Assessment of Heavy Metal Toxicity in Four Species of Freshwater Ciliates (Spirotrichea:Ciliophora) from Delhi, India

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Tubular epithelial cells in renal clear cell carcinoma express high RIPK1/3 and show increased susceptibility to TNF receptor 1-induced necroptosis.

We previously reported that renal clear cell carcinoma cells (RCC) express both tumor necrosis factor receptor (TNFR)-1 and -2, but that, in organ culture, a TNF mutein that only engages TNFR1, but not TNFR2, causes extensive cell death. Some RCC died by apoptosis based on detection of cleaved caspase 3 in a minority TUNEL-positive cells but the mechanism of death in the remaining cells was unexplained. Here, we underpin the mechanism of TNFR1-induced cell death in the majority of TUNEL-positive RCC cells, and show that they die by necroptosis. Malignant cells in high-grade tumors displayed threefold to four fold higher expression of both receptor-interacting protein kinase (RIPK)1 and RIPK3 compared with non-tumor kidney tubular epithelium and low-grade tumors, but expression of both enzymes was induced in lower grade tumors in organ culture in response to TNFR1 stimulation. Furthermore, TNFR1 activation induced significant MLKL(Ser358) and Drp1(Ser616) phosphorylation, physical interactions in RCC between RIPK1-RIPK3 and RIPK3-phospho-MLKL(Ser358), and coincidence of phospho-MLKL(ser358) and phospho-Drp1(Ser616) at mitochondria in TUNEL-positive RCC. A caspase inhibitor only partially reduced the extent of cell death following TNFR1 engagement in RCC cells, whereas three inhibitors, each targeting a different step in the necroptotic pathway, were much more protective. Combined inhibition of caspases and necroptosis provided additive protection, implying that different subsets of cells respond differently to TNF-α, the majority dying by necroptosis. We conclude that most high-grade RCC cells express increased amounts of RIPK1 and RIPK3 and are poised to undergo necroptosis in response to TNFR1 signaling.National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre , Kidney Research UK and NIH grant R01-HL36003.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Nature Publishing Group

Simulated Changes in Storm Morphology Associated with a Sea-Breeze Air Mass

The central east coast of Australia is frequently impacted by large hail and damaging winds associated with severe convective storms, with individual events recording damages exceeding AUD 1 billion. These storms present a significant challenge for forecasting because of their development in seemingly marginal environments. They often have been observed to intensify upon approaching the coast, with case studies and climatological analyses indicating that interactions with the sea breeze are key to this process. The relative importance of the additional lifting and vorticity along the sea-breeze front in comparison with the change to a cooler, moister air mass with stronger low-level shear behind the front has yet to be investigated. Here, the role of the sea-breeze air mass is isolated using idealized numerical simulations of storms developing in a horizontally homogeneous environment. The base-state substitution (BSS) modeling technique is utilized to introduce the sea-breeze air mass following initial storm development. Relative to a simulation without BSS, the storm is longer lived and more intense, ultimately developing supercell characteristics including increased updraft rotation, deviant motion to the left of the mean wind vector, and a strong reflectivity gradient on the inflow edge. Separately simulating the changes in the thermodynamic and wind fields reveals that the enhanced storm longevity and intensity are primarily due to the latter. The change in the low-level environmental winds slows gust-front propagation, allowing the storm to continue to ingest warm, potentially buoyant environmental air. At the same time, increased low-level shear promotes the development of persistent updraft rotation that causes the storm to make a transition from a multicell to a supercell

Effects of seasonal and pandemic influenza on health-related quality of life, work and school absence in England: results from the Flu Watch cohort study

BACKGROUND: Estimates of health-related quality of life (HRQoL) and work/school absences for influenza are typically based on medically-attended cases or those meeting influenza-like-illness (ILI) case definitions, and thus biased towards severe disease. Although community influenza cases are more common, estimates of their effects on HRQoL and absences are limited. OBJECTIVES: To measure Quality-Adjusted Life Days and Years (QALDs and QALYs) lost and work/school absences among community cases of acute respiratory infections (ARI), ILI and influenza A and B and to estimate community burden of QALY loss and absences from influenza. PATIENTS/ METHODS: Flu Watch was a community cohort in England from 2006-2011. Participants were followed-up weekly. During respiratory illness they prospectively recorded daily symptoms, work/school absences and EQ-5D-3L data and submitted nasal swabs for RT-PCR influenza testing. RESULTS: Average QALD lost was 0.26, 0.93, 1.61 and 1.84 for ARI, ILI, H1N1pdm09 and influenza B cases respectively. 40% of influenza A cases and 24% of influenza B cases took time off work/school with an average duration of 3.6 days and 2.4 days respectively. In England, community influenza cases lost 24,300 QALYs in 2010/11 and had an estimated 2.9 million absences per season based on data from 2006/07 - 2009/10. CONCLUSIONS: Our QALDs and QALYs lost and work and school absence estimates are lower than previous estimates because we focus on community cases, most of which are mild, may not meet ILI definitions and do not result in healthcare consultations. Nevertheless, they contribute a substantial loss of HRQoL on a population level. This article is protected by copyright. All rights reserved

Metabolomics demonstrates divergent responses of two Eucalyptus species to water stress

Past studies of water stress in Eucalyptus spp. generally highlighted the role of fewer than five “important” metabolites, whereas recent metabolomic studies on other genera have shown tens of compounds are affected. There are currently no metabolite profiling data for responses of stress-tolerant species to water stress. We used GC–MS metabolite profiling to examine the response of leaf metabolites to a long (2 month) and severe (Ψpredawn < −2 MPa) water stress in two species of the perennial tree genus Eucalyptus (the mesic Eucalyptus pauciflora and the semi-arid Eucalyptus dumosa). Polar metabolites in leaves were analysed by GC–MS and inorganic ions by capillary electrophoresis. Pressure–volume curves and metabolite measurements showed that water stress led to more negative osmotic potential and increased total osmotically active solutes in leaves of both species. Water stress affected around 30–40% of measured metabolites in E. dumosa and 10–15% in E. pauciflora. There were many metabolites that were affected in E. dumosa but not E. pauciflora, and some that had opposite responses in the two species. For example, in E. dumosa there were increases in five acyclic sugar alcohols and four low-abundance carbohydrates that were unaffected by water stress in E. pauciflora. Re-watering increased osmotic potential and decreased total osmotically active solutes in E. pauciflora, whereas in E. dumosa re-watering led to further decreases in osmotic potential and increases in total osmotically active solutes. This experiment has added several extra dimensions to previous targeted analyses of water stress responses in Eucalyptus, and highlights that even species that are closely related (e.g. congeners) may respond differently to water stress and re-waterin

No man’s land: information needs and resources of men with metastatic castrate resistant prostate cancer

The majority of men treated for prostate cancer will eventually develop castrate resistant disease (CRPC) with metastases (mCRPC). There are several options for further treatment: chemotherapy, third-line hormone therapy, radium, immunotherapy and palliation. Current ASCO guidelines for survivors of prostate cancer recommend that an individual’s information needs at all stages of disease are assessed, and that patients are provided with or referred to the appropriate sources for information and support. Earlier reviews have highlighted the dearth of such services and we wished to see if the situation had improved more recently. Unfortunately we conclude that there is still a lack of good quality congruent information easily accessible specifically for men with mCRPC and insufficient data regarding the risks, harms and benefits of different management plans. More research providing a clear evidence base about treatment consequences using patient reported outcome measures is required

A systematic approach to performing a comprehensive transesophageal echocardiogram. A call to order

<p>Abstract</p> <p>Background</p> <p>While the order for a clinical transthoracic examination is fairly standardized, there is considerable variability between laboratories and even among physicians in the same laboratory with regard to the order for transesophageal echocardiograms (TEE). A systematic approach is desirable for more efficient use of physician and patient time, avoidance of inadvertent omission of important views, and to facilitate study review.</p> <p>Methods</p> <p>We propose a standardized approach to TEE data acquisition in which cardiac structures are systematically identified and characterized at sequential positions and imaging planes to facilitate organized, efficient and comprehensive assessment.</p> <p>Results</p> <p>Our approach to TEE study begins in the mid-esophagus with the imaging plane at 0°. Based on the specific indication for the TEE, a cardiac structure (e.g., mitral valve, left atrial appendage, or interatrial septum) is chosen as the primary focal point for a comprehensive, multiplane analysis. This structure is assessed in 20° – 30° increments as the imaging plane is advanced from 0° to 165°. Using the aortic valve as a reference point, pertinent cardiac structures are then assessed as the imaging plane is reduced to 135°, to 90°, to 40 – 60° and then back to 0°. The probe is then advanced into the stomach to obtain transgastric images at 0°, 90°, and 120°. Finally, the thoracic aorta and pulmonary artery are assessed as the probe is withdrawn from the body. Using this method, an organized and comprehensive TEE can be performed in 10 – 15 minutes.</p> <p>Conclusion</p> <p>A standardized and systematic TEE approach is described for efficient and comprehensive TEE study.</p

Oneida nation of New York: health needs assessment 1990

This is the report of a health needs assessment for the Oneida Indian Nation of New York (ONNY). This needs assessment was conducted in order to collect population-based data related to behavioral risks and reproductive health for Oneida males and females. The survey of the Oneida was initiated because there is almost no risk factor data available on Indian tribes of the northeast, and none available for the Oneida Nation of New York. There are four primary goals for the 1990 Oneida Nation Health Needs Assessment. They are 1) to collect behavioral risk factor and reproductive health data for adult Oneida Nation members living on or near Oneida Nation lands, 2) to assess the current basic health needs of the ONNY, 3) to document the medical providers and hospitals which are currently being utilized by the Nation members and. 4) to develop recommendations for use by health planners from this baseline data.The Oneida Nation Health Needs Assessment (ONHNA) was carried out among enrolled members of the Oneida Nation who were 18 years of age and older who lived in the six counties that are contiguous to the Oneida Nation lands. The Nation Enrollment List was used to identify the Oneida population located in the six-county area. The choice to interview only adults was made to avoid legal difficulties in interviewing minors. Interviewing was conducted in each household face-to-face rather than using mailed questionnaires or telephone contact. All interviewers were enrolled Oneida Nation members. Interviews were conducted by interviewers of the same sex as the respondent. All interviewers participated in one week of training prior to the start of the field work. Four types of data were collected. First, the behavioral risk factors surveyed were related to the 10 leading causes of death in the United States. Behavioral factors include seat belt usage, physical exercise, diet, cigarette and smokeless tobacco usage, alcohol consumption, and the existence of high blood pressure. The second data set included health needs. The survey questions dealt with the prevalence of current diseases and health problems among the Oneidas, and with whether the Oneida people have routine screening tests such as cholesterol, diabetes, and hypertension, and eye exams, pap smears, breast exams, and rectal exams. The third set of data questions focused on reproductive health factors. Questions covered topics such as fertility, contraception, and general maternal-child health conditions. The fourth and final set of questions gathered data on health care utilization. This data will be used to establish health provider contracts with physicians, dentists, pediatricians, and hospitals to provide quality health care for a more reasonable cost. For each risk factor, comparisons were made between the Oneida Nation and data from the 1988 New York State Behavioral Risk Factor Survey.The individual completion rates were 54% for females and 69% for males for a total of 211 respondents in all. The following is an abbreviated summary of selected data from the survey. Seat belt use was only slightly lower than for all New Yorkers. Non-use was highest among young drivers. Sixty percent of Oneida males and 78 percent of Oneida females reported having their blood pressure taken within a year of the survey. All Oneida members were more active physically than the general New York population. However, all Oneida members were more likely to be overweight by comparison Forty percent of all Oneida people are smokers compared to 25 percent of the New York population. Fifty-seven percent of Oneida males and 32 percent of Oneida females are classified as acute and heavy drinkers. Percentages for regular health checks across all factors vary considerably among the Oneida people. Several areas of concern were identified including cholesterol checks, diabetes screening, rectal exams and mammograms. The completed fertility of the Oneida women in this survey is 2.1 children which is lower than that of all U.S. women surveyed in the 1980 census. Female sterilization is the most prevalent contraceptive method among Oneida women. as it is among the general U.S. population.With respect to behavioral risks, cigarette smoking and alcohol consumption are of major concern. This impacts on concerns for overall reproductive health. The task now is to identify the highest priority objectives and to secure resources needed to accomplish these tasks

Vestibular Facilitation of Optic Flow Parsing

Simultaneous object motion and self-motion give rise to complex patterns of retinal image motion. In order to estimate object motion accurately, the brain must parse this complex retinal motion into self-motion and object motion components. Although this computational problem can be solved, in principle, through purely visual mechanisms, extra-retinal information that arises from the vestibular system during self-motion may also play an important role. Here we investigate whether combining vestibular and visual self-motion information improves the precision of object motion estimates. Subjects were asked to discriminate the direction of object motion in the presence of simultaneous self-motion, depicted either by visual cues alone (i.e. optic flow) or by combined visual/vestibular stimuli. We report a small but significant improvement in object motion discrimination thresholds with the addition of vestibular cues. This improvement was greatest for eccentric heading directions and negligible for forward movement, a finding that could reflect increased relative reliability of vestibular versus visual cues for eccentric heading directions. Overall, these results are consistent with the hypothesis that vestibular inputs can help parse retinal image motion into self-motion and object motion components

Early and efficient detection of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures.

Early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings. In a developing-country setting, we prospectively evaluated two methods for culturing and detecting M. tuberculosis in sputum. Sputum samples were cultured in liquid assay (micro broth culture) in microplate wells and growth was detected by microscopic observation, or in Löwenstein-Jensen (LJ) solid media where growth was detected by visual inspection for colonies. Sputum samples were collected from 321 tuberculosis (TB) suspects attending Bugando Medical Centre, in Mwanza, Tanzania, and were cultured in parallel. Pulmonary tuberculosis cases were diagnosed using the American Thoracic Society diagnostic standards. There were a total of 200 (62.3%) pulmonary tuberculosis cases. Liquid assay with microscopic detection detected a significantly higher proportion of cases than LJ solid culture: 89.0% (95% confidence interval [CI], 84.7% to 93.3%) versus 77.0% (95% CI, 71.2% to 82.8%) (p = 0.0007). The median turn around time to diagnose tuberculosis was significantly shorter for micro broth culture than for the LJ solid culture, 9 days (interquartile range [IQR] 7-13), versus 21 days (IQR 14-28) (p<0.0001). The cost for micro broth culture (labor inclusive) in our study was US $4.56 per sample, versus US$11.35 per sample for the LJ solid culture. The liquid assay (micro broth culture) is an early, feasible, and inexpensive method for detection of pulmonary tuberculosis in resource limited settings