Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy.

The quality and quantity of tumor-infiltrating lymphocytes, particularly CD8 <sup>+</sup> T cells, are important parameters for the control of tumor growth and response to immunotherapy. Here, we show in murine and human cancers that these parameters exhibit circadian oscillations, driven by both the endogenous circadian clock of leukocytes and rhythmic leukocyte infiltration, which depends on the circadian clock of endothelial cells in the tumor microenvironment. To harness these rhythms therapeutically, we demonstrate that efficacy of chimeric antigen receptor T cell therapy and immune checkpoint blockade can be improved by adjusting the time of treatment during the day. Furthermore, time-of-day-dependent T cell signatures in murine tumor models predict overall survival in patients with melanoma and correlate with response to anti-PD-1 therapy. Our data demonstrate the functional significance of circadian dynamics in the tumor microenvironment and suggest the importance of leveraging these features for improving future clinical trial design and patient care

Turner syndrome and associated problems in turkish children: A multicenter study

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population. Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014. Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosi) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto’s thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%. Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespan. © Journal of Clinical Research in Pediatric Endocrinology

Economic analysis of soilless and soil-based greenhouse cucumber production in Turkey

Since the onset of the commercial application of soilless culture, this production approach has evoluted at a fast pace, gaining popularity among growers throughout the world. As a result, a lot of information has been developed by growers, advisors, researchers, and suppliers of equipment and substrate. This study aimed to determine the cost and return of soilless greenhouse cucumber (Cucumis sativus L.) production and to prepare a sample budget for growers. Soilless cultivation is an alternative production method for Turkish growers and it is being practised on a commercial basis on 180 ha. Cost and return budgets can be useful for growers because they allows growers to compare total production cost and revenue varying grower type, production time, geographical location, operation size, and cost structure. Growers can identify items in their budget that have a greater effect on profitability, and make adjustments. In this study, economic aspects of soilless and soil-based greenhouse cucumber production was analysed as comparative. Total costs were subtracted from total gross revenue to calculate the net return of soilless and soil-based greenhouse cucumber production. The cost items of soilless and soil-based greenhouse cucumber production were initial investment costs, variable costs, and fixed costs. Net return obtained from cucumbers grown in a mixture of perlite and zeolite was determined as € 1.84 m-2, whereas it was € 1.48 m-2 in conventional soil-based production. Production and market risks both affect profitability and economic viability of soilless grown vegetables.Desde o início da implantação de cultivos comerciais sem solo suas técnicas de produção tem evoluido em ritmo acelerado, ganhando popularidade entre agricultores de todo o mundo. Como resultado, uma grande quantidade de informação tem sido desenvolvida pelos produtores, consultores, pesquisadores e fornecedores de equipamentos e substratos. Determinaram-se o custo e retorno financeiro da produção de pepino (Cucumis sativus L.) e preparou-se um exemplo de orçamento para produtores. Na Turquia o cultivo sem solo é um método alternativo de produção para agricultores e é praticado em bases comerciais em 180 hectares. Por conseguinte, avaliações de custos e retornos podem ser úteis para produtores porque permitem aos mesmos comparar o custo total da produção e o retorno segundo variações de tipo de olericultor, tempo de produção, localização geográfica, tamanho do empreendimento e custo das estruturas. Os produtores podem assim identificar quais itens em seus orçamantos tem maior efeito na rentabilidade e fazer ajustes. Nesse estudo aspectos econômicos de cultivos de pepino em casas de vegetação sem solo e com solo foram analisados e comparados.Os custos totais foram subtraidos das receitas brutas para fins de cálculo do retorno líquido de produções de pepino em cultivos com e sem solo. Os custos dos itens dos cultivos com e sem solo foram: investimentos iniciais, custos variáveis e custos fixos. O retorno líquido obtido pelos produtores de pepino cultivados em um substrato de perlita e zeolita foi de € 1.84 m-2 e de € 1.48 m-2 para o cultivo convencional com solo. Contudo, riscos de produção e de mercado afetam a rentabilidade e viabilidade econômica de hortaliças cultivadas sem solo

Outlook for clean air in the context of sustainable development goals

Air pollution is linked with many of the United Nations Sustainable Development Goals. Strategies aiming at the improved air quality interact directly with climate mitigation targets, access to clean energy services, waste management, and other aspects of socio-economic development. Continuation of current policies in the key emitting sectors implies that a number of sustainability goals will likely not be met within the next two decades: emissions of air pollutants would cause 40% more premature deaths from outdoor air pollution than today, carbon emissions would rise globally by 0.4% per year, while nearly two billion people would not have access to clean cooking. This paper examines integrated policies to put the world on track towards three interlinked goals of achieving universal energy access, limiting climate change and reducing air pollution. Scenario analysis suggests that these goals can be attained simultaneously with substantial benefits. By 2040, emissions of main pollutants are projected to drop by 60–80% relative to today, and associated health impacts are quantified at two million avoided deaths from ambient and household air pollution combined. In comparison to costs needed for the decarbonization of global economy, additional investments in air pollution control and access to clean fuels are very modest against major societal gains. However, holistic and systemic policy assessment is required to avoid potential trade-offs

Genital ulcer severity score and genital health quality of life in Behçet's disease

Background: Behçet's Disease (BD) is a chronic auto-inflammatory, multisystem relapsing/remitting disorder of unknown aetiology. Oro-genital ulceration is a key feature of the disease and has a major impact on the patients' quality of life. Other clinical manifestations include ocular inflammation, rheumatologic and skin involvement, while CNS and vascular complications can lead to considerable morbidity. The availability of a valid monitoring tool for BD activity is crucial in evaluating the impact of the disease on daily life activity. The aims of this study were to validate a novel tool for monitoring genital ulceration severity in BD and to assess the impact of genital ulcers on the Genital Health Quality of Life (GHQoL). Methods: Genital Ulcer Severity Score (GUSS) was developed using six genital ulcer characteristics: number, size, duration, ulcer-free period, pain and site. A total of 207 BD patients were examined, (137 females: mean age∈±∈SD: 39.83∈±∈13.42 and 70 males: mean age∈±∈SD: 39.98∈±∈11.95) from the multidisciplinary Behçet's Centre of Excellence at Barts Health NHS Trust. GUSS was used in conjunction with Behçet's Disease Current Activity Form (BDCAF). Results: The over-all score of GUSS showed a strong correlation with all genital ulcer characteristics, and the strongest correlation was with the pain domain (r∈=∈0.936; P∈2: 0.600; P∈<∈0.0001). Conclusions: This study established the practicality of GUSS as a severity monitoring tool for BD genital ulcers and validated its use in 207 patients. Genital ulcers of BD have a considerable impact on the patients GHQoL

Adaptation and Validation of QUick, Easy, New, CHEap, and Reproducible (QUENCHER) Antioxidant Capacity Assays in Model Products Obtained from Residual Wine Pomace

Evaluation of the total antioxidant capacity of solid matrices without extraction steps is a very interesting alternative for food researchers and also for food industries. These methodologies have been denominated QUENCHER from QUick, Easy, New, CHEap, and Reproducible assays. To demonstrate and highlight the validity of QUENCHER (Q) methods, values of Q-method validation were showed for the first time, and they were tested with products of well-known different chemical properties. Furthermore, new QUENCHER assays to measure scavenging capacity against superoxide, hydroxyl, and lipid peroxyl radicals were developed. Calibration models showed good linearity (R2 > 0.995), proportionality and precision (CV < 6.5%), and acceptable detection limits (<20.4 nmol Trolox equiv). The presence of ethanol in the reaction medium gave antioxidant capacity values significantly different from those obtained with water. The dilution of samples with powdered cellulose was discouraged because possible interferences with some of the matrices analyzed may take place.The autonomous government of Castilla y León (Project BU268A11-2

Changing climate both increases and decreases European river floods

Climate change has led to concerns about increasing river floods resulting from the greater water-holding capacity of a warmer atmosphere. These concerns are reinforced by evidence of increasing economic losses associated with flooding in many parts of the world, including Europe. Any changes in river floods would have lasting implications for the design of flood protection measures and flood risk zoning. However, existing studies have been unable to identify a consistent continental-scale climatic-change signal in flood discharge observations in Europe, because of the limited spatial coverage and number of hydrometric stations. Here we demonstrate clear regional patterns of both increases and decreases in observed river flood discharges in the past five decades in Europe, which are manifestations of a changing climate. Our results—arising from the most complete database of European flooding so far—suggest that: increasing autumn and winter rainfall has resulted in increasing floods in northwestern Europe; decreasing precipitation and increasing evaporation have led to decreasing floods in medium and large catchments in southern Europe; and decreasing snow cover and snowmelt, resulting from warmer temperatures, have led to decreasing floods in eastern Europe. Regional flood discharge trends in Europe range from an increase of about 11 per cent per decade to a decrease of 23 per cent. Notwithstanding the spatial and temporal heterogeneity of the observational record, the flood changes identified here are broadly consistent with climate model projections for the next century, suggesting that climate-driven changes are already happening and supporting calls for the consideration of climate change in flood risk management