The new COSMIN guidelines confront traditional concepts of responsiveness

The recently published "COSMIN" guidelines aim to rate properties of outcome instruments and state two issues with regard to responsiveness which is the instrument's ability to detect change over time. These issues are comparison of score changes with change of an external criterion using correlations and the judgement of traditional methods as inappropriate. The latter are the "transition" concept, a global rating of change, and parametric measures of responsiveness, for example, effect sizes. It can be shown that the methodology proposed by the guidelines has important weaknesses and that denunciation of traditional methods is not appropriate. Some claims of the guidelines about responsiveness do not match the demands of clinical reality and confront findings of numerous epidemiological studies

Expression of a barley cystatin gene in maize enhances resistance against phytophagous mites by altering their cysteine-proteases

Phytocystatins are inhibitors of cysteine-proteases from plants putatively involved in plant defence based on their capability of inhibit heterologous enzymes. We have previously characterised the whole cystatin gene family members from barley (HvCPI-1 to HvCPI-13). The aim of this study was to assess the effects of barley cystatins on two phytophagous spider mites, Tetranychus urticae and Brevipalpus chilensis. The determination of proteolytic activity profile in both mite species showed the presence of the cysteine-proteases, putative targets of cystatins, among other enzymatic activities. All barley cystatins, except HvCPI-1 and HvCPI-7, inhibited in vitro mite cathepsin L- and/or cathepsin B-like activities, HvCPI-6 being the strongest inhibitor for both mite species. Transgenic maize plants expressing HvCPI-6 protein were generated and the functional integrity of the cystatin transgene was confirmed by in vitro inhibitory effect observed against T. urticae and B. chilensis protein extracts. Feeding experiments impaired on transgenic lines performed with T. urticae impaired mite development and reproductive performance. Besides, a significant reduction of cathepsin L-like and/or cathepsin B-like activities was observed when the spider mite fed on maize plants expressing HvCPI-6 cystatin. These findings reveal the potential of barley cystatins as acaricide proteins to protect plants against two important mite pests

High origin of a testicular artery: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Although variations in the origin of the testicular artery are not uncommon, few reports about a high origin from the abdominal aorta exist in the literature. We discuss the case of a high origin of the testicular artery, its embryology, classification systems, and its clinical significance.</p> <p>Case presentation</p> <p>We report a very rare case of high origin of the left testicular artery in a 68-year-old Caucasian male cadaver. The artery originated from the anterolateral aspect of the abdominal aorta, 2 cm cranially to the ipsilateral renal artery. Approximately 1 cm after its origin, it branched off into the inferior suprarenal artery. During its course, the artery crossed anterior to the left renal artery.</p> <p>Conclusions</p> <p>A knowledge of the variant origin of the testicular artery is important during renal and testicular surgery. The origin and course must be carefully identified in order to preserve normal blood circulation and prevent testicular atrophy. A reduction in gonadal blood flow may lead to varicocele under circumstances. A knowledge of this variant anatomy may be of interest to radiologists and helpful in avoiding diagnostic errors.</p

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Molecular survey of pyrethroid resistance mechanisms in Mexican field populations of Rhipicephalus (Boophilus) microplus

Susceptibility to synthetic pyrethroids (SP´s) and the role of two major resistance mechanisms were evaluated in Mexican Rhipicephalus microplus tick populations. Larval packet test (LPT), knock-down (kdr) PCR allele-specific assay (PASA) and esterase activity assays were conducted in tick populations for cypermethrin, flumethrin and deltamethrin. Esterase activity did not have a significant correlation with SP´s resistance. However a significant correlation (p < 0.01) was found between the presence of the sodium channel mutation, and resistance to SP´s as measured by PASA and LPT respectively. Just over half the populations (16/28) were cross-resistant to flumethrin, deltamethrin and cypermethrine, 21.4% of the samples (6/28) were susceptible to all of the three pyrethroids 10.7 of the samples (3/28) were resistant to flumethrin, 3.4 of the samples (1/28) were resistant to deltamethrin only and 7.1% (2/28) were resistant to flumethrin and deltamethrin. The presence of the kdr mutation correlates with resistance to the SP´s as a class. Target site insensitivity is the major mechanism of resistance to SP´s in Mexican R. microplus field strains, involving the presence of a sodium channel mutation, however, esterase-based, other mutations or combination of mechanisms can also occur

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events

Structural and micro-anatomical changes in vertebrae associated with idiopathic-type spinal curvature in the curveback guppy model

Background: The curveback lineage of guppy is characterized by heritable idiopathic-type spinal curvature thatdevelops during growth. Prior work has revealed several important developmental similarities to the human idiopathicscoliosis (IS) syndrome. In this study we investigate structural and histological aspects of the vertebrae that areassociated with spinal curvature in the curveback guppy and test for sexual dimorphism that might explain a femalebias for severe curve magnitudes in the population.Methods: Vertebrae were studied from whole-mount skeletal specimens of curved and non-curved adult males andfemales. A series of ratios were used to characterize structural aspects of each vertebra. A three-way analysis of variancetested for effects of sex, curvature, vertebral position along the spine, and all 2-way interactions (i.e., sex and curvature,sex and vertebra position, and vertebra position and curvature). Histological analyses were used to characterize microarchitecturalchanges in affected vertebrae and the intervertebral region.Results: In curveback, vertebrae that are associated with curvature demonstrate asymmetric shape distortion,migration of the intervertebral ligament, and vertebral thickening on the concave side of curvature. There is sexualdimorphism among curved individuals such that for several vertebrae, females have more slender vertebrae than domales. Also, in the region of the spine where lordosis typically occurs, curved and non-curved females have a reducedwidth at the middle of their vertebrae, relative to males.Conclusions: Based on similarities to human spinal curvatures and to animals with induced curves, the concaveconvexbiases described in the guppy suggest that there is a mechanical component to curve pathogenesis incurveback. Because idiopathic-type curvature in curveback is primarily a sagittal deformity, it is structurally more similarto Scheuermann kyphosis than IS. Anatomical differences between teleosts and humans make direct biomechanicalcomparisons difficult. However, study of basic biological systems involved in idiopathic-type spinal curvature incurveback may provide insight into the relationship between a predisposing aetiology, growth, and biomechanics.Further work is needed to clarify whether observed sex differences in vertebral characteristics are related to the femalebias for severe curves that is observed in the population

Mutational processes contributing to the development of multiple myeloma.

To gain insight into multiple myeloma (MM) tumorigenesis, we analyzed the mutational signatures in 874 whole-exome and 850 whole-genome data from the CoMMpass Study. We identified that coding and non-coding regions are differentially dominated by distinct single-nucleotide variant (SNV) mutational signatures, as well as five de novo structural rearrangement signatures. Mutational signatures reflective of different principle mutational processes-aging, defective DNA repair, and apolipoprotein B editing complex (APOBEC)/activation-induced deaminase activity-characterize MM. These mutational signatures show evidence of subgroup specificity-APOBEC-attributed signatures associated with MAF translocation t(14;16) and t(14;20) MM; potentially DNA repair deficiency with t(11;14) and t(4;14); and aging with hyperdiploidy. Mutational signatures beyond that associated with APOBEC are independent of established prognostic markers and appear to have relevance to predicting high-risk MM

Work-life conflict and associations with work- and nonwork-related factors and with physical and mental health outcomes: a nationally representative cross-sectional study in Switzerland

BACKGROUND: The aim of the present cross-sectional study was to examine work- and nonwork-related factors and physical and mental health outcomes associated with combined time- and strain-based work-life conflict (WLC) among adult employees living and working in Switzerland as well as possible gender differences in this regard. METHODS: The data used for the study were taken from wave 6 of the nationally representative Swiss Household Panel (SHP) collected in 2004. The analysis was restricted to 4'371 employees aged 20 to 64 years. Trivariate crosstabulations and multivariate linear and logistic regression analyses stratified by gender were performed in order to calculate gender-specific prevalence rates (%), beta coefficients (SZ) and crude as well as multiple adjusted odds ratios (OR) as measures of association. RESULTS: Every eighth person (12.5%) within the study population has a high or very high WLC score. Prevalence rates are clearly above average in men and women with higher education, in executive positions or managerial functions, in full-time jobs, with variable work schedules, regular overtime, long commuting time to work and job insecurity. Working overtime regularly, having variable work schedules and being in a management position are most strongly associated with WLC in men, whereas in women the level of employment is the strongest explanatory variable by far, followed by variable work schedules and high job status (managerial position). In both men and women, WLC is associated with several physical and mental health problems. Employees with high or very high WLC show a comparatively high relative risk of self-reported poor health, anxiety and depression, lack of energy and optimism, serious backache, headaches, sleep disorders and fatigue. While overall prevalence rate of (very) high WLC is higher in men than in women, associations between degrees of WLC and most health outcomes are stronger in women than in men. CONCLUSIONS: This important issue which up to now has been largely neglected in public health research needs to be addressed in future public health research and, if the findings are confirmed by subsequent (longitudinal) studies, to be considered in workplace health promotion and interventions in Switzerland as elsewhere