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BACKGROUND AND OBJECTIVES: Knowledge about the current spectrum of dermatomycoses is important for diagnosis and therapy. PATIENTS AND METHODS: A retrospective, monocentric analysis of mucocutaneous fungal infections diagnosed at a large European academic dermatology department in Munich was conducted; 87,229 samples from 48,916 patients from January 1, 2011, to August 30, 2020, were included. RESULTS: Fungi were detected in 11,513 samples from 48,916 (23.54%), and 36 different species were identified. Candida (C.) albicans was the most common pathogen (5,055 detections; 43.91% of all positive samples), followed by Trichophyton (T.) rubrum (3,076 detections; 26.72% of all positive samples) and Candida parapsilosis (923 detections; 8.02% of all positive samples). Rare pathogens such as Trichophyton raubitschekii were also detected. Coinfections with multiple species were detected in 44 cases. CONCLUSIONS: Even though C. albicans, T. rubrum, and C. parapsilosis were confirmed as the most common pathogens, rare pathogens should also be considered in clinical practice. The predominant spectrum of fungi differed from that reported in other countries. Furthermore, a difference in the pathogen spectrum could be observed depending on the age group and body site.
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STUDY QUESTION: What are the downstream endocrine and paracrine consequences of letrozole (LZ) cotreatment during ovarian stimulation and is follicle growth and recruitment affected? SUMMARY ANSWER: Letrozole cotreatment induces marked changes in both the follicular and luteal phase endocrinology causing potentiation of follicle diameter and an improved corpus luteum function without affecting the secondarily recruited follicle cohort. WHAT IS KNOWN ALREADY: Letrozole is a third-generation aromatase inhibitor that is well-established as an effective ovulatory agent, while its possible benefits in standard in vitro fertilization protocols are less thoroughly investigated. STUDY DESIGN, SIZE, DURATION: This study included a double-blinded, placebo-controlled, randomized study with LZ or placebo intervention during ovarian stimulation for IVF treatment, an observational preceding baseline natural cycle and a succeeding follow-up visit. Participants were enrolled between August 2016 and November 2018. Data from the randomized, stimulated cycle were part of a larger RCT, which was previously published. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at a public fertility clinic at Herlev Hospital, Denmark, including 31 healthy, normo-responding women eligible for IVF treatment. They underwent a natural baseline cycle and were subsequently randomized to receive either LZ 5 mg (n = 16) or placebo (n = 15) daily during ovarian stimulation from cycle day (CD) 2-3 until induction of ovulation. Throughout both cycles, monitoring was performed every third day with transvaginal ultrasound for assessment of follicle count and diameter, and blood analyses for the determination of twelve endocrine and paracrine parameters. A follow-up assessment was performed at CD2-3 in the succeeding cycle. In the randomized part of the study, we determined differences in blood parameters, follicle recruitment, and follicle diameter. In the observational part of the study, we assessed follicle recruitment in between cycles and its correlation to endocrine parameters. MAIN RESULTS AND THE ROLE OF CHANCE: Letrozole cotreatment significantly suppressed oestradiol (E2) concentrations in the follicular phase (area under the curve (AUC) -58% (95% CI [-70%; -43%], P < 0.001)) and luteal phase (AUC -39% [-63%; -1%], P = 0.046). This had a marked effect on the endocrine and paracrine output with increased follicular phase luteinizing hormone (AUC +37% [3%; 82%], P = 0.033), androstenedione (AUC +36% [6%; 74%], P = 0.016), testosterone (AUC +37% [7%; 73%], P = 0.013) and 17-OH-progesterone (AUC +114% [10%; 318%], P = 0.027). Furthermore, follicle-stimulating hormone (FSH) was increased at stimulation day 5 in the LZ group (P < 0.05). In the luteal phase, increased corpus luteum output was reflected by elevated progesterone (AUC +44% [1%; 104%], P = 0.043), inhibin A (AUC +52% [11%; 108%], P = 0.011), androstenedione (AUC +31% [9%; 58%], P = 0.006) and testosterone (AUC +29% [6%; 57%], P = 0.012) in the LZ group. The altered balance between oestrogens and androgens was reflected in a markedly reduced SHBG concentration in the LZ group throughout the luteal phase (AUC -35% [-52%; -11%], P = 0.009). Endocrine and paracrine parameters were similar between groups at the follow-up visit. Letrozole cotreatment significantly increased the mean number of follicles >16 mm at oocyte retrieval (7.2 vs 5.2, difference: 2.0, 95% CI [0.1; 3.8], P = 0.036), while the mean total number of follicles at oocyte retrieval was the same (23.7 vs 23.5, difference: 0.2 [-5.8; 6.1], P = 0.958), and the mean FSH consumption during the stimulated cycle was similar (1500 vs 1520 IU, difference -20 IU [-175; 136], P = 0.794). Between cycles, the mean antral follicle count at CD2-3 was unchanged (natural cycle 19.0, stimulated cycle 20.9, follow-up cycle 19.7, P = 0.692) and there was no effect of LZ cotreatment on the recruitment of the next follicle cohort (test for interaction, P = 0.821). LIMITATIONS, REASONS FOR CAUTION: This study included a relatively small, selected group of healthy women with an expected normal ovarian function and reserve, and the effects of LZ may therefore be different in other patient groups. WIDER IMPLICATIONS OF THE FINDINGS: We confirm some previous findings concerning increased follicle growth and increased endogenous FSH and androgen production, which support the rationale for further studies on the use of LZ cotreatment, for example, as a form of endogenous androgen priming sensitizing the follicle to FSH. Letrozole appears to improve the luteal phase with better stimulation of corpus luteum and progesterone secretion. STUDY FUNDING/COMPETING INTEREST(S): The authors declare no conflicts of interest relating to the present work. TRIAL REGISTRATION NUMBER: NCT02939898.
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Letrozol , Indução da Ovulação , Androgênios , Androstenodiona , Método Duplo-Cego , Feminino , Fertilização in vitro/métodos , Hormônio Foliculoestimulante/uso terapêutico , Humanos , Letrozol/farmacologia , Indução da Ovulação/métodos , Progesterona , TestosteronaRESUMO
OBJECTIVE: Evaluating the validity of pre-eclampsia registration in the Medical Birth Registry of Norway (MBRN) according to both broader and restricted disease definitions. DESIGN: Retrospective nested cohort study. SETTING: Multicenter study. POPULATION: In this study, two cohorts of women with pre-eclamptic pregnancies registered in the MBRN were selected. Study group 1 contained 966 pregnancies from 1967 to 2002. Concomitant participation in the Nord-Trøndelag Health Study 2 was required. Study group 2 comprised 1138 pregnancies recorded in 1967-2005, examined as a pre-eclampsia biobank was established. METHODS: Diagnostic criteria vary. The broader criteria for pre-eclampsia, used by the MBRN, are one measurement of hypertension and proteinuria (Criterion A). Criteria used internationally today require two measurements of hypertension and proteinuria (Criterion B). The diagnostic validities in Study groups 1 and 2 were judged against medical records according to Criterion A and B, respectively. MAIN OUTCOME MEASURES: Positive predictive value (PPV) and trend analyses. RESULTS: The diagnosis was confirmed in 88.3% of pregnancies in Study group 1, and in 63.6% in Study group 2. PPV was high for Study group 1 throughout the period. For Study group 2, results improved significantly after 1986. CONCLUSIONS: This study ascertains high PPV of pre-eclampsia in the MBRN using broader traditional criteria, although the PPV decreases through assessment using restricted modern criteria. This illustrates how inclusion of direct measurements may improve registration of complex disorders defined by changing diagnostic criteria.
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Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Sistema de Registros , Estudos de Coortes , Feminino , Humanos , Noruega/epidemiologia , Valor Preditivo dos Testes , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: The objective of the study was to investigate the prognostic impact of deoxyribonucleic acid (DNA) ploidy in endometrial carcinoma in a routine diagnostic series as compared with a research series. STUDY DESIGN: We studied a population-based series of 363 endometrial carcinomas prospectively collected, with long and complete follow-up. The prognostic value of DNA ploidy was investigated in a routine diagnostic series (n=262) and compared with the results from a previous research series (n=101). RESULTS: The proportion of DNA aneuploid tumors was 21% in the research series and 25% in the routine diagnostic series (P=NS). In both series, DNA aneuploidy was significantly correlated to higher age at diagnosis, nonendometrioid subtype, and high histologic grade. Patients with DNA aneuploid tumors had significantly poorer survival, adjusted for established clinicopathologic prognostic factors. CONCLUSION: DNA ploidy estimation in endometrial carcinoma adds independent prognostic information in a routine diagnostic setting.
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Biomarcadores Tumorais/genética , DNA/genética , Neoplasias do Endométrio/genética , Idoso , Aneuploidia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Ploidias , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
Many psychiatric patient groups smoke heavily, but little is known regarding the effects of this habit on functional brain imaging results. The present report assesses the effect of chronic smoking on the blood oxygen level-dependent (BOLD) response to a simple visual activation (VA) task and a breath hold (BH) task in patients with schizophrenia. Eight healthy controls and twelve patients with schizophrenia were studied. Half of each group had never smoked and the other half of each group had smoked for more than 10 pack years. Responses to the VA task were assessed in the visual cortex and responses to the BH task were assessed in gray matter generally. There were four fMRI-dependent measures: (1) median percent signal change; (2) activation volume (in voxels); (3) time-to-peak of the impulse response function (IRF); and (4) time-to-trough of the IRF. All measures were tested as dependent variables in an ANCOVA with diagnosis and smoking status as crossed factors and age as a covariate. Heavy smokers had 22% larger percent signal change for the VA task and 50% larger percent signal change for the BH task. Patients had a 40% larger percent signal change for the breath hold task. Other statistically significant effects of smoking history on activation volume and the timing of the brain responses were noted. If replicated, the results may have important implications for fMRI studies comparing groups with markedly different smoking habits, such as studies comparing patients with schizophrenia, 60-90% of whom smoke, and healthy controls, who smoke with a much lower frequency.
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Oxigênio/sangue , Esquizofrenia/sangue , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Fumar/fisiopatologia , Percepção Visual/fisiologia , Adulto , Envelhecimento/fisiologia , Circulação Cerebrovascular/fisiologia , Feminino , Movimentos da Cabeça/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Mecânica Respiratória/fisiologia , Córtex Visual/fisiologiaRESUMO
This research examined hand preference and postural characteristics of aimed throwing in capuchin monkeys and humans. We sought to directly compare the throwing performances of these primates, particularly the extent to which target distance influences hand preference, throwing posture, and throwing accuracy. For both species we found positive correlations between target distances for throwing accuracy, direction and strength of hand preference, percentage of bipedal vs tripedal throws, and percentage of overarm vs underarm throws. Throwing accuracy did not vary as a function of right vs left hand use although for monkeys throwing accuracy was positively associated with hand preference strength. We noted a sex difference among humans as males threw more accurately than did females. Between-species analysis indicated that humans exhibited greater right- vs left-hand use, greater hand preference strength, a greater relative percentage of bipedal vs tripedal throws, and a lower relative percentage of overarm vs underarm throws than did monkeys. We believe that the capuchin monkey is an informative nonhuman primate model of aimed throwing in humans and that research examining the throwing behavior of capuchins provides insight into the neurological and behavioral characteristics that underlie coordinated multi-joint movements across the primate order.
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Lateralidade Funcional , Destreza Motora , Orientação , Desempenho Psicomotor , Adulto , Animais , Cebus , Feminino , Humanos , Masculino , Modelos Animais , Postura , Especificidade da EspécieRESUMO
This research examined token-mediated tool-use in a tufted capuchin monkey (Cebus apella). We conducted five experiments. In experiment 1 we examined the use of plastic color-coded chips to request food, and in experiments 2-5 we examined the use of color-coded chips to request tools. Our subject learned to use chips to request tools following the same general pattern seen in great apes performing analogous tasks, that is, initial discrimination followed by an understanding of the relationship among tokens, tools, and their functions. Our findings are consistent with the view that parallel representational processes underlie the tool-related behavior of capuchins and great apes.