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Author(s): Shilpi Khare [1]; Advait S. Nagle [1]; Agnes Biggart [1]; Yin H. Lai [1]; Fang Liang [1]; Lauren C. Davis [1]; S. Whitney Barnes [1]; Casey J. N. Mathison [...]

Although suboptimal bone health has been reported in children and adolescents with low motor competence (LMC), it is not known whether such deficits are present at the time of peak bone mass. We examined the impact of LMC on bone mineral density (BMD) in 1043 participants (484 females) from the Raine Cohort Study. Participants had motor competence assessed using the McCarron Assessment of Neuromuscular Development at 10, 14, and 17 years, and a whole‐body dual‐energy X‐ray absorptiometry (DXA) scan at 20 years. Bone loading from physical activity was estimated from the International Physical Activity Questionnaire at the age of 17 years. The association between LMC and BMD was determined using general linear models that controlled for sex, age, body mass index, vitamin D status, and prior bone loading. Results indicated LMC status (present in 29.6% males and 21.9% females) was associated with a 1.8% to 2.6% decrease in BMD at all load‐bearing bone sites. Assessment by sex showed that the association was mainly in males. Osteogenic potential of physical activity was associated with increased BMD dependent on sex and LMC status, with males with LMC showing a reduced effect from increasing bone loading. As such, although engagement in osteogenic physical activity is associated with BMD, other factors involved in physical activity, eg, diversity, movement quality, may also contribute to BMD differences based upon LMC status. The finding of lower peak bone mass for individuals with LMC may reflect a higher risk of osteoporosis, especially for males; however, further research is required. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

In this paper, we assess the impact of extended reality technologies as they relate to sexual forms of harassment. We begin with a brief history of the nature of sexual harassment itself. We then offer an account of extended reality technologies focusing specifically on psychological and hardware elements most likely to comprise what has been referred to as "the metaverse". Although different forms of virtual spaces exist (i.e., private, semi-private, and public), we focus on public social metaverse spaces. We do this to better explain how the concept of sexual harassment must be adjusted to such spaces and how approaches aimed at mitigating harassment must be sensitive to the type of metaverse spaces users utilize. We then offer a typology of sexual harassment for the metaverse focusing on three distinct forms of sexual harassment: (1) invariant (2) mixed variance or modified and (3) unique or metaverse specific. Although existing normative and legal frameworks may function well with respect to the first and, possibly, second forms of harassment, we argue such frameworks will not helpfully address metaverse-specific harassment. Ultimately, the changing nature of privately owned public spaces (POPS) which metaverses are likely to represent pose distinct ethical and regulatory challenges. [ABSTRACT FROM AUTHOR]

Individuals at risk of Developmental Coordination Disorder (DCD) have low levels of physical activity in childhood due to impaired motor competence; however, physical activity levels in adulthood have not been established. This study sought to determine the impact of DCD risk on physical activity levels in adults using accelerometry measurement. Participants (n = 656) from the Arvo Ylppö Longitudinal Study cohort had their motor competence assessed at the age of five years, and their physical activity quantified via device assessment at the age of 25 years. Between group differences were assessed to differentiate physical activity measures for individuals based on DCD risk status, with general linear modeling performed to control for the effects of sex, body mass index (BMI), and maternal education. Participants at risk of DCD were found to have a lower total number of steps (d = 0.3, p = 0.022) than those not at risk. Statistical modeling indicated that DCD risk status increased time spent in sedentary light activity (β = 0.1, 95% CI 0.02 to 0.3, p = 0.026) and decreased time spent in vigorous physical activity via interaction with BMI (β = 0.04, 95% CI 0.001 to 0.1, p = 0.025). Sensitivity analysis found that visuomotor impairment did not significantly impact physical activity but did increase the role of DCD risk status in some models. This 20‐year‐longitudinal study indicated that DCD risk status continues to negatively impact on levels of physical activity into early adulthood. [ABSTRACT FROM AUTHOR]

Concurrent optical and electrical measurements have been used to characterize the physical phenomena associated with the prebreakdown and flashover behavior of high-voltage alumina ceramic insulator samples having both conventional and unconventional conical geometries. The critical parameters are the threshold voltage for initiating flashover events, the stable interelectrode current-voltage relationship, the luminescence pattern, and the breakdown rate as a function of time. These measurements have revealed that a well-conditioned sample of unconventional conical geometry can have very low, i.e., approaching zero, breakdown rate. Physical explanations of the findings are based on the current understanding of flashover mechanisms and the prediction from simulations using a field plotting technique. Index Terms - Ceramics, conical insulators, flashover, high-voltage, vacuum.

Abstract Background The paper examines the key issues experienced in recruiting and retaining practice involvement in a large complex intervention trial in Australian General Practice. Methods Reflective notes made by research staff and telephone interviews with staff from general practices which expressed interest, took part or withdrew from a trial of a complex general practice intervention. Results Recruitment and retention difficulties were due to factors inherent in the demands and context of general practice, the degree of engagement of primary care organisations (Divisions of General Practice), perceived benefits by practices, the design of the trial and the timing and complexity of data collection. Conclusion There needs to be clearer articulation to practices of the benefits of the research to participants and streamlining of the design and processes of data collection and intervention to fit in with their work practices. Ultimately deeper engagement may require additional funding and ongoing participation through practice research networks. Trial Registration Current Controlled Trials ACTRN12605000788673

The F1FO‐ATP synthase is required for growth and viability of Mycobacterium tuberculosis and is a validated clinical target. A mycobacterium‐specific loop of the enzyme's rotary γ subunit plays a role in the coupling of ATP synthesis within the enzyme complex. We report the discovery of a novel antimycobacterial, termed GaMF1, that targets this γ subunit loop. Biochemical and NMR studies show that GaMF1 inhibits ATP synthase activity by binding to the loop. GaMF1 is bactericidal and is active against multidrug‐ as well as bedaquiline‐resistant strains. Chemistry efforts on the scaffold revealed a dynamic structure activity relationship and delivered analogues with nanomolar potencies. Combining GaMF1 with bedaquiline or novel diarylquinoline analogues showed potentiation without inducing genotoxicity or phenotypic changes in a human embryonic stem cell reporter assay. These results suggest that GaMF1 presents an attractive lead for the discovery of a novel class of anti‐tuberculosis F‐ATP synthase inhibitors. [ABSTRACT FROM AUTHOR]

Aims and objectives: This study aims to explore nurses' perceptions and experiences regarding pressure injuries caused by medical devices and to understand the perceived challenges and barriers nurses face in preventing medical device‐related pressure injuries. Background: Nurses have a responsibility to prevent pressure injuries and play a major role in their prevention. As there has been a lack of research on medical device‐related pressure injuries, not much is known about nurses' perceptions and experiences. This therefore hinders the establishment of effective and efficient interventions in nurses' education and in the practical environment. Design: A descriptive qualitative design was adopted, and the COREQ checklist was employed to report on the current study. Methods: The study was conducted at an acute care hospital in Singapore. Purposive sampling was used, and a total of 21 enrolled and registered nurses who had recent experiences with medical device‐related pressure injuries were recruited between August and December 2018. Face‐to‐face interviews were conducted using a semi‐structured interview guide. A thematic analysis was performed to analyse the qualitative data. Results: Five themes emerged regarding pressure injuries: (1) preventable yet unavoidable, (2) everyone's responsibility, (3) harmonising theory with practice reality, (4) pre‐existing conditions may limit injury prevention and management; and (5) nurses expressed a need for experiential training. Conclusions: The study's findings could be used to develop improvements in nursing practice and policy at acute care hospitals, as well as to improve awareness of medical device‐related pressure injuries among healthcare professionals. Moreover, the findings can also inform future research studies to develop effective evidence‐based practices and improve patient outcomes. Relevance to the clinical practice: This study reveals the unique challenges and dilemmas that nurses face and will help to inform healthcare institutions and management in developing programmes and improving protocols to reduce the incidence rate of pressure injuries caused by medical device. [ABSTRACT FROM AUTHOR]

The goal of this study was to quantify the apicoincisal extent of the proximal contact area (PCA) between the eight maxillary anterior teeth. A total of 140 PCA sites and 160 crown lengths were measured in 20 healthy patients. The percentage ratio of PCA to clinical crown length was computed and defined as the proximal contact area proportion (PCAP). Mean PCA dimensions between central incisors (CI/CI), central and lateral incisors (CI/LI), lateral incisors and canines (LI/CA), and canines and first premolars (CA/PM) were 4.2, 2.9, 2.0, and 1.5 mm, respectively. Mesial mean PCAPs were 41%, 32%, 20%, and 18%, respectively. The paired sample t test demonstrated significant differences between all PCAs (P < .0001), except for CA/PM sites (P = .24). Contact areas, not contact points, were observed between neighboring maxillary anterior teeth. Natural PCAPs emerged as well defined in the maxillary anterior dentition bilaterally. Therefore, PCAPs should be taken into consideration for clinical anterior restorations since they determine the papillary and incisal embrasures. [ABSTRACT FROM AUTHOR]

Two hundred forty interdental papilla sites in 20 healthy patients were investigated. Interdental papilla heights of maxillary anterior teeth were measured from the gingival zenith, along with clinical crown lengths. Percentages of papilla height to crown length were computed and defined as papilla proportion, mesial papilla proportion (MPP), and distal papilla proportion (DPP). Mean interdental papilla heights of maxillary anterior teeth were 4 mm mesially and 4.1 mm distally. Mean MPP was 42% (n = 120), and mean DPP was 43% (n = 120). No significant differences were found between MPP and DPP for maxillary incisors (P ≥.5). Canines demonstrated a trend toward increased distal papilla heights. Papilla proportions were approximately 40% for all tooth groups. A more apical position of distal papilla heights from anterior to posterior teeth, mentioned in the literature, was not confirmed by the present data. [ABSTRACT FROM AUTHOR]

Purpose: The location of the gingival zenith in a medial-lateral position relative to the vertical tooth axis of the maxillary anterior teeth remains to be clearly defined. In addition, the apex of the free gingival margin of the lateral incisor teeth relative to the gingival zeniths of the adjacent proximal teeth remains undetermined. Therefore, this investigation evaluated two clinical parameters: (1) the gingival zenith position (GZP) from the vertical bisected midline (VBM) along the long axis of each individual maxillary anterior tooth; and (2) the gingival zenith level (GZL) of the lateral incisors in an apical-coronal direction relative to the gingival line joining the tangents of the GZP of the adjacent central incisor and canine teeth under healthy conditions. Materials and Methods: A total of 240 sites in 20 healthy patients (13 females, 7 males) with an average age of 27.7 years were evaluated. The inclusion patient criteria were absence of periodontal disease, gingival recession, or gingival hypertrophy as well as teeth without loss of interdental papillae, spacing, crowding, existing restorations, and incisal attrition. GZP dimensions were measured with calibrated digital calipers for each individual tooth and within each tooth group in a medial-lateral direction from the VBM. GZLs were measured in an apical-coronal direction from a tangent line drawn on the diagnostic casts from the GZPs of the adjacent teeth. Results: This study demonstrated that all central incisors displayed a distal GZP from the VBM, with a mean average of 1 mm. Lateral incisors showed a deviation of the gingival zenith by a mean of 0.4 mm. In 97.5% of the canine population, the GZP was centralized along the long axis of the canine. The mean distance of the contour of the gingival margin in an apical-coronal direction of the lateral incisors (GZL) relative to gingival line joining the tangent of the adjacent central and canine GZPs was approximately 1 mm. Conclusion: This investigation revealed a GZP mean value of 1 mm distal from the VBM for the central incisor tooth group. The lateral incisors showed a mean average of 0.4 mm. Thecanine tooth group demonstrated almost no deviations of the GZP from the VBM. The GZL of the lateral incisors relative to the adjacent central incisor and canine teeth were more coronal by approximately 1 mm. These data could be used as reference points during esthetic anterior oral rehabilitation. CLINICAL SIGNIFICANCE The information presented in this article can be clinically applied to reestablish the proper intratooth GZPs of the maxillary anterior teeth during periodontal crown lengthening or root coverage procedures. In addition, the intra-arch gingival level of the lateral incisor gingival zenith relative to the adjacent central and canine teeth can be appropriately established. [ABSTRACT FROM AUTHOR]

Background: The paper examines the key issues experienced in recruiting and retaining practice involvement in a large complex intervention trial in Australian General Practice Methods: Reflective notes made by research staff and telephone interviews with staff from general practices which expressed interest, took part or withdrew from a trial of a complex general practice intervention. Results: Recruitment and retention difficulties were due to factors inherent in the demands and context of general practice, the degree of engagement of primary care organisations (Divisions of General Practice), perceived benefits by practices, the design of the trial and the timing and complexity of data collection, Conclusion: There needs to be clearer articulation to practices of the benefits of the research to participants and streamlining of the design and processes of data collection and intervention to fit in with their work practices. Ultimately deeper engagement may require additional funding and ongoing participation through practice research networks. [ABSTRACT FROM AUTHOR]

Keywords: COVID-19; Infectious diseases; Respiratory tract infections; Thrombosis; Vaccine preventable disease EN COVID-19 Infectious diseases Respiratory tract infections Thrombosis Vaccine preventable disease 19 19 1 07/06/21 20210701 NES 210701 Clinical record A 44-year-old male health care worker presented with fevers, fatigue and head "fogginess" with abdominal discomfort and increased bowel frequency 8 days after receiving his first dose of the COVID-19 vaccine (ChAdOx1-S [recombinant]) (AstraZeneca). VITT should be considered when patients present at day 4-28 after vaccination with unusual site thrombosis: splanchnic and/or central venous sinus thrombosis, or thrombocytopenia (or falling platelets) and markedly elevated D-dimer. It is doctrine in the management of heparin-induced thrombocytopenia that, in addition to immediate cessation of all heparins, a non-heparin anticoagulant is commenced to prevent (further) thrombosis. [Extracted from the article]

Keeping students engaged and motivated during online or class discussion may be challenging. Artificial intelligence has potential to facilitate active learning by enhancing student engagement, motivation, and learning outcomes. The purpose of this study was to develop, test usability of, and explore undergraduate nursing students' perceptions toward the Artificial Intelligence-Teaching Assistant System. The system was developed based on three main components: machine tutor intelligence, a graphical user interface, and a communication connector. They were included in the system to support contextual machine tutoring. A field-testing study design, a mixed-method approach, was utilized with questionnaires and focus group interview. Twenty-one undergraduate nursing students participated in this study, and they interacted with the system for 2 hours following the required activity checklist. The students completed the validated usability questionnaires and then participated in the focus group interview. Descriptive statistics were used to analyze quantitative data, and thematic analysis was used to analyze qualitative data from the focus group interviews. The results showed that the Artificial Intelligence-Teaching Assistant System was user-friendly. Four main themes emerged, namely, functionality, feasibility, artificial unintelligence, and suggested learning modality. However, Artificial Intelligence-Teaching Assistant System functions, user interface, and content can be improved before full implementation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Radium-223 (Ra-223) radioisotope has been reported to increase median survival in bone metastatic prostate carcinoma. The addition of Ra-223 to abiraterone was associated with an increased risk of bone fractures. There has been no comprehensive data for using Ra-223 in veterans who were exposed to Agent Orange (AO+)., Methods: We present a retrospective study of veterans with bone metastatic castration-resistant prostate cancer (CRPC) who received standard doses of Ra-223 and other sequential therapies at US Department of Veterans Affairs Pittsburgh Healthcare System in Pennsylvania from January 2014 to January 2019. Veterans were divided into 2 groups: those who were exposed to Agent Orange (AO+) and those who had no exposure (AO-). Time to study was calculated from the initiation of Ra-223. Time to skeletal-related events (SRE), progression of prostate specific antigen (PSA), bone metastasis, and alkaline phosphatase (ALP) were calculated in months using unpaired t test with 2-tailed P values. Median survival was calculated by Kaplan Meier R log-rank test., Results: There were 34 veterans with bone metastatic CRPC: 17 veterans (50%) were AO+ and 17 veterans (50%) were AO-. The mean age of diagnosis of AO+ veterans was 62 years and 69 years ( P = .005) for AO- veterans (the mean Gleason score 8.2 and 8.0, respectively [ P = .71]). The median number of Ra-223 cycles was 6 (60%). Ten veterans received Ra-223 as first line (29%) and 24 veterans received Ra-223 later (71%). There were 12 SREs with median survival of 15 months. There was no difference in mean time to SRE between AO+ (8 veterans, 10.6 months) and AO- (4 veterans, 10.3 months) ( P = .93). The mean time to PSA progression for AO+ was 5.4 months and AO- was 6.8 months ( P = .28). Mean time to bone progression for AO+ was 7.6 months and AO- was 10.1 months ( P = .16). Mean time to ALP progression for AO+ and AO- was 6.3 months and 8.7 months, respectively ( P = .05). Twenty veterans (58%) had died. Median survival for Ra-223 first was 32 months and for Ra-223 later was 15 months ( P = .14; hazard ratio [HR] 0.48; 95% CI, 0.17-1.3). Median survival for AO+ and AO- veterans was 12 months and 18 months, respectively ( P = .15; HR, 2.0; 95% CI, 0.77-5.0)., Conclusions: There was no statistical difference between AO+ and AO- veterans in terms of time to SRE, PSA, bone and ALP progression, even though there was a trend of shorter duration in AO+ veterans. There was no median survival difference between Ra-223 first vs Ra-223 later as well as between AO+ and AO- but there is a trend of worse survival in AO+ veterans., Competing Interests: Author disclosures A poster was presented at ESMO (European Society of Medical Oncology) meeting in Singapore, November 22–24, 2019. An abstract was published in Annals of Oncology, 30 (suppl 9), November 2019. The authors report no actual or potential conflicts of interest with regard to this article., (Copyright © 2020 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Objectives: Developmental coordination disorder (DCD) compromises bone health purportedly due to lower levels of physical activity. The potential of an exercise intervention to improve bone health parameters in adolescents with DCD has not previously been studied. This study thus aimed to determine the impact of a multimodal exercise intervention on bone health in this population at-risk of secondary osteoporosis., Methods: Twenty-eight adolescents (17 male, 11 female) aged between 12-17 years (M age =14.1) with DCD participated in a twice weekly, 13-week generalised multimodal exercise intervention. Peripheral quantitative computed tomography scans of the tibia (4% and 66%) were performed over a six month period. Generalised estimating equations were used to examine the impact of fitness measures on bone parameters over time., Results: An overall improvement trend was observed for bone health, with significant increases at the 66% tibial site for bone mass (4.12% increase, d cohen =0.23, p=0.010) and cortical area (5.42% increase, η 2 =12.09, p=0.014). Lower body fitness measures were significantly associated with improvements in bone health parameters, tempered by the degree of motor impairment., Conclusion: A multimodal exercise intervention may be effective in improving bone health of adolescents with DCD. Given the impact of motor impairments, gains may be greater over an extended period of study., Competing Interests: The authors have no conflict of interest.

Understanding how bones are innately designed, robustly developed and delicately maintained through intricate anatomical features and physiological processes across the lifespan is vital to inform our assessment of normal bone health, and essential to aid our interpretation of adverse clinical outcomes affecting bone through primary or secondary causes. Accordingly this review serves to introduce new researchers and clinicians engaging with bone and mineral metabolism, and provide a contemporary update for established researchers or clinicians. Specifically, we describe the mechanical and non-mechanical functions of the skeleton; its multidimensional and hierarchical anatomy (macroscopic, microscopic, organic, inorganic, woven and lamellar features); its cellular and hormonal physiology (deterministic and homeostatic processes that govern and regulate bone); and processes of mechanotransduction, modelling, remodelling and degradation that underpin bone adaptation or maladaptation. In addition, we also explore commonly used methods for measuring bone metabolic activity or material features (imaging or biochemical markers) together with their limitations., Competing Interests: The authors have no conflict of interest.

The F 1 F O -ATP synthase is required for growth and viability of Mycobacterium tuberculosis and is a validated clinical target. A mycobacterium-specific loop of the enzyme's rotary γ subunit plays a role in the coupling of ATP synthesis within the enzyme complex. We report the discovery of a novel antimycobacterial, termed GaMF1, that targets this γ subunit loop. Biochemical and NMR studies show that GaMF1 inhibits ATP synthase activity by binding to the loop. GaMF1 is bactericidal and is active against multidrug- as well as bedaquiline-resistant strains. Chemistry efforts on the scaffold revealed a dynamic structure activity relationship and delivered analogues with nanomolar potencies. Combining GaMF1 with bedaquiline or novel diarylquinoline analogues showed potentiation without inducing genotoxicity or phenotypic changes in a human embryonic stem cell reporter assay. These results suggest that GaMF1 presents an attractive lead for the discovery of a novel class of anti-tuberculosis F-ATP synthase inhibitors., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The antiplasmodial activity of a series of spirotetrahydro beta-carbolines is described. Racemic spiroazepineindole (1) was identified from a phenotypic screen on wild type Plasmodium falciparum with an in vitro IC(50) of 90 nM. Structure-activity relationships for the optimization of 1 to compound 20a (IC(50) = 0.2 nM) including the identification of the active 1R,3S enantiomer and elimination of metabolic liabilities is presented. Improvement of the pharmacokinetic profile of the series translated to exceptional oral efficacy in the P. berghei infected malaria mouse model where full cure was achieved in four of five mice with three daily doses of 30 mg/kg.