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BACKGROUND: Patients with inherited ichthyosis suffer from scaling due to mutations affecting the epidermal barrier. Symptomatic treatment with ointments, bathing and mechanical scale removal can alleviate the disease, but therapy is time and cost intensive. OBJECTIVES: We investigated costs, time and disease burden of ichthyoses. The study addresses difficulties of the healthcare situation for patients with ichthyoses and reveals potential improvements. MATERIALS AND METHODS: We developed a questionnaire addressing time and financial effort for the treatment. Additionally, we collected data of the Dermatology Life Quality Index (DLQI) and the Pruritus Life Quality (5PLQ) questionnaires to determine the impact of ichthyosis and associated pruritus on quality of life (QoL). RESULTS: We recruited 144 patients with ichthyosis (median age: 23; 53.5% female) from the Department of Dermatology in Muenster (Germany) and the German patient support group including common, rare and syndromic subtypes. Eighty-seven percent reported applying topical therapeutics at least once per day, 66.4% several times with an overall median duration of 15 min. Highest single expenditure of time was due to balneotherapy (n = 115; median bathing time: 40 min). In 81.9%, the health insurance did not completely cover the costs for topical treatment causing additional financial burden to the patient with a median of 71 per quarter, herein creams being the largest cost factor (50 ). Patients with Netherton syndrome showed the highest median expenditure (170 ). The QoL impairment under treatment was moderate (median DLQI: 8.5 points). Pruritus was prevalent in 79.9% and showed a distinct impact on QoL (median 5PLQ: 7.5 points) without any significant difference between the subtypes (p = 0.37). CONCLUSION: Patients suffering from ichthyoses have a large and lifelong overall burden in mild and severe subtypes. Since continuous topical treatment is required, financial and psychosocial support needs to be considered beyond dermatological care.
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OBJECTIVES: To evaluate the theoretical added value of two types of non-invasive prenatal screening (NIPS) expansions in pregnancies without major structural anomalies over the commonly used NIPS for chromosomes 13, 18, 21, X and Y (5-NIPS) and to compare them with the added value of chromosomal microarray analysis (CMA). METHODS: This was a retrospective cohort study based on CMA results of all pregnancies with normal ultrasound (including pregnancies with soft markers and with abnormal maternal serum screening) that had undergone amniocentesis between January 2013 to February 2022 and were registered in the database of the Rabin Medical Center genetic laboratory. We calculated the theoretical yield of 5-NIPS and compared the added value of expanded 5-NIPS for common microdeletions (1p36.3-1p36.2, 4p16.3-4p16.2, 5p15.3-5p15.1, 15q11.2-15q13.1 and 22q11.2) and genome-wide NIPS (including variants > 5 Mb) with the added value of CMA in the overall cohort and in subgroups according to indication for invasive testing. RESULTS: Among the 8605 examined pregnancies, 122 (1.4%) clinically significant CMA results were demonstrated. Of these, 44 (36.1%) were theoretically detectable on 5-NIPS, with the rates of 1.56% in 642 pregnancies with abnormal maternal serum screening, 0.63% in 318 pregnancies with soft markers, 0.62% in 4378 women with advanced maternal age (≥ 35 years) and 0.15% in 3267 women younger than 35 years. In addition to aneuploidies detectable on 5-NIPS, three (0.03%) cases detectable on 5-NIPS expanded for common microdeletions and nine (0.10%) cases detectable on genome-wide NIPS (excluding common microdeletions) were identified in the overall cohort. The added value of expanded NIPS tools over 5-NIPS was significantly lower compared with that of CMA, for the overall cohort and subgroups. CONCLUSIONS: 5-NIPS and even genome-wide NIPS would miss 63.9% and 54.1% of clinically significant CMA findings, respectively. The added value of 5-NIPS expanded to detect common microdeletions over 5-NIPS is about 0.035%, and the overall added value of genome-wide NIPS aimed at large CNVs is about 0.14%, both much lower compared with the added value of CMA (0.91%). These findings should assist healthcare practitioners in guiding couples towards informed decision-making regarding the choice between prenatal invasive testing and NIPS. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
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Amniocentese , Aneuploidia , Gravidez , Feminino , Humanos , Adulto , Estudos Retrospectivos , Análise em Microsséries , Cromossomos , Diagnóstico Pré-Natal/métodos , Aberrações Cromossômicas , Variações do Número de Cópias de DNARESUMO
INTRODUCTION: In recent years, improved diagnosis of prostate cancer has allowed the development of focal therapy, in order to reduce the morbidity of treatments. Our study assesses the medium-term oncological and functional results of FocalOne® HIFU treatment in localized prostate cancer. METHODS: This is a retrospective, multicentre study including patients with low- or intermediate-risk localized prostate cancer treated with Focal one HIFU between November 2014 and December 2019. The primary endpoint was the retreatment rate and subgroup analyses were performed to identify predictive factors of retreatment. RESULTS: One hundred and thirty-seven patients were included with a median follow-up of 25.5 months. Seventy percent of patients had clinical stage T2, 64% had an ISUP score of 2 or 3 on initial biopsies and 38% were treated with hemi-ablation. Follow-up biopsies were performed in 76.6% of patients during follow-up with 21.8% having clinically significant cancers. The retreatment rate at 24 months was 37.2%, with positive biopsies being the primary criterion for retreatment. Patients with a PSA>8ng/mL had a significantly higher retreatment rate. Finally, morbidity remained acceptable with 5.8% of patients requiring reoperation for complications and 21% for de novo erectile dysfunction. CONCLUSION: Our results are in agreement with those of the literature, seeming to indicate a lower morbidity of the focal treatment by HIFU compared to the radical treatments while offering an acceptable oncological control. Prospective randomized trials are ongoing.
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Neoplasias da Próstata , Ultrassom Focalizado Transretal de Alta Intensidade , Masculino , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Estudos Prospectivos , Neoplasias da Próstata/cirurgia , Ultrassom Focalizado Transretal de Alta Intensidade/métodos , Antígeno Prostático EspecíficoRESUMO
Children with severe cerebral palsy are prone to low bone mineral density. No clear recommendation exists for an optimal use of standing frame to enhance bone health in this context. Used in real life, this study suggests for the first time that standing practice improved bone mineralization by limiting bone resorption. INTRODUCTION: To compare the bone health of children with severe cerebral palsy who use a static standing frame in real life to that of children who do not. METHODS: A total of 24 children with severe cerebral palsy GMFCS IV & V were included in the study and were divided into two groups: 13 were using a passive standing frame and 11 were not. We performed a single center retrospective cross-sectional study comparing the two groups using dual X-ray absorptiometry data and tests on biological samples, including bone remodeling factors. RESULTS: Total body (less head) bone mineral content was significantly higher in children who used a standing frame for an average of 30 min/day. This was confirmed in the lumbar spine. Although the total body bone mineral density (less head and proximal femur) densitometric data were not significantly higher, a positive trend favored the use of a standing frame in the children. Bone resorptive factors (CTX) were higher in the non-standing-frame group, whereas there was no difference among osteoformation factors. No difference in fracture history was found. CONCLUSIONS: We show that non-ambulant children with cerebral palsy who use a static standing frame in real life have better bone health, with lower bone resorption, than children who do not. Further studies are needed to determine how standing practice could impact bone mineralization over time in real life and to explore more bone remodeling factors.
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Reabsorção Óssea , Paralisia Cerebral , Absorciometria de Fóton , Densidade Óssea , Remodelação Óssea , Criança , Estudos Transversais , Humanos , Vértebras Lombares , Estudos RetrospectivosRESUMO
OBJECTIVE: To compare acute treatment responses and long-term outcome in leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis. METHODS: Retrospective case series of 118 patients with LGI1 antibody encephalitis evaluated at Mayo Clinic across all US sites from 1 May 2008 to 31 March 2019. Patient clinical data were identified and analysed through the neuroimmunology laboratory and electronic medical record. LGI1 antibody detection was by cell-based indirect immunofluorescence assay of serum, cerebrospinal fluid or both. Clinical outcomes were faciobrachial dystonic seizure (FBDS) resolution, modified Rankin Scale (mRS) score, Kokmen Short Test of Mental Status (STMS) score (0-38 point scale) and neuropsychometric testing results. RESULTS: Compared with intravenous immunoglobulin (IVIg) (n=21), patients treated with single-agent acute corticosteroids (intravenous, oral or both) (n=49) were more likely to experience resolution of FBDS (61% vs 7%, p=0.002) and improvements in mRS score (ΔmRS score 2 vs 0, p=0.008) and median Kokmen STMS scores (ΔKokmen STMS score 5 points vs 0 points, p=0.01). In 54 patients with long-term follow-up (≥2 years), the median mRS score was 1 (range 0-6) and the median Kokmen STMS score was 36 (range 24-38) after all combinations of immunotherapy. Neuropsychometric testing in 32 patients with long-term follow-up (≥2 years) demonstrated short-term memory impairments in 37%. CONCLUSIONS: Corticosteroids appeared more effective acutely than IVIg in improving LGI1 antibody encephalitis in this retrospective comparison of immunotherapies. While improvement with immunotherapy is typical and long-term outcome is favourable, short-term memory deficits are noted in approximately a third of the patients.
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Corticosteroides/uso terapêutico , Autoanticorpos , Doenças Autoimunes/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Encefalite Límbica/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/imunologia , Feminino , Humanos , Encefalite Límbica/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Child burns rank among the most frequent domestic accidents in France. COVID-19 lockdown between March 16th and May 11th of 2020 increased time spent at home by children. MATERIAL: This retrospective, observational study described the epidemiological impact of COVID-19 lockdown on child burns in a pediatric surgery department compared with previous five years. Child burns in the previous five years constituted the "before COVID-19 group" as the reference group. Child burns during the first lockdown formed the "COVID-19 group". Demographics characteristics, the delay before first attendance at the surgery department, burns characteristics, the place of the incident, need of skin graft, and child reactions to trauma or isolation were recorded for these two groups. RESULTS: A total of thirty-seven children were included, 16 of them in the COVID-19 group. In the COVID-19 group, burned children were mainly boys, with a median age of 18 months. The median time before first attendance was four days. Main burns characteristics were to be deep partial thickness burns, involved lower limbs, caused by scalding. All burns occurred at home. Half parents reported child reactions to trauma or isolation among their children before burn injury. CONCLUSION: The incidence of child burn injuries in the COVID-19 group was higher compared to the before COVID-19 group, but no increased delay to attendance recorded. Time spent at home and psychosocial impact of lockdown might partially explain this high incidence rate of child burns. LEVEL OF EVIDENCE: IV.
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Acidentes Domésticos/estatística & dados numéricos , Queimaduras/epidemiologia , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pandemias , Estudos Retrospectivos , Distribuição por SexoRESUMO
According to the developmental origins of health and disease (DOHaD) hypothesis, changes in the maternal environment are known to reprogram the metabolic response of offspring. Known for its redox modulation, caloric restriction extends the lifespan of some species, which contributes to diminished cellular damage. Little is known about the effects of gestational caloric restriction, in terms of antioxidant parameters and molecular mechanisms of action, on the reproductive organs of offspring. This study assessed the effects of moderate (20%) caloric restriction on redox status parameters, molecular expression of sirtuin (SIRT) 1 and SIRT3 and histopathological markers in the ovaries and testes of adult rats that were subjected to gestational caloric restriction. Although enzyme activity was increased, ovaries from female pups contained high levels of oxidants, whereas testes from male pups had decreased antioxidant enzyme defences, as evidenced by diminished glyoxalase I activity and reduced glutathione content. Expression of SIRT3, a deacetylase enzyme related to cellular bioenergetics, was increased in both ovaries and testes. Previous studies have suggested that, in ovaries, diminished antioxidant metabolism can lead to premature ovarian failure. Unfortunately, there is little information regarding the redox profile in the testis. This study is the first to assess the redox network in both ovaries and testes, suggesting that, although intrauterine caloric restriction improves molecular mechanisms, it has a negative effect on the antioxidant network and redox status of reproductive organs of young adult rats.
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Restrição Calórica/efeitos adversos , Mitocôndrias/metabolismo , Ovário/metabolismo , Efeitos Tardios da Exposição Pré-Natal , Sirtuínas/análise , Testículo/metabolismo , Animais , Antioxidantes/análise , Antioxidantes/metabolismo , Feminino , Masculino , Ovário/química , Oxirredução , Gravidez , Ratos , Ratos Wistar , Sirtuína 1/análise , Sirtuína 3/análise , Testículo/químicaRESUMO
INTRODUCTION: Capnocytophagacanimorsus (C. canimorsus), a commensal Gram-negative bacillus found in the oral cavity of dogs and cats, is pathogenic for humans, with the most common clinical manifestations being septicemia, meningitis and endocarditis. Herein we report a case of CC bacteremia manifesting as multiple plaques of erythema annulare centrifugum associated with monoarthritis of the knee. PATIENTS AND METHODS: A 66-year-old man consulted for a skin rash and monoarthritis of the right knee with fever following an insect bite on his right hallux. Cutaneous examination revealed numerous erythematous annular plaques on the trunk and limbs with centrifugal extension. Analysis of synovial fluid from the right knee showed an inflammatory liquid with a sterile bacteriological culture and PCR was negative for Borrelia. C. canimorsus bacteria were isolated from blood cultures. 16S RNA PCR performed on the synovial fluid was positive for the same organism. The patient's history revealed that his hallux wound had been licked by his dog. DISCUSSION: C. canimorsus most frequently affects immunosuppressed subjects. Cutaneous signs are seen in half of all cases, most frequently presenting as cellulitis, pathological livedo or thrombotic purpura. We report herein a case of CC bacteremia in an immunocompetent patient manifesting as multiple plaques of erythema annulare centrifugum, an unusual sign, and monoarthritis of one knee.
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Artrite/microbiologia , Bacteriemia/complicações , Capnocytophaga , Eritema/microbiologia , Infecções por Bactérias Gram-Negativas/complicações , Articulação do Joelho , Dermatopatias Genéticas/microbiologia , Idoso , Animais , Doenças do Cão/microbiologia , Doenças do Cão/transmissão , Cães , Eritema/patologia , Humanos , Masculino , Dermatopatias Genéticas/patologiaRESUMO
INTRODUCTION AND PURPOSE: The objective of this work was to identify the risk factors (RFs) of active surveillance (AS) interruption in a prostate cancer (PCa) single-center retrospective cohort of patients. MATERIAL AND METHOD: All patients in AS between January 2011 and October 2019 were retrospectively included in a computerized database. The group of patients who had an AS interruption was compared to the one still under AS, in order to identify potential risk factors for the interruption of the surveillance protocol. RESULTS: Two hundred and two patients have been included in the AS cohort with a median follow-up of 32months. At the time of analysis, 72 patients (36%) were not under the AS protocol anymore, 118 (58%) were still under AS and 12 (6%) were lost of follow-up. Sixty-six patients (92%) had left SA due to PCa progression, 4 (5%) by personal choice and 2 (3%) switched to watchful waiting. A PSA doubling Time<3years (PSADT<3years) has been identified as the only statistically significant RF for AS interruption, both in the unvaried (P<0.001) and multivariate (OR=5.403, P<0.01) analysis. It was also the only RF of AS interruption in the early analysis in the first three years of AS, in the unvaried analysis (P=0.021) and the multivariate analysis (OR=3.612, P=0.018). CONCLUSION: PSADT was the only RF of AS early and late interruption in our study. It represents a major inclusion criterion in AS protocol during the initial assessment. LEVEL OF EVIDENCE: 3.
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Neoplasias da Próstata/terapia , Conduta Expectante , Idoso , Estudos de Coortes , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Fatores de TempoRESUMO
Intra-Subject Variability (ISV), a potential index of catecholaminergic regulation, is elevated in several disorders linked with altered dopamine function. ISV has typically been defined as reaction time standard deviation. However, the ex-Gaussian and spectral measures capture different aspects and may delineate different underlying sources of ISV; thus reflecting different facets of the construct. We examined the impact of factors associated with dopamine metabolism, namely, Catechol-O-Methyltransferase Val158Met (COMT) genotype and Working Memory (WM) and response-switching on ISV facets in young healthy adults. The Met allele was associated with overall increased variability. The rather exclusive sensitivity of ex-Gaussian tau to frequencies below 0.025â¯Hz and the quasi-periodic structure of particularly slow responses support the interpretation of tau as low frequency fluctuations of neuronal networks. Sigma, by contrast, may reflect neural noise. Regarding cognitive demands, a WM load-related increase in variability was present for all genotypes and all ISV facets. Contrastingly, ISV facets reacted differently to variations in response-switching as, across genotypes, sigma was elevated for rare target trials whereas tau was elevated for frequent standard trials, particularly for Met homozygotes. Our findings support the significant role of COMT in regulating behavioural ISV with its facetted structure and presumed underlying neural processes.
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Catecol O-Metiltransferase/genética , Memória de Curto Prazo/fisiologia , Tempo de Reação/genética , Alelos , Cognição/fisiologia , Potenciais Evocados , Feminino , Genótipo , Voluntários Saudáveis , Humanos , Masculino , Tempo de Reação/fisiologia , Adulto JovemRESUMO
Atherosclerosis is a disease which affects the whole arterial vascular tree. In particular patients with peripheral arterial occlusive disease (PAOD) often suffer from additional atherosclerotic manifestations in other vascular territories. This has a direct impact on cardiovascular prognosis. Atherosclerosis is an inflammatory disease. A high inflammatory burden is associated with polyvascular atherosclerosis and also with the occurrence of cardiovascular events. Control of cardiovascular risk factors is crucial for the treatment of patients with polyvascular atherosclerosis. In addition, anticoagulation treatment is very important in patients with atherosclerosis. Moreover, exercise training is an important treatment option in PAOD patients not only to improve walking distance but also for multiple additional positive effects. So far the role of anti-inflammatory treatment is not clear and must be further elaborated by future clinical research.
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Arteriopatias Oclusivas , Aterosclerose , Doença Arterial Periférica , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Humanos , Doença Arterial Periférica/complicações , PrognósticoRESUMO
INTRODUCTION: Inborn errors of tetrahydrobiopterin (BH4) biosynthesis or recycling are a group of very rare neurometabolic diseases. Following growing awareness and improved availability of drug treatment the number of patients with BH4 disorders reaching adulthood is constantly increasing. Pregnancy care of patients with these disorders is therefore a new challenge for clinicians. METHODS: This retrospective study summarises for the first time clinical and biochemical monitoring data of 16 pregnancies in seven women with different disorders of BH4 metabolism and evaluates treatment regimens before and during pregnancy in relation to the obstetrical outcome and paediatric follow-up. RESULTS: Worsening of pre-existing neurological symptoms or occurrence of new symptoms during pregnancy was not observed in most of the cases. Treatment regimens remained mostly unchanged. Pregnancies were not complicated by disease-specific features. Organ abnormalities, miscarriage, prematurity, IUGR and chromosomal changes were occasionally reported, without showing any association with the standard drug treatment for BH4 deficiencies. CONCLUSION: Although our data on 16 pregnancies in seven patients did not present any association of standard drug treatment with an increased rate of pregnancy complications, abnormal obstetrical or paediatric outcome, an intensive clinical and biochemical supervision by a multidisciplinary team before, during and after the pregnancy in any BH4 deficiency is essential since available data on pregnancies in patients with BH4 deficiencies is limited.
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Biopterinas/análogos & derivados , Fenilcetonúrias/tratamento farmacológico , Complicações na Gravidez/etiologia , Resultado da Gravidez , Adolescente , Adulto , Biopterinas/uso terapêutico , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações na Gravidez/prevenção & controle , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: A pilot study to assess the efficacy and safety of a novel specs device developed to alleviate chronic dizziness using eyeglasses with referential marks fixed on the lenses. MATERIALS AND METHODS: Forty patients with stable symptoms of chronic dizziness for more than 3 months participated in a 4-week, double-blind, randomized treatment with Active-Specs or Sham-Specs. Efficacy was assessed using validated semiquantitative scales and questionnaires of vertigo, dizziness and anxiety. Safety evaluation included monitoring of any adverse event. RESULTS: Thirty-six participants were included in the efficacy analysis, 18 in each group. Twelve of 18 subjects (67%) treated with Active-Specs reported substantial improvement of symptoms compared to six (33%) with Sham-Specs showing a significant improvement on Clinical Global Impressions scale (P = .017). The Active-Specs group showed significant reduction in the Vertigo Visual Analogue Scale (P = .017) and a nonsignificant but consistent trend of improvement measured by the Dizziness Handicap Inventory and Beck Anxiety Inventory. There were no adverse events related to the treatment. CONCLUSIONS: This novel specs device seems to be a safe and promising novel treatment for chronic dizziness. We hypothesize that marks in specific zones of the peripheral visual field could strengthen information of real head motion counteracting the mismatch sensory and locomotor information causing chronic dizziness. The results of this pilot study should be followed up by additional studies aimed at confirming the present encouraging findings.
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Tontura/diagnóstico , Tontura/terapia , Óculos/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/terapia , Doença Crônica , Tontura/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Inquéritos e Questionários , Vertigem/diagnóstico , Vertigem/epidemiologia , Vertigem/terapiaRESUMO
Milk-fat globule epidermal growth factor (EGF) 8 protein (MFGE8), also known as lactadherin, promotes cell adhesion in an Arg-Gly-Asp (RGD)-dependent modus via integrins. In the present study, the expression of MFGE8 was examined in equine endometrium during oestrus and at Days 12 and 16 after ovulation in pregnant and non-pregnant mares and in mares during the 5th month of gestation. Results demonstrated that MFGE8 is expressed at the embryo- and fetal-maternal interface in equine pregnancy. In non-pregnant endometrium its expression was upregulated by oestrogen, a finding that was confirmed using endometrial explant culture. MFGE8 was expressed at similar levels by conceptuses collected 13 and 14 days after ovulation and by allantochorion sampled during the 5th month of gestation. Pericytes of endometrial blood vessels displayed strong MFGE8 expression upon in situ hybridisation. During the 5th month of gestation, the fetal side of the allantochorionic villi in particular displayed pronounced staining upon in situ hybridisation, confirming that MFGE8 expression is not restricted to early pregnancy but persists and is present at the fetal-maternal interface. Potential roles of MFGE8 in equine pregnancy include mediating cell-cell adhesion, promotion of angiogenesis and placental transfer of fatty acids.
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Antígenos de Superfície/metabolismo , Endométrio/metabolismo , Proteínas do Leite/metabolismo , Placenta/metabolismo , Animais , Endométrio/efeitos dos fármacos , Estradiol/farmacologia , Feminino , Cavalos , Placenta/efeitos dos fármacos , GravidezRESUMO
OBJECTIVES: The proportion of deaths attributed to hypertensive diseases (HYPDs) was only 50% of that registered for cerebrovascular diseases (CBVDs) in 2013 in Brazil. This article aims to evaluate mortality related to HYPDs and CBVDs as multiple causes of death, in Brazil from 2004 to 2013. STUDY DESIGN: Analysis of historical series of secondary data obtained from Brazilian official registries. METHODS: Data about the deaths were obtained from the Mortality Information System of the Brazilian Ministry of Health, available on the DATASUS website. CBVDs and HYPDs were evaluated according to their mentions as the underlying cause of death or entry in any line of the death certificates (DCs), according to their International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. RESULTS: When CBVDs were the underlying causes of death, HYPDs were mentioned in 40.9% of the DCs. When HYPDs were the underlying causes of death, CBVDs were mentioned in only 5.0%. When CBVDs were mentioned without HYPDs, they were selected as the underlying cause of death 74.4% of the time. When HYPDs were mentioned in DCs without CBVDs, HYPDs were selected 30.0% of the time. In 2004, the frequency of any mention of HYPDs relative to the frequency of HYPDs cited as underlying causes increased fourfold and was followed by a plateau until 2013. In contrast, the frequency of any mention of CBVDs relative to the frequency of CBVDs as underlying causes decreased in the same period. Because this study was based on DC records, it was limited by the way these documents were completed, which may have included lack of record of the causes related to the sequence that culminated in death. CONCLUSION: When deaths related to HYPDs were evaluated as multiple causes of death, they were mentioned up to four times more often than when they were selected as underlying causes of death. This reinforces the need for better control of hypertension to prevent deaths.
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Transtornos Cerebrovasculares/mortalidade , Hipertensão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Causas de Morte/tendências , Atestado de Óbito , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Palliative sedation (PS) serves as a therapeutic option in cases of otherwise intractable suffering. As the use of sedative and hypnotic medication in many diverse situations is a core competency of anesthesiology, anesthesiologists are confronted with questions of sedative therapy at the end of life in institutions for specialized palliative care, in intensive care units and intermediate care wards. In recent years a number of guidelines have been published internationally but so far no official guidelines exist in Germany. The most recognized document is the European Association for Palliative Care (EAPC) framework on PS. This project aims to develop a German language template for the preparation, application, documentation and evaluation of PS according to the current frameworks, especially the EAPC framework on PS. METHODS: A first draft of the template was generated by the project team using the EAPC framework and individual templates of various institutions, which had been collected during a previous project. Professionals (nâ¯= 136) from inpatient and outpatient specialist palliative and hospice care were invited to assess all items of the draft regarding "relevance", "wording" and "feasibility" in an online Delphi survey (Unipark®, Questback, Cologne, Germany). After the second Delphi round an expert panel was asked to reflect the results and generate a final draft. Approval was granted if acceptance exceeded 75% of participants. RESULTS: The 3 rounds of the Delphi process were completed by 64, 46 and 41 participants, respectively. The Delphi process as well as the expert panel led to significant changes of the template. The indications for PS had to be clarified. The significance of documentation of vital parameters, such as oxygen saturation, blood pressure or respiratory rate during PS was intensively discussed. In many teams, predominantly hospice or outpatient palliative care teams, it seems to be difficult to measure these parameters or it is regarded as inappropriate in a palliative care setting. In contrast, the EAPC framework recommends monitoring of vital parameters in cases of intermittent or respite sedation. Finally, a solution was found to support documentation of additional data without the explicit mentioning of specific parameters. After the third Delphi round, all 16 items of the documentation template reached consensus with respect to relevance (82.9-100%), clarity of wording (80.5-100%), and feasibility in practice (78-100%). CONCLUSION: This article provides an empirically based, multiprofessional consented documentation template for PS. Core elements of the documentation of PS are the indications and the decision process towards PS. During the treatment, at least the level of sedation and the symptom burden have to be recorded. The documentation of vital signs during PS remains a highly disputed topic. The presented data suggest that especially in outpatient settings and in hospices measuring and documentation of vital parameters is uncommon and therefore is often regarded as not feasible. This template can help to support the medically and ethically sound use of PS and facilitate research. The template can be accessed at http://www.palliativmedizin.uk-erlangen.de/forschung/downloads/ .
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Sedação Profunda/normas , Documentação/normas , Guias como Assunto , Cuidados Paliativos/normas , Anestesia , Consenso , Tomada de Decisões , Atenção à Saúde , Alemanha , Humanos , Idioma , Inquéritos e QuestionáriosRESUMO
Vacuolar protein sorting 35 (VPS35) is a core component of the retromer complex, crucial to endosomal protein sorting and intracellular trafficking. We recently linked a mutation in VPS35 (p.D620N) to familial parkinsonism. Here, we characterize human VPS35 and retromer function in mature murine neuronal cultures and investigate neuron-specific consequences of the p.D620N mutation. We find VPS35 localizes to dendritic spines and is involved in the trafficking of excitatory AMPA-type glutamate receptors (AMPARs). Fundamental neuronal processes, including excitatory synaptic transmission, AMPAR surface expression and synaptic recycling are altered by VPS35 overexpression. VPS35 p.D620N acts as a loss-of-function mutation with respect to VPS35 activity regulating synaptic transmission and AMPAR recycling in mouse cortical neurons and dopamine neuron-like cells produced from induced pluripotent stem cells of human p.D620N carriers. Such perturbations to synaptic function likely produce chronic pathophysiological stress upon neuronal circuits that may contribute to neurodegeneration in this, and other, forms of parkinsonism.
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Mutação de Sentido Incorreto , Neurônios/metabolismo , Doença de Parkinson/genética , Receptores de Glutamato/metabolismo , Proteínas de Transporte Vesicular/genética , Animais , Espinhas Dendríticas/metabolismo , Humanos , Camundongos , Transporte Proteico , Sinapses/metabolismoRESUMO
The Banff working group on preimplantation biopsy was established to develop consensus criteria (best practice guidelines) for the interpretation of preimplantation kidney biopsies. Digitally scanned slides were used (i) to evaluate interobserver variability of histopathologic findings, comparing frozen sections with formalin-fixed, paraffin-embedded tissue of wedge and needle core biopsies, and (ii) to correlate consensus histopathologic findings with graft outcome in a cohort of biopsies from international medical centers. Intraclass correlations (ICCs) and univariable and multivariable statistical analyses were performed. Good to fair reproducibility was observed in semiquantitative scores for percentage of glomerulosclerosis, arterial intimal fibrosis and interstitial fibrosis on frozen wedge biopsies. Evaluation of frozen wedge and core biopsies was comparable for number of glomeruli, but needle biopsies showed worse ICCs for glomerulosclerosis, interstitial fibrosis and tubular atrophy. A consensus evaluation form is provided to help standardize the reporting of histopathologic lesions in donor biopsies. It should be recognized that histologic parameters may not correlate with graft outcome in studies based on organs deemed to be acceptable after careful clinical assessment. Significant limitations remain in the assessment of implantation biopsies.
Assuntos
Transplante de Rim , Rim/patologia , Rim/cirurgia , Doadores de Tecidos , Biópsia por Agulha , Consenso , HumanosAssuntos
Anticorpos Antineoplásicos/imunologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Tumores Neuroendócrinos/imunologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/tratamento farmacológicoRESUMO
This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.