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1,836 result(s) for "Werner, Robert"
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The solid angle hidden in polyhedron gravitation formulations
Formulas of a homogeneous polyhedron’s gravitational potential typically include two arctangent terms for every edge of every face and a special term to eliminate a possible facial singularity. However, the arctangent and singularity terms are equivalent to the face’s solid angle viewed from the field point. A face’s solid angle can be evaluated with a single arctangent, saving computation.
ACTB, CDKN1B, GAPDH, GRB2, RHOA and SDCBP Were Identified as Reference Genes in Neuroendocrine Lung Cancer via the nCounter Technology
Neuroendocrine lung cancer (NELC) represents 25% of all lung cancer cases and large patient collectives exist as formalin-fixed, paraffin-embedded (FFPE) tissue only. FFPE is controversially discussed as source for molecular biological analyses and reference genes for NELC are poorly establishes. Forty-three representative FFPE-specimens were used for mRNA expression analysis using the digital nCounter technology (NanoString). Based on recent literature, a total of 91 mRNA targets were investigated as potential tumor markers or reference genes. The geNorm, NormFinder algorithms and coefficient of correlation were used to identify the most stable reference genes. Statistical analysis was performed by using the R programming environment (version 3.1.1). RNA integrity (RIN) ranged from 1.8 to 2.6 and concentrations from 34 to 2,109 ng/μl. However, the nCounter technology gave evaluable results for all samples tested. ACTB, CDKN1B, GAPDH, GRB2, RHOA and SDCBP were identified as constantly expressed genes with high stability (M-)values according to geNorm, NormFinder and coefficients of correlation. FFPE-derived mRNA is suitable for molecular biological investigations via the nCounter technology, although it is highly degraded. ACTB, CDKN1B, GAPDH, GRB2, RHOA and SDCBP are potent reference genes in neuroendocrine tumors of the lung.
miRNA regulation is important for DNA damage repair and recognition in malignant pleural mesothelioma
Platin-containing regimes are currently considered as state-of-the-art therapies in malignant pleural mesotheliomas (MPM) but show dissatisfying response rates ranging from 6 to 16% only. Still, the reasons for the rather poor efficacy remain largely unknown. A clear stratification of patients based on new biomarkers seems to be a promising approach to enhance clinical management, which would be a long-needed improvement for MPM patients but does not seem likely soon unless new biomarkers can be validated. Twenty-four formalin-fixed, paraffin-embedded (FFPE) tumour specimens were subjected to a miRNA expression screening of 800 important miRNAs using digital quantification via the nCounter technique (NanoString). We defined a small subset of miRNAs regulating the key enzymes involved in the repair of platin-associated DNA damage. Particularly, the TP53 pathway network for DNA damage recognition as well as genes related to the term “BRCAness” are the main miRNA targets within this context. The TP53 pathway network for DNA damage recognition as well as genes related to the term “BRCAness” are the main players for risk stratification in patients suffering from this severe disease. Taking the specific molecular profile of the tumour into account can help to enhance the clinical management prospectively and to smooth the way to better response prediction.
Effect of Small-Molecule Natural Compounds on Pathologic Mast Cell/Basophil Activation in Allergic Diseases
Pathologic mast cells and basophils, key effector cells in allergic reactions, play pivotal roles in initiating and perpetuating IgE-mediated allergic responses. Conventional therapies for allergies have limitations, prompting exploration into alternative approaches such as small-molecule natural compounds derived from botanical sources. This review synthesizes the existing literature on the effects of these compounds on pathologic mast cells and basophils, highlighting their potential in allergy management, and utilizes the PubMed database for literature acquisition, employing keyword-based searches to identify relevant peer-reviewed sources. Additionally, mechanistic insights were evaluated to contextualize how small-molecule natural compounds can inhibit mast cell/basophil activation, degranulation, and signaling pathways crucial for IgE-mediated allergic reactions. Small-molecule natural compounds exhibit promising anti-allergic effects, yet despite these findings, challenges persist in the development and translation of natural compound-based therapies, including bioavailability and standardization issues. Future research directions include optimizing dosing regimens, exploring synergistic effects with existing therapies, and employing systems pharmacology approaches for a holistic understanding of their mechanisms of action. By harnessing the therapeutic potential of small-molecule natural compounds, effective treatments for allergic diseases may be realized, offering hope for individuals with allergies.
An Investigation of Modifying Effects of Metallothionein Single-Nucleotide Polymorphisms on the Association between Mercury Exposure and Biomarker Levels
Background: Recent studies have suggested that several genes that mediate mercury metabolism are polymorphic in humans. Objective: We hypothesized that single-nucleotide polymorphisms (SNPs) in metallothionein (MT) genes may underlie interindividual differences in mercury biomarker levels. We studied the potential modifying effects of MT SNPs on mercury exposure-biomarker relationships. Methods: We measured total mercury in urine and hair samples of 515 dental professionals. We also surveyed occupational and personal exposures to dental amalgam and dietary fish consumption, from which daily methyimercury (MeHg) intake was estimated. Log-transformed urine and hair levels were modeled in multivariable linear regression separately against respective exposure surrogates, and the effect modification of 13 MT SNPs on exposure was investigated. Results: The mean mercury levels in urine (1.06 μg/L) and hair (0.51 μg/g) were not significantly different from the U.S. general population (0.95 μg/L and 0.47 μg/g, respectively). The mean estimated daily MeHg intake was 0.084 μg/kg/day (range, 0-0.98 μg/kg/day), with 25% of study population intakes exceeding the current U.S. Environmental Protection Agency reference dose of 0.1 μg/kg/day. Multivariate regression analysis showed that subjects with the MT1M (rs2270836) AA genotype (n = 10) or the MT2A (rs 10636) CC genotype (n = 42) had lower urinary mercury levels than did those with the MT1Mot MT2A GG genotype (n = 329 and 251, respectively) after controlling for exposure and potential confounders. After controlling for MeHg intake, subjects with MT1A (rs8052394) GA and GG genotypes (n = 24) or the MT1M (rs9936741) TT genotype (n = 459) had lower hair mercury levels than did subjects with MT1A AA (n = 113) or MT1MTC and CC genotypes (n = 15), respectively. Conclusion: Our findings suggest that some MT genetic polymorphisms may influence mercury biomarker concentrations at levels of exposure relevant to the general population.
Peptide YY (PYY) Is Associated with Cardiovascular Risk in Patients with Acute Myocardial Infarction
Aims: Recent studies have found circulating concentrations of the gastrointestinal hormone GLP-1 to be an excellent predictor of cardiovascular risk in patients with myocardial infarction. This illustrates a yet not appreciated crosstalk between the gastrointestinal and cardiovascular systems, which requires further investigation. The gut-derived hormone Peptide YY (PYY) is secreted from the same intestinal L-cells as GLP-1. Relevance of PYY in the context of cardiovascular disease has not been explored. In this study, we aimed to investigate PYY serum concentrations in patients with acute myocardial infarction and to evaluate their association with cardiovascular events. Material and Methods: PYY levels were assessed in 834 patients presenting with acute myocardial infarction (553 Non-ST-Elevation Myocardial Infarction (NSTEMI) and 281 ST-Elevation Myocardial Infarction (STEMI)) at the time of hospital admission. The composite outcomes of first occurrence of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke (3-P-MACE), and all-cause mortality were assessed with a median follow-up of 338 days. Results: PYY levels were significantly associated with age and cardiovascular risk factors, including hypertension, diabetes, and kidney function in addition to biomarkers of heart failure (NT-pro BNP) and inflammation (hs-CRP). Further, PYY was significantly associated with 3-P-MACE (HR: 1.7; 95% CI: 1–2.97; p = 0.0495) and all-cause mortality (HR: 2.69; 95% CI: 1.61–4.47; p = 0.0001) by univariable Cox regression analyses, which was however lost after adjusting for multiple confounders. Conclusions: PYY levels are associated with parameters of cardiovascular risk as well as cardiovascular events and mortality in patients presenting with acute myocardial infarction. However, this significant association is lost after adjustment for further confounders.
Evaluation of Work-Related Carpal Tunnel Syndrome
Carpal tunnel syndrome (CTS) is common in the industrial setting but there are still some advocates who argue that CTS is not a work related problem. There are also controversies about the proper way to establish the diagnosis and whether screening for CTS in the industrial setting is warranted. A comprehensive literature review. The literature does demonstrate that the prevalence of CTS in the industrial setting is significantly higher than in the general population. Numerous epidemiologic studies have identified independent risk factors, which include repetitiveness of work, forceful exertions, mechanical stress, posture, and vibration as well as several personal co-factors. The strength of these associations are discussed. The diagnostic criteria for establishing work-related CTS are discussed as well as the effectiveness of various screening methods that are commonly used in the workplace. The sensitivity and specificity of nerve conduction studies to establish or confirm the diagnosis of CTS is presented along with normative data for the industrial worker. CTS has both work-related and personal risk factors. The diagnosis is best established using a combination of history, symptom distribution and confirmation using the relative latency of median sensory testing using normative data. Screening for CTS in the industrial setting has questionable benefit.
Compliance with referral of sick children: a survey in five districts of Afghanistan
Background Recognition and referral of sick children to a facility where they can obtain appropriate treatment is critical for helping reduce child mortality. A well-functioning referral system and compliance by caretakers with referrals are essential. This paper examines referral patterns for sick children, and factors that influence caretakers’ compliance with referral of sick children to higher-level health facilities in Afghanistan. Methods The study was conducted in 5 rural districts of 5 Afghan provinces using interviews with parents or caretakers in 492 randomly selected households with a child from 0 to 2 years old who had been sick within the previous 2 weeks with diarrhea, acute respiratory infection (ARI), or fever. Data collectors from local nongovernmental organizations used a questionnaire to assess compliance with a referral recommendation and identify barriers to compliance. Results The number of referrals, 99 out of 492 cases, was reasonable. We found a high number of referrals by community health workers (CHWs), especially for ARI. Caretakers were more likely to comply with referral recommendations from community members (relative, friend, CHW, traditional healer) than with recommendations from health workers (at public clinics and hospitals or private clinics and pharmacies). Distance and transportation costs did not create barriers for most families of referred sick children. Although the average cost of transportation in a subsample of 75 cases was relatively high (US$11.28), most families (63%) who went to the referral site walked and hence paid nothing. Most caretakers (75%) complied with referral advice. Use of referral slips by health care providers was higher for urgent referrals, and receiving a referral slip significantly increased caretakers’ compliance with referral. Conclusions Use of referral slips is important to increase compliance with referral recommendations in rural Afghanistan.
A Longitudinal Study of Industrial and Clerical Workers: Predictors of Upper Extremity Tendonitis
Upper extremity tendonitis (UET) associated with work activity is common but the true incidence and risk factors can best be determined by a prospective cohort study. This study followed a cohort of 501 active workers for an average of 5.4 years. Incident cases were defined as workers who were asymptomatic at baseline testing and had no prior history of UET and went on to be diagnosed with an UET during the follow-up period or at the follow-up evaluation. The incident cases were compared to the subset of the cohort who also had no history of an UET and did not develop tendonitis during the study. The cumulative incidence in this cohort was 24.3% or 4.5% annually. The factors found to have the highest predictive value for identifying a person who is likely to develop an UET in the near future included age over 40, a BMI over 30, a complaint at baseline of a shoulder or neck discomfort, a history of CTS and a job with a higher shoulder posture rating. The risk profile identifies both ergonomic and personal health factors as risks and both categories of factors may be amenable to prevention strategies.