Disrupted Structural Brain Connectome Is Related to Cognitive Impairment in Patients With Ischemic Leukoaraiosis

Ischemic leukoaraiosis (ILA) is related to cognitive impairment and vascular dementia in the elderly. One possible mechanism could be the disruption of white matter (WM) tracts and network function that connect distributed brain regions involved in cognition. The purpose of this study was to investigate the relationship between structural connectome and cognitive functions in ILA patients. A total of 89 patients with ILA (Fazekas score ≥ 3) and 90 healthy controls (HCs) underwent comprehensive neuropsychological examinations and diffusion tensor imaging scans. The tract-based spatial statistics approach was employed to investigate the WM integrity. Graph theoretical analysis was further applied to construct the topological architecture of the structural connectome in ILA patients. Partial correlation analysis was used to investigate the relationships between network measures and cognitive performances in the ILA group. Compared with HCs, the ILA patients showed widespread WM integrity disruptions. The ILA group displayed increased characteristic path length (Lp) and decreased global network efficiency at the level of the whole brain relative to HCs, and reduced nodal efficiencies, predominantly in the frontal–subcortical and limbic system regions. Furthermore, these structural connectomic alterations were associated with cognitive impairment in ILA patients. The association between WM changes (i.e., fractional anisotropy and mean diffusivity measures) and cognitive function was mediated by the structural connectivity measures (i.e., local network efficiency and Lp). In conclusion, cognitive impairment in ILA patients is related to microstructural disruption of multiple WM fibers and topological disorganization of structural networks, which have implications in understanding the relationship between ILA and the possible attendant cognitive impairment

Plastics in the marine environment are reservoirs for antibiotic and metal resistance genes

Plastics have been accumulated offshore and in the deep oceans at an unprecedented scale. Microbial communities have colonized the plastisphere, which has become a reservoir for both antibiotic and metal resistance genes (ARGs and MRGs). This is the first analysis of the diversity, abundance, and co-occurrence of ARGs and MRGs, and their relationships within the microbial community, using metagenomic data of plastic particles observed in the North Pacific Gyre obtained from the National Centre for Biotechnology Information Sequence Read Archive database. The abundance of ARGs and MRGs in microbial communities on the plastics were in the ranges 7.07 x 10(-4)-1.21 x 10(-2) and 5.51 x 10(-3)-4.82 x 10(-2) copies per 16S rRNA, respectively. Both the Shannon-Wiener indices and richness of ARGs and MRGs in plastics microbiota were significantly greater than those of ARGs and MRGs in seawater microbiota in the North Pacific Gyre via one-way analysis of variance. Multidrug resistance genes and multi-metal resistance genes were the main classes of genes detected in plastic microbiota. There were no significant differences in the abundance or diversity of ARGs and MRGs between macroplastics biota and microplastics biota, indicating that particle size had no effect on resistance genes. Procrustes analysis suggested that microbial community composition was the determining factor of the ARG profile but not for MRG. Some ARGs and MRGs had a higher incidence of non-random co-occurrence, suggesting that the co-effects of selection for antibiotic or metal resistance are important factors influencing the resistome of the microbiota on the plastic particles

MD-2 is required for disulfide HMGB1-dependent TLR4 signaling

Innate immune receptors for pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) orchestrate inflammatory responses to infection and injury. Secreted by activated immune cells or passively released by damaged cells, HMGB1 is subjected to redox modification that distinctly influences its extracellular functions. Previously, it was unknown how the TLR4 signalosome distinguished between HMGB1 isoforms. Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2–deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. By screening HMGB1 peptide libraries, we identified a tetramer (FSSE, designated P5779) as a specific MD-2 antagonist preventing MD-2–HMGB1 interaction and TLR4 signaling. P5779 does not interfere with lipopolysaccharide-induced cytokine/chemokine production, thus preserving PAMP-mediated TLR4–MD-2 responses. Furthermore, P5779 can protect mice against hepatic ischemia/reperfusion injury, chemical toxicity, and sepsis. These findings reveal a novel mechanism by which innate systems selectively recognize specific HMGB1 isoforms. The results may direct toward strategies aimed at attenuating DAMP-mediated inflammation while preserving antimicrobial immune responsiveness

Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination

Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR. Within the Ig locus, DNA repair pathways are diverted from their canonical role in maintaining genomic integrity to permit AID-directed mutation and deletion of gene coding segments. Recently identified proteins, genes, and regulatory networks have provided new insights into the temporally and spatially coordinated molecular interactions that control the formation and repair of DSBs within the Ig locus. Unravelling the genetic program that allows B cells to selectively alter the Ig coding regions while protecting non-Ig genes from DNA damage advances our understanding of the molecular processes that maintain genomic integrity as well as humoral immunity

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

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

Increasing flood risk under climate change and social development in the Second Songhua River basin in Northeast China

Study region: Second Songhua River basin (SSRB), Northeast China. Study focus: Accurately assessing future flood risks is the premise and foundation of flood control and water resources management. At present, studies are still lacking in assessing future watershed flood risks that consider climate change and social development in Northeast China and the relative flood risk assessment framework. This study proposed an integrated flood assessment framework containing the AHP, entropy weight, and GCM downscaling methods, which was implemented in the SSRB, a typical watershed in Northeast China, to estimate future basin flood risks under climate change and social development. New hydrological insights for the region: The flood risk in the SSRB will increase significantly in the mid-term (2051–2075) and long-term (2076–2100) future. The areas under the four scenarios with greater than high-risk levels will expand by 28.9 %, 105.6 %, 165.6 %, and 156.7 %, respectively, compared to the historical scenario. The newly added areas mainly located in the lower reaches. Precipitation changes are the primary reason for the future flood risks. The increased GDP under a higher forcing degree will also significantly increase the flood risk in the long-term future in the lower reaches. Based on these above findings, extreme precipitation forecasting and flood management in downstream areas in the basin need to be enhanced. Energy-saving and emission-reduction measures should be simultaneously implemented

Effect of heat treatment temperatures on microstructure and mechanical property of linear friction welded joints of titanium alloys TC17(α+β)/TC17(β)

The heat treatment experiments were carried on titanium alloys (TC17 (α+β) + TC17 (β)) linear friction welded joint. Optical microscope (OM), scanning electron microscope (SEM) and microhardness instrument were used to investigate the effects of different heat treatment temperatures on the microstructure and mechanical properties of welded joints. The results show that recrystallization occurs at the weld zone (as weld). Metastable β phase structure is formed at the weld interface of as-welded joint. The microhardness of as-welded joint is lower than base metal and high cycle fatigue strength of as-welded joints is 345 MPa. Because welding speed is rapid, a large number of primary α phase is retained in thermal mechanically affected zone (TMAZ) of TC17 (α+β). After post-weld heat treatment, the metastable β phase structure is decomposed and dispersed (α+β) phase is separated out at the welded joints. With the increase of the heat treatment temperature, small secondary α phase is grown up and phases are partly spheroidized. After heat treatment, because metastable β phase structure is decomposed, the micro-hardness is greatly increased at the weld zone and TMAZ, and fatigue strength is increased by an average of 65 MPa at the welded joints. With the increase of the heat treatment temperature, the fracture toughness is improved at the TMAZ of welded joints