Bridging the gap: a resident-led transitional care clinic to improve post hospital care in a safety-net academic community hospital.

The transitional period between hospital discharge and primary care follow-up is a vulnerable time for patients that can result in adverse health outcomes and preventable hospital readmissions. This is especially true for patients of safety-net hospitals (SNHs) who often struggle to secure primary care access when leaving the hospital due to social, economic and cultural barriers. In this study, we describe a resident-led postdischarge clinic that serves patients discharged from NYU Langone Hospital-Brooklyn, an urban safety-net academic hospital. In our multivariable analysis, there was no statistical difference in the readmission rate between those who completed the transitional care management and those who did not (OR 1.32 (0.75-2.36), p=0.336), but there was a statistically significant increase in primary care provider (PCP) engagement (OR 0.53 (0.45-0.62), p<0.001). Overall, this study describes a postdischarge clinic model embedded in a resident clinic in an urban SNH that is associated with increased PCP engagement, but no reduction in 30-day hospital readmissions.

"What if that's your last sleep?" A qualitative exploration of the trauma of incarceration and sleep.

Study Background/Objectives: Sleep is an underexplored factor in the health of people involved in the criminal legal system. This study addresses the paucity of research on how individual, social, and physical environmental factors impact sleep health during and after incarceration by highlighting the voices of people involved in the criminal legal system through a community-engaged qualitative research approach. Methods: We conducted 20 semi-structured interviews with men recently released from prison for a study on trauma and healthcare during incarceration and after release. Interviews were coded and analyzed using reflexive thematic analysis and a critical realist framework. Our research team included people with a history of incarceration who performed central roles in the research process. Results: Three themes emerged from participants' descriptions of sleep during and after incarceration: (1) concerns about health contributing to sleep problems, (2) lack of access to treatment for sleep disorders leading to ongoing sleep problems, and (3) issues of safety contributing to sleep problems during incarceration and after release. Conclusions: This study identifies factors and domains influencing sleep during and after incarceration. By identifying which interpersonal, environmental, and structural factors impact sleep quality, medical and carceral staff are better equipped to ameliorate sleep health disparities within populations with a history of incarceration and those actively bound by the criminal legal system. Future research should examine other factors impacting sleep in incarcerated and recently released populations and develop multi-level interventions to improve sleep health. This paper is part of the Sleep and Circadian Health in the Justice System Collection.

Strategies for combating antibiotic resistance in bacterial biofilms.

Biofilms, which are complexes of microorganisms that adhere to surfaces and secrete protective extracellular matrices, wield substantial influence across diverse domains such as medicine, industry, and environmental science. Despite ongoing challenges posed by biofilms in clinical medicine, research in this field remains dynamic and indeterminate. This article provides a contemporary assessment of biofilms and their treatment, with a focus on recent advances, to chronicle the evolving landscape of biofilm research.

Compact zinc finger architecture utilizing toxin-derived cytidine deaminases for highly efficient base editing in human cells.

Nucleobase editors represent an emerging technology that enables precise single-base edits to the genomes of eukaryotic cells. Most nucleobase editors use deaminase domains that act upon single-stranded DNA and require RNA-guided proteins such as Cas9 to unwind the DNA prior to editing. However, the most recent class of base editors utilizes a deaminase domain, DddAtox, that can act upon double-stranded DNA. Here, we target DddAtox fragments and a FokI-based nickase to the human CIITA gene by fusing these domains to arrays of engineered zinc fingers (ZFs). We also identify a broad variety of Toxin-Derived Deaminases (TDDs) orthologous to DddAtox that allow us to fine-tune properties such as targeting density and specificity. TDD-derived ZF base editors enable up to 73% base editing in T cells with good cell viability and favorable specificity.

The Impact of Intergrain Phases on the Ionic Conductivity of the LAGP Solid Electrolyte Material Prepared by Spark Plasma Sintering.

Li1.5Al0.5Ge1.5(PO4)3 (LAGP) is a promising oxide solid electrolyte for all-solid-state batteries due to its excellent air stability, acceptable electrochemical stability window, and cost-effective precursor materials. However, further improvement in the ionic conductivity performance of oxide solid-state electrolytes is hindered by the presence of grain boundaries and their associated morphologies and composition. These key factors thus represent a major obstacle to the improved design of modern oxide based solid-state electrolytes. This study establishes a correlation between the influence of the grain boundary phases, their 3D morphology, and compositions formed under different sintering conditions on the overall LAGP ionic conductivity. Spark plasma sintering has been employed to sinter oxide solid electrolyte material at different temperatures with high compacity values, whereas a combined potentiostatic electrochemical impedance spectroscopy, 3D FIB-SEM tomography, XRD, and solid-state NMR/materials modeling approach provides an in-depth analysis of the influence of the morphology, structure, and composition of the grain boundary phases that impact the total ionic conductivity. This work establishes the first 3D FIB-SEM tomography analysis of the LAGP morphology and the secondary phases formed in the grain boundaries at the nanoscale level, whereas the associated 31P and 27Al MAS NMR study coupled with materials modeling reveals that the grain boundary material is composed of Li4P2O7 and disordered Li9Al3(P2O7)3(PO4)2 phases. Quantitative 31P MAS NMR measurements demonstrate that optimal ionic conductivity for the LAGP system is achieved for the 680 °C SPS preparation when the disordered Li9Al3(P2O7)3(PO4)2 phase dominates the grain boundary composition with reduced contributions from the highly ordered Li4P2O7 phases, whereas the 27Al MAS NMR data reveal that minimal structural change is experienced by each phase throughout this suite of sintering temperatures.

Individual variation in and lateral asymmetry of mouse epididymal draining lymph nodes.

PROBLEM: Draining lymph nodes (LNs) are pivotal sites for maintaining tolerance to self-antigens as well as eliciting immune responses to exogenous antigens. The epididymis is a male reproductive organ with a unique local immune environment. Although mice are the most commonly used laboratory animals for immunology research, there are no detailed descriptions of the anatomical location and function of LNs that drain the epididymis. METHOD OF STUDY: Evans blue labeling was utilized to explore lymphatic drainage of the epididymis in eight- to ten-week-old male C57BL/6 mice. We confirmed the lymphatic drainage of the epididymis in mice using the objective technique of carboxyfluorescein succinimidyl ester (CFSE)-labeled cells. RESULTS: By combined Evans blue labeling and fluorescent labeling, we found that 1) the patterns of epididymal LN drainage are highly heterogeneous between individual mice; 2) the leftside LNs participate in drainage more frequently than the right-side LNs; and 3) epididymal lymphatic drainage bypasses both the paraaortic and renal LNs in some mice. CONCLUSIONS: These data highlighted the need to consider the individual variation in and lateral asymmetry of draining LNs when characterizing the regional immunology of the mouse epididymis.

Are we facing an increasing surgical demand for high myopic traction maculopathies? A 12-year study from Hong Kong.

PURPOSE: We aimed to investigate the longitudinal change in the number of surgically operated myopic traction maculopathies (MTM) cases at a tertiary eye centre. METHODS: A retrospective study of all consecutive cases of surgically operated MTM over 12 years (2009-2020) was conducted in a myopia prevalent region. We compared outcomes among three groups: (1) myopic macular hole (MH), (2) myopic macular hole with retinal detachment (MHRD), and (3) myopic foveoschisis with retinal detachment (MFRD). RESULTS: Fifty-one cases were included in the study (8 cases of MH, 33 cases of MHRD and 10 cases of MFRD). The overall mean age was 63.8 +/- 8.7 with a female preponderance (2:1). The mean age of the MH group (58.6) was significantly younger than the MHRD group (64.2) and MFRD group (66.6) (p = 0.02). Subgroup analysis using ATN classification did not show its correlation with both visual improvement and anatomical success. When comparing the first 6-year period (2009-2014) with the second 6-year period (2015-2020), there was a significant increase in the number of cases (p = 0.01). CONCLUSION: We observe an increase in the number of surgically operated MTM. This follows the trend of the global rise in the prevalence of myopia and baby boomers entering retirement.

Longitudinal Use of Telehealth During the COVID-19 Pandemic and Utility of Asynchronous Testing for Subspecialty-Level Ophthalmic Care.

Importance: Telehealth in ophthalmology has traditionally focused on preventive disease screening with limited use in outpatient evaluation. The unique conditions of the COVID-19 pandemic afforded the opportunity to evaluate different implementations of teleophthalmology at scale, providing insight into expanding teleophthalmology care. Objective: To compare telehealth use in ophthalmology with other specialties and assess the feasibility of augmenting ophthalmic telehealth encounters with asynchronous testing during the COVID-19 pandemic. Design, Setting, and Participants: This quality improvement study evaluated retrospective, longitudinal, observational data from the first 18 months of the COVID-19 pandemic (January 1, 2020, through July 31, 2021) for 881 080 patients receiving care from outpatient primary care, cardiology, neurology, gastroenterology, surgery, neurosurgery, urology, orthopedic surgery, otolaryngology, obstetrics/gynecology, and ophthalmology clinics of the University of California, San Francisco. Asynchronous testing was evaluated for teleophthalmology encounters. Interventions: A hybrid care model wherein ophthalmic testing data were acquired asynchronously and used to augment telehealth encounters. Main Outcomes and Measures: Telehealth as a percentage of total volume of ambulatory care and use of asynchronous testing for ophthalmic conditions. Results: The volume of in-person outpatient visits dropped by 83.3% (39 488 of 47 390) across the evaluated specialties at the onset of shelter-in-place orders for the COVID-19 pandemic, and the initial use of telehealth increased for these specialties before stabilizing over the 18-month study period. In ophthalmology, telehealth use peaked at 488 of 1575 encounters (31.0%) early in the pandemic and returned to mostly in-person visits as COVID-19 restrictions lifted. Elective use of telehealth was highest in gastroenterology, urology, neurology, and neurosurgery and lowest in ophthalmology. Asynchronous testing was combined with 126 teleophthalmology encounters, resulting in change of clinical management for 32 patients (25.4%) and no change for 91 (72.2%). Conclusions and Relevance: Telehealth increased across various specialties during the COVID-19 pandemic. Combining teleophthalmic visits with asynchronous testing suggested that this approach is feasible for subspecialty-level evaluation. Additional study is needed to evaluate whether asynchronous testing outside the same institution could provide an effective and lasting approach for expanding the reach of ophthalmic telehealth.

Effects of syphilis infection among HIV-1-positive individuals on suppressive antiretroviral therapy.

INTRODUCTION: Incident syphilis leads to changes in plasma HIV-1 RNA and CD4 + T-cell level in people with HIV (PWH) with viraemia. Its effect in PWH on suppressive antiretroviral therapy (ART) is less clear. METHODS: PWH on suppressive ART (plasma HIV-1 RNA < 50copies/mL) followed at the Queen Elizabeth Hospital, Hong Kong, China were regularly screened for syphilis. Their plasma HIV-1 RNA, CD4 + and CD8 + T-cell, and total lymphocyte levels before syphilis, during syphilis, and after successful treatment were compared. RESULTS: Between 2005 and 2020, 288 syphilis episodes from 180 individuals were identified; 287 episodes were related to male, with a median age of 41 at diagnosis; 221 (77%) were syphilis re-infection. The rates of plasma HIV-1 suppression were statistically unchanged across the time-points (97% pre-syphilis, 98% during syphilis, and 99% post-treatment). Total lymphocyte, CD4+ and CD8+ T-cell levels decreased during incident syphilis (p<0.01), and rebounded post-treatment (p<0.01). VDRL titre was associated with declines in CD4+ T-cell (p=0.045), CD8+ T-cell (p=0.004), and total lymphocyte levels (p=0.021). Pre-syphilis CD4/CD8 ratio was associated with increases in CD8+ T-cell (p=0.001) and total lymphocyte levels (p=0.046) during syphilis. Syphilis re-infection was associated with an increase in total lymphocyte level (p=0.037). In the multivariable analysis, only pre-syphilis CD4/CD8 ratio was independently associated with increases in CD8+ T-cell (p=0.014) and total lymphocyte levels (p=0.039) during syphilis. CONCLUSIONS: Among virally-suppressed PWH, total lymphocyte, CD4+, and CD8+ T-cell levels declined during incident syphilis but rebounded post-treatment. The status of plasma HIV suppression was unaffected by syphilis.

Human IFNAR2 Mutant Generated by CRISPR/Cas9-Induced Exon Skipping Upregulates a Subset of Tonic-Like Interferon-Stimulated Genes Upon IFNß Stimulation.

Type I interferons (IFN-Is) play central roles in regulating immune responses. The role of IFNAR2 in IFN-I signaling is an open question since a previous report showed that IFNß was still functional in the absence of IFNAR2 in mice. In this study, we report that IFN-I signaling in human monocyte-derived THP1 cells absolutely depends on IFNAR2, as determined by using a knockout mutant made by CRISPR/Cas9. Additionally, we demonstrated that a 7-bp deletion mutant (Δ7) of IFNAR2 remains responsive to IFNß stimulation and upregulates a subset of interferon-stimulated genes (s-ISGs). The s-ISGs largely overlap with tonic ISGs, which depend on the basal expression level of IFN-I. We also showed that IFN signaling in Δ7 still depends on IFNAR2. Then, we found that the 7-bp deletion in the genome results in the loss of the entire third exon (42 bp) from the mRNA and in the expression of a functionally impaired IFNAR2. These findings clarified the requirement of IFNAR2 for human IFN-I signaling and highlighted that caution should be used with CRISPR/Cas9 technology to prevent misleading interpretations caused by residual protein expression due to exon skipping or other mechanisms.

Pathophysiology of Pulmonary Fibrosis in the Context of COVID-19 and Implications for Treatment: A Narrative Review.

Pulmonary fibrosis (PF) is a feared outcome of many pulmonary diseases which results in a reduction in lung compliance and capacity. The development of PF is relatively rare, but it can occur secondary to viral pneumonia, especially COVID-19 infection. While COVID-19 infection and its complications are still under investigation, we can look at a similar outbreak in the past to gain better insight as to the expected long-term outcomes of COVID-19 patient lung function. In the current article, we review the literature relative to PF via PubMed. We also performed a literature search for COVID-related pathological changes in the lungs. Finally, the paper was reviewed and summarized based on the studies' integrity, relative, or power calculations. This article provides a narrative review that endeavors to elucidate the current understanding of the pathophysiological mechanisms underlying PF and therapeutic strategies. We also discussed the potential for preventing progression to the fibrotic state within the context of the COVID-19 pandemic. With the massive scale of the COVID-19 pandemic, we expect there should more instances of PF due to COVID-19 infection. Patients who survive severe COVID-19 infection may suffer from a high incidence of PF.

Citrullinated Histone H3 Mediates Sepsis-Induced Lung Injury Through Activating Caspase-1 Dependent Inflammasome Pathway.

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection that often results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). An emerging mechanism of sepsis-induced ARDS involves neutrophils/macrophages undergoing cell death, releasing nuclear histones to cause tissue damage that exacerbates pulmonary injury. While published studies focus on unmodified histones, little is known about the role of citrullinated histone H3 (CitH3) in the pathogenesis of sepsis and ALI. In this study, we found that levels of CitH3 were elevated in the patients with sepsis-induced ARDS and correlated to PaO2/FiO2 in septic patients. Systematic administration of CitH3 peptide in mice provoked Caspase-1 activation in the lung tissue and caused ALI. Neutralization of CitH3 with monoclonal antibody improved survival and attenuated ALI in a mouse sepsis model. Furthermore, we demonstrated that CitH3 induces ALI through activating Caspase-1 dependent inflammasome in bone marrow derived macrophages and bone marrow derived dendritic cells. Our study suggests that CitH3 is an important mediator of inflammation and mortality during sepsis-induced ALI.

Peptidylarginine Deiminase 2 in Host Immunity: Current Insights and Perspectives.

Peptidylarginine deiminases (PADs) are a group of enzymes that catalyze post-translational modifications of proteins by converting arginine residues into citrullines. Among the five members of the PAD family, PAD2 and PAD4 are the most frequently studied because of their abundant expression in immune cells. An increasing number of studies have identified PAD2 as an essential factor in the pathogenesis of many diseases. The successes of preclinical research targeting PAD2 highlights the therapeutic potential of PAD2 inhibition, particularly in sepsis and autoimmune diseases. However, the underlying mechanisms by which PAD2 mediates host immunity remain largely unknown. In this review, we will discuss the role of PAD2 in different types of cell death signaling pathways and the related immune disorders contrasted with functions of PAD4, providing novel therapeutic strategies for PAD2-associated pathology.

Stable cross-linked lyotropic gyroid mesophases from single-head/single-tail cross-linkable monomers.

A single-head/single-tail surfactant with a polymerizable group at each end is presented as a new simplified motif for intrinsically cross-linkable, gyroid-phase lyotropic mesogens. The resulting nanoporous polymer networks exhibit excellent structural stability in various solvents and are capable of molecular size discrimination.

Effects of structural modification of (alkyldiene-imidazolium bromide)-based gemini monomers on the formation of the lyotropic bicontinuous cubic phase.

Seven homologues of an amphiphilic gemini monomer were synthesized and screened for the ability to form a bicontinuous cubic (Q) lyotropic liquid crystal phase. Four of these homologues form a Q phase with glycerol or water that can be cross-linked with retention of the nanoporous structure, with one exhibiting a well-ordered Q phase with a wider phase window than the parent monomer.

Measuring Collaboration Through Concurrent Electronic Health Record Usage: Network Analysis Study.

BACKGROUND: Collaboration is vital within health care institutions, and it allows for the effective use of collective health care worker (HCW) expertise. Human-computer interactions involving electronic health records (EHRs) have become pervasive and act as an avenue for quantifying these collaborations using statistical and network analysis methods. OBJECTIVE: We aimed to measure HCW collaboration and its characteristics by analyzing concurrent EHR usage. METHODS: By extracting concurrent EHR usage events from audit log data, we defined concurrent sessions. For each HCW, we established a metric called concurrent intensity, which was the proportion of EHR activities in concurrent sessions over all EHR activities. Statistical models were used to test the differences in the concurrent intensity between HCWs. For each patient visit, starting from admission to discharge, we measured concurrent EHR usage across all HCWs, which we called temporal patterns. Again, we applied statistical models to test the differences in temporal patterns of the admission, discharge, and intermediate days of hospital stay between weekdays and weekends. Network analysis was leveraged to measure collaborative relationships among HCWs. We surveyed experts to determine if they could distinguish collaborative relationships between high and low likelihood categories derived from concurrent EHR usage. Clustering was used to aggregate concurrent activities to describe concurrent sessions. We gathered 4 months of EHR audit log data from a large academic medical center's neonatal intensive care unit (NICU) to validate the effectiveness of our framework. RESULTS: There was a significant difference (P<.001) in the concurrent intensity (proportion of concurrent activities: ranging from mean 0.07, 95% CI 0.06-0.08, to mean 0.36, 95% CI 0.18-0.54; proportion of time spent on concurrent activities: ranging from mean 0.32, 95% CI 0.20-0.44, to mean 0.76, 95% CI 0.51-1.00) between the top 13 HCW specialties who had the largest amount of time spent in EHRs. Temporal patterns between weekday and weekend periods were significantly different on admission (number of concurrent intervals per hour: 11.60 vs 0.54; P<.001) and discharge days (4.72 vs 1.54; P<.001), but not during intermediate days of hospital stay. Neonatal nurses, fellows, frontline providers, neonatologists, consultants, respiratory therapists, and ancillary and support staff had collaborative relationships. NICU professionals could distinguish high likelihood collaborative relationships from low ones at significant rates (3.54, 95% CI 3.31-4.37 vs 2.64, 95% CI 2.46-3.29; P<.001). We identified 50 clusters of concurrent activities. Over 87% of concurrent sessions could be described by a single cluster, with the remaining 13% of sessions comprising multiple clusters. CONCLUSIONS: Leveraging concurrent EHR usage workflow through audit logs to analyze HCW collaboration may improve our understanding of collaborative patient care. HCW collaboration using EHRs could potentially influence the quality of patient care, discharge timeliness, and clinician workload, stress, or burnout.

Comparison of automated and expert human grading of diabetic retinopathy using smartphone-based retinal photography.

PURPOSE: The aim of this study is to investigate the efficacy of a mobile platform that combines smartphone-based retinal imaging with automated grading for determining the presence of referral-warranted diabetic retinopathy (RWDR). METHODS: A smartphone-based camera (RetinaScope) was used by non-ophthalmic personnel to image the retina of patients with diabetes. Images were analyzed with the Eyenuk EyeArt® system, which generated referral recommendations based on presence of diabetic retinopathy (DR) and/or markers for clinically significant macular oedema. Images were independently evaluated by two masked readers and categorized as refer/no refer. The accuracies of the graders and automated interpretation were determined by comparing results to gold standard clinical diagnoses. RESULTS: A total of 119 eyes from 69 patients were included. RWDR was present in 88 eyes (73.9%) and in 54 patients (78.3%). At the patient-level, automated interpretation had a sensitivity of 87.0% and specificity of 78.6%; grader 1 had a sensitivity of 96.3% and specificity of 42.9%; grader 2 had a sensitivity of 92.5% and specificity of 50.0%. At the eye-level, automated interpretation had a sensitivity of 77.8% and specificity of 71.5%; grader 1 had a sensitivity of 94.0% and specificity of 52.2%; grader 2 had a sensitivity of 89.5% and specificity of 66.9%. DISCUSSION: Retinal photography with RetinaScope combined with automated interpretation by EyeArt achieved a lower sensitivity but higher specificity than trained expert graders. Feasibility testing was performed using non-ophthalmic personnel in a retina clinic with high disease burden. Additional studies are needed to assess efficacy of screening diabetic patients from general population.

Peptidylarginine Deiminases 2 Mediates Caspase-1-Associated Lethality in Pseudomonas aeruginosa Pneumonia-Induced Sepsis.

BACKGROUND: Pseudomonas aeruginosa (PA) is a pathogenic bacterium that causes severe pneumonia in critically ill and immunocompromised patients. Peptidylarginine deiminase (PAD) 2, PAD4, and caspase-1 are important enzymes in mediating host response to infection. The goal of this study was to determine the interplay between PAD2, PAD4, and caspase-1 in PA pneumonia-induced sepsis. METHODS: Pneumonia was produced in wild-type, Pad2-/-, and Pad4-/- mice by intranasal inoculation of PA (2.5 × 106 colony-forming units per mouse), and survival (n = 15/group) was monitored for 10 days. Bone marrow-derived macrophages (BMDMs) were isolated for in vitro studies. Samples were collected at specific timepoints for Western blot, bacterial load determination, and flow cytometry analysis. RESULTS: Caspase-1-dependent inflammation was diminished in PA-inoculated Pad2-/- mice, contributing to reduced macrophage death and enhanced bacterial clearance. In addition, Pad2-/- mice exhibited improved survival and attenuated acute lung injury after PA infection. In contrast, Pad4-/- mice did not display diminished caspase-1 activation, altered bacterial loads, or improved survival. CONCLUSIONS: Peptidylarginine deiminase 2 plays an essential role in the pathogenesis of pulmonary sepsis by mediating caspase-1 activation. This goes against previous findings of PAD4 in sepsis. Our study suggests that PAD2 is a potential therapeutic target of PA pneumonia-induced sepsis.

Enhancing gene editing specificity by attenuating DNA cleavage kinetics.

Engineered nucleases have gained broad appeal for their ability to mediate highly efficient genome editing. However the specificity of these reagents remains a concern, especially for therapeutic applications, given the potential mutagenic consequences of off-target cleavage. Here we have developed an approach for improving the specificity of zinc finger nucleases (ZFNs) that engineers the FokI catalytic domain with the aim of slowing cleavage, which should selectively reduce activity at low-affinity off-target sites. For three ZFN pairs, we engineered single-residue substitutions in the FokI domain that preserved full on-target activity but showed a reduction in off-target indels of up to 3,000-fold. By combining this approach with substitutions that reduced the affinity of zinc fingers, we developed ZFNs specific for the TRAC locus that mediated 98% knockout in T cells with no detectable off-target activity at an assay background of ~0.01%. We anticipate that this approach, and the FokI variants we report, will enable routine generation of nucleases for gene editing with no detectable off-target activity.