G rs2476601 A rs1217406 T rs3789609 haplotype turned out to be a low risk factor for RHD (P = 0.0042) predisposition in females and adult patients. This study suggests PTPN22 haplotype may modulate the risk to RHD in North Indians.

Molecular characterization of oxytocin receptor gene in water buffalo (Bubalus bubalis).

Buffaloes are known for their productivity as compared to average yielding cows due to higher fat percentage, better feed conversion ability and disease resistance. On the other hand, the reproductive performances of buffaloes are often considered as poor owing to late sexual maturity, weak/silent oestrus, repeat breeder and prolonged intercalving interval. The study of cascade of events during oestrus and oestrous cycle can be useful for the improvement of reproductive efficiency of buffaloes. More precisely, the hormonal changes initiated at the molecular level within the animal determine the reproductive nature of the species. Nucleotide/protein sequence analysis serves as a vital tool in analysing the binding of the hormones for their effect or functions. In this study, we have reported cloning and characterization of the complete coding (cDNA) sequence of oxytocin receptor gene (OXTR) in buffaloes. Buffalo OXTR gene contains an uninterrupted ORF of 1176 nucleotides corresponding to an inferred polypeptide length of 391 amino acids (aa). The molecular weight of the deduced aa sequence was found to be 43 kDa with an isoelectric point of 9.253 and 16.328 charge at pH 7.0. The deduced protein sequence consists of 38 strongly basic (+) (K,R), 22 strongly acidic (-) (D,E), 186 hydrophobic (A, I, L, F, W, V) and 95 Polar (N, C, Q, S, T, Y) aa. Results indicated that aspartate (D) at aa position 85 and D, R and C at aa positions 136, 137 and 138, respectively, are conserved in buffaloes. The buffalo OXTR gene shared a per cent similarity ranging from 84.7 to 98.1 and 88.5 to 97.7 at nucleotide and deduced aa sequence levels, respectively, with that of other species. Phylogram constructed on the basis of either nucleotide or deduced aa sequences of buffalo OXTR gene showed that buffalo, cattle and sheep have diverged from human and swine and formed a separate clad. The buffalo sequence has shown maximum similarity and closeness with cattle followed by sheep both at nucleotide and at aa level.

IFN-τ acts in a dose-dependent manner on prostaglandin production by buffalo endometrial stromal cells cultured in vitro.

Interferon-τ (IFN-τ) has been recognized as the primary embryonic signal responsible for maternal recognition of pregnancy. Uterine endometrium produces both prostaglandin F2α (PGF2α ) and prostaglandin E2 (PGE2 ). PGF2α is responsible for the luteolysis; however, PGE2 favours establishment of pregnancy by its luteoprotective action. In this study, the dose-response effect of recombinant bovine IFN-τ (rbIFN-τ) on prostaglandin (PG) production by buffalo endometrial stromal cells cultured in vitro was studied. Buffalo endometrial stromal cells were isolated by double enzymatic digestion, initially with trypsin III followed by a cocktail of trypsin III, collagenase type II and DNase I and subsequently cultured till confluence. Further, cells were treated with different doses of rbIFN-τ (0.001, 0.01, 0.1, 1.0 and 10 µg/ml) and keeping a separate set of control. Culture supernatant was collected after 6, 12 and 24 h of treatment. PG levels in the culture supernatant were measured by enzyme immune assay (EIA) and total cellular protein estimated by Bradford method. Results indicated that buffalo endometrial stromal cells following rbIFN-τ treatment enhanced the secretion of both PGE2 and PGF2α , and also its ratio in a strict dose-dependent manner with a significant increase (p < 0.01) in PGE2 production at 1 µg/ml dose of rbIFN-τ and maximal stimulation for both PG was observed at 10 µg/ml. Further, both PG production and its ratio were increased significantly (p < 0.01) in a time-dependent fashion in all the groups at 6, 12 and 24 h post-treatment with highest level achieved at 24 h as compared with control. Absolute levels of PGE2 remained higher than PGF2α indicating PGE2 as the major PG produced by endometrial stromal cells. The dose-dependent response of rbIFN-τ signifies the importance of optimum concentration of IFN-τ for the embryonic development especially during the critical period to establish successful pregnancy.

Identification of pregnancy-associated glycoproteins by peptide mass fingerprinting in water buffalo (Bubalus bubalis).

Ruminant placentas synthesize pregnancy-associated glycoproteins (PAGs) during pregnancy, which serve as biomarkers of pregnancy. The present study was conducted to verify, whether PAGs are expressed in buffalo placenta by using lectin-based affinity chromatography and peptide mass finger printing (PMF). Fetal cotyledonary tissues were collected from gravid uteri procured from slaughtered house. Proteins were extracted and subjected to wheat germ agglutinin (WGA) lectin affinity chromatography to isolate the PAGs. The isolated glycoproteins were separated by one-dimensional SDS-PAGE. PMF results of the 75 kDa protein revealed presence of two PAGs (PAG-7 and -11). The PAG-7 consisted of about 170 mass signals, of which 16 were assigned to corresponding/translated cDNA sequences of buffalo PAG-7, leading to sequence coverage of 40%. PMF result of PAG-11 showed 170 mass signals, of which 15 were assigned to buffalo PAG-11, leading to sequence coverage of 34%. In conclusion, the glycoprotein isolated from placental extract corresponding to 75 kDa band on SDS PAGE gel was a mixture of PAG-7 and -11, which may help in development of suitable diagnostics for pregnancy in buffalo.

Association of angiotensin I-converting enzyme gene insertion/deletion polymorphism with rheumatic heart disease in Indian population and meta-analysis.

Rheumatic heart disease (RHD) is one of the most severe consequences of rheumatic fever. It has been suggested that angiotensin I-converting enzyme (ACE) may be involved in the increased valvular fibrosis and calcification in the pathogenesis of RHD. We conducted a case-control study to look for association of ACE I/D polymorphism with RHD in Indian population. The study incorporated 300 patients (170 males and 130 females) with RHD, and 200 controls (118 males and 82 females). We also subgrouped RHD patients into mitral valve lesion (MVL) and combined valve lesion (CVL). ACE I/D polymorphism was identified using polymerase chain reaction method. We also performed a meta-analysis of three published studies and the present study (636 RHD cases and 533 controls) to evaluate the association between the ACE I/D polymorphisms and RHD risk. A significant difference in ACE ID and DD genotypes distribution between RHD cases (OR = 1.62, 95% CI = 1.11-2.36 and OR = 2.08, 95% CI = 1.02-4.15, respectively) and corresponding controls was observed. On comparing the ACE genotypes of MVL and CVL subgroups with controls, ID and DD genotypes were also significantly associated with CVL (FDR Pcorr = 0.009, OR = 2.19 and FDR Pcorr = 0.014, OR = 3.29, respectively). Meta-analysis also suggested association of the ACE D allele (FDR Pcorr = 0.036, OR-1.22, 95% CI 1.02-1.45) with RHD. In conclusion, ACE ID and DD genotypes are associated with an increased risk of RHD, particularly CVL. This suggests that the ACE I/D gene polymorphism may play an important role in the pathogenesis of RHD.

The Austrian syndrome: a case report and review of the literature.

A 61-year-old man presented with fever and altered mental status. He was intubated for respiratory distress and was found to have multilobar pneumonia for which antibiotic therapy was instituted. However, his mental status continued to deteriorate despite appropriate antibiotic therapy for his pneumonia. The results from lumar puncture revealed meningitis and endocarditis was evident on a trans-esophageal echocardiogram. His blood and respiratory cultures grew Streptococcus pneumoniae. The patient was diagnosed with Austrian syndrome. After appropriate changes to his antibiotic regimen and an aortic valve replacement, he recovered and was discharged.

HIV associated renal disease: a pilot study from north India.

BACKGROUND & OBJECTIVES: HIV/AIDS patients may have renal involvement also, however, Indian data are sparse. The present study was done to find the spectrum of renal diseases in HIV/AIDS patients in north India. METHODS: In this prospective pilot study, HIV positive patients aged >18 yr were screened for renal involvement [serum creatinine >1.5 mg% and/or significant proteinuria (>500 mg /day)]. Patients who were positive on screening were followed up prospectively and underwent kidney biopsy if indicated. RESULTS: A total of 526 patients were screened, of these, 91 (17.3%) were found to have renal involvement. Group A (Treatment naοve) comprised 392 patients who were not on antiretroviral treatment (ART) and group B (patients on ART) comprised 134 patients. More patients (74/392, 18.9%) in group A had renal involvement as compared to patients in group B (17/134, 12.7%). Of the 91 patients with renal involvement, 26 were followed up and underwent kidney biopsy. Thirteen patients had only proteinuria and another 13 had renal dysfunction with or without proteinuria. Most common histological diagnosis was mesangioproliferative glomerulonephritis (mes PGN) (10/26). Two patients had collapsing FSGS (focal segmental glomerulosclerosis) and three patients had immune complex glomerulonephritis. Seven patients had acute kidney injury, whom six totally recovered from their renal function. All patients with mesPGN tolerated angiotensin converting enzyme (ACE) inhibitors well. There was mixed response of collapsing FSGS to steroids. Both patients with MPGN (membranoproliferative glomerulonephritis) did well on low dose of steroid and ART. INTERPRETATION & CONCLUSIONS: Renal involvement was found to be common in HIV positive patients (17.3%). A low occurrence of renal involvement found in patients already on ART suggests some renoprotective effect of ART. Our preliminary results showed that collapsing FSGS was not rare in Indian HIV positive population, but classical HIV associated nephropathy was not seen. Longitudinal studies with robust study design and large sample size need to be done to confirm the findings.

Somatic mutation of the MEN1 gene in parathyroid tumours.

Primary hyperparathyroidism is a common disorder with an annual incidence of approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown. Parathyroid adenomas are usually monoclonal, suggesting that one important step in tumour development is a mutation in a progenitor cell. Approximately 30% of sporadic parathyroid tumours show loss of heterozygosity (LOH) for polymorphic markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the question of whether such sporadic parathyroid tumours are caused by sequential inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene and identified MEN1 germline mutations in fourteen of fifteen kindreds with familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among 33 tumours we found somatic MEN1 gene mutation in 7, while the corresponding MEN1 germline sequence was normal in each patient. All tumours with MEN1 gene mutation showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant allele. Thus, somatic MEN1 gene mutation for the mutant allele. Thus, somatic MEN1 gene mutation contributes to tumorigenesis in a substantial number of parathyroid tumours not associated with the MEN1 syndrome.

HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome.

We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.

A pilot study on area under curve of mycophenolic acid as a guide for its optimal use in renal transplant recipients.

BACKGROUND & OBJECTIVES: The immunosuppressants administered to renal transplant subjects are usually monitored therapeutically to prevent graft rejection and drug toxicity. Mycophenolic acid (MPA) is an immunosuppressant. The present prospective study was undertaken to establish the utility of plasma level monitoring of MPA and to correlate it with clinical outcomes in renal transplant receipients. METHODS: MPA plasma level at 2, 4 and 9 h and the area under concentration-time curve (AUC) were estimated using high performance liquid chromatography in 24 renal transplant recipients receiving immunosuppressant MPA plus tacrolimus and steroid. RESULTS: There was wide inter-individual variation in MPA plasma level and the AUC. The incidences of gastrointestinal adverse drug events (diarrhoea and acidity) were significantly more in the high MPA AUC patients. Though biopsy proven acute rejection was not found, of the six subjects with lower MPA AUC (<30 mg.h/l), three were clinically diagnosed to develop tacrolimus nephrotoxicity. The Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) scores represented better health related quality of life in lower MPA AUC than in the higher MPA AUC (>60 mg.h/l). INTERPRETATION & CONCLUSIONS: The present findings suggest the MPA AUC of 30 - 60 mg.h/l in the maintenance stage of renal transplant patients to have optimum clinical benefit and relegated adverse events profile indicating the usefulness of AUC of MPA with limited sampling strategy in optimizing its use.

Giant coronary artery aneurysm following implantation of Endeavour stent presenting with fever.

Coronary artery aneurysms are a known but uncommon complication of percutaneous coronary intervention (PCI) probably related to effects of vessel wall trauma and possibly a combination of hypersensitivity and incomplete endothelisation associated with drug-eluting stents (DES). We present here a case of giant coronary artery aneurysm 3 months following implantation of a zotarolimus eluting endeavour stent presenting with fever.

Perceived weight status, overweight diagnosis, and weight control among US adults: the NHANES 2003-2008 Study.

OBJECTIVES: To examine the association between perceived overweight status and weight control, discrepancies between perceived and measured weight status, and opportunities for health care professionals (HCPs) to correct weight perception among US adults. DESIGN: Population-based cross-sectional study. SUBJECTS: In all, 16,720 non-pregnant adults from the 2003 to 2008 National Health and Nutrition Examination Survey. RESULTS: Overall, 64% (73% women, 55% men) reported a desire to weigh less and 48% (57% women, 40% men) reported pursuing weight control. Weight control was positively associated with overweight perception (odds ratio (OR) women 3.74; 95% confidence interval (CI) 2.96, 4.73; OR men 2.82; 95% CI 2.11, 3.76) and an HCP diagnosis of overweight/obesity (OR women 2.22; 95% CI 1.69, 2.91; OR men 2.14; 95% CI 1.58, 2.91), independent of measured weight status. A large proportion of overweight individuals (23% women, 48% men) perceived themselves as having the right weight. Also, 74% of overweight and 29% of obese individuals never had an HCP diagnosis of overweight/obesity. Although the majority of overweight/obese individuals (74% women, 60% men) pursued at least one weight management strategy, fewer (39% women, 32% men) pursued both dietary change and physical activity. Among overweight/obese adults, those with an HCP diagnosis of overweight/obesity were more likely to diet (74 versus 52%), exercise (44 versus 34%), or pursue both (41 versus 30%, all P<0.01) than those who remained undiagnosed. CONCLUSION: HCPs have unused opportunities to motivate their patients to control and possibly lose weight by correcting weight perceptions and offering counseling on healthy weight loss strategies.

Hemodialysis of patients with HCV infection: isolation has a definite role.

HCV infection in patients on hemodialysis varies from 10 to 60% in various centers. There is controversy regarding the isolation of patients with HCV infection during hemodialysis. Guidelines developed by the Centers for Disease Control and Prevention do not suggest isolation of these patients. In this opposite view, evidence is being given to support the view that there is a definite role of isolation of HCV-infected patients during hemodialysis.

Phenotypic and genotypic methods for the detection of methicillin resistant coagulase negative staphylococci: a comparative study.

CONS are the major cause of nosocomial infection in last decade and methicillin resistant CoNS has emerged as a major clinical problem. The present study was to compare different phenotypic methods with genotypic method PCR, for the detection of methicillin resistance in CoNS. 100 CoNS isolates from different samples were studied for the detection of mecA gene. PCR was considered as "gold standard". Oxacillin and cefoxitin antibiotics were used for different phenotypic tests (DD, Agar dilution and MHOX). The sensitivities of oxacillin and cefoxitin disks for all CONS were found to be 92.30% and 88.46% respectively and the specificities were 87.5% and 100% respectively. The sensitivities of the agar dilution test for oxacillin and cefoxitin were 86.53% and 80.76%, respectively, where as the specificities were 79.16% and 85.41%, respectively. The sensitivity of MHOX was observed to be 96.16% and specificity 72.91%. Cefoxitin D.D and oxacillin AD methods could be used as initial test for the determination of methicillin resistance in CoNS isolates. The result of MHOX shows that it could be the best single method for the evaluation of oxacillin resistance mediated by the mecA gene for all CoNS species.

The impact of VKORC1-1639 G>A polymorphism on the maintenance dose of oral anticoagulants for thromboembolic prophylaxis in North India: A pilot study.

BACKGROUND: The dose requirements for oral anticoagulants in thromboembolic events are influenced by promoter polymorphism in the VKORC1 gene. However, limited data are available on the influence of the polymorphism in various Indian populations. The present study aimed at determining the relationship between the VKORC1-1639 G>A genotypes and maintenance doses of oral anticoagulants for therapeutically stable INR values in patients taking Acitrom after valve replacement surgery. MATERIALS AND METHODS: Fifty patients from the northern Indian region were genotyped for VKORC1-1639 G>A by polymerase chain reaction and restriction fragment length polymorphism. Means of the weight-normalized daily Acitrom dose were calculated for every patient. RESULTS AND DISCUSSION: The VKORC1 1639G>A minor allele frequency in the study population (n = 50) was found to be 22%. The patients with a wild type genotype required the maximum drug dose as suggested for full functionality of the enzyme. Heterozygous patients were found to have an intermediate drug dose and the patients with a variant homozygous genotype had the minimum maintenance drug dose requirement. These findings are in concurrence with the effect of the promoter polymorphism on vitamin K epoxide reductase activity.1639G>A minor allele frequency in the study population (n = 50) was found to be 22%. The patients with a wild type genotype required the maximum drug dose as suggested for full functionality of the enzyme. Heterozygous patients were found to have an intermediate drug dose and the patients with a variant homozygous genotype had the minimum maintenance drug dose requirement. These findings are in concurrence with the effect of the promoter polymorphism on vitamin K epoxide reductase activity. CONCLUSION: The VKORC1-1639 G>A status can be indicative of establishing the therapeutic dose of oral anticoagulants in Indian patients.