Effect of Related and Unrelated Donor Haematopoietic Stem-Cell Transplantation on Outcome in Adults With High Risk Hematological Disease: An intention-to-treat Analysis of 410 Patients at a Single Center Institution

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De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis.

We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk

Evaluating the Sustainability of a Small-Scale Low-Input Organic Vegetable Supply System in the United Kingdom

www.mdpi.com/journal/sustainabilit

Are there differences in acute phase inflammation markers regarding the type of heart failure?

This study aimed to determine if there are differences in inflammatory markers in the acute phase between systolic heart failure and heart failure with preserved systolic function. One hundred and thirty-one patients with acute heart failure were recruited consecutively. At admission, plasma fibrinogen, C-reactive protein, sialic acid, von Willebrand factor, vascular endothelial growth factor, interleukin-6 and NTproBNP were all evaluated. If the ejection fraction was 45% or over patients were included in the HF-PSF group; the remaining patients were included in the SHF group. The HF-PSF patients were older (72±10 vs 63±12 years, P<0.001), presented a higher rate of atrial fibrillation (56.1 vs 21.3%, P<0.001), and had a lower rate of hemoglobin (12.2±2 vs 13.3±2.1 g/dL, P<0.01). No significant differences were observed in the inflammation markers analyzed among SHF and HF-PSF groups. In the acute phase of heart failure there is a marked elevation of inflammatory markers but there are no differences in the inflammatory markers analyzed between the two different types of heart failure

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Multiple pathways for apoptotic nuclear fragmentation.

We analyzed the ultrastructure of apoptotic nuclear fragmentation in U937 cells treated with many different apoptogenic agents. We found that this characteristic apoptotic feature can be achieved through multiple alternative pathways, depending on the apoptogenic inducer, leading to slightly different final nuclear morphologies. In most instances, the irregularly shaped nucleus of U937 rounds up; then, chromatin condenses at the nuclear periphery. Condensed chromatin can form protruding patches, which eventually bud from the nucleus in sealed vesicles through a process which is actin-dependent, since it could be blocked by cytochalasins. Alternatively, chromatin condenses in tiny, nonprotruding crescents, and a cleavage in the nuclear sap forms, beginning from the inner nuclear membrane and growing inward, thus splitting the nucleus. In U937 induced to apoptosis by hydrogen peroxide in the presence of ADP-ribosylation inhibitors, the nuclei fragment in many vesicles before chromatin even begins to condense: chromatin condensation probably occurs as a consequence. While all the apoptotic morphologies described above evolve from interphase cells, a peculiar apoptotic morphology, possibly deriving from mitotic cells, is detected upon oxidative stress, recalling the formation of micronuclei by clastogenic treatments; it shows partially membrane-bound chromatin patches, which look midway between condensed chromosomes and apoptotic condensed chromatin. The existence of these multiple pathways for nuclear fragmentation may indicate an evolutionary convergence, suggesting that this event may play an important physiological role in apoptosis

Possible role of perineal ultrasound in the diagnosis of cystocele

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