Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

水稻株高和抽穗期數量性狀基因座於兩個亞種雜交族群之圖譜分析及稻屬間之比較

Two inter-subspecific segregating populations were constructed to map quantitative trait loci (QTLs) for plant height (PH) and heading date (HD) in rice. A total of 99 and 95 polymorphic SSR and STS markers were used to establish linkage maps in japonica TK8 x indica IR1545-339 and japonica Nipponbare x IR1545-339, respectively. By employing composite interval mapping verified by single point analysis, ten PH and seven HD QTLs were located on seven and six chromosomes, respectively; only Qph1.2 and Qhd3 were common in the two populations. The phenotypic variance explained (PVE) by major PH and HD QTLs was 22.07% (Qph6.1) and 12.98% (Qph6.2), and 35.74% (Qhd3) and 15.54% (Qhd3), for TK8/IR1545-339 and Nipponbare/IR1545-339, respectively. Comparative genetic analysis of QTL intervals on rice pseudomolecules showing the convergence of QTLs affecting PH and HD across the Oryza genus revealed all QTLs uncovered in the two populations possibly allelic to QTLs previously published. By comparative mapping and candidate gene approach, we specified three PH, Qph1.2, Qph4, and Qph6.1, and one HD QTL, Qhd10, without high-resolution mapping, and the reality of QTLs identified by interval mapping were discussed herein

(64(4):253-278)The Development and Application of Molecular Markers of Wild Rice

野生稻具有高度遺傳歧異度，對於極端環境有著較高之耐受性，若將野生稻的基因體以分子輔助育種的策略應用於現代栽培種的水稻育種，可因應詭譎多變的氣候變遷與世界糧食需求激增等挑戰。本研究最終目的為將野生稻Oryza officinalis (IRGC. 100986；CC 基因體) 和Oryza australiensis (IRGC. 100882；EE 基因體)之重要基因導入於亞洲栽培稻Oryza sativa (AA 基因體) 之秈稻「台中秈10 號」(‘TCS10’) 和稉稻「台農67 號」(‘TNG67’)，現階段之目標為開發多型性分子標幟。篩選249 個亞洲栽培稻 (O. sativa) 簡單重複序列 (simple sequence repeat; SSR) 分子標幟，結果在O. officinalis 可擴增的分子標幟總計100 個，轉移率為40%，而在O. australiensis 可擴增的分子標幟總計67 個，轉移率為27%。在這些可擴增之SSR 分子標幟中，O. officinalis vs. ‘TCS10’ 和O. officinalis vs. ‘TNG67’ 間有72 個 (72%) 和71 個 (71%) 多型性分子標幟；在O. australiensis vs. ‘TCS10’ 和O. australiensis vs. ‘TNG67’ 間則有51 (76%) 和53 (79%) 個。此外，以生物資訊方法進行栽培種與野生種的基因體序列比較，依據插入/缺失 (indel) DNA 片段，一共設計了123 個分子標幟，分析結果發現在O. officinalis 和O. australiensis 可擴增的分子標幟分別為109 (89%) 和103 (84%) 個，大幅提升可擴增之分子標幟。並發現在O. officinalis vs. ‘TCS10’ 和O. officinalis vs. ‘TNG67’ 間有79 (72%) 與82 (75%) 個多型性分子標幟；而在O. australiensis vs. ‘TCS10’ 和O. australiensis vs. ‘TNG67’ 間則有64 (62%) 和65 (63%) 個多型性分子標幟。進一步以得到的多型性分子標幟分析O. officinalis × ‘TNG67’ 衍生之BC1F1 和BC2F1 世代，結果發現異型合子比例由86.7% (BC1F1) 下降為18.1% (BC2F1)，而 ‘TNG67’ 同型合子比例則大幅提升，顯示野生稻之染色體片段迅速地自子代染色體中剔除，因此不易建立完整的染色體片段置換系。 Wild rice has high genetic diversity and high tolerance to extreme environments. If genomes of wild rice can be applied into modern rice breeding programs by marker-assisted selection, newly bred cultivars can endure mercurial climate and meet sharply increased demands of food in the world. The goal for this research is to introgress genes/chromosome segments of Oryza officinalis with CC genome and Oryza australiensis with EE genome into Oryza sativa ssp. indica cv. ‘TCS10’ and ssp. japonica cv. ‘TNG67’ with AA genome, respectively. Currently, polymorphic markers were surveyed and developed. A total of 249 SSR (simple sequences repeat) had been applied but only 100 (40%) and 67 (27%) of markers could be amplified successfully in O. officinalis and O. australiensis, respectively. Among polymorphic SSR markers, 72 (72%) and 71 (71%) of markers were polymorphic between O. officinalis vs. ‘TCS10’ and ‘TNG67’, respectively; 57 (76%) and 53 (79%) of markers were polymorphic between O. australiensis vs. ‘TCS10’ and O. australiensis vs. ‘TNG67’, respectively. To effectively obtain polymorphic markers, the BES (BAC end sequence) of wild and the genome sequence of ssp. japonica cv. ‘Nipponbare’ were aligned to search for indel markers flanking with conserved sequences. A total of 123 markers had been developed, and 109 (89%) and 103 (84%) markers could be amplified successfully in O. officinalis and O. australiensis, respectively. Among which, 79 (72%) and 82 (75%) of markers were polymorphic between O. officinalis vs. ‘TCS10’ and ‘TNG67’, respectively; 64 (62%) and 65 (63%) of markers were polymorphic between O. australiensis vs. ‘TCS10’ and O. australiensis vs. ‘TNG67’, respectively. From genotypes of BC1F1 and BC2F1 populations derived from O. officinalis × ‘TNG67’, the ratio of heterozygotes was 86.7% (BC1F1) and abruptly decreased to 18.1% (BC2F1). It indicated that the chromosome segments of wild rice were excluded rapidly in backcrossed progenies, implying that it is very difficult to develop a complete chromosome segment substitute line (CSSL) population, which carried the chromosome segment from different genome of wild species into O. sativa background