An interactive atlas of three-dimensional syndromic facial morphology.

Craniofacial phenotyping is critical for both syndrome delineation and diagnosis because craniofacial abnormalities occur in 30% of characterized genetic syndromes. Clinical reports, textbooks, and available software tools typically provide two-dimensional, static images and illustrations of the characteristic phenotypes of genetic syndromes. In this work, we provide an interactive web application that provides three-dimensional, dynamic visualizations for the characteristic craniofacial effects of 95 syndromes. Users can visualize syndrome facial appearance estimates quantified from data and easily compare craniofacial phenotypes of different syndromes. Our application also provides a map of morphological similarity between a target syndrome and other syndromes. Finally, users can upload 3D facial scans of individuals and compare them to our syndrome atlas estimates. In summary, we provide an interactive reference for the craniofacial phenotypes of syndromes that allows for precise, individual-specific comparisons of dysmorphology.

Caenorhabditis elegans establishes germline versus soma by balancing inherited histone methylation.

Formation of a zygote is coupled with extensive epigenetic reprogramming to enable appropriate inheritance of histone methylation and prevent developmental delays. In Caenorhabditis elegans, this reprogramming is mediated by the H3K4me2 demethylase SPR-5 and the H3K9 methyltransferase, MET-2. In contrast, the H3K36 methyltransferase MES-4 maintains H3K36me2/3 at germline genes between generations to facilitate re-establishment of the germline. To determine whether the MES-4 germline inheritance pathway antagonizes spr-5; met-2 reprogramming, we examined the interaction between these two pathways. We found that the developmental delay of spr-5; met-2 mutant progeny is associated with ectopic H3K36me3 and the ectopic expression of MES-4-targeted germline genes in somatic tissues. Furthermore, the developmental delay is dependent upon MES-4 and the H3K4 methyltransferase, SET-2. We propose that MES-4 prevents crucial germline genes from being repressed by antagonizing maternal spr-5; met-2 reprogramming. Thus, the balance of inherited histone modifications is necessary to distinguish germline versus soma and prevent developmental delay.This article has an associated 'The people behind the papers' interview.

Chloramphenicol treatment revisited - demographics, clinical characteristics, and outcomes of hospitalized patients.

Limited literature exists on chloramphenicol's clinical use. In this retrospective, single-center case-series, we examined 183 chloramphenicol-treated and 81 piperacillin-tazobactam-treated medical patients. Chloramphenicol recipients were older, more debilitated, cognitively impaired, and penicillin allergic, while increased need for inotropics, higher leukocyte count, and higher creatinine levels were notable in the piperacillin-tazobactam group. Pneumonia was the most common indication, with no mortality difference between groups. While acknowledging its antimicrobial activity and potential benefit in specific conditions such as pneumonia, further clinical studies are needed to assess the role of chloramphenicol in the setting where other alternatives are available.

Physical activity counseling in primary care: Insights from public health and behavioral economics.

Physical inactivity has reached epidemic proportions in modern society. Abundant evidence points to a causal link between physical inactivity and increased risk for numerous noncommunicable diseases, such as some types of cancer and heart disease, as well as premature mortality. Yet, despite this overwhelming evidence, many individuals do not meet the recommended amount of physical activity required to achieve maximum health benefits. Because primary care physicians' advice is highly regarded, clinicians have the unique opportunity to play an important role in enabling patients to modify their behavior at the point of care with the goal of guiding patients to adopt and maintain an active lifestyle. In the current study, the authors evaluate pertinent literature from the fields of medicine/public health and economics/psychology to suggest a comprehensive approach to physical activity counseling at the primary care level. They first examine the public health approach to physical activity counseling, and then proceed to offer insights from behavioral economics, an emerging field that combines principles from psychology and economics. The application of key behavioral economics tools (eg, precommitment contracts, framing) to physical activity counseling in primary care is elaborated. CA Cancer J Clin 2017;67:233-244. © 2017 American Cancer Society.

Reasons for Migration and Their Associations with HIV Risk and Prevention Among Cisgender Sexual Minority Men: A Latent Class Analysis.

The immigrant population in the United States (U.S.) is rapidly growing; yet there is limited knowledge about how reasons for migrating to the U.S. are associated with HIV prevention behaviors. Using data from the American Men's Internet Survey (2018-2020), we performed a Latent Class Analysis (LCA) to identify patterns in reasons for migration among cisgender gay, bisexual, and other sexual minority men (SMM) who born outside the U.S. We used multivariable logistic regression controlling for demographic characteristics to assess class associations with the following in the past 12 months: condomless anal sex (CAS), illicit drug use, marijuana use, HIV testing, and PrEP use. LCA identified six distinct patterns in reasons for migration among the sample (n = 1,657): (1) Family and friends (14%); (2) Financial (17%); (3) Personal freedom related to being gay (10%); (4) Pursuit of opportunities while living openly as SMM (12%); (5) Educational purposes (18%); (6) Not my decision (29%). While HIV testing (range = 57.6-65.4%) and PrEP use (range = 15.6-21.4%) did not vary by class (p > .05 for all), CAS and illicit drug use were significantly different (p < .05). SMM who migrated to pursue opportunities while living openly and whose reasons were not their decision had greater odds of CAS than SMM who migrated for educational purposes (aOR:1.72, 95% confidence interval [95%CI]:1.15-2.59; 1.57, 1.13-2.19, respectively). Reasons for migration among SMM were associated with behaviors that can increase HIV risk, but not testing or PrEP. Push and pull factors related to migration should be considered when developing behavioral HIV interventions for immigrant SMM.

RESUMEN: La población inmigrante en los Estados Unidos (EE. UU.) está creciendo rápidamente; sin embargo, hay un conocimiento limitado acerca de cómo las razones para migrar a los EE. UU. se asocian con comportamientos de prevención del VIH. Utilizando datos del American Men's Internet Survey (2018­2020), realizamos un Análisis de Clases Latentes (ACL) para identificar patrones en las razones de migración entre hombres cisgénero gays, bisexuales y otros hombres de minorías sexuales (HMS) que reportaron haber nacido fuera de los EE. UU. Utilizamos regresión logística multivariable controlando las características demográficas para evaluar las asociaciones de clases con los siguientes comportamientos en los últimos 12 meses: sexo anal sin condón (SAC), consumo de drogas ilícitas, uso de marihuana, prueba del VIH y uso de PrEP. El ACL identificó seis patrones distintos en las razones de migración en la muestra (n = 1,657): (1) Familia y amigos (14%); (2) Motivos financieros (17%); (3) Libertad personal relacionada con ser gay (10%); (4) Búsqueda de oportunidades mientras viven abiertamente como HMS (12%); (5) Propósitos educativos (18%); (6) No fue decisión propia (29%). Mientras que las pruebas del VIH (rango = 57.6­65.4%) y el uso de PrEP (rango = 15.6­21.4%) no variaron según la clase (p > .05 para todos), el SAC y el consumo de drogas ilícitas fueron significativamente diferentes (p < .05). Los HMS que emigraron para perseguir oportunidades mientras vivían abiertamente, y aquellos cuyas razones no fueron decisión propia, tuvieron mayores probabilidades de tener SAC que los HMS que emigraron con propósitos educativos (razón de probabilidades ajustada [aOR]: 1.72, intervalo de confianza del 95% [IC 95%]: 1.15­2.59; 1.57, 1.13­2.19, respectivamente). Las razones de migración a los EE. UU. entre los HMS estuvieron asociadas con comportamientos que pueden aumentar el riesgo de VIH, pero no con pruebas o PrEP. Los factores que impulsan y atraen relacionados con la migración deben considerarse al desarrollar intervenciones de prevención del VIH para HMS inmigrantes.

Behavior Change Among HIV-Negative Men Who Have Sex with Men Not Using PrEP in the United States.

This study measures changes in condomless anal sex (CAS) among HIV-negative men who have sex with men (MSM) who are not taking pre-exposure prophylaxis (PrEP). It considers the 2014-2019 cycles of the American Men's Internet Survey, a serial, cross-sectional web-based survey of US cisgender MSM aged ≥ 15 years, in which ~ 10% of each year's sample is drawn from the previous year. Among those surveyed for 2 years who remained HIV-negative and off PrEP, reports of having any CAS and of CAS partner number were compared across years. We disaggregated by partner HIV status, and considered demographic predictors. The overall population saw a significant 2.2 percentage-point (pp) increase in reports of any CAS year-over-year. Sub-populations with the largest year-on-year increases were 15-24-year-olds (5.0-pp) and Hispanic respondents (5.1-pp), with interaction (young Hispanic respondents = 12.8-pp). On the relative scale, these numbers correspond to 3.2%, 7.2%, 7.3% and 18.7%, respectively. Absolute increases were concentrated among partners reported as HIV-negative. Multivariable analyses for CAS initiation found effects concentrated among Hispanic and White youth and residents of fringe counties of large metropolitan areas. CAS partner number increases were similarly predicted by Hispanic identity and young age. Although condom use remains more common than PrEP use, increasing CAS among MSM not on PrEP suggests potential new HIV transmission pathways. Concentration of increases among 18-24-year-old MSM portends future increases in the proportion of newly diagnosed HIV that occur among youth. Concentration among young Hispanic MSM will likely expand existing disparities. Although reducing barriers to PrEP remains vital, condom promotion for MSM remains a key public health practice and appears to be missing key audiences. LGBTQ+-inclusive sex education is one avenue for enhancing these efforts.

"We're On The Same Team": A Qualitative Study On Communication And Care Coordination Surrounding The Requirement To Quit Smoking Prior To Elective Orthopaedic Surgery.

INTRODUCTION: Many surgeons require patients to quit smoking prior to elective surgeries to reduce the risk of postoperative complications. Our aim was to qualitatively evaluate the communication and care experiences of patients and clinicians involved in conversations about quitting smoking prior to elective orthopaedic surgery. METHODS: A qualitative interview study of rural-residing Veterans, primary care providers (PCPs), and Veterans Administration (VA) orthopaedic surgery staff and pharmacists, who care for rural Veterans. We performed a combination of deductive and inductive approaches to support conventional content analysis using a Patient-Centered Care framework. RESULTS: Patients appreciated a shared approach with their PCP on the plan and reasons for cessation. Despite not knowing if the motivation for elective surgeries served as a teachable moment to facilitate long-term abstinence, almost all clinicians believed it typically helped in the short-term. There was a lack of standardized workflow between primary care and surgery, especially when patients used care delivered outside of VA. CONCLUSIONS: While clinician-provided information about the reasons behind the requirement to quit smoking preoperatively was beneficial, patients appreciated the opportunity to collaborate with their care teams on developing a plan for cessation and abstinence. Other aspects of patient-centered care need to be leveraged, such as the therapeutic alliance or patient-as-person, to build trust and improve communication surrounding tobacco use treatment. System-level changes may need to be made to improve coordination and connection of clinicians within and across disciplines. IMPLICATIONS: This study included perspectives from patients, primary care teams, and surgical teams and found that, in addition to providing information, clinicians need to address other aspects of patient-centered care such as the therapeutic alliance and patient-as-person domains to promote patient engagement in tobacco use treatment. This, in turn, could enhance the potential of surgery as a teachable moment and patient success in quitting smoking.

A C. elegans LSD1 demethylase contributes to germline immortality by reprogramming epigenetic memory.

Epigenetic information undergoes extensive reprogramming in the germline between generations. This reprogramming may be essential to establish a developmental ground state in the zygote. We show that mutants in spr-5, the Caenorhabditis elegans ortholog of the H3K4me2 demethylase LSD1/KDM1, exhibit progressive sterility over many generations. This sterility correlates with the misregulation of spermatogenesis-expressed genes and transgenerational accumulation of the histone modification dimethylation of histone H3 on lysine 4 (H3K4me2). This suggests that H3K4me2 can serve as a stable epigenetic memory, and that erasure of H3K4me2 by LSD/KDM1 in the germline prevents the inappropriate transmission of this epigenetic memory from one generation to the next. Thus, our results provide direct mechanistic insights into the processes that are required for epigenetic reprogramming between generations.

Characterizing the Communication Networks of Spanish- and English-Speaking Latinx Sexual Minority Men and Their Roles in Pre-Exposure Prophylaxis Uptake.

While pre-exposure prophylaxis (PrEP) has demonstrated efficacy in preventing HIV transmission, disparities in access persist in the United States, especially among Hispanic/Latinx sexual minority men (SMM). Language barriers and differences in how Latinx SMM obtain information may impact access to PrEP and HIV prevention. This study used data from the 2021 American Men's Internet Survey (AMIS) to examine differences in communication networks and PrEP use among Latinx SMM by primary language (Spanish vs. English). We examined the associations between Latinx SMM's individual- and meso-level communication networks and PrEP-related outcomes using modified Poisson regression with robust variances. Spanish-speaking Latinx SMM in the study were less likely to test for HIV, be aware of PrEP, and use daily PrEP, compared to English-speaking participants. Sexuality disclosure to a healthcare provider was positively associated with PrEP uptake among all participants and predicted STI testing over the past 12 months among English-speaking Latinx SMM. Findings highlight disparities in PrEP awareness and uptake among Latinx SMM, especially among those whose primary language is Spanish. Addressing these disparities through targeted interventions, including improved communication with healthcare providers, may help facilitate PrEP access and use in this population.

Unique molecular characteristics and microglial origin of Kv1.3 channel-positive brain myeloid cells in Alzheimer's disease.

Kv1.3 potassium channels, expressed by proinflammatory central nervous system mononuclear phagocytes (CNS-MPs), are promising therapeutic targets for modulating neuroinflammation in Alzheimer's disease (AD). The molecular characteristics of Kv1.3-high CNS-MPs and their cellular origin from microglia or CNS-infiltrating monocytes are unclear. While Kv1.3 blockade reduces amyloid beta (Aß) burden in mouse models, the downstream immune effects on molecular profiles of CNS-MPs remain unknown. We show that functional Kv1.3 channels are selectively expressed by a subset of CD11b+CD45+ CNS-MPs acutely isolated from an Aß mouse model (5xFAD) as well as fresh postmortem human AD brain. Transcriptomic profiling of purified CD11b+Kv1.3+ CNS-MPs, CD11b+CD45int Kv1.3neg microglia, and peripheral monocytes from 5xFAD mice revealed that Kv1.3-high CNS-MPs highly express canonical microglial markers (Tmem119, P2ry12) and are distinct from peripheral Ly6chigh/Ly6clow monocytes. Unlike homeostatic microglia, Kv1.3-high CNS-MPs express relatively lower levels of homeostatic genes, higher levels of CD11c, and increased levels of glutamatergic transcripts, potentially representing phagocytic uptake of neuronal elements. Using irradiation bone marrow CD45.1/CD45.2 chimerism in 5xFAD mice, we show that Kv1.3+ CNS-MPs originate from microglia and not blood-derived monocytes. We show that Kv1.3 channels regulate membrane potential and early signaling events in microglia. Finally, in vivo blockade of Kv1.3 channels in 5xFAD mice by ShK-223 reduced Aß burden, increased CD11c+ CNS-MPs, and expression of phagocytic genes while suppressing proinflammatory genes (IL1b). Our results confirm the microglial origin and identify unique molecular features of Kv1.3-expressing CNS-MPs. In addition, we provide evidence for CNS immunomodulation by Kv1.3 blockers in AD mouse models resulting in a prophagocytic phenotype.

Desalination and transboundary water governance in conflict settings.

Desalination can reduce both water scarcity and variability in supplies, two factors identified as drivers of transboundary water conflict. As such, some have predicted that increasing development of desalination capacity may reduce conflict over shared waters. Others have claimed that desalination may become a source of new conflicts. Additionally, desalination may open up new avenues for cooperation, but also may allow for unilateral action by parties, thereby decreasing cooperation. This study looks at the impact of the introduction of desalination on hydro-political relations in two protracted conflict settings: the island of Cyprus and the Arab-Israeli conflict. Using both quantitative and qualitative assessments, we find that desalination has fundamentally altered hydro-political relations, but find no consistent trends in terms of levels of conflict and cooperation. These findings suggest that the influence of desalination on hydro-political relations is likely to be a function of, rather than a transformer of, the larger geopolitical context.

Hansel, Gretel, and the Consequences of Failing to Remove Histone Methylation Breadcrumbs.

Like breadcrumbs in the forest, cotranscriptionally acquired histone methylation acts as a memory of prior transcription. Because it can be retained through cell divisions, transcriptional memory allows cells to coordinate complex transcriptional programs during development. However, if not reprogrammed properly during cell fate transitions, it can also disrupt cellular identity. In this review, we discuss the consequences of failure to reprogram histone methylation during three crucial epigenetic reprogramming windows: maternal reprogramming at fertilization, embryonic stem cell (ESC) differentiation, and the continuous maintenance of cell identity in differentiated cells. In addition, we discuss how following the wrong breadcrumb trail of transcriptional memory provides a framework for understanding how heterozygous loss-of-function mutations in histone-modifying enzymes may cause severe neurodevelopmental disorders.

Changes in Oral and Anal Sex With Opposite-Sex Partners Among Sexually Active Females and Males Aged 15 to 44 Years in the United States: National Survey of Family Growth, 2011-2019.

BACKGROUND: Oral and anal sex with opposite-sex partners is common and associated with sexually transmitted infection (STI) transmission. Trends in these behaviors over the last decade, during which bacterial STI diagnoses have reached historic highs while HIV diagnoses have decreased, are not well understood. We examined recent trends in oral and anal sex and associated condom use with opposite-sex partners among females and males. METHODS: We analyzed data from 16,926 female and 13,533 male respondents aged 15 to 44 years who reported sex with an opposite-sex partner in the past 12 months from the National Survey of Family Growth, 2011-2019. We used survey-weighted linear or logistic regression to evaluate linear temporal trends in oral and anal sex behaviors. RESULTS: From 2011-2013 to 2017-2019, reports of oral sex and number of oral sex partners in the past 12 months increased among females (85.4% in 2011-2013 to 89.4% in 2017-2019; odds ratio [OR], 1.05 [95% confidence interval {CI}, 1.02-1.09], and ß = 0.014 [95% CI, 0.005-0.023]; respectively) but not males (ranges, 87.9%-89.1%; 1.27-1.31). Condom use at last oral sex decreased among both females and males (6.3%-4.3%: OR, 0.93 [95% CI, 0.88-0.99]; 5.9%-4.4%: OR, 0.95 [95% CI, 0.91-1.00]). Anal sex (ranges, 21.0%-23.3% [females] and 23.3%-24.6% [males]), number of anal sex partners (females, 0.22-0.25; males, 0.26-0.30), and condom use at last anal sex (females, 15.3%-18.2%; males, 27.0%-28.7%) remained stable. CONCLUSIONS: The frequency of oral and anal sex with opposite-sex partners among U.S. 15- to 44-year-olds, paired with limited and-for oral sex-decreasing condom use, demonstrates the need to understand the role of these behaviors in increasing STI diagnosis rates and the potential role of extragenital screening and condoms in reducing STI transmission.

Variation in ontogenetic trajectories of limb dimensions in humans is attributable to both climatic effects and neutral evolution.

Previous studies showed that there is variation in ontogenetic trajectories of human limb dimensions and proportions. However, little is known about the evolutionary significance of this variation. This study used a global sample of modern human immature long bone measurements and a multivariate linear mixed-effects model to study 1) whether the variation in ontogenetic trajectories of limb dimensions is consistent with ecogeographic predictions and 2) the effects of different evolutionary forces on the variation in ontogenetic trajectories. We found that genetic relatedness arising from neutral (nonselective) evolution, allometric variation associated with the change in size, and directional effects from climate all contributed to the variation in ontogenetic trajectories of all major long bone dimensions in modern humans. After accounting for the effects of neutral evolution and holding other effects considered in the current study constant, extreme temperatures have weak, positive associations with diaphyseal length and breadth measurements, while mean temperature shows negative associations with diaphyseal dimensions. The association with extreme temperatures fits the expectations of ecogeographic rules, while the association with mean temperature may explain the observed among-group variation in intralimb indices. The association with climate is present throughout ontogeny, suggesting an explanation of adaptation by natural selection as the most likely cause. On the other hand, genetic relatedness among groups, as structured by neutral evolutionary factors, is an important consideration when interpreting skeletal morphology, even for nonadult individuals.

Condom Use Behaviors, Risk Perception, and Partner Communication Following Oral HIV Self-testing Among Adolescents and Young Adults in Kenya: A Cohort Study.

HIV self-testing (HIVST) can improve testing completion among adolescents and young adults (AYA), although its influence on sexual behaviors is unclear. We evaluated whether HIVST was associated with changes in talking with sexual partners about HIVST, condom use, and HIV risk perception among AYA ages 15-24 years in a study of HIVST distribution through homes, pharmacies, and nightclubs in Nairobi, Kenya. All participants had negative HIVST results. Regression models were used to evaluate changes between pre-HIVST and 4 months post-HIVST. Overall, there was a significant increase in talking with sexual partners about HIVST. There was a significant reduction in number of condomless sex acts among AYA recruited through pharmacies and homes. Unexpectedly, among females, there was a significant decrease in consistent condom use with casual partners. HIVST services for AYA may benefit from including strategies to support condom use and partner communication about self-testing adapted to specific populations and partnerships.

Changes in Sexual Behaviors with Opposite-Sex Partners and Sexually Transmitted Infection Outcomes Among Females and Males Ages 15-44 Years in the USA: National Survey of Family Growth, 2008-2019.

Rates of reported gonorrhea and chlamydial infections have increased substantially over the past decade in the USA and disparities persist across age and race/ethnicity. We aimed to understand potential changes in sexual behaviors, sexual network attributes, and sexually transmitted infection (STI) screening that may be contributing to these trends. We analyzed data from 29,423 female and 24,605 male respondents ages 15-44 years from the National Survey of Family Growth, 2008-2019. We used survey-weighted linear or logistic regression to evaluate linear temporal trends in sexual behaviors with opposite-sex partners, network attributes, and STI testing, treatment, and diagnosis. Significant declines were observed in condom use at last vaginal sex, mean number of vaginal sex acts, proportion of condom-protected sex acts in the past 4 weeks, and racial/ethnic homophily with current partners among males and females from 2008-2010 through 2017-2019. Among males, mean number of female partners in the past 12 months and concurrency also declined, while the percent reporting ever having sex with another male increased. Past-year testing for chlamydia and any STI increased among females. Research is needed to understand how these changes interact and potentially contribute to increasing reported gonorrhea and chlamydia diagnoses and identify avenues for future intervention.

Implementation fidelity to HIV assisted partner services (aPS) during scale-up in western Kenya: a convergent mixed methods study.

BACKGROUND: HIV assisted partner services (aPS) is an intervention to improve HIV status awareness among sex and drug-injecting partners of people newly diagnosed with HIV (index clients). Implementation fidelity-the degree to which an intervention is conducted as intended - is critical to effectiveness, but there are limited data about aPS fidelity when delivered by HIV testing service (HTS) providers. We explored factors affecting implementation fidelity to aPS in two high-HIV prevalence counties in western Kenya. METHODS: We used convergent mixed methods adapting the conceptual framework for implementation fidelity within the aPS scale-up project. This was an implementation study examining scale-up of APS within HTS programs in Kisumu and Homa Bay counties that recruited male sex partners (MSPs) of female index clients. We defined implementation fidelity as the extent to which HTS providers followed the protocol for phone and in-person participant tracing at six expected tracing attempts. Quantitative data were collected from tracing reports in 31 facilities between November 2018 and December 2020, and in-depth interviews (IDIs) were conducted with HTS providers. Descriptive statistics were used to describe tracing attempts. IDIs were analyzed using thematic content analysis. RESULTS: Overall, 3017 MSPs were mentioned of whom 98% (2969/3017) were traced, with most tracing attempts being successful (2831/2969, 95%). Fourteen HTS providers participated in the IDIs-mostly females (10/14, 71%) with a median age of 35 years (range 25-52), who all had post-secondary education (14/14, 100%). The proportion of tracing attempts occurring by phone ranged from 47 to 66%, with the highest proportion occurring on the first attempt and lowest on the sixth attempt. Contextual factors either enhanced or impeded implementation fidelity to aPS. Positive provider attitudes towards aPS and conducive work environment factors promoted implementation fidelity, while negative MSP responses and challenging tracing conditions impeded it. CONCLUSION: Interactions at the individual (provider), interpersonal (client-provider), and health systems (facility) levels affected implementation fidelity to aPS. As policymakers prioritize strategies to reduce new HIV infections, our findings highlight the importance of conducting fidelity assessments to better anticipate and mitigate the impact of contextual factors during the scale-up of interventions.

The inhibition of LSD1 via sequestration contributes to tau-mediated neurodegeneration.

Tauopathies are a class of neurodegenerative diseases associated with pathological tau. Despite many advances in our understanding of these diseases, the direct mechanism through which tau contributes to neurodegeneration remains poorly understood. Previously, our laboratory implicated the histone demethylase LSD1 in tau-induced neurodegeneration by showing that LSD1 localizes to pathological tau aggregates in Alzheimer's disease cases, and that it is continuously required for the survival of hippocampal and cortical neurons in mice. Here, we utilize the P301S tauopathy mouse model to demonstrate that pathological tau can exclude LSD1 from the nucleus in neurons. In addition, we show that reducing LSD1 in these mice is sufficient to highly exacerbate tau-mediated neurodegeneration and tau-induced gene expression changes. Finally, we find that overexpressing LSD1 in the hippocampus of tauopathy mice, even after pathology has formed, is sufficient to significantly delay neurodegeneration and counteract tau-induced expression changes. These results suggest that inhibiting LSD1 via sequestration contributes to tau-mediated neurodegeneration. Thus, LSD1 is a promising therapeutic target for tauopathies such as Alzheimer's disease.

Faith Community Engagement to Mitigate COVID-19 Transmission Associated with Mass Gathering, Uman, Ukraine, September 2021.

Annually, ≈30,000 Hasidic and Orthodox Jews travel to Uman, Ukraine, during the Jewish New Year to pray at the burial place of the founder of the Breslov Hasidic movement. Many pilgrims come from the northeastern United States. The global health implications of this event were seen in 2019 when measles outbreaks in the United States and Israel were linked to the pilgrimage. The 2020 pilgrimage was cancelled as part of the COVID-19 travel restrictions imposed by the government of Ukraine. To prepare for the 2021 event, the National Public Health Institute, the Public Health Center of Ukraine, organized mitigation measures for pilgrims arriving in Uman, and the CDC COVID-19 International Task Force assisted with mitigation measures for pilgrims coming from the United States. We describe efforts to support COVID-19 mitigation measures before, during, and after this mass gathering and lessons learned for future mass gatherings during pandemics.

Abdominal CT and MRI Findings of Portal Hypertension in Children and Adults with Fontan Circulation.

Background Portal hypertension in the Fontan circulation is a function of elevated systemic venous pressure and liver fibrosis. Purpose To quantify the prevalence of radiologic evidence of portal hypertension and elevated VAST score (one point each for varices, ascites, splenomegaly, and thrombocytopenia) of 2 or greater in children and adults with Fontan circulation and to determine the association with hemodynamics and adverse outcomes. Materials and Methods This was a retrospective study of individuals with Fontan circulation who underwent abdominal MRI or CT for focal liver lesion surveillance between January 2012 and December 2019. Portal hypertension was defined as the presence of at least two of the following: varices, ascites, or splenomegaly. Fontan deterioration was defined as a composite of heart failure signs or symptoms requiring diuretic escalation, placement of a ventricular assist device, heart transplant, or death. Relationships between variables and the composite end point were assessed using univariable and multivariable logistic regression. Results A total of 123 patients (age range, 9-55 years; 32 children) were evaluated (median age, 23 years; IQR, 17-30 years; 63 male patients). Median time since diagnosis of Fontan circulation was 16 years (IQR, 12-23 years). Twenty-five of the 123 patients (20%) had radiologic evidence of portal hypertension, and 34 (28%) had a VAST score of 2 or greater. Fontan deterioration occurred in 25 of the 123 patients (20%); median follow-up duration was 0.4 year (IQR, 0.1-3.1 years). Compared with patients who had Fontan circulation without deterioration, patients with Fontan deterioration were more likely to have moderate or severe ventricular systolic dysfunction (P < .01), moderate or severe atrioventricular valve regurgitation (P < .01), higher Fontan pressure (P = .01), radiologic evidence of portal hypertension (P < .01), and VAST score of 2 or greater (P < .01). Conclusion Radiologic evidence of portal hypertension at abdominal imaging in children and adults with Fontan circulation was associated with higher venous pressures and an increased risk for Fontan deterioration. These characteristics may be used to identify patients who warrant comprehensive hemodynamic evaluation. © RSNA, 2022.