Improving preparedness for introducing and scaling up long-acting HIV pre-exposure prophylaxis in Asia.

Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.

The International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD) guidelines for prevention of traumatic dental injuries: Part 1: General introduction.

The Guidelines for Prevention of Traumatic Dental Injuries were reviewed and approved by the Board of Directors of the International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD).

The International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD) guidelines for prevention of traumatic dental injuries: Part 4: Faceshields for the prevention of dental and oral trauma.

The Guidelines for Prevention of Traumatic Dental Injuries were reviewed and approved by the Board of Directors of the International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD).

The International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD) guidelines for prevention of traumatic dental injuries: Part 5: Secondary prevention of dental injuries.

The Guidelines for Prevention of Traumatic Dental Injuries were reviewed and approved by the Board of Directors of the International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD).

The International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD) guidelines for prevention of traumatic dental injuries: Part 3: Mouthguards for the prevention of dental and oral trauma.

The Guidelines for Prevention of Traumatic Dental Injuries were reviewed and approved by the Board of Directors of the International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD).

The International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD) guidelines for prevention of traumatic dental injuries: Part 10: First aid education.

The Guidelines for Prevention of Traumatic Dental Injuries were reviewed and approved by the Board of Directors of the International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD).

The International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD) guidelines for prevention of traumatic dental injuries: Part 2: Primary prevention of dental trauma across the life course.

The Guidelines for Prevention of Traumatic Dental Injuries were reviewed and approved by the Board of Directors of the International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD).

The International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD) guidelines for prevention of traumatic dental injuries: Part 6: Education.

The Guidelines for Prevention of Traumatic Dental Injuries were reviewed and approved by the Board of Directors of the International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD).

The International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD) guidelines for prevention of traumatic dental injuries: Part 8: ToothSOS app.

The Guidelines for Prevention of Traumatic Dental Injuries were reviewed and approved by the Board of Directors of the International Association of Dental Traumatology (IADT) and the Academy for Sports Dentistry (ASD).

Differentiated service delivery for HIV treatment models in Thailand: A cross-sectional assessment of real-world implementation and uptake.

OBJECTIVES: First, to describe the antiretroviral therapy (ART) delivery models available in Thailand to understand differentiated service delivery for further service system optimization and expansion of best practices; second, to determine the client characteristics associated with model uptake. METHODS: Across-sectional assessment using secondary data was conducted to describe ART models implemented as routine services at four public hospitals in three major provinces with a high-HIV burden in Thailand. From April to October 2020, ART clients were screened consecutively according to the inclusion criteria: Thai, aged ≥18 years, and on ART for ≥6 months. HIV treatment models were categorised based on the service type, location, provider, and frequency. Logistic regression was used to identify the associated factors. RESULTS: Seven individual ART delivery models were identified: four were facility-based and three were out-of-facility. No group models were identified. Of 3,366 records of ART clients reviewed, 3,213 (95.5%) met the study criteria and received ART through the following models: conventional (32.6%), nurse-led clinical consultation (10.0%), fast-track refill (29.0%), after-hours clinic (10.6%), pharmacist-led pickup center (3.6%), key population-led community-based organisation (2.7%), and mailing (11.5%). Age, population, duration on ART, and viral load were associated with the uptake of certain alternative service models when compared to the conventional model. CONCLUSIONS: Among the variety of ART delivery approaches available in Thailand, facility-based models remain the most prevalent. Future work should investigate the role of client preference and choice in choosing service models and service utilisation patterns over time, and assess the acceptability and effectiveness of these models.

The Tooth Protector in Early Professional Baseball.

Protection of athletes during sporting activities was of some concern even in the late 1800s. That concern continues, over 140 years later. In baseball, safety for the catcher was of primary concern because of inherent risks of being "behind the plate" while balls are pitched, bats are swung, and runners attempting to score come barreling in. Doug Allison was the skilled catcher for the 1869 Cincinnati Red Stockings who was known to use certain objects for self-protection, including George Wright's rubber "Mouthpiece." This report reviews earliest development of mouth protection in baseball, as known through reports of the times, and Doug Allison's career.

Drug-drug Interactions Among Thai Transgender Women Living with Human Immunodeficiency Undergoing Feminizing Hormone Therapy and Antiretroviral Therapy: The iFACT Study.

BACKGROUND: Drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are a major concern among transgender women (TGW), which may lead to suboptimal ART adherence and inappropriate FHT dosage. To evaluate potential drug-drug interactions between FHT and ART, we performed intensive measurements of the pharmacokinetic (PK) parameters of blood tenofovir (TFV), efavirenz (EFV), and estradiol (E2). METHODS: Twenty TGW with newly diagnosed human immunodeficiency virus (HIV) infection were enrolled. FHT (E2 valerate 2 mg/d and cyproterone acetate 25 mg/d) was prescribed at baseline until week 5 and restarted at week 8. ART (TFV disoproxil fumarate/emtricitabine/EFV at 300/200/600 mg) was initiated at week 3. The E2 PK parameters were measured intensively at weeks 3 (without ART) and 5 (with ART), and TFV and EFV PK parameters were measured intensively at weeks 5 (with FHT) and 8 (without FHT). RESULTS: The median (interquartile range) age and body mass index were 25.5 (22.5-31.0) years and 20.6 (19.3-23.1) kg/m2, respectively. The differences in geometric mean ratios between weeks 3 and 5 were as follows for E2 area under the curve, maximum concentration, and concentration at 24 hours (C24), respectively: 0.72 (90% confidence interval, .64-.81; P < .001), 0.81 (.72-.92; P = .006), and 0.64 (.50-.83; P = .004). The differences in geometric mean ratios between weeks 5 and 8 were as follows for TFV AUC, TFV C24, and EFV C24: 0.86 (90% confidence interval, .80-.93; P = .002), 0.83 (.75-.93; P = .006), and 0.91 (.85-.97; P = .02). CONCLUSIONS: Among HIV-positive TGW, E2 PK parameters were significantly lower in the presence of TFV disoproxil fumarate/emtricitabine/EFV, and some TFV and EFV PK parameters were lower in the presence of FHT. Further studies should determine whether these reductions are clinically significant and whether they occur with other FHT or ART regimens.

Effect of temperature on the Arabidopsis cryptochrome photocycle.

Cryptochromes are blue light-absorbing photoreceptors found in plants and animals with many important signalling functions. These include control of plant growth, development, and the entrainment of the circadian clock. Plant cryptochromes have recently been implicated in adaptations to temperature variation, including temperature compensation of the circadian clock. However, the effect of temperature directly on the photochemical properties of the cryptochrome photoreceptor remains unknown. Here we show that the response to light of purified Arabidopsis Cry1 and Cry2 proteins was significantly altered by temperature. Spectral analysis at 15°C showed a pronounced decrease in flavin reoxidation rates from the biologically active, light-induced (FADH°) signalling state of cryptochrome to the inactive (FADox) resting redox state as compared to ambient (25°C) temperature. This result indicates that at low temperatures, the concentration of the biologically active FADH° redox form of Cry is increased, leading to the counterintuitive prediction that there should be an increased biological activity of Cry at lower temperatures. This was confirmed using Cry1 cryptochrome C-terminal phosphorylation as a direct biological assay for Cry activation in vivo. We conclude that enhanced cryptochrome function in vivo at low temperature is consistent with modulation by temperature of the cryptochrome photocycle.

The continuing HIV epidemic among men who have sex with men and transgender women in the ASEAN region: implications for HIV policy and service programming.

Men who have sex with men (MSM) in Western urban areas have seen substantive decreases in new diagnoses of HIV infection. This paper explores whether such declines are present among MSM and transgender women (TGW) in Southeast Asia and discusses implications for HIV policies and programming. A scoping review was conducted of scientific publications and selected documents regarding the spread of HIV infection among MSM and TGW in major urban centres of the Association of Southeast Asian Nations (ASEAN) region. Continued high HIV prevalence and incidence among MSM are found in integrated behavioural and biological surveillance (IBBS) and research studies. HIV prevalence among MSM under IBBS decreased only in Bangkok from 28.6% in 2014 to 10.3% in 2018, whereas it was increasing in Kuala Lumpur, Ho Chi Minh City, Vientiane, and Phnom Penh. HIV/AIDS case reports regarding new HIV infection diagnoses among MSM have started to decrease in Singapore since 2011 and have been plateauing in Metropolitan Manila since 2017. Where data were available, it was found that HIV prevalence among TGW was high and if IBBS was conducted, it was increasing. HIV prevalence among TGW under IBBS in Jakarta had risen to 34.0% (2015) and 14.0% (2019) in Phnom Penh. These findings suggest that most ASEAN member states have so far failed to effectively implement and scale-up scientifically proven biomedical HIV prevention measures and counter stigma and discrimination that impedes access to appropriate HIV prevention and treatment services for MSM and TGW.

Co(II) is not oxidized during turnover in the copper amine oxidase from Hansenula polymorpha.

Co(II) substitution into the copper amine oxidases (CAOs) has been an effective tool for evaluating the mechanism of oxygen reduction in these enzymes. However, formation of hydrogen peroxide during turnover raises questions about the relevant oxidation state of the cobalt in these enzymes and, therefore, the interpretation of the activity of the metal-substituted enzyme with respect to its mechanism of action. In this study, Co(II) was incorporated into the CAO from Hansenula polymorpha (HPAO). The effect of hydrogen peroxide on the catalytic activity of cobalt-substituted HPAO was evaluated. Hydrogen peroxide, either generated during turnover or added exogenously, caused a decrease in the activity of the enzyme but did not oxidize Co(II) to Co(III). These results are in strong contrast with results from the CAO from Arthrobacter globiformis (AGAO), where hydrogen peroxide causes an increase in the activity of the enzyme as the Co(II) is oxidized to Co(III). The results of this study with HPAO support previous reports that have shown that this enzyme acts by transferring an electron directly from the reduced TPQ cofactor to dioxygen rather than passing the electron through the bound metal ion. Furthermore, these results provide additional evidence to support the idea that different CAOs use different mechanisms for catalysis.

Alcohol-Induced Interleukin-17 Expression Causes Murine Lung Fibroblast-to-Myofibroblast Transdifferentiation via Thy-1 Down-Regulation.

BACKGROUND: Alcohol exposure induces TGFß1 and renders the lung susceptible to injury and disrepair. We determined that TGFß1 regulates myofibroblast differentiation through the loss of Thy-1 expression and consequent induction of α-SMA. TGFß1 is important for T helper 17 (Th17) differentiation and IL-17 secretion, which in turn participates in tissue repair. We hypothesized that alcohol induces Th17 differentiation via TGFß1 and that IL-17 produced by these cells contributes to the development of profibrotic lung myofibroblasts. METHODS: Primary lung fibroblasts (PLFs) were treated with alcohol, TGFß1, and IL-17 and then analyzed for Thy-1 expression and cell morphology. Naïve and Th17-polarized CD4+ T cells were exposed to alcohol and assessed for IL-17 expression. CD4+ T cells from alcohol-fed mice were analyzed for Th17 and IL-17 expression. Lungs of control-fed, bleomycin-treated and alcohol-fed, bleomycin-treated mice were analyzed for IL-17 protein expression. RESULTS: Alcohol-treated PLFs expressed lower levels of Thy-1 than untreated cells. TGFß1 or IL-17 exposure suppressed PLF Thy-1 expression. When administered together, TGFß1 and IL-17 additively down-regulated Thy-1 expression. Exposure of naïve and Th17-polarized CD4+ T cells to alcohol induced the Th17 phenotype and augmented their production of IL-17. CD4+ Th17+ levels are elevated in the peripheral compartment but not in the lungs of alcohol-fed animals. Treatment of the PLFs with IL-17 and alcohol induced α-SMA expression. Induction of α-SMA and myofibroblast morphology by IL-17 occurred selectively in a Thy-1- fibroblast subpopulation. Chronic alcohol ingestion augmented lung-specific IL-17 expression following bleomycin-induced lung injury. CONCLUSIONS: Alcohol exposure skews T cells toward a Th17 immune response that in turn primes the lung for fibroproliferative disrepair through loss of Thy-1 expression and induction of myofibroblast differentiation. These effects suggest that IL-17 and TGFß1 contribute to fibroproliferative disrepair in the lung and targeting these proteins could limit morbidity and mortality following lung injury in alcoholic individuals.

Correlates of nonadherence to key population-led HIV pre-exposure prophylaxis services among Thai men who have sex with men and transgender women.

BACKGROUND: Based on government estimates from the Asian Epidemic Model, new infections among men who have sex with men (MSM) and transgender women (TGW) in Thailand are forecast to proportionally increase over time. Daily oral Pre-exposure prophylaxis (PrEP) protects against HIV acquisition when used as prescribed. The "Princess PrEP" program is the first key population-led (PrEP) initiative under Thai royal patronage with an aim to scale up countrywide implementation of PrEP. METHODS: Retention in and adherence to key population-led HIV PrEP services among HIV-uninfected Thai MSM and TGW was examined in four provinces: Bangkok, Chonburi, Chiang Mai, and Songkhla. HIV, HBsAg, creatinine tests, and self-administered questionnaires were performed during baseline measures. Participants were followed up after month 1, at month 3, then every 3 months. Correlates of nonadherence and loss to follow up at 1 month were assessed using linear regression models. RESULTS: 37.4% of the participants reported low adherence to services (≤ 3 pills/week or missed clinic schedule at month 1). Factors associated with low adherence included younger age (25 years and under) (adjusted odds ratio (aOR): 1.49, 95% confidence interval (95% CI: 1.01-2.21, p = 0.044), being a TGW (aOR: 2.2, 95% CI: 1.27-3.83, p = 0.005), and whether the participant had not previously accessed services at the clinic (aOR = 1.68, 95% CI: 1.03-2.76, p = 0.04). Additionally, participants in Chonburi (the only TGW site) showed significantly lower adherence than those in the other three provinces (aOR: 2.91, 95% CI: 1.55-5.45, p = 0.001). CONCLUSION: Urgent, innovative interventions for early PrEP adherence support among vulnerable sub-populations such as younger users, TGW, and new clients are needed to maximize prevention strategy in Thailand.

MiR-21-Mediated Suppression of Smad7 Induces TGFß1 and Can Be Inhibited by Activation of Nrf2 in Alcohol-Treated Lung Fibroblasts.

BACKGROUND: We previously demonstrated that chronic alcohol ingestion augments TGFß1 expression in the lung fibroblast and increases the risk of fibroproliferative disrepair in a mouse model of acute lung injury. The effect of alcohol on TGFß1 is mitigated by treatment with sulforaphane (SFP), which can activate nuclear factor (erythroid-derived 2)-like 2 (Nrf2). However, the mechanisms by which alcohol amplifies, or SFP attenuates, TGFß1 expression in the fibroblast are not known. MicroRNA (miR)-21 has been shown to inhibit Smad7, a TGFß1 signaling inhibitor. In this study, we hypothesized that alcohol augments TGFß1 expression through up-regulation of miR-21, which subsequently inhibits Smad7. METHODS: Primary mouse lung fibroblasts were cultured ± alcohol ± SFP and assessed for gene expression of miR-21, and gene and/or protein expression of Nrf2, Nrf2-regulated antioxidant enzymes, Smad7, STAT3, and TGFß1. NIH 3T3 fibroblasts were transfected with a miR-21 inhibitor and cultured ± alcohol. α-SMA, Smad7, and TGFß1 protein expression were then assessed. In parallel, NIH 3T3 lung fibroblasts were transfected with Nrf2 silencing RNA (siRNA) and cultured ± alcohol ± SFP. Gene expression of miR-21, Nrf2, Smad7, and TGFß1 was assessed. RESULTS: MiR-21 gene expression was increased by 12-fold at 48 hours, and Smad7 gene expression and protein expression were reduced by ~30% in alcohol-treated fibroblasts. In parallel, inhibition of miR-21 attenuated alcohol-mediated decrease in Smad7 and increase in TGFß1 and α-SMA protein expression. Treatment with SFP mitigated the effect of alcohol on miR-21, Smad7 and total and phosphorylated STAT3, and restored Nrf2-regulated antioxidant gene expression. Silencing of Nrf2 prevented the effect of SFP on miR-21, Smad7, and TGFß1 gene expression in alcohol-treated NIH 3T3 fibroblasts. CONCLUSIONS: Alcohol treatment increases TGFß1 in fibroblasts, at least in part, through augmentation of miR-21, which then inhibits Smad7 expression. These effects can be attenuated by activation of Nrf2 with SFP.