Nation-wide surveillance of ticks (Acari: Argasidae) on bats (Chiroptera) in Singapore.

Bats and ticks are important sources of zoonotic pathogens. Therefore, understanding the diversity, distribution, and ecology of both groups is crucial for public health preparedness. Soft ticks (Argasidae) are a major group of ectoparasites commonly associated with bats. The multi-host life cycle of many argasids make them important vectors of pathogens. Over nine years (2011-2020), surveillance was undertaken to identify the ticks associated with common bats in Singapore. During this period, the bat tick Ornithodoros batuensis was detected within populations of two cave roosting bat species: Eonycteris spelaea and Penthetor lucasi. We examined the relationship between bat species, roosting behaviour, and probability of O. batuensis infestation. We also estimated the relationship between bat life history variables (body condition index, sex, and age) on the probability of infestation and tick count. This represents the first detection of O. batuensis and the genus Ornithodoros within Singapore. We also provide evidence of the continued persistence of Argas pusillus in Singapore with the second local record.

Temporal tau asymmetry spectrum influences divergent behavior and language patterns in Alzheimer's disease.

Understanding the psychiatric symptoms of Alzheimer s disease (AD) is crucial for advancing precision medicine and therapeutic strategies. The relationship between AD behavioral symptoms and asymmetry in spatial tau PET patterns is not well-known. Braak tau progression implicates the temporal lobes early. However, the clinical and pathological implications of temporal tau laterality remain unexplored. This cross-sectional study investigated the correlation between temporal tau PET asymmetry and behavior assessed using the neuropsychiatric inventory and composite scores for memory, executive function, and language, using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. In the entire cohort, continuous right and left temporal tau contributions to behavior and cognition were evaluated, controlling for age, sex, education, and tau burden on the contralateral side. Additionally, a temporal tau laterality index was calculated to define "asymmetry-extreme" groups (individuals with laterality indices greater than two standard deviations from the mean). 695 individuals (age = 73.9 ±â€¯7.6 years, 372(53.5 %) females) were included, comprising 281(40 %) cognitively unimpaired (CU) amyloid negative, 185(27 %) CU amyloid positive, and 229(33 %) impaired (CI) amyloid positive participants. In the full cohort analysis, right temporal tau was associated with worse behavior (B = 8.14, p-value = 0.007), and left temporal tau was associated with worse language (B = 1.4, p-value < 0.001). Categorization into asymmetry-extreme groups revealed 20 right- and 27 left-asymmetric participants. Within these extreme groups, there was additional heterogeneity along the anterior-posterior dimension. Asymmetrical tau burden is associated with distinct behavioral and cognitive profiles. Wide multi-cultural implementation of social cognition measures is needed to understand right-sided asymmetry in AD.

Modular Multiwell Viscoelastic Hydrogel Platform for Two- and Three-Dimensional Cell Culture Applications.

Hydrogels have gained significant popularity as model platforms to study reciprocal interactions between cells and their microenvironment. While hydrogel tools to probe many characteristics of the extracellular space have been developed, fabrication approaches remain challenging and time-consuming, limiting multiplexing or widespread adoption. Thus, we have developed a modular fabrication approach to generate distinct hydrogel microenvironments within the same 96-well plate for increased throughput of fabrication as well as integration with existing high-throughput assay technologies. This approach enables in situ hydrogel mechanical characterization and is used to generate both elastic and viscoelastic hydrogels across a range of stiffnesses. Additionally, this fabrication method enabled a 3-fold reduction in polymer and up to an 8-fold reduction in fabrication time required per hydrogel replicate. The feasibility of this platform for two-dimensional (2D) cell culture applications was demonstrated by measuring both population-level and single-cell-level metrics via microplate reader and high-content imaging. Finally, a 96-well hydrogel array was utilized for three-dimensional (3D) cell culture, demonstrating the ability to support high cell viability. Together, this work demonstrates a versatile and easily adaptable fabrication approach that can support the ever-expanding tool kit of hydrogel technologies for cell culture applications.

Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer's disease.

Emerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer's disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly understood. Here, we identify compartment-specific metabolic and inflammatory dysregulations that are induced by HFHC diet in the 5xFAD mouse model of AD pathology. We observe that both male and female 5xFAD mice display exacerbated adiposity, cholesterolemia, and dysregulated insulin signaling. Independent of biological sex, HFHC diet also resulted in altered inflammatory cytokine profiles across the gastrointestinal, circulating, and central nervous systems (CNS) compartments demonstrating region-specific impacts of metabolic inflammation. Interestingly, inhibiting the inflammatory cytokine, soluble tumor necrosis factor (TNF) with the brain-permeant soluble TNF inhibitor XPro1595 was able to restore aspects of HFHC-induced metabolic inflammation, but only in male mice. Targeted transcriptomics of CNS regions revealed that inhibition of soluble TNF was sufficient to alter expression of hippocampal and cortical genes associated with beneficial immune and metabolic responses. Collectively, these results suggest that HFHC diet impairs metabolic and inflammatory pathways in an AD-relevant genotype and that soluble TNF has sex-dependent roles in modulating these pathways across anatomical compartments. Modulation of energy homeostasis and inflammation may provide new therapeutic avenues for AD.

The Acute Effects in Postural Sway as a Result of Self-Myofascial Release on the Lower Extremities in Collegiate Female Athletes.

Myofascial release is a popular therapy technique used to manipulate connective muscle tissue to become more pliable. The maintenance of body posture relies on mechanoreceptors located in connective tissue, thus manipulation of connective tissue should affect postural control. The effects of this phenomenon have not been well studied, leaving room for this investigation. PURPOSE: To observe if postural sway scores changed before and after foam rolling proximal (quadriceps and hamstrings) in comparison to distal (calves) muscles. METHODS: Thirty-six, college-aged female athletes (age 20.39 ± 0.25 years, mass 68.70 ± 1.97 kg, height 170.18 ± 1.56 cm.) performed approximately two and one-half minutes of moderate intensity foam rolling to their calves (n = 19, Group A) or to their hamstrings and quadricep muscle (n = 17, Group B). Center of Pressure (CoP) and Limit of Stability (LoS) testing was assessed both pre- and post-foam rolling using a computerized posturography balance plate. CoP sway was measured under both eyes open (EO) and eye closed (EC) Conditions on both stable and unstable surfaces. LoS was measured in the Anterior, Posterior, Left, and Right Directions. Effects of foam rolling on CoP and LoS were assessed using a repeated-measures MANOVA (α = 0.05). RESULTS: Eyes Open Stable Surface had the lowest postural sway (p = 0.001). However, CoP did not differ for any condition either between Groups (p ≥ 0.6) or from pre- to post-foam rolling (p = 0.3). LoS significantly differed between Directions such that LoS was greater in the frontal plane than in the sagittal plane (p = 0.011). There was also a significant Time X Group X Direction interaction effect (p = 0.001) such that LoS for Group A decreased after foam rolling (mean change = -1.621 cm) but increased for Group B after foam rolling (mean change = + 0.878 cm). No differences were found for any other Direction (p ≥ 0.1). CONCLUSION: This study demonstrated CoP and LoS improvements between the two groups based on acute effects of foam rolling intervention. Further research is suggested to determine if long-term gains are observed within or between groups.

Prevalence, stability, and clinical significance of an isolated low FEV1 spirometry pattern in children.

OBJECTIVES: In adults, an isolated low FEV1 pattern (an FEV1 below the lower limit of normal with a preserved FVC and FEV1/FVC) has been associated with the risk of developing airway obstruction. Our objective was to examine the prevalence, stability, and clinical significance of an isolated low FEV1 pattern in the pediatric population. METHODS: We conducted a retrospective study of spirometries from children ages 6-21 years and categorized tests into spirometry patterns according to published guidelines and recent literature. In a subgroup of tests with an isolated low FEV1 pattern, we evaluated spirometry technique. We also examined the association of having a test with an isolated low FEV1 pattern with clinical markers of disease severity in a subgroup of children with cystic fibrosis (CF). RESULTS: The isolated low FEV1 pattern was uncommon across the 29,979 tests included (n = 645 [2%]). In the 263 children with an isolated low FEV1 pattern who had a follow-up test performed, the most frequent spirometry pattern at last test was normal (n = 123 [47%]). A primary diagnosis of CF was associated with increased odds of having at least one test with an isolated low FEV1 pattern (OR = 8.37, 95% CI = 4.70-15.96, p < .001). The spirometry quality in a subgroup of tests with an isolated low FEV1 pattern (n = 50) was satisfactory. In the subgroup of children with CF (n = 102), those who had a test with an isolated low FEV1 pattern had higher odds of using oral antibiotics in the last 12 months than those who had a normal pattern (OR = 3.50, 95% CI = 1.15-10.63, p = .03). CONCLUSIONS: The isolated low FEV1 pattern can occur repeatedly over time, usually transitions to a normal pattern, is not due to a poor spirometry technique, and could be clinically relevant in children with chronic lung diseases.

Brodifacoum contamination of synthetic cannabinoid causing unexplained coagulopathy in multiple trauma: A case report.

An 18-year-old female presented to the emergency department after a motor vehicle collision. Initial imaging revealed a liver laceration. Subsequent labs showed significantly elevated prothrombin time, international normalized ratio, and activated partial thromboplastin time. Thromboelastography demonstrated a flatline tracing. The patient denied use of anticoagulation but admitted to synthetic cannabinoid use. It was believed the patient had taken synthetic cannabinoid contaminated by brodifacoum. She was therefore given prothrombin complex concentrate and vitamin K with blood products. The patient underwent sequential embolization, laparotomy, thoracotomy, and repair of the vena cava with a shunt. Thirty minutes postoperatively, her coagulation tests and thromboelastography were much improved. Two and a half hours postoperatively, it was determined she had sustained non-survivable injuries. The patient experienced brain death due to prolonged hypotension as a result of hemorrhagic shock with bleeding exacerbated by brodifacoum. To our knowledge, this is the first case reported of a trauma-induced coagulopathy exacerbated by brodifacoum-contaminated synthetic cannabinoid. Her coagulopathy was clearly not due to trauma alone and contributed greatly to the difficulty in controlling hemorrhage. The synthetic cannabinoid-associated coagulopathy rendered her otherwise potentially survivable injuries fatal. Given the frequency of multiple trauma and the recent increase in the prevalence of synthetic cannabinoid, it can be expected that the incidence of trauma complicated by synthetic cannabinoid-associated coagulopathy will increase in the near future. For patients that present with prolonged prothrombin time and/or activated partial thromboplastin time, it is important to inquire about recent synthetic cannabinoid use.

Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer's disease.

Emerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer's disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly understood. Here, we identify compartment-specific metabolic and inflammatory dysregulations that are induced by HFHC diet in the 5xFAD mouse model of AD pathology. We observe that both male and female 5xFAD mice display exacerbated adiposity, cholesterolemia, and dysregulated insulin signaling. Independent of biological sex, HFHC diet also resulted in altered inflammatory cytokine profiles across the gastrointestinal, circulating, and central nervous systems (CNS) compartments demonstrating region-specific impacts of metabolic inflammation. In male mice, we note that HFHC triggered increases in amyloid beta, an observation not seen in female mice. Interestingly, inhibiting the inflammatory cytokine, soluble tumor necrosis factor (TNF) with the brain-permeant soluble TNF inhibitor XPro1595 was able to restore aspects of HFHC-induced metabolic inflammation, but only in male mice. Targeted transcriptomics of CNS regions revealed that inhibition of soluble TNF was sufficient to alter expression of hippocampal and cortical genes associated with beneficial immune and metabolic responses. Collectively, these results suggest that HFHC diet impairs metabolic and inflammatory pathways in an AD-relevant genotype and that soluble TNF has sex-dependent roles in modulating these pathways across anatomical compartments. Modulation of energy homeostasis and inflammation may provide new therapeutic avenues for AD.

Quantifying methane emissions from United States landfills.

Methane emissions from solid waste may represent a substantial fraction of the global anthropogenic budget, but few comprehensive studies exist to assess inventory assumptions. We quantified emissions at hundreds of large landfills across 18 states in the United States between 2016 and 2022 using airborne imaging spectrometers. Spanning 20% of open United States landfills, this represents the most systematic measurement-based study of methane point sources of the waste sector. We detected significant point source emissions at a majority (52%) of these sites, many with emissions persisting over multiple revisits (weeks to years). We compared these against independent contemporaneous in situ airborne observations at 15 landfills and established good agreement. Our findings indicate a need for long-term, synoptic-scale monitoring of landfill emissions in the context of climate change mitigation policy.

Exploring Facilitators and Barriers to Physical Activity for Families of Rural Preschoolers Participating in a Motor Skill Program.

While schools provide one opportunity to encourage physical activity, caregivers play an exceedingly important role in creating an environment conducive to preschool children's physical activity. Yet, little is known regarding the perceptions of caregivers, important choice agents for young children's physical activity behavior after participating in a motor skill program. The purpose of this study was to examine caregivers' perceptions of facilitators and barriers to children's physical activity at home among rural, low-income families who participated in a school-based early childhood physical activity program, SKIPping with PALS, designed to increase physical activity and improve motor development. Eleven caregivers consented to participate in a semi-structured interview regarding their perceptions of physical activity and their experience after six months of participation in the program. An inductive, naturalistic evaluation approach was utilized for qualitative data analysis, following the six recursive phases of thematic analysis. A review of the interview transcripts revealed that all caregivers valued physical activity and encouraged their children to be active. Four major facilitators, four major barriers, and an overarching theme of parental support for childhood physical activity were identified. These factors are largely circumstantial and attitudinal and, thus, are difficult to modify but are important to be cognizant of when designing interventions.

Obesity-associated epigenetic alterations and the obesity-breast cancer axis.

Both breast cancer and obesity can regulate epigenetic changes or be regulated by epigenetic changes. Due to the well-established link between obesity and an increased risk of developing breast cancer, understanding how obesity-mediated epigenetic changes affect breast cancer pathogenesis is critical. Researchers have described how obesity and breast cancer modulate the epigenome individually and synergistically. In this review, the epigenetic alterations that occur in obesity, including DNA methylation, histone, and chromatin modification, accelerated epigenetic age, carcinogenesis, metastasis, and tumor microenvironment modulation, are discussed. Delineating the relationship between obesity and epigenetic regulation is vital to furthering our understanding of breast cancer pathogenesis.

State mechanisms of change in eating disorder symptoms and fears during an online imaginal exposure treatment for eating disorders.

Anxiety and fear are key characteristics of eating disorders (EDs). Exposure therapy is a specific type of intervention aimed at reducing fear and anxiety and is efficacious in treating a variety of anxiety and related disorders. A growing body of research suggests that exposure therapy is also efficacious for the treatment of EDs. However, there is currently little research investigating mechanisms of change during exposure therapy for EDs. The current study (N = 143) expanded on an open series trial of imaginal exposure for EDs that found significant reductions in ED symptoms and core ED fears. In the current study we investigated change in state drive for thinness, body dissatisfaction, and anxiety as mechanisms underpinning change in ED symptoms and core ED fears during four sessions of online imaginal exposure treatment for EDs. We found that state body dissatisfaction, but not state drive for thinness or anxiety, was a mechanism of change for ED symptoms and some core ED fears. Our findings suggest that body dissatisfaction may be a mechanism driving change during exposure therapy for EDs. Optimizing exposure treatments to focus on body dissatisfaction may improve treatment outcomes for EDs.

Pharmacokinetic Modeling to Guide Preclinical Development of an Islatravir-Eluting Reservoir-Style Biodegradable Implant for Long-Acting HIV PrEP.

Long-acting injectable cabotegravir is more effective than daily oral PrEP at preventing HIV transmission due to improved adherence, but requires bi-monthly large-volume intramuscular injections. Subcutaneous (SC) contraceptive implants can be formulated with antiretrovirals for extended-duration HIV PrEP. Islatravir (ISL) is a first-in-class, investigational antiretroviral with pharmacologic properties well-suited for implant delivery. We performed preclinical studies for the development of a reservoir-style, poly(ε-caprolactone) ISL-eluting implant by conducting a single-dose SC ISL dose-ranging pharmacokinetic (PK) study of 0.1, 0.3, and 1 mg/kg in adult Wistar rats. Non-compartmental analysis was conducted, and dose proportionality assessed for ISL plasma and intracellular islatravir-triphosphate (ISL-tp). Population PK models estimated ISL's unit impulse response to deconvolve ISL-implant in vivo absorption rate (mg/day) and cumulative mass (mg) from published rat plasma PK (n = 10). Drug release was interpreted using four kinetic models. Dose proportionality was affirmed for ISL and ISL-tp. A first-order, two-compartment model fitted the SC ISL bolus data. Mean (SD) absorption rate from 0 to 154 days was 0.072 ± 0.024 mg/day, and cumulative mass at 154 days was 8.67 ± 3.22 mg. ISL absorption was well-described by zero-order (r2 = 0.95) and Ritger-Peppas (r2 = 0.98). Our zero-order ISL-release poly(ε-caprolactone) implant is projected to achieve clinical PK above ISL-tp's PrEP efficacy threshold. Continued development for HIV PrEP applications is warranted.

Repeated exposure to physiologically effective doses of contraceptive hormones ethinyl estradiol or levonorgestrel do not alter the reinforcing effects of a brief visual stimulus in ovary-intact rats.

Estradiol and progesterone potentiate and attenuate reward processes, respectively. Despite these well-characterized effects, there is minimal research on the effects of synthetic estrogens (e.g., ethinyl estradiol, or EE) and progestins (e.g., levonorgestrel, or LEVO) contained in clinically-utilized hormonal contraceptives. The present study characterized the separate effects of repeated exposure to EE or LEVO on responding maintained by a reinforcing visual stimulus. Forty ovary-intact female Sprague-Dawley rats received either sesame oil vehicle (n = 16), 0.18 µg/day EE (n = 16), or 0.6 µg/day LEVO (n = 8) subcutaneous injections 30-min before daily one-hour sessions. Rats' responding was maintained by a 30-sec visual stimulus on a Variable Ratio-3 schedule of reinforcement. The day after rats' last session, we determined rats estrous cycle phase via vaginal cytology before sacrifice and subsequently weighing each rat's uterus to further verify the contraceptive hormone manipulation. The visual stimulus functioned as a reinforcer, but neither EE nor LEVO enhanced visual stimulus maintained responding. Estrous cytology was consistent with normal cycling in vehicle rats and halting of normal cycling in EE and LEVO rats. EE increased uterine weights consistent with typical uterotrophic effects observed with estrogens, further confirming the physiological impacts of our EE and LEVO doses. In conclusion, a physiologically effective dose of neither EE nor LEVO did not alter the reinforcing efficacy of a visual stimulus reinforcer. Future research should characterize the effects of hormonal contraceptives on responding maintained by other reinforcer types to determine the generality of the present findings.

Treatment Goals and Preferences of Black Veterans with Chronic Musculoskeletal Pain.

Understanding patient goals and preferences is critical in the context of complex conditions such as chronic pain. This need may be especially pronounced for Black patients, who experience significant health and healthcare disparities. The primary aim of this study was to describe the treatment goals and preferences of Black veterans with chronic musculoskeletal pain who were enrolled in the intervention arm of a randomized controlled trial testing a coaching intervention. In the coaching sessions, participants (n = 106) identified their most important pain-related treatment goals and preferences. Participants' top treatment goals were to improve physical functioning (61%), increase engagement in valued activities (45%), and reduce pain intensity (37%). Most participants (73%) preferred non-pharmacological treatments (eg, physical therapy, exercise, acupuncture, yoga). The 17% of participants who identified medications as a preferred treatment demonstrated higher levels of depression and anxiety compared to those who did not. Approximately 42% and 21% of participants stated a preference to avoid pharmacological and surgical pain treatments, respectively. Black patients with chronic pain prioritize improving physical functioning and pain intensity in service of increasing their engagement in exercise, work, relationships, and leisure activities. Also, in the current study, patients expressed a clear preference for non-pharmacological pain treatments. Future research should investigate ways to improve communication of goals and preferences with providers and facilitate access to non-pharmacological treatments for Black patients with chronic pain. PERSPECTIVE: This article describes the treatment goals and preferences of Black veterans with chronic pain. Most patients prioritized goals to improve physical functioning, pain severity, and participation in valued activities. Patients primarily preferred non-pharmacological treatments. This emphasizes the need for clear communication with Black patients regarding pain-related goals and non-pharmacological treatment options.

Bilateral Vitiligo-Like Depigmentation of Choroid and Retinal Pigment Epithelium Associated with Ipilimumab-Nivolumab Therapy for Metastatic Cutaneous Melanoma.

Introduction: Ipilimumab and nivolumab are checkpoint inhibitors that are known to cause a multitude of inflammatory ocular adverse events. Here we report a patient with poliosis and symptomatic depigmentation of the choroid and retinal pigment epithelium (RPE) associated with checkpoint inhibitor therapy for cutaneous melanoma. Case Presentation: The patient presented with floaters in both eyes and concerns for intraocular metastases of metastatic cutaneous melanoma after 1 month of therapy with ipilimumab and nivolumab. External examination revealed poliosis of her eyebrows and eyelashes. Fundus photography demonstrated multiple 1-3 disc-diameter hypopigmented placoid flat areas in the RPE/choroid exposing underlying choroidal vessels in both eyes. At subsequent evaluation 7 months later (after an additional 6 months of checkpoint inhibitor therapy), the lesions appeared more blanched. Evaluation nearly 20 months after the initial presentation showed no significant changes from her prior visit despite cessation of checkpoint inhibitor therapy for 13 months. Conclusion: Checkpoint inhibitor therapy for cutaneous melanoma metastases can cause depigmentation of the choroid and RPE that must be differentiated from progression of intraocular melanoma.

Diagnosis of Pancreatic Cancer after Cholecystectomy in the Elderly.

BACKGROUND: Previous studies evaluating whether recent cholecystectomy is associated with a pancreas cancer diagnosis are limited. We aimed to examine if cholecystectomy was performed more frequently in the year prior to cancer diagnosis than would be expected in a similar non-cancer population. METHODS: SEER-Medicare linked files were used to identify patients with pancreatic adenocarcinoma. Cancer diagnoses were considered to be "timely" if within 2 months of cholecystectomy or "delayed" if 2-12 months after cholecystectomy. Clinical factors and survival outcomes were compared using chi-square and Kaplan-Meier analyses. RESULTS: Rate of cholecystectomy in the year prior to diagnosis of cancer was 1.9% for the cancer group, compared to .4% in the non-cancer group (OR = 4.7, 95% CI 4.4-5.1). Differences in the cancer vs non-cancer cohorts at the time of cholecystectomy included a higher age (74 vs 70, P < .0001), more males (49.9% vs 41.7%, P < .0001), and more frequent open technique (21.0% vs 9.4%, P < .0001). Acute pancreatitis was nearly twice as common in the cancer cohort (19.1%) vs the non-cancer cohort (10.7%), P < .0001. There were no differences between patients who had a timely diagnosis after cholecystectomy compared to a delayed diagnosis with regard to age, gender, comorbidity index, race, or rural/urban designation. The rates of localized disease and subsequent resection were also similar between the delayed and timely groups. Overall unadjusted survival was no different between timely and delayed diagnoses, P = .96. DISCUSSION: Elderly patients diagnosed with pancreatic adenocarcinoma are more likely to have had a recent cholecystectomy compared to those without.

Low daily oral PrEP adherence and low validity of self-report in a randomized trial among PWID in Ukraine.

BACKGROUND: The efficacy of daily oral pre-exposure prophylaxis (PrEP) in preventing HIV transmission among people who inject drugs (PWID) was demonstrated over a decade ago. However, only a few studies among PWID have since measured PrEP adherence using laboratory markers. METHODS: In this trial, we randomized recently injecting PWID in Kyiv, Ukraine, to receive daily oral TDF/FTC with or without SMS reminders. Enrollment and PrEP initiation took place at an HIV clinic. Subsequent visits at months 1, 3, and 6 were conducted at a community harm reduction center and included a structured interview, adherence counseling, PrEP dispensing, and dried blood spot collection. PrEP adherence was assessed using standard self-reported measures and TDF/FTC biomarkers. RESULTS: A total of 199 PWID (99 SMS, 100 No-SMS) were enrolled, of whom 24 % were women, with a median age of 37. At month 6, 79.4 % (158/199) of participants were retained, with 84 % (133/158) reporting opioid injection and 20 % (31/158) reporting stimulant injection in the past 30 days. 77 % (122/158) reported taking >95 % of PrEP doses in the past month, and 87 % reported taking the last dose within 2 days. Tenofovir diphosphate was detected in 17 % (28/158) of participants, and emtricitabine triphosphate was detected in 25 % (40/158). Only 3 % (5/158) had metabolite levels indicative of consistent PrEP uptake at 4+ doses per week. There was no association between the SMS intervention and TDF/FTC metabolite detection. CONCLUSION: Adherence to daily oral PrEP among actively injecting PWID, without daily supervision or incentives, was extremely low, despite supportive counseling and SMS reminders. We also observed a high rate of discordance between self-report and classification by a validated biomarker of adherence. Given the scarcity of evidence and emerging data suggesting low oral PrEP adherence among PWID, additional implementation studies with TDF/FTC biomarkers are needed to study whether a sufficient level of adherence to daily PrEP is attainable among PWID, especially as long-acting injectable PrEP offers a promising alternative.

Effect of cognitive behavioural therapy and yoga for generalised anxiety disorder on sleep quality in a randomised controlled trial: the role of worry, mindfulness, and perceived stress as mediators.

Sleep disturbances are present in ~65% of individuals with generalised anxiety disorder (GAD). Although both Kundalini yoga (KY) and cognitive behavioural therapy (CBT) are effective treatment options for GAD, little is known about how these treatments compare in improving sleep for GAD and what drives these changes. Accordingly, we examined the effects of CBT, KY, and stress education (SEdu; an attention control condition) on subjective sleep quality (as measured by the Pittsburgh Sleep Quality Index [PSQI] and Insomnia Severity Index [ISI]) in a randomised controlled trial of 226 adults with GAD (mean age 33.37 years; 70% female; 79% White). We hypothesised that both CBT and KY would outperform SEdu in improving sleep disturbances. Three potential mediators of sleep improvement (worry, mindfulness, perceived stress) were also examined. In line with hypotheses, PSQI and ISI scores significantly improved from pre- to post-treatment for all three treatment groups (all p < 0.001, all d > 0.97). However, contrary to predictions, sleep changes were not significantly greater for CBT or KY compared to SEdu. In mediation analyses, within-person deviations in worry, mindfulness, and stress each significantly mediated the effect of time on sleep outcomes. Degree of change in sleep attributable to worry (CBT > KY > SEdu) and perceived stress (CBT, KY > SEdu) was moderated by treatment group. Personalised medicine as well as combined treatment approaches should be studied to help reduce sleep difficulties for patients with GAD who do not respond.