Selective decontamination of the digestive tract in a burns unit reduces the incidence of hospital-acquired infections: A retrospective before-and-after cohort study.

OBJECTIVE: To evaluate the effect of selective decontamination of the digestive tract (SDD) on hospital-acquired infections (HAIs) in patients with acute burn injury requiring admission to a Burns Unit (BU). DESIGN: Retrospective before-and-after cohort study, between January 2017 and June 2023. SDD was implemented in March 2019, dividing patients into two groups. SETTING: Four-bed BU, in a referral University Hospital in Spain. PATIENTS: All the patients admitted during the study period were eligible for analysis. Patients who died or were discharged within 48hours of admission, and patients with an estimated survival less than 10% not considered for full escalation of therapy were excluded. INTERVENTION: SDD comprised the administration of a 4-day course of an intravenous antibiotic, and an oral suspension and oral topical paste of non-absorbable antibiotics during the stay in the BU. MAIN VARIABLE OF INTEREST: Incidence of HAIs during the stay in the BU. SECONDARY OUTCOMES: incidence of specific types of infections by site (bacteremia, pneumonia, skin and soft tissue infection) and microorganism (Gram-positive, Gram-negative, fungi), and safety endpoints. RESULTS: We analyzed 72 patients: 27 did not receive SDD, and 45 received SDD. The number of patients who developed HAIs were 21 (77.8%) and 21 (46.7%) in the non-SDD and the SDD groups, respectively (p=0.009). The number of hospital-acquired infectious episodes were 2.52 (1.21-3.82) and 1.13 (0.54-1.73), respectively (p=0.029). CONCLUSIONS: SDD was associated with a reduced incidence of bacterial HAIs and a decrease in the number of infectious episodes per patient.

A retrospective clinical study to compare the ability of cone-beam computed tomographic images and periapical radiographs to reveal cracked teeth, split teeth, and teeth with vertical root fractures.

BACKGROUND: This retrospective clinical study aimed to compare the sensitivity of cone-beam computed tomographic (CBCT) images and periapical (PA) radiographs to reveal cracked teeth, split teeth, and teeth with vertical root fractures (VRFs). METHODS: The authors included 98 patients (98 teeth) diagnosed with a longitudinal tooth fracture (LTF) (cracked tooth, split tooth, VRF) through direct visualization after extraction and with comprehensive clinical and radiographic records. They collected demographic, clinical, and radiographic data. The authors evaluated PA radiographs and CBCT images to identify fractures, fracture lines, and the different patterns of bone loss associated with these teeth. They used the McNemar test to compare PA radiographs and CBCT scans when assessing bone loss. They used the Fisher test to determine statistical relationships between fracture types and demographic, clinical, and radiologic traits. They used an analysis of variance test to compare patient age with fracture types. RESULTS: CBCT images were significantly more effective (P < .05) in detecting bone loss patterns associated with LTFs than with PA radiographs, with 71% of cases detected via CBCT images compared with 42% via radiographs. Mean age was significantly greater (P < .05) in patients with teeth with VRFs than in patients with split teeth. A significant relationship was observed between the type of fracture and the following variables: root canal treatment (split, VRF, P = .002), deep probing depth (≥ 5 mm) (VRF, P = .026), and having more than 8 teeth extracted from the mouth (VRF, P = .032). Overall, there was a significant difference (P < .001) between the visualization of fracture lines (45% on PA radiographs, 65% on CBCT images). CONCLUSIONS: CBCT scans provided more information on LTFs than PA radiographs, particularly in the identification of periradicular bone changes. PRACTICAL IMPLICATIONS: CBCT imaging can assist in making the clinical diagnosis of LTFs through observation of bone loss patterns, providing more information than PA radiographs.

Genetic diversity of the banana Fusarium wilt pathogen in Cuba and across Latin America and the Caribbean.

Fusarium wilt of bananas (FWB) is a severe plant disease that leads to substantial losses in banana production worldwide. It remains a major concern for Cuban banana cultivation. The disease is caused by members of the soil-borne Fusarium oxysporum species complex. However, the genetic diversity among Fusarium species infecting bananas in Cuba has remained largely unexplored. In our comprehensive survey, we examined symptomatic banana plants across all production zones in the country, collecting 170 Fusarium isolates. Leveraging genotyping-by-sequencing and whole-genome comparisons, we investigated the genetic diversity within these isolates and compared it with a global Fusarium panel. Notably, typical FWB symptoms were observed in Bluggoe cooking bananas and Pisang Awak subgroups across 14 provinces. Our phylogenetic analysis revealed that F. purpurascens, F. phialophorum, and F. tardichlamydosporum are responsible for FWB in Cuba, with F. tardichlamydosporum dominating the population. Furthermore, we identified between five and seven distinct genetic clusters, with F. tardichlamydosporum isolates forming at least two subgroups. This finding underscores the high genetic diversity of Fusarium spp. contributing to FWB in the Americas. Our study sheds light on the population genetic structure and diversity of the FWB pathogen in Cuba and the broader Latin American and Caribbean regions.

Linear Regression of Sampling Distributions of the Mean.

We show that the simple and multiple linear regression coefficients and the coefficient of determination R2 computed from sampling distributions of the mean (with or without replacement) are equal to the regression coefficients and coefficient of determination computed with individual data. Moreover, the standard error of estimate is reduced by the square root of the group size for sampling distributions of the mean. The result has applications when formulating a distance measure between two genes in a hierarchical clustering algorithm. We show that the Pearson R coefficient can measure how differential expression in one gene correlates with differential expression in a second gene.

Climate-driven shifts in the diversity of plants in the Neotropical seasonally dry forest: Evaluating the effectiveness of protected areas.

Given the current environmental crisis, biodiversity protection is one of the most urgent socio-environmental priorities. However, the effectiveness of protected areas (PAs), the primary strategy for safeguarding ecosystems, is challenged by global climate change (GCC), with evidence showing that species are shifting their distributions into new areas, causing novel species assemblages. Therefore, there is a need to evaluate PAs' present and future effectiveness for biodiversity under the GCC. Here, we analyzed changes in the spatiotemporal patterns of taxonomic and phylogenetic diversity (PD) of plants associated with the Neotropical seasonally dry forest (NSDF) under GCC scenarios. We modeled the climatic niche of over 1000 plant species in five representative families (in terms of abundance, dominance, and endemism) of the NSDF. We predicted their potential distributions in the present and future years (2040, 2060, and 2080) based on an intermediate scenario of shared socio-economic pathways (SSP 3.70), allowing species to disperse to new sites or constrained to the current distribution. Then, we tested if the current PAs network represents the taxonomic and phylogenetic diversities. Our results suggest that GCC could promote novel species assemblages with local responses (communities' modifications) across the biome. In general, models predicted losses in the taxonomic and phylogenetic diversities of all the five plant families analyzed across the distribution of the NSDF. However, in the northern floristic groups (i.e., Antilles and Mesoamerica) of the NSDF, taxonomic and PD will be stable in GCC projections. In contrast, across the NSDF in South America, some cores will lose diversity while others will gain diversity under GCC scenarios. PAs in some NSDF regions appeared insufficient to protect the NSDF diversity. Thus, there is an urgent need to assess how the PA system could be better reconfigured to warrant the protection of the NSDF.

Dada la actual crisis ambiental, la protección de la biodiversidad se presenta como una de las prioridades socio ambientales más urgentes. Sin embargo, la efectividad de las áreas protegidas (AP), la estrategia principal para salvaguardar los ecosistemas, se ve desafiada por el cambio climático global (CCG), con evidencia que muestra que las especies están desplazando sus distribuciones hacia nuevas áreas, provocando conjuntos de especies novedosos. Por lo tanto, es necesario evaluar la efectividad actual y futura de las AP para la biodiversidad bajo el CCG. En este contexto, analizamos cambios en los patrones espacio­temporales de diversidad taxonómica y filogenética de plantas asociadas al bosque estacionalmente seco neotropical (BES) bajo escenarios de CCG. Modelamos el nicho climático de más de 1,000 especies de plantas en cinco familias representativas (en términos de abundancia, dominancia y endemismo) del BES. Pronosticamos sus distribuciones potenciales en los años actuales y futuros (2040, 2060 y 2080) basándonos en un escenario intermedio de trayectorias socioeconómicas compartidas (SSP 3.70), permitiendo que las especies se dispersen a nuevos sitios o estén limitadas a la distribución actual. Luego, evaluamos si la red actual de AP representa las diversidades taxonómicas y filogenéticas. Nuestros resultados sugieren que el CCG podría promover conjuntos de especies novedosos con respuestas locales (modificaciones en las comunidades) en todo el bioma. En general, los modelos pronosticaron pérdidas en las diversidades taxonómicas y filogenéticas de las cinco familias de plantas analizadas en la distribución del BES. Sin embargo, en los grupos florísticos del norte (es decir, Antillas y Mesoamérica) del BSDN, la diversidad taxonómica y filogenética se mantendrá estable en las proyecciones de CCG. En cambio, en toda la región del BES en América del Sur, algunos núcleos perderán diversidad mientras que otros ganarán diversidad bajo escenarios de CCG. Algunas AP en regiones del BES parecen ser insuficientes para proteger la diversidad del bioma. Por lo tanto, es urgente evaluar cómo se podría reconfigurar mejor el sistema de AP para garantizar la protección del BES.

Identification of keystone taxa in root canals and periapical lesions of post-treatment endodontic infections: Next generation microbiome research.

AIM: The aim of this study was to analyse and compare the microbiome present in root canals and periapical lesions of teeth with post-treatment infections, and to identify the presence of keystone taxa in both habitats using next-generation sequencing analysis. METHODOLOGY: Apices and periapical lesions of patients with post-treatment apical periodontitis were surgically extracted. Specimens were cryo-pulverized, bacterial DNA was extracted, and the V3-V4 hypervariable regions of the 16S rRNA gene were sequenced using the Illumina Miseq platform. Bioinformatic analysis was carried out with Mothur software, whilst diversity indices were obtained using operational taxonomic units (OTUs). The diversity indices were compared with the Kruskal-Wallis test, and community composition differences were explored with Permutational Multivariate Analysis of Variance (PERMANOVA). A bacterial functional study was performed with the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. Co-occurrence network analyses were performed using the Sparse Correlations for Compositional data (SparCC). Eigencentrality, clr-based abundance and ubiquitousness were applied to infer keystone taxa. P values <.05 were considered statistically significant. RESULTS: Thirty-two apices and thirty-nine periapical lesions were sequenced and analysed. A similar alpha-diversity (p < .05) and community composition (p = .91) was observed for apices and lesion samples. The most abundant OTUs identified amongst all samples included Fusobacterium nucleatum, Prevotella loescheii, Streptococcus intermedius, Porphyromonas gingivalis, Parvimonas micra, Synergistetes bacterium, Tannerella forsythia and Peptostreptococcus stomatis. The metabolic pathways with >0.81% abundances included membrane transport, genetic information processing and metabolic pathways. F. nucleatum was identified as a keystone taxon as it showed ubiquitousness, an eigenvector centrality value of 0.83 and a clr-based abundance >4. CONCLUSIONS: The microbiome in apices and periapical lesions of post-treatment endodontic infections showed a similar diversity and taxonomic composition. Co-occurrence network analyses at OTU level identified F. nucleatum as a keystone taxon candidate in these infections.

Implications of the three-dimensional chromatin organization for genome evolution in a fungal plant pathogen.

The spatial organization of eukaryotic genomes is linked to their biological functions, although it is not clear how this impacts the overall evolution of a genome. Here, we uncover the three-dimensional (3D) genome organization of the phytopathogen Verticillium dahliae, known to possess distinct genomic regions, designated adaptive genomic regions (AGRs), enriched in transposable elements and genes that mediate host infection. Short-range DNA interactions form clear topologically associating domains (TADs) with gene-rich boundaries that show reduced levels of gene expression and reduced genomic variation. Intriguingly, TADs are less clearly insulated in AGRs than in the core genome. At a global scale, the genome contains bipartite long-range interactions, particularly enriched for AGRs and more generally containing segmental duplications. Notably, the patterns observed for V. dahliae are also present in other Verticillium species. Thus, our analysis links 3D genome organization to evolutionary features conserved throughout the Verticillium genus.

The soil-borne white root rot pathogen Rosellinia necatrix expresses antimicrobial proteins during host colonization.

Rosellinia necatrix is a prevalent soil-borne plant-pathogenic fungus that is the causal agent of white root rot disease in a broad range of host plants. The limited availability of genomic resources for R. necatrix has complicated a thorough understanding of its infection biology. Here, we sequenced nine R. necatrix strains with Oxford Nanopore sequencing technology, and with DNA proximity ligation we generated a gapless assembly of one of the genomes into ten chromosomes. Whereas many filamentous pathogens display a so-called two-speed genome with more dynamic and more conserved compartments, the R. necatrix genome does not display such genome compartmentalization. It has recently been proposed that fungal plant pathogens may employ effectors with antimicrobial activity to manipulate the host microbiota to promote infection. In the predicted secretome of R. necatrix, 26 putative antimicrobial effector proteins were identified, nine of which are expressed during plant colonization. Two of the candidates were tested, both of which were found to possess selective antimicrobial activity. Intriguingly, some of the inhibited bacteria are antagonists of R. necatrix growth in vitro and can alleviate R. necatrix infection on cotton plants. Collectively, our data show that R. necatrix encodes antimicrobials that are expressed during host colonization and that may contribute to modulation of host-associated microbiota to stimulate disease development.

Aberrant Right and Left Gastric Veins as a Cause of Hepatic Pseudolesions: A Report of Three Cases.

The complex structure of the liver and its elaborate hemodynamics can cause hepatic pseudolesions on contrast-enhanced imaging, making the interpretation of diagnostic liver imaging challenging. Aberrant gastric veins are rare; most of their epidemiology data comes from small single-center studies. While current literature suggests that pseudolesions originating from aberrant gastric veins mainly present as hyperdense defects, some cases can also show up as hypodense, as shown in these cases. Differences in flow rates between the portal and aberrant veins and the timing of the scans could explain this contradiction. Identifying aberrant gastric veins on cross-sectional imaging is crucial because they could be misdiagnosed as liver lesions, granting further unnecessary workups or invasive procedures. Aberrant gastric veins can also act as pathways for the spread of gastric cancer. This manuscript presents one aberrant right gastric vein and two aberrant left gastric veins causing hepatic pseudolesions.

Current knowledge gaps in extracorporeal respiratory support.

Extracorporeal life support (ECLS) for acute respiratory failure encompasses veno-venous extracorporeal membrane oxygenation (V-V ECMO) and extracorporeal carbon dioxide removal (ECCO2R). V-V ECMO is primarily used to treat severe acute respiratory distress syndrome (ARDS), characterized by life-threatening hypoxemia or ventilatory insufficiency with conventional protective settings. It employs an artificial lung with high blood flows, and allows improvement in gas exchange, correction of hypoxemia, and reduction of the workload on the native lung. On the other hand, ECCO2R focuses on carbon dioxide removal and ventilatory load reduction ("ultra-protective ventilation") in moderate ARDS, or in avoiding pump failure in acute exacerbated chronic obstructive pulmonary disease. Clinical indications for V-V ECLS are tailored to individual patients, as there are no absolute contraindications. However, determining the ideal timing for initiating extracorporeal respiratory support remains uncertain. Current ECLS equipment faces issues like size and durability. Innovations include intravascular lung assist devices (ILADs) and pumpless devices, though they come with their own challenges. Efficient gas exchange relies on modern oxygenators using hollow fiber designs, but research is exploring microfluidic technology to improve oxygenator size, thrombogenicity, and blood flow capacity. Coagulation management during V-V ECLS is crucial due to common bleeding and thrombosis complications; indeed, anticoagulation strategies and monitoring systems require improvement, while surface coatings and new materials show promise. Moreover, pharmacokinetics during ECLS significantly impact antibiotic therapy, necessitating therapeutic drug monitoring for precise dosing. Managing native lung ventilation during V-V ECMO remains complex, requiring a careful balance between benefits and potential risks for spontaneously breathing patients. Moreover, weaning from V-V ECMO is recognized as an area of relevant uncertainty, requiring further research. In the last decade, the concept of Extracorporeal Organ Support (ECOS) for patients with multiple organ dysfunction has emerged, combining ECLS with other organ support therapies to provide a more holistic approach for critically ill patients. In this review, we aim at providing an in-depth overview of V-V ECMO and ECCO2R, addressing various aspects of their use, challenges, and potential future directions in research and development.

Quantitative analyses of T cell motion in tissue reveals factors driving T cell search in tissues.

T cells are required to clear infection, and T cell motion plays a role in how quickly a T cell finds its target, from initial naive T cell activation by a dendritic cell to interaction with target cells in infected tissue. To better understand how different tissue environments affect T cell motility, we compared multiple features of T cell motion including speed, persistence, turning angle, directionality, and confinement of T cells moving in multiple murine tissues using microscopy. We quantitatively analyzed naive T cell motility within the lymph node and compared motility parameters with activated CD8 T cells moving within the villi of small intestine and lung under different activation conditions. Our motility analysis found that while the speeds and the overall displacement of T cells vary within all tissues analyzed, T cells in all tissues tended to persist at the same speed. Interestingly, we found that T cells in the lung show a marked population of T cells turning at close to 180o, while T cells in lymph nodes and villi do not exhibit this "reversing" movement. T cells in the lung also showed significantly decreased meandering ratios and increased confinement compared to T cells in lymph nodes and villi. These differences in motility patterns led to a decrease in the total volume scanned by T cells in lung compared to T cells in lymph node and villi. These results suggest that the tissue environment in which T cells move can impact the type of motility and ultimately, the efficiency of T cell search for target cells within specialized tissues such as the lung.

Real-world evidence of sorafenib for the treatment of hepatocellular carcinoma: A single-center study.

Context: Hepatocellular carcinoma is the third leading cause of cancer death. Currently, sorafenib is the treatment of choice in advanced hepatocarcinoma. Aims: Assessing the effectiveness and toxicity of sorafenib in real-word clinical practice in patients with hepatocarcinoma. Settings and Design: Single-centered observational retrospective study. Methods and Material: We included patients with hepatocarcinoma who began treatment with sorafenib between 2008 and 2018. We evaluated overall survival, time to progression, and response using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events version 5. 2020. Statistical Analysis Used: Kaplan-Meier curves and the log-rank test were used to determine the survival time and estimate factors associated with these events. Data were analyzed with SPSS 19.0 software. Results: We included 36 patients (88.9% male) with an average age of 64 ± 3.4 years. The tumor stage was advanced (C) in 21 patients (61.8%). We obtained a median overall survival of 8.5 months (IQR 3.14-18.9) and a time to progression of 4.5 months (IQR 2.4-8.8). The main degree of response was progression in 19 patients (36.1%), followed by stable disease in 13 (52.8%). The most commonly reported adverse reactions were: constitutional (83.3%), gastrointestinal (55%) and dermatological symptoms (50.0%). The development of grades 3 or 4 toxicity was not associated with increased overall survival (P = 0.719). Conclusions: The findings of the survival analysis obtained in real practice are similar to those obtained in pivotal clinical trials. Adverse reactions were different from those expected.

Effects of changes in trunk inclination on ventilatory efficiency in ARDS patients: quasi-experimental study.

BACKGROUND: Trunk inclination from semirecumbent head-upright to supine-flat positioning reduces driving pressure and increases respiratory system compliance in patients with acute respiratory distress syndrome (ARDS). These effects are associated with an improved ventilatory ratio and reduction in the partial pressure of carbon dioxide (PaCO2). However, these physiological effects have not been completely studied, and their mechanisms have not yet been elucidated. Therefore, this study aimed to evaluate the effects of a change in trunk inclination from semirecumbent (45°) to supine-flat (10°) on physiological dead space and ventilation distribution in different lung regions. RESULTS: Twenty-two ARDS patients on pressure-controlled ventilation underwent three 60-min steps in which trunk inclination was changed from 45° (baseline) to 10° (intervention) and back to 45° (control) in the last step. Tunk inclination from a semirecumbent (45°) to a supine-flat (10°) position resulted in a higher tidal volume [371 (± 76) vs. 433 (± 84) mL (P < 0.001)] and respiratory system compliance [34 (± 10) to 41 (± 12) mL/cmH2O (P < 0.001)]. The CO2 exhaled per minute improved from 191 mL/min (± 34) to 227 mL/min (± 38) (P < 0.001). Accordingly, Bohr's dead space ratio decreased from 0.49 (± 0.07) to 0.41 (± 0.06) (p < 0.001), and PaCO2 decreased from 43 (± 5) to 36 (± 4) mmHg (p < 0.001). In addition, the impedance ratio, which divides the ventilation activity of the ventral region by the dorsal region ventilation activity in tidal images, dropped from 1.27 (0.83-1.78) to 0.86 (0.51-1.33) (p < 0.001). These results, calculated from functional EIT images, indicated further ventilation activity in the dorsal lung regions. These effects rapidly reversed once the patient was repositioned at 45°. CONCLUSIONS: A change in trunk inclination from a semirecumbent (45 degrees) to a supine-flat position (10 degrees) improved Bohr's dead space ratio and reduced PaCO2 in patients with ARDS. This effect is associated with an increase in tidal volume and respiratory system compliance, along with further favourable impedance ventilation distribution toward the dorsal lung regions. This study highlights the importance of considering trunk inclination as a modifiable determinant of physiological parameters. The angle of trunk inclination is essential information that must be reported in ARDS patients.

The circadian and photoperiodic clock of the pea aphid.

The pea aphid, Acyrthosiphon pisum, is a paradigmatic photoperiodic species that exhibits a remarkable annual life cycle, which is tightly coupled to the seasonal changes in day length. During spring and summer, characterised by longer days, aphid populations consist exclusively of viviparous females that reproduce parthenogenetically. When autumn comes and the days shorten, aphids switch their reproductive mode and generate males and oviparous sexual females, which mate and produce cold-resistant eggs that overwinter and survive the unfavourable season. While the photoperiodic responses have been well described, the nature of the timing mechanisms which underlie day length discrimination are still not completely understood. Experiments from the 1960's suggested that aphids rely on an 'hourglass' clock measuring the elapsed time during the dark night by accumulating a biochemical factor, which reaches a critical threshold at a certain night length and triggers the switch in reproduction mode. However, the photoperiodic responses of aphids can also be attributed to a strongly dampened circadian clock. Recent studies have uncovered the molecular components and the location of the circadian clock in the brain of the pea aphid and revealed that it is well connected to the neurohormonal system controlling aphid reproduction. We provide an overview of the putative mechanisms of photoperiodic control in aphids, from the photoreceptors involved in this process to the circadian clock and the neuroendocrine system.

Pigment-dispersing factor is present in circadian clock neurons of pea aphids and may mediate photoperiodic signalling to insulin-producing cells.

The neuropeptide pigment-dispersing factor (PDF) plays a pivotal role in the circadian clock of most Ecdysozoa and is additionally involved in the timing of seasonal responses of several photoperiodic species. The pea aphid, Acyrthosiphon pisum, is a paradigmatic photoperiodic species with an annual life cycle tightly coupled to the seasonal changes in day length. Nevertheless, PDF could not be identified in A. pisum so far. In the present study, we identified a PDF-coding gene that has undergone significant changes in the otherwise highly conserved insect C-terminal amino acid sequence. A newly generated aphid-specific PDF antibody stained four neurons in each hemisphere of the aphid brain that co-express the clock protein Period and have projections to the pars lateralis that are highly plastic and change their appearance in a daily and seasonal manner, resembling those of the fruit fly PDF neurons. Most intriguingly, the PDF terminals overlap with dendrites of the insulin-like peptide (ILP) positive neurosecretory cells in the pars intercerebralis and with putative terminals of Cryptochrome (CRY) positive clock neurons. Since ILP has been previously shown to be crucial for seasonal adaptations and CRY might serve as a circadian photoreceptor vital for measuring day length, our results suggest that PDF plays a critical role in aphid seasonal timing.

Nuclear genome organization in fungi: from gene folding to Rabl chromosomes.

Comparative genomics has recently provided unprecedented insights into the biology and evolution of the fungal lineage. In the postgenomics era, a major research interest focuses now on detailing the functions of fungal genomes, i.e. how genomic information manifests into complex phenotypes. Emerging evidence across diverse eukaryotes has revealed that the organization of DNA within the nucleus is critically important. Here, we discuss the current knowledge on the fungal genome organization, from the association of chromosomes within the nucleus to topological structures at individual genes and the genetic factors required for this hierarchical organization. Chromosome conformation capture followed by high-throughput sequencing (Hi-C) has elucidated how fungal genomes are globally organized in Rabl configuration, in which centromere or telomere bundles are associated with opposite faces of the nuclear envelope. Further, fungal genomes are regionally organized into topologically associated domain-like (TAD-like) chromatin structures. We discuss how chromatin organization impacts the proper function of DNA-templated processes across the fungal genome. Nevertheless, this view is limited to a few fungal taxa given the paucity of fungal Hi-C experiments. We advocate for exploring genome organization across diverse fungal lineages to ensure the future understanding of the impact of nuclear organization on fungal genome function.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.