Kropf- und Muskelmageninhalt von Öko-Masthühnern und Legehennen

The objective of this study was to evaluate the variation of feed intake from pasture in organic broilers and in laying hens. In the broiler experiment, in total 288 broilers of breeds Ross 708 (fast growth; FG), Isa 657 (medium growth; MG) and Isa 757 (slow growth, SG) were kept in mixed groups. Between week 7 and 12 of life birds were slaughtered, crops and gizzards were collected and investigated for contents of feed, grit and plant particles. FG broilers had higher feed proportions in crops than MG and SG broilers. Proportions of plant particles have been higher in SG broilers than in MG and FG broilers. SG broilers had higher proportions of plant particles and grit in the gizzard. It is estimated that the proportion of plant particles amounts to 5-10 % of daily feed intake in slow growing broilers kept under organic conditions. In the laying hen experiment 60 young and 60 old laying hens were used. The crop and the gizzard content were analyzed in the morning, at noon and in the afternoon in the same way as in broilers. Proportions of plant particles varied between 6 and 12 %and between 32 and 38 % in the crop and the gizzard, respectively. It is estimated that the intake of plant particles amounts to 20-25 % of daily feed intake in laying hens

Recientes cambios en glaciares y sistemas paraglaciares, Antártica Marítima

The article investigates changes in paraglacial systems and interconnections with glacial shrinkage on King George Island, Maritime Antarctica. The proglacial environment, as a result of recent deglaciation, was analyzed, and the types of landforms and at different scales were identified. These records are useful for successive evolutionary stages paraglacial system reconstruction. Glaciers and paraglacial systems showed rapid changes and new landscapes were detected on King George Island. Glaciers presented an important change between 2000 and 2018, where its classification has changed from marine-terminating to landterminating glacier (no-marine). There are currently 21 glaciers land-terminating on King George Island (corresponding to 31% of the glaciers) and 11 are present in Admiralty Bay. 25% of these glaciers were marine in 2000. The new paraglacial environments (since 2000) has 1.7 km2 of the total area. Ecology, Wanda, Windy, Anna South and Baranowski Glaciers showed outwash plain, talus slopes and fluvial channels landforms in recent paraglacial system. Geomorphological mapping shows that paraglacial processes which differ between environments marginal to glacier ice are not standardized.O artigo investiga alterações nos sistemas paraglaciais e interconexões com a retração glacial em setores da ilha Rei George, Antártica Marítima. Foi analisado o ambiente proglacial, resultado da deglaciação recente, e identificados os tipos de formas de relevo em suas diferentes escalas. Estes registros são úteis para a reconstrução de estágios sucessivos evolutivos do sistema paraglacial. Os resultados demonstraram que o ambiente marginal às geleiras e sistemas paraglaciais estão evoluindo na ilha Rei George e há novas paisagens. Algumas geleiras apresentaram uma mudança importante entre 2000 e 2019, onde sua classificação mudou de geleira de terminação marinha para geleira de terminação terrestre (não-marinha). Atualmente há 21 geleiras com término em terra na ilha Rei George (correspondendo a 31% das geleiras) e 11 destas estão localizadas na Baía do Almirantado. 25% destas geleiras eram marinhas em 2000. Os novos ambientes paraglaciais (desde 2000) têm 1,7 km2 ao total de área. Os ambientes marginais às geleiras (como as geleiras Ecology, Wanda, Windy, Anna Sul e Baranowski) mostraram formas de gênese não glacial, como planície de lavagem, depositos de tálus, ravinas e canais fluviais no sistema paraglacial recente. O mapeamento geomorfológico evidencia que os processos paraglaciais se diferenciam entre os ambientes marginais ao gelo das geleiras, não são padronizados.El artículo investiga los cambios en los sistemas paraglaciares y las interconexiones con la retracción de los glaciares en la isla Rey Jorge, Antártica Marítima. Se analizó el ambiente proglacial, resultado de la deglaciación reciente, y se identificaron los tipos de formas de relieve en sus diferentes escalas. Estos registros son útiles para la reconstrucción de sucesivas etapas evolutivas en el sistema paraglacial. Los glaciares y los sistemas paraglaciares están evolucionando rápidamente y se están detectando nuevos paisajes en la isla Rey Jorge. Los glaciares mostraron un cambio importante entre 2000 y 2018, donde su clasificación cambió de glaciar de terminación marina a glaciar de terminación terrestre (no marino). Actualmente hay 21 glaciares de terminación terrestres en la isla Rey Jorge (que corresponden al 31% de los glaciares) y 11 están presentes en la Bahía del Almirantazgo. El 25% de estos glaciares eran marinos en 2000. Los nuevos entornos paraglaciares (desde 2000) cubren 1,7 km2 del área total. Los glaciares Ecology, Wanda, Windy, Anna Sul y Baranowski mostraron formas de llanuras de lavado, depósitos de tálus, barrancos y flujos superficiales fluviais en el sistema paraglacial reciente. El mapeo geomorfológico muestra que los procesos paraglaciares que difieren entre ambientes marginales al hielo glaciar no están estandarizados

Combined Analysis of Myocardial Deformation and Oxygenation Detects Inducible Ischemia Unmasked by Breathing Maneuvers in Chronic Coronary Syndrome.

Introduction In patients with chronic coronary syndromes, hyperventilation followed by apnea has been shown to unmask myocardium susceptible to inducible deoxygenation. The aim of this study was to assess whether such a provoked response is co-localized with myocardial dysfunction. Methods A group of twenty-six CAD patients with a defined stenosis (quantitative coronary angiography > 50%) underwent a cardiovascular magnetic resonance (CMR) exam prior to revascularization. Healthy volunteers older than 50 years served as controls (n = 12). Participants hyperventilated for 60s followed by brief apnea. Oxygenation-sensitive images were analyzed for changes in myocardial oxygenation and strain. Results In healthy subjects, hyperventilation resulted in global myocardial deoxygenation (-10.2 ± 8.2%, p 0.05), yet this was significant for both myocardial oxygenation [area under the curve (AUC): 0.88, p > 0.001] and peak strain (AUC: 0.73, p = 0.023) measured with apnea. A combined analysis of myocardial oxygenation and peak strain resulted in an incrementally higher AUC of 0.91, p < 0.001 than strain alone. Conclusion In myocardium of patients with chronic coronary syndromes and primarily intermediate coronary stenoses, cine oxygenation-sensitive CMR can identify an impaired vascular and functional response to a vasoactive breathing maneuver stimulus indicative of inducible ischemia

Phase 2 randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis

Purpose: To evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for treating moderate-to-severe neurotrophic keratitis (NK), a rare degenerative corneal disease resulting from impaired corneal innervation. Design: Phase 2 multicenter, randomized, double-masked, vehicle-controlled trial. Participants: Patients with stage 2 (moderate) or stage 3 (severe) NK in 1 eye. Methods: The REPARO phase 2 study assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 μg/ml, 20 μg/ml, or vehicle. Treatment was administered 6 drops per day for 8 weeks. Patients then entered a 48- or 56-week follow-up period. Safety was assessed in all patients who received study treatment, whereas efficacy was by intention to treat. Main Outcome Measures: Corneal healing (defined as <0.5-mm maximum diameter of fluorescein staining in the lesion area) was assessed by masked central readers at week 4 (primary efficacy end point) and week 8 (key secondary end point) of controlled treatment. Corneal healing was reassessed post hoc by masked central readers using a more conservative measure (0-mm staining in the lesion area and no other persistent staining). Results: At week 4 (primary end point), 19.6% of vehicle-treated patients achieved corneal healing (<0.5-mm lesion staining) versus 54.9% receiving rhNGF 10 μg/ml (+35.3%; 97.06% confidence interval [CI], 15.88–54.71; P < 0.001) and 58.0% receiving rhNGF 20 μg/ml (+38.4%; 97.06% CI, 18.96–57.83; P < 0.001). At week 8 (key secondary end point), 43.1% of vehicle-treated patients achieved less than 0.5-mm lesion staining versus 74.5% receiving rhNGF 10 μg/ml (+31.4%; 97.06% CI, 11.25–51.49; P = 0.001) and 74.0% receiving rhNGF 20 μg/ml (+30.9%; 97.06% CI, 10.60–51.13; P = 0.002). Post hoc analysis of corneal healing by the more conservative measure (0-mm lesion staining and no other persistent staining) maintained statistically significant differences between rhNGF and vehicle at weeks 4 and 8. More than 96% of patients who healed after controlled rhNGF treatment remained recurrence free during follow-up. Treatment with rhNGF was well tolerated; adverse effects were mostly local, mild, and transient. Conclusions: Topical rhNGF is safe and more effective than vehicle in promoting healing of moderate-to-severe NK

Phase I trial of recombinant human nerve growth factor for neurotrophic keratitis

Neurotrophic keratitis/keratopathy (NK), a rare degenerative corneal disease, lacks effective pharmacologic therapies.1 Because NK pathology involves trigeminal nerve damage and loss of corneal innervation, nerve growth factor (NGF) is surmised to promote healing of NK.2 Preliminary studies with murine NGF demonstrated efficacy for treating corneal neurotrophic ulcers;3 however, the complex tertiary structure of NGF has complicated the production of recombinant human NGF (rhNGF) suitable for clinical development. To this end, we developed an Escherichia coli–derived rhNGF formulation that demonstrated to be well tolerated and safe for topical ophthalmic use in a phase I study in healthy volunteers.4 We report phase I results of topical rhNGF for patients with moderate-to-severe NK

Mechanistic insight into RET kinase inhibitors targeting the DFG-out conformation in RET-rearranged cancer

Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. Here, we provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors such as AD80 or ponatinib that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors. Using chemical genomics in conjunction with phosphoproteomic analyses in RET-rearranged cells we identify the CCDC6-RETI788N mutation and drug-induced MAPK pathway reactivation as possible mechanisms, by which tumors may escape the activity of RET inhibitors. Our data provide mechanistic insight into the druggability of RET kinase fusions that may be of help for the development of effective therapies targeting such tumors

The feasibility of novel point-of-care diagnostics for febrile illnesses at health centres in Southeast Asia: a mixed-methods study

Background The decline of malaria in Southeast Asia means other causes of fever are increasingly relevant, but often undiagnosed. The objective of this study was to assess the feasibility of point-of-care tests to diagnose acute febrile illnesses in primary care settings. Methods A mixed-methods study was conducted at nine rural health centres in western Cambodia. Workshops introduced health workers to the STANDARD(TM) Q Dengue Duo, STANDARD(TM) Q Malaria/CRP Duo and a multiplex biosensor detecting antibodies and/or antigens of eight pathogens. Sixteen structured observation checklists assessed users’ performances and nine focus group discussions explored their opinions. Results All three point-of-care tests were performed well under assessment, but sample collection was difficult for the dengue test. Respondents expressed that the diagnostics were useful and could be integrated into routine clinical care, but were not as convenient to perform as standard malaria rapid tests. Health workers recommended that the most valued point-of-care tests would directly inform clinical management (e.g. a decision to refer a patient or to provide/withhold antibiotics). Conclusions Deployment of new point-of-care tests to health centres could be feasible and acceptable if they are user-friendly, selected for locally circulating pathogens and are accompanied by disease-specific education and simple management algorithms

Cognitive reserve and cognitive performance of patients with focal frontal lesions

The Cognitive reserve (CR) hypothesis was put forward to account for the variability in cognitive performance of patients with similar degrees of brain pathology. Compensatory neural activity within the frontal lobes has often been associated with CR. For the first time we investigated the independent effects of two CR proxies, education and NART IQ, on measures of executive function, fluid intelligence, speed of information processing, verbal short term memory (vSTM), naming, and perception in a sample of 86 patients with focal, unilateral frontal lesions and 142 healthy controls. We fitted multiple linear regression models for each of the cognitive measures and found that only NART IQ predicted executive and naming performance. Neither education nor NART IQ predicted performance on fluid intelligence, processing speed, vSTM or perceptual abilities. Education and NART IQ did not modify the effect of lesion severity on cognitive impairment. We also found that age significantly predicted performance on executive tests and the majority of our other cognitive measures, except vSTM and GNT. Age was the only predictor for fluid intelligence. This latter finding suggests that age plays a role in executive performance over and above the contribution of CR proxies in patients with focal frontal lesions. Overall, our results suggest that the CR proxies do not appear to modify the relationship between cognitive impairment and frontal lesions

Production of YP170 Vitellogenins Promotes Intestinal Senescence in Caenorhabditis elegans

During aging, etiologies of senescence cause multiple pathologies, leading to morbidity and death. To understand aging requires identification of these etiologies. For example, C. elegans hermaphrodites consume their own intestinal biomass to support yolk production, which in later life drives intestinal atrophy and ectopic yolk deposition. Yolk proteins (vitellogenins) exist as 3 abundant species: YP170, derived from vit-1 - vit-5, and YP115 and YP88, derived from vit-6. Here we show that inhibiting YP170 synthesis leads to a reciprocal increase in YP115/YP88 levels and vice versa, an effect involving post-transcriptional mechanisms. Inhibiting YP170 production alone, despite increasing YP115/YP88 synthesis, reduces intestinal atrophy as much as inhibition of all YP synthesis, which increases lifespan. By contrast, inhibiting YP115/YP88 production alone accelerates intestinal atrophy and reduces lifespan, an effect that is dependent upon increased YP170 production. Thus, despite copious abundance of both YP170 and YP115/YP88, only YP170 production is coupled to intestinal atrophy and shortened lifespan. In addition, increasing levels of YP115/YP88 but not of YP170 increases resistance to oxidative stress; thus, longevity resulting from reduced vitellogenin synthesis is not attributable to oxidative stress resistance

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS &gt;5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p&lt;0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice