The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor.

Mammalian Toll-like receptors (TLRs) 3, 7, 8 and 9 initiate immune responses to infection by recognizing microbial nucleic acids; however, these responses come at the cost of potential autoimmunity owing to inappropriate recognition of self nucleic acids. The localization of TLR9 and TLR7 to intracellular compartments seems to have a role in facilitating responses to viral nucleic acids while maintaining tolerance to self nucleic acids, yet the cell biology regulating the transport and localization of these receptors remains poorly understood. Here we define the route by which TLR9 and TLR7 exit the endoplasmic reticulum and travel to endolysosomes in mouse macrophages and dendritic cells. The ectodomains of TLR9 and TLR7 are cleaved in the endolysosome, such that no full-length protein is detectable in the compartment where ligand is recognized. Notably, although both the full-length and cleaved forms of TLR9 are capable of binding ligand, only the processed form recruits MyD88 on activation, indicating that this truncated receptor, rather than the full-length form, is functional. Furthermore, conditions that prevent receptor proteolysis, including forced TLR9 surface localization, render the receptor non-functional. We propose that ectodomain cleavage represents a strategy to restrict receptor activation to endolysosomal compartments and prevent TLRs from responding to self nucleic acids

Examining the Influence of Ethnic/Racial Socialization on Aggressive Behaviors Among Juvenile Offenders

Risk assessment instruments are commonly used within the juvenile justice system to estimate a juvenile's likelihood of reoffending or engaging in aggressive or violent behavior. Although such instruments assess a broad range of factors, the influence of culture is often excluded. The current study examines the unique effect of ethnic/racial socialization on recent aggressive behaviors above and beyond three well-established risk and protective factors: delinquency history, moral disengagement, and social support. Participants were 95 juveniles who were either on probation or in detention centers in three Midwestern counties and who completed structured surveys related to personal experiences within and outside of the juvenile justice system. The findings provided partial support for our hypotheses: Consistent with previous findings, delinquency history and moral disengagement were significant predictors of recent aggressive behavior. Furthermore, when ethnic/racial socialization was added to the model, promotion of mistrust provided additional predictive validity for aggressive behavior above and beyond the other factors assessed. Based on these findings, the inclusion of education on culture may prove to be an important supplement to established intervention tools for juvenile offenders

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Assessing the Forms and Functions of Aggression Using Self-Report: Factor Structure and Invariance of the Peer Conflict Scale in Youths

This study examined the structure of a self-report measure of the forms and functions of aggression in 855 adolescents (582 boys, 266 girls) aged 12 to 19 years recruited from high school, detained, and residential settings. The Peer Conflict Scale (PCS) is a 40-item measure that was developed to improve upon existing measures and provide an efficient, reliable, and valid assessment of four dimensions of aggression (i.e., reactive overt, reactive relational, proactive overt, and proactive relational) in youths. Confirmatory factor analyses showed that a 4-factor model represented a satisfactory solution for the data. The factor structure fit well for both boys and girls and across high school, detained, and residential samples. Internal consistency estimates were good for the 4 factors, and they showed expected associations with externalizing variables (i.e., arrest history, callous-unemotional traits, and delinquency). Reactive and proactive subtypes showed unique associations consistent with previous literature. Implications for the use of the PCS to assess aggression and inform intervention decisions in diverse samples of youths are discussed

MsFLASH Participants’ Priorities for Alleviating Menopausal Symptoms

Objective To describe self-reported menopausal symptom priorities and their association with demographics and other symptoms among participants in an intervention trial for vasomotor symptoms (VMS). Methods Cross-sectional study embedded in the MsFLASH 02 trial, a three-by-two factorial design of yoga vs. exercise vs. usual activity and omega-3-fatty acid vs. placebo. At baseline, women (n = 354) completed hot flush diaries, a card sort task to prioritize symptoms they would most like to alleviate, and standardized questionnaires. Results The most common symptom priorities were: VMS (n = 322), sleep (n = 191), concentration (n = 140), and fatigue (n = 116). In multivariate models, women who chose VMS as their top priority symptom (n = 210) reported significantly greater VMS severity (p = 0.004) and never smoking (p = 0.012), and women who chose sleep as their top priority symptom (n = 100) were more educated (p ≤ 0.001) and had worse sleep quality (p < 0.001). ROC curves identified sleep scale scores that were highly predictive of ranking sleep as a top priority symptom. Conclusions Among women entering an intervention trial for VMS and with relatively low prevalence of depression and anxiety, VMS was the priority symptom for treatment. A card sort may be a valid tool for quickly assessing symptom priorities in clinical practice and research

A community survey of coverage and adverse events following country-wide triple-drug mass drug administration for lymphatic filariasis elimination, Samoa 2018

The Global Programme to Eliminate Lymphatic Filariasis has made considerable progress but is experiencing challenges in meeting targets in some countries. Recent World Health Organization guidelines have recommended two rounds of triple-drug therapy with ivermectin, diethylcarbamazine (DEC), and albendazole (IDA), in areas where mass drug administration (MDA) results with two drugs (DEC and albendazole) have been suboptimal, as is the case in Samoa. In August 2018, Samoa was the first country in the world to implement countrywide triple-drug MDA. This paper aims to describe Samoa’s experience with program coverage and adverse events (AEs) in the first round of triple-drug MDA. We conducted a large cross-sectional community survey to assess MDA awareness, reach, compliance, coverage and AEs in September/October 2018, 7–11 weeks after the first round of triple-drug MDA. In our sample of 4420 people aged ≥2 years (2.2% of the population), age-adjusted estimates indicated that 89.0% of the eligible population were offered MDA, 83.9% of the eligible population took MDA (program coverage), and 80.2% of the total population took MDA (epidemiological coverage). Overall, 83.8% (2986/3563) reported that they did not feel unwell at all after taking MDA. Mild AEs (feeling unwell but able to do normal everyday things) were reported by 13.3% (476/3563) and moderate or severe AEs (feeling unwell and being unable to do normal everyday activities such as going to work or school) by 2.9% (103/3563) of participants. This study following the 2018 triple-drug MDA in Samoa demonstrated a high reported program awareness and reach of 90.8% and 89.0%, respectively. Age-adjusted program coverage of 83.9% of the total population showed that MDA was well accepted and well tolerated by the community

Female Sexual Function Index Short Version: A MsFLASH Item Response Analysis

The Female Sexual Function Index (FSFI) is a psychometrically sound and popular 19-item self-report measure, but its length may preclude its use in studies with multiple outcome measures, especially when sexual function is not a primary endpoint. Only one attempt has been made to create a shorter scale, resulting in the Italian FSFI-6, later translated into Spanish and Korean without further psychometric analysis. Our study evaluated whether a subset of items on the 19-item English-language FSFI would perform as well as the full-length FSFI in peri- and post-menopausal women. We used baseline data from 898 peri- and post-menopausal women recruited from multiple communities, ages 42–62 years, and enrolled in randomized controlled trials for vasomotor symptom management. Goals were to (1) create a psychometrically sound, shorter version of the FSFI for use in peri- and post-menopausal women as a continuous measure and (2) compare it to the Italian FSFI-6. Results indicated that a 9-item scale provided more information than the FSFI-6 across a spectrum of sexual functioning, was able to capture sample variability, and showed sufficient range without floor or ceiling effects. All but one of the items from the Italian 6-item version were included in the 9-item version. Most omitted FSFI items focused on frequency of events or experiences. When assessment of sexual function is a secondary endpoint and subject burden related to questionnaire length is a priority, the 9-item FSFI may provide important information about sexual function in English-speaking peri- and post-menopausal women

Evaluating Molecular Xenomonitoring as a Tool for Lymphatic Filariasis Surveillance in Samoa, 2018–2019

Molecular xenomonitoring (MX), the detection of filarial DNA in mosquitoes using molecular methods (PCR), is a potentially useful surveillance strategy for lymphatic filariasis (LF) elimination programs. Delay in filarial antigen (Ag) clearance post-treatment is a limitation of using human surveys to provide an early indicator of the impact of mass drug administration (MDA), and MX may be more useful in this setting. We compared prevalence of infected mosquitoes pre- and post-MDA (2018 and 2019) in 35 primary sampling units (PSUs) in Samoa, and investigated associations between the presence of PCR-positive mosquitoes and Ag-positive humans. We observed a statistically significant decline in estimated mosquito infection prevalence post-MDA at the national level (from 0.9% to 0.3%, OR 0.4) but no change in human Ag prevalence during this time. Ag prevalence in 2019 was higher in randomly selected PSUs where PCR-positive pools were detected (1.4% in ages 5–9; 4.8% in ages ≥10), compared to those where PCR-positive pools were not detected (0.2% in ages 5–9; 3.2% in ages ≥10). Our study provides promising evidence for MX as a complement to human surveys in post-MDA surveillance

Complex patterns of the HIV-1 epidemic in Kuala Lumpur, Malaysia: Evidence for expansion of circulating recombinant form CRF33_01B and detection of multiple other recombinants

AbstractThe HIV protease-reverse transcriptase (PR-RT) (1047 bp), gp120-env (891 bp) and gp41-env (547 bp) regions from the plasma of 115 HIV-1-infected patients in Kuala Lumpur (KL), Malaysia were sequenced. Detailed phylogenetic and bootscanning analyses were performed to determine the mosaic structure of the HIV-1 strains and their recombination breakpoint(s). Among the 50 patient samples in which all three regions could be amplified, the HIV-1 CRF01_AE subtype (46%) was predominant followed by subtypes B (10%) and B′ (6%). A total of 9/50 (18%) patients were infected with a CRF01_AE/B inter-subtype recombinant, displaying a recombinant form (RF)PR-RT, CRF01_AEgp120-env and CRF01_AEgp41-env. This RF was derived from the Thai variants of CRF01_AE and B′ subtype, with two distinct B′ subtype segments in the backbone of CRF01_AE, similar to the newly identified CRF33_01B. In addition, one sample demonstrated a close structural relationship with the new CRF33_01B in the PR-RT region but displayed B′ segment in part of the env region (RFPR-RT, CRF01_AE/B′gp120-env and B′gp41-env) indicating continuing evolution of CRF33_01B. The remaining 18% of samples were identified as unique recombinant forms (URFs)