Genotyping and antibiotic resistance patterns of Campylobacter fetus subsp.venerealis from cattle farms in India.

Bovine genital campylobacteriosis caused by Campylobacter fetus subsp. venerealis (Cfv) is of considerable economic importance to the cattle industry worldwide. Cfv causes syndrome of temporary infertility in female cattle, early embryonic mortality, aberrant oestrus cycles, delayed conception, abortions and poor calving rates. In the present study, a total of 200 samples obtained from vaginal swabs, cervicovaginal mucous (CVM), preputial washes and semen straws were investigated that were obtained from organized cattle farm of MLRI, Manasbal and unorganized sectors. Out of a total of 200 samples, 49 (47·57%) vaginal swabs, 1 (3·33%) preputial wash and 8 (25%) carried out CVM samples were positive for Cfv, whereas none of the semen straws were positive for Cfv. A total of eleven isolates of Cfv were recovered. PFGE (Pulse field gel electrophoresis) analysis revealed four different pulsotypes (I-IV) circulating in the screened farms. A common pulsotype circulating among farms could not be established. Insertion element (ISCfe1), a 233 bp amplicon of Cfv, was sequenced and the sequence was deposited in GenBank (accession no: MK475662).

Efficacy of a hospital policy of selective digestive decontamination for carbapenem-resistant Enterobacterales carriers: prospective before-after study.

A single-centre interrupted time series quasi-experimental study was undertaken to assess whether a hospital policy of selective digestive decontamination (SDD, gentamicin/amikacin with neomycin) administered to carbapenem-resistant Enterobacterales (CRE) carriers would reduce the duration of carriage and contain the spread of CRE. No significant difference in time to CRE eradication was observed between the observation (12 months, 120 patients) and intervention (12 months, 101 patients) periods. No change in the trend of new in-hospital CRE acquisitions or bacteraemia during the intervention was detected. As such, administration of SDD to CRE carriers was not effective for the eradication of carriage or controlling in-hospital CRE transmissions.

Trans-implant treatment of chronic recurrent maxillary sinusitis via dynamic implants with an internal port: Experience with 31 cases.

This study was performed to test a protocol for trans-implant treatment of chronic recurrent maxillary sinusitis (CRS), via implants with an internal removable sealing screw. The appropriate indications for treatment, optimal number of treatment sessions, and general schedule of treatment and follow-up were assessed. This was a retrospective study of 31 patients with CRS who were managed with trans-implant lavage. Of these patients, 28 (referred for a sinus elevation procedure) underwent a simultaneous implantation procedure and treatment of the sinusitis. Three patients received treatment for sinusitis via an already existing implant. The suggested sinusitis treatment protocol includes the drainage of pus through the punctured sinus floor and three sessions of antral irrigation/lavage, four cone beam computed tomography scans, and four transnasal endoscopic observations. The suggested combined protocol includes the simultaneous evaluation of the implant status and the sinusitis treatment results on days 30 and 60 after surgery. Of the 31 patients, 28 (90%) had complete relief of most of their symptoms (nasal obstruction/discharge, anosmia/hyposmia) up to day 30 postoperative. Follow-up nasal endoscopy demonstrated no evidence of active sinus disease. Twenty-seven implants were well-osseointegrated and were still in use for prosthetic purposes. In one case, the implantation failed because of poor bone quality. For the remaining 30 cases, both clinical and radiological results showed stability of the implants and no CRS recurrence during the whole follow-up period. The dental implant with an internal central port and an integral sealing screw may be used for drainage, irrigation, observation, and further treatment of the maxillary sinus in cases of CRS.

From self-induced to perceived errors - A generalized over-monitoring activity in obsessive-compulsive disorder.

Well-functioning error monitoring of the inner and outer environments is essential for adaptively altering behavior, while malfunction characterizes conditions such as obsessive-compulsive disorder (OCD). The underlying brain processing is manifested as Error-Related Negativity (ERN) signal elicited following error comission, and Perceived Error Related Theta Activity (PERTA) signal elicited following detection of discrepancy in the environment. Yet, while enhanced ERN was repeatedly demonstrated in OCD patients and was found to be potentiated among their unaffected first degree relatives, no comparable observations were reported with regard to PERTA. We recorded EEG activity while OCD patients, OCD patients' siblings (Family), and healthy controls (HC) performed computerized tasks. For the examination of ERN we used the Stroop task and for the examination of PERTA we presented correct and incorrect mathematical equations. Increased ERN (0-120 ms post response) was observed in both the OCD and Family groups, but only the OCD patients' signal significantly differed from that of HC's. Similarly, modified PERTA activity was observed in both the OCD and Family groups in the N1 peak (65-125 ms post perceived error), but only for the OCD group this activity significantly differed from that of HC. Both ERN and PERTA's N1 are fast occurring peaks, which suggests that OCD is associate with a constantly over-activated detection system that monitors the inner and outer environment and reacts promptly following detection of a mistake. Furthermore, the modified but non-significantly different activity of the Family group suggests that the pathological condition evolves in vulnerable individuals with neuronal predisposition.

Cytotoxic Potential and Molecular Characterization of Fungal Endophytes from Selected High Value Medicinal Plants of the Kashmir Valley - India.

The present study explores the fungal endophytes from selected high value medicinal plants to check their activities at in-vitro and in-vivo level. The in-vitro cytotoxicity of selected endophytes revealed potent growth inhibition against human cancer cell lines of leukemia (THP-1), lung (A549), prostate (PC-3), colon (Caco-2), neuroblastoma (IMR-32) and breast (MCF-7) at a concentration of 100 µg/ml. Among them the endophytic strains I. e., IIIM2, IIIM3, IIIM7 and IIIM8 showed most significant growth inhibition against colon (Caco-2), prostate (PC-3), lung (A549) and leukemia (THP-1) cancer cell lines. At the in-vivo level maximum (58.95%) tumor growth inhibition was documented with the extract of IIIM2 against Ehrlich Ascites Carcinoma mouse modal. All the potent fungal endophytic strains were characterized using ITS 4 and ITS 5 region sequencing and phylogenetic analysis was ascertained among them. This paper confirms the 2 elite endophytic fungal strains, IIIM2 and IIIM8, have the potential to act as a source of new anticancer compounds.

Factors affecting outcome after the use of the Ponseti method for the management of idiopathic clubfoot, a retrospective study in an orthopaedic referral institute.

TIn the last few decades Ponseti method has replaced soft tissue releases as the gold standard in the management of idiopathic clubfoot. However, the recurrence of the deformity is common without post tenotomy bracing. The purpose of this study was to retrospectively see various attributes of the patients associated with poor outcome after use of Ponseti method in idiopathic clubfoot management. Seventy nine consecutive patients with one hundred and twenty three idiopathic clubfeet treated with Ponseti method by single orthopaedic surgeon were followed for a period of two years and recurrence of the deformity was studied in relation to age of patient at presentation (< 3 months or more), sex of the patient, severity of the deformity ( moderate to severe verses (Vs.) very severe), compliance to post tenotomy bracing (compliant Vs. non compliant), educational level of parents (high school or less) and access of parents to internet (Yes or No) and odds ratio for recurrence and level of significance determined for each using Fisher's exact t-test. Non compliance in seventeen patients (17.7%) with post tenotomy bracing was the most important factor related to the recurrence, with an odds ratio of 6.22 (P =0.0059). Educational level (less than high school) of parents (36.7%) was the second most important factor with odds ratio of 5.5 (P=0.0073). Fifteen patients with severe Demiglio scoring feet had an odds ratio of 5.3 (P= 0.0097) for the recurrence of the deformity. Inaccess of the parents to the internet had an odds ratio of 6.33 (P =0.011) for the recurrence of the deformity. Age and sex of the patients was not found to have a significant effect on the recurrence of the deformity. In conclusion, the risk factors associated with recurrence of the idiopathic clubfoot deformity except severity of the deformity are modifiable and extra minutes can be spent with risk group parents during follow up visits to prevent a recurrence by making them understand natural history of the corrected foot without post tenotomy bracing, encouraging them for regular follow up visits, arranging interactive sessions with other patients who are regular in their follow up and compliant with bracing, and encouraging the literate parents to update their information about clubfoot from internet.

Pre-operative staging of rectal cancer using multi-detector row computed tomography with multiplanar reformations: single center experience.

BACKGROUND: Technical advancement in imaging has helped to stage and plan treatment modality for carcinoma rectum with still some objectives controversial. AIMS: The aim of our study was to evaluate the accuracy of multidetector row computed tomography (MDCT) with multiplanar reformations in the pre-operative staging of rectal carcinoma and correlation with intraoperative and histopathologic staging of retrieved specimen with respect to the depth of tumor invasion (T-staging), lymph node metastasis (N-staging) and mesorectal fascia (MRF) involvement. MATERIALS AND METHODS: The study was a prospective one and consisted of 52 patients with biopsy proved rectal carcinoma. MDCT studies were performed on a 64-slice computed tomography system. Images were reconstructed in axial, coronal and sagittal planes. MDCT findings were compared with intraoperative and pathologic (reference standard) findings. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were assessed. RESULTS: The diagnostic accuracy of MDCT for T1/T2, T3 and T4 lesions was 77%, 86.5% and 100%, respectively. For perirectal lymph node metastasis (N+), the diagnostic accuracy of MDCT was 84.1%. The diagnostic accuracy of MDCT for MRF involvement was 91%. CONCLUSION: MDCT is a reliable radiological tool for local staging of rectal cancer with excellent accuracy rates for T and N-staging of rectal cancer.

Dendritic cells in multiple sclerosis: key players in the immunopathogenesis, key players for new cellular immunotherapies?

Many studies have demonstrated the role of the adaptive immune system in the pathogenesis of multiple sclerosis (MS). Recent data suggest that dendritic cells (DCs), which are innate immune cells, also contribute to the pathogenesis of MS. In patients with MS, DCs are abundantly present in brain lesions, and display an altered phenotype and/or function as compared with this in healthy controls. DCs are thus in the position to pathologically influence the effector function of (auto-reactive) T and B cells. Interestingly, current first-line immunomodulating therapies for MS have been shown to restore DC phenotype and function, albeit in a non-specific manner. To date, clinical trials using agents specifically targeting DC function are ongoing. Moreover, several studies worldwide are currently investigating possible strategies to develop tolerogenic DCs. This review focuses on the phenotypic and functional alterations of conventional DCs and plasmacytoid DCs in patients with MS. Furthermore, we discuss how existing immunomodulating therapies for MS patients affect DC function and address future perspectives in the development of immunotherapies specifically targeting DCs.

What are the factors that predict outcome at relapse after previous esophagectomy and adjuvant therapy in high-risk esophageal cancer?

OBJECTIVES: The present study investigated factors affecting outcome at relapse after previous surgery and adjuvant chemoradiation (crt) in high-risk esophageal cancer patients. PATIENTS AND METHODS: From 1989 to 1999, we followed high-risk resected esophageal cancer patients who had completed postoperative crt therapy. Patients who relapsed with a disease-free interval of less than 3 months were treated with palliative crt when appropriate. Patients with a disease-free interval of 3 months or more were treated with best supportive care. Post-recurrence survival was estimated using the Kaplan-Meier technique, and statistical comparisons were made using log-rank chi-square tests and Cox regression. RESULTS: Of the 69 patients treated with adjuvant crt after esophagectomy, 46 experienced recurrence. Median time to relapse was 28 months (range: 0.1-40 months). Among the 46 relapsed patients, median age was 61 years (range: 37-82 years), and 42 were men. At the initial staging, 44 of 46 were node-positive; 31 of 46 had adenocarcinoma. In 33 of 46, post-esophagectomy resection margins were clear. Median follow-up after recurrence was 30.5 months (range: 1.3-100 months). Median overall survival after recurrence was 5.8 months, and the 12-month, 24-month, and 36-month survival rates were 20%, 10%, and 5% respectively. Of the prognostic factors analyzed, only resection margin status and interval to recurrence were statistically significant for patient outcome in univariate and multivariate analysis. Patients who had positive resection margins and who relapsed 12 or fewer months after surgery and adjuvant crt had a median post-recurrence overall survival of 0.85 months as compared with 6.0 months in other patients (more than 12 months to relapse, or negative resection margins, or both; log-rank p = 0.003). CONCLUSIONS: Resection margin status and interval to disease relapse are significant independent prognostic factors for patient outcome after adjuvant crt therapy.

Distribution and regulation of stochasticity and plasticity in Saccharomyces cerevisiae.

Stochasticity is an inherent feature of complex systems with nanoscale structure. In such systems information is represented by small collections of elements (e.g., a few electrons on a quantum dot), and small variations in the populations of these elements may lead to big uncertainties in the information. Unfortunately, little is known about how to work within this inherently noisy environment to design robust functionality into complex nanoscale systems. Here, we look to the biological cell as an intriguing model system where evolution has mediated the trade-offs between fluctuations and function, and in particular we look at the relationships and trade-offs between stochastic and deterministic responses in the gene expression of budding yeast (Saccharomyces cerevisiae). We find gene regulatory arrangements that control the stochastic and deterministic components of expression, and show that genes that have evolved to respond to stimuli (stress) in the most strongly deterministic way exhibit the most noise in the absence of the stimuli. We show that this relationship is consistent with a bursty two-state model of gene expression, and demonstrate that this regulatory motif generates the most uncertainty in gene expression when there is the greatest uncertainty in the optimal level of gene expression.

Postoperative extended-volume external-beam radiation therapy in high-risk esophageal cancer patients: a prospective experience.

BACKGROUND AND PURPOSE: Extended-volume external-beam radiation therapy (RT) following esophagectomy is controversial. The present prospective study evaluates the feasibility of extended-volume RT treatment in high-risk esophagectomy patients with a cervical anastomosis receiving postoperative combined chemoradiation therapy. PATIENTS AND METHODS: From 2001 to 2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study to evaluate the adverse effects of extended-volume RT. Postoperative management was carried out at London Regional Cancer Program. Eligibility criteria were pathology-proven esophageal malignancy (T3-4, N0-1), disease amenable to surgical resection, and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous RT were excluded. All 15 study patients received 4 cycles of 5-fluorouracil-based chemotherapy. External-beam RT was conducted using conformal computed tomography planning, with multi-field arrangement tailored to the pathology findings, with coverage of a clinical target volume encompassing the primary tumour bed and the anastomotic site in the neck. The radiation therapy dose was 50.40 Gy at 1.8 Gy per fraction. The RT was delivered concurrently with the third cycle of chemotherapy. The study outcomes-disease-free survival (DFS) and overall survival (OS)-were calculated by the Kaplan-Meier method. Treatment-related toxicities were assessed using the U.S. National Cancer Institute's Common Toxicity Criteria. RESULTS: The study accrued 10 men and 5 women of median age 64 years (range: 48-80 years) and TNM stages T3N0 (n = 1), T2N1 (n = 2), T3N1 (n = 11), and T4N1 (n = 1). Histopathology included 5 adenocarcinomas and 10 squamous-cell carcinomas. Resection margins were clear in 10 patients. The median follow-up time was 19 months (range: 3.5-53.4 months). Before radiation therapy commenced, delay in chemotherapy occurred in 20% of patients, and dose reduction was required in 13.3%. During the concurrent chemoradiation therapy phase, 20% of the patients experienced chemotherapy delay, and 6.6% experienced dose reduction. No patient experienced treatment-related acute and chronic esophagitis above grade 2. Disease recurred in 40% of the patients (6/15), and median time to relapse was 24 months. No tumour recurred at the anastomotic site. The median DFS was 23 months, and the median OS was 21 months. CONCLUSIONS: Extended-volume external-beam RT encompassing the tumour bed and the anastomotic site is feasible and safe for high-risk T3-4, N0-1 esophageal cancer patients after esophagectomy.

Poster - Thurs Eve-01: Comparison of clinical IMRT plan quality and delivery accuracy: Few large segments vs many small segments.

Commercial radiation treatment planning systems for intensity modulation use optimization algorithms that can vary multi-leaf collimator (MLC) segment sizes, segment number and the minimum number of monitor units (MU) per segment. These parameters are varied according to the treatment site, size, location, and proximity to the organs at risk. This study compares the utility of optimization using (Case A) few large segments and a higher minimum MU per segment to that of (case B) using many smaller segments with a lower minimum MU per segment. For Case A, the patient benefits from a reduced treatment time associated with fewer MUs and fewer MLC movements and an increased accuracy in dose delivery. Also, shorter treatment times may lead to fewer patient movement uncertainties. The accumulated MLC leakage dose is reduced, the patient specific quality assurance (QA) is more manageable and small field modeling inaccuracies are reduced. Pinnacle-3 (v8) plans are generated with direct machine parameter optimization (DMPO) for both scenarios. Three dimensional dose distributions and dose volume histograms are used to compare plan quality. We compare plans using few large MLC segments with those using many small MLC segments for some clinical cases. Improved plan quality is demonstrated using fewer MLC segments. Dose QAs are performed and compared for each scenario using MapCheck and film. When comparing dose delivery accuracy between different MU per segment settings, a decrease in delivery errors with minimum MU size is observed. In conclusion, few large MLC segments with larger area should be used when possible.

Gene network shaping of inherent noise spectra.

Recent work demonstrates that stochastic fluctuations in molecular populations have consequences for gene regulation. Previous experiments focused on noise sources or noise propagation through gene networks by measuring noise magnitudes. However, in theoretical analysis, we showed that noise frequency content is determined by the underlying gene circuits, leading to a mapping between gene circuit structure and the noise frequency range. An intriguing prediction from our previous studies was that negative autoregulation shifts noise to higher frequencies where it is more easily filtered out by gene networks--a property that may contribute to the prevalence of autoregulation motifs (for example, found in the regulation of approximately 40% of Escherichia coli genes). Here we measure noise frequency content in growing cultures of E. coli, and verify the link between gene circuit structure and noise spectra by demonstrating the negative autoregulation-mediated spectral shift. We further demonstrate that noise spectral measurements provide mechanistic insights into gene regulation, as perturbations of gene circuit parameters are discernible in the measured noise frequency ranges. These results suggest that noise spectral measurements could facilitate the discovery of novel regulatory relationships.

Usefulness of thallium-201 SPECT scintimammography to differentiate benign from malignant breast masses in mammographically dense breasts.

The purpose of this study was to assess the usefulness of thallium-201 (Tl-201) single-photon emission-computed tomography (SPECT) scintimammography to differentiate benign from malignant breast masses in 32 female Taiwanese patients with indeterminate mammographic probability of malignancy because of mammographically dense breasts. All breast masses were removed, and final histopathological diagnoses were obtained in all cases. The results showed that thallium-201 SPECT scintimammography findings were true-positive in 22 cases, false-positive in 1 case, true-negative in 7 cases, and false-negative in 2 cases. The diagnostic sensitivity, specificity, and accuracy were 91.7%, 87.5%, and 90.6%, respectively, for detecting breast cancer in mammographically dense breasts. In conclusion, thallium-201 SPECT scintimammography is a useful tool for differentiating benign from malignant breast masses in patients with indeterminate mammograms because of mammographically dense breasts.

The role of surgery and postoperative chemoradiation therapy in patients with lymph node positive esophageal carcinoma.

BACKGROUND: Patients who have undergone resection for lymph node positive esophageal carcinoma are at high risk of disease recurrence and early death. The role of postoperative adjuvant therapy in this population needs to be determined. METHODS: A retrospective review of all patients with resected esophageal carcinoma between 1991 and 1997 was performed. Lymph node positive (N1) patients who received concurrent or sequential postoperative radiotherapy (50 grays) and chemotherapy (cisplatin, 5-fluorouracil with or without epirubicin) were compared with N1 patients who underwent surgery alone. The disease free and overall survival rates were calculated using the Kaplan-Meier method, and groups were compared with the log-rank test. Prognostic variables were entered into a Cox regression model controlling for age, weight loss, T status, Eastern Cooperative Oncology Group (ECOG) score, and treatment received. RESULTS: A total of 165 patients were reviewed: Twenty-eight N1 patients underwent surgery alone (S group), and 38 N1 patients underwent surgery and received postoperative chemoradiation therapy (CRT group). Preoperative risk factors, tumor characteristics, ECOG scores, and lengths of hospital stay were similar. The disease free survival rates were similar (S group, 10.6 months; CRT group, 10.2 months), although the S group had more local disease recurrences (S group, 35%; CRT group, 13%; P = 0.09). The overall survival rate according to the Kaplan-Meier analysis showed a significant survival advantage with postoperative CRT radiation (log-rank test; P = 0.001). The median overall survival for the CRT group was 47.5 months, which was significantly longer than that of the S group (14.1 months). The ECOG score, T status, and treatment received all were found to influence survival significantly on univariate analysis. In the multivariate model, postoperative CRT was a predictor of survival (P = 0.007; risk ratio for mortality, 0.35; 95% confidence interval, 0.16-0.76) and was correlated with a significantly decreased risk of death in patients with lymph node positive, resected esophageal carcinoma. CONCLUSIONS: Postoperative CRT appears to prolong survival in patients with lymph node positive, resected esophageal carcinoma.

Compulsivity and obsessionality in opioid addiction.

Seventy-one individuals with opioid dependence undergoing ambulatory treatment participated in a personal interview assessing the importance of their opioid-use rituals, the severity of compulsivity and obsessionality in relation to their drug use, and the number of obsessive compulsive disorder (OCD) symptoms. The level of compulsivity and obsessionality in opioid dependence was comparable to that found in OCD and alcohol addiction. The importance of rituals was inversely related to the number of opioid lapses during rehabilitation treatment and positively correlated with the number of non-drug-related OCD symptoms. Based on established norms for OCD symptoms, we estimated that 11.4% of our sample would meet diagnostic criteria for OCD, a rate which is over 4 times higher than the rate of OCD in the general population.

Realism of confidence in obsessive-compulsive checkers.

The study examined whether obsessive-compulsive (OC) checkers have reduced confidence in their knowledge. OC checkers were compared with panic disorder (PD) patients and nonpatient controls using a calibration-of-knowledge procedure. Participants completed a general knowledge questionnaire, rated their confidence in each answer, and estimated the total number of correct answers. These responses were converted to 2 measures of confidence relative to performance--over/underconfidence and over/underestimation. OC checkers had lower scores than nonpatients did on both measures, whereas the PD patients did not differ from either group. For the OC checkers, relative confidence was inversely related to the severity of obsessions. The authors speculate that confidence may depend on a confirmation bias in testing hypotheses and that the reduced confidence in OC checkers may reflect a disconfirmation bias in this population.

Advantages of bias and prejudice: an exploration of their neurocognitive templates.

Bias is common in mental-processing tasks as diverse as target recognition, heuristic estimation and social judgment. This paper holds that cognitive biases stem from the covert operation of neural modules, which evolved to subserve adaptive behavior. Such modules can be innate or forged early in development. Research shows links between (i) biases in cognitive tasks and (ii) neural devices, which may mediate them. Evidence is included from biases that arise spontaneously in artificial neural networks during recognition/decision tasks. Two linked propositions follow. First, there are continuities in biasing strategies across different levels of cognitive processing. Second, a proclivity for stereotyping and prejudice depends on the biased functions of lower-level neural modules that promote adaptations to social environments. The propositions rest on evidence of biological preparedness for stereotyping and of deficits in social judgment in patients with neurological lesions. To test such claims, research studies are suggested at the boundary of cognitive neuroscience and social psychology. Advantages of bias and prejudice as evolved tools may include their: (1) speeding of scrutiny and improving of target detection in changing or uncertain situations; (2) aiding of a rapid choice of practical short-term rather than optimal longer term plans; (3) allowing appraisal of a workable world by creating fairly stable categories; (4) motivating of exploration and completion of problem-solving which might otherwise be abandoned too early. The biological priming of social biases need not mean that they are immutable; understanding them could lead to better ways of controlling them.