Evidence of novel Treponema phylotypes implicated in contagious ovine digital dermatitis and association of treponemes with major lameness causing foot pathogens.

In this study 269 swabs collected from 254 ovine foot lesions and 15 apparently healthy ovine feet were screened by PCR for the presence of major lameness causing foot pathogens viz. Treponema species, D. nodosus, F. necrophorum and T. pyogenes with the presumption that ovine foot lesion positive for Treponema species alone or in association with other three pathogens were categorized as contagious ovine digital dermatitis (CODD). While samples positive for D. nodosus alone or its combination with F. necrophorum and T. pyogenes were considered as footrot (FR) and samples in which F. necrophorum or T. pyogenes was found either alone or in combination were considered as interdigital dermatitis (ID). The overall occurrence of Treponema sp. in ovine foot lesions was 48.0%, and ranged from 33 to 58%. In Treponema positive samples D. nodosus, F. necrophorum and T. pyogenes were present in 34 (27.4%), 66 (54.4%) and 84 (68.5%) in contrast to Treponema negative samples in which these were present in 15 (11.1%), 20 (14.12%) and 17 (12.6%) samples, respectively. The data signifies that Treponema sp. are significantly associated with these foot pathogens and their different combinations with Treponema sp. influence the severity of CODD lesion. The identification of Treponema phylotypes was done by sequencing the 16S rRNA gene fragment of ten representative samples. Out of ten sequences, four (Trep-2, Trep-4, Trep-7 and Trep-10) were identical to Treponema sp. phylotype 1 (PT1) that belongs to phylogroup T. refringens-like, one sequence (Trep-1) was genetically close (90% sequence homology) to Treponema brennaborense while five sequences (Trep-3, Trep-5, Trep-6, Trep-8 and Trep-9) matched with uncultured bacterium clones of treponemes forming separate monophyletic group in phylogenetic tree and could represent new digital dermatitis phylogroup presently containing five ovine specific phylotypes. This is the first report on the presence of Treponema phylotypes other than three digital dermatitis (DD) Treponema phylogroups viz. T. phagedenis-like, T. medium/T. vincentii-like, and T. pedis-like that are frequently detected in CODD lesions. Metagenomic analysis of two representative samples revealed the abundance of genus Treponema in CODD lesion while this genus was absent in swab collected from clinically healthy foot suggesting that it might play primary role in producing CODD. These findings may further aid in understanding the etiopathogenesis of CODD and could help to develop appropriate treatment and mitigation strategies to combat the disease.

Automated chest radiography and mass systematic screening for tuberculosis.

BACKGROUND: Systematic screening for TB using automated chest radiography (ACR) with computer-aided detection software (CAD4TB) has been implemented at scale in Karachi, Pakistan. Despite evidence supporting the use of ACR as a pre-screen prior to Xpert® MTB/RIF diagnostic testing in presumptive TB patients, there has been no data published on its use in mass screening in real-world settings.METHOD: Screening was undertaken using mobile digital X-ray vehicles at hospital facilities and community camps. Chest X-rays were offered to individuals aged ≥15 years, regardless of symptoms. Those with a CAD4TB score of ≥70 were offered Xpert testing. The association between Xpert positivity and CAD4TB scores was examined using data collected between 1 January and 30 June 2018 using a custom-built data collection tool.RESULTS: Of the 127 062 individuals screened, 97.2% had a valid CAD4TB score; 11 184 (9.1%) individuals had a CAD4TB score ≥70. Prevalence of Xpert positivity rose from 0.7% in the <50 category to 23.5% in the >90 category. The strong linear association between CAD4TB score and Xpert positivity was found in both community and hospital settings.CONCLUSION: The strong association between CAD4TB scores and Xpert positivity provide evidence that an ACR-based pre-screening performs well when implemented at scale in a high-burden setting.

Immunotherapy utilization for hepatobiliary cancer in the United States: disparities among patients with different socioeconomic status.

BACKGROUND: Patients with advanced hepatobiliary cancer (HBC) have a dismal prognosis and limited treatment options. Immunotherapy has been considered as a promising treatment, especially for cancers not amenable to surgery. METHODS: Between 2004, and 2015, patients diagnosed with hepatocellular carcinoma (HCC), intra- and extrahepatic cholangiocarcinoma and gallbladder cancer (GBC) were identified in the National Cancer Database. RESULTS: Among 249,913 patients with HBC, only 585 (0.2%) patients received immunotherapy. Among patients who received immunotherapy, most patients were diagnosed between 2012 and 2015, had private insurance, as well as an income ≥$46,000 and were treated at an academic facility. The use of immunotherapy among HBC patients varied by diagnosis (HCC, 67.7%; bile duct cancer, 14%). On multivariable analysis, a more recent period of diagnosis (OR 1.80, 95% CI: 1.44-2.25), median income >$46,000 (OR 1.43, 95% CI: 1.11-1.87), and higher tumor stage (stage III, OR 2.22, 95% CI: 1.65-3.01; stage IV, OR 3.24, 95% CI: 2.41-4.34) were associated with greater odds of receiving immunotherapy. CONCLUSIONS: Overall utilization of immunotherapy in the US among patients with HBC was very low, yet has increased over time. Certain socioeconomic factors were associated with an increased likely of receiving immunotherapy, suggesting disparities in access of patients with lower socioeconomic status.

Variable characteristics of viscosity and thermal conductivity in peristalsis of magneto-Carreau nanoliquid with heat transfer irreversibilities.

BACKGROUND: Peristaltic is a basic way of fluid transportation in physiology, engineering and nuclear industry. Importance of peristalsis is due to its contraction and compulsion property of symmetric and asymmetric type channel walls. Another beauty of this mechanism is that the channel walls propagates and push the material along the tube/conduit channel walls. This mechanism shows its presence in physiology while food particles are transferred through esophagus and stomach, urine through intestines, spermatoza transportation in reproductive tract. In industry it is found in roller and finger pumps, drug delivery and various nuclear materials e.g. toxic, corrosive, noxious etc. Magnetic field in peristalsis is found helpful in treatment of various treatments using magnets. Actually earth and human body as a whole comprises of magnetic and electric fields. The medical specialists found that unbalances of electromagnetic field in human body is the reason for emotional and physical disturbance. In addition it has significant and potential utilizations in modification of medical, industrial and chemical, procedures for example MRI, evaporation, convection, thermoregulation, MHD throttles, and in various types of tumor treatments. Entropy production work out irreversibility in complex systems which are frequently encountered in industrial mechanisms. In view of that, this methodology is effectually implemented in distinct technological applications covering porous media, propulsion ducts, electronic cooling, turbo-machinery and combustion. METHOD: Modelled flow mechanism is nonlinear and coupled due to considered assumptions (i.e. nanofluid, nonlinear porous channel, mixed convection, variable viscosity and thermal conductivity, activation energy and chemical reaction). Such nonlinear and coupled system is difficult to tackle analytically. Thus to obtain the solution we employed RK algorithm for numerical simulations. RESULTS: Stronger magnetic parameter shows resistive characteristics to the flow field. Nonlinear Darcy medium assists the fluid motion at channel center and resits at walls vicinity. Variable characteristics of thermal conductivity moderate the soak or disperse up heat ability which corresponds to temperature reduction. Thermal slip quantity increase the temperature whereas concentration slip deduct the concentration of Carreau nanomaterial. Entropy and Bejan number shows maximum response for higher dissipation estimations. Brownian and thermopherotic motions aspects has reverse impact on nanomaterial concentration. CONCLUSION: Entropy and Bejan number deduces for higher variable thermal conductivity values. Carreau material variable enhance the entropy of the system as a whole.

Corrigendum to "Transport of hybrid type nanomaterials in peristaltic activity of viscous fluid considering nonlinear radiation, entropy optimization and slip effects" [Computer methods and programs in biomedicine 184 (2020) 105,086].

In this published paper, a mathematical modeling has been conducted for the peristaltic transport in flow of hybrid nanofluid between rotating channel in the presence of nonlinear thermal radiation, slip effects and entropy generation. This corrigendum correct the flow geometry, figures captions and plots "Transport of hybrid type nanomaterials in peristaltic activity of viscous fluid considering nonlinear radiation, entropy optimization and slip effects" [Computer Methods and Programs in Biomedicine 184 (2020) 105,086] where these mistake are occurred during production process and therefore, some captions are shuffled. The difference in the captions and plots however does not affect the authenticity and mathematical validity of the problem in purpose of this published research article is to investigate the peristaltic transport in flow of hybrid nanofluid between rotating channel subject to nonlinear thermal radiation, slip effects and entropy generation. However, the flow geometry and the captions and plots should be arranged.

Transport of hybrid type nanomaterials in peristaltic activity of viscous fluid considering nonlinear radiation, entropy optimization and slip effects.

BACKGROUND: In last few decades, a new class of working materials which comprises from two solid materials dispersed in a continuous phase liquid was established and deeply scrutinized. These materials are called hybrid nanomaterials. This research article aims to investigate entropy optimization in hybrid nanomaterial flow through a rotating peristaltic channel walls. Flow behavior is analyzed between the channels which is caused by propagation of sinusoidal waves. Viscosity of fluid is considered variable instead of constant characteristics. Fluid saturates through porous attributes of channel walls. Nonliear radiative flux and convective condition are considered. Slip conditions are imposed at the boundary of walls. METHODS: Built-in-Shooting technique is employed to obtain the numerical outcomes for the considered flow problem. RESULTS: Impacts of sundry variables on the entropy, temperature and velocity are scrutinized through different graphs. Numerical result presents that the axial velocity escalates with the inclusion of hybrid nanomaterial. The temperature of fluid enhances through higher estimations of hybrid nanoparticles. CONCLUSIONS: Here the flow behavior is discussed between the channels which are caused by propagation of sinusoidal waves with speed c. Entropy generation rate is minimum for variable viscosity and maximum for hybrid nanoparticles. Hybrid nanoparticles increase the temperature of fluid. Bejan number presents the similar impact for variable viscosity and thermal slip parameters. Temperature field decays through higher values of Brinkman number.

Phase I dose escalation study of the PI3kinase pathway inhibitor BKM120 and the oral poly (ADP ribose) polymerase (PARP) inhibitor olaparib for the treatment of high-grade serous ovarian and breast cancer.

Background: Based upon preclinical synergy in murine models, we carried out a phase I trial to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and biomarkers of response for the combination of BKM120, a PI3K inhibitor, and olaparib, a PARP inhibitor. Patients and methods: Olaparib was administered twice daily (tablet formulation) and BKM120 daily on a 28-day cycle, both orally. A 3 + 3 dose-escalation design was employed with the primary objective of defining the combination MTD, and secondary objectives were to define toxicities, activity, and pharmacokinetic profiles. Eligibility included recurrent breast (BC) or ovarian cancer (OC); dose-expansion cohorts at the MTD were enrolled for each cancer. Results: In total, 69 of 70 patients enrolled received study treatment; one patient never received study treatment because of ineligibility. Twenty-four patients had BC; 46 patients had OC. Thirty-five patients had a germline BRCA mutation (gBRCAm). Two DLTs (grade 3 transaminitis and hyperglycemia) were observed at DL0 (BKM120 60 mg/olaparib and 100 mg b.i.d.). The MTD was determined to be BKM120 50 mg q.d. and olaparib 300 mg b.i.d. (DL8). Additional DLTs included grade 3 depression and transaminitis, occurring early in cycle 2 (DL7). Anticancer activity was observed in BC and OC and in gBRCAm and gBRCA wild-type (gBRCAwt) patients. Conclusions: BKM120 and olaparib can be co-administered, but the combination requires attenuation of the BKM120 dose. Clinical benefit was observed in both gBRCAm and gBRCAwt pts. Randomized phase II studies will be needed to further define the efficacy of PI3K/PARP-inhibitor combinations as compared with a PARP inhibitor alone.

Tumor lysis syndrome after starting treatment with Gleevec in a patient with chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is one of the myeloproliferative disorders. It accounts for 15-20% of all leukemias in adults. The mainstay of diagnosis is the detection of Philadelphia chromosome or one of its products. Tyrosine kinase inhibitors changed the paradigm of treating such disease with the good responses. However, they do have side effects. In our case we will report tumor lysis syndrome happening after starting Imatinib myselate. We did a literature review and looked all the cases that documented this complication.

Surveillance for risk factors of cardiovascular disease among an industrial population in southern India.

BACKGROUND: We assessed (i) the risk of cardiovascular disease in an industrial population in Chennai, southern India and (ii) whether the status of treatment and control of diabetes and hypertension would be different in an industrial population, which is provided free healthcare, compared with the general population of Chennai. METHODS: Subjects residing in the residential areas of 2 industries (Indian Airlines and Integral Coach Factory) in Chennai in southern India were recruited. The subjects were employees (n = 440) selected by an age- and sex-stratified random sampling method, and their family members (n = 727) in the age group of 20-69 years; a total of 1167 subjects. Fasting plasma glucose, lipid estimations and anthropometric measurements were done in all the subjects. Information on demographic and lifestyle determinants was obtained using a questionnaire. Diabetes was diagnosed using the American Diabetes Association criteria and metabolic syndrome was defined by the Adult Treatment Panel III criteria with modified waist definition for Asian Indians. RESULTS: Age-adjusted prevalence of major risk factors for cardiovascular disease using the 2001 Census of India were as follows: diabetes 11.9%; hypertension 25.4%; dyslipidaemia 40.2%; hypertriglyceridaemia 28.3%; overweight (body mass index > or = 23 kg/m2) 60.2%; and metabolic syndrome 34.1%. Use of tobacco in any form was present in 22.9% of men and 0.5% of women; 79% of the subjects followed a sedentary lifestyle. Among subjects receiving medication, 42.1% of subjects with diabetes and 55.3% of subjects with hypertension had their disease under adequate control. A comparison of these results with the general population of Chennai showed that the industrial population had a higher prevalence of cardiovascular risk factors in spite of having better access to healthcare facilities. CONCLUSIONS: The prevalence of cardiovascular disease was high in this industrial population of Chennai. Although the overall treatment and control of diabetes and hypertension was better than that in the general population, it was still inadequate and this emphasizes the need for greater awareness about non-communicable diseases.

Prevalence, awareness and control of hypertension in Chennai--The Chennai Urban Rural Epidemiology Study (CURES-52).

OBJECTIVE: To study the prevalence, awareness and control of hypertension in Chennai representing Urban South India. METHODS: The Chennai Urban Rural Epidemiology Study (CURES) is one of the largest epidemiological studies on diabetes carried out in India, where 26,001 individuals aged > or = 20 years were screened using systematic random sampling method. Every tenth subject recruited in Phase 1 of CURES was requested to participate in Phase 3 of CURES and the response rate was 2,350/26,001 or 90.4%. An oral glucose tolerance test was performed in all individuals except self-reported diabetic subjects. Anthropometric measurements and lipid estimations were done in all subjects. Hypertension was diagnosed in all subjects who were on drug treatment for hypertension or if the blood pressure > or = 140/90 mmHg. RESULTS: Hypertension was present in 20% [men:23.2% vs. women:17.1%, p<0.001] of the study population. Isolated systolic hypertension (Systolic BP > or = 140 and Diastolic BP<90 mmHg) was present in 6.6% while isolated diastolic hypertension (DBP > or = 90 and SBP<140 mmHg) was present in 4.2% of the population. Among the elderly population (aged > or = 60 years), 25.2% had isolated systolic hypertension. Age, body mass index, smoking, serum cholesterol and triglycerides were found to be strongly associated with hypertension. Among the total hypertensive subjects, only 32.8% were aware of their blood pressure, of these, 70.8% were under treatment and 45.9% had their blood pressure under control. CONCLUSION: Hypertension was present in one-fifth of this urban south Indian population and isolated systolic hypertension was more common among elderly population. Majority of hypertensive subjects still remain undetected and the control of hypertension is also inadequate. This calls for urgent prevention and control measures for hypertension.

Secular trends in the prevalence of diabetes and impaired glucose tolerance in urban South India--the Chennai Urban Rural Epidemiology Study (CURES-17).

AIMS/HYPOTHESIS: The aim of this study was to determine the secular trends in prevalence of diabetes and IGT in urban India. MATERIALS AND METHODS: The Chennai Urban Rural Epidemiology Study (CURES) screened 26,001 individuals aged > or =20 years using the American Diabetes Association fasting capillary glucose criteria. The study population, which was representative of Chennai, was recruited by systematic random sampling. Every tenth subject from Phase 1 of CURES was invited to participate in Phase 3 for screening by World Health Organization (WHO) plasma glucose criteria. The response rate was 90.4% (2,350 responders from 2,600 potential subjects). The prevalences of diabetes and IGT in CURES were compared with three earlier studies: two conducted on a representative population of Chennai in 1989 and 1995, and the other the National Urban Diabetes Survey (NUDS) completed in 2000. RESULTS: The overall crude prevalence of diabetes using WHO criteria in CURES was 15.5% (age-standardised 14.3%), while that of IGT was 10.6% (age-standardised 10.2%). Prevalence of diabetes increased by 39.8% (8.3-11.6%) from 1989 to 1995; by 16.3% (11.6-13.5%) between 1995 and 2000; and by 6.0% (13.5-14.3%) between 2000 and 2004. Thus within a span of 14 years, the prevalence of diabetes increased by 72.3% (chi (2) trend 22.23, p < 0.0001). The prevalence of IGT increased by 9.6% from 1989 to 1995 and by 84.6% between 1995 and 2000 (chi 2 trend 52.9, p < 0.0001). However, it decreased by 39.3% between 2000 and 2004 (p < 0.0001). There was a shift in the age at diagnosis of diabetes to a younger age in CURES compared with NUDS. CONCLUSIONS/INTERPRETATION: Compared with earlier studies, the prevalence of diabetes in Chennai, representing urban India, has increased while that of IGT has decreased.

Modeling gas adsorption and transport in small-pore titanium silicates.

Engelhard titanium silicate, ETS-4, is a promising new adsorbent for size-selective separation of mixtures of small gases, a leading industrially important example of which is methane-nitrogen separation. Single component equilibrium and kinetics of oxygen, nitrogen, and methane adsorption in Na-ETS-4 and cation-exchanged Sr-ETS-4, measured in an earlier study over a wide range of temperatures and pressures, are analyzed in this study. The adsorbent crystals were synthesized and pelletized under pressure (without any binder), thus giving rise to a bidispersed pore structure with controlling resistance in the micropores. Change in equilibrium and kinetics of adsorption of the aforementioned gases in Sr-ETS-4 due to pore shrinkage with progressively increasing dehydration temperature has also been investigated. Differential uptakes have been measured at various levels of adsorbate loading, which has allowed the elucidation of the nature of concentration dependence of micropore diffusivity. Both homogeneous and heterogeneous models are examined on the equilibrium data, while a bidispersed pore diffusion model is able to capture the differential uptakes very well. On the basis of chemical potential gradient as the driving force for diffusion, the impact of isotherm models on the concentration dependence of micropore diffusivity is also analyzed. It is shown that pore tailoring at the molecular scale by dehydration can improve the kinetic selectivity of nitrogen over methane in Sr-ETS-4 to a promising level. The models investigated are evaluated to identify essential details necessary to reliably simulate a methane-nitrogen separation process using the promising new Sr-ETS-4 adsorbent.

A heterogeneous model for gas transport in carbon molecular sieves.

A dual resistance model with distribution of either barrier or pore diffusional activation energy is proposed in this work for gas transport in carbon molecular sieve (CMS) micropores. This is a novel approach in which the equilibrium is homogeneous, but the kinetics is heterogeneous. The model seems to provide a possible explanation for the concentration dependence of the thermodynamically corrected barrier and pore diffusion coefficients observed in previous studies from this laboratory on gas diffusion in CMS. The energy distribution is assumed to follow the gamma distribution function. It is shown that the energy distribution model can fully capture the behavior described by the empirical model established in earlier studies to account for the concentration dependence of thermodynamically corrected barrier and pore diffusion coefficients. A methodology is proposed for extracting energy distribution parameters, and it is further shown that the extracted energy distribution parameters can effectively predict integral uptake and column breakthrough profiles over a wide range of operating pressures.

Identification of a novel zinc finger gene, zf5-3, as a potential mediator of neuroblastoma differentiation.

We established a unique parental neuroblastoma cell line, NUB-7, which mimics the bipotentiality of neuroblastoma in vivo along neuronal and Schwann cell lineages following dibutyryl cAMP and retinoic acid treatments, respectively. Differential display identified a putative novel zinc finger gene as a potential differentiation-responsive gene coincident with retinoic acid treatment of NUB-7. This cDNA clone, now designated zf5-3, was mapped to chromosome 19 using somatic cell hybrids, and a larger cDNA clone further localized this gene to band 13.1-13.2 by fluorescent in situ hybridization. zf5-3 possesses 4 characteristic zinc finger DNA-binding motifs as determined by its nucleic acid and proposed amino acid sequence. Expression of zf5-3 is restricted to fetal neuronal, hepatic and renal tissues and their tumor-derived cell lines, including 8/9 neuroblastomas and 2/2 malignant rhabdoid tumors of kidney. The restricted expression in the kidney of zf5-3 to collecting tubules and ureter epithelium is suggestive of an ectodermal histogenesis of malignant rhabdoid tumors of kidney. During development of the fetal human brain, high levels of zf5-3 mRNA are restricted to the mitotically active, undifferentiated neuroblasts. Morphological evidence of overt differentiation was generally accompanied by a marked loss in zf5-3 expression. Therefore, the neuronal tissue expression profile and the down-regulation coincident with retinoic acid-induced neuroblastoma maturation implicate zf5-3 as a potential mediator of their differentiation.

Determination of cis-thymine glycol in DNA by gas chromatography-mass spectrometry with selected ion recording and multiple reaction monitoring.

A novel method for the determination of cis-thymine glycol in DNA has been developed, using gas chromatography-mass spectrometry with selected ion recording or multiple reaction monitoring. The procedure involves acidic hydrolysis of DNA in the presence of the internal standard cis-[2H3]thymine glycol, followed by derivatisation with N-methyl-N-(tert.-butyldimethylsilyl)trifluoroacetamide. The method was validated on DNA that had been oxidatively modified in vitro by radiation treatment, and was then applied to determine cis-thymine glycol in human placental DNA. Background levels of 5.45+/-2.98 ng cis-thymine glycol/mg DNA were observed in the human samples.