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Atrial Natriuretic Peptide (ANP) plays an important role in blood pressure regulation. Low levels of ANP correlate with the development of salt-sensitive hypertension (SS-HTN). Our previous studies indicated that ANP deficiency exacerbated renal function decline in SS-HTN. In the heart and fat tissue, ANP was reported to affect lipid peroxidation and mitochondrial bioenergetics but the effects of ANP on mitochondrial function in the kidney are unexplored. We hypothesized that ANP deficiency in SS-HTN causes renal bioenergetic shift, leading to disruption of mitochondrial network and oxidative stress. To address the hypothesis, we placed Dahl SS wild-type (SSWT) and ANP knockout (SSNPPA-/-) rats on 4% NaCl high salt (HS) diet to induce HTN or maintained them on 0.4% NaCl normal salt (NS) diet and assessed mitochondrial bioenergetics and dynamics using spectrofluorimetry, Seahorse assay, electron paramagnetic resonance (EPR) spectroscopy, Western blotting, electron microscopy, PCR and cytokine assays. We report that under high salt conditions, associated with hypertension and renal damage, the SSNPPA-/- rats exhibit a decrease in mitochondrial membrane potential and elevation in mitochondrial ROS levels compared to SSWT. The redox shift is also evident by the presence of more pronounced medullar lipid peroxidation in the SSNPPA-/- strain. We also revealed fragmented, more damaged mitochondria in the SSNPPA-/- rats, accompanied by increased turnover and biogenesis. Overall, our data indicate that ANP deficiency causes disruptions in mitochondrial bioenergetics and dynamics which likely contributes to aggravation of the renal damage and hypertension in the Dahl SS rat; the major pathological effects are evident in the groups subjected to a combined salt and ANP deficiency-induced mitochondrial stress.
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Factor Natriurético Atrial , Metabolismo Energético , Hipertensión , Mitocondrias , Ratas Endogámicas Dahl , Animales , Factor Natriurético Atrial/metabolismo , Mitocondrias/metabolismo , Ratas , Hipertensión/metabolismo , Hipertensión/etiología , Hipertensión/patología , Masculino , Estrés Oxidativo , Corteza Renal/metabolismo , Corteza Renal/patología , Cloruro de Sodio Dietético/efectos adversosRESUMEN
The aesthetic preferences of potential mates have driven the evolution of a baffling diversity of elaborate ornaments. Which fitness benefit-if any-choosers gain from expressing such preferences is controversial, however. Here, we simulate the evolution of preferences for multiple ornament types (e.g., "Fisherian," "handicap," and "indicator" ornaments) that differ in their associations with genes for attractiveness and other components of fitness. We model the costs of preference expression in a biologically plausible way, which decouples costly mate search from cost-free preferences. Ornaments of all types evolved in our model, but their occurrence was far from random. Females typically preferred ornaments that carried information about a male's quality, defined here as his ability to acquire and metabolize resources. Highly salient ornaments, which key into preexisting perceptual biases, were also more likely to evolve. When males expressed quality-dependent ornaments, females invested readily in costly mate search to locate preferred males. In contrast, the genetic benefits associated with purely arbitrary ornaments were insufficient to sustain highly costly mate search. Arbitrary ornaments could nonetheless "piggyback" on mate-search effort favored by other, quality-dependent ornaments. We further show that the potential to produce attractive male offspring ("sexy sons") can be as important as producing offspring of high general quality ("good genes") in shaping female preferences, even when preferred ornaments are quality dependent. Our model highlights the importance of mate-search effort as a driver of aesthetic coevolution.
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Evolución Biológica , Aptitud Genética , Preferencia en el Apareamiento Animal , Selección Sexual , Animales , Femenino , MasculinoRESUMEN
Allylsilanes can be regioselectively transformed into the corresponding 3-silylfluorohydrin in good yield using a sequence of epoxidation followed by treatment with HF·Et3N with or without isolation of the intermediate epoxide. Various silicon-substitutions are tolerated, resulting in a range of 2-fluoro-3-silylpropan-1-ol products from this method. Whereas other fluorohydrin syntheses by epoxide opening using HF·Et3N generally require more forcing conditions (e.g., higher reaction temperature), opening of allylsilane-derived epoxides with this reagent occurs at room temperature. We attribute this rate acceleration along with the observed regioselectivity to a ß-silyl effect that stabilizes a proposed cationic intermediate. The use of enantioenriched epoxides indicates that both SN1- and SN2-type mechanisms may be operable depending on substitution at silicon. Conformational analysis by NMR and theory along with a crystal structure obtained by X-ray diffraction points to a preference for silicon and fluorine to be proximal to one another in the products, perhaps favored due to electrostatic interactions.
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BACKGROUND: Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity that causes progressive constriction of the cheeks and mouth accompanied by severe pain and reduced mouth opening. OSF has a significant impact on eating and swallowing, affecting quality of life. There is an increased risk of oral malignancy in people with OSF. The main risk factor for OSF is areca nut chewing, and the mainstay of treatment has been behavioural interventions to support habit cessation. This review is an update of a version last published in 2008. OBJECTIVES: To evaluate the benefits and harms of interventions for the management of oral submucous fibrosis. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 5 September 2022. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) of adults with a biopsy-confirmed diagnosis of OSF treated with systemic, locally delivered or topical drugs at any dosage, duration or delivery method compared against placebo or each other. We considered surgical procedures compared against other treatments or no active intervention. We also considered other interventions such as physiotherapy, ultrasound or alternative therapies. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. participant-reported resumption of normal eating, chewing and speech; 2. change or improvement in maximal mouth opening (interincisal distance); 3. improvement in range of jaw movement; 4. change in severity of oral/mucosal burning pain/sensation; 5. ADVERSE EFFECTS: Our secondary outcomes were 6. quality of life; 7. postoperative discomfort or pain as a result of the intervention; 8. participant satisfaction; 9. hospital admission; 10. direct costs of medication, hospital bed days and any associated inpatient costs for the surgical interventions. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included 30 RCTs (2176 participants) in this updated review. We assessed one study at low risk of bias, five studies at unclear risk of bias and 24 studies at high risk of bias. We found diverse interventions, which we categorised according to putative mechanism of action. We present below our main findings for the comparison 'any intervention compared with placebo or no active treatment' (though most trials included habit cessation for all participants). Results for head-to-head comparisons of active interventions are presented in full in the main review. Any intervention versus placebo or no active treatment Participant-reported resumption of normal eating, chewing and speech No studies reported this outcome. Interincisal distance Antioxidants may increase mouth opening (indicated by interincisal distance (mm)) when measured at less than three months (mean difference (MD) 3.11 mm, 95% confidence interval (CI) 0.46 to 5.77; 2 studies, 520 participants; low-certainty evidence), and probably increase mouth opening slightly at three to six months (MD 8.83 mm, 95% CI 8.22 to 9.45; 3 studies, 620 participants; moderate-certainty evidence). Antioxidants may make no difference to interincisal distance at six-month follow-up or greater (MD -1.41 mm, 95% CI -5.74 to 2.92; 1 study, 90 participants; low-certainty evidence). Pentoxifylline may increase mouth opening slightly (MD 1.80 mm, 95% CI 1.02 to 2.58; 1 study, 106 participants; low-certainty evidence). However, it should be noted that these results are all less than 10 mm, which could be considered the minimal change that is meaningful to someone with oral submucous fibrosis. The evidence was very uncertain for all other interventions compared to placebo or no active treatment (intralesional dexamethasone injections, pentoxifylline, hydrocortisone plus hyaluronidase, physiotherapy). Burning sensation Antioxidants probably reduce burning sensation visual analogue scale (VAS) scores at less than three months (MD -30.92 mm, 95% CI -31.57 to -30.27; 1 study, 400 participants; moderate-certainty evidence), at three to six months (MD -70.82 mm, 95% CI -94.39 to -47.25; 2 studies, 500 participants; moderate-certainty evidence) and at more than six months (MD -27.60 mm, 95% CI -36.21 to -18.99; 1 study, 90 participants; moderate-certainty evidence). The evidence was very uncertain for the other interventions that were compared to placebo and measured burning sensation (intralesional dexamethasone, vasodilators). Adverse effects Fifteen studies reported adverse effects as an outcome. Six of these studies found no adverse effects. One study evaluating abdominal dermal fat graft reported serious adverse effects resulting in prolonged hospital stay for 3/30 participants. There were mild and transient general adverse effects to systemic drugs, such as dyspepsia, abdominal pain and bloating, gastritis and nausea, in studies evaluating vasodilators and antioxidants in particular. AUTHORS' CONCLUSIONS: We found moderate-certainty evidence that antioxidants administered systemically probably improve mouth opening slightly at three to six months and improve burning sensation VAS scores up to and beyond six months. We found only low/very low-certainty evidence for all other comparisons and outcomes. There was insufficient evidence to make an informed judgement about potential adverse effects associated with any of these treatments. There was insufficient evidence to support or refute the effectiveness of the other interventions tested. High-quality, adequately powered intervention trials with a low risk of bias that compare biologically plausible treatments for OSF are needed. It is important that relevant participant-reported outcomes are evaluated.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Fibrosis de la Submucosa Bucal , Pentoxifilina , Adulto , Humanos , Fibrosis de la Submucosa Bucal/terapia , Vasodilatadores , Dolor Abdominal , Antioxidantes , DexametasonaRESUMEN
BACKGROUND: Alternative sources of oral health information are likely to be of benefit to the public, particularly where access to dental services is limited. There is evidence that community pharmacists are willing to advocate for oral health, but it is unclear what is needed to develop this role. OBJECTIVES: The aims of this study were to obtain the views of community pharmacy staff on the frequency and type of oral health conditions they encounter challenges in management and training/research priorities. METHODS: An anonymous online survey targeted pharmacy staff and elicited quantitative data related to the types and frequencies of oral health conditions experienced. Participants were stratified by age, gender, ethnicity, experience and setting. Free text responses allowed participants to detail challenging aspects of patient management, their priorities for service development and future research. Reflexive thematic analysis of free text responses identified key themes. RESULTS: Oral/facial pain and swelling were seen weekly by most respondents, and daily by 28.8%. Other commonly presenting conditions were ulcers, dry-mouth, thrush and denture issues. Challenges in managing oral health conditions included: access to NHS dentistry, awareness of referral pathways, examination/diagnosis and understanding 'Red Flags'. CONCLUSION: Acute and chronic oral health conditions commonly present to community pharmacists who lack necessary knowledge/training, which may result in missing 'red flag' symptoms for oral cancer or acute facial swellings which can be life threatening. There is a need to support pharmacists, who are willing to act as oral health advocates, in recognition, prevention and onward referral for oral diseases.
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Servicios Comunitarios de Farmacia , Enfermedades de la Boca , Humanos , Farmacéuticos , Salud Bucal , Actitud del Personal de Salud , Encuestas y Cuestionarios , Enfermedades de la Boca/prevención & controlRESUMEN
PURPOSE: Our aim was to determine if the AUA-recommended prophylaxis (vancomycin + gentamicin alone) for primary inflatable penile prosthesis surgery is associated with a higher infection risk than nonstandard regimens. MATERIALS AND METHODS: We performed a multicenter, retrospective study of patients undergoing primary inflatable penile prosthesis surgery. Patients were divided into those receiving vancomycin + gentamicin alone and those receiving any other regimen. A Cox proportional-hazards model was constructed adjusted for major predictors. A subgroup analysis to identify the appropriate dosage of gentamicin was also performed. RESULTS: A total of 4,161 patients underwent primary inflatable penile prosthesis placement (2,411 received vancomycin + gentamicin alone and 1,750 received other regimens). The infection rate was similar between groups, 1% vs 1.2% for standard vs nonstandard prophylaxis. In the multivariable analysis, vancomycin + gentamicin (HR: 2.7, 95% CI: 1.4 to 5.4, P = .004) and diabetes (HR: 1.9, 95% CI: 1.03 to 3.4, P = .04) were significantly associated with a higher risk of infection. Antifungals (HR: 0.08, 95% CI: 0.03 to 0.19, P < .001) were associated with lower risk of infection. There was no statistically significant difference in infection rate between weight-based gentamicin compared to 80 mg gentamicin (HR: 2.9, 95% CI: 0.83 to 10, P = .1). CONCLUSIONS: Vancomycin + gentamicin alone for antibiotic prophylaxis for primary inflatable penile prosthesis surgery is associated with a higher infection risk than nonstandard antibiotic regimens while antifungal use is associated with lower infection risk. A critical review of the recommended antimicrobial prophylactic regimens is needed. Prospective research is needed to further elucidate best practices in inflatable penile prosthesis antimicrobial prophylaxis.
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Disfunción Eréctil , Implantación de Pene , Prótesis de Pene , Masculino , Humanos , Profilaxis Antibiótica , Vancomicina/uso terapéutico , Estudios Retrospectivos , Estudios Prospectivos , Complicaciones Posoperatorias/cirugía , Prótesis de Pene/efectos adversos , Gentamicinas/uso terapéutico , Disfunción Eréctil/cirugía , Estudios Multicéntricos como AsuntoRESUMEN
A novel mode-hop-free (MHF) tunable external cavity diode laser (ECDL) is demonstrated without mechanical pivot-point tuning. By corotating a periscope with an etalon and a narrow band pass (NBP) filter inside an external cavity, the cavity single longitudinal mode selection can be maintained, and continuous tuning can be achieved with optimal synchronization. A MHF continuous tuning range of 1.7 THz has been achieved with a semiconductor gain chip at the wavelength of 652 ± 2â nm experimentally, and the theoretical tuning range can reach over 4.8 THz. The laser linewidth is estimated to be less than 1â MHz (FWHM) by a scanning Fabry-Perot (F-P) and a Michelson interferometer. 1â mW output power with variation of less than 10% in the tuning region of roughly 1.7 THz has been demonstrated.
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We investigated the determinants of daily PrEP use and coverage of condomless anal sex (CAS) by PrEP among men who have sex with men in Wales, UK. We measured PrEP use by electronic monitors and CAS by secure online surveys. We defined PrEP use based on daily medication cap openings and coverage as CAS episodes preceded by ≥ 3 days of PrEP use and followed by ≥ 2 days of PrEP use. We included 57 participants (5463 observations). An STI diagnosis was associated with lower PrEP use but also lower PrEP coverage. Older adults had higher PrEP use. A belief that other PrEP users took PrEP as prescribed was associated with lower PrEP coverage. An STI diagnosis is an important cue for an intervention, reflecting episodes of high-risk sexual behaviour and low PrEP coverage. Other results provide a basis for the development of an evidence-informed intervention for promoting coverage of PrEP.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Masculino , Humanos , Anciano , Homosexualidad Masculina/psicología , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Gales/epidemiología , Conducta Sexual , Profilaxis Pre-Exposición/métodos , Fármacos Anti-VIH/uso terapéutico , Cumplimiento de la MedicaciónRESUMEN
Stigma may influence the use of HIV pre-exposure prophylaxis (PrEP). However, there is an absence of robust measures for PrEP-related stigma. We describe an adaptation of a HIV stigma scale for use in PrEP users and experiences of PrEP users in Wales (UK) with regards to PrEP-related stigma. A mixed methods study was conducted where PrEP users completed questionnaire items about PrEP-related stigma and a subset were interviewed about their experiences of taking PrEP. We adapted items from the HIV stigma scale and assessed construct validity and internal consistency. We analysed interview data using a framework approach, with themes focussing on enacted and anticipated stigma in order to identify areas for scale refinement. Our measure had good psychometric properties but additional items may be useful (e.g. specific instances of enacted stigma, concerns around homonegativity). Further work is needed to develop this scale and validate it in a larger sample.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Profilaxis Pre-Exposición/métodos , Psicometría , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéuticoRESUMEN
BACKGROUND: Although adolescent basketballers differ in body size, shape, and composition, less is known about how these factors interact during physical development. AIM: We used ontogenetic allometry to identify the optimal body size and shape characteristics associated with physical performance in adolescent basketball players, and investigated the effects of training experience, training volume, maturity status, and club characteristics on physical performance development. SUBJECTS AND METHODS: Two hundred and sixty-four male basketballers, from five age-cohorts (11-15 years of age), were followed consecutively over three years. Three physical performance components, anthropometrics, training information, and biological maturation were assessed bi-annually. Longitudinal multiplicative allometric models were developed. RESULTS: Players with a physique that had a dominant ectomorphic component performed better in all physical performance components. When adjusting for confounders other than size, the development of running speed was independent of body size. Players advanced in maturation were physically fitter. Training data had no significant effect on developmental trajectories of running speed or lower body explosive strength. Club characteristics had no significant association with any physical performance trajectories. CONCLUSION: Leaner players have advantages in physical performance and individual characteristics play an important role, over and beyond club structure, in developing physical performance.
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Rendimiento Atlético , Baloncesto , Humanos , Masculino , Adolescente , Niño , Tamaño Corporal , Antropometría , Rendimiento Físico FuncionalRESUMEN
Recent spinal cord literature abounds with descriptions of genetic preprogramming and the molecular control of circuit formation. In this paper, we explore to what extent circuit formation based on learning rather than preprogramming could explain the selective formation of the monosynaptic projections between muscle spindle primary afferents and homonymous motoneurons. We adjusted the initially randomized gains in the neural network according to a Hebbian plasticity rule while exercising the model system with spontaneous muscle activity patterns similar to those observed during early fetal development. Normal connectivity patterns developed only when we modeled ß motoneurons, which are known to innervate both intrafusal and extrafusal muscle fibers in vertebrate muscles but were not considered in previous literature regarding selective formation of these synapses in animals with paralyzed muscles. It was also helpful to correctly model the greatly reduced contractility of extrafusal muscle fibers during early development. Stronger and more coordinated muscle activity patterns such as observed later during neonatal locomotion impaired projection selectivity. These findings imply a generic functionality of a musculoskeletal system to imprint important aspects of its mechanical dynamics onto a neural network, without specific preprogramming other than setting a critical period for the formation and maturation of this general pattern of connectivity. Such functionality would facilitate the successful evolution of new species with altered musculoskeletal anatomy, and it may help to explain patterns of connectivity and associated reflexes that appear during abnormal development.NEW & NOTEWORTHY A novel model of self-organization of early spinal circuitry based on a biologically realistic plant, sensors, and neuronal plasticity in conjunction with empirical observations of fetal development. Without explicit need for guiding genetic rules, connection matrices emerge that support functional self-organization of the mature pattern of Ia to motoneuron connectivity in the spinal circuitry.
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Neuronas Motoras , Médula Espinal , Animales , Locomoción/fisiología , Neuronas Motoras/fisiología , Husos Musculares , Médula Espinal/fisiología , SinapsisRESUMEN
BACKGROUND: Longitudinal data analysis can improve our understanding of the influences on health trajectories across the life-course. There are a variety of statistical models which can be used, and their fitting and interpretation can be complex, particularly where there is a nonlinear trajectory. Our aim was to provide an accessible guide along with applied examples to using four sophisticated modelling procedures for describing nonlinear growth trajectories. METHODS: This expository paper provides an illustrative guide to summarising nonlinear growth trajectories for repeatedly measured continuous outcomes using (i) linear spline and (ii) natural cubic spline linear mixed-effects (LME) models, (iii) Super Imposition by Translation and Rotation (SITAR) nonlinear mixed effects models, and (iv) latent trajectory models. The underlying model for each approach, their similarities and differences, and their advantages and disadvantages are described. Their application and correct interpretation of their results is illustrated by analysing repeated bone mass measures to characterise bone growth patterns and their sex differences in three cohort studies from the UK, USA, and Canada comprising 8500 individuals and 37,000 measurements from ages 5-40 years. Recommendations for choosing a modelling approach are provided along with a discussion and signposting on further modelling extensions for analysing trajectory exposures and outcomes, and multiple cohorts. RESULTS: Linear and natural cubic spline LME models and SITAR provided similar summary of the mean bone growth trajectory and growth velocity, and the sex differences in growth patterns. Growth velocity (in grams/year) peaked during adolescence, and peaked earlier in females than males e.g., mean age at peak bone mineral content accrual from multicohort SITAR models was 12.2 years in females and 13.9 years in males. Latent trajectory models (with trajectory shapes estimated using a natural cubic spline) identified up to four subgroups of individuals with distinct trajectories throughout adolescence. CONCLUSIONS: LME models with linear and natural cubic splines, SITAR, and latent trajectory models are useful for describing nonlinear growth trajectories, and these methods can be adapted for other complex traits. Choice of method depends on the research aims, complexity of the trajectory, and available data. Scripts and synthetic datasets are provided for readers to replicate trajectory modelling and visualisation using the R statistical computing software.
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Densidad Ósea , Modelos Estadísticos , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Modelos Lineales , Masculino , Rotación , Adulto JovenRESUMEN
This study presents the first part of a mixed-methods exploration of couple sexual communication. Typologies of heterosexual couples in committed, sexual relationships were created for further exploration of group differences in sexual communication. A cluster analysis categorized couples into four different couple typologies: mutually satisfied, satisfied men/dissatisfied women, satisfied women/dissatisfied men, and mutually dissatisfied. Using a MANOVA approach, the couple typologies were used to identify differences in how the couple types communicated about sex. The results revealed significant differences among the differing couple types, which will be explored qualitatively in part two of this analysis.
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Conducta Sexual , Parejas Sexuales , Análisis por Conglomerados , Comunicación , Femenino , Heterosexualidad , Humanos , MasculinoRESUMEN
This study presents the second part of a mixed methods exploration of couple sexual communication. The purpose of this study was to better understand the sexual communication processes that characterize various couple typologies. A qualitative content analysis was used to examine the responses of couples who were grouped together according to the typologies developed from the cluster analysis conducted in Part I of this study (Jones & Lucero Jones, 2022). The results revealed 3 primary themes regarding sexual communication: sexual communication behaviors, sexual decision-making processes, and sexual communication outcomes. Most importantly, the 15 subthemes revealed the inner workings of sexual communication in couples of varying typologies. Clinicians may use the findings from this study to recognize communication patterns in couples that may be contributing to sexual dissatisfaction. Furthermore, the study highlights critical sexual communication behaviors and patterns for improvement and connection in the sexual relationship.
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Conducta Sexual , Parejas Sexuales , Comunicación , Emociones , HumanosRESUMEN
BACKGROUND: Hand-wrist radiography is the gold standard for the assessment of skeletal age (SA) and the assignment of biological maturation (BM) status. However, its practical use in the field is questioned, prompting the development of anthropometric equations to estimate BM. However, there is no consensus on the reliability of these equations in relation to hand-wrist X-rays. OBJECTIVE: To test the reliability of the BM estimated from predictive equations with the results of hand-wrist X-rays. METHODS: One-hundred forty-four young athletes (38%-males, 62%-females; 12.3 ± 1.4 years) were recruited. SA was assessed by analyzing X-rays of the hand-wrist using the Greulich-Pyle protocol. SA was predicted using the anthropometric equations of Cabral and Macêdo. By subtracting chronological age from SA, a measure of BM or biological age (BA) was computed. In addition, a BA of years from peak height velocity (PHV) was predicted using the anthropometric equations of Mirwald and Moore. RESULTS: Relative to X-ray, Cabral's equations showed high reliability in estimating BM in both sexes (p < .0001) while Macêdo's equations showed substantial reliability or males (p < .0001) only. Mirwald and Moore's equations showed weak reliability (p < .05 and p = .043, respectively). CONCLUSION: The prediction of SA using anthropometric equations was found to be reliable in categorizing individuals as late, synchronized, and/or early maturers in both sexes. However, the predictive equations of years from PHV only reliably categorized late and synchronized maturation stages in males and the synchronized maturers in females.
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Determinación de la Edad por el Esqueleto , Muñeca , Determinación de la Edad por el Esqueleto/métodos , Femenino , Humanos , Masculino , Radiografía , Reproducibilidad de los Resultados , Muñeca/diagnóstico por imagen , Rayos XRESUMEN
INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) involves the use of antiretroviral medication in HIV-negative individuals considered to be at risk of acquiring HIV. It has been shown to prevent HIV and has been available in Wales since July 2017. Measuring and understanding adherence to PrEP is complex as it relies on the simultaneous understanding of both PrEP use and sexual activity. We aimed to understand the experiences of men who have sex with men (MSM) living in Wales initiating, implementing and persisting with HIV PrEP. METHODS: We conducted semistructured interviews with MSM PrEP users in Wales who participated in a cohort study of PrEP use and sexual behaviour. Following completion of the cohort study, participants were invited to take part in a semistructured interview about their experiences of taking PrEP. We aimed to include both individuals who had persisted with and discontinued PrEP during the study. The interview topic guide was informed by the ABC taxonomy for medication adherence and the theory of planned behaviour. We analysed our data using reflexive thematic analysis. RESULTS: Twenty-one participants were interviewed, five having discontinued PrEP during the cohort study. The developed themes focused on triggers for initiating PrEP, habitual behaviour, drivers for discontinuation and engagement with sexual health services. Stigma surrounding both PrEP and HIV permeated most topics, acting as a driver for initiating PrEP, an opportunity to reduce discrimination against people living with HIV, but also a concern around the perception of PrEP users. CONCLUSION: This is the first study to investigate PrEP-taking experiences incorporating established medication adherence taxonomy. We highlight key experiences regarding the initiation, implementation and persistence with PrEP and describe how taking PrEP may promote positive engagement with sexual health services. These findings may be useful for informing PrEP rollout programmes and need to be explored in other key populations. PATIENT AND PUBLIC CONTRIBUTION: PrEP users, in addition to PrEP providers and representatives of HIV advocacy and policy, were involved in developing the topic guide for this study.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Fármacos Anti-VIH/uso terapéutico , Estudios de Cohortes , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino , Conducta SexualRESUMEN
We aim to (1) estimate age of attainment of the peak mid-growth spurt in stature (age-at-peak MGS) in pre-adolescent boys and girls; (2) identify the timing, intensity, and sequences of physical fitness (PF) spurts aligned by the age-at-peak MGS; and (3) identify any sex differences in PF spurts aligned by age-at-peak MGS. The sample included 180 Portuguese children (90 girls) aged 6 to 10 years at study entry who were followed annually for 4 years. Height, health-, and performance-related PF were assessed. Age-at-peak MGS and PF spurts were estimated using a non-smooth mathematical procedure. Boys' and girls' age-at-peak MGS occurred at 7.8 ± 0.47 years and 8.0 ± 0.72 years, respectively. PF spurts' timing aligned by age-at-peak MGS were as follows: (1) before age-at-peak MGS: boys - static strength, aerobic capacity, explosive leg strength, and flexibility; girls - speed, agility, aerobic capacity, and upper body strength; (2) coincident with age-at-peak MGS: girls - explosive leg strength and flexibility; (3) after age-at-peak MGS: boys - abdominal strength, upper body strength, agility, and speed; girls - abdominal strength and static strength. Boys and girls attained their MGS at relatively similar ages. However, the timing and sequences of PF spurts, aligned on age-at-MGS, were different between boys and girls.
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Estatura , Aptitud Física , Músculos Abdominales , Adolescente , Niño , Femenino , Humanos , Estudios Longitudinales , MasculinoRESUMEN
BACKGROUND: Good communication is fundamental to provision of information and patient engagement in orthodontic treatment. Images can be used to support verbal and written information, but little is known about how laypeople interpret orthodontic images. OBJECTIVE: To explore laypeople's understanding and preferences for images (clinical photographs and medical illustrations) relating to orthodontic diagnoses and treatments. DESIGN: Cross-sectional survey. SETTING: UK. POPULATION: Laypeople aged ⩾16 years. METHODS: Participants were recruited through social media to complete an online questionnaire containing six pairs of images (clinical photograph and medical illustration) relating to orthodontic diagnoses and treatment. Photographs were selected from a bank with input from laypeople, then a matching medical illustration was created. Images were presented with questions relating to interpretation, preferences and reasons for preferences. RESULTS: A total of 898 people completed the questionnaire. Interpretation of images by laypeople was variable and, in some cases, normal intra-oral features and image orientation caused confusion. A combination of photograph and illustration were preferred for images representing diagnosis (by 41%-50% participants), whereas the illustration alone or both photograph and illustration together was preferred for explaining treatment (43%-48% and 35%-44%, respectively). Photographs were liked for their realism and relatability, while illustrations were often found to be clearer. Arrows aided participants' understanding of the images, but annotations were requested to further improve the value of images. Only 26% of participants reported having previously been shown dental images, but 96% felt they would be helpful to support verbal and written information. CONCLUSION: Laypeople may not interpret orthodontic images in the way that professionals expect, and unfamiliar intra-oral features may distract people from the intended focus of the image. A combination of photographs and illustrations together may improve the usefulness of images, alongside annotation or explanation.
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Estética Dental , Medios de Comunicación Sociales , Anciano , Estudios Transversales , Humanos , Encuestas y CuestionariosRESUMEN
This article discusses three important pieces of work that the Competition and Markets Authority has completed over the last year. The first two are market studies: The Mobile Ecosystems Market Study was launched over concerns that Apple and Google have too much control over operating systems (iOS and Android), app stores (App Store and Play Store), and web browsers (Safari and Chrome) that together form their 'ecosystems'; the Electric Vehicles Charging Market Study took actions and provided recommendations in a nascent but critically important market. The final piece of work is "State of Competition": a research project that assesses the evolution of competition in the UK over the past two decades.
RESUMEN
Invasive candidiasis, mainly caused by Candida albicans, is a serious healthcare problem with high mortality rates, particularly in immunocompromised patients. Innate immune cells express pathogen recognition receptors (PRRs) including C-type lectin-like receptors (CLRs) that bind C. albicans to initiate an immune response. Multiple CLRs including Dectin-1, Dectin-2 and Mincle have been proposed individually to contribute to the immune response to C. albicans. However how these receptors collaborate to clear a fungal infection is unknown. Herein, we used novel multi-CLR knockout (KO) mice to decipher the individual, collaborative and collective roles of Dectin-1, Dectin-2 and Mincle during systemic C. albicans infection. These studies revealed an unappreciated and profound role for CLR co-operation in anti-fungal immunity. The protective effect of multiple CLRs was markedly greater than any single receptor, and was mediated through inflammatory monocytes via recognition and phagocytosis of C. albicans, and production of C. albicans-induced cytokines and chemokines. These CLRs were dispensable for mediating similar responses from neutrophils, likely due to lower expression of these CLRs on neutrophils compared to inflammatory monocytes. Concurrent deletion of Dectin-1 and Dectin-2, or all three CLRs, resulted in dramatically increased susceptibility to systemic C. albicans infection compared to mice lacking a single CLR. Multi-CLR KO mice were unable to control fungal growth due to an inadequate early inflammatory monocyte-mediated response. In response to excessive fungal growth, the multi-CLR KO mice mounted a hyper-inflammatory response, likely leading to multiple organ failure. Thus, these data reveal a critical role for CLR co-operation in the effective control of C. albicans and maintenance of organ function during infection.