The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Axis.

Chikungunya virus (CHIKV), an emerging alphavirus, has infected millions of people. However, the factors modulating disease outcome remain poorly understood. Here, we show in germ-free mice or in oral antibiotic-treated conventionally housed mice with depleted intestinal microbiomes that greater CHIKV infection and spread occurs within 1 day of virus inoculation. Alteration of the microbiome alters TLR7-MyD88 signaling in plasmacytoid dendritic cells (pDCs) and blunts systemic production of type I interferon (IFN). Consequently, circulating monocytes express fewer IFN-stimulated genes and become permissive for CHIKV infection. Reconstitution with a single bacterial species, Clostridium scindens, or its derived metabolite, the secondary bile acid deoxycholic acid, can restore pDC- and MyD88-dependent type I IFN responses to restrict systemic CHIKV infection and transmission back to vector mosquitoes. Thus, symbiotic intestinal bacteria modulate antiviral immunity and levels of circulating alphaviruses within hours of infection through a bile acid-pDC-IFN signaling axis, which affects viremia, dissemination, and potentially transmission.

A computationally designed inhibitor of an Epstein-Barr viral Bcl-2 protein induces apoptosis in infected cells.

Because apoptosis of infected cells can limit virus production and spread, some viruses have co-opted prosurvival genes from the host. This includes the Epstein-Barr virus (EBV) gene BHRF1, a homolog of human Bcl-2 proteins that block apoptosis and are associated with cancer. Computational design and experimental optimization were used to generate a novel protein called BINDI that binds BHRF1 with picomolar affinity. BINDI recognizes the hydrophobic cleft of BHRF1 in a manner similar to other Bcl-2 protein interactions but makes many additional contacts to achieve exceptional affinity and specificity. BINDI induces apoptosis in EBV-infected cancer lines, and when delivered with an antibody-targeted intracellular delivery carrier, BINDI suppressed tumor growth and extended survival in a xenograft disease model of EBV-positive human lymphoma. High-specificity-designed proteins that selectively kill target cells may provide an advantage over the toxic compounds used in current generation antibody-drug conjugates.

De novo design of proteins housing excitonically coupled chlorophyll special pairs.

Natural photosystems couple light harvesting to charge separation using a 'special pair' of chlorophyll molecules that accepts excitation energy from the antenna and initiates an electron-transfer cascade. To investigate the photophysics of special pairs independently of the complexities of native photosynthetic proteins, and as a first step toward creating synthetic photosystems for new energy conversion technologies, we designed C2-symmetric proteins that hold two chlorophyll molecules in closely juxtaposed arrangements. X-ray crystallography confirmed that one designed protein binds two chlorophylls in the same orientation as native special pairs, whereas a second designed protein positions them in a previously unseen geometry. Spectroscopy revealed that the chlorophylls are excitonically coupled, and fluorescence lifetime imaging demonstrated energy transfer. The cryo-electron microscopy structure of a designed 24-chlorophyll octahedral nanocage with a special pair on each edge closely matched the design model. The results suggest that the de novo design of artificial photosynthetic systems is within reach of current computational methods.

Structures, activity and mechanism of the Type IIS restriction endonuclease PaqCI.

Type IIS restriction endonucleases contain separate DNA recognition and catalytic domains and cleave their substrates at well-defined distances outside their target sequences. They are employed in biotechnology for a variety of purposes, including the creation of gene-targeting zinc finger and TAL effector nucleases and DNA synthesis applications such as Golden Gate assembly. The most thoroughly studied Type IIS enzyme, FokI, has been shown to require multimerization and engagement with multiple DNA targets for optimal cleavage activity; however, details of how it or similar enzymes forms a DNA-bound reaction complex have not been described at atomic resolution. Here we describe biochemical analyses of DNA cleavage by the Type IIS PaqCI restriction endonuclease and a series of molecular structures in the presence and absence of multiple bound DNA targets. The enzyme displays a similar tetrameric organization of target recognition domains in the absence or presence of bound substrate, with a significant repositioning of endonuclease domains in a trapped DNA-bound complex that is poised to deliver the first of a series of double-strand breaks. PaqCI and FokI share similar structural mechanisms of DNA cleavage, but considerable differences in their domain organization and quaternary architecture, facilitating comparisons between distinct Type IIS enzymes.

Structure, substrate binding and activity of a unique AAA+ protein: the BrxL phage restriction factor.

Bacteriophage exclusion ('BREX') systems are multi-protein complexes encoded by a variety of bacteria and archaea that restrict phage by an unknown mechanism. One BREX factor, termed BrxL, has been noted to display sequence similarity to various AAA+ protein factors including Lon protease. In this study we describe multiple CryoEM structures of BrxL that demonstrate it to be a chambered, ATP-dependent DNA binding protein. The largest BrxL assemblage corresponds to a dimer of heptamers in the absence of bound DNA, versus a dimer of hexamers when DNA is bound in its central pore. The protein displays DNA-dependent ATPase activity, and ATP binding promotes assembly of the complex on DNA. Point mutations within several regions of the protein-DNA complex alter one or more in vitro behaviors and activities, including ATPase activity and ATP-dependent association with DNA. However, only the disruption of the ATPase active site fully eliminates phage restriction, indicating that other mutations can still complement BrxL function within the context of an otherwise intact BREX system. BrxL displays significant structural homology to MCM subunits (the replicative helicase in archaea and eukaryotes), implying that it and other BREX factors may collaborate to disrupt initiation of phage DNA replication.

Nuclear Medicine Imaging Tools in Fever of Unknown Origin: Time for a Revisit and Appropriate Use Criteria.

Fever of unknown origin (FUO) is a clinical conundrum for patients and clinicians alike, and imaging studies are often performed as part of the diagnostic workup of these patients. Recently, the Society of Nuclear Medicine and Molecular Imaging convened and approved a guideline on the use of nuclear medicine tools for FUO. The guidelines support the use of 2-18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in adults and children with FUO. 18F-FDG PET/CT allows detection and localization of foci of hypermetabolic lesions with high sensitivity because of the 18F-FDG uptake in glycolytically active cells that may represent inflammation, infection, or neoplasia. Clinicians should consider and insurers should cover 18F-FDG PET/CT when evaluating patients with FUO, particularly when other clinical clues and preliminary studies are unrevealing.

Hyperspectral signals in the soil: Plant-soil hydraulic connection and disequilibrium as mechanisms of drought tolerance and rapid recovery.

Predicting soil water status remotely is appealing due to its low cost and large-scale application. During drought, plants can disconnect from the soil, causing disequilibrium between soil and plant water potentials at pre-dawn. The impact of this disequilibrium on plant drought response and recovery is not well understood, potentially complicating soil water status predictions from plant spectral reflectance. This study aimed to quantify drought-induced disequilibrium, evaluate plant responses and recovery, and determine the potential for predicting soil water status from plant spectral reflectance. Two species were tested: sweet corn (Zea mays), which disconnected from the soil during intense drought, and peanut (Arachis hypogaea), which did not. Sweet corn's hydraulic disconnection led to an extended 'hydrated' phase, but its recovery was slower than peanut's, which remained connected to the soil even at lower water potentials (-5 MPa). Leaf hyperspectral reflectance successfully predicted the soil water status of peanut consistently, but only until disequilibrium occurred in sweet corn. Our results reveal different hydraulic strategies for plants coping with extreme drought and provide the first example of using spectral reflectance to quantify rhizosphere water status, emphasizing the need for species-specific considerations in soil water status predictions from canopy reflectance.

The novel anti-CRISPR AcrIIA22 relieves DNA torsion in target plasmids and impairs SpyCas9 activity.

To overcome CRISPR-Cas defense systems, many phages and mobile genetic elements (MGEs) encode CRISPR-Cas inhibitors called anti-CRISPRs (Acrs). Nearly all characterized Acrs directly bind Cas proteins to inactivate CRISPR immunity. Here, using functional metagenomic selection, we describe AcrIIA22, an unconventional Acr found in hypervariable genomic regions of clostridial bacteria and their prophages from human gut microbiomes. AcrIIA22 does not bind strongly to SpyCas9 but nonetheless potently inhibits its activity against plasmids. To gain insight into its mechanism, we obtained an X-ray crystal structure of AcrIIA22, which revealed homology to PC4-like nucleic acid-binding proteins. Based on mutational analyses and functional assays, we deduced that acrIIA22 encodes a DNA nickase that relieves torsional stress in supercoiled plasmids. This may render them less susceptible to SpyCas9, which uses free energy from negative supercoils to form stable R-loops. Modifying DNA topology may provide an additional route to CRISPR-Cas resistance in phages and MGEs.

Predictive Factors for Successful Same-Day Discharge After Minimally Invasive Colectomy and Stoma Reversal.

BACKGROUND: Same-day discharge after minimally invasive colorectal surgery is a safe, effective practice in specific patients that can enhance the efficiency of enhanced recovery pathways. OBJECTIVE: To identify predictive factors associated with success or failure of same-day discharge. DESIGN: Prospective cohort study from January 2020 to March 2023. SETTINGS: Tertiary colorectal center. PATIENTS: Adult patients eligible for same-day discharge with remote postdischarge follow-up included those with minimal comorbidities, residing near the hospital, having sufficient home support, and owning a mobile device. INTERVENTIONS: Patients were discharged on the day of surgery upon meeting specific criteria, including adequate pain control, tolerance of oral intake, independent mobility, urination, and the absence of complications. Successful same-day discharge was defined as discharge on the day of surgery without unplanned visits in the first 72 hours. MAIN OUTCOME MEASURES: Factors associated with successful or failed same-day discharge after minimally invasive colorectal surgery. RESULTS: A total of 175 patients (85.3%) were discharged on the day of surgery, with 14 patients (8%) having an unplanned visit within 72 hours. Overall, 161 patients (78.5%) were categorized as same-day discharge success and 44 patients (21.5%) as same-day discharge failure. The same-day discharge failure group had a higher Charlson Comorbidity Index (3.7 vs 2.8, p = 0.03). Mean length of stay (0.8 vs 3.0, p = 0.00), 30-day complications (10% vs 48%, p = 0.00), and readmissions (8% vs 27%, p = 0.00) were higher in the same-day discharge failure group. Regression analysis showed that failed same-day discharge was associated with higher comorbidities (OR 0.79; 95% CI, 0.66-0.95) and prolonged postanesthesia care unit time (OR 0.99; 95% CI, 0.99-0.99). Individuals who received a regional nerve block (OR 4.1; 95% CI, 1.2-14) and those who did not consume postoperative opioids (OR 4.6; 95% CI, 1-21) were more likely to have successful same-day discharge. LIMITATIONS: Single-center study. CONCLUSIONS: Our findings indicate that comorbidities and prolonged postanesthesia care unit stays were associated with same-day discharge failure, whereas regional nerve blocks and minimal postoperative opioids were related to success. These factors may inform future research aiming to enhance colorectal surgery recovery protocols. See Video Abstract . FACTORES PREDICTIVOS PARA UN ALTA EXITOSA EL MISMO DA DESPUS DE UNA COLECTOMA MNIMAMENTE INVASIVA Y REVERSIN DEL ESTOMA: ANTECEDENTES:El alta el mismo día después de una cirugía colorrectal mínimamente invasiva es una práctica segura y eficaz en pacientes específicos que puede mejorar la eficiencia de las vías de recuperación mejoradas.OBJETIVO:Identificar factores predictivos asociados con el éxito o fracaso del alta el mismo día.DISEÑO:Estudio de cohorte prospectivo del 01/2020 al 03/2023.AJUSTES:Centro colorrectal terciario.PACIENTES:Los pacientes adultos elegibles para el alta el mismo día con seguimiento remoto posterior al alta incluyeron aquellos con comorbilidades mínimas, que residían cerca del hospital, tenían suficiente apoyo en el hogar y poseían un dispositivo móvil.INTERVENCIONES:Los pacientes fueron dados de alta el día de la cirugía al cumplir con criterios específicos, incluido un control adecuado del dolor, tolerancia a la ingesta oral, movilidad independiente, micción y ausencia de complicaciones. El alta exitosa el mismo día se definió como el alta el día de la cirugía sin visitas no planificadas en las primeras 72 horas.PRINCIPALES MEDIDAS DE RESULTADO:Factores asociados con el alta exitosa o fallida el mismo día después de una cirugía colorrectal mínimamente invasiva.RESULTADOS:Un total de 175 (85,3%) pacientes fueron dados de alta el día de la cirugía y 14 (8%) pacientes tuvieron una visita no planificada dentro de las 72 horas. En total, 161 (78,5%) pacientes se clasificaron como éxito del alta el mismo día y 44 (21,5%) pacientes como fracaso del alta el mismo día. El grupo de fracaso del alta el mismo día tuvo un índice de comorbilidad de Charlson más alto (3,7, 2,8, p = 0,03). La duración media de la estancia hospitalaria (0,8, 3,0, p = 0,00), las complicaciones a los 30 días (10%, 48%, p = 0,00) y los reingresos (8%, 27%, p = 0,00) fueron mayores en el mismo día grupo de fallo de descarga. El análisis de regresión mostró que el alta fallida el mismo día se asoció con mayores comorbilidades (OR 0,79; IC del 95 %: 0,66; 0,95) y tiempo prolongado en la unidad de cuidados postanestésicos (OR 0,99; IC del 95 %: 0,99; 0,99). Las personas que recibieron un bloqueo nervioso regional (OR 4,1; IC del 95 %: 1,2, 14) y aquellos que no consumieron opioides posoperatorios (OR 4,6, IC del 95 %: 1-21) tuvieron más probabilidades de tener éxito en el mismo día -descarga.LIMITACIONES:Estudio unicéntrico.CONCLUSIONES:Nuestros hallazgos indican que las comorbilidades y las estancias prolongadas en la unidad de cuidados postanestésicos se asociaron con el fracaso del alta el mismo día, mientras que los bloqueos nerviosos regionales y los opioides postoperatorios mínimos se relacionaron con el éxito. Estos factores pueden informar investigaciones futuras destinadas a mejorar los protocolos de recuperación de la cirugía colorrectal. (Traducción-Yesenia Rojas-Khalil ).

De novo design of a fluorescence-activating ß-barrel.

The regular arrangements of ß-strands around a central axis in ß-barrels and of α-helices in coiled coils contrast with the irregular tertiary structures of most globular proteins, and have fascinated structural biologists since they were first discovered. Simple parametric models have been used to design a wide range of α-helical coiled-coil structures, but to date there has been no success with ß-barrels. Here we show that accurate de novo design of ß-barrels requires considerable symmetry-breaking to achieve continuous hydrogen-bond connectivity and eliminate backbone strain. We then build ensembles of ß-barrel backbone models with cavity shapes that match the fluorogenic compound DFHBI, and use a hierarchical grid-based search method to simultaneously optimize the rigid-body placement of DFHBI in these cavities and the identities of the surrounding amino acids to achieve high shape and chemical complementarity. The designs have high structural accuracy and bind and fluorescently activate DFHBI in vitro and in Escherichia coli, yeast and mammalian cells. This de novo design of small-molecule binding activity, using backbones custom-built to bind the ligand, should enable the design of increasingly sophisticated ligand-binding proteins, sensors and catalysts that are not limited by the backbone geometries available in known protein structures.

The impact of patient activation on the effectiveness of digital health remote post-discharge follow-up and same-day-discharge after elective colorectal surgery.

BACKGROUND: Low patient activation (PA) is associated with worse postoperative outcomes, however, its impact on the effectiveness of digital health interventions is unknown. We sought to determine the impact of PA on the effectiveness of digital health application for remote post-discharge follow-up for patients undergoing elective colectomy. METHODS: Data analysis included a control cohort (CC) of patients undergoing elective colorectal surgery from 10/2017 to 04/2018 without the digital health intervention and a digital application cohort (DAC) that received a smart phone application for remote post-discharge follow-up from 03/2021 to 08/2022, including a subset of same-day discharge (SDD) patients. PA was measured using the Patient Activation Measure (PAM; score 0-100) and categorized into low (< 55.1) and high (≥ 55.1). The PAM was administered 4-6 weeks before surgery in the DAC group and on postoperative day (POD) 1 in the CC group. The main outcome measure was 30-day emergency department (ED) visits. RESULTS: A total of 164 patients were included (89DAC with 50 SDD, 75CC), with no differences in patient characteristics other than more stoma closures in the DAC group. Overall, 77% of patients had high PA level, with no difference between CC and DAC (77% vs. 81%, p = 0.25). There was no difference in ED visits between CC and DAC (19% vs. 18%, p = 0.90). Overall, low PA was associated more ED visits (29% vs 14%, p = 0.04). In the SDD subgroup, low PA patients had more ED visits (38% vs. 7%, p = 0.015). PA level did not affect app usage metrics. On multiple regression, only low PA remained independently associated with ED visits (OR 3.42, 95%CI 1.27, 9.24). CONCLUSION: Low PA remains an important predictor of surgical outcomes after elective colorectal surgery regardless of the use of a digital health application for remote post-discharge follow-up. This suggests that improving PA levels may improve postoperative outcomes.

Environmental Factors Influencing Stem Rot Development in Peanut: Predictors and Action Thresholds for Disease Management.

Peanuts grown in tropical, subtropical, and temperate regions are susceptible to stem rot, which is a soilborne disease caused by Athelia rolfsii. Due to the lack of reliable environmental-based scheduling recommendations, stem rot control relies heavily on fungicides that are applied at predetermined intervals. We conducted inoculated field experiments for six site-years in North Florida to examine the relationship between germination of A. rolfsii sclerotia: the inoculum, stem rot symptom development in the peanut crop, and environmental factors such as soil temperature (ST), soil moisture, relative humidity (RH), precipitation, evapotranspiration, and solar radiation. Window-pane analysis with hourly and daily environmental data for 5- to 28-day periods before each disease assessment were evaluated to select model predictors using correlation analysis, regularized regression, and exhaustive feature selection. Our results indicated that within-canopy ST (at 0.05 m belowground) and RH (at 0.15 m aboveground) were the most important environmental variables that influenced the progress of mycelial activity in susceptible peanut crops. Decision tree analysis resulted in an easy-to-interpret one-variable model (adjusted R2 = 0.51, Akaike information criterion [AIC] = 324, root average square error [RASE] = 14.21) or two-variable model (adjusted R2 = 0.61, AIC = 306, RASE = 10.95) that provided an action threshold for various disease scenarios based on number of hours of canopy RH above 90% and ST between 25 and 35°C in a 14-day window. Coupling an existing preseason risk index for stem rot, such as Peanut Rx, with the environmentally based predictors identified in this study would be a logical next step to optimize stem rot management. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Where should "Humans" be in "One Health"? Lessons from COVID-19 for One Health.

The culling of animals that are infected, or suspected to be infected, with COVID-19 has fuelled outcry. What might have contributed to the ongoing debates and discussions about animal rights protection amid global health crises is the lack of a unified understanding and internationally agreed-upon definition of "One Health". The term One Health is often utilised to describe the imperative to protect the health of humans, animals, and plants, along with the overarching ecosystem in an increasingly connected and globalized world. However, to date, there is a dearth of research on how to balance public health decisions that could impact all key stakeholders under the umbrella of One Health, particularly in contexts where human suffering has been immense. To shed light on the issue, this paper discusses whether One Health means "human-centred connected health" in a largely human-dominated planet, particularly amid crises like COVID-19. The insights of this study could help policymakers make more informed decisions that could effectively and efficiently protect human health while balancing the health and well-being of the rest of the inhabitants of our shared planet Earth.

Identification and characterization of the WYL BrxR protein and its gene as separable regulatory elements of a BREX phage restriction system.

Bacteriophage exclusion ('BREX') phage restriction systems are found in a wide range of bacteria. Various BREX systems encode unique combinations of proteins that usually include a site-specific methyltransferase; none appear to contain a nuclease. Here we describe the identification and characterization of a Type I BREX system from Acinetobacter and the effect of deleting each BREX ORF on growth, methylation, and restriction. We identified a previously uncharacterized gene in the BREX operon that is dispensable for methylation but involved in restriction. Biochemical and crystallographic analyses of this factor, which we term BrxR ('BREX Regulator'), demonstrate that it forms a homodimer and specifically binds a DNA target site upstream of its transcription start site. Deletion of the BrxR gene causes cell toxicity, reduces restriction, and significantly increases the expression of BrxC. In contrast, the introduction of a premature stop codon into the BrxR gene, or a point mutation blocking its DNA binding ability, has little effect on restriction, implying that the BrxR coding sequence and BrxR protein play independent functional roles. We speculate that elements within the BrxR coding sequence are involved in cis regulation of anti-phage activity, while the BrxR protein itself plays an additional regulatory role, perhaps during horizontal transfer.

UFMylation inhibits the proinflammatory capacity of interferon-γ-activated macrophages.

Macrophages activated with interferon-γ (IFN-γ) in combination with other proinflammatory stimuli, such as lipopolysaccharide or tumor necrosis factor-α (TNF-α), respond with transcriptional and cellular changes that enhance clearance of intracellular pathogens at the risk of damaging tissues. IFN-γ effects must therefore be carefully balanced with inhibitory mechanisms to prevent immunopathology. We performed a genome-wide CRISPR knockout screen in a macrophage cell line to identify negative regulators of IFN-γ responses. We discovered an unexpected role of the ubiquitin-fold modifier (Ufm1) conjugation system (herein UFMylation) in inhibiting responses to IFN-γ and lipopolysaccharide. Enhanced IFN-γ activation in UFMylation-deficient cells resulted in increased transcriptional responses to IFN-γ in a manner dependent on endoplasmic reticulum stress responses involving Ern1 and Xbp1. Furthermore, UFMylation in myeloid cells is required for resistance to influenza infection in mice, indicating that this pathway modulates in vivo responses to infection. These findings provide a genetic roadmap for the regulation of responses to a key mediator of cellular immunity and identify a molecular link between the UFMylation pathway and immune responses.

Regional lymph node evaluation in pediatric conventional melanoma subtype: a single-center 10-year review.

PURPOSE: To assess the prognostic and therapeutic significance of sentinel lymph node biopsy (SLNB) and completion lymph node dissection (CLND) in pediatric conventional melanoma (CM), while evaluating potential predictive factors for outcomes. METHODS: We conducted a retrospective analysis of medical records spanning 2009-2020, focusing on patients aged 18 or younger with localized cutaneous conventional melanoma. RESULTS: Among the 33 patients, SLNB detected metastasis in 57.6% of cases, with 52.6% undergoing CLND. Positive SLN patients had higher relapse risk (HR 5.92; 95% CI 1.27-27.7; P = 0.024) but similar overall survival (HR 3.19; 95% CI 0.31-33.1, P = 0.33). No significant differences in disease-free survival (DFS) and OS were found between patients who underwent CLND and those who did not (HR 1.91; 95% CI 0.49-7.43, P = 0.35, and HR 0.52; 95% CI 0.03-8.32, P = 0.64, respectively). Univariate analysis showed age at diagnosis (P = 0.02) correlated with higher recurrence risk, with a 21% hazard increase per additional year of age. CONCLUSIONS: Positive SLN status and age at diagnosis were associated with worse DFS in CM patients. Our study did not find any prognostic or therapeutic value in CLND for pediatric melanoma. Further multicenter trials are needed to confirm our single-institution experience. LEVEL OF EVIDENCE: Level IV.

Culture matters: Chinese mental health professionals' fear of losing face in routine outcome monitoring.

OBJECTIVE: The culturally salient fear of losing face might influence Chinese therapists' attitudes toward and use of routine outcome monitoring (ROM). We tested a model wherein self-face concern is associated with ROM use by way of attitudes toward ROM, and whether this process is weakened when therapists report high counseling self-efficacy and perspective-taking. METHOD: A national sample of Chinese mental health professionals (N = 371) completed questionnaires on their fear of losing face, attitudes toward ROM, ROM use, counseling self-efficacy, and perspective-taking. RESULTS: Regression-based analyses showed that fear of losing face was linked to greater negative attitudes toward ROM and lower ROM use. Greater negative attitudes mediated the relationship between fear of losing face and ROM use. However, neither counseling self-efficacy nor perspective-taking mitigated the relationship between self-face concern and ROM use; instead, they exacerbated this relationship through different paths. In the mediated pathway, counseling self-efficacy in coping with clients with difficult problems interacted with self-face concern to predict negative attitudes toward ROM. Perspective-taking served as a moderator that exacerbated the direct relationship between self-face concern and ROM use. CONCLUSIONS: Findings suggest the importance of considering culturally salient factors in implementing ROM in China and other non-Western contexts.

A Mobile Phone App Improves Patient-Physician Communication and Reduces Emergency Department Visits After Colorectal Surgery.

BACKGROUND: Emergency visits after colorectal surgery are common and require significant health care resources. However, many visits may be avoidable with alternative access to care. Mobile health technologies can facilitate patient access to health care providers. OBJECTIVE: We hypothesized that a mobile app for postdischarge monitoring with patient-provider communication ability would reduce emergency visits after elective abdominopelvic colorectal surgery. DESIGN: This is a prospective cohort study with a regression analysis after coarsened exact matching. SETTING: The study was conducted at a single colorectal referral center from May 2019 to September 2020. PATIENTS: A total of 114 patients were recruited to the intervention and were matched to a retrospective cohort of 608 patients from the 24 months before the study. All patients were managed according to an enhanced recovery pathway. INTERVENTIONS: A mobile phone app comprised of patient education material, daily questionnaires assessing postdischarge recovery, and patient-provider chat function was used. MAIN OUTCOME MEASURES: The primary outcomes included potentially preventable 30-day emergency visits defined according to a validated algorithm. Secondary outcomes included length of stay, complications, total emergency department visits, readmissions, and app usability. RESULTS: Coarsened-exact matching resulted in a matched sample of 94 prospective intervention patients and 256 retrospective control patients. The prospective group was associated with fewer preventable emergency department visits (incidence rate ratio 0.34; p = 0.043) and shorter length of stay (-1.62 days; p = 0.011). There were no differences in 30-day complications, total number of emergency visits, or readmissions. Patient-reported usability of the mobile app was high, with 88% of patients reporting that the app improved their ability to communicate with their surgeon. LIMITATIONS: We did not account for patient activation or perform a cost-analysis. CONCLUSION: Use of a mobile app was associated with fewer potentially preventable emergency visits and shorter length of stay after major elective colorectal surgery, which may be due to enhanced postdischarge monitoring and patient-provider communication. See Video Abstract at http://links.lww.com/DCR/B878 . APLICACIN DE TELFONO MVIL MEJORA LA COMUNICACIN ENTRE MDICO Y PACIENTE Y REDUCE LAS VISITAS AL DEPARTAMENTO DE EMERGENCIAS DESPUS DE CIRUGA COLORECTAL: ANTECEDENTES:Las visitas de emergencia después de la cirugía colorrectal son frecuentes y requieren importantes recursos sanitarios. Sin embargo, muchas visitas pueden evitarse con un acceso alternativo a la atención. Las tecnologías de salud móviles pueden facilitar el acceso de los pacientes a los proveedores de atención médica.OBJETIVO:Se planteó la hipótesis de que una aplicación móvil para el seguimiento posterior al alta con capacidad de comunicación entre el paciente y el médico reduciría las visitas de emergencia después de cirugía colorrectal abdominopélvica electiva.DISEÑO:Este es un estudio de cohorte prospectivo con un análisis de regresión después de un emparejamiento exacto aproximado.ENTORNO CLINICO:El estudio se llevó a cabo en un solo centro de referencia colorrectal entre 05/2019 y 09/2020.PACIENTES:Se reclutó un total de 114 pacientes para la intervención y se emparejaron con una cohorte retrospectiva de 608 pacientes de los 24 meses anteriores al estudio. Todos los pacientes fueron tratados con protocolo de enhanced recovery .INTERVENCIONES:Se utilizó una aplicación para teléfono móvil compuesta de material educativo para el paciente, cuestionarios diarios que evalúan la recuperación posterior al alta y una función de chat entre el paciente y el médico.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios incluyeron visitas a la emergencia en 30 días potencialmente prevenibles, definidas según un algoritmo validado. Los resultados secundarios incluyeron la duración de la estancia, complicaciones, total de visitas al departamento de emergencias, reingresos y la usabilidad de la aplicación.RESULTADOS:El emparejamiento aproximado-exacto resultó en una muestra emparejada de 94 APP + y 256 APP-. APP + se asoció con menos visitas evitables al servicio de urgencias (IRR 0,34, p = 0,043) y una estancia más corta (-1,62 días, p = 0,011). No hubo diferencias en las complicaciones a los 30 días, número total de visitas de emergencia y reingresos. La usabilidad de la aplicación móvil informada por los pacientes fue alta, y el 88% de los pacientes informaron que la aplicación mejoró su capacidad para comunicarse con su cirujano.LIMITACIONES:No contabilizamos la activación del paciente ni realizamos un análisis de costos.CONCLUSIÓNES:El uso de una aplicación móvil se asoció con menos visitas a la emergencia potencialmente prevenibles y una estadía más corta después de una gran cirugía colorrectal electiva, lo que puede deberse a una mejor monitorización posterior al alta y a la comunicación entre el paciente y el médico. Consulte Video Resumen en http://links.lww.com/DCR/B878 . (Traducción-Dr. Francisco M. Abarca-Rendon ).

Post-pandemic policy imperatives to stem violence against women in China.

Violence against women is rampant in China. Even though meaningful strides have been made in the country, it remains disturbingly common for men to assault women-verbally or physically, who may or may not be their partners-in broad daylight in China. To make the situation worse, COVID-19, along with its restrictions, has both undermined women's ability to escape from abuse or violence and society's ability to provide timely help to victims. In light of the rising violence against women post-COVID, in this paper, we discuss the policy imperatives for countries like China to establish effective guardrails and support systems to protect women from the dehumanizing and destabilizing crime that is violence against women-a social malaise that not only harms and undermines the safety of society's daughters, mothers, and grandmothers, but also the integrity of local communities and social contract, let along shared humanity and global solidarity at large.

A new era in cystic fibrosis care: always changing and adapting.

PURPOSE OF REVIEW: This review focuses on sharing the current and changing cystic fibrosis (CF) care model. This includes changes in CF care as a chronic disease with availability of new revolutionary, highly effective therapies as well as incorporation of shared decision-making, coproduction of care, quality improvement, telemedicine, and remote patient monitoring. RECENT FINDINGS: Changes in the CF management, the CF patient population, and CF care team are described as well as how CF care has adapted to these changes. SUMMARY: CF is a chronic, multisystem disease requiring a large specialized multidisciplinary care team for effective treatment. With improvements in CF care and new treatments, people with CF are living longer and healthier lives. As new issues arise, the CF team needs to adapt. This was highlighted by the introduction of highly effective cystic fibrosis transmembrane conductance regulator modulator therapy, which targets the cellular defect in CF, the COVID-19 pandemic, which lead to the incorporation of telehealth and remote patient monitoring into the CF care model, and the partnering with people with CF and families through shared decision-making and coproduction.