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TAZ, one of the key effectors in the Hippo pathway, is often dysregulated in breast cancer, leading to cancer stemness, survival, and metastasis. However, the mechanistic bases of these tumor outcomes are incompletely understood and even less is known about the potential role played by the non-malignant cellular constituents of the tumor microenvironment (TME). Here, we revealed an inverse correlation between TAZ expression and survival in triple-negative breast cancer (TNBC), but not other subtypes of breast cancer. We found that TAZ knockdown in two murine TNBC tumor cell line models significantly inhibited tumor growth and metastasis in immune competent but not immune deficient hosts. RNA-seq analyses identified substantial alterations in immune components in TAZ knockdown tumors. Using mass cytometry analysis, we found that TAZ-deficiency altered the immune landscape of the TME leading to significant reductions in immune suppressive populations, namely myeloid-derived suppressor cells (MDSCs) and macrophages accompanied by elevated CD8+ T cell/myeloid cell ratios. Mechanistic studies demonstrated that TAZ-mediated tumor growth was MDSC-dependent in that MDSC depletion led to reduced tumor growth in control, but not TAZ-knockdown tumor cells. Altogether, we identified a novel non-cancer cell-autonomous mechanism by which tumor-intrinsic TAZ expression aids tumor progression. Thus, our findings advance an understanding of the crosstalk between tumor-derived TAZ expression and the immune contexture within the TME, which may lead to new therapeutic interventions for TNBC or other TAZ-driven cancers.

Nearly two years since the start of the SARS-CoV-2 pandemic, which has caused over 5 million deaths, the world continues to be on high COVID-19 alert. The World Health Organization (WHO), in collaboration with national authorities, public health institutions and scientists have been closely monitoring and assessing the evolution of SARS-CoV-2 since January 2020 (WHO 2021a; WHO 2021b). The emergence of specific SARS-CoV-2 variants were characterised as Variant of Interest (VOI) and Variant of Concern (VOC), to prioritise global monitoring and research, and to inform the ongoing global response to the COVID-19 pandemic. The WHO and its international sequencing networks continuously monitor SARS-CoV-2 mutations and inform countries about any changes that may be needed to respond to the variant, and prevent its spread where feasible. Multiple variants of the virus have emerged and become dominant in many countries since January 2021, with the Alpha, Beta, Gamma and Delta variants being the most prominent to date. (Table 1).

During 2018, Heartland virus RNA was detected in an Amblyomma americanum tick removed from a resident of Suffolk County, New York, USA. The persons showed seroconversion. Tick surveillance and white-tailed deer (Odocoileus virginianus) serosurveys showed widespread distribution in Suffolk County, emphasizing a need for disease surveillance anywhere A. americanum ticks are established or emerging.

Objective To examine rural-urban differences in reproductive-aged Wisconsin women's expectations for contraceptive and abortion care at a hypothetical Catholic hospital. Study design Between October 2019 and April 2020, we fielded a 2-stage, cross-sectional survey to Wisconsin women aged 18 to 45, oversampling rural census tracts and rural counties served by Catholic sole community hospitals. We presented a vignette about a hypothetical Catholic-named hospital; among participants perceiving it as Catholic, we conducted multivariable analyses predicting expectations for contraceptive services (birth control pills, Depo-Provera, intrauterine device or implant, tubal ligation) and abortion in the case of serious fetal indications. Results The response rate was 37.6% for the screener and 83.4% for the survey (N = 675). Among respondents (N = 376) perceiving the hospital as Catholic, expecting the full range of contraceptive methods was more common among rural (70.9%) vs urban (46.7%) participants (adjusted odds ratio = 3.99, 95% confidence interval: 1.99–7.99). In adjusted models, odds of expecting each contraceptive method were at least 3 times greater among rural vs urban participants. About one-third expected provision of abortion for serious fetal indications, with no difference by rurality (p > 0.05). Conclusions In Wisconsin, rural women were more likely than urban women to expect a hypothetical Catholic hospital to provide the full range of contraceptive methods as well as each method individually. Disparities were especially large for tubal ligation and long-acting reversible contraceptives—methods that other studies suggest are least-likely to be available in Catholic healthcare settings—which may indicate a mismatch between patients’ expectations and service availability. Implications Many reproductive-aged Wisconsin women—especially in rural areas—hold misperceptions about availability of reproductive care in Catholic hospitals. Policies mandating greater transparency in service restrictions and interventions enabling patients to make informed decisions about care may help connect patients to the care they need more quickly.

Background Lecanemab, a humanized IgG1 monoclonal antibody that targets soluble aggregated Aβ species (protofibrils), has demonstrated robust brain fibrillar amyloid reduction and slowing of clinical decline in early AD. The objective of this analysis is to report results from study 201 blinded period (core), the open-label extension (OLE), and gap period (between core and OLE) supporting the effectiveness of lecanemab. Methods The lecanemab study 201 core was a double-blind, randomized, placebo-controlled study of 856 patients randomized to one of five dose regimens or placebo. An OLE of study 201 was initiated to allow patients to receive open-label lecanemab 10mg/kg biweekly for up to 24 months, with an intervening off-treatment period (gap period) ranging from 9 to 59 months (mean 24 months). Results At 12 and 18 months of treatment in the core, lecanemab 10 mg/kg biweekly demonstrated dose-dependent reductions of brain amyloid measured PET and corresponding changes in plasma biomarkers and slowing of cognitive decline. The rates of clinical progression during the gap were similar in lecanemab and placebo subjects, with clinical treatment differences maintained after discontinued dosing over an average of 24 months in the gap period. During the gap, plasma Aβ42/40 ratio and p-tau181 levels began to return towards pre-randomization levels more quickly than amyloid PET. At OLE baseline, treatment differences vs placebo at 18 months in the randomized period were maintained across 3 clinical assessments. In the OLE, lecanemab 10 mg/kg biweekly treatment produced dose-dependent reductions in amyloid PET SUVr, improvements in plasma Aβ42/40 ratio, and reductions in plasma p-tau181. Conclusions Lecanemab treatment resulted in significant reduction in amyloid plaques and a slowing of clinical decline. Data indicate that rapid and pronounced amyloid reduction correlates with clinical benefit and potential disease-modifying effects, as well as the potential to use plasma biomarkers to monitor for lecanemab treatment effects. Trial registration ClinicalTrials.gov NCT01767311.

Introduction:The coronavirus disease 2019 (COVID-19) pandemic challenged health care systems in an unprecedented way. Due to the enormous amount of hospital ward and intensive care unit (ICU) admissions, regular care came to a standstill, thereby overcrowding ICUs and endangering (regular and COVID-19-related) critical care. Acute care coordination centers were set up to safely manage the influx of COVID-19 patients. Furthermore, treatments requiring ICU surveillance were postponed leading to increased waiting lists.Hypothesis:A coordination center organizing patient transfers and admissions could reduce overcrowding and optimize in-hospital capacity.Methods:The acute lack of hospital capacity urged the region West-Netherlands to form a new regional system for patient triage and transfer: the Regional Capacity and Patient Transfer Service (RCPS). By combining hospital capacity data and a new method of triage and transfer, the RCPS was able to effectively select patients for transfer to other hospitals within the region or, in close collaboration with the National Capacity and Patient Transfer Service (LCPS), transfer patients to hospitals in other regions within the Netherlands.Results:From March 2020 through December 2021 (22 months), the RCPS West-Netherlands was requested to transfer 2,434 COVID-19 patients. After adequate triage, 1,720 patients with a mean age of 62 (SD = 13) years were transferred with the help of the RCPS West-Netherlands. This concerned 1,166 ward patients (68%) and 554 ICU patients (32%). Overcrowded hospitals were relieved by transferring these patients to hospitals with higher capacity.Conclusion:The health care system in the region West-Netherlands benefitted from the RCPS for both ward and ICU occupation. Due to the coordination by the RCPS, regional ICU occupation never exceeded the maximal ICU capacity, and therefore patients in need for acute direct care could always be admitted at the ICU. The presented method can be useful in reducing the waiting lists caused by the delayed care and for coordination and transfer of patients with new variants or other infectious diseases in the future.

Our objective was to examine the construct validity of the Brief Test of Adult Cognition by Telephone (BTACT) and its relationship to traumatic brain injury (TBI) of differing severities. Data were analyzed on 1422 patients with TBI and 170 orthopedic trauma controls (OTC) from the multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Participants were assessed at 6 months post-injury with the BTACT and an in-person neuropsychological battery. We examined the BTACT's factor structure, factorial group invariance, convergent and discriminant validity, and relationship to TBI and TBI severity. Confirmatory factor analysis supported both a 1-factor model and a 2-factor model comprising correlated Episodic Memory and Executive Function (EF) factors. Both models demonstrated strict invariance across TBI severity and OTC groups. Correlations between BTACT and criterion measures suggested that the BTACT memory indices predominantly reflect verbal episodic memory, whereas the BTACT EF factor correlated with a diverse range of cognitive tests. Although the EF factor and other BTACT indices showed significant relationships with TBI and TBI severity, some group effect sizes were larger for more comprehensive in-person cognitive tests than the BTACT. The BTACT is a promising, brief, phone-based cognitive screening tool for patients with TBI. Although the BTACT's memory items appear to index verbal Episodic Memory, items that purport to assess EFs may reflect a broader array of cognitive domains. The sensitivity of the BTACT to TBI severity is lower than domain-specific neuropsychological measures, suggesting it should not be used as a substitute for comprehensive, in-person cognitive testing at 6 months post-TBI.

The triarchic model was advanced as an integrative, trait-based framework for investigating psychopathy using different assessment methods and across developmental periods. Recent research has shown that the triarchic traits of boldness, meanness, and disinhibition can be operationalized effectively in youth, but longitudinal research is needed to realize the model's potential to advance developmental understanding of psychopathy. We report on the creation and validation of scale measures of the triarchic traits using questionnaire items available in the University of Southern California Risk Factors for Antisocial Behavior (RFAB) project, a large-scale longitudinal study of the development of antisocial behavior that includes measures from multiple modalities (self-report, informant rating, clinical-diagnostic, task-behavioral, physiological). Using a construct-rating and psychometric refinement approach, we developed triarchic scales that showed acceptable reliability, expected intercorrelations, and good temporal stability. The scales showed theory-consistent relations with external criteria including measures of psychopathy, internalizing/externalizing psychopathology, antisocial behavior, and substance use. Findings demonstrate the viability of measuring triarchic traits in the RFAB sample, extend the known nomological network of these traits into the developmental realm, and provide a foundation for follow-up studies examining the etiology of psychopathic traits and their relations with multimodal measures of cognitive-affective function and proneness to clinical problems.

The COVID-19 pandemic is among the deadliest infectious diseases to have emerged in recent history. As with all past pandemics, the specific mechanism of its emergence in humans remains unknown. Nevertheless, a large body of virologic, epidemiologic, veterinary, and ecologic data establishes that the new virus, SARS-CoV-2, evolved directly or indirectly from a β-coronavirus in the sarbecovirus (SARS-like virus) group that naturally infect bats and pangolins in Asia and Southeast Asia. Scientists have warned for decades that such sarbecoviruses are poised to emerge again and again, identified risk factors, and argued for enhanced pandemic prevention and control efforts. Unfortunately, few such preventive actions were taken resulting in the latest coronavirus emergence detected in late 2019 which quickly spread pandemically. The risk of similar coronavirus outbreaks in the future remains high. In addition to controlling the COVID-19 pandemic, we must undertake vigorous scientific, public health, and societal actions, including significantly increased funding for basic and applied research addressing disease emergence, to prevent this tragic history from repeating itself.

While immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape in oncology, they are effective in select subsets of patients. Efficacy may be limited by tumor-driven immune suppression, of which 1 key mechanism is the development of myeloid-derived suppressor cells (MDSCs). A fundamental gap in MDSC therapeutics is the lack of approaches that target MDSC biogenesis. We hypothesized that targeting MDSC biogenesis would mitigate MDSC burden and bolster tumor responses to ICIs. We tested a class of agents, dihydroorotate dehydrogenase (DHODH) inhibitors, that have been previously shown to restore the terminal differentiation of leukemic myeloid progenitors. DHODH inhibitors have demonstrated preclinical safety and are under clinical study for hematologic malignancies. Using mouse models of mammary cancer that elicit robust MDSC responses, we demonstrated that the DHODH inhibitor brequinar (a) suppressed MDSC production from early-stage myeloid progenitors, which was accompanied by enhanced myeloid maturation; (b) augmented the antitumor and antimetastatic activities of programmed cell death 1-based (PD-1-based) ICI therapy in ICI-resistant mammary cancer models; and (c) acted in concert with PD-1 blockade through modulation of MDSC and CD8+ T cell responses. Moreover, brequinar facilitated myeloid maturation and inhibited immune-suppressive features in human bone marrow culture systems. These findings advance the concept of MDSC differentiation therapy in immuno-oncology.

Background Vector-borne pathogens must survive and replicate in the hostile environment of an insect’s midgut before successful dissemination. Midgut microbiota interfere with pathogen infection by activating the basal immunity of the mosquito and by synthesizing pathogen-inhibitory metabolites. Methods The goal of this study was to assess the influence of Zika virus (ZIKV) infection and increased temperature on Aedes albopictus midgut microbiota. Aedes albopictus were reared at diurnal temperatures of day 28 °C/night 24 °C (L) or day 30 °C/night 26 °C (M). The mosquitoes were given infectious blood meals with 2.0 × 108 PFU/ml ZIKV, and 16S rRNA sequencing was performed on midguts at 7 days post-infectious blood meal exposure. Results Our findings demonstrate that Elizabethkingia anophelis albopictus was associated with Ae. albopictus midguts exposed to ZIKV infectious blood meal. We observed a negative correlation between ZIKV and E. anophelis albopictus in the midguts of Ae. albopictus. Supplemental feeding of Ae. albopictus with E. anophelis aegypti and ZIKV resulted in reduced ZIKV infection rates. Reduced viral loads were detected in Vero cells that were sequentially infected with E. anophelis aegypti and ZIKV, dengue virus (DENV), or chikungunya virus (CHIKV). Conclusions Our findings demonstrate the influence of ZIKV infection and temperature on the Ae. albopictus microbiome along with a negative correlation between ZIKV and E. anophelis albopictus. Our results have important implications for controlling vector-borne pathogens. Graphical Abstract

Food limitation is a universal stressor for wildlife populations and is increasingly exacerbated by human activities. Anthropogenic environmental change can significantly alter the availability and quality of food resources for reservoir hosts and impact host–pathogen interactions in the wild. The state of the host's nutritional reserves at the time of infection is a key factor influencing infection outcomes by altering host resistance. Combining experimental and model-based approaches, we investigate how an environmental stressor affects host resistance to West Nile virus (WNV). Using American robins (Turdus migratorius), a species considered a superspreader of WNV, we tested the effect of acute food deprivation immediately prior to infection on host viraemia. Here, we show that robins food deprived for 48 h prior to infection, developed higher virus titres and were infectious longer than robins fed normally. To gain an understanding about the epidemiological significance of food-stressed hosts, we developed an agent-based model that simulates transmission dynamics of WNV between an avian host and the mosquito vector. When simulating a nutritionally stressed host population, the mosquito infection rate rose significantly, reaching levels that represent an epidemiological risk. An understanding of the infection disease dynamics in wild populations is critical to predict and mitigate zoonotic disease outbreaks.

The Multidimensional Personality Questionnaire (MPQ) is a normal range inventory for assessing a variety of empirically derived primary traits. These trait scores can be differentially weighted to estimate higher-order broad dimensions such as Positive Emotionality (PEM), Negative Emotionality (NEM), and Constraint (CON). However, broad trait scores are estimated using proprietary regression equations and necessitate near complete administration of the inventory. We aimed to increase measurement efficiency by creating abbreviated item-based approximations of these weighted scores. To parsimoniously delineate and differentiate the broad traits, classical test theory and item response theory approaches were used to identify five items from each primary trait scale approximating the weighted estimates while also maintaining the breadth of MPQ content coverage. Initial scale development relied on the MPQ-276 (standard form) normative sample (n = 1,237), which was followed by cross-validation using two samples of twins and cotwins from the Minnesota Twin Family Study (n = 1,304, n = 1,305). Additional validation was conducted using a third sample of undergraduate students (n = 201).The resulting item-based scales (PEM-20, NEM-15, CON-15) demonstrated strong convergence with the established proprietary broad trait estimates. Furthermore, these abbreviated scales exhibited similar associations with the external measures of personality and psychopathology. Abbreviated item-based scales may have utility for efficient estimation of the same broadband personality dimensions assessed by longer forms of the MPQ. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Neuropsychiatric symptoms are common, comorbid, and often disabling for patients with traumatic brain injury (TBI). Identifying transdiagnostic symptom dimensions post-TBI may help overcome limitations of traditional psychiatric diagnoses and advance treatment development. We characterized the dimensional structure of neuropsychiatric symptoms at 2-weeks postinjury in n = 1,732 TBI patients and n = 238 orthopedic-injured trauma controls (OTC) from the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Symptoms were reported on the Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, PTSD Checklist for DSM-5, PROMIS Pain Intensity scale, and Insomnia Severity Index. We established a novel factor model of neuropsychiatric symptoms and evaluated how 3 TBI severity strata and OTC patients differed in symptom severity. The final factor model had 6 first-order factors subsumed by 2 second-order factors: Internalizing (encompassing Depression, Anxiety, and Fear) and Somatic symptoms (Sleep, Physical, Pain). Somatic symptoms fit better as a correlated factor of (vs. a lower-order factor within) Internalizing. All symptom dimensions except for Pain were more severe in 1 or more TBI subgroups, as compared to the OTC group. Milder brain injury was generally associated with more severe symptoms, whereas more general injury severity (higher level of care, e.g., emergency department, intensive care unit) was associated with more pain. The findings indicate a broad factor resembling the internalizing factor of general psychopathology in traumatically injured patients, alongside a distinct somatic symptom factor. Brain injury, especially milder brain injury, may exacerbate liabilities toward these symptoms. These neuropsychiatric dimensions may help advance more precision medicine research for TBI. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

We tested 700 serum samples collected throughout Panama from 2015 to 2016 for detecting antibodies and RNA of arboviruses. In convalescent specimens, microsphere immunoassay detected an antibody prevalence of 59.3% for dengue virus (DENV) and 30.3% for Zika virus (ZIKV), which included samples that were collected before the Panamanian surveillance system reported the first case of Zika in the country. For acute sera, the most common arbovirus was DENV with 18 positive samples (6%), followed by four (1.3%) of ZIKV and one (0.6%) of chikungunya virus (CHIKV). Our results indicate a change in the chronology of when ZIKV was first detected in Panama and stress the importance of integrating various approaches to enable improved surveillance of both endemic and emerging arboviruses.

DNA, when folded into nanostructures with a specific shape, is capable of spacing and arranging binding sites into a complex geometric pattern with nanometre precision. Here we demonstrate a designer DNA nanostructure that can act as a template to display multiple binding motifs with precise spatial pattern-recognition properties, and that this approach can confer exceptional sensing and potent viral inhibitory capabilities. A star-shaped DNA architecture, carrying five molecular beacon-like motifs, was constructed to display ten dengue envelope protein domain III (ED3)-targeting aptamers into a two-dimensional pattern precisely matching the spatial arrangement of ED3 clusters on the dengue (DENV) viral surface. The resulting multivalent interactions provide high DENV-binding avidity. We show that this structure is a potent viral inhibitor and that it can act as a sensor by including a fluorescent output to report binding. Our molecular-platform design strategy could be adapted to detect and combat other disease-causing pathogens by generating the requisite ligand patterns on customized DNA nanoarchitectures., DNA is capable of self-assembling into a wide range of user-defined structures and so can be used as a scaffold to arrange binding motifs with nanometre precision. Now, DNA has been used to accurately display aptamers that fit the repeated epitope pattern of a dengue viral antigen to produce a nanostructure that can be a potent viral inhibitor or a fluorescent sensor.

Rabensburg virus (RBGV; Flaviviridae, Flavivirus) has been classified as both a novel flavivirus and a unique lineage of West Nile virus (WNV). RBGV and WNV share approximately 76% sequence homology, yet RBGV does not replicate to high viral titers within vertebrate cell lines at physiological temperatures and has not been naturally isolated from a vertebrate host. These unique genetic and biological characteristics make RBGV a viable tool to identify the genetic determinants of flavivirus infectivity and fitness in vertebrate hosts. Using experimental evolution, we characterized mutated variants of RBGV that have altered capacity for infection and replication in various cell lines. Shared genetic differences within these variants were identified throughout the genome, with a large majority found in the NS3 and NS5 genes. Our results support a role for the replication complex in host utilization and suggest that epistatic interactions likely contribute to host-specific fitness and emergence.

Zika virus (ZIKV) is an enveloped RNA virus from the flavivirus family that can cause fetal neural abnormalities in pregnant women. Previously, we established that ZIKV-EP (envelope protein) binds to human placental chondroitin sulfate (CS), suggesting that CS may be a potential host cell surface receptor in ZIKV pathogenesis. In this study, we further characterized the GAG disaccharide composition of other biological tissues (i.e., mosquitoes, fetal brain cells, and eye tissues) in ZIKV pathogenesis to investigate the role of tissue specific GAGs. Heparan sulfate (HS) was the major GAG, and levels of HS-6-sulfo, HS 0S (unsulfated HS), and CS 4S disaccharides were the main differences in the GAG composition of Aedes aegypti and Aedes albopictus mosquitoes. In human fetal neural progenitor and differentiated cells, HS 0S and CS 4S were the main disaccharides. A change in disaccharide composition levels was observed between undifferentiated and differentiated cells. In different regions of the bovine eyes, CS was the major GAG, and the amounts of hyaluronic acid or keratan sulfate varied depending on the region of the eye. Next, we examined heparin (HP) of various structures to investigate their potential in vitro antiviral activity against ZIKV and Dengue virus (DENV) infection in Vero cells. All compounds effectively inhibited DENV replication; however, they surprisingly promoted ZIKV replication. HP of longer chain lengths more strongly promoted activity in ZIKV replication. This study further expands our understanding of role of GAGs in ZIKV pathogenesis and carbohydrate-based antivirals against flaviviral infection.

Background Fetal growth restriction is, despite advances in neonatal care and uptake of antenatal ultrasound scanning, still a major cause of perinatal morbidity. Neonates with birth weight > 10th percentile are assumed to be appropriate-for-gestational-age (AGA), although many are at increased risk of perinatal morbidity, because of undetected mild restriction of growth potential. We hypothesized that within AGA neonates, reduced fetal growth velocities are associated with adverse neonatal outcome. Methods A retrospective cohort study of singleton pregnancies, in the Maastricht University Medical Centre (MUMC) between 2010 and 2016. Women had two fetal biometry scans (18–22 weeks and 30–34 weeks of gestational age) and delivered a newborn with a birth weight between the 10th–80th percentile. Differences in growth velocities of the abdominal circumference (AC), biparietal diameter (BPD), head circumference (HC) and femur length (FL) were compared between the suboptimal AGA (sAGA) (birth weight centiles 10–50) and optimal AGA (oAGA) (birth weight centiles 50–80) group. We assessed the association between velocities and neonatal outcomes. Results We included 934 singleton pregnancies. In the suboptimal AGA group, fetal growth velocities were lower (in mm/week): AC 10.72 ± 1.00 vs 11.23 ± 1.00 (p

Contraceptives are used to prevent unwanted pregnancies and treat certain gynecologic conditions, but many women report non-use or inconsistent use because of method dissatisfaction. The sexual acceptability of contraception-how birth control methods affect users' sexual well-being-is likely an important component of contraceptive satisfaction but has yet to be systematically examined.This study aimed to assess contraceptive satisfaction among new-start contraceptive users and examine whether sexual acceptability measures predict contraceptive satisfaction at 3 months while controlling for more commonly measured contraceptive side effects.This analysis used data derived from the baseline, 1-month, and 3-month surveys of the HER Salt Lake Contraceptive Initiative, a prospective cohort study of new contraceptive clients. From March 2016 to March 2017, enrolled participants received their desired contraceptive method at no cost and could switch or discontinue at any time (up to 3 years). This analysis included individuals who continued their new contraceptive method for at least 1 month and completed all relevant survey measures. We used ordered logistic regression modeling to predict contraceptive satisfaction at 3 months. Primary predictor variables included changes in sexual functioning (6-item Female Sexual Function Index), sexual satisfaction (New Sexual Satisfaction Scale), and perceived impact of the contraceptive method on sex life at 1 month. Covariates included vaginal bleeding changes, physical side effects, and mood-related side effects.Our analytical sample included 1879 individuals. At 3 months, 52.1% of participants were "completely satisfied" with their contraceptive method, 30.7% were "somewhat satisfied," 4.2% were "neither satisfied nor dissatisfied," 6.9% were "somewhat dissatisfied," and 6.2% were "completely dissatisfied." Compared with patients who said their contraceptive method made their sex life "a lot" worse at 1 month, patients whose method improved their sex life "a lot" had a 7.7 times increased odds of greater satisfaction at 3 months (95% confidence interval, 4.02-14.60; P.0001) and patients whose method improved their sex life a "little" had a 5.88 times increased odds of greater satisfaction (confidence interval, 3.12-11.11; P.001). To a much lesser degree, experiencing less or no bleeding was significantly associated with increased satisfaction, whereas worsening of physical side effects was linked to decreased satisfaction. The only other factors significantly associated with satisfaction were changes in bleeding and physical side effects.Our findings suggest that patients' sexual experiences of their contraceptive methods are important correlates of satisfaction. Clinicians may wish to underscore that sexual experiences of birth control methods matter and encourage patients to find a contraceptive method that works for them sexually.

BACE1 (beta-site amyloid precursor protein cleaving enzyme 1) was initially cloned and characterized in 1999. It is required for the generation of all monomeric forms of amyloid-β (Aβ), including Aβ42, which aggregates into bioactive conformational species and likely initiates toxicity in Alzheimer's disease (AD). BACE1 concentrations and rates of activity are increased in AD brains and body fluids, thereby supporting the hypothesis that BACE1 plays a critical role in AD pathophysiology. Therefore, BACE1 is a prime drug target for slowing down Aβ production in early AD. Besides the amyloidogenic pathway, BACE1 has other substrates that may be important for synaptic plasticity and synaptic homeostasis. Indeed, germline and adult conditional BACE1 knockout mice display complex neurological phenotypes. Despite BACE1 inhibitor clinical trials conducted so far being discontinued for futility or safety reasons, BACE1 remains a well-validated therapeutic target for AD. A safe and efficacious compound with high substrate selectivity as well as a more accurate dose regimen, patient population, and disease stage may yet be found. Further research should focus on the role of Aβ and BACE1 in physiological processes and key pathophysiological mechanisms of AD. The functions of BACE1 and the homologue BACE2, as well as the biology of Aβ in neurons and glia, deserve further investigation. Cellular and molecular studies of BACE1 and BACE2 knockout mice coupled with biomarker-based human research will help elucidate the biological functions of these important enzymes and identify their substrates and downstream effects. Such studies will have critical implications for BACE1 inhibition as a therapeutic approach for AD. ispartof: BIOLOGICAL PSYCHIATRY vol:89 issue:8 pages:745-756 ispartof: location:United States status: published

Few large, longitudinal studies document multiple contraceptive methods' effects on sexual functioning, satisfaction, and well-being. We leveraged data from the HER Salt Lake Contraceptive Initiative, a prospective cohort study with patient surveys at baseline, one month, and three months. Surveys assessed bleeding changes, contraceptive-related side effects, sexual functioning and satisfaction, and perceptions of methods' impact on sexual well-being. Individuals in the final sample (N = 2,157) initiated either combined oral contraceptives, levonorgestrel intrauterine devices (IUDs), copper IUDs, implants, injectables, or vaginal rings. Across methods, participants exhibited minimal changes in sexual function (Female Sexual Function Index-6 scores) or satisfaction (New Scale of Sexual Satisfaction scores) over three months. However, many perceived contraception-related changes to sexual well-being. Half (51%) reported their new method had made their sex life better; 15% reported it had made their sex life worse. Sexual improvements were associated with decreased vaginal bleeding, fewer side effects, and IUD use. Negative sexual impacts were associated with physical side effects (e.g., bloating and breast tenderness), increased bleeding, and vaginal ring use. In conclusion, contraceptive users did not experience major changes in sexual functioning or satisfaction over three months, but they did report subjective sexual changes, mostly positive, due to their method.

Background Parasites that infect cats include protozoa, helminths and arthropods, many of which are transmissible to humans. Effective control relies on a good knowledge of parasite distribution and the risk factors for infection. The present study was aimed at evaluating the prevalence of major feline parasites in Italy and the risk factors associated with their occurrence. Methods Over a 12-month study period, feces, hair and ectoparasites from naturally infected cats from feral colonies, shelters and private households were analyzed at 13 study centers across Italy. Samples from these cats (n = 987) were analyzed at all centers using the same diagnostic methods. Prevalence values and risk factors were evaluated statistically for the identification of predictors of risk. Results The overall prevalence of gastro-intestinal and broncho-pulmonary (BP) nematodes was 35.9% (354/987). Toxocara cati was the most prevalent species (253/987; 25.6%), followed by Ancylostomatidae (98/987; 9.9%). Among BP nematodes, Aelurostrongylus abstrusus was the most common (76/987; 7.7%). Approximately 35.7% (352/987) of the study population was infested by ectoparasites, of which the most common were fleas (29.4%, 290/987), followed by ear mites Otodectes cynotis (9.8%, 97/987). Predictors of risk for parasite infection included age, a predominantly or exclusively outdoor lifestyle, geographic area and lack of antiparasitic treatment. Conclusions Both ecto- and endoparasites are still common in cats throughout Italy, many of them being of zoonotic concern and vectors of pathogens to humans. Given the presence of parasites throughout the entire study period, year-round treatment should be considered. Furthermore, data confirm the need to protect the human–animal bond using proper endo- and ectoparasiticides to reduce the risk of human infection, in application of the One-Health concept. Graphical abstract

Background Lecanemab (BAN2401), an IgG1 monoclonal antibody, preferentially targets soluble aggregated amyloid beta (Aβ), with activity across oligomers, protofibrils, and insoluble fibrils. BAN2401-G000-201, a randomized double-blind clinical trial, utilized a Bayesian design with response-adaptive randomization to assess 3 doses across 2 regimens of lecanemab versus placebo in early Alzheimer’s disease, mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD dementia. Methods BAN2401-G000-201 aimed to establish the effective dose 90% (ED90), defined as the simplest dose that achieves ≥90% of the maximum treatment effect. The primary endpoint was Bayesian analysis of 12-month clinical change on the Alzheimer’s Disease Composite Score (ADCOMS) for the ED90 dose, which required an 80% probability of ≥25% clinical reduction in decline versus placebo. Key secondary endpoints included 18-month Bayesian and frequentist analyses of brain amyloid reduction using positron emission tomography; clinical decline on ADCOMS, Clinical Dementia Rating-Sum-of-Boxes (CDR-SB), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14); changes in CSF core biomarkers; and total hippocampal volume (HV) using volumetric magnetic resonance imaging. Results A total of 854 randomized subjects were treated (lecanemab, 609; placebo, 245). At 12 months, the 10-mg/kg biweekly ED90 dose showed a 64% probability to be better than placebo by 25% on ADCOMS, which missed the 80% threshold for the primary outcome. At 18 months, 10-mg/kg biweekly lecanemab reduced brain amyloid (−0.306 SUVr units) while showing a drug-placebo difference in favor of active treatment by 27% and 30% on ADCOMS, 56% and 47% on ADAS-Cog14, and 33% and 26% on CDR-SB versus placebo according to Bayesian and frequentist analyses, respectively. CSF biomarkers were supportive of a treatment effect. Lecanemab was well-tolerated with 9.9% incidence of amyloid-related imaging abnormalities-edema/effusion at 10 mg/kg biweekly. Conclusions BAN2401-G000-201 did not meet the 12-month primary endpoint. However, prespecified 18-month Bayesian and frequentist analyses demonstrated reduction in brain amyloid accompanied by a consistent reduction of clinical decline across several clinical and biomarker endpoints. A phase 3 study (Clarity AD) in early Alzheimer’s disease is underway. Trial registration Clinical Trials.govNCT01767311.

Periodontal disease, an inflammatory bone disease of the oral cavity, affects more than 50% of the United States population over the age of 30. The Gram-negative, anaerobic bacterium Porphyromonas gingivalis, the etiological agent of periodontal disease, is known to induce dysbiosis of the oral microbiome while promoting inflammatory bone loss. We have recently reported that P. gingivalis can also alter the gut microbiota of mice prone to develop inflammatory atherosclerosis. However, it is still unknown whether P. gingivalis induces similar changes to the gut microbiome as it does to oral microbiome. In this study, we demonstrate that P. gingivalis infection increases the diversity of the oral microbiome, allowing for colonization of potentially opportunistic species in the oral microbiome and overgrowth of commensal species in both the oral and gut microbiomes. Since periodontal disease treatment in humans typically involves antibiotic treatment, we also examined the combined effect of P. gingivalis infection on mice pretreated with oral antibiotics. By correlating the oral and cecal microbiota of P. gingivalis-infected mice fed a normal chow diet, we identified blooms of the Gram-negative genera Barnesiella and Bacteroides and imbalances of mucin-degrading bacteria. These disrupted community structures were predicted to have increased detrimental functional capacities including increased flavonoid degradation and l -histidine fermentation. Though antibiotic pretreatment (without P. gingivlais) had a dominant impact on the cecal microbiome, P. gingivalis infection of mice with or without antibiotic pretreatment increased the abundance of the phylum Firmicutes and the Porphyromonadaceae family in the cecum. Collectively, our study demonstrates that P. gingivalis oral infection disrupted the oral and cecal microbiomes of otherwise unperturbed mice, altering their community membership and functional potential.

Objective To estimate prevalence of being turned away from a Catholic healthcare setting without receiving desired reproductive care among Wisconsin women and to document firsthand accounts of these experiences. Study design Between October 2019 and April 2020, we fielded a two-stage survey to Wisconsin women aged 18-45, oversampling rural census tracts and rural counties served by Catholic sole community hospitals. We present prevalence of ever being turned away from a Catholic hospital or clinic without receiving desired contraceptive or fertility care and document accounts of referrals, perceived barriers, and wait times to acquire services elsewhere. Results The screener response rate was 37.6% (N = 828) and the survey response rate was 83.4% (N = 675). While only 23 (2.0%) of Wisconsin women had ever been turned away from a Catholic hospital or clinic without receiving desired contraceptive or fertility care (95% confidence interval: 1.2%-3.5%), these experiences were more common among women in counties served by Catholic sole community hospitals (n = 9, 8.1% [4.0%-15.6%]) compared to women in other rural census tracts (n = 6, 2.8% [1.3%-6.2%]) and urban census tracts (n = 8, 1.5% [0.7%-3.2%]). Sixteen (69.6%) cited religious restrictions as a barrier to accessing care. Some women – especially those denied tubal ligation – experienced long delays in acquiring time-sensitive care elsewhere. Conclusions About 1-in-12 women in Wisconsin rural counties served by Catholic sole community hospitals reported ever being turned away from a Catholic healthcare setting without receiving desired reproductive care. After tubal ligation denials in Catholic facilities, many women faced long wait times to receive care elsewhere. Implications Wisconsin women in rural counties served by Catholic sole community hospitals were about three times more likely than urban women to have ever been turned away from a Catholic facility. As Catholic healthcare expands nationally, it will be increasingly important to better understand how healthcare prohibitions influence patients’ lives.

Background Mayaro virus (MAYV; Alphavirus, Togaviridae) is an emerging pathogen endemic in South American countries. The increase in intercontinental travel and tourism-based forest excursions has resulted in an increase in MAYV spread, with imported cases observed in Europe and North America. Intriguingly, no local transmission of MAYV has been reported outside South America, despite the presence of potential vectors. Methods We assessed the vector competence of Aedes albopictus from New York and Anopheles quadrimaculatus for MAYV. Results The results show that Ae. albopictus from New York and An. quadrimaculatus are competent vectors for MAYV. However, Ae. albopictus was more susceptible to infection. Transmission rates increased with time for both species, with rates of 37.16 and 64.44% for Ae. albopictus, and of 25.15 and 48.44% for An. quadrimaculatus, respectively, at 7 and 14 days post-infection. Conclusions Our results suggest there is a risk of further MAYV spread throughout the Americas and autochthonous transmission in the USA. Preventive measures, such as mosquito surveillance of MAYV, will be essential for early detection.

All 4 dengue viruses (DENV) cause sporadic outbreaks of human disease in the Rio Grande Valley along the US-Mexico border. In addition, West Nile virus (WNV) is enzootic in most border communities, and is the only arbovirus known to cause human disease in the El Paso, Texas community. In an effort to determine if DENV were also endemic in the El Paso community, a serosurvey was conducted among mothers at the time of delivery of their babies in selected hospitals. Cord-blood plasma samples obtained from mothers were tested for DENV antibody by an enzyme-linked immuno-sorbent assay (ELISA), plaque reduction neutralization test (PRNT) and a multiplex microsphere immunoassay. All DENV antibody positive plasma samples were also tested for WNV antibody by the same assays to consider the possibility that DENV antibody positive samples reflected WNV cross reactive antibody. The results indicated that 0.74% (11/1,472) of the mothers had a previous DENV infection and that 3.3% (48/1,472) had a previous WNV infection. Of these mothers, 0.20% (3/1,472) had antibody to both DENV and WNV as evidence of infection by both viruses. The results indicated that 0.2% (3/1472) of the mothers were positive for antibody to only WNV envelope, thus suggesting an undetermined flavivirus infection. Although 6 of the 11 DENV antibody positive mothers did not have a history of travel to a DENV endemic country, the findings of this survey provided further evidence of local transmission of WNV and suggested the possibility of focal autochthonous transmission of DENV in the El Paso community.

Many flaviviruses including the Dengue virus (DENV), Zika virus (ZIKV), West Nile virus, Yellow Fever virus, and Japanese encephalitis virus are significant human pathogens, unfortunately without any specific therapy. Here, we demonstrate that methylene blue, an FDA-approved drug, is a broad-spectrum and potent antiviral against Zika virus and Dengue virus both in vitro and in vivo. We found that methylene blue can considerably inhibit the interactions between viral protease NS3 and its NS2B co-factor, inhibit viral protease activity, inhibit viral growth, protect 3D mini-brain organoids from ZIKV infection, and reduce viremia in a mouse model. Mechanistic studies confirmed that methylene blue works in both entry and post entry steps, reduces virus production in replicon cells and inhibited production of processed NS3 protein. Overall, we have shown that methylene blue is a potent antiviral for management of flavivirus infections, particularly for Zika virus. As an FDA-approved drug, methylene blue is well-tolerated for human use. Therefore, methylene blue represents a promising and easily developed therapy for management of infections by ZIKV and other flaviviruses.

Flaviviruses causes significant human disease. Recent outbreaks of the Zika virus highlight the need to develop effective therapies for this class of viruses. Previously we identified niclosamide as a broad-spectrum inhibitor for flaviviruses by targeting the interface between viral protease NS3 and its cofactor NS2B. Here, we screened a small library of niclosamide derivatives and identified a new analogue with improved pharmacokinetic properties. Compound JMX0207 showed improved efficacy in inhibition of the molecular interaction between NS3 and NS2B, better inhibition of viral protease function, and enhanced antiviral efficacy in the cell-based antiviral assay. The derivative also significantly reduced Zika virus infection on 3D mini-brain organoids derived from pluripotent neural stem cells. Intriguingly, the compound significantly reduced viremia in a Zika virus (ZIKV) animal model. In summary, a niclosamide derivative, JMX0207, was identified, which shows improved pharmacokinetics and efficacy against Zika virus both in vitro and in vivo.

The Polyneuropathy And Treatment with Hizentra (PATH) study required subjects with chronic inflammatory demyelinating polyneuropathy (CIDP) to show dependency on immunoglobulin G (IgG) and then be restabilized on IgG before being randomized to placebo or one of two doses of subcutaneous immunoglobulin (SCIG). Nineteen of the 51 subjects (37%) randomized to placebo did not relapse over the next 24 weeks. This article explores the reasons for this effect. A post‐hoc analysis of the PATH placebo group was undertaken. A literature search identified other placebo‐controlled CIDP trials for review and comparison. In PATH, subjects randomized to placebo who did not relapse were significantly older, had more severe disease, and took longer to deteriorate in the IgG dependency period compared with those who relapsed. Published trials in CIDP, whose primary endpoint was stability or deterioration, had a mean non‐deterioration (placebo effect) of 43%, while trials with a primary endpoint of improvement had a placebo response of only 11%. Placebo is an important variable in the design of CIDP trials. Trials designed to show clinical improvement will have a significantly lower effect of this phenomenon than those designed to show stability or deterioration.

Background: Identifying separate dimensions of concussion symptoms may inform a precision medicine approach to treatment. It was previously reported that a bifactor model identified distinct acute postconcussion symptom dimensions. Purpose: To replicate previous findings of a bifactor structure of concussion symptoms in the Concussion Assessment Research and Education (CARE) Consortium sample, examine measurement invariance from pre- to postinjury, and evaluate whether factors are associated with other clinical and biomarker measures. Study Design: Cohort study (Diagnosis); Level of evidence, 2. Methods: Collegiate athletes were prospectively evaluated using the Sport Concussion Assessment Tool–3 (SCAT-3) during preseason (N = 31,557); 2789 were followed at Results: The optimal structure for each time point was a 7-factor bifactor model: a General factor, on which all items loaded, and 6 specific factors—Vestibulo-ocular, Headache, Sensory, Fatigue, Cognitive, and Emotional. The model manifested strict invariance across the 2 postinjury time points but only configural invariance from baseline to postinjury. From Conclusion: Bifactor modeling supported the predominant unidimensionality of concussion symptoms while revealing multidimensional properties, including a large dominant General factor and 6 independent factors: Headache, Vestibulo-ocular, Sensory, Cognitive, Fatigue, and Emotional. Unlike the widely used SCAT-3 symptom severity score, which declines gradually after injury, the bifactor model revealed separable symptom dimensions that have distinct trajectories in the acute postinjury period and different patterns of association with other markers of injury severity and outcome. Clinical Relevance: The SCAT-3 total score remains a valuable, robust index of overall concussion symptom severity, and the specific factors identified may inform management strategies. Because some symptom dimensions continue to worsen in the first 24 to 48 hours after injury (ie, Sensory, Fatigue, Emotional), routine follow-up in this time frame may be valuable to ensure that symptoms are managed effectively.

Objectives We aimed to estimate the association between Medicaid unbundling of payment for long-acting reversible contraceptives (LARC) from the global delivery fee and immediate postpartum (IPP) LARC provision, in a state outside a select group of early-adopters. We also examine the potential moderating roles of hospital academic affiliation and Catholic status on the association between unbundling and IPP LARC provision. Methods We used a pre–post design to examine the association between unbundling and IPP LARC provision. We observed Medicaid-covered childbirth deliveries in Wisconsin hospitals between January 2016 and December 2017 (n = 45,200) in the State Inpatient Database from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. We conducted multivariate regressions using generalized linear mixed models. Results From 2016 to 2017, IPP LARC provision increased from 0.28% to 0.44% of deliveries (p = .003). In our adjusted model, IPP LARC provision was 1.55 times more likely in the post–period versus the pre-period (95% confidence interval, 1.12–2.13). Both before and after unbundling, IPP LARC provision was significantly more common in academic versus nonacademic settings and was exceedingly rare in Catholic institutions. Conclusions In contrast with many early adopting states, in this later adopting state, Wisconsin Medicaid's unbundling of LARC from the global fee did not meaningfully change the rates of IPP LARC provision. These results indicate that delivery hospital characteristics are strong correlates of access to IPP LARC and suggest the need for interventions—perhaps outside of the inpatient setting—to ensure that patients can access desired contraceptive methods promptly postpartum.

The immune system plays a critical role in cancer progression and response to therapy. However, the immune system can be compromised during the neoplastic process. Notably, the myeloid lineage, which gives rise to granulocytic cells, including neutrophils, is a well-recognized target of tumor-mediated immune suppression. Ordinarily, granulocytic cells are integral for host defense, but in neoplasia the normal process of granulocyte differentiation (i.e., granulopoiesis) can be impaired leading instead to the formation of granulocytic (or PMN)-myeloid-derived suppressor cells (MDSCs). Such cells comprise various stages of myeloid differentiation and are defined functionally by their highly pro-tumorigenic and immune suppressive activities. Thus, considerable interest has been devoted to impeding the negative contributions of PMN-MDSCs to the antitumor response. Understanding their biology has the potential to unveil novel therapeutic opportunities to hamper PMN-MDSC production in the bone marrow, their mobilization, or their effector functions within the tumor microenvironment and, therefore, bolster anticancer therapies that require a competent myeloid compartment. In this review, we will highlight mechanisms by which the neoplastic process skews granulopoiesis to produce PMN-MDSCs, summarize mechanisms by which they execute their pro-tumorigenic activities and, lastly, underscore strategies to obstruct their role as negative regulators of antitumor immunity.

The Asian tiger mosquito (Aedes albopictus) is an important vector of a number of arboviruses, including Zika (ZIKV), dengue (DENV), and chikungunya (CHIKV) viruses, and has recently expanded its range in the eastern United States to southern New England and New York. Given the recent establishment and proliferation of Ae. albopictus in this region and the increasing amount of international travel between the United States and endemic countries, there is a need to elucidate the public health risk posed by this mosquito species in the Northeast. Accordingly, we evaluated the competence of four Ae. albopictus populations from Connecticut and New York, for two strains each of ZIKV, DENV serotype 2 (DENV-2), and CHIKV, currently circulating in the Americas, to evaluate the local transmission risk by this vector. We found that local Ae. albopictus populations are susceptible to infection by all three viruses but are most capable of transmitting CHIKV. Variation in competence was observed for ZIKV and CHIKV, driven by the virus strains and mosquito population, whereas competence was more homogeneous for the DENV-2 strains under evaluation. These results suggest that under optimal circumstances, Ae. albopictus could support localized transmission of these viruses and emphasize the importance of maintaining mosquito surveillance and control programs to suppress Ae. albopictus populations and limit further range expansion of this species.

Surveillance for the emerging infectious disease Eastern equine encephalitis, and its causative virus in mosquitoes, continued within New York State from 2013 to 2019. There were increases in geographic area and number of consecutive years, with cases in four mammalian species, and virus in 11 mosquito species. The first cases in a goat and in an emu were reported. The first detection of virus in Aedes cinereus was reported. Virus in phylogenetic group NY4 was isolated from a horse and from mosquitoes 6 kilometers and 13 days apart in 2013. Phylogenetic groups NY4 and NY5 were found 15 days apart in two towns 280 kilometers distant in 2013. Within four adjacent counties there was a pattern of overlap, where four had NY5, two adjacent counties had NY6, two adjacent counties had NY7, and one county had NY5, NY6, and NY7, reducible to a Euler diagram. Virus in phylogenetic group NY5, found within an 11-kilometer wide area in New York State, was related to FL4 found in Florida 1,398 kilometers distant. This was consistent with a phylogenetic group originating in Florida, then being moved to a specific location in New York State, by migratory birds in consecutive years 2013 and 2014.

The termination of many clinical trials of amyloid-targeting therapies for the treatment of Alzheimer’s disease (AD) has had a major impact on the AD clinical research enterprise. However, positive signals in recent studies have reinvigorated support for the amyloid hypothesis and amyloid-targeting strategies. In December 2019, the EU-US Clinical Trials on Alzheimer’s Disease (CTAD) Task Force met to share learnings from these studies in order to inform future trials and promote the development of effective AD treatments. Critical factors that have emerged in studies of anti-amyloid monoclonal antibody therapies include developing a better understanding of the specific amyloid species targeted by different antibodies, advancing our insight into the mechanism by which those antibodies may reduce pathology, implementing more comprehensive repertoires of biomarkers into trials, and identifying appropriate doses. Studies suggest that Amyloid-Related Imaging Abnormalities – effusion type (ARIA-E) are a manageable safety concern and that caution should be exercised before terminating studies based on interim analyses. The Task Force concluded that opportunities for developing effective treatments include developing new biomarkers, intervening in early stages of disease, and use of combination therapies.

Increases in tick-borne disease prevalence and transmission are important public health issues. Efforts to control these emerging diseases are frustrated by the struggle to control tick populations and to detect and treat infections caused by the pathogens that they transmit. This review covers tick-borne infectious diseases of nonrickettsial bacterial, parasitic, and viral origins. While tick surveillance and tracking inform our understanding of the importance of the spread and ecology of ticks and help identify areas of risk for disease transmission, the vectors are not the focus of this document. Here, we emphasize the most significant pathogens that infect humans as well as the epidemiology, clinical features, diagnosis, and treatment of diseases that they cause. Although detection via molecular or immunological methods has improved, tick-borne diseases continue to remain underdiagnosed, making the scope of the problem difficult to assess. Our current understanding of the incidence of tick-borne diseases is discussed in this review. An awareness of the diseases that can be transmitted by ticks in specific locations is key to detection and selection of appropriate treatment. As tick-transmitted pathogens are discovered and emerge in new geographic regions, our ability to detect, describe, and understand the growing public health threat must also grow to meet the challenge.

Serious mental health conditions peak in prevalence and incidence during the transition to adulthood (approximately ages 16–25). Young adults are at high risk for discontinuation of care when no longer eligible for child mental health services. This study uses state administrative data to examine service continuation among those aging out of child system services in Texas (N = 3135). Most (63.5%) did not enroll in adult services following their 18th birthday. Binary logistic regression analyses found that significant predictors of child-to-adult service continuation included (1) a serious primary mental health diagnosis (i.e., schizophrenia, bipolar disorder, major depressive disorder), (2) risks to self and others, and (3) number of prior-year mental health services received. These findings suggest that historical mental health policies and practices may contribute to service disconnection at age 18 in Texas. Implications for mental health policy and system reform locally and nationally are discussed.

We critique Roy et al.'s (2020; this issue) approach to characterizing the item-level factor structure of the three scales of the Triarchic Psychopathy Measure (TriPM), in light of the manner in which the TriPM scales were developed, the purposes they were designed to serve, and the growing body of evidence supporting their construct validity. We focus on three major points: (1) The TriPM scales are item-based factor scales - i.e., item sets designed to index broad factors of larger multi-scale (parent) inventories; (2) item-level structural analysis can be useful for representing broad dimensions tapped by such scales, but it cannot be expected to provide an accurate picture of narrower subdimensions (facets) assessed by their parent inventories; and (3) it is critical to consider the nomological networks of the TriPM scales (and other triarchic scale measures) in appraising their effectiveness as operationalizations of the triarchic model constructs. We illustrate the first and second of these points by applying Roy et al.'s analytic approach to the trait scales of the NEO-FFI, which were developed to index broad personality dimensions of the multi-scale NEO-PI-R. We address the third point with reference to the growing body of literature supporting the construct validity of the TriPM scales and demonstrating their utility for advancing an integrative understanding of psychopathy. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied oral cancer. However, there is a void regarding the role that the oral microbiome may play in OSCC. Although the relationship between microbial community composition and OSCC has been thoroughly investigated, microbial profiles of the human microbiome in cancer are understudied. Here we performed a small pilot study of community-wide metatranscriptome analysis to profile mRNA expression in the entire oral microbiome in OSCC to reveal molecular functions associated with this disease. Fusobacteria showed a statistically significantly higher number of transcripts at tumour sites and tumour-adjacent sites of cancer patients compared to the healthy controls analysed. Regardless of the community composition, specific metabolic signatures were consistently found in disease. Activities such as iron ion transport, tryptophanase activity, peptidase activities and superoxide dismutase were over-represented in tumour and tumour-adjacent samples when compared to the healthy controls. The expression of putative virulence factors in the oral communities associated with OSCC showed that activities related to capsule biosynthesis, flagellum synthesis and assembly, chemotaxis, iron transport, haemolysins and adhesins were upregulated at tumour sites. Moreover, activities associated with protection against reactive nitrogen intermediates, chemotaxis, flagellar and capsule biosynthesis were also upregulated in non-tumour sites of cancer patients. Although they are preliminary, our results further suggest that Fusobacteria may be the leading phylogenetic group responsible for the increase in expression of virulence factors in the oral microbiome of OSCC patients., Oncology: bacteria may contribute to oral cancer development A search of the oral microbiome has revealed a group of bacteria closely associated with the most common type of oral cancer, and whose activity may play a role in its development. Oral squamous cell carcinoma (OSCC) has been linked to tobacco and alcohol consumption, but there’s increasing interest in the role bacteria might play in its initiation and growth. To better understand the behaviour of the various microbes present in the mouths of healthy people and those with OSCC, Jorge Frias-Lopez at the University of Florida in Gainesville and his colleagues carried out a metatranscriptome analysis, which identifies the most actively expressed genes. This revealed significant differences in their microbial communities, with Fusidobacteria particularly enriched and hyperactive in patients with OSCC. The team also identified microbial activities that were consistently associated with cancer.

BACKGROUND Approximately 20% to 40% of trauma survivors experience posttraumatic stress disorder (PTSD). The American College of Surgeons Committee on Trauma reports that early screening and referral has the potential to improve outcomes and that further study of screening and intervention for PTSD would be beneficial. This prospective randomized study screened hospitalized patients for traumatic stress reactions and assessed the effect of a brief intervention in reducing later development of PTSD. METHODS The Primary Care PTSD (PC-PTSD) screen was administered to admitted patients. Patients with symptoms were randomized to an intervention or control group. The brief intervention focused on symptom education and normalization, coping strategies, and utilizing supports. The control group received a 3-minute educational brochure review. Both groups completed in-hospital interviews, then 45- and 90-day telephone interviews. Follow-up collected the PTSD checklist-civilian (PCL-C) assessment and qualitative data on treatment-seeking barriers. RESULTS The PC-PTSD screen was successful in predicting later PTSD symptoms at both 45 days (β = 0.43, p < 0.001) and 90 days (β = 0.37, p < 0.001) even after accounting for depression. Correlations of the intervention with the PCL-C scores and factor score estimates did not reach statistical significance at either time point (p = 0.827; p = 0.838), indicating that the brief intervention did not decrease PTSD symptoms over time. Of those at or above the PCL-C cutoff at follow-ups, a minority had sought treatment for their symptoms (43.2%). Primary barriers included focusing on their injury or ongoing rehabilitation, financial concerns, or location of residence. CONCLUSION The PC-PTSD screen identified patients who later assess positive for PTSD using the PCL-C. The brief intervention did not reduce 45- and 90-day PTSD development. Follow-up interviews revealed lack of treatment infrastructure in the community. It will be important for trauma centers to align with community resources to address the treatment needs of at-risk patients. LEVEL OF EVIDENCE Prospective randomized controlled trial, level II.

Objectives: Concussions cause diverse symptoms that are often measured through a single symptom severity score. Researchers have postulated distinct dimensions of concussion symptoms, raising the possibility that total scores may not accurately represent their multidimensional nature. This study examined to what degree concussion symptoms, assessed by the Sport Concussion Assessment Tool 3 (SCAT3), reflect a unidimensional versus multidimensional construct to inform how the SCAT3 should be scored and advance efforts to identify distinct phenotypes of concussion. Methods: Data were aggregated across two prospective studies of sport-related concussion, yielding 219 high school and college athletes in the acute (Results: The best-fitting model was a five-factor bifactor model that included a general factor on which all items loaded and four specific factors reflecting emotional symptoms, torpor, sensory sensitivities, and headache symptoms. The bifactor model demonstrated better discriminant validity than the counterpart higher-order model, in which the factors were highly correlated (r=.55–.91). Conclusions: The SCAT3 contains items that appear unidimensional, suggesting that it is appropriate to quantify concussion symptoms with total scores. However, evidence of multidimensionality was revealed using bifactor modeling. Additional work is needed to clarify the nature of factors identified by this model, explicate their clinical and research utility, and determine to what degree the model applies to other stages of injury recovery and patient subgroups. (JINS, 2018, 24, 793–804)

Background The year 1971 was the first time in New York State (NYS) that Eastern equine encephalitis virus (EEEV) was identified in mosquitoes, in Culiseta melanura and Culiseta morsitans. At that time, state and county health departments began surveillance for EEEV in mosquitoes. Methods From 1993 to 2012, county health departments continued voluntary participation with the state health department in mosquito and arbovirus surveillance. Adult female mosquitoes were trapped, identified, and pooled. Mosquito pools were tested for EEEV by Vero cell culture each of the twenty years. Beginning in 2000, mosquito extracts and cell culture supernatant were tested by reverse transcriptase-polymerase chain reaction (RT-PCR). Results During the years 1993 to 2012, EEEV was identified in: Culiseta melanura, Culiseta morsitans, Coquillettidia perturbans, Aedes canadensis (Ochlerotatus canadensis), Aedes vexans, Anopheles punctipennis, Anopheles quadrimaculatus, Psorophora ferox, Culex salinarius, and Culex pipiens-restuans group. EEEV was detected in 427 adult mosquito pools of 107,156 pools tested totaling 3.96 million mosquitoes. Detections of EEEV occurred in three geographical regions of NYS: Sullivan County, Suffolk County, and the contiguous counties of Madison, Oneida, Onondaga and Oswego. Detections of EEEV in mosquitoes occurred every year from 2003 to 2012, inclusive. EEEV was not detected in 1995, and 1998 to 2002, inclusive. Conclusions This was the first time in NYS that EEEV was detected in Cx. salinarius, Ps. ferox and An. punctipennis. The detection of EEEV in mosquitoes every year for 10 years was the longest time span since surveillance began in 1971. The calendar date of the earliest annual appearance of EEEV in mosquitoes did not change during surveillance spanning 42 years.

Objective To investigate whether demographic, socioeconomic, and reproductive health characteristics affect long-acting reversible contraceptive (LARC) use differently by race-ethnicity. Results may inform the dialogue on racial pressure and bias in LARC promotion. Study design Data derived from the 2011–2013 and 2013–2015 National Surveys of Family Growth (NSFG). Our study sample included 9321 women aged 15–44. Logistic regression analyses predicted current LARC use (yes vs. no). We tested interaction terms between race-ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic) and covariates (for example, education, parity, poverty level) to explore whether their effects on LARC use vary by race-ethnicity. Results In the race-interactions model, data did not show that low income and education predict LARC use more strongly among Black and Hispanic women than among White women. There was just one statistically significant race-interaction: experience of unintended pregnancy (p=.014). Among Whites and Hispanics, women who reported ever experiencing an unintended pregnancy had a higher predicted probability of LARC use than those who did not. On the other hand, among Black women, the experience of unintended pregnancy was not associated with a higher predicted probability of LARC use. Conclusions With the exception of the experience of unintended pregnancy, findings from this large, nationally representative sample of women suggest similar patterns in LARC use by race-ethnicity. Implications Results from this analysis of NSFG data do not provide evidence that observed differences in LARC use by race-ethnicity represent socioeconomic disparities, and may assuage some concerns about reproductive coercion among women of color. Nevertheless, it is absolutely critical that providers use patient-centered approaches for contraceptive counseling that promote women's autonomy in their reproductive health care decision-making.

Aedes albopictus (Diptera: Culicidae) is an invasive mosquito, native to Asia, that has expanded its range worldwide. It is considered to be a public health threat as it is a competent vector of viruses of medical importance, including dengue, chikungunya, and Zika. Despite its medical importance there is almost no information on biologically important traits of Ae. albopictus in Argentina. We studied life cycle traits, demographic parameters and analyzed the competence of this mosquito as a virus vector. In addition, we determined the prevalence of Wolbachia strains in Ae. albopictus as a first approach to investigate the potential role of this bacteria in modulating vector competence for arboviruses. We observed low hatch rates of eggs, which led to a negative growth rate. We found that Ae. albopictus individuals were infected with Wolbachia in the F1 but while standard superinfection with wAlbA and wAlbB types was found in 66.7% of the females, 16.7% of the females and 62.5% of the males were single-infected with the wAlbB strain. Finally, despite high levels of infection and dissemination, particularly for chikungunya virus, Ae. albopictus from subtropical Argentina were found to be relatively inefficient vectors for transmission of both chikungunya and dengue viruses., Centro de Estudios Parasitológicos y de Vectores

We assessed the vector competence of Aedes caspius and Aedes albopictus mosquitoes in Spain for the transmission of Zika virus. Whereas Ae. albopictus mosquitoes were a competent vector, Ae. caspius mosquitoes were unable to transmit Zika virus. We also identified high levels of vertical transmission of Zika virus in Ae. albopictus mosquitoes