Sniffin' Sticks Screening 12 test: Presentation of odours on filter paper improves the recognition rate.

To the Editor: Monitoring of olfactory function and diagnosis of olfactory disorders using the pen-based "Sniffin' Sticks test" is problematic during the SARS-CoV-2 pandemic due to hygienic concerns. The aim of this study was to find out whether the results of olfactory testing obtained by presenting odours on a single-use filter paper is identical to performing the test by presenting the odour pens according to the manufacturer's manual.

Prevalence and risk factors of smell dysfunction - a comparison between five German population-based studies.

BACKGROUND: The prevalence of olfactory impairment increases with age and is known to be an early sign of different neurodegenerative diseases. Only few population-based studies examined the prevalence of olfactory impairment and comparisons across studies are scarce. Aim of this analysis was to compare the prevalence and determinants of normosmia across five population based studies in Germany. METHODOLOGY: Data from five population-based, cross-sectional studies were included. They were independently conducted and used the same test system (Sniffin' Sticks Screening 12) to measure olfactory function. This system consists of 12 odor-dispensing felt-tip pens; the task is a forced-choice selection among four alternative odors per pen. Sociodemographic information and comorbidities were assessed in face-to-face interviews. Univariate, descriptive statistics and multivariable logistic regression models stratified by study, were performed to determine risks, i.e. prevalence odds ratios, associated with olfactory function. RESULTS: The prevalence of normosmic participants varied considerably across studies. Olfactory function was lower in men, decreased with age, and increased with higher education. Several individual comorbidities and a comorbidity index were associated with olfactory dysfunction. Recognition performance for three of the 12 pens was especially low in all studies. CONCLUSION: Four factors, well known to describe population composition, contribute to explain differences in the prevalence of olfactory function between studies when the same test system is used. Our results indicate that comorbidities and educational level should always be considered when test systems based on smell recognition are used in population-based studies.

Effects of pen bedding and feeding high crude protein diets on manure composition and greenhouse gas emissions from a feedlot pen surface.

Greenhouse gas (GHG) emissions from concentrated animal feeding operations vary by stage of production and management practices. The objective of this research was to study the effect of two dietary crude protein levels (12 and 16%) fed to beef steers in pens with or without corn stover bedding. Manure characteristics and GHG emissions were measured from feedlot pen surfaces. Sixteen equal-sized feedlot pens (19 x 23 m) were used. Eight were bedded approximately twice a week with corn stover and the remaining eight feedlot pens were not bedded. Angus steers (n = 138) were blocked by live weights (lighter and heavier) with 7 to 10 animals per pen. The trial was a 2 x 2 factorial design with factors of two protein levels and two bedding types (bedding vs. non bedding), with four replicates. The study was conducted from June through September and consisted of four -28-day periods. Manure from each pen was scrapped once every 28 days and composite manure samples from each pen were collected. Air samples from pen surfaces were sampled in Tedlar bags using a Vac-U-Chamber coupled with a portable wind tunnel and analyzed with a greenhouse gas gas chromatograph within 24 hr of sampling. The manure samples were analyzed for crude protein (CP), total nitrogen (TN), ammonia (NH3), total volatile fatty acid (TVFA), total carbon (TC), total phosphorus (TP), and potassium (K). The air samples were analyzed for methane (CH4), carbon dioxide (CO2), and nitrous oxide (N2O) concentrations. The concentration of TN was significantly higher (p < 0.05) in manure from pens with cattle fed the high protein diets. The volatile fatty acids (VFAs) such as acetic, propionic, isobutyric, butyric, isovaleric, and valeric acids concentrations were similar across both treatments. There were no significant differences in pen surface GHG emissions across manure management and dietary crude protein levels.

Ventilatory strategies in septic patients. Results from a nationwide observational trial.

BACKGROUND: Mortality in intensive care unit (ICU) patients is affected by multiple variables. The possible impact of the mode of ventilation has not yet been clarified; therefore, a secondary analysis of the "epidemiology of sepsis in Germany" study was performed. The aims were (1) to describe the ventilation strategies currently applied in clinical practice, (2) to analyze the association of the different modes of ventilation with mortality and (3) to investigate whether the ratio between arterial partial pressure of oxygen and inspired fraction of oxygen (PF ratio) and/or other respiratory variables are associated with mortality in septic patients needing ventilatory support. METHODS: A total of 454 ICUs in 310 randomly selected hospitals participated in this national prospective observational 1-day point prevalence of sepsis study including 415 patients with severe sepsis or septic shock according to the American College of Chest Physicians/Society of Critical Care Medicine criteria. RESULTS: Of the 415 patients, 331 required ventilatory support. Pressure controlled ventilation (PCV) was the most frequently used ventilatory mode (70.6 %) followed by assisted ventilation (AV 21.7 %) and volume controlled ventilation (VCV 7.7 %). Hospital mortality did not differ significantly among patients ventilated with PCV (57 %), VCV (71 %) or AV (51 %, p=0.23). A PF ratio equal or less than 300 mmHg was found in 83.2 % of invasively ventilated patients (n=316). In AV patients there was a clear trend to a higher PF ratio (204±70 mmHg) than in controlled ventilated patients (PCV 179±74 mmHg, VCV 175±75 mmHg, p=0.0551). Multiple regression analysis identified the tidal volume to pressure ratio (tidal volume divided by peak inspiratory airway pressure, odds ratio OR=0.94, 95 % confidence interval 95% CI=0.89-0.99), acute renal failure (OR=2.15, 95% CI=1.01-4.55) and acute physiology and chronic health evaluation (APACHE) II score (OR=1.09, 95% CI=1.03-1.15) but not the PF ratio (univariate analysis OR=0.998, 95 % CI=0.995-1.001) as independent risk factors for in-hospital mortality. CONCLUSIONS: This representative survey revealed that severe sepsis or septic shock was frequently associated with acute lung injury. Different ventilatory modes did not affect mortality. The tidal volume to inspiratory pressure ratio but not the PF ratio was independently associated with mortality.

BRCA1/2 testing: uptake, phenocopies, and strategies to improve detection rates in initially negative families.

In families with clustering of breast and ovarian cancer, molecular testing of the major susceptibility genes BRCA1/2 helps to identify patients with disease mutations and healthy persons at high risk who can participate in targeted intervention programs. We investigated 5559 families from the German Consortium for Hereditary Breast and Ovarian Cancer included between 1997 and 2008 and treated under clinical routine conditions. In each family an index patient/person had been screened for deleterious mutations in BRCA1/2. Healthy relatives agreed to predictive testing in 888 of 1520 BRCA1/2 mutation-positive families (58%). Of 2646 eligible unaffected first-degree relatives 1143 decided to be tested (43%). In 325 families with BRCA1/2-positive index patients one related BC/OC patient was tested and 39 (12.0%; 95% confidence interval: 8.7-16.0%) discrepant cases found. A second related individual was screened in 163 of 3388 (4.9%) families with BRCA1/2-negative index patient and in eight families a BRCA1/2 mutation was found. In BRCA1/2 mutation-positive families, BC/OC patients lacking the familial mutation have to be expected at a rather high rate. In families with BRCA1/2-negative index patient we recommend a second screening if another patient with a high probability of carrying a BRCA1/2 mutation is available.

Student tutors are able to teach basic sonographic anatomy effectively - a prospective randomized controlled trial.

PURPOSE: Ultrasound is a widely used diagnostic tool. In medical education, it can be used to teach sonographic anatomy as well as the basics of ultrasound diagnostics. Some medical schools have begun implementing student tutor-led teaching sessions in sonographic abdominal anatomy in order to meet the growing demand in ultrasound teaching. However, while this teaching concept has proven to be feasible and well accepted, there is limited data regarding its effectiveness. We investigated whether student tutors teach sonographic anatomy as effectively as faculty staff sonographers. MATERIALS AND METHODS: 50 medical students were randomly assigned to one of two groups. 46 of these could be included in the analysis. One group was taught by student tutors (ST) and the other by a faculty staff sonographer (FS). Using a pre/post-test design, students were required to locate and label 15 different abdominal structures. They printed out three pictures in three minutes and subsequently labeled the structures they were able to identify. The pictures were then rated by two blinded faculty staff sonographers. A mean difference of one point in the improvement of correctly identified abdominal structures between the pre-test and post-test among the two groups was regarded as equivalent. RESULTS: In the pre-test, the ST (FS) correctly identified 1.6 ± 1.0 (2.0 ± 1.1) structures. Both the ST and FS group showed improvement in the post-test, correctly identifying 7.8 ± 2.8 vs. 8.9 ± 2.9 structures, respectively (p < .0001 each). Comparing the improvement of the ST (6.2 ± 2.8 structures) versus the FS (6.9 ± 3.2) showed equivalent results between the two groups (p < .05 testing for equivalence). CONCLUSION: Basic abdominal sonographic anatomy can be taught effectively by student tutors.

Predictors of cardiopulmonary fitness in cancer-affected and -unaffected women with a pathogenic germline variant in the genes BRCA1/2 (LIBRE-1).

Physical activity (PA) helps prevention and aftercare of sporadic breast cancer (BC), cardiopulmonary fitness (CPF) being an age-independent predictor of tumor-specific mortality. Therefore, we wanted to identify predictors of CPF (represented by peak oxygen uptake: VO2peak) in BRCA1/2 mutation carriers whose risk of developing BC is high. We used cross-sectional data from 68 BRCA1/2 germline mutation carrying women participating in the randomized, prospective, controlled clinical study LIBRE-1. Assessments included cardiopulmonary exercise testing, medical and lifestyle history plus socioeconomic status. Additionally, the participants completed a psychological questionnaire regarding their attitude, subjective norms, perceived behavior control and intention towards PA. A multivariate logistic regression model was used to identify predictors for participants reaching their age- and sex-adjusted VO2peak reference values. 22 participants (median age: 40 years, interquartile range (IQR) 33-46) were cancer-unaffected and 46 cancer-affected (median age: 44 years, IQR 35-50). The strongest predictor for reaching the reference VO2peak value was attitude towards PA (Odds Ratio 3.0; 95% Confidence Interval 1.3-8.4; p = 0.021). None of the other predictors showed a significant association. A positive attitude towards PA seems to be associated with VO2peak, which should be considered in developing therapeutic and preventive strategies.Trial registrations: NCT02087592; DRKS00005736.

Attentional bias, craving and cannabis use in an inpatient sample of adolescents and young adults diagnosed with cannabis use disorder: The moderating role of cognitive control.

Motivational processes like attentional bias and craving have been related to substance use. However, results are inconclusive. The present cross-sectional study was designed to replicate and extend previous research by investigating the relationships between attentional bias, craving, cognitive control and (severity of) cannabis use in a sample of inpatient adolescents and young adults (aged 18-30) diagnosed with CUD according to DSM-5. Contrary to expectations, our sample did not show attentional bias for cannabis words, neither did attentional bias correlate with craving, cognitive control or (severity of) cannabis use. In line with our hypotheses, however, increased session-induced craving was correlated to more daily cannabis use and reduced cognitive control. Furthermore, participants who displayed reduced cognitive control used more cannabis per day. A bootstrapped hierarchical regression model showed that, contrary to expectations, cognitive control did not modulate the relationships between attentional bias, craving and cannabis use. This study highlights the unique role of craving in relation to cannabis use and extends previous findings that cognitive control appears to have no moderating role regarding cannabis use disorder. Based on our results, it might well be that the underlying mechanisms of cannabis use disorder differ from those in other substance use disorders.

An End-to-End Solution for Automatic Contouring of Tumor Region in Intraoperative Images of Breast Lumpectomy.

Breast-conserving surgery, also known as lumpectomy, is an early stage breast cancer treatment that aims to spare as much healthy breast tissue as possible. A risk associated with lumpectomy is the presence of cancer positive margins post operation. Surgical navigation has been shown to reduce cancer positive margins but requires manual segmentation of the tumor intraoperatively. In this paper, we propose an end-to-end solution for automatic contouring of breast tumor from intraoperative ultrasound images using two convolutional neural network architectures, the U-Net and residual U-Net. The networks are trained on annotated intraoperative breast ultrasound images and evaluated on the quality of predicted segmentations. This work brings us one step closer to providing surgeons with an automated surgical navigation system that helps reduce cancer-positive margins during lumpectomy.

Association of hormone receptor status with grading, age of onset, and tumor size in BRCA1-associated breast cancer.

BRCA1-associated breast cancer frequently presents with estrogen-receptor (ERalpha) and progesterone-receptor (PR) negativity, grade 3, and early onset. In contrast, in BRCA1-deficient mice, ERalpha is highly expressed in early tumorigenesis. In a retrospective cohort study on 587 breast cancer patients with deleterious BRCA1 mutations, the correlation of ER, PR status, grading, age of onset, and tumor size was investigated. ERalpha and PR expression decreased from 62% in ductal carcinoma in situ (DCIS) to 20% and 16% in pT3, respectively (p value for ER 0.025 and PR 0.035, Fisher's exact test). The percentage of grade 1/2 tumors decreased from 44% in DCIS to 17% in pT3 (p value 0.074). Moreover, ER/PR positivity increased with increasing age. Our data suggest that early stage BRCA1-associated breast cancers are more frequently ERalpha and PR positive and low grade than advanced stages.

Tetrachloroanisol: a source of musty taste in eggs and broilers.

Ingestion by hens and broilers of specific chloroanisols present in some wood shavings used in poultry cages can result in a musty taste in poultry products.

Lherzolite, anorthosite, gabbro, and basalt dredged from the mid-Indian ocean ridge.

The Central Indian Ridge is mantled with flows of low-potassium basalt of uniform composition. Gabbro, anorthosite, and garnet-bearing lherzolite are exposed in cross fractures, and lherzolite is the bedrock at the center of the ridge. The Iherzolites are upper-mantle rock exposed by faulting.

Lunar rock compositions and some interpretations.

Samples of igneous "gabbro," "basalt," and lunar regolith have compositions fundamentally different from all meteorites and terrestrial basalts. The lunar rocks are anhydrous and without ferric iron. Amounts of titanium as high as 7 weight percent suggest either extreme fractionation of lunar rocks or an unexpected solar abundance of titanium. The differences in compositions of the known, more "primitive" rocks in the planetary system indicate the complexities inherent in defining the solar abundances of elemizents and the initial compositions of the earth and moon.

Alga-like forms in onverwacht series, South Africa: oldest recognized lifelike forms on Earth.

Spheroidal and cupshaped, carbonaceous alga-like bodies, as well as filamentous structures and amorphous carbonaceous matter occur in sedimentary rocks of the Onverwacht Series (Swaziland System) in South Africa. The Onverwacht sediments are older than 3.2 eons, and they are probably the oldest, littlealtered sedimentary rocks on Earth. The basal Onverwacht sediments lie approximately 10,000 meters stratigraphically below the Fig Tree sedimentary rocks, from which similar organic microstructures have been interpreted as alga-like microfossils. The Onverwacht spheroids and filaments are best preserved in black, carbonrich cherts and siliceous argillites interlayered with thick sequences of lavas. These lifelike forms and the associated carbonaceous substances are probably biological in origin. If so, the origins of unicellular life on Earth are buried in older rocks now obliterated by igneous and metamorphic events.

Guidelines for the clinical management of familial adenomatous polyposis (FAP).

BACKGROUND: Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, which is responsible for <1% of all colorectal cancer (CRC) cases. The syndrome is characterised by the development of hundreds to thousands of adenomas in the colorectum. Almost all patients will develop CRC if they are not identified and treated at an early stage. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the APC gene. Recently, a second gene has been identified that also gives rise to colonic adenomatous polyposis, although the phenotype is less severe than typical FAP. The gene is the MUTYH gene and the inheritance is autosomal recessive. In April 2006 and February 2007, a workshop was organised in Mallorca by European experts on hereditary gastrointestinal cancer aiming to establish guidelines for the clinical management of FAP and to initiate collaborative studies. Thirty-one experts from nine European countries participated in these workshops. Prior to the meeting, various participants examined the most important management issues according to the latest publications. A systematic literature search using Pubmed and reference lists of retrieved articles, and manual searches of relevant articles, was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described herein may be helpful in the appropriate management of FAP families. In order to improve the care of these families further, prospective controlled studies should be undertaken.

The influence of coastal topography, circulation patterns, and rafting in structuring populations of an intertidal alga.

Understanding the dispersal processes that influence genetic structure in marine species requires estimating gene flow in a dynamic, fluid environment that is often poorly characterized at scales relevant to multiple dispersive stages (e.g. spores, gametes, zygotes, larvae, adults). We examine genetic structure in the marine alga Fucus vesiculosus L., which inhabits moderately exposed shores in the northern Atlantic but releases gametes only under sunny, calm conditions. We predicted genetic structure would correlate with coastal topography because weather frequently varies across coastal promontories on the Maine shore when F. vesiculosus is reproductive, which causes one side to experience high levels of water motion (= no gamete release) while one side is calm (= gamete release). Furthermore, we expected that the effect of low dispersal capacities of gametes and zygotes would result in spatial genetic structure over short distances. Using surface drifters, we characterized near-shore circulation patterns around the study sites to investigate whether directionality of gene flow was correlated with directionality of currents. We found significant genetic differentiation among sites sampled at two different peninsulas, but patterns of differentiation were unrelated to coastal topography and there was no within-site spatial structuring. Our genetic and near-shore circulation data, combined with an examination of gamete longevity, support the dependency of gene flow on storm-detached, rafting, reproductive adults. This study highlights the significance of rafting as a mechanism for structuring established populations of macroalgae and associated biota and demonstrates the importance of coupling population genetics' research with relevant hydrodynamic studies.

Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer).

Lynch syndrome (hereditary non-polyposis colorectal cancer) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The discovery of these genes, 15 years ago, has led to the identification of large numbers of affected families. In April 2006, a workshop was organised by a group of European experts in hereditary gastrointestinal cancer (the Mallorca-group), aiming to establish guidelines for the clinical management of Lynch syndrome. 21 experts from nine European countries participated in this workshop. Prior to the meeting, various participants prepared the key management issues of debate according to the latest publications. A systematic literature search using Pubmed and the Cochrane Database of Systematic Reviews reference lists of retrieved articles and manual searches of relevant articles was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described in this manuscript may be helpful for the appropriate management of families with Lynch syndrome. Prospective controlled studies should be undertaken to improve further the care of these families.

Pharmacodynamic equivalence of two orlistat capsule formulations in healthy volunteers under fed conditions.

OBJECTIVE: Orlistat is a reversible lipase inhibitor for obesity management. Orlistat exerts its pharmacological activity in the lumen of the stomach and small intestine by binding with the active site of gastric and pancreatic lipases, with the consequent inhibition of the systemic absorption of dietary fat. The undigested triglycerides are not absorbed, resulting in caloric deficit and positive effect in weight control. The objective of this study was to assess, using fat excreted in feces, the pharmacodynamic equivalence of orlistat when administered as generic and innovator capsule formulations. MATERIALS AND METHODS: A total of 18 healthy volunteers (12 males and 6 females) followed a 5-day run-in diet period in order to become accustomed to a high fat diet. Subjects were then randomized to receive under fed conditions oral doses of orlistat (120 mg) 3 times daily for 10 consecutive days as the generic (Ranbaxy Laboratories) or innovator (Xenical, Roche Laboratories, Nutley, NJ, USA) capsule formulations. Subjects followed a standardized diet (2,500 kcal/day, 30% as fat) for the entire study. Feces were collected over the last 2 days of the run-in period (baseline) and over the last 5 days of the 2 treatment periods. The amount of fat in meals and feces was assayed with a limit of detection of 0.1 and 0.2%, respectively. Fecal fat excretion over 24 hours (FFE(24), calculated as the percentage of amount of fat excreted in feces relative to the amount of fat ingested) was used as a pharmacodynamic endpoint to assess the therapeutic equivalence between the 2 orlistat formulations. An analysis of variance (ANOVA) was performed on FFE(24) parameters. RESULTS: Mean FFE(24) values at baseline and after repeated oral administrations of the generic and innovator formulations of orlistat were 6.48, 20.0 and 19.6%, respectively. The ratio of least-squares means (LSM) of FFE(24) of the generic to the innovator formulation was 99.1%, with 90% confidence intervals of 83.8 -114.5%. Adverse events for the generic and innovator products were similar in nature and frequency. CONCLUSION: Mean FFE(24) values were used as pharmacodynamic endpoints to assess equivalence between 2 formulations of orlistat. Results from this study suggest that pharmacodynamics of the generic capsule formulation of orlistat were similar to the marketed capsule formulation based on FFE(24) values.

The diverse world of coenzyme A binding proteins.

Coenzyme A is involved in a number of important metabolic pathways. Recently the structures of several coenzyme A binding proteins have been determined. We compare in some detail the structures of seven different coenzyme A protein complexes. These seven proteins all have distinctly different folds.