Efficacy and safety of long-acting cabotegravir compared with daily oral tenofovir disoproxil fumarate plus emtricitabine to prevent HIV infection in cisgender men and transgender women who have sex with men 1 year after study unblinding: a secondary analysis of the phase 2b and 3 HPTN 083 randomised controlled trial.

BACKGROUND: Injectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate plus emtricitabine for HIV prevention in two clinical trials. Both trials had the primary aim of establishing the HIV prevention efficacy of long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) compared with tenofovir disoproxil fumarate plus emtricitabine daily oral PrEP. Long-acting PrEP was associated with diagnostic delays and integrase strand-transfer inhibitor (INSTI) resistance. This report presents findings from the first unblinded year of the HIV Prevention Trials Network (HPTN) 083 study. METHODS: The HPTN 083 randomised controlled trial enrolled HIV-uninfected cisgender men and transgender women at elevated HIV risk who have sex with men, from 43 clinical research sites in Africa, Asia, Latin America, and the USA. Inclusion criteria included: a negative HIV serological test at the screening and study entry, undetectable HIV RNA levels within 14 days of study entry, age 18 years or older, overall good health as determined by clinical and laboratory evaluations, and a creatinine clearance of 60 mL/min or higher. Participants were randomly allocated to receive long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP. After study unblinding, participants remained on their original regimen awaiting an extension study. HIV infections were characterised retrospectively at a central laboratory. Here we report the secondary analysis of efficacy and safety for the first unblinded year. The primary outcome was incident HIV infection. Efficacy analyses were done on the modified intention-to-treat population using a Cox regression model. Adverse events were compared across treatment groups and time periods (blinded vs unblinded). This trial is registered with ClinicalTrials.gov, NCT02720094. FINDINGS: Of the 4488 participants who contributed person-time to the blinded analysis, 3290 contributed person-time to the first unblinded year analysis between May 15, 2020, and May 14, 2021. Updated HIV incidence in the blinded phase was 0·41 per 100 person-years for long-acting injectable cabotegravir PrEP and 1·29 per 100 person-years for daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP (hazard ratio [HR] 0·31 [95% CI 0·17-0·58], p=0·0003). HIV incidence in the first unblinded year was 0·82 per 100 person-years for long-acting PrEP and 2·27 per 100 person-years for daily oral PrEP (HR 0·35 [0·18-0·69], p=0·002). Adherence to both study products decreased after study unblinding. Additional infections in the long-acting PrEP group included two with on-time injections; three with one or more delayed injections; two detected with long-acting PrEP reinitiation; and 11 more than 6 months after their last injection. Infection within 6 months of cabotegravir exposure was associated with diagnostic delays and INSTI resistance. Adverse events were generally consistent with previous reports; incident hypertension in the long-acting PrEP group requires further investigation. INTERPRETATION: Long-acting injectable cabotegravir PrEP retained high efficacy for HIV prevention in men and transgender women who have sex with men during the first year of open-label follow-up, with a near-identical HR for HIV risk reduction between long-acting injectable cabotegravir and daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP during the first year after unblinding compared with the blinded period. Extended follow-up further defined the risk period for diagnostic delays and emergence of INSTI resistance. FUNDING: Division of AIDS at the National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and Gilead Sciences.

Efficacy, safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis in transgender women: a secondary analysis of the HPTN 083 trial.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial showed that long-acting injectable cabotegravir was more effective than tenofovir disoproxil fumarate plus emtricitabine in preventing HIV in cisgender men and transgender women who have sex with men. We aimed to characterise the cohort of transgender women included in HPTN 083. METHODS: HPTN 083 is an ongoing, phase 2b/3, randomised, multicentre, double-blind, double-dummy clinical trial done at 43 sites in seven countries (Argentina, Brazil, Peru, the USA, South Africa, Thailand, and Viet Nam). HIV-negative participants were randomly assigned (1:1) to receive injectable cabotegravir or tenofovir disoproxil fumarate plus emtricitabine. The study design and primary outcomes of the blinded phase of HPTN 083 have already been reported. An enrolment minimum of 10% transgender women was set for the trial. Here we characterise the cohort of transgender women enrolled from Dec 6, 2016, to May 14, 2020, when the study was unblinded. We report sociodemographic characteristics, use of gender affirming hormone therapy, and behavioural assessments of the transgender women participants. Laboratory testing and safety evaluations are also reported. The trial is registered at ClinicalTrials.gov, NCT02720094. FINDINGS: HPTN 083 enrolled 570 transgender women (304 tenofovir disoproxil fumarate plus emtricitabine; 266 injectable cabotegravir). Transgender women were primarily from Asia (225 [39%]) and Latin America (205 [36%]); 330 (58%) reported using gender affirming hormone therapy. Intimate partner violence was common (270 [47%] reported emotional abuse and 172 [30%] reported physical abuse) and 323 (57%) reported a history of childhood sexual abuse. 159 (28%) transgender women disagreed that they were at risk for HIV, and 142 (25%) screened positive for depressive symptoms. During study follow-up, incidence of syphilis was 16·25% (95% CI 13·28-19·69), rectal gonorrhoea was 11·66% (9·14-14·66), and chlamydia was 20·61% (17·20-24·49). Frequency of adverse events was similar between the treatment groups. Nine seroconversions occurred among transgender women during the blinded phase of the study (seven in the tenofovir disoproxil fumarate plus emtricitabine group and two in the injectable cabotegravir group); overall incidence was 1·19 per 100 person-years (95% CI 0·54-2·25): 1·80 per 100 person-years (0·73-3·72) in the tenofovir disoproxil fumarate plus emtricitabine group and 0·54 per 100 person-years (0·07-1·95) in the injectable cabotegravir group (hazard ratio 0·34 [95% CI 0·08-1·56]). Cabotegravir concentrations did not differ by gender affirming hormone therapy use. INTERPRETATION: HIV prevention strategies for transgender women cannot be addressed separately from social and structural vulnerabilities. Transgender women were well represented in HPTN 083 and should continue to be prioritised in HIV prevention studies. Our results suggest that injectable cabotegravir is a safe and effective pre-exposure prophylaxis option for transgender women. FUNDING: National Institute of Allergy and Infectious Diseases and ViiV Healthcare.

Influence of Neck Pain, Cervical Extensor Muscle Fatigue, and Manual Therapy on Wrist Proprioception.

OBJECTIVE: The purpose of this study was to examine the effects of submaximal isometric neck muscle fatigue and manual therapy on wrist joint position sense (JPS) within healthy individuals and individuals with subclinical neck pain (SCNP). METHODS: Twelve healthy participants and 12 participants with SCNP were recruited. Each group completed 2 sessions, with 48 hours between sessions. On day 1, both groups performed 2 wrist JPS tests using a robotic device. The tests were separated by a submaximal isometric fatigue protocol for the cervical extensor muscles (CEM). On day 2, both groups performed a wrist JPS test, followed by a cervical treatment consisting of manual therapy (SCNP) or neck rest (20 minutes, control group) and another wrist JPS test. Joint position sense was measured as the participant's ability to recreate a previously presented wrist angle. Each wrist JPS test included 12 targets, 6 into wrist flexion and 6 into wrist extension. Kinematic data from the robot established absolute, variability, and constant error. RESULTS: Absolute error significantly decreased (P = .01) from baseline to post-fatigue in the SCNP group (baseline = 4.48 ± 1.58°; post-fatigue = 3.90 ± 1.45°) and increased in the control group (baseline = 3.12 ± 0.98°; post-fatigue = 3.81 ± 0.90°). The single session of manual cervical treatment significantly decreased absolute error in participants with SCNP (P = .004). CONCLUSION: This study demonstrated that neck pain or fatigue can lead to altered afferent input to the central nervous system and can affect wrist JPS. Our findings demonstrate that acute wrist proprioception may be improved in individuals with SCNP by a single cervical manual therapy session.

Characterization of Human Immunodeficiency Virus (HIV) Infections in Women Who Received Injectable Cabotegravir or Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Prevention: HPTN 084.

BACKGROUND: HIV Prevention Trials Network 084 demonstrated that long-acting injectable cabotegravir (CAB) was superior to daily oral tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) for preventing human immunodeficiency virus (HIV) infection in sub-Saharan African women. This report describes HIV infections that occurred in the trial before unblinding. METHODS: Testing was performed using HIV diagnostic assays, viral load testing, a single-copy RNA assay, and HIV genotyping. Plasma CAB, plasma TFV, and intraerythrocytic TFV-diphosphate concentrations were determined by liquid chromatography-tandem mass spectrometry. RESULTS: Forty HIV infections were identified (CAB arm, 1 baseline infection, 3 incident infections; TDF/FTC arm, 36 incident infections). The incident infections in the CAB arm included 2 with no recent drug exposure and no CAB injections and 1 with delayed injections; in 35 of 36 cases in the TDF/FTC arm, drug concentrations indicated low or no adherence. None of the cases had CAB resistance. Nine women in the TDF/FTC arm had nonnucleoside reverse-transcriptase inhibitor resistance; 1 had the nucleoside reverse-transcriptase inhibitor resistance mutation, M184V. CONCLUSIONS: Almost all incident HIV infections occurred in the setting of unquantifiable or low drug concentrations. CAB resistance was not detected. Transmitted nonnucleoside reverse-transcriptase inhibitor resistance was common; 1 woman may have acquired nucleoside reverse-transcriptase inhibitor resistance from study drug exposure.

Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women.

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).

Regular maintenance appointments after non-surgical scaling and root planing support periodontal health in patients with or without dry mouth: A retrospective study.

OBJECTIVE: Non-surgical scaling and root planing (SRP), as an initial form of periodontal treatment, followed by ongoing periodontal maintenance appointments is necessary to manage periodontal disease and prevent tooth loss. Saliva also has an essential role in oral health though the relationship between low salivary flow and periodontal outcomes has not been extensively investigated. This study determined if patients with dry mouth have similar clinical outcomes as patients without dry mouth when receiving regular periodontal maintenance after SRP. MATERIALS AND METHODS: This is a retrospective study that investigated clinical periodontal outcomes in patients with (n = 34) or without (n = 85) dry mouth who had undergone SRP 1 to 5 years prior and had routine periodontal maintenance. The presence of dry mouth was established based on a patient's unstimulated salivary flow rate. RESULTS: Probing depth for both patients with or without dry mouth was similar between groups and maintained 1 to 5 years following initial SRP. Improved probing depth achieved post-SRP was sustained regardless of dry mouth status. CONCLUSION: Patients with or without dry mouth did not exhibit different probing depths.

Patients undergoing periodontal procedures commonly use dietary supplements: A consideration in the design of intervention trials.

OBJECTIVE: Diet and dietary supplement use are associated with periodontal health while a cause and effect relationship is less clear. Although associations with specific nutrients and supplements suggest a potential benefit to healing of periodontal tissues after periodontal procedures, this study determined if patients undergoing periodontal surgery currently take dietary supplements to gage whether patients may accept use of such supplements as a potential intervention. MATERIALS AND METHODS: Patients who were undergoing implant placement or soft tissue graft surgery completed a questionnaire indicating any dietary supplements they consumed. Patient demographics, such as age, sex, and smoking status, were gathered from patients' charting records. RESULTS: Data on dietary supplement usage were collected from 221 patients. More than half (64.7%) the population surveyed reported using one or more dietary supplements. The most commonly used dietary supplements were vitamin D (31%), multivitamin (28%), and B-complex (17.2%). Females were more likely to be taking calcium, vitamin B12, and magnesium than males. Adults, aged 51 years and older, were more likely to be taking dietary supplements than their younger counterparts. They were also more likely to be taking four or more supplements than those under the age of 50 years. There was no association between supplement use and sex, but when the number of different supplements being used was assessed, females were more likely than males to be taking four or more different supplements. CONCLUSIONS: The majority of the study population is already taking dietary supplements as part of their routine. Based on this study, future studies to determine if supplement usage, potentially at levels higher than current levels of intake, can be used to maintain or promote periodontal health seem highly feasible.

Comparative Performance of Five Commercially Available Serologic Assays To Detect Antibodies to SARS-CoV-2 and Identify Individuals with High Neutralizing Titers.

Accurate serological assays to detect antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) donation. This study compared the performances of commercial enzyme immunoassays (EIAs) with respect to detection of IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAbs). The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) for detection of IgG or total antibodies to SARS-CoV-2 was evaluated using cross-sectional samples from potential CCP donors who had prior molecular confirmation of SARS-CoV-2 infection (n = 214) and samples from prepandemic emergency department patients without SARS-CoV-2 infection (n = 1,099). Of the 214 potential CCP donors, all were sampled >14 days since symptom onset and only a minority (n = 16 [7.5%]) had been hospitalized due to COVID-19; 140 potential CCP donors were tested by all five EIAs and a microneutralization assay. Performed according to the protocols of the manufacturers to detect IgG or total antibodies to SARS-CoV-2, the sensitivity of each EIA ranged from 76.4% to 93.9%, and the specificity of each EIA ranged from 87.0% to 99.6%. Using a nAb titer cutoff value of ≥160 as the reference representing a positive test result (n = 140 CCP donors), the empirical area under the receiver operating curve for each EIA ranged from 0.66 (Roche) to 0.90 (Euroimmun). Commercial EIAs with high diagnostic accuracy to detect SARS-CoV-2 antibodies did not necessarily have high diagnostic accuracy to detect high nAb titers. Some but not all commercial EIAs may be useful in the identification of individuals with high nAb titers among convalescent individuals.

Comparative performance of five commercially available serologic assays to detect antibodies to SARS-CoV-2 and identify individuals with high neutralizing titers.

Accurate serological assays to detect antibodies to SARS-CoV-2 are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for COVID-19 convalescent plasma (CCP) donation. This study compared the performance of commercial enzyme immunoassays (EIAs) to detect IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAb). The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) to detect IgG or total antibodies to SARS-CoV-2 was evaluated from cross-sectional samples of potential CCP donors that had prior molecular confirmation of SARS-CoV-2 infection for sensitivity (n=214) and pre-pandemic emergency department patients for specificity (n=1,102). Of the 214 potential CCP donors, all were sampled >14 days since symptom onset and only a minority had been hospitalized due to COVID-19 (n=16 [7.5%]); 140 potential CCP donors were tested by all five EIAs and a microneutralization assay. When performed according to the manufacturers' protocol to detect IgG or total antibodies to SARS-CoV-2, the sensitivity of each EIA ranged from 76.4% to 93.9%, and the specificity of each EIA ranged from 87.0% to 99.6%. Using a nAb titer cutoff of ≥160 as the reference positive test (n=140 CCP donors), the empirical area under receiver operating curve of each EIA ranged from 0.66 (Roche) to 0.90 (Euroimmun). Commercial EIAs with high diagnostic accuracy to detect SARS-CoV-2 antibodies did not necessarily have high diagnostic accuracy to detect high nAbs. Some but not all commercial EIAs may be useful in the identification of individuals with high nAbs in convalescent individuals.

Increased dairy product consumption as part of a diet and exercise weight management program improves body composition in adolescent females with overweight and obesity-A randomized controlled trial.

BACKGROUND: Exercise can improve body composition in adolescents and adults with overweight/obesity. Consumption of dairy foods, as part of a healthy lifestyle program, can also promote favourable body composition changes in adults with overweight/obesity. However, the few studies examining these combined effects on body composition in adolescents are inconclusive. OBJECTIVE: To determine whether increased dairy product consumption, as part of a lifestyle modification program featuring exercise training and dietary guidance promotes favourable body composition changes in adolescent females with overweight/obesity. METHODS: Fifty-four participants (age: 14.8 ± 2.2y; BMI percentile: 95th ± 6) assigned to three groups completed the study. There were two experimental groups: recommended dairy (RDa; n = 24) and low dairy (LDa; n = 22), and a no-intervention control group (Con; n = 8). RDa and LDa participated in a 12-week, eucaloric, lifestyle modification intervention consisting of mixed-mode exercise (3x/week), and nutritional counselling. RDa was provided 4 servings/day of dairy foods, while LDa and Con maintained habitually low intakes (0-2 servings/day). Body weight/composition, waist/hip circumference, cardiovascular fitness and food intake were assessed at weeks 0 and 12. RESULTS: Weight did not significantly change in any group. RDa significantly decreased fat mass (FM) and increased lean mass (LM) more than LDa and Con (FM: -1.3 ± 2.1 kg, -1.1 ± 2.0 kg, 0.8 ± 1.8 kg; LM: 1.5 ± 1.9 kg, 0.7 ± 1.6 kg, 0.5 ± 1.4 kg, respectively). LDa also significantly decreased FM and increased LM more than Con (P < .005; all interactions). CONCLUSION: The inclusion of dairy foods in the diet of adolescent females with overweight/obesity, as part of a diet and exercise intervention, favourably improves body composition in the absence of weight loss.

Determination of HIV status and identification of incident HIV infections in a large, community-randomized trial: HPTN 071 (PopART).

INTRODUCTION: The HPTN 071 (PopART) trial evaluated the impact of an HIV combination prevention package that included "universal testing and treatment" on HIV incidence in 21 communities in Zambia and South Africa during 2013-2018. The primary study endpoint was based on the results of laboratory-based HIV testing for> 48,000 participants who were followed for up to three years. This report evaluated the performance of HIV assays and algorithms used to determine HIV status and identify incident HIV infections in HPTN 071, and assessed the impact of errors on HIV incidence estimates. METHODS: HIV status was determined using a streamlined, algorithmic approach. A single HIV screening test was performed at centralized laboratories in Zambia and South Africa (all participants, all visits). Additional testing was performed at the HPTN Laboratory Center using antigen/antibody screening tests, a discriminatory test and an HIV RNA test. This testing was performed to investigate cases with discordant test results and confirm incident HIV infections. RESULTS: HIV testing identified 978 seroconverter cases. This included 28 cases where the participant had acute HIV infection at the first HIV-positive visit. Investigations of cases with discordant test results identified cases where there was a participant or sample error (mixups). Seroreverter cases (errors where status changed from HIV infected to HIV uninfected, 0.4% of all cases) were excluded from the primary endpoint analysis. Statistical analysis demonstrated that exclusion of those cases improved the accuracy of HIV incidence estimates. CONCLUSIONS: This report demonstrates that the streamlined, algorithmic approach effectively identified HIV infections in this large cluster-randomized trial. Longitudinal HIV testing (all participants, all visits) and quality control testing provided useful data on the frequency of errors and provided more accurate data for HIV incidence estimates.

Bone structure is largely unchanged in growing male CD-1 mice fed lower levels of vitamin D and calcium than in the AIN-93G diet.

BACKGROUND: Calcium (Ca) and vitamin D (vit D) in the AIN-93G diet may be higher than required for healthy bone development, and mask the potential benefit of a dietary intervention. OBJECTIVE: The objective was to determine if lower levels of Ca and vit D than is present in the AIN-93G diet supports bone development in growing male CD-1 mice. METHODS: Weanling male CD-1 mice were randomized to modified AIN-93G diets containing either 100 (Trial 1) or 400 (Trial 2) IU vit D/kg diet within one of two or three Ca levels (0.35, 0.30, or 0.25% Ca diet in Trial 1 or 0.35% or 0.25% in Trial 2) or the AIN-93G diet (1000 IU/kg vit D and 0.5% Ca) from weaning to 4 months of age (n = 13-15/group). At 2 and 4 months of age, BMD and structural properties of the tibia were analyzed in vivo. Structure of lumbar vertebra 4 (L4) and mandible, and femur strength were assessed ex vivo at age 4 months. RESULTS: There were no differences in tibia, L4, and mandible structure between the AIN-93G diet and the 0.35% Ca groups at either vit D level. A few structure outcomes were compromised with the 0.25 and/or 0.3% Ca diets but there were no differences in femur biomechanical strength compared to AIN-93G group in either Trial. CONCLUSION: At 400 or 100 IU vit D/kg diet, Ca can be lowered to 0.35% without detriment to BMD or bone structure while bone strength is not altered at lower Ca (0.25%) compared to CD-1 mice fed AIN-93G diet. Because of genetic variation in CD-1 mice among different breeding facilities, results in CD-1 mice from other facilities may differ from the present study.

Bone development in growing female mice fed calcium and vitamin D at lower levels than is present in the AIN-93G reference diet.

BACKGROUND: The AIN-93G reference (REF) diet is used to allow the comparison within and between studies of different research groups but its levels of vitamin D (vit D) and calcium (Ca) may be higher than required for healthy bone structure and bone mineral density (BMD). OBJECTIVE: To determine if lower dietary levels of Ca (3.5, 3 or 2.5 g Ca/kg diet) at 1 of 2 levels of vit D (100 or 400 IU/kg diet) supports similar development of bone structure and BMD compared to AIN-93G reference (REF) diet in female CD-1 mice at 2 and 4 months of age. METHODS: Within a trial, weanling female mice (n = 12-15/group) were randomized to 1 of 4 diets until necropsy at 4 months of age: Trial 1: 100 IU vit D/kg + 3.5, 3 or 2.5 g Ca/kg diet or 1000 IU vit D/kg + 5 g Ca/kg diet (REF); and Trial 2: 400 IU vit D/kg + 3.5, 3 or 2.5 g Ca/kg diet or 1000 IU vit D/kg + 5 g/kg diet (REF). At age 2 and 4 months, in vivo bone structure and BMD were assessed using micro-computed tomography (µCT) at the proximal and midpoint tibia. At age 4 months, lumbar vertebra 4 (L4) and mandible structure were analyzed ex vivo, femur strength at midpoint and neck was assessed and serum 25(OH)D3 and PTH were quantified. RESULTS: For Trial 1 (100 IU vit D/kg), there were no differences in tibia structure at age 2 and 4 months nor L4 or mandible structure or femur strength at the midpoint or neck at 4 months of age despite lower serum 25(OH)D3 among all groups compared to REF. For Trial 2 (400 IU vit D/kg), mice fed 2.5 g Ca/kg diet had lower (p < 0.05) Ct.Ar/Tt.Ar and Ct.Th at the tibia midpoint compared to REF. Furthermore, Ct.Th. was greater in REF and 3.5 g Ca/kg diet compared to 2.5 g Ca/kg diet at age 2 but not 4 months of age. At L4, BV/TV was lower (p < 0.05) in the 3 g Ca/kg diet group compared to REF at age 4 months. There were no differences among groups for serum 25(OH)D3 or femur strength at the midpoint or neck. Serum PTH was not elevated compared to REF in either Trial. CONCLUSION: Lowering both dietary vit D (100 IU/kg) and Ca (2.5 g/kg) in AIN-93G diet did not result in differences in bone development of female CD-1 mice at early adulthood. Translational relevance of bone studies conducted using the AIN-93G diet may be affected by its high vit D and Ca content.

Investigation of factors that influence pain experienced and the use of pain medication following periodontal surgery.

AIMS: To determine the relationship between anticipated pain and actual pain experienced following soft tissue grafting or implant surgery; to identify the factors that predict actual pain experienced and the use of pain medication following soft tissue grafting or implant surgery. MATERIALS AND METHODS: Prior to dental implant placement (n = 98) or soft tissue grafting (n = 115) and for seven days following the procedure, patients completed a visual analog scale indicating anticipated or experienced pain, respectively. The use of pain medication and alcohol, and smoking were measured. RESULTS: Actual pain experienced on day 1 was lower (p < .01) than anticipated pain and continued to decrease (p ≤ .01) for each of the 7 consecutive days. Anticipated and actual pain were positively correlated. Increasing age (p < .05), having sedation during the surgery (p < .05), and lower use of pain pills (p < .01) predicted lower pain experienced. Actual pain experienced was a predictor of pain pill use (p < .01). Greater nervousness (p < .01) prior to surgery was a predictor of greater anticipated pain. CONCLUSIONS: Patients anticipated more pain than they actually experienced. Sedation, age and number of pain pills used predicted pain experienced. This trial was registered with clinicaltrials.gov as NCT03064178.

Proposed Sources of Coaching Efficacy: A Meta-Analysis.

Coaching efficacy refers to the extent to which a coach believes that he or she has the capacity to affect the learning and performance of his or her athletes. The purpose of the current study was to empirically synthesize findings across the extant literature to estimate relationships between the proposed sources of coaching efficacy and each of the dimensions of coaching efficacy. A literature search yielded 20 studies and 278 effect size estimates that met the inclusion criteria. The overall relationship between the proposed sources of coaching efficacy and each dimension of coaching efficacy was positive and ranged from small to medium in size. Coach gender and level coached moderated the overall relationship between the proposed sources of coaching efficacy and each of the dimensions of coaching efficacy. Results from this meta-analysis provided some evidence for both the utility of, and possible revisions to, the conceptual model of coaching efficacy.

The Effect of Different Phases of Synchrony on Pain Threshold in a Drumming Task.

Behavioral synchrony has been linked to endorphin activity (Cohen et al., 2010; Sullivan and Rickers, 2013; Sullivan et al., 2014; Tarr et al., 2015, 2016; Weinstein et al., 2016). This has been called the synchrony effect. Synchrony has two dominant phases of movement; in-phase and anti-phase. The majority of research investigating synchrony's effect on endorphin activity has focused on in-phase synchrony following vigorous activities. The only research to investigate the effects of anti-phase synchrony on endorphin activity found that anti-phase synchronized rowing did not produce the synchrony effect (Sullivan et al., 2014). Anti-phase synchrony, however, is counter-intuitive to the sport of rowing and may have interfered with the synchrony effect. This study investigated the effect of anti-phase synchrony on endorphin activity in a different task (i.e., drumming). University students (n = 30) were asked to drum solo and in in-phase and anti-phase pairs for 3 min. Pain threshold was assessed as an indirect indicator of endorphin activity prior to and following the task. Although the in-phase synchrony effect was not found, a repeated measures ANOVA found that there was a significant difference in pain threshold change among the three conditions [F(2,24) = 4.10, = 0.255, p < 0.05). Post hoc t-tests showed that the anti-phase condition had a significantly greater pain threshold change than both the solo and in-phase conditions at p < 0.05. This is the first time that anti-phase synchrony has been shown to produce the synchrony effect. Because anti-phase drumming may have required more attention between partners than in-phase synchrony, it may have affected self-other merging (Tarr et al., 2014). These results support Tarr et al.'s (2014) model that multiple mechanisms account for the effect of synchrony on pain threshold, and suggest that different characteristics of the activity may influence the synchrony effect.

Are Athletes' Doping-Related Attitudes Predicted by Their Perceptions of Coaches' Confrontation Efficacy?

BACKGROUND: The coaching process is complex and dynamic. Coaches are known to affect athlete attitudes indirectly, through athletes' perceptions and interpretations. This process has been verified with a variety of ethical behaviors. OBJECTIVES: The current study investigated the relationships between athletes' perceived doping confrontation efficacy of their coaches and athlete's anti-doping attitudes. METHODS: A sample of athletes (N = 96) completed a version of the Doping Confrontation Efficacy Scale that was modified to assess their perception of their coaches' anti-doping confrontation efficacy, and the PEAS (Performance Enhancing Attitude Scale), which assessed their performance-enhancing attitudes. RESULTS: The results of a multiple linear regression model showed that perceived confrontation efficacy significantly predicted athletes' anti-doping attitudes. Specifically, the factor of efficacy with respect to intimacy was the sole significant predictor. CONCLUSIONS: These results show that a pattern of athletes' interpretation of coaches' values is related to their own attitudes, much like with cheating and sportsmanship. This finding is consistent with the conceptualization of confrontation in general independent of sport.

Lifelong intake of flaxseed or menhaden oil to provide varying n-6 to n-3 PUFA ratios modulate bone microarchitecture during growth, but not after OVX in Sprague-Dawley rats.

SCOPE: Skeletal health is a lifelong process impacted by environmental factors, including nutrient intake. The n-3 source and PUFA ratio affect bone health in growing rats, or following ovariectomy (OVX), but no study has investigated the longitudinal effect of PUFA-supplementation throughout these periods of bone development. METHODS AND RESULTS: One-month-old, Sprague-Dawley rats (n = 98) were randomized to receive one of four diets from 1 through 6 months of age. Diets were modified from AIN-93G to contain a varying amount and source of n-3 (flaxseed versus menhaden oil) to provide an n-6 to n-3 ratio of 10:1 or 5:1. At 3 (prior to SHAM or OVX) and 6 months of age, bone microarchitecture of the tibia was quantified using in vivo micro-computed tomography (SkyScan 1176, Bruker microCT). Providing 5:1 (flaxseed) resulted in lower trabecular thickness and medullary area and greater cortical area fraction during growth compared to diets with a 10:1 PUFA ratio, but many of these differences were not apparent following OVX. CONCLUSION: PUFA-supplementation at levels attainable in human diet modulates some bone structure outcomes during periods of growth, but is not an adequate strategy for the prevention of OVX-induced bone loss in rats.

Oral Health, Nutritional Choices, and Dental Fear and Anxiety.

Oral health is an integral part of overall health. Poor oral health can lead to an increased risk of chronic diseases including diabetes mellitus, cardiovascular disease, and some types of cancer. The etiology of these diseases could be linked to the individual's inability to eat a healthy diet when their dentition is compromised. While periodontal or implant surgery may be necessary to reconstruct tissue around natural teeth or replace missing teeth, respectively, some individuals avoid such interventions because of their associated fear and anxiety. Thus, while the relationship between poor oral health, compromised nutritional choices and fear and anxiety regarding periodontal procedures is not entirely new, this review provides an up-to-date summary of literature addressing aspects of this complex relationship. This review also identifies potential strategies for clinicians to help their patients overcome their fear and anxiety associated with dental treatment, and allow them to seek the care they need.

Improved Pulsed Laser Operation with Engineered Nanomaterials.

The power efficiency of a diode-pumped solid state laser was improved by encasing the Nd:YAG lasing medium with gold nanorod-doped epoxy. Gold nanorods were synthesized with a specific aspect ratio tuned to absorb at the Nd:YAG lasing wavelength of 1064 nm. The surfactant-stabilized nanorods in aqueous solution were then treated with a sequential, two-step functionalization in order to improve nanorod solubility in organic solvents. This process required treating the gold nanorods with a thiol-containing polyethylene glycol (PEG) polymer followed by replacing the PEG-SH polymer with a multidentate thiol containing block copolymer synthesized using RAFT synthesis. With a multidentate polymer, the nanorods were soluble in traditional epoxies that could be used to coat the outside of Nd:YAG rods. By absorbing excess lateral 1064 nm emission, the gold nanorod coating attenuates amplified spontaneous emission (ASE), a parasitic, incoherent process that limits power produced by Q-switch laser designs. Laser power increased by nearly 2-fold with addition of the 1064 nm absorbing gold nanorod coating. Gold nanorod epoxy coatings stand out as attractive materials for attenuating ASE by avoiding the fabrication difficulties of samarium oxide ceramics and the photostability limitations of organic dyes.