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Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.
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Instabilidade Genômica , Micronúcleos com Defeito Cromossômico , Animais , Humanos , Camundongos , Cromossomos/genética , Dano ao DNA , Instabilidade Genômica/genética , Fenótipo , Sirtuína 1 , Mutações Sintéticas LetaisRESUMO
The hippocampus plays a critical role in the formation of declarative memories, and hippocampal damage leads to significant impairments in new memory formation. Drawing can serve as a form of multi-modal encoding that improves declarative memory performance relative to other multimodal encoding strategies such as writing. We examined whether, and to what extent, patients with hippocampal damage could benefit from the mnemonic strategy of drawing. Three patients with focal hippocampal damage, and one patient with both hippocampal and cortical lesions, in addition to 22 age-, sex-, and education-matched controls, were shown a list of words one at a time during encoding and instructed to either draw a picture or repeatedly write each word for 40 s. Following a brief filled delay, free recall and recognition memory for words from both encoding trial types were assessed. Controls showed enhanced recall and recognition memory for words drawn versus those that were written, an effect that was even more pronounced in patients with focal hippocampal damage. By contrast, the patient with both hippocampal and cortical lesions showed no drawing-mediated boost in either recall or recognition memory. These findings demonstrate that drawing is an effective encoding strategy, likely accruing from the engagement of extra-hippocampal processes including the integration of cortical-based motor, visual, and semantic processing, enabling more elaborative encoding.
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INTRODUCTION: We compare demographic, socioeconomic, and anthropometric characteristics and blood pressure (BP), between rural and urban Peruvian indigenous women. These are preliminary results from a project on urbanization, migration, and health. METHODS: Data were collected cross-sectionally (2019) and compared between a rural (n = 92) and an urban (n = 93) community. RESULTS: Height: µ = 148.3 ± 5.0 cm (range = 137-162), weight: µ = 62.0 ± 11.5 (range = 37.5-108.7), median waist circumference = 89.0 (IQR = 15.8, range = 64.0-126.0), BMI = 28.3 (IQR = 6.2, range = 16.7-40.0), with no significant rural-urban differences. Systolic but not diastolic BP was significantly higher in urban versus rural women (median = 110, IQR = 18, range = 80-170 vs. median = 120, IQR = 10, range = 90-170, p = .002 and median = 70, IQR = 17, range = 50-100 vs. median = 70, IQR = 10, range = 60-100, p = .354), respectively. CONCLUSIONS: Despite major lifestyle differences, there were no anthropometric differences between rural and urban women. Higher systolic BP in urban women may reflect social/economic stressors rather than dietary factors.
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População Rural , Urbanização , Humanos , Feminino , Peru , População Urbana , AntropometriaRESUMO
Plasmodium coatneyi has been proposed as an animal model for human Plasmodium falciparum malaria as it appears to replicate many aspects of pathogenesis and clinical symptomology. As part of the ongoing evaluation of the rhesus macaque model of severe malaria, a detailed ultrastructural analysis of the interaction between the parasite and both the host erythrocytes and the microvasculature was undertaken. Tissue (brain, heart and kidney) from splenectomized rhesus macaques and blood from spleen-intact animals infected with P. coatneyi were examined by electron microscopy. In all three tissues, similar interactions (sequestration) between infected red blood cells (iRBC) and blood vessels were observed with evidence of rosette and auto-agglutinate formation. The iRBCs possessed caveolae similar to P. vivax and knob-like structures similar to P. falciparum. However, the knobs often appeared incompletely formed in the splenectomized animals in contrast to the intact knobs exhibited by spleen intact animals. Plasmodium coatneyi infection in the monkey replicates many of the ultrastructural features particularly associated with P. falciparum in humans and as such supports its use as a suitable animal model. However, the possible effect on hostparasite interactions and the pathogenesis of disease due to the use of splenectomized animals needs to be taken into consideration.
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Malária , Plasmodium , Animais , Eritrócitos/parasitologia , Interações Hospedeiro-Parasita , Macaca mulatta/parasitologia , Malária/parasitologiaRESUMO
Interventions that increase population physical activity are required to promote health and wellbeing. parkrun delivers community-based, 5 km events worldwide yet 43% who register never participate in a parkrun event. This research had two objectives; i) explore the demographics of people who register for parkrun in United Kingdom, Australia, Ireland, and don't initiate or maintain participation ii) understand the barriers to participating in parkrun amongst these people. Mandatory data at parkrun registration provided demographic characteristics of parkrun registrants. A bespoke online survey distributed across the three countries captured the reasons for not participating or only participating once. Of 680,255 parkrun registrants between 2017 and 19, 293,542 (43%) did not participate in any parkrun events and 147,148 (22%) only participated in one parkrun event. Females, 16-34 years and physically inactive were more likely to not participate or not return to parkrun. Inconvenient start time was the most frequently reported barrier to participating, with females more likely than males to report the psychological barrier of feeling too unfit to participate. Co-creating strategies with and for people living with a chronic disease, women, young adults, and physically inactive people, could increase physical activity participation within parkrun.
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Exercício Físico , Promoção da Saúde , Austrália , Feminino , Humanos , Masculino , Inquéritos e Questionários , Reino Unido , Adulto JovemRESUMO
The Editors have retracted this article [1] as is it is not clear whether parental consent was provided for publication of the images and case. Given the age of the article we have been unable to verify this, therefore the article is no longer available online in order to protect the privacy of the individual. Both authors agree to this retraction.
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OBJECTIVE: Sex-related differences in skin properties may be expected to impact dandruff formation and treatment. A meta-analysis approach was undertaken to investigate potential differences between males and females in response to zinc pyrithione (ZnPT) treatment vs. non-anti-dandruff (AD) shampoo. A separate pooled statistical analysis of ceramide and total protein loss endpoints was also undertaken to assess potential sex-related differences in stratum corneum properties that might influence response to ZnPT vs. non-AD shampoo in subjects with dandruff. METHODS: The meta-analysis approach included data from 17 half-head, double-blind, randomized studies (N = 2088) undertaken in Asia to assess the effectiveness of 1% ZnPT shampoo and/or non-AD shampoo in reducing dandruff severity, as assessed by Total Weighted Head Score Adherent Flake (TWHS-AF) methodology. Treatment duration was 4 weeks, with TWHS-AF measured at weekly intervals. Data from an additional three studies (N = 143) conducted in Asia were included in the pooled analysis of ceramide levels and protein loss from scalp skin of subjects with dandruff. RESULTS: Response to 1% ZnPT vs. non-AD shampoo was greater in males than in females at all time points; after 4 weeks, the between-treatment difference in TWHS-AF was -17.5 (95% confidence interval [CI] -19.5, -15.5) in males and -11.1 (-13.2, -8.9) in females. Sex-related differences were observed between males and females in response to both 1% ZnPT and non-AD shampoos. Males had a stronger response than females to treatment with 1% ZnPT shampoo, while dandruff decreased to a greater extent in females than in males when using non-AD shampoo. Statistically significant sex-related differences in ceramide levels and total protein loss were observed (both P < 0.01). Ceramide levels were 0.76 times lower (95% CI 0.60, 0.97) in males than in females, while total protein loss was 1.4 times greater (95% CI 1.1, 1.9) in males than in females. CONCLUSION: Males show a greater response than females to 1% ZnPT shampoo, while females show a greater response than males to non-AD shampoo. These findings may in part be explained by the sex-related differences observed in stratum corneum properties, which may make males more prone to dandruff than females.
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Caspa/prevenção & controle , Preparações para Cabelo , Compostos Organometálicos/farmacologia , Piridinas/farmacologia , Fatores Sexuais , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Erythropoietin (EPO) rapidly decreases on return to sea level (SL) after chronic altitude exposure. Acute hypoxia may provide an additional stimulus to prevent the decline in EPO. Proinflammatory cytokines, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα) have been shown to inhibit EPO production. Optimal normobaric hypoxic exposure has not been established; therefore, investigation of methods eliciting the greatest response in EPO to limit physiological stress is required. Eight men (age 27 ± 4 years, body mass 77.5 ± 9.0 kg, height 179 ± 6 cm) performed four passive exposures to different normobaric hypoxic severities [FiO2 : 0.209 (SL), FiO2 : ~0.135 (3600 m), FiO2 : ~0.125 (4200 m) and FiO2 : ~0.115 (4800 m)] in a hypoxic chamber for 2 h. Venous blood was drawn pre-exposure and then at 1, 2, 4, 6, and 8 h to determine EPO concentration ([EPO]), IL-6, and TNFα. During 4200 and 4800 m, [EPO] increased from 5.9 ± 1.5 to 8.1 ± 1.5 mU/mL (P = 0.009) and 6.0 ± 1.4 to 8.9 ± 2.0 mU/mL (P = 0.037), respectively, with [EPO] increase peaking at 4 h (2 h post-exposure). There were no differences in IL-6 or TNFα during or post-exposure. Increased [EPO] was found 2 h post hypoxic exposure as result of 2 h of normobaric hypoxia ≥4200 m. There was no dose-response relationship in [EPO] between simulated hypoxia severities.
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Altitude , Eritropoetina/sangue , Hipóxia/sangue , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto , Humanos , Masculino , Método Simples-Cego , Fatores de Tempo , Adulto JovemRESUMO
Intravenous delivery of adenoviruses is the optimal route for many gene therapy applications. Once in the blood, coagulation factor X (FX) binds to the adenovirus capsid and protects the virion from natural antibody and classical complement-mediated neutralisation in mice. However, to date, no studies have examined the relevance of this FX/viral immune protective mechanism in human samples. In this study, we assessed the effects of blocking FX on adenovirus type 5 (Ad5) activity in the presence of human serum. FX prevented human IgM binding directly to the virus. In individual human sera samples (n=25), approximately half of those screened inhibited adenovirus transduction only when the Ad5-FX interaction was blocked, demonstrating that FX protected the virus from neutralising components in a large proportion of human sera. In contrast, the remainder of sera tested had no inhibitory effects on Ad5 transduction and FX armament was not required for effective gene transfer. In human sera in which FX had a protective role, Ad5 induced lower levels of complement activation in the presence of FX. We therefore demonstrate for the first time the importance of Ad-FX protection in human samples and highlight subject variability and species-specific differences as key considerations for adenoviral gene therapy.
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Adenoviridae/imunologia , Fator X/imunologia , Técnicas de Transferência de Genes , Terapia Genética/métodos , Adenoviridae/genética , Linhagem Celular Tumoral , Vetores Genéticos/sangue , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Células HEK293 , Humanos , Imunoglobulina M/imunologia , Injeções Intravenosas/métodosRESUMO
BACKGROUND AND PURPOSE: Clinical management after transient ischaemic attack (TIA) is focused on stroke prevention; however, a number of small studies suggest that patients may experience ongoing residual impairments. METHODS: This was a retrospective matched-cohort study using anonymized electronic primary care records from The Health Improvement Network database, which covers approximately 6% of the UK population. Adults (≥ 18 years old) who experienced a first TIA between 2009 and 2013 were matched in a ratio of 1:5 to controls by age, sex and general practice. The time to first consultation for fatigue, psychological impairment or cognitive impairment was estimated by Kaplan-Meier survivor functions and adjusted hazard ratios. RESULTS: A total of 9419 TIA patients and 46 511 controls were included. The Kaplan-Meier curves showed that TIA patients were more likely than controls to consult for all three impairments (P < 0.0001). Within 7.1 months (95% confidence interval (CI), 6.2-8.2), 25% of TIA patients consulted for psychological impairment compared with 23.5 months (95% CI, 22.5-24.6) for controls. Hazard ratios for TIA patients were 1.43 (95% CI, 1.33-1.54) for consulting for fatigue, 1.26 (95% CI, 1.20-1.31) for psychological impairment and 1.45 (95% CI, 1.28-1.65) for cognitive impairment. CONCLUSIONS: Transient ischaemic attack is associated with significantly increased subsequent consultation for fatigue, psychological impairment and cognitive impairment. These findings suggest that impairments exist after initial symptoms of TIA have resolved, which should be considered by clinicians when treating TIA patients.
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Disfunção Cognitiva/etiologia , Fadiga/etiologia , Ataque Isquêmico Transitório/complicações , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde , Estudos RetrospectivosRESUMO
OBJECTIVE: To describe the quality assurance (QA) processes and their impact on visualization of postmenopausal ovaries in the ultrasound arm of a multicenter screening trial for ovarian cancer. METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 50 639 women aged 50-74 years were randomized to the ultrasound arm and underwent annual transvaginal ultrasound (TVS) examinations. QA processes were developed during the course of the trial and included regular monitoring of the visualization rate (VR) of the right ovary. Non-subjective factors identified previously as impacting on VR of the right ovary were included in a generalized estimating equation model for binary outcomes to enable comparison of observed vs adjusted VR between individual sonographers who had undertaken > 1000 scans during the trial and comparison between centers. Observed and adjusted VRs of sonographers and centers were ranked according to the highest VR. Analysis of annual VRs of sonographers and those of the included centers was undertaken. RESULTS: Between June 2001 and December 2010, 48 230 of 50 639 women attended one of 13 centers for a total of 270 035 annual TVS scans. One or both ovaries were seen in 228 145 (84.5%) TVS scans. The right ovary was seen on 196 426 (72.7%) of the scans. For the 78 sonographers included in the model, the median difference between observed and adjusted VR was -0.7% (range, -7.9 to 5.9%) and the median change in VR rank after adjustment was 3 (range, 0-18). For the 13 centers, the median difference between observed and adjusted VR was -0.5% (range, -2.2 to 1%), with no change in ranking after adjustment. The median adjusted VR was 73% (interquartile range (IQR), 65-82%) for sonographers and 74.7% (IQR, 67.1-79.0%) for centers. Despite the increasing age of the women being scanned, there was a steady decrease in the number of sonographers with VR < 60% (21.4% in 2002 vs 2.0% in 2010) and an increase in sonographers with VR > 80% (14.3% in 2002 vs 40.8% in 2010). The median VR of the centers increased from 65.5% (range, 55.7-81.0%) in 2001 to 80.3% (range, 74.5-90.9%) in 2010. CONCLUSIONS: A robust QA program can improve visualization of postmenopausal ovaries and is an essential component of ultrasound-based ovarian cancer screening trials. While VR should be adjusted for non-subjective factors that impact on ovarian visualization, subjective factors are likely to be the largest contributors to differences in VR.
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Detecção Precoce de Câncer/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Neoplasias Ovarianas/diagnóstico por imagem , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Idoso , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Feminino , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Ovário/diagnóstico por imagem , Garantia da Qualidade dos Cuidados de Saúde/métodos , Ultrassonografia/métodos , Ultrassonografia/normas , Ultrassonografia/estatística & dados numéricos , Reino UnidoRESUMO
Malaria remains one of the most significant public health concerns in the world today. Approximately half the human population is at risk for infection, with children and pregnant women being most vulnerable. More than 90% of the total human malaria burden, which numbers in excess of 200 million annually, is due to Plasmodium falciparum. Lack of an effective vaccine and a dwindling stockpile of antimalarial drugs due to increased plasmodial resistance underscore the critical need for valid animal models. Plasmodium coatneyi was described in Southeast Asia 50 years ago. This plasmodium of nonhuman primates has been used sporadically as a model for severe malaria, as it mimics many of the pathophysiologic features of human disease. This review covers the reported macroscopic, microscopic, ultrastructural, and molecular pathology of P. coatneyi infection in macaques, specifically focusing on the rhesus macaque, as well as describing the critical needs still outstanding in the validation of this crucial model of human disease.
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Modelos Animais de Doenças , Macaca mulatta , Malária/patologia , Plasmodium/citologia , Animais , Criança , Feminino , Humanos , Malária/parasitologia , GravidezRESUMO
BACKGROUND: Exercise at altitude places additional physiological stress on the individual in comparison with sea-level performance. This study examines the effect of a moderate hypoxic environment (FiO2=~17%) on intermittent sprint exercise performance. METHODS: Nine male games players completed two consecutive sets of a 40 minute cycling intermittent sprint protocol (CISP×2) in a hypoxic (HYP; FiO2=~17%) and normoxic (NORM; FiO2=~21%) environment. During each sprint peak power output (PPO; the highest power during each 5 s sprint), mean power output (MPO; the average power during the 3 s sprint) were measured and total work done (WD; force applied from the highest 3 s period of power output) was calculated. Physiological responses were recorded throughout the testing procedure. RESULTS: Reductions were found in PPO (944±155 vs. 983±167 W), MPO (900±176 vs. 853±177 W) and WD (102±20 vs. 108±20 kJ) during the CISP×2 (P<0.05) at HYP compared to NORM. Reductions in PPO, MPO and WD were also found between the 1st half and 2nd half CISP (P<0.05) and there was a greater decline from the 1st half CISP to the 2nd half CISP in PPO, MPO and WD at HYP. Heart rate was higher and peripheral arterial oxygen saturation lower during HYP compared to NORM (P<0.05). CONCLUSION: Moderate hypoxia significantly reduced PPO (~4%), MPO (~5%) and WD (~5%) compared to normoxia. The results suggest athletes will be at a disadvantage when performing intermittent sprinting at moderate altitude.
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Altitude , Desempenho Atlético/fisiologia , Ciclismo/fisiologia , Hipóxia/fisiopatologia , Adulto , Teste de Esforço , Humanos , Masculino , Força Muscular/fisiologia , Adulto JovemRESUMO
OBJECTIVE: In humans, the process of hair shedding, referred to as exogen, is believed to occur independently of the other hair cycle phases. Although the actual mechanisms involved in hair shedding are not fully known, it has been hypothesized that the processes leading to the final step of hair shedding may be driven by proteases and/or protease inhibitor activity. In this study, we investigated the presence of proteases and protease activity in naturally shed human hairs and assessed enzyme inhibition activity of test materials. METHODS: We measured enzyme activity using a fluorescence-based assay and protein localization by indirect immunohistochemistry (IHC). We also developed an ex vivo skin model for measuring the force required to pull hair fibres from skin. RESULTS: Our data demonstrate the presence of protease activity in the tissue material surrounding club roots. We also demonstrated the localization of specific serine protease protein expression in human hair follicle by IHC. These data provide evidence demonstrating the presence of proteases around the hair club roots, which may play a role during exogen. We further tested the hypothesis that a novel protease inhibitor system (combination of Trichogen) and climbazole) could inhibit protease activity in hair fibre club root extracts collected from a range of ethnic groups (U.K., Brazil, China, first-generation Mexicans in the U.S.A., Thailand and Turkey) in both males and females. Furthermore, we demonstrated that this combination is capable of increasing the force required to remove hair in an ex vivo skin model system. CONCLUSION: These studies indicate the presence of proteolytic activity in the tissue surrounding the human hair club root and show that it is possible to inhibit this activity with a combination of Trichogen and climbazole. This technology may have potential to reduce excessive hair shedding.
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Folículo Piloso/enzimologia , Serina Proteases/metabolismo , Inibidores de Serina Proteinase/farmacologia , Animais , Feminino , Folículo Piloso/efeitos dos fármacos , Humanos , Masculino , SuínosRESUMO
OBJECTIVE: To assess pain and overall experience of transvaginal sonography (TVS) in asymptomatic postmenopausal women. METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 50 639 postmenopausal women were randomized to undergo annual TVS at 13 trial centers in England, Wales and Northern Ireland. Together with the appointment letter for their annual scan, a random sample of 150 women per center was sent a detailed 48-item postal questionnaire regarding the screening experience. It included a specific question about pain using a score of 0-5, where 5 was severe pain and 3 was discomfort. To assess factors that might affect a woman's reported pain experience, the pain score was regressed on age, hormone replacement therapy use, body mass index, a history of hysterectomy, prolonged scanning time, ovarian visualization, scan result, sonographer's visualization rates and opinion of the women regarding the sonographer who performed the scan. RESULTS: Between 7 July and 9 September 2009, 1950 randomly chosen women (150 per regional center) were sent the questionnaire. Of the 800 (41.0%) who returned the questionnaire, 651 could be linked to their TVS appointment. One-hundred and fifty-two (23.3%) women reported pain/discomfort (score 3-5) during TVS and 473 (72.7%) reported no discomfort (score 0-2). Only 23 (3.5%) women reported experiencing moderate/severe pain. Increasing discomfort/pain was independently associated with a history of hysterectomy and participant's reporting of prolonged scan time. Women who experienced pain on TVS were less compliant (odds ratio = 0.87) with the following year's scan compared with those who did not experience pain. CONCLUSIONS: The majority of postmenopausal women found TVS acceptable. Pain influenced compliance and correlated with women's perception of increased scanning time and previous hysterectomy.
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Detecção Precoce de Câncer/efeitos adversos , Programas de Rastreamento/efeitos adversos , Neoplasias Ovarianas/diagnóstico por imagem , Medição da Dor/métodos , Dor/etiologia , Idoso , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Satisfação do Paciente , Pós-Menopausa , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Ultrassonografia , Reino UnidoRESUMO
OBJECTIVE: Transvaginal sonography (TVS) is core to any ovarian cancer screening strategy. General-population screening involves older postmenopausal women in whom ovarian visualization is difficult because of decreasing ovarian size and lack of follicular activity. We report on factors affecting the visualization of postmenopausal ovaries in the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). METHODS: The UKCTOCS is a randomized controlled trial of 202 638 postmenopausal women with 50 639 women in the ultrasound scan arm. TVS is the primary screening modality in the ultrasound scan arm. Age, education, ethnicity, body mass index (BMI), previous pelvic surgery, lifestyle and reproductive factors, and a personal/family history of cancer were assessed for their effects on ovarian visualization at the initial TVS. RESULTS: Between 11 June 2001 and 18 August 2007, 43 867 women underwent TVS. The median age and BMI of the women were 60.6 (interquartile range (IQR), 9.9) years and 25.7 (IQR, 5.8), respectively. The right ovary was visualized in 29 297 (66.8%) and the left ovary was visualized in 28 726 (65.5%). Visualization of ovaries decreased with previous hysterectomy (odds ratio (OR) = 0.534; 95% CI, 0.504-0.567), previous tubal ligation (OR = 0.895; 95% CI, 0.852-0.940), increasing age (OR = 0.953; 95% CI, 0.950-0.956), unilateral oophorectomy (OR = 0.224; 95% CI, 0.186-0.269) and being overweight (OR = 0.918; 95% CI, 0.876-0.962) or obese (OR = 0.715; 95% CI, 0.677-0.755). Increased visualization was observed with a history of infertility (OR = 1.134; 95% CI, 1.005-1.279) and increasing age (in years) at menopause (OR = 1.005; 95% CI, 1.001-1.009). CONCLUSIONS: Several factors affect the visualization of postmenopausal ovaries. Their impact needs to be taken into consideration when developing quality assurance for ovarian ultrasound scanning or comparing study results as their prevalence may differ between populations.
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Neoplasias Ovarianas/diagnóstico por imagem , Ovário/diagnóstico por imagem , Pós-Menopausa , Fatores Etários , Idoso , Índice de Massa Corporal , Detecção Precoce de Câncer , Feminino , Humanos , Histerectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Tamanho do Órgão , Ovariectomia/estatística & dados numéricos , Ovário/patologia , Esterilização Tubária/estatística & dados numéricos , UltrassonografiaRESUMO
Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).
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Genes Supressores de Tumor/genética , Predisposição Genética para Doença/genética , Neoplasias Primárias Múltiplas/genética , Proteínas/genética , Neoplasias Cutâneas/genética , Proteínas Supressoras de Tumor , Sequência de Aminoácidos , Domínio Catalítico , Cromossomos Humanos Par 16/genética , Clonagem Molecular , Mapeamento de Sequências Contíguas , Enzima Desubiquitinante CYLD , Éxons/genética , Feminino , Genes Dominantes/genética , Mutação em Linhagem Germinativa/genética , Humanos , Perda de Heterozigosidade/genética , Masculino , Dados de Sequência Molecular , Mutação/genética , Neoplasias Primárias Múltiplas/patologia , Polimorfismo Genético/genética , Proteínas/química , RNA Mensageiro/análise , RNA Mensageiro/genética , Homologia de Sequência de Aminoácidos , Sitios de Sequências Rotuladas , Neoplasias Cutâneas/patologia , Tioléster Hidrolases/química , Ubiquitina TiolesteraseRESUMO
Dandruff is a common complaint and is suffered by as much as half of the population at some time post puberty. The condition is characterized by the presence of flakes on the scalp and in the hair, and is often accompanied by itch. The most common treatment for dandruff is the use of shampoo formulations that contain fungistatic agents such as zinc pyrithione (ZPT) and octopirox. Whilst most antidandruff shampoos are effective in resolving the symptoms of dandruff these shampoos can often result in hair condition that is less than acceptable to consumers which can lead to a tendency for them to revert to use of a non-antidandruff shampoo. This can result in a rapid return of dandruff symptoms. The aim of this investigation was to study the impact of using a combination of antidandruff actives and silicones on the resolution of dandruff and to deliver superior sensory properties to the hair. We have demonstrated that shampoo containing the dual active system of ZPT/Climbazole deposits both active agents onto a model skin surface (VitroSkin) and reduces Malassezia furfur regrowth in vitro. Clinical evaluation of the dual active shampoo demonstrated superior efficacy and retained superiority during a regression phase where all subjects reverted to using a non-antidandruff shampoo. We have also demonstrated that it is possible to deposit silicone materials from antidandruff shampoo uniformly over both virgin and damaged hair fibres that results in smoother hair fibres (as evidenced by reduced dry friction). This combination of antidandruff agents and conditioning silicones delivered from a shampoo provides subjects with superior antidandruff efficacy and desired end sensory benefits ensuring compliance and longer term dandruff removal.
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Preparações para Cabelo , Imidazóis/farmacologia , Compostos Organometálicos/farmacologia , Piridinas/farmacologia , Humanos , Espectrometria por Raios XRESUMO
The taxonomic status of the zooplanktivorous cichlids Copadichromis mloto and C. virginalis has been confused since their original descriptions by lles in 1960. Whilst two forms of C. virginalis, 'Kaduna' and 'Kajose', were distinguished in the type material, C. mloto has not been positively identified since its original description. Here we re-examined the types as well as 54 recently collected specimens from multiple sampling locations. Genome sequencing of 51 recent specimens revealed two closely related but reciprocally monophyletic clades. Geometric morphological analysis indicated that one clade morphologically encompasses the type specimens of C. virginalis identified by Iles as the Kaduna form, including the holotype, whilst the other clade encompasses not only the paratypes identified as the Kajose form, but also the type series of C. mloto. Given that all three forms in Iles's type series are from the same locality, that there are no meristic or character states to differentiate them and that there are no records of adult male C. mloto in breeding colours, we conclude that the Kajose form previously identified as C. virginalis represents relatively deeper bodied sexually active or maturing individuals of C. mloto. Supplementary Information: The online version contains supplementary material available at 10.1007/s10750-022-05025-1.