James Leigh Cellars Wine Descriptions

These proof copies of labels that will adhere to the back of a wine bottle describe the 2003 Walla Walla Valley Spofford Station Merlot, the 2003 Walla Walla Valley Cabernet Sauvignon, the 2003 Walla Walla Valley Palette and the 2003 Walla Walla Valley Spofford Station Syrah, all from James Leigh Cellars. The Merlot, Cabernet Sauvignon, and Syrah all received accolades from Wine Enthusiast

Time to achieve remission determines time to be in remission

Contains fulltext : 87665.pdf (publisher's version ) (Open Access)INTRODUCTION: Though remission is currently a treatment goal in patients with rheumatoid arthritis (RA), the number of patients who achieve and sustain remission in daily practice is still small. It is suggested that early remission will be associated with sustainability of remission. The aim was to study the association between time-to-remission and sustainability of remission in a cohort of early RA patients treated according to daily practice. METHODS: For this study, three-year follow-up data were used from the Nijmegen RA Inception Cohort of patients included between 1985 and 2005 (N=753). Patients were included upon diagnosis (ACR criteria), were systematically evaluated at three-monthly visits and treated according to daily practice. Remission was defined according to the Disease Activity Score (DAS)<1.6 and the ACR remission criteria. Remission of at least 6 months duration was regarded as sustained remission. Predictors for time-to-remission were identified by Cox-regression analyses. The relation between time-to-remission and sustained remission was analyzed using longitudinal binary regression. RESULTS: N=398 (52%) patients achieved remission with a median time-to-remission of 12 months. Male gender, younger age and low DAS at baseline were predictive to reach remission rapidly. There were n=142 (36%) patients experiencing sustained remission, which was determined by a shorter time-to-remission only. The relationship between time-to-remission and sustained remission was described by a significant odds ratio (1.11) (1.10 to 1.12-95% CI) that was constant over the whole period 1985 to 2005. Results obtained with the ACR remission criteria were similar. CONCLUSIONS: A shorter time-to-remission is related to sustainability of remission, supporting striving for early remission in patients with RA

The zebrafish mutants dre, uki, and lep encode negative regulators of the hedgehog signaling pathway.

Proliferation is one of the basic processes that control embryogenesis. To identify factors involved in the regulation of proliferation, we performed a zebrafish genetic screen in which we used proliferating cell nuclear antigen (PCNA) expression as a readout. Two mutants, hu418B and hu540A, show increased PCNA expression. Morphologically both mutants resembled the dre (dreumes), uki (ukkie), and lep (leprechaun) mutant class and both are shown to be additional uki alleles. Surprisingly, although an increased size is detected of multiple structures in these mutant embryos, adults become dwarfs. We show that these mutations disrupt repressors of the Hedgehog (Hh) signaling pathway. The dre, uki, and lep loci encode Su(fu) (suppressor of fused), Hip (Hedgehog interacting protein), and Ptc2 (Patched2) proteins, respectively. This class of mutants is therefore unique compared to previously described Hh mutants from zebrafish genetic screens, which mainly show loss of Hh signaling. Furthermore, su(fu) and ptc2 mutants have not been described in vertebrate model systems before. Inhibiting Hh activity by cyclopamine rescues uki and lep mutants and confirms the overactivation of the Hh signaling pathway in these mutants. Triple uki/dre/lep mutants show neither an additive increase in PCNA expression nor enhanced embryonic phenotypes, suggesting that other negative regulators, possibly Ptc1, prevent further activation of the Hh signaling pathway. The effects of increased Hh signaling resulting from the genetic alterations in the uki, dre, and lep mutants differ from phenotypes described as a result of Hh overexpression and therefore provide additional insight into the role of Hh signaling during vertebrate development

Generation and Characterization of Fmr1 Knockout Zebrafish

Fragile X syndrome (FXS) is one of the most common known causes of inherited mental retardation. The gene mutated in FXS is named FMR1, and is well conserved from human to Drosophila. In order to generate a genetic tool to study FMR1 function during vertebrate development, we generated two mutant alleles of the fmr1 gene in zebrafish. Both alleles produce no detectable Fmr protein, and produce viable and fertile progeny with lack of obvious phenotypic features. This is in sharp contrast to published results based on morpholino mediated knock-down of fmr1, reporting defects in craniofacial development and neuronal branching in embryos. These phenotypes we specifically addressed in our knock-out animals, revealing no significant deviations from wild-type animals, suggesting that the published morpholino based fmr1 phenotypes are potential experimental artifacts. Therefore, their relation to fmr1 biology is questionable and morpholino induced fmr1 phenotypes should be avoided in screens for potential drugs suitable for the treatment of FXS. Importantly, a true genetic zebrafish model is now available which can be used to study FXS and to derive potential drugs for FXS treatment

Community engagement in deprived neighbourhoods during the COVID-19 crisis: perspectives for more resilient and healthier communities

The current COVID-19 pandemic confines people to their homes, disrupting the fragile social fabric of deprived neighbourhoods and citizen’s participation options. In deprived neighbourhoods, community engagement is central in building community resilience, an important resource for health and a prerequisite for effective health promotion programmes. It provides access to vulnerable groups and helps understand experiences, assets, needs and problems of citizens. Most importantly, community activities, including social support, primary care or improving urban space, enhance health through empowerment, strengthened social networks, mutual respect and providing a sense of purpose and meaning. In the context of inequalities associated with COVID-19, these aspects are crucial for citizens of deprived neighbourhoods who often feel their needs and priorities are ignored. In this perspectives paper, illustrated by a varied overview of community actions in the UK and The Netherlands, we demonstrate how citizens, communities and organizations may build resilience and community power. Based on in-depth discussion among the authors we distilled six features of community actions: increase in mutual aid and neighbourhood ties, the central role of community-based organizations (CBOs), changing patterns of volunteering, use of digital media and health promotion opportunities. We argue that in order to enable and sustain resilient and confident, ‘disaster-proof’, communities, areas which merit investment include supporting active citizens, new (digital) ways of community engagement, transforming formal organizations, alignment with the (local) context and applying knowledge in the field of health promotion in new ways, focussing on learning and co-creation with citizen initiatives

Модель взаємовідносин між державою та фінансово-промисловими групами для різних бізнес-систем

Мета дослідження - визначення пріоритетів та стратегічних напрямків формування ефективної моделі взаємодії української держави з вітчизняними фінансово-промисловими групами в сучасних умовах економічного розвитку

Cardiorespiratory fitness and physical activity in children with cancer

Purpose: This study assessed cardiorespiratory fitness (CRF), physical activity (PA), and sedentary behavior (SB), as well as factors associated with these outcomes in children during or shortly after cancer treatment. Methods: Cross-sectionally, CRF data, obtained by the cardiopulmonary exercise test, and PA and SB data, obtained by an accelerometer, were assessed in children with cancer (8–18 years old). Linear regression models were used to determine associations between CRF, PA, or SB and patient characteristics. Results: Among 60 children with cancer, mean age 12.6 years, 35 boys, 28 % were during cancer treatment. CRF, reported as the z score of VO2peak, showed that 32 children had a VO2peakz score which was −2 below the predicted value. CRF was significantly associated with PA and SB: eac

Reproductive ability in survivors of childhood, adolescent, and young adult Hodgkin lymphoma:a review

Background: Owing to a growing number of young and adolescent Hodgkin lymphoma (HL) survivors, awareness of (long-term) adverse effects of anticancer treatment increases. The risk of impaired reproductive ability is of great concern given its impact on quality of life. There is currently no review available on fertility after childhood HL treatment. Objective and Rationale: The aim of this narrative review was to summarize existing literature on different aspects of reproductive function in male and female childhood, adolescent, and young adult HL survivors. Search Methods: PubMed and EMBASE were searched for articles evaluating fertility in both male and female HL survivors aged &lt;25 years at diagnosis. In females, anti-Müllerian hormone (AMH), antral follicle count, premature ovarian insufficiency (POI), acute ovarian failure, menstrual cycle, FSH, and pregnancy/live births were evaluated. In males, semen-analysis, serum FSH, inhibin B, LH, testosterone, and reports on pregnancy/live births were included. There was profound heterogeneity among studies and a lack of control groups; therefore, no meta-analyses could be performed. Results were presented descriptively and the quality of studies was not assessed individually. Outcomes: After screening, 75 articles reporting on reproductive markers in childhood or adolescent HL survivors were included. Forty-one papers reported on 5057 female HL survivors. The incidence of POI was 6-34% (median 9%; seven studies). Signs of diminished ovarian reserve or impaired ovarian function were frequently seen (low AMH 55-59%; median 57%; two studies. elevated FSH 17-100%; median 53%; seven studies). Most survivors had regular menstrual cycles. Fifty-one studies assessed fertility in 1903 male HL survivors. Post-treatment azoospermia was highly prevalent (33-100%; median 75%; 29 studies). Long-term follow-up data were limited, but reports on recovery of semen up to 12 years post-treatment exist. FSH levels were often elevated with low inhibin B (elevated FSH 0-100%; median 51.5%; 26 studies. low inhibin B 19-50%; median 45%; three studies). LH and testosterone levels were less evidently affected (elevated LH 0-57%, median 17%; 21 studies and low testosterone 0-43%; median 6%; 15 studies). In both sexes, impaired reproductive ability was associated with a higher dose of cumulative chemotherapeutic agents and pelvic radiotherapy. The presence of abnormal markers before treatment indicated that the disease itself may also negatively affect reproductive function (Females: AMH&lt;p10 9%; one study and Males: azoospermia 0-50%; median 10%; six studies). Reports on chance to achieve pregnancy during survivorship are reassuring, although studies had their limitations and the results are difficult to evaluate. In the end, a diminished ovarian reserve does not exclude the chance of a live birth, and males with aberrant markers may still be able to conceive. Wider Implications: This review substantiates the negative effect of HL treatment on gonadal function and therefore young HL survivors should be counseled regarding their future reproductive life, and fertility preservation should be considered. The current level of evidence is insufficient and additional trials on the effects of HL and (current) treatment regimens on reproductive function are needed. In this review, we make a recommendation on reproductive markers that could be assessed and the timing of (repeated) measurements.</p