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Brachiocephalic arteriovenous fistulas (AVF) makeup approximately one third of prevalent dialysis vascular accesses. The most common cause of malfunction with this access is cephalic arch stenosis (CAS). The accepted requirement for treatment of a venous stenosis lesion is ⩾50% stenosis associated with hemodynamically abnormalities. However, the correlation between percentage stenosis and a clinically significant decrease in access blood flow (Qa) is low. The critical parameter is the absolute minimal luminal diameter (MLD) of the lesion. This is the parameter that exerts the key restrictive effect on Qa and results in hemodynamic and functional implications for the access. CAS is the result of low wall shear stress (WSS) resulting from the effects of increased blood flow and the unique anatomical configuration of the CAS. Decrease in WSS has a linear relationship to increased blood flow velocity and neointimal hyperplasia exhibits an inverse relationship with WSS. The result is a stenotic lesion. The presence of downstream venous stenosis causes an inflow-outflow mismatch resulting in increased pressure within the access. Qa in this situation may be decreased, increased, or within a normal range. Over time, the increased intraluminal pressure can result in marked aneurysmal changes within the AVF, difficulties with cannulation and the dialysis treatment, and ultimately, increasing risk of access thrombosis. Complete characterization of the lesion both hemodynamically and anatomically should be the first step in developing a strategy for management. This requires both access flow measurement and angiographic imaging. Patients with CAS present a relatively broad spectrum as relates to both of these parameters. These data should be used to determine whether primary treatment of CAS should be directed toward the anatomical lesion (small MLD and low Qa) or the pathophysiology (large MLD and high Qa).

Neural representations have emerged as a new paradigm for applications in rendering, imaging, geometric modeling, and simulation. Compared to traditional representations such as meshes, point clouds, or volumes they can be flexibly incorporated into differentiable learning-based pipelines. While recent improvements to neural representations now make it possible to represent signals with fine details at moderate resolutions (e.g., for images and 3D shapes), adequately representing large-scale or complex scenes has proven a challenge. Current neural representations fail to accurately represent images at resolutions greater than a megapixel or 3D scenes with more than a few hundred thousand polygons. Here, we introduce a new hybrid implicit-explicit network architecture and training strategy that adaptively allocates resources during training and inference based on the local complexity of a signal of interest. Our approach uses a multiscale block-coordinate decomposition, similar to a quadtree or octree, that is optimized during training. The network architecture operates in two stages: using the bulk of the network parameters, a coordinate encoder generates a feature grid in a single forward pass. Then, hundreds or thousands of samples within each block can be efficiently evaluated using a lightweight feature decoder. With this hybrid implicit-explicit network architecture, we demonstrate the first experiments that fit gigapixel images to nearly 40 dB peak signal-to-noise ratio. Notably this represents an increase in scale of over 1000x compared to the resolution of previously demonstrated image-fitting experiments. Moreover, our approach is able to represent 3D shapes significantly faster and better than previous techniques; it reduces training times from days to hours or minutes and memory requirements by over an order of magnitude., Comment: J. N. P. Martel and D. B. Lindell equally contributed to this work

Background Despite many options for upper lip reconstruction, each method's advantages and disadvantages are unclear. Objective To summarize complications and functional and aesthetic outcomes of localized skin flaps for oncological reconstruction of the upper cutaneous lip (PROSPERO CRD42020157244). Methods The search was conducted in Ovid MEDLINE, Ovid EMBASE, and CENTRAL on December 14, 2019. Two reviewers screened 2,958 results for eligibility. Bias assessment was conducted using ROBINS-I criteria. Results Our search identified 12 studies reporting outcomes of V-Y advancement, ergotrid, rotation, Karapandzic, alar crescent, and propeller facial artery perforator flaps. Flap complications (infection, hemorrhage/hematoma, wound dehiscence, and flap necrosis) ranged from 0% to 7.69%. Functional outcomes (salivary continence, microstomia, and paresthesia) were poorest for Karapandzic flaps. Aesthetic outcomes, when reported, stated satisfaction rates greater than 90%. V-Y advancement flaps reported the highest rates of poor scarring (0%-20%) and need for revision surgery (0%-46.7%). Conclusion Our results provide dermatologic surgeons an overview of upper cutaneous lip flap outcomes reported in the literature. In general, we noted high patient satisfaction rates and low complication rates. Additional research into outcomes of other commonly used flaps is needed. Standardization of reported outcomes could allow further comparison across different flaps or across studies of the same flap.

A mega fistula can be defined as generalized aneurysmal dilatation of arteriovenous fistula. Mega fistulae can lead to complications like high output cardiac failure, steal syndrome, skin ulceration and rupture. We describe a series of ten patients who were referred to our interventional nephrology practice for evaluation of mega fistula which had not been in use for a long time. Nine out of ten patients were post-transplant while one was pre dialysis. Five patients had Radiocephalic while four had Brachiocephalic and one had Brachial artery to Median Cubital vein fistula. All except one patient had severe outflow stenosis. The most common site of stenosis in Radiocepahlic and Brachiocepahlic fistula was cephalic vein at the elbow and cephalic arch respectively. Half of the patients had chronic total occlusion of the outflow vein. Successful angioplasty was done in only two patients. Seven patients underwent ligation while one had spontaneous thrombosis of the fistula. None of the patients had regular surveillance of their access for a long time as they were not on dialysis. Unrecognized and uncorrected outflow stenosis over a long time period can lead to creation of mega fistula. Once a mega fistula develops there are not many treatment options other than ligation. This leads to loss of the access which might be needed in future. Continuous access surveillance in patients who are not on dialysis is important to prevent complications like mega fistula.

Several recent reports have raised concern that infected coworkers may be an important source of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) acquisition by healthcare personnel. In a suspected outbreak among emergency department personnel, sequencing of SARS-CoV-2 confirmed transmission among coworkers. The suspected 6-person outbreak included 2 distinct transmission clusters and 1 unrelated infection.

Oligodendrocyte (OL) maturation arrest in human white matter injury contributes significantly to the failure of endogenous remyelination in multiple sclerosis (MS) and newborn brain injuries such as hypoxic ischemic encephalopathy (HIE) that cause cerebral palsy. In this study, we identify an oligodendroglial-intrinsic factor that controls OL maturation specifically in the setting of injury. We find a requirement for the ring finger protein Rnf43 not in normal development but in neonatal hypoxic injury and remyelination in the adult mammalian CNS. Rnf43, but not the related Znrf3, is potently activated by Wnt signaling in OL progenitor cells (OPCs) and marks activated OPCs in human MS and HIE. Rnf43 is required in an injury-specific context, and it promotes OPC differentiation through negative regulation of Wnt signal strength in OPCs at the level of Fzd1 receptor presentation on the cell surface. Inhibition of Fzd1 using UM206 promotes remyelination following exvivo and invivo demyelinating injury.

This paper provides meta-analyses of the published findings relating the respiratory health of occupants of schools with visible dampness, water damage, visible mold, and/or mold odor. Random effects models were used to develop central estimates and confidence limits for the associations of respiratory health effects with school dampness and mold. Eleven studies, all with cross-sectional designs, were included in the meta-analyses; however, analyses for some health outcomes were based on as few as four studies. Analyses were performed using data from adults and children combined, using only data from children, and using data from adults and children after excluding two studies. The central estimates of odds ratios from the meta-analyses were consistently above unity. The evidence of adverse health effects was strongest for cough and wheeze, which had confidence limits excluding unity in some or all analyses. The odds ratios of 1.32 for cough and 1.68 for wheeze suggest moderate increases in health risk. Studies not included in the meta-analyses provide additional evidence that dampness and mold in schools are associated with adverse health outcomes. These meta-analyses and the published literature not included in the meta-analyses suggest that dampness and mold in schools are associated with adverse respiratory health effects.

Rationale: “Noninfectious” pulmonary complications are significant causes of morbidity and mortality after allogeneic hematopoietic cell transplant. Early-onset viral reactivations or infections ar...

Background High systolic blood pressure (SBP) increases cardiac afterload, whereas low diastolic blood pressure (DBP) may lead to impaired coronary perfusion. Thus, wide pulse pressure (high systolic, low diastolic [HSLD]) may contribute to myocardial ischemia and also be a predictor of adverse cardiovascular events. Objectives The purpose of this study was to determine the relationship between pre-procedural blood pressure and long-term outcome following percutaneous coronary intervention (PCI). Methods The study included 10,876 consecutive patients between August 2009 and December 2016 from the Melbourne Interventional Group registry undergoing PCI with pre-procedural blood pressure recorded. Patients with ST-segment elevation myocardial infarction, cardiogenic shock, and out-of-hospital cardiac arrest were excluded. Patients were divided into 4 groups according to SBP (high ≥120 mm Hg, low 70 mm Hg, low ≤70 mm Hg). Results Mean pulse pressure was 60 ± 21 mm Hg. Patients with HSLD were older and more frequently women, with higher rates of hypercholesterolemia, renal impairment, diabetes, and multivessel and left main disease (all p ≤ 0.0001). There was no difference in 30-day major adverse cardiac events, but at 12 months the HSLD group had a greater incidence of myocardial infarction (p = 0.018) and stroke (p = 0.013). Long-term mortality was highest for HSLD (7.9%) and lowest for low systolic, high diastolic (narrow pulse pressure) at 2.1% (p = 0.0002). Cox regression analysis demonstrated significantly lower long-term mortality in the low systolic, high diastolic cohort (hazard ratio: 0.50; 99% confidence interval: 0.25 to 0.98; p = 0.04). Conclusions Pulse pressure at the time of index PCI is associated with long-term outcomes following PCI. A wide pulse pressure may serve as a surrogate marker for risk following PCI and represents a potential target for future therapies.

Disruption of the blood-brain barrier (BBB) is critical to initiation and perpetuation of disease in multiple sclerosis (MS). We report an interaction between oligodendroglia and vasculature in MS that distinguishes human white matter injury from normal rodent demyelinating injury. We find perivascular clustering of oligodendrocyte precursor cells (OPCs) in certain active MS lesions, representing an inability to properly detach from vessels following perivascular migration. Perivascular OPCs can themselves disrupt the BBB, interfering with astrocyte endfeet and endothelial tight junction integrity, resulting in altered vascular permeability and an associated CNS inflammation. Aberrant Wnt tone in OPCs mediates their dysfunctional vascular detachment and also leads to OPC secretion of Wif1, which interferes with Wnt ligand function on endothelial tight junction integrity. Evidence for this defective oligodendroglial-vascular interaction in MS suggests that aberrant OPC perivascular migration not only impairs their lesion recruitment but can also act as a disease perpetuator via disruption of the BBB.

Objectives: Despite the recognized importance of neuromuscular exercises, there is currently no widely accepted clinical outcome measure focused on neuromuscular control for patients with knee osteoarthritis (OA). The purposes of the present study were to investigate the test-retest reliability, concurrent validity and longitudinal validity of the star excursion balance test (SEBT) in patients with knee OA. Design: 74 patients performed the SEBT on two sessions within 7 days, and on a third session after completing 12 weeks of a home exercise program focused on neuromuscular control. A subgroup of 37 performed the SEBT while in the field of view of a motion capture system to estimate concurrent validity. The SEBT was recorded in cm and also normalized to leg length (LL). Participants also completed the 40 m fast-paced walk test and patient-reported outcomes before and after the exercise program. Results: Intraclass correlation coefficients (95% confidence intervals) were 0.94 (0.91 to 0.96) and 0.93 (0.89 to 0.96) and standard errors of measurement were +/- 2.68 cm and +/- 3.05% LL for raw and normalized composite scores, respectively. The minimum detectable change at the 95% confidence level for the composite score was 7.44 cm and 8.45% LL. Correlations between observer and motion capture measures were very high (Pearson r > 0.96). There was a significant increase in SEBT following the exercise program (standardized response mean = 0.74). The change in SEBT had low correlations with changes in 40 m walk times (r = 0.26) and pain (r = 0.28). Conclusion: The SEBT has suitable measurement properties for use in patients with knee OA. (c) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Poor air quality affects the health and wellbeing of large populations around the globe. Although source controls are the most effective approaches for improving air quality and reducing health risks, individuals can also take actions to reduce their personal exposure by staying indoors, reducing physical activity, altering modes of transportation, filtering indoor air, and using respirators and other types of face masks. A synthesis of available evidence on the efficacy, effectiveness, and potential adverse effects or unintended consequences of personal interventions for air pollution is needed by clinicians to assist patients and the public in making informed decisions about use of these interventions. To address this need, the American Thoracic Society convened a workshop in May of 2018 to bring together a multidisciplinary group of international experts to review the current state of knowledge about personal interventions for air pollution and important considerations when helping patients and the general public to make decisions about how best to protect themselves. From these discussions, recommendations were made regarding when, where, how, and for whom to consider personal interventions. In addition to the efficacy and safety of the various interventions, the committee considered evidence regarding the identification of patients at greatest risk, the reliability of air quality indices, the communication challenges, and the ethical and equity considerations that arise when discussing personal interventions to reduce exposure and risk from outdoor air pollution.

BACKGROUND Despite numerous options for nasal ala reconstruction, advantages and disadvantages of each method are unclear. OBJECTIVE To summarize reported outcomes of local flaps without the use of grafts for nasal ala oncologic reconstructive surgery. METHODS A nasal ala-specific protocol was adapted from a previous head- and neck-specific PROSPERO submission (CRD42017071596). The search was conducted in MEDLINE, EMBASE, and CENTRAL on December 23, 2017 and updated on May 10, 2019. Two reviewers screened 9,313 results from head and neck literature. Study bias was evaluated with the ROBINS-I tool. RESULTS Subunit-based categorization of included studies identified 12 nasal ala-specific publications. Complications (flap necrosis, hematoma, wound infections, trapdoor deformities, and dehiscence), functional (nasal valve or respiratory dysfunction), and cosmetic (alar rim distortion/asymmetry/notching, secondary/revisionary procedures, and patient satisfaction) outcomes were extracted. CONCLUSION Generally favorable outcomes are seen in all flaps. Careful consideration of donor sites for interpolation flaps is needed for optimal cosmetic outcomes. Transposition flaps, including laterally based bilobed and trilobed flaps, created good outcomes, although melolabial transposition flaps may produce poorer outcomes compared with melolabial island pedicle advancement flaps. Caution is needed for rotation flaps to prevent nasal valve/respiratory dysfunction due to alar crease contracture or ridge elevation. Further research is needed.

Central nervous system demyelination in multiple sclerosis (MS) and subsequent axonal degeneration represents a major cause of clinical morbidity. Learning, salient experiences, and stimulation of neuronal activity induce new myelin formation in rodents and in animal models of demyelination, remyelination can be enhanced by via experience- and activity-dependent mechanisms. Furthermore, preliminary studies in MS patients supports the use of neuromodulation and rehabilitation exercises for symptomatic improvement, suggesting that these interventions may represent non-pharmacological strategies for promoting remyelination. Here, we review the literature on myelin plasticity processes and assess the potential to leverage these mechanisms to develop remyelinating therapies. This article is protected by copyright. All rights reserved.

Background While HIV/STI testing rates among Gay, bisexual and other men who have sex with men (GBMSM) are increasing worldwide, they remain suboptimal in a variety of settings. Methods The study is a pragmatic, randomized controlled trial design to evaluate a popular web drama video series developed by a community-based organization in Singapore for GBMSM. A total of 300 HIV-negative, GBMSM men in Singapore aged 18 to 29 years old were recruited and block-randomized into the intervention (n=150) and control arms (n=150). Primary outcomes included changes in self-reported intention to test for, actual testing for, and regularity of testing for HIV, Syphilis, Chlamydia and Gonorrhoea, while secondary outcomes include changes in a variety of other knowledge-based and psychosocial measures at the end of the study period. Results Overall, 125 out of 150 participants (83.3%) in the intervention arm completed the proof of completion survey, compared to 133 out of 150 participants (88.7%) in the control arm (Chi-square test, p=0.715). We found statistically significant differences in self-reporting as a regular (at least yearly) tester for HIV (Chi-square test, p=0.016), as well as chlamydia and gonorrhoea (Chi-square test, p=0.009), indicating that the intervention had positively impacted these outcomes compared to the control condition. We also found statistically significant differences in participants’ intentions to test for HIV (Chi-square test, p=0.009), syphilis (Chi-square test, p=0.014), as well as chlamydia and gonorrhoea (Chi-square test, p=0.008) in the next three months, indicating that the intervention was effective in positively impacting intention for HIV and other STI testing among participants. Conclusions There are benefits for promoting intentions to test especially in tandem with interventions that address structural barriers to testing. This intervention has potential to reach GBMSM without access to conventional HIV/STI prevention messaging, and who do not frequent physical venues where such messaging targets.

BackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564

Rationale & Objective Evidence is mixed regarding the optimal choice of the first permanent vascular access for elderly patients receiving hemodialysis (HD). Lacking data from randomized controlled trials, we used a target trial emulation approach to compare arteriovenous fistula (AVF) versus arteriovenous graft (AVG) creation among elderly patients receiving HD. Study Design Retrospective cohort study. Setting & Participants Elderly patients included in the US Renal Data System who initiated HD with a catheter and had an AVF or AVG created within 6 months of starting HD. Exposure Creation of an AVF versus an AVG as the incident arteriovenous access. Outcomes All-cause mortality, all-cause and cause-specific hospitalization, and sepsis. Analytical Approach Target trial emulation approach, high-dimensional propensity score and inverse probability of treatment weighting, and instrumental variable analysis using the proclivity of the operating physician to create a fistula as the instrumental variable. Results A total of 19,867 patients were included, with 80.1% receiving an AVF and 19.9% an AVG. In unweighted analysis, AVF creation was associated with significantly lower risks of mortality and hospitalization, especially within 6 months after vascular access creation. In inverse probability of treatment weighting analysis, AVF creation was associated with lower incidences of mortality and hospitalization within 6 months after creation (hazard ratios of 0.82 [95% CI, 0.75-0.91] and 0.82 [95% CI, 0.78-0.87] for mortality and all-cause hospitalization, respectively), but not between 6 months and 3 years after access creation. No association between AVF creation and mortality, sepsis, or all-cause, cardiovascular disease–related, or infection-related hospitalization was found in instrumental variable analyses. However, AVF creation was associated with a lower risk of access-related hospitalization not due to infection. Limitations Potential for unmeasured confounding, analyses limited to elderly patients, and absence of data on actual access use during follow-up. Conclusions Using observational data to emulate a target randomized controlled trial, the type of initial arteriovenous access created was not associated with the risks of mortality, sepsis, or all-cause, cardiovascular disease–related, or infection-related hospitalization among elderly patients who initiated HD with a catheter.

Severe cognitive decline is a hallmark of Alzheimer's disease (AD). In addition to gray matter loss, significant white matter pathology has been identified in AD patients. Here, we characterized the dynamics of myelin generation and loss in the APP/PS1 mouse model of AD. Unexpectedly, we observed a dramatic increase in the rate of new myelin formation in APP/PS1 mice, reminiscent of the robust oligodendroglial response to demyelination. Despite this increase, overall levels of myelination are decreased in the cortex and hippocampus of APP/PS1 mice and postmortem AD tissue. Genetically or pharmacologically enhancing myelin renewal, by oligodendroglial deletion of the muscarinic M1 receptor or systemic administration of the pro-myelinating drug clemastine, improved the performance of APP/PS1 mice in memory-related tasks and increased hippocampal sharp wave ripples. Taken together, these results demonstrate the potential of enhancing myelination as a therapeutic strategy to alleviate AD-related cognitive impairment.

The inflammatory environment of demyelinated lesions in multiple sclerosis (MS) patients contributes to remyelination failure. Inflammation activates a cytoprotective pathway, the integrated stress response (ISR), but it remains unclear whether enhancing the ISR can improve remyelination in an inflammatory environment. To examine this possibility, the remyelination stage of experimental autoimmune encephalomyelitis (EAE), as well as a mouse model that incorporates cuprizone-induced demyelination along with CNS delivery of the proinflammatory cytokine IFN-γ were used here. We demonstrate that either genetic or pharmacological ISR enhancement significantly increased the number of remyelinating oligodendrocytes and remyelinated axons in the inflammatory lesions. Moreover, the combined treatment of Sephin1 with the oligodendrocyte differentiation enhancing reagent bazedoxifene increased myelin thickness of remyelinated axons to pre-lesion levels. Taken together, our findings indicate that prolonging the ISR protects remyelinating oligodendrocytes and promotes remyelination in the presence of inflammation, suggesting that ISR enhancement may provide reparative benefit to MS patients.

We have witnessed rapid progress on 3D-aware image synthesis, leveraging recent advances in generative visual models and neural rendering. Existing approaches however fall short in two ways: first, they may lack an underlying 3D representation or rely on view-inconsistent rendering, hence synthesizing images that are not multi-view consistent; second, they often depend upon representation network architectures that are not expressive enough, and their results thus lack in image quality. We propose a novel generative model, named Periodic Implicit Generative Adversarial Networks ($\pi$-GAN or pi-GAN), for high-quality 3D-aware image synthesis. $\pi$-GAN leverages neural representations with periodic activation functions and volumetric rendering to represent scenes as view-consistent 3D representations with fine detail. The proposed approach obtains state-of-the-art results for 3D-aware image synthesis with multiple real and synthetic datasets.

Psoriasis is a chronic inflammatory skin disease affecting 2% to 3% of individuals worldwide. However, the majority of clinical data are in white patients, with limited data in patients of color. We present 3 cases of psoriasis representative of patients presenting to an urban and racially diverse hospital-based dermatology clinic in Toronto, Ontario, Canada, to illustrate the differences in psoriasis in patients of color compared to white patients. We review the differences in the morphology, presentation, treatment, and psychosocial impact of psoriasis in this population. We also discuss the importance of early diagnosis, treatment considerations, and education in dermatology training programs regarding psoriasis in patients of color.

This paper presents pollutant concentrations and performance data for code-required mechanical ventilation equipment in 23 low-income apartments at 4 properties constructed or renovated 2013-2017. All apartments had natural gas cooking burners. Occupants pledged to not use windows for ventilation during the study but several did. Measured airflows of range hoods and bathroom exhaust fans were lower than product specifications. Only eight apartments operationally met all ventilation code requirements. Pollutants measured over one week in each apartment included time-resolved fine particulate matter (PM2.5 ), nitrogen dioxide (NO2 ), formaldehyde and carbon dioxide (CO2 ) and time-integrated formaldehyde, NO2 and nitrogen oxides (NOX ). Compared to a recent study of California houses with code-compliant ventilation, apartments were smaller, had fewer occupants, higher densities, and higher mechanical ventilation rates. Mean PM2.5 , formaldehyde, NO2 , and CO2 were 7.7µg/m3 , 14.1, 18.8, and 741ppm in apartments; these are 4% lower, 25% lower, 165% higher, and 18% higher compared to houses with similar cooking frequency. Four apartments had weekly PM2.5 above the California annual outdoor standard of 12µg/m3 and also discrete days above the World Health Organization 24-hour guideline of 25µg/m3 . Two apartments had weekly NO2 above the California annual outdoor standard of 30ppb.

This work provides the design methodology of a radioisotope thermophotovoltaic system (RTPV) using spectral control for space missions. The focus is on the feasibility of a practical system by using two-dimensional micropatterned photonic crystal emitters, selecting the proper thermophotovoltaic cell and insulation material to exclude material incompatibilities, to optimize the system efficiency by impedance matching and to design a radiator with minimum mass. In the last section, a design example is presented based on the tested indium gallium arsenide antimonide (InGaAsSb) cells. It is shown computationally that, in using the experimentally tested InGaAsSb cells, the RTPV generator is expected to reach an efficiency of 8.6% and a specific power of 10.1 W∕kg with advanced radiators. Using the more efficient InGaAs cells, the system can expect to triple the figure of merits of the radioisotope thermoelectric generator, promising to reach ∼18% and 21 W∕kg, respectively. With a high performance device, the results of this work can lead to a functional prototype for further research focusing on manufacturability and reliability., Army Research Office through the Institute for Soldier Nanotechnologies (Contracts W911NF-07-D0004, MAST 892730 and S3TEC DE-SC0001299)

Objective Usability of electronic health records (EHRs) remains challenging, and poor EHR design has patient safety implications. Heuristic evaluation detects usability issues that can be classified by severity. The National Institute of Standards and Technology provides a safety scale for EHR usability. Our objectives were to investigate the relationship between heuristic severity ratings and safety scale ratings in an effort to analyze EHR safety. Materials and Methods Heuristic evaluation was conducted on seven common mobile EHR tasks, revealing 58 heuristic violations and 28 unique usability issues. Each usability issue was independently scored for severity by trained hospitalists and a Human Factors researcher and for safety severity by two physician informaticists and two clinical safety professionals. Results Results demonstrated a positive correlation between heuristic severity and safety severity ratings. Regression analysis demonstrated that 49% of safety risk variability by clinical safety professionals (r = 0.70; n = 28) and 42% of safety risk variability by clinical informatics specialists (r = 0.65; n = 28) was explained by usability severity scoring of problems outlined by heuristic evaluation. Higher severity ratings of the usability issues were associated with increased perceptions of patient safety risk. Discussion This study demonstrated the use of heuristic evaluation as a technique to quickly identify usability problems in an EHR that could lead to safety issues. Detection of higher severity ratings could help prioritize failures in EHR design that more urgently require design changes. This approach is a cost-effective technique for improving usability while impacting patient safety. Conclusion Results from this study demonstrate the efficacy of the heuristic evaluation technique to identify usability problems that impact safety of the EHR. Also, the use of interdisciplinary teams for evaluation should be considered for severity assessment.

There is currently a lack of precise predictive biomarkers for patient selection in clinical trials of inhibitors targeting replication stress (RS) response proteins ATR and CHK1. The objective of this study was to identify novel predictive biomarkers for the response to these agents in treating non–small cell lung cancer (NSCLC). A genome-wide loss-of-function screen revealed that tumor suppressor PPP2R2A, a B regulatory subunit of protein phosphatase 2 (PP2A), determines sensitivity to CHK1 inhibition. A synthetic lethal interaction between PPP2R2A deficiency and ATR or CHK1 inhibition was observed in NSCLC in vitro and in vivo and was independent of p53 status. ATR and CHK1 inhibition resulted in significantly increased levels of RS and altered replication dynamics, particularly in PPP2R2A-deficient NSCLC cells. Mechanistically, PPP2R2A negatively regulated translation of oncogene c-Myc protein. c-Myc activity was required for PPP2R2A deficiency-induced alterations of replication initiation/RS and sensitivity to ATR/CHK1 inhibitors. We conclude that PPP2R2A deficiency elevates RS by upregulating c-Myc activity, rendering cells reliant on the ATR/CHK1 axis for survival. Our studies show a novel synthetic lethal interaction and identify PPP2R2A as a potential new predictive biomarker for patient stratification in the clinical use of ATR and CHK1 inhibitors.Significance:This study reveals new approaches to specifically target PPP2R2A-deficient lung cancer cells and provides a novel biomarker that will significantly improve treatment outcome with ATR and CHK1 inhibitors.

Atopic dermatitis (AD) is a chronic skin disease characterized by barrier dysfunction and immune dysregulation that affects approximately 20% of children and 2-5% of adults worldwide. Traditionally, AD has been considered a disease of childhood with many cases resolving before adulthood. However, in recent years, the prevalence of adult AD is increasingly recognized to be substantial, but it is uncertain whether this increase is due to increased childhood-persistent or relapsed AD, or new adult-onset AD. This highlights a need for further investigation into the adult AD population and evaluation of phenotypes in the adult-onset cohort. In this literature review, we examine five studies focused on adult-onset AD phenotype, conducted between 2013 and 2017. The most commonly reported body regions affected in adult-onset AD were the hands, eyelids, neck, and flexural surfaces of the upper limbs. These vary from childhood-onset AD findings, which are less specific to body regions other than flexural areas. These findings have implications for diagnostic accuracy and treatment of AD, including considerations for therapeutic choices and inclusion and exclusion criteria in clinical trials.

Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive ablative treatment for essential tremor. The size and location of therapeutic lesions producing the optimal clinical benefits while minimizing adverse effects are not known. We examined these relationships in patients with essential tremor undergoing MRgFUS. We studied 66 patients with essential tremor who underwent MRgFUS between 2012 and 2017. We assessed the Clinical Rating Scale for Tremor (CRST) scores at 3 months after the procedure and tracked the adverse effects (sensory, motor, speech, gait, and dysmetria) 1 day (acute) and 3 months after the procedure. Clinical data associated with the postoperative Day 1 lesions were used to correlate the size and location of lesions with tremor benefit and acute adverse effects. Diffusion-weighted imaging was used to assess whether acute adverse effects were related to lesions encroaching on nearby major white matter tracts (medial lemniscus, pyramidal, and dentato-rubro-thalamic). The area of optimal tremor response at 3 months after the procedure was identified at the posterior portion of the ventral intermediate nucleus. Lesions extending beyond the posterior region of the ventral intermediate nucleus and lateral to the lateral thalamic border were associated with increased risk of acute adverse sensory and motor effects, respectively. Acute adverse effects on gait and dysmetria occurred with lesions inferolateral to the thalamus. Lesions inferolateral to the thalamus or medial to the ventral intermediate nucleus were also associated with acute adverse speech effects. Diffusion-weighted imaging revealed that lesions associated with adverse sensory and gait/dysmetria effects compromised the medial lemniscus and dentato-rubro-thalamic tracts, respectively. Lesions associated with adverse motor and speech effects encroached on the pyramidal tract. Lesions larger than 170 mm3 were associated with an increased risk of acute adverse effects. Tremor improvement and acute adverse effects of MRgFUS for essential tremor are highly dependent on the location and size of lesions. These novel findings could refine current MRgFUS treatment planning and targeting, thereby improving clinical outcomes in patients.

We estimate postmeter methane (CH4) emissions from California's residential natural gas (NG) system using measurements and analysis from a sample of homes and appliances. Quiescent whole-house emissions (i.e., pipe leaks and pilot lights) were measured using a mass balance method in 75 California homes, while CH4 to CO2 emission ratios were measured for steady operation of individual combustion appliances and, separately, for transient operation of three tankless water heaters. Measured quiescent whole-house emissions are typically 10 g CH4/day. Most operating appliances yield undetectable CH4 to CO2 enhancements in steady operation (

// Samaneh K. Sarvestani 1, * , Steven A. Signs 1, * , Veronique Lefebvre 2 , Stephen Mack 3 , Ying Ni 4 , Andrew Morton 1, 5 , Ernest R. Chan 6 , Xiaoxia Li 7 , Paul Fox 2 , Angela Ting 4 , Matthew F. Kalady 1, 8 , Michael Cruise 9 , Jean Ashburn 10 , Jennifer Stiene 1 , Wei Lai 1 , David Liska 1, 8 , Shao Xiang 1 and Emina H. Huang 1, 8 1 Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA 2 Department of Cell and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio, USA 3 Department of Pediatrics Baylor College of Medicine, Houston, Texas, USA 4 Department of Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA 5 Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA 6 Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA 7 Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA 8 Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio, USA 9 Department of Pathology, Cleveland Clinic, Cleveland, Ohio, USA 10 Department of Surgery, Wake Forest School of Medicine, Salem, North Carolina, USA * These authors have contributed equally to this work Correspondence to: Emina H. Huang, email: huange2@ccf.org Keywords: ulcerative colitis; organoids; inflammation; H3K27Ac enhancer chromatin mark; colitis associated cancer Received: December 09, 2017 Accepted: May 24, 2018 Published: June 19, 2018 ABSTRACT Ulcerative colitis (UC) is a prevalent form of inflammatory bowel disease (IBD) whose pathogenic mechanisms remain unclear. Elucidating these mechanisms is important to reduce UC symptoms and to prevent UC progression into colitis-associated colon cancer (CAC). Our goal was to develop and validate faithful, human-derived, UC models and analyze them at histologic, transcriptomic and epigenetic levels to allow mechanistic studies of UC and CAC pathogenesis. We generated patient-derived primary-organoid cultures from UC and non-IBD colonic epithelium. We phenotyped them histologically and used next-generation-sequencing approaches to profile whole transcriptomes and epigenomes of organoids and primary tissues. Tissue organization and expression of mucin 2 (MUC2) and lysozyme (LYZ) demonstrated histologic faithfulness of organoids to healthy and diseased colonic epithelium. Transcriptomic analyses showed increased expression of inflammatory pathways in UC patient-derived organoids and tissues. Profiling for active enhancers using the H3K27ac histone modification revealed UC-derived organoid enrichment for pathways indicative of gastrointestinal cancer, including S100 calcium-binding protein P ( S100P ), and revealed novel markers for GI cancer, including both LYZ and neuropeptide S receptor 1 ( NPSR1 ). Immunolocalization showed increased levels of LYZ, S100P, and NPSR1 proteins in UC and CAC. In conclusion, primary colonic organoid cultures from UC and non-IBD patients can be established that faithfully represent diseased or normal colonic states. These models reveal precancerous molecular pathways that are already activated in UC. The findings demonstrate the suitability of primary organoids for dissecting UC and CAC pathogenic mechanisms and suggest new targets for therapeutic intervention.

A cross-industry survey was conducted to assess the landscape of preclinical quantitative systems pharmacology (QSP) modeling within pharmaceutical companies. This article presents the survey results, which provide insights on the current state of preclinical QSP modeling in addition to future opportunities. Our results call attention to the need for an aligned definition and consistent terminology around QSP, yet highlight the broad applicability and benefits preclinical QSP modeling is currently delivering.

Percutaneous coronary intervention (PCI) continues to evolve with shifting patient demographics, treatments, and outcomes. We sought to document the specific changes observed over a 9-year period in a contemporary Australian PCI cohort. The Melbourne Interventional Group is an established multicenter PCI registry in Melbourne, Australia. Data were collected prospectively with 30-day and 12-month follow-ups. Demographic, procedural, and outcome data for all consecutive patients were analyzed with a year-to-year comparison from 2005 to 2013. National Death Index linkage was performed for long-term mortality analysis; 19,858 procedures were captured over 9 years. Patient complexity and acuity increased with a higher proportion of traditional risk factors and more elderly patients who underwent PCI. Angiographic lesion complexity increased with more multivessel coronary artery disease and more American College of Cardiology/American Heart Association type B2/C lesions proceeding to PCI. The 30-day rate of death, myocardial infarction, or target vessel revascularization has not changed nor has 12-month mortality, myocardial infarction, or major adverse cardiovascular event rates. The strongest independent predictor of long-term mortality was cardiogenic shock at presentation (hazard ratio [HR] 2.95, p

Background Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath’s four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Results Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18–20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Conclusions Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.

Previous research has shown that under-ventilation of classrooms is common and negatively impacts student health and learning. To advance understanding of contributing factors, this study visited 104 classrooms from 11 schools that had recently been retrofitted with new heating, ventilation, and air-conditioning (HVAC) units. CO2 concentration, room and supply air temperature and relative humidity, and door opening were measured for four weeks in each classroom. Field inspections identified HVAC equipment, fan control, and/or filter maintenance problems in 51% of the studied classrooms. Across 94 classrooms with valid data, average CO2 concentrations measured during school hours had a mean of 895 ppm and a standard deviation (SD) of 263 ppm. Ventilation rates (VRs), estimated using the daily maximum 15-min CO2 in each classroom, had a mean of 5.2 L/s-person and a SD of 2.0 L/s-person across 94 classrooms. Classrooms with economizers, with or without demand control ventilation (DCV), tended to have lower mean CO2. Improperly selected equipment, lack of commissioning, incorrect fan control settings and maintenance issues (heavily loaded filters) were all associated with under-ventilation in classrooms. Many classrooms in this sample were frequently too warm to support learning. There were 23 out of 103 classrooms that had indoor air temperature above 25.6 °C for more than 20% of the school hours. Better oversight on HVAC system installation and commissioning are needed to ensure adequate classroom ventilation. Periodic testing of ventilation systems and/or continuous real-time CO2 monitoring (either as stand-alone monitors or incorporated into thermostats) is recommended to detect and correct ventilation problems.

As one special type of sustainable energy source, radioisotopes have extremely high energy densities. Electrical generators using the decay heat from these radioisotopes can provide long-lasting power when other types of energy, such as solar or chemical energy, are not available. Starting from the 1960s, radioisotope generators were safely used in numerous space and terrestrial missions, and have powered systems from interstellar spacecraft to lighthouses along the arctic coast. This work reviewed the generator development and critical components that constitute a functional system. Started with a brief generator history, the paper focused on technological aspects including fuel manufacturing, energy conversion elements, thermal insulation, structural materials, prototype measurements, future improvements, and concluded with the safety aspects for both space and terrestrial applications. Radioisotope generators are one example of using nuclear energy in a peaceful way to benefit human be-ings. Plutonium fuel productions were resumed and accelerated in the United States and americium fuel research was actively sponsored by the European Space Agency. It is promis-ing that more and more high performance generators will be used in future land and space missions., Army Research Office through the Institute for Soldier Nanotechnologies (Contracts W911NF-07-D0004, MAST 892730 and S3TEC DE-SC0001299)

Long-term survivors after hematopoietic stem cell transplantation are at high risk of infection, which accounts for one-third of all deaths related to stem cell transplantation. Little is known about the cause of inferior host defense after immune cell reconstitution. Here, we exploited a murine syngeneic BM transplantation (BMT) model of late infection with murine gammaherpesvirus 68 (MHV-68) to determine the role of conventional DC (cDC) trafficking in adaptive immunity in BMT mice. After infection, the expression of chemokine Ccl21 in the lung is reduced and the migration of cDCs into lung draining lymph nodes (dLNs) is impaired in BMT mice, limiting the opportunity for cDCs to prime Th cells in the dLNs. While cDC subsets are redundant in priming Th1 cells, Notch2 functions in cDC2s are required for priming increased Th17 responses in BMT mice, and cDC1s can lessen this activity. Importantly, Th17 cells can be primed both in the lungs and dLNs, allowing for increased Th17 responses without optimum cDC trafficking in BMT mice. Taken together, impaired cDC trafficking in BMT mice reduces protective Th1 responses and allows increased pathogenic Th17 responses. Thus, we have revealed a previously unknown mechanism for BMT procedures to cause long-term inferior immune responses to herpes viral infection.

Hypercalcemia most often results from primary hyperparathyroidism and malignancy. Adynamic bone disease (ABD) is a form of renal osteodystrophy characterized by reduced bone turnover, which can limit the ability of bone to release or store calcium, potentially leading to low, normal, or high serum calcium levels. We describe a 51‐year‐old dialysis‐dependent female with hypercalcemia after parathyroidectomy. A demeclocycline‐labeled bone biopsy confirmed adynamic bone disease. Teriparatide, a recombinant form of parathyroid hormone (PTH) used to treat postmenopausal osteoporosis, was prescribed for 12 months and normalized serum calcium levels. Although previous case reports and series have described favorable changes in spine bone mineral density when teriparatide was prescribed for ABD, ours is the first documented case in which teriparatide resolved hypercalcemia due to ABD. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Antidepressants are the primary form of pharmacotherapy in the treatment of depression and anxiety, however they have been known to vary widely in response and cause undesirable adverse effects among patients. As antidepressant response has been proven to have a genetic basis, pharmacogenetics may hold the key to unlocking personalized medicine, which can greatly benefit patients, physicians, and the healthcare system. This chapter addresses the current stance in psychiatric pharmacogenetics, and discusses the outlook for the field. Within depression and anxiety, variants within the cytochrome P450 enzymes, the serotonin transporter, and the norepinephrine transporter genes have yielded the strongest findings. With respect to clinical applicability, there is wide consensus for use of pharmacokinetic genes to inform treatment and to mitigate adverse events, while recommendations to include pharmacodynamic genes remain inconclusive. This testifies to the need for further research and to test genetically based algorithms.

Rationale & objective Creation of an arteriovenous fistula (AVF), compared to an AV graft (AVG), is associated with longer initial catheter dependence after starting hemodialysis but longer access survival and lower long-term catheter dependence. The extent of these potential long-term benefits in elderly patients is unknown. We assessed catheter dependence after AVF or AVG placement among elderly patients who initiated HD without a permanent access in place. Study design Retrospective cohort study. Setting& participants Patients ≥67 years of age identified in the United States Renal Data System (USRDS) who had a first AVF (n=14,532) or AVG (n=3391) placed within 1 year after HD initiation between May 2012 and May 2017. Exposure AVF versus AVG placement in first year of hemodialysis. Outcome Catheter dependence after AVF or AVG placement assessed using CROWNWeb data. ANALYTICAL APPROACH: - Generalized estimating equations and negative binomial regression for catheter use over time and Cox proportional hazards models for mortality. Results Creation of an AVF versus AVG was associated with greater catheter dependence at one month (95.6% vs. 92.5%) and at three months (82.8% vs. 41.2%), but lower catheter dependence at 12 months (14.2% vs. 15.8%) and at 36 months (8.2% vs. 15.0%). Creation of an AVF, however, remained significantly associated with greater cumulative catheter-dependent days (80.1 vs 54.6 days per person-year) and a lower proportion of catheter-free survival time (78.1% vs 85.1%) after three years of follow-up. Limitations Potential for unmeasured confounding and analyses limited to elderly patients. Conclusions Creation of an AVF was associated with significantly greater cumulative catheter dependence than placement of an AVG in an elderly population initiating HD without a permanent access. As the long-term benefits in terms of catheter dependency of an AVF are not realized in many elderly patients, specific patient characteristics should be considered when making decisions regarding vascular access.

We present a technology that efficiently harnesses the energy content of hydrocarbon fuels in a volume that is only a fraction of a cubic inch. A propane-fueled microcombustor heats a photonic crystal emitter to incandescence and the resulting spectrally-confined thermal radiation drives low-bandgap PV cells to generate electricity. We overcome the technical challenges that are currently limiting thermophotovoltaics in the following ways: we develop new fabrication processes; we adopt high-temperature alloys to improve the thermo-mechanical stability; we adopt commercial polycrystalline tantalum to fabricate large-area photonic crystals; and finally, we develop a passivation coating for improved thermo-chemical stability. We demonstrate unprecedented heat-to-electricity efficiencies exceeding 4%, greater than the 2–3% efficiencies that were previously thought to be the practical limit, and we predict that over 12% efficiency is achievable with only engineering optimization. For reference, a 1.5% efficiency corresponds to the energy density of lithium ion batteries. This work opens new opportunities to free portable electronics, robots, and small drones from the constraints of bulky power sources.

This work describes RTPV-PhC-1, an initial prototype for a radioisotope thermophotovoltaic (RTPV) system using a two-dimensional photonic crystal emitter and low bandgap thermophotovoltaic (TPV) cell to realize spectral control. We validated a system simulation using the measurements of RTPV-PhC-1 and its comparison setup RTPV-FlatTa-1 with the same configuration except a polished tantalum emitter. The emitter of RTPV-PhC-1 powered by an electric heater providing energy equivalent to one plutonia fuel pellet reached 950 °C with 52 W of thermal input power and produced 208 mW output power from 1 cm2 TPV cell. We compared the system performance using a photonic crystal emitter to a polished flat tantalum emitter and found that spectral control with the photonic crystal was four times more efficient. Based on the simulation, with more cell areas, better TPV cells, and improved insulation design, the system powered by a fuel pellet equivalent heat source is expected to reach an efficiency of 7.8%.

BACKGROUND: Although induction of labor (IOL) of low-risk nulliparous women at 39 weeks reduces the risk of cesarean delivery compared with expectant management, concern regarding more frequent use of labor induction remains given that this intervention historically has been thought to incur greater resource utilization. OBJECTIVE: To determine whether planned elective labor induction at 39 weeks among low-risk nulliparous women, compared with expectant management, was associated with differences in health care resource utilization from the time of randomization through 8 weeks postpartum. STUDY DESIGN: This is a planned secondary analysis of a multi-center randomized trial in which low-risk nulliparous women were assigned to IOL at 39 weeks or expectant management. We assessed resource utilization post-randomization in three time periods: antepartum (AP), delivery admission, and discharge through 8 weeks postpartum (PP). RESULTS: Of 6096 women with data available, those in the IOL group (n = 3059) were significantly less likely in the AP period after randomization to have at least one ambulatory visit for routine prenatal care (32.4% vs. 68.4%), unanticipated care (0.5% vs. 2.6%), or urgent care (16.2% vs. 44.3%), or at least one antepartum hospitalization (0.8% vs. 2.2%, p0.05 for all). CONCLUSIONS: Women randomized to IOL had longer durations in labor and delivery, but significantly fewer AP visits, tests, and treatments, and shorter maternal and neonatal hospital durations post-delivery. These results demonstrate that the health outcome advantages associated with IOL are gained without incurring uniformly greater health care resource use. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01990612

The underlying cellular mechanisms of catatonia, an executive "psychomotor" syndrome that is observed across neuropsychiatric diseases, have remained obscure. In humans and mice, reduced expression of the structural myelin protein CNP is associated with catatonic signs in an age-dependent manner, pointing to the involvement of myelin-producing oligodendrocytes. Here, we showed that the underlying cause of catatonic signs is the low-grade inflammation of white matter tracts, which marks a final common pathway in Cnp-deficient and other mutant mice with minor myelin abnormalities. The inhibitor of CSF1 receptor kinase signaling PLX5622 depleted microglia and alleviated the catatonic symptoms of Cnp mutants. Thus, microglia and low-grade inflammation of myelinated tracts emerged as the trigger of a previously unexplained mental condition. We observed a very high (25%) prevalence of individuals with catatonic signs in a deeply phenotyped schizophrenia sample (n = 1095). Additionally, we found the loss-of-function allele of a myelin-specific gene (CNP rs2070106-AA) associated with catatonia in 2 independent schizophrenia cohorts and also associated with white matter hyperintensities in a general population sample. Since the catatonic syndrome is likely a surrogate marker for other executive function defects, we suggest that microglia-directed therapies may be considered in psychiatric disorders associated with myelin abnormalities.