RESUMEN
Task-specific dystonia leads to loss of sensorimotor control for a particular motor skill. Although focal in nature, it is hugely disabling and can terminate professional careers in musicians. Biomarkers for underlying mechanism and severity are much needed. In this study, we designed a keyboard device that measured the forces generated at all fingertips during individual finger presses. By reliably quantifying overflow to other fingers in the instructed (enslaving) and contralateral hand (mirroring) we explored whether this task could differentiate between musicians with and without dystonia. 20 right-handed professional musicians (11 with dystonia) generated isometric flexion forces with the instructed finger to match 25%, 50% or 75% of maximal voluntary contraction for that finger. Enslaving was estimated as a linear slope of the forces applied across all instructed/uninstructed finger combinations. Musicians with dystonia had a small but robust loss of finger dexterity. There was increased enslaving and mirroring, primarily during use of the symptomatic hand (enslaving p = 0.003; mirroring p = 0.016), and to a lesser extent with the asymptomatic hand (enslaving p = 0.052; mirroring p = 0.062). Increased enslaving and mirroring were seen across all combinations of finger pairs. In addition, enslaving was exaggerated across symptomatic fingers when more than one finger was clinically affected. Task-specific dystonia therefore appears to express along a gradient, most severe in the affected skill with subtle and general motor control dysfunction in the background. Recognition of this provides a more nuanced understanding of the sensorimotor control deficits at play and can inform therapeutic options for this highly disabling disorder.
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Trastornos Distónicos , Dedos , Destreza Motora , Música , Humanos , Dedos/fisiopatología , Dedos/fisiología , Masculino , Adulto , Femenino , Trastornos Distónicos/fisiopatología , Destreza Motora/fisiología , Persona de Mediana Edad , Adulto JovenRESUMEN
This investigation examined whether the mode of locomotion matters in how 8-, 10-, 12-, and 14-year-old children (N = 91) judge dynamic affordances in a complex perception-action task with significant safety risks. The primarily European American children in the sample came from the area of Iowa City, Iowa and were balanced for gender. The same children crossed a single lane of continuous traffic on foot and on bike (order counterbalanced) in identical immersive virtual environments. We found that although 8-year-olds chose significantly larger gaps when crossing on bike than on foot, these gaps were not large enough to compensate for their delay in entering the gap and their slowness in crossing the road. As a result, they ended up with less time to spare when exiting the roadway on bike than on foot. In contrast, 14-year-olds exhibited no difference in their gap choices on bike than on foot, nor did they exhibit a difference in their timing of entry into the gap. However, they crossed the road much more quickly on bike, resulting in significantly more time to spare when crossing on bike than on foot. The 10- and 12-year-olds' performance fit neatly between that of the 8- and 14-year-olds. We conclude that as children gained better control over the bike with age, they were better able to match their gap decisions with their crossing movements such that bicycling afforded even safer road-crossing than walking for 14-year-olds. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Ciclismo , Caminata , Humanos , Niño , Locomoción , Interfaz Usuario-Computador , Factores de EdadRESUMEN
Musician's dystonia presents with a persistent deterioration of motor control during musical performance. A predominant hypothesis has been that this is underpinned by maladaptive neural changes to the somatotopic organization of finger representations within primary somatosensory cortex. Here, we tested this hypothesis by investigating the finger-specific activity patterns in the primary somatosensory and motor cortex using functional MRI and multivariate pattern analysis in nine musicians with dystonia and nine healthy musicians. A purpose-built keyboard device allowed characterization of activity patterns elicited during passive extension and active finger presses of individual fingers. We analysed the data using both traditional spatial analysis and state-of-the art multivariate analyses. Our analysis reveals that digit representations in musicians were poorly captured by spatial analyses. An optimized spatial metric found clear somatotopy but no difference in the spatial geometry between fingers with dystonia. Representational similarity analysis was confirmed as a more reliable technique than all spatial metrics evaluated. Significantly, the dissimilarity architecture was equivalent for musicians with and without dystonia. No expansion or spatial shift of digit representation maps were found in the symptomatic group. Our results therefore indicate that the neural representation of generic finger maps in primary sensorimotor cortex is intact in musician's dystonia. These results speak against the idea that task-specific dystonia is associated with a distorted hand somatotopy and lend weight to an alternative hypothesis that task-specific dystonia is due to a higher-order disruption of skill encoding. Such a formulation can better explain the task-specific deficit and offers alternative inroads for therapeutic interventions.
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Distonía , Trastornos Distónicos , Música , Corteza Sensoriomotora , Humanos , Dedos , Corteza Somatosensorial/diagnóstico por imagenRESUMEN
Ergonomics is the scientific study of people and their working conditions, aiming to improve effectiveness. Improved ergonomics of orthopaedic theatres and equipment would reduce the risk of occupational injury and help to encourage more women into an underrepresented specialty.
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Procedimientos Ortopédicos , Ortopedia , Ergonomía , Femenino , Predicción , HumanosRESUMEN
Following periarterial sympathectomy, patients with recurrent digital ischemia due to vasospastic or vaso-occlusive disease have few remaining treatment options. We performed a retrospective review from 1997 to 2019 to determine the safety and efficacy of revision periarterial sympathectomy. Eleven patients were identified who underwent revision periarterial sympathectomy, performed on average 84 months after their initial procedure. Preoperatively, all patients had worsening ischemic pain and five had non-healing digital ulcers. Revision digital periarterial sympathectomy alone was performed in seven patients, while four had a more extensive sympathectomy. Mean follow-up after revision was 23 months (range 3 to 76). Eight patients had symptomatic improvement and four healed their digital ulcers. Three patients developed new ulcers during follow-up, of which two healed with conservative management and one required three digital amputations. Revision periarterial sympathectomy is effective in providing symptomatic improvement and digital ulcer healing with minimal postoperative complications.Level of evidence: IV.
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Arterias , Isquemia , Dedos/cirugía , Humanos , Isquemia/etiología , Isquemia/cirugía , Estudios Retrospectivos , SimpatectomíaRESUMEN
BACKGROUND: Task specific dystonia (TSD) is a subtype of dystonia with no cure and significant limitations on treatments. Few studies have investigated the outcomes of rehabilitative therapy from the patient's perspective. PURPOSE OF THE STUDY: This study explored the interventions that patients have utilized and their perceived effectiveness in treating and managing their TSD, specifically musicians' dystonia (MD) and writer's dystonia (WD). Symptoms and the effect of TSD on the perceived performance of every day and specific tasks, and possible reasons why the condition developed, were also investigated. STUDY DESIGN: Descriptive survey. METHODS: Patients diagnosed with TSD, treated at a private hand therapy unit, who had consented to being contacted for research purposes, were emailed a link to an online survey (or posted if email was not available), administered via KwikSurveys. The survey consisted of 4 subsections: personal information, general medical history, dystonia medical history and dystonia treatment history. RESULTS: Invitations were sent to 105 patients of whom 90% (n = 95/105) responded. Results for both the MD and WD groups were similar. There was a significant association between the 2 groups as to what they viewed may have led to the development of TSD (a change in technique; P < .001) and the most effective treatments (massage P< .043, modifications to the instrument P< .002; ultrasound therapy P< .013.) All reported that daily activities were affected by their condition. DISCUSSION: Although full levels of task specific function (playing their instrument or writing) were not usually regained, participants with both MD and WD perceived improvement in symptoms with rehabilitation intervention. Three treatments were perceived to be most effective in achieving this, suggesting that these should be considered for inclusion within treatment plans. CONCLUSIONS: From the perspective of people with TSD, a range of rehabilitation interventions are effective in enhancing symptom management, providing further evidence to support their use.
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Distonía , Trastornos Distónicos , Música , Trastornos Distónicos/diagnóstico , Trastornos Distónicos/terapia , HumanosRESUMEN
Thumb carpometacarpal osteoarthritis (CMC OA) is a common pathology of the hand that is characterized by pain, loss of grip and pinch strength, and deformity. Although conservative management is often preferred in earlier stage of CMC OA, surgical techniques can be used when symptoms are not fully relieved, especially with subluxation. We report a case series of 26 patients (32 operations) with Eaton stage I and II CMC OA who underwent a novel surgical technique that anatomically restores the CMC joint with autologous double ligament reconstruction. All cases were retrospectively reviewed as a prospective study and performed at a single regional health system from 2012 to 2016. Preoperative and postoperative radiographs, grip and pinch strength measurements, and DASH scores were collected to evaluate the outcomes. The mean CMC subluxation ratio decreased from 0.59±0.14 to 0.35±0.21 (P<0.0001). The mean grip strength increased from 44.34±17.36 pounds to 52.97±18.92 pounds (P=0.017), and the mean pinch strength increased from 10.16±4.59 pounds to 12.75±4.52 pounds (P=0.00027). The mean DASH scores decreased from 42.32±14.99 to 19.94±14.47 (P<0.0001). The average follow-up period was 39.44±14.94 months. Three patients had postoperative thumb stiffness that resolved with physical therapy. One patient had postoperative pain, attributed to carpal tunnel syndrome. One surgery required revision. All other patients (84.38%) reported significant improvement in pain and the ability to return to previous levels of work. This surgical technique is therefore a feasible option for patients with Eaton stage I or II CMC OA, and should be recommended for wider surgical use.
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Articulaciones Carpometacarpianas , Pulgar , Articulaciones Carpometacarpianas/cirugía , Humanos , Ligamentos , Estudios Prospectivos , Estudios Retrospectivos , Pulgar/cirugíaRESUMEN
COVID-19 has had profound management implications for orthopaedic management due to balancing patient outcomes with clinical safety and limited resources. The BOAST guidelines on outpatient orthopaedic fracture management took a pragmatic approach. At Great Western Hospital, Swindon, a closed loop audit was performed looking at a selection of these guidelines, to assess if our initial changes were sufficient and what could be improved. METHOD: An audit was designed around fracture immobilisation, type of initial fracture clinic assessment, default virtual follow up clinic and late imaging. Interventions were implemented and re-audited. RESULTS: Initially 223 patients were identified over 4 weeks. Of these, 100% had removable casts and 99% did not have late imaging. 96% of patients were initially assessed virtually or had initial orthopaedic approval to be seen in face to face clinic. 97% had virtual follow up or had documented reasons why not. The 26 patients who were initially seen face to face were put through a simulated virtual fracture clinic. 22 appointments and 13 Xray attendances could have been avoided. We implemented a change of requiring all patients to be assessed at consultant level before having a face to face appointment. The re-audit showed over 99% achievement in all areas. CONCLUSION: Virtual fracture clinics, both triaging new patients and follow-up clinics have dramatically changed our outpatient management, helping the most appropriate patients to be seen face to face. Despite their limitations, they have been well tolerated by patients and improved patient safety and treatment.
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COVID-19/prevención & control , Fracturas Óseas/terapia , Ortopedia/organización & administración , Servicio Ambulatorio en Hospital/organización & administración , Telemedicina/organización & administración , Cuidados Posteriores/organización & administración , Cuidados Posteriores/normas , Cuidados Posteriores/estadística & datos numéricos , COVID-19/epidemiología , Control de Enfermedades Transmisibles/normas , Inglaterra , Fijación de Fractura , Fracturas Óseas/diagnóstico , Adhesión a Directriz/estadística & datos numéricos , Implementación de Plan de Salud , Humanos , Auditoría Médica/estadística & datos numéricos , Visita a Consultorio Médico/estadística & datos numéricos , Ortopedia/normas , Ortopedia/estadística & datos numéricos , Servicio Ambulatorio en Hospital/normas , Servicio Ambulatorio en Hospital/estadística & datos numéricos , Pandemias/prevención & control , Seguridad del Paciente , Guías de Práctica Clínica como Asunto , Evaluación de Programas y Proyectos de Salud , Sociedades Médicas/normas , Telemedicina/normas , Telemedicina/estadística & datos numéricos , Resultado del TratamientoRESUMEN
INTRODUCTION: With almost 50% of cases preventable and the Australian National Bowel Cancer Screening Program in place, colorectal cancer (CRC) is a prime candidate for investment to reduce the cancer burden. The challenge is determining effective ways to reduce morbidity and mortality and their implementation through policy and practice. Pathways-Bowel is a multistage programme that aims to identify best-value investment in CRC control by integrating expert and end-user engagement; relevant evidence; modelled interventions to guide future investment; and policy-driven implementation of interventions using evidence-based methods. METHODS AND ANALYSIS: Pathways-Bowel is an iterative work programme incorporating a calibrated and validated CRC natural history model for Australia (Policy1-Bowel) and assessing the health and cost outcomes and resource use of targeted interventions. Experts help identify and prioritise modelled evaluations of changing trends and interventions and critically assess results to advise on their real-world applicability. Where appropriate the results are used to support public policy change and make the case for optimal investment in specific CRC control interventions. Fourteen high-priority evaluations have been modelled or planned, including evaluations of CRC outcomes from the changing prevalence of modifiable exposures, including smoking and body fatness; potential benefits of daily aspirin intake as chemoprevention; increasing CRC incidence in people aged <50 years; increasing screening participation in the general and Aboriginal and Torres Strait Islander populations; alternative screening technologies and modalities; and changes to follow-up surveillance protocols. Pathways-Bowel is a unique, comprehensive approach to evaluating CRC control; no prior body of work has assessed the relative benefits of a variety of interventions across CRC development and progression to produce a list of best-value investments. ETHICS AND DISSEMINATION: Ethics approval was not required as human participants were not involved. Findings are reported in a series of papers in peer-reviewed journals and presented at fora to engage the community and policymakers.
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Neoplasias Colorrectales/prevención & control , Modelos Teóricos , Algoritmos , Australia , Erradicación de la Enfermedad , Detección Precoz del Cáncer , Conductas Relacionadas con la Salud , Promoción de la Salud , Humanos , Prevención PrimariaRESUMEN
This study aimed to determine if having an overweight or obese range body mass index (BMI) at time of beginning school is associated with increased fracture incidence in childhood. A dynamic cohort was created from children presenting for routine preschool primary care screening, collected in the Information System for Research in Primary Care (SIDIAP) platform in Catalonia, Spain. Data were collected from 296 primary care centers representing 74% of the regional pediatric population. A total of 466,997 children (48.6% female) with a validated weight and height measurement within routine health care screening at age 4 years (±6 months) between 2006 and 2013 were included, and followed up to the age of 15, migration out of region, death, or until December 31, 2016. BMI was calculated at age 4 years and classified using WHO growth tables, and fractures were identified using previously validated ICD10 codes in electronic primary care records, divided by anatomical location. Actuarial lifetables were used to calculate cumulative incidence. Cox regression was used to investigate the association of BMI category and fracture risk with adjustment for socioeconomic status, age, sex, and nationality. Median follow-up was 4.90 years (interquartile range [IQR] 2.50 to 7.61). Cumulative incidence of any fracture during childhood was 9.20% (95% confidence interval [CI] 3.79% to 14.61%) for underweight, 10.06% (9.82% to 10.29%) for normal weight, 11.28% (10.22% to 12.35%) for overweight children, and 13.05% (10.69% to 15.41%) for children with obesity. Compared with children of normal range weight, having an overweight and obese range BMI was associated with an excess risk of lower limb fracture (adjusted hazard ratio [HR] = 1.42 [1.26 to 1.59]; 1.74 [1.46 to 2.06], respectively) and upper limb fracture (adjusted HR = 1.10 [1.03 to 1.17]; 1.19 [1.07 to 1.31]). Overall, preschool children with an overweight or obese range BMI had increased incidence of upper and lower limb fractures in childhood compared with contemporaries of normal weight. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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Obesidad , Sobrepeso , Índice de Masa Corporal , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Obesidad/complicaciones , Obesidad/epidemiología , Factores de Riesgo , Instituciones Académicas , España/epidemiologíaRESUMEN
OBJECTIVE: Australia's HPV vaccination and HPV-based cervical screening programs are changing the landscape in cervical cancer prevention. We aim to identify areas which can make the biggest further impact on cervical cancer burden. This protocol describes the first stage of a program of work called Pathways-Cervix that aims to generate evidence from modelled evaluations of interventions across the cervical cancer spectrum. METHODS: Based on evidence from literature reviews and guidance from a multi-disciplinary Scientific Advisory Committee (SAC), the most relevant evaluations for prevention, diagnosis and treatment were identified. RESULTS: Priority evaluations agreed by the SAC included: increasing/decreasing and retaining vaccination uptake at the current level; vaccinating older women; increasing screening participation; methods for triaging HPV-positive women; improving the diagnosis of cervical intraepithelial neoplasia (CIN) and cancer; treating cervical abnormalities and cancer; and vaccinating women treated for CIN2/3 to prevent recurrence. Evaluations will be performed using a simulation model, Policy1-Cervix previously used to perform policy evaluations in Australia. Exploratory modelling of interventions using idealised scenarios will initially be conducted in single birth cohorts. If these have a significant impact on findings then evaluations with more realistic assumptions will be conducted. Promising strategies will be investigated further by multi-cohort simulations predicting health outcomes, resource use and cost outcomes. CONCLUSIONS: Pathways-Cervix will assess the relative benefits of strategies and treatment options in a systematic and health economic framework, producing a list of 'best buys' for future decision-making in cervical cancer control.
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Erradicación de la Enfermedad/métodos , Modelos Teóricos , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Adulto , Australia , Erradicación de la Enfermedad/normas , Detección Precoz del Cáncer , Femenino , Política de Salud , Humanos , Modelos Biológicos , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/transmisión , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus/administración & dosificación , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/prevención & control , Displasia del Cuello del Útero/virologíaRESUMEN
INTRODUCTION: The Oxford Hip Score (OHS) is a commonly used patient-reported outcome measure (PROM), comprising 12 questions. We present the incidental finding that one of the 12 questions is ambiguous. MATERIALS AND METHODS: As part of a 10-year follow-up of patients treated with hip resurfacing the OHS was posted to 148 patients; 135 (91%) replied. Scores were read by 2 orthopaedic surgery trainees and entered into a database. It was noted that Question 5 was frequently mis-interpreted. RESULTS: Thirteen patients' questionnaires (10%) showed the same inconsistency: question 5 was scored as 0 points but the other 11 questions were scored as either 3 or 4 in 97% of cases. The ethnic group of all 13 patients was recorded in hospital data as being White-British. CONCLUSION: Question 5 of the OHS is ambiguous to 10% of native English-speakers. These patients rated their hip function highly, as reflected by the fact that 97% of the questions other than question 5 scored 3 or 4, indeed 87% of them scored 4. We hypothesise that the wording of the zero score option "Not at all" is being mis-interpreted as a response indicating that the patient does not suffer any pain at all. The effect is an error of 4 points out of 48 (8%); this may under-estimate the patient's hip score. Surgeons are under great scrutiny to prove efficacy of surgical interventions; this is often provided by PROMs. We should strive to formulate the most accurate, reproducible and least ambiguous PROMs questionnaires.
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Artroplastia de Reemplazo de Cadera/métodos , Predicción , Articulación de la Cadera/fisiopatología , Medición de Resultados Informados por el Paciente , Rango del Movimiento Articular/fisiología , Encuestas y Cuestionarios , Estudios de Seguimiento , Articulación de la Cadera/cirugía , Humanos , LenguajeRESUMEN
PROBLEM: In women, the use of progestin-based contraception may increase the risk of vaginal HIV acquisition. We previously showed in macaques that there is a significantly higher simian-human immunodeficiency virus (SHIV) acquisition rate in the luteal phase of the menstrual cycle, which presents a naturally high-progesterone state, and this may be attributable to altered expression of innate immune factors. We hypothesized that progestin-based contraception, especially depot medroxyprogesterone acetate (DMPA), would, in a similar way, affect mucosal immune factors that influence HIV acquisition risk. METHOD OF STUDY: We used a pig-tailed macaque model to evaluate the effects of two progestin-based contraceptives, DMPA, and levonorgestrel (LNG)/ethinyl estradiol (EE)-based combined oral contraceptives (COCs), on innate mucosal factors. We compared the vaginal epithelial thickness data from previous studies and used cytokine profiling and microarray analysis to evaluate contraception-induced molecular changes in the vagina. RESULTS: The administration of DMPA caused a reduction in the thickness of the vaginal epithelium relative to that of the follicular or luteal phase. DMPA also induced a significant increase in vaginal levels of the anti-inflammatory cytokine IL-10. Both DMPA- and LNG-based contraception induced a signature of gene expression similar to that of the luteal phase, only more exacerbated, including widespread downregulation of antiviral genes. CONCLUSION: The use of progestin-based contraception might engender a milieu that poses an increased risk of HIV acquisition as compared to both the luteal and follicular phases of the menstrual cycle.
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Anticoncepción/efectos adversos , Anticonceptivos Femeninos/efectos adversos , Etinilestradiol/efectos adversos , Infecciones por VIH/transmisión , Levonorgestrel/efectos adversos , Acetato de Medroxiprogesterona/efectos adversos , Progestinas/efectos adversos , Vagina/efectos de los fármacos , Animales , Anticoncepción/métodos , Anticonceptivos Femeninos/farmacología , Etinilestradiol/farmacología , Femenino , Infecciones por VIH/patología , Interleucina-10/metabolismo , Levonorgestrel/farmacología , Macaca nemestrina , Acetato de Medroxiprogesterona/farmacología , Membrana Mucosa/metabolismo , Progestinas/farmacología , Factores de RiesgoRESUMEN
Despite calls for more socio-technical research on energy, there is little practical advice to how narratives collected through qualitative research may be melded with technical knowledge from the physical sciences such as engineering and then applied in energy efficiency social action strategies. This is despite established knowledge in the environmental management literature about domestic energy use regarding the utility of social practice theory and narrative framings that socialise everyday consumption. Storytelling is positioned in this paper both as a focus for socio-technical energy research, and as one potential practical tool that can arguably enhance energy efficiency interventions. We draw upon the literature on everyday social practices, and storytelling, to present our framework called 'collective video storytelling' that combines scientific and lay knowledge about domestic energy use to offer a practical tool for energy efficiency management. Collective video storytelling is discussed in the context of Energy+Illawarra, a 3-year cross-disciplinary collaboration between social marketers, human geographers, and engineers to target energy behavioural change within older low-income households in regional NSW, Australia.
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Comunicación , Conservación de los Recursos Energéticos , Mercadeo Social , Australia , Humanos , Narración , Investigación CualitativaRESUMEN
Currently, there are mounting data suggesting that HIV-1 acquisition in women can be affected by the use of certain hormonal contraceptives. However, in non-human primate models, endogenous or exogenous progestin-dominant states are shown to increase acquisition. To gain mechanistic insights into this increased acquisition, we studied how mucosal barrier function and CD4+ T-cell and CD68+ macrophage density and localization changed in the presence of natural progestins or after injection with high-dose DMPA. The presence of natural or injected progestins increased virus penetration of the columnar epithelium and the infiltration of susceptible cells into a thinned squamous epithelium of the vaginal vault, increasing the likelihood of potential virus interactions with target cells. These data suggest that increasing either endogenous or exogenous progestin can alter female reproductive tract barrier properties and provide plausible mechanisms for increased HIV-1 acquisition risk in the presence of increased progestin levels.
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Interacciones Huésped-Patógeno/efectos de los fármacos , Macrófagos/efectos de los fármacos , Membrana Mucosa/efectos de los fármacos , Progestinas/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios/efectos de los fármacos , Vagina/efectos de los fármacos , Animales , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/virología , Cuello del Útero/efectos de los fármacos , Cuello del Útero/inmunología , Cuello del Útero/metabolismo , Cuello del Útero/virología , Preparaciones de Acción Retardada , Femenino , Inyecciones Intramusculares , Activación de Linfocitos/efectos de los fármacos , Macaca mulatta , Macaca nemestrina , Activación de Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/virología , Acetato de Medroxiprogesterona/administración & dosificación , Acetato de Medroxiprogesterona/uso terapéutico , Ciclo Menstrual , Membrana Mucosa/inmunología , Membrana Mucosa/metabolismo , Membrana Mucosa/virología , Progestinas/administración & dosificación , Progestinas/metabolismo , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/inmunología , Virus de la Inmunodeficiencia de los Simios/fisiología , Vagina/inmunología , Vagina/metabolismo , Vagina/virología , Internalización del Virus/efectos de los fármacosRESUMEN
INTRODUCTION: Hormonal contraception with depot medroxyprogesterone acetate (DMPA) may increase HIV acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. In this study, we test the impact of a low DMPA dose, designed to resemble human contraceptive use, on Simian-Human Immunodeficiency Virus (SHIV) acquisition risk in pigtail macaques (Macaca nemestrina). METHODS: Macaques metabolize DMPA faster than humans. We previously identified a per-weight DMPA dose and administration frequency that achieves long-lasting suppression of ovulation in macaques. Eight macaques were given 1.5-mg/kg DMPA monthly, whereas 11 were untreated controls. For comparison, women receive 150 mg (approximately 2 mg/kg) every 3 months. We exposed monkeys to 20 suboptimal SHIV challenges, designed to slowly infect half of controls and allow increased infection in the DMPA group. RESULTS: It took a median 5.5 viral challenges to infect DMPA-treated macaques and 9 challenges for controls (P = 0.27; exact conditional logistic regression). The exact odds ratio was 2.2 (CI: 0.6 to 8.3). Ovulation was suppressed, and the vaginal epithelium was thinned after DMPA treatment in all animals (mean, 30 and 219 mm in DMPA-treated and control macaques, respectively, P = 0.03, t test using the Satterthwaite degrees-of-freedom approximation). CONCLUSIONS: SHIV infections in DMPA-treated macaques were 2.2 times those of controls, but this was not statistically significant. The result is remarkably similar to studies of human DMPA use, which have shown HIV risk increases of a similar magnitude and of variable significance. Taken together with previous studies of higher DMPA doses in macaques, the results suggest a dose-dependent effect of DMPA on Simian Immunodeficiency Virus (SIV) or SHIV acquisition.
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Anticonceptivos Femeninos/administración & dosificación , Anticonceptivos Femeninos/farmacología , Acetato de Medroxiprogesterona/administración & dosificación , Acetato de Medroxiprogesterona/farmacología , Síndrome de Inmunodeficiencia Adquirida del Simio/transmisión , Virus de la Inmunodeficiencia de los Simios/efectos de los fármacos , Vagina/virología , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Macaca nemestrina , Síndrome de Inmunodeficiencia Adquirida del Simio/virologíaRESUMEN
Task-specific dystonia is a form of isolated focal dystonia with the peculiarity of being displayed only during performance of a specific skilled motor task. This distinctive feature makes task-specific dystonia a particularly mysterious and fascinating neurological condition. In this review, we cover phenomenology and its increasingly broad-spectrum risk factors for the disease, critically review pathophysiological theories and evaluate current therapeutic options. We conclude by highlighting the unique features of task-specific dystonia within the wider concept of dystonia. We emphasise the central contribution of environmental risk factors, and propose a model by which these triggers may impact on the motor control of skilled movement. By viewing task-specific dystonia through this new lens which considers the disorder a modifiable disorder of motor control, we are optimistic that research will yield novel therapeutic avenues for this highly motivated group of patients.
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Distonía/fisiopatología , Trastornos Distónicos/fisiopatología , Mano/fisiopatología , Movimiento/fisiología , Diagnóstico Diferencial , Ambiente , Humanos , Enfermedades Profesionales/fisiopatología , Factores de RiesgoRESUMEN
OBJECTIVES: The Health Impact Assessment (HIA) was conducted to evaluate the potential community health implications of a proposed oil drilling and production project in Hermosa Beach, California. The HIA considered 17 determinants of health that fell under 6 major categories (i.e., air quality, water and soil quality, upset conditions, noise and light emissions, traffic, and community livability). MATERIAL AND METHODS: This paper attempts to address some of the gaps within the HIA practice by presenting the methodological approach and results of this transparent, comprehensive HIA; specifically, the evaluation matrix and decision-making framework that have been developed for this HIA and form the basis of the evaluation and allow for a clear conclusion to be reached in respect of any given health determinant (i.e., positive, negative, neutral). RESULTS: There is a number of aspects of the project that may positively influence health (e.g., increased education funding, ability to enhance green space), and at the same time there have been potential negative effects identified (e.g., odor, blowouts, property values). Except for upset conditions, the negative health outcomes have been largely nuisance-related (e.g., odor, aesthetics) without irreversible health impacts. The majority of the health determinants, that had been examined, have revealed that the project would have no substantial effect on the health of the community. CONCLUSIONS: Using the newly developed methodology and based on established mitigation measures and additional recommendations provided in the HIA, the authors have concluded that the project will have no substantial effect on community health. This approach and methodology will assist practitioners, stakeholders and decision-makers in advancing the HIA as a useful, reproducible, and informative tool.
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Evaluación del Impacto en la Salud/métodos , Política de Salud , Promoción de la Salud/métodos , Enfermedades Profesionales/prevención & control , Industria del Petróleo y Gas , California/epidemiología , Humanos , Incidencia , Enfermedades Profesionales/epidemiologíaRESUMEN
BACKGROUND: HIV acquisition in the female genital tract remains incompletely understood. Quantitative data on biological HIV risk factors, the influence of reproductive hormones, and infection risk are lacking. We evaluated vaginal epithelial thickness during the menstrual cycle in pigtail macaques (Macaca nemestrina). This model previously revealed increased susceptibility to vaginal infection during and after progesterone-dominated periods in the menstrual cycle. METHODS: Nucleated and nonnucleated (superficial) epithelial layers were quantitated throughout the menstrual cycle of 16 macaques. We examined the relationship with previously estimated vaginal SHIVSF162P3 acquisition time points in the cycle of 43 different animals repeatedly exposed to low virus doses. RESULTS: In the luteal phase (days 17 to cycle end), the mean vaginal epithelium thinned to 66% of mean follicular thickness (days 1-16; P = 0.007, Mann-Whitney test). Analyzing 4-day segments, the epithelium was thickest on days 9 to 12 and thinned to 31% thereof on days 29 to 32, with reductions of nucleated and nonnucleated layers to 36% and 15% of their previous thickness, respectively. The proportion of animals with estimated SHIV acquisition in each cycle segment correlated with nonnucleated layer thinning (Pearson r = 0.7, P < 0.05, linear regression analysis), but not nucleated layer thinning (Pearson r = 0.6, P = 0.15). CONCLUSIONS: These data provide a detailed picture of dynamic cycle-related changes in the vaginal epithelium of pigtail macaques. Substantial thinning occurred in the superficial, nonnucleated layer, which maintains the vaginal microbiome. The findings support vaginal tissue architecture as susceptibility factor for infection and contribute to our understanding of innate resistance to SHIV infection.