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Stem cell research endeavors to generate specific subtypes of classically defined "cell types." Here, we generate >90% pure human artery or vein endothelial cells from pluripotent stem cells within 3-4 days. We specified artery cells by inhibiting vein-specifying signals and vice versa. These cells modeled viral infection of human vasculature by Nipah and Hendra viruses, which are extraordinarily deadly (â¼57%-59% fatality rate) and require biosafety-level-4 containment. Generating pure populations of artery and vein cells highlighted that Nipah and Hendra viruses preferentially infected arteries; arteries expressed higher levels of their viral-entry receptor. Virally infected artery cells fused into syncytia containing up to 23 nuclei, which rapidly died. Despite infecting arteries and occupying â¼6%-17% of their transcriptome, Nipah and Hendra largely eluded innate immune detection, minimally eliciting interferon signaling. We thus efficiently generate artery and vein cells, introduce stem-cell-based toolkits for biosafety-level-4 virology, and explore the arterial tropism and cellular effects of Nipah and Hendra viruses.
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Vírus Hendra , Vírus Nipah , Células-Tronco Pluripotentes , Artérias , Células Endoteliais , Vírus Hendra/genética , Humanos , TropismoRESUMO
Eukaryotic cells decide in late G1 phase of the cell cycle whether to commit to another round of division. This point of cell cycle commitment is termed "Restriction Point" in mammals and "Start" in the budding yeast Saccharomyces cerevisiae. At Start, yeast cells integrate multiple signals such as pheromones and nutrients, and will not pass Start if nutrients are lacking. However, how cells respond to nutrient depletion after the Start decision remains poorly understood. Here, we analyze how post-Start cells respond to nutrient depletion, by monitoring Whi5, the cell cycle inhibitor whose export from the nucleus determines Start. Surprisingly, we find that cells that have passed Start can re-import Whi5 into the nucleus. In these cells, the positive feedback loop activating G1/S transcription is interrupted, and the Whi5 repressor re-binds DNA. Cells which re-import Whi5 become again sensitive to mating pheromone, like pre-Start cells, and CDK activation can occur a second time upon replenishment of nutrients. These results demonstrate that upon starvation, the commitment decision at Start can be reversed. We therefore propose that cell cycle commitment in yeast is a multi-step process, similar to what has been suggested for mammalian cells.
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Proteínas de Saccharomyces cerevisiae , Saccharomycetales , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Ciclo Celular , Divisão Celular , Fase G1 , Saccharomycetales/metabolismoRESUMO
Open Hardware-based microcontrollers, especially the Arduino platform, have become a comparably easy-to-use tool for rapid prototyping and implementing creative solutions. Such devices in combination with dedicated front-end electronics can offer low-cost alternatives for student projects, slow control and independently operating small-scale instrumentation. The capabilities can be extended to data taking and signal analysis at mid-level rates. Two detector realizations are presented, which cover the readouts of proportional counter tubes and of scintillators or wavelength-shifting fibers with silicon photomultipliers (SiPMs). The SiPMTrigger realizes a small-scale design for coincidence readout of SiPMs as a trigger or veto detector. It consists of a custom mixed signal front-end board featuring signal amplification, discrimination and a coincidence unit for rates of up to 200 kHz. The nCatcher transforms an Arduino Nano to a proportional counter readout with pulse shape analysis: time over threshold measurement and a 10-bit analog-to-digital converter for pulse heights. The device is suitable for low-to-medium-rate environments up to 5 kHz, where a good signal-to-noise ratio is crucial. We showcase the monitoring of thermal neutrons. For data taking and slow control, a logger board is presented that features an SD card and GSM/LoRa interface.
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BACKGROUND: Patients with neurogenic lower urinary tract dysfunction (NLUTD) often rely on some type of catheterization for bladder emptying. Intermittent catheterization (IC) is considered the gold standard and is preferred over continuous catheterization, since it is considered to cause fewer urinary tract infections (UTIs) than indwelling catheterization. The main objective of our study was to describe UTI prevalence (at visit) and incidence (within the last 12 months) and urine culture characteristics between patients using an indwelling catheter versus (vs) those performing IC. METHODS: In this cross-sectional study, we prospectively evaluated from 02/2020 to 01/2021 patients with NLUTD undergoing urine cultures for prophylactic reasons or due to UTI symptoms. At visit, all patients underwent a standardized interview on current UTI symptoms as well as UTI history and antibiotic consumption within the past year. Patients using an indwelling catheter (n = 206) or IC (n = 299) were included in the analysis. The main outcome was between-group differences regarding UTI characteristics. RESULTS: Patients using an indwelling catheter were older (indwelling catheter vs IC: median 66 (Q1-Q3: 55-77) vs 55 (42-67) years of age) and showed a higher Charlson comorbidity index (indwelling catheter vs IC: median 4 (Q1-Q3: 2-6) vs 2 (1-4) (both p < 0·001). A total of 40 patients from both groups were diagnosed with a UTI at visit (indwelling catheters vs IC: 8% (16/206) vs 8% (24/299); p = 0·782), and the number of UTIs within the past 12 months was not significantly different between groups. Overall, Escherichia coli (21%), Enterococcus faecalis (17%), and Klebsiella spp. (12%) were the most frequently detected bacteria. CONCLUSIONS: In this cohort of patients with NLUTD, we did not find relevant differences in UTI frequency between groups. These results suggest that UTI-related concerns should not be given undue emphasis when counseling patients for catheter-related bladder emptying methods.
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Cateteres de Demora , Infecções Urinárias , Humanos , Cateteres de Demora/efeitos adversos , Bexiga Urinária , Cateterismo Urinário/efeitos adversos , Estudos Transversais , Infecções Urinárias/etiologia , Infecções Urinárias/microbiologia , Escherichia coliRESUMO
The soil bacteria isolated in this study, including three strains of actinobacteria and one Paraburkholderia sp., showed decolorization activity of azo dyes in the resting cell assay and were shown to use methyl red as the sole carbon source to proliferate. Therefore, their ability to degrade, bioabsorb, or a combination of both mechanism was investigated using the substrate brilliant black. The strains DP-A9 and DP-L11, within 24 h of incubation, showed complete biodegradation of 173.54 mg/L brilliant black and the strains DP-D10 and DP-P12 showed partial decolorization of 83.3 mg/L and 36.4 mg/L, respectively, by both biosorption and biodegradation. In addition, the shotgun assembled genome of these strains showed a highly diverse set of genes encoding for candidate dye degrading enzymes, providing avenues to study azo dye metabolism in more detail.
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Actinobacteria , Actinobacteria/genética , Actinobacteria/metabolismo , Compostos Azo/metabolismo , Bactérias , Biodegradação Ambiental , Corantes/metabolismoRESUMO
Surgical therapy of non-palpable malignant breast lesions requires precise preoperative localisation. Recently, radioactive iodine seed localisation has excelled among the number of localisation methods. We present our first experience with this method at our department. We describe the structure of the radioactive iodine seed, the principles of preoperative localisation and peroperative detection of the seed, the specimen transport process, histopathological examination, storage and disposal of the seed, as well as aspects of radiation protection.
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Neoplasias da Mama , Iodo , Neoplasias da Glândula Tireoide , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Radioisótopos do Iodo , Mastectomia , Mastectomia SegmentarRESUMO
Farber disease (FD) is a debilitating lysosomal storage disorder characterized by severe inflammation and neurodegeneration. FD is caused by mutations in the ASAH1 gene, resulting in deficient acid ceramidase (ACDase) activity. Patients with ACDase deficiency exhibit a broad clinical spectrum. In classic cases, patients develop hepatosplenomegaly, nervous system involvement, and childhood mortality. Ocular manifestations include decreased vision, a grayish appearance to the retina with a cherry red spot, and nystagmus. That said, the full effect of ACDase deficiency on the visual system has not been studied in detail. We previously developed a mouse model that is orthologous for a known patient mutation in Asah1 that recapitulates human FD. Herein, we report evidence of a severe ocular pathology in Asah1P361R/P361R mice. Asah1P361R/P361R mice exhibit progressive retinal and optic nerve pathology. Through noninvasive ocular imaging and histopathological analyses of these Asah1P361R/P361R animals, we revealed progressive inflammation, the presence of retinal dysplasia, and significant storage pathology in various cell types in both the retina and optic nerves. Lipidomic analyses of retinal tissues revealed an abnormal accumulation of ceramides and other sphingolipids. Electroretinograms and behavioral tests showed decreased retinal and visual responses. Taken together, these data suggest that ACDase deficiency leads to sphingolipid imbalance, inflammation, dysmorphic retinal and optic nerve pathology, and severe visual impairment.
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Ceramidase Ácida/genética , Lipogranulomatose de Farber , Mutação de Sentido Incorreto , Nervo Óptico , Retina , Transtornos da Visão , Ceramidase Ácida/metabolismo , Substituição de Aminoácidos , Animais , Ceramidas/genética , Ceramidas/metabolismo , Modelos Animais de Doenças , Lipogranulomatose de Farber/enzimologia , Lipogranulomatose de Farber/genética , Lipogranulomatose de Farber/patologia , Inflamação/enzimologia , Inflamação/genética , Inflamação/patologia , Camundongos , Camundongos Mutantes , Nervo Óptico/enzimologia , Nervo Óptico/patologia , Retina/enzimologia , Retina/patologia , Esfingolipídeos/genética , Esfingolipídeos/metabolismo , Transtornos da Visão/enzimologia , Transtornos da Visão/genética , Transtornos da Visão/patologiaRESUMO
OBJECTIVE: To provide a chronological overview of the evolution of continent urinary diversion (CUD) over the last 50 years and to highlight important milestones. METHODS: We performed an extensive literature review and analysed different forms of urinary diversion worldwide. After the evaluation of surgical techniques, we assessed the advantages and disadvantages of assorted CUD approaches based on published long-term follow-up data. RESULTS: A wide variety of surgical options for CUD is available and feasible to date, although consensus among urologists regarding the 'gold standard' is still lacking. Several forms of orthotopic bladder substitutes and continent cutaneous urinary reservoirs have been shown to provide excellent long-term results. CONCLUSION: The last 50 years of CUD have seen constant evolution and refinement of techniques, but the best surgical approach remains unclear and there is no 'one-size-fits-all' option, but rather tailor-made approaches are necessary to ensure patient satisfaction.
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Bexiga Urinária/cirurgia , Derivação Urinária , Coletores de Urina , Cistectomia , Humanos , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
BACKGROUND AND OBJECTIVES: Stage II colon cancer is primarily a surgical disease. Only a still not well-defined subset of patients may benefit from postoperative adjuvant chemotherapy. The relationship between adjuvant chemotherapy and survival after relapse is furthermore still not definitely explored in this group of patients. A number of reports suggest some association between defective mismatch repair (dMMR) and colorectal cancer stage II prognosis, but due to contradictory results from existing studies, the exact predictive role is still not fully understood. METHODS: Retrospective multicenter study including 451 stage II colon cancer patients. The proficiency or deficiency of mismatch repair was tested using immunohistochemistry and analyzed in relationship to two survival outcomes: overall survival (OS) and postrelapse survival. RESULTS: Patients with dMMR (20.4%) derived no OS benefit from adjuvant chemotherapy (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.47-2.38; P = .897). Patients with proficient mismatch repair (pMMR) tumors receiving adjuvant chemotherapy had the significantly better OS in comparison to those not receiving chemotherapy (HR, 0.54; 95% CI, 0.35-0.82; P = .004). This relationship remained significant in multivariable analysis (HR, 0.42; 95% CI, 0.22-0.78; P = .007). Patients with pMMR relapsing after adjuvant treatment lived significantly longer than those relapsing without previous adjuvant treatment (HR, 0.55; 95% CI, 0.32-0.96; P = .033) and this result remained significant in the multivariable model (HR, 0.49; 95% CI, 0.26-0.93; P = .030). CONCLUSION: In stage II CC patients, adjuvant chemotherapy improves therapeutic outcomes only in patients with pMMR tumors. Survival after relapse in patients having received adjuvant chemotherapy is significantly longer for patients with pMMR. No survival benefit from adjuvant chemotherapy was seen among patients with dMMR tumors.
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BACKGROUND: The phased withdrawal of oral polio vaccine (OPV) and the introduction of inactivated poliovirus vaccine (IPV) is central to the polio 'end-game' strategy. METHODS: We analyzed the cost implications in Chile of a switch from the vaccination scheme consisting of a pentavalent vaccine with whole-cell pertussis component (wP) plus IPV/OPV vaccines to a scheme with a hexavalent vaccine with acellular pertussis component (aP) and IPV (Hexaxim®) from a societal perspective. Cost data were collected from a variety of sources including national estimates and previous vaccine studies. All costs were expressed in 2017 prices (US$ 1.00 = $Ch 666.26). RESULTS: The overall costs associated with the vaccination scheme (4 doses of pentavalent vaccine plus 1 dose IPV and 3 doses OPV) from a societal perspective was estimated to be US$ 12.70 million, of which US$ 8.84 million were associated with the management of adverse events related to wP. In comparison, the cost associated with the 4-dose scheme with a hexavalent vaccine (based upon the PAHO reference price) was US$ 19.76 million. The cost of switching to the hexavalent vaccine would be an additional US$ 6.45 million. Overall, depending on the scenario, the costs of switching to the hexavalent scheme would range from an additional US$ 2.62 million to US$ 6.45 million compared with the current vaccination scheme. CONCLUSIONS: The switch to the hexavalent vaccine schedule in Chile would lead to additional acquisition costs, which would be partially offset by improved logistics, and a reduction in adverse events associated with the current vaccines.
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Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/economia , Substituição de Medicamentos/economia , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/economia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/economia , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/economia , Vacina Antipólio Oral/administração & dosagem , Vacina Antipólio Oral/economia , Vacinação/economia , Chile , Custos e Análise de Custo , Humanos , Esquemas de Imunização , Lactente , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/economiaRESUMO
The aim of this study was to screen for and determine the prevalence, severity and determinants of anaemia in pregnant women attending antenatal clinics in south of Tanzania. In this facility-based cross-sectional descriptive study, pregnant women attending antenatal clinics were selected through a convenient non-probability sampling in one district hospital in south of Tanzania. Interviews using standardized questionnaires were conducted, physical examination and determination of haemoglobin levels done. Data analysis was done using SPPS V20.0. A total of 356 pregnant women werw included in this analysis. Their mean mean age was 24.5 ±2.4 years. The mean haemoglobin level was 10.74 ± 1.39g/dL and the point-prevalence of anemia in pregnancy was 46.3%. Pregnant women who had severe anaemia were 14(8.5%), while maternal education status, woman's occupation, religion, family average monthly income, breastfeeding patterns and parity were all found to be statistically significant independent predictors for maternal anemia in pregnancy. Anaemia in pregnancy is a serious public health problem in south of Tanzania. We recommend strengthening measures to prevent anaemia in pregnant and women of reproductive age in the study area.
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Anemia/epidemiologia , Complicações Hematológicas na Gravidez/epidemiologia , Cuidado Pré-Natal/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Escolaridade , Feminino , Humanos , Gravidez , Prevalência , Fatores de Risco , Inquéritos e Questionários , Tanzânia/epidemiologia , Adulto JovemRESUMO
Urologic Emergencies: Paraphimosis Abstract. Paraphimosis presents a rare but acute urological emergency whereby the foreskin becomes entrapped behind the coronary sulcus of the penis. Therapy is quick and feasible, even in an outpatient setting. In most cases compression of the preputial edema and subsequent reposition of the prepuce is sufficient. Rarely, surgical intervention in form of a dorsal incision of the constriction is required. With partial or full phimosis being the underlying condition, paraphimosis occurs predominantly in infants and toddlers. However, persistent or secondary phimosis can lead to paraphimosis in advanced age.
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Parafimose/diagnóstico , Parafimose/cirurgia , Parafimose/terapia , Fimose , Pré-Escolar , Emergências , Serviço Hospitalar de Emergência , Humanos , MasculinoRESUMO
Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have promising potential for opening new avenues in regenerative medicine. However, since the tumorigenic potential of undifferentiated pluripotent stem cells (PSCs) is a major safety concern for clinical transplantation, inducible Caspase-9 (iC9) is under consideration for use as a fail-safe system. Here, we used targeted gene editing to introduce the iC9 system into human iPSCs, and then interrogated the efficiency of inducible apoptosis with normal iPSCs as well as diseased iPSCs derived from patients with acute myeloid leukemia (AML-iPSCs). The iC9 system induced quick and efficient apoptosis to iPSCs in vitro. More importantly, complete eradication of malignant cells without AML recurrence was shown in disease mouse models by using AML-iPSCs. In parallel, it shed light on several limitations of the iC9 system usage. Our results suggest that careful use of the iC9 system will serve as an important countermeasure against posttransplantation adverse events in stem cell transplantation therapies.
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Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Animais , Apoptose , Caspase 9/genética , Caspase 9/metabolismo , Diferenciação Celular , Linhagem Celular , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Células-Tronco Pluripotentes/metabolismoRESUMO
Farber disease (FD) is a rare lysosomal storage disorder (LSD) characterized by systemic ceramide accumulation caused by a deficiency in acid ceramidase (ACDase). In its classic form, FD manifests with painful lipogranulomatous nodules in extremities and joints, respiratory complications, and neurological involvement. Hepatosplenomegaly is commonly reported, and severe cases of FD cite liver failure as a cause of early death. Mice homozygous for an orthologous patient mutation in the ACDase gene (Asah1P361R/P361R) recapitulate the classical form of human FD. In this study, we demonstrate impaired liver function and elevation of various liver injury markers in Asah1P361R/P361R mice as early as 5 weeks of age. Histopathology analyses demonstrated significant formation and recruitment of foamy macrophages, invasion of neutrophils, progressive tissue fibrosis, increased cell proliferation and death, and significant storage pathology within various liver cell types. Lipidomic analyses revealed alterations to various lipid concentrations in both serum and liver tissue. A significant accumulation of ceramide and other sphingolipids in both liver and hepatocytes was noted. Sphingolipid acyl chains were also altered, with an increase in long acyl chain sphingolipids coinciding with a decrease in ultra-long acyl chains. Hepatocyte transcriptome analyses revealed significantly altered gene transcription. Molecular pathways related to inflammation were found activated, and molecular pathways involved in lipid metabolism were found deactivated. Altered gene transcription within the sphingolipid pathway itself was also observed. The data presented herein demonstrates that deficiency in ACDase results in liver pathology as well as sphingolipid and gene transcription profile changes that lead to impaired liver function.
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Lipogranulomatose de Farber/patologia , Fígado/patologia , Animais , Morte Celular , Modelos Animais de Doenças , Lipogranulomatose de Farber/complicações , Lipogranulomatose de Farber/metabolismo , Hepatócitos/metabolismo , Hepatomegalia/etiologia , Inflamação/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Fígado/ultraestrutura , Cirrose Hepática/etiologia , Camundongos , Esfingolipídeos/metabolismo , Transcrição GênicaRESUMO
BACKGROUND: Little is known about the social learning of students within community-based clinical placements and ways in which it can be supported. In an allied health service-learning program, we analysed students' learning relationships to quantify what, and from whom students learnt. METHODS: We conducted a social learning network survey in four domains of learning (clinical knowledge, procedural skills, professional development, and complex determinants of health) to explore learning relationships (ties) with other people (alters) that students (egos) formed during their placement. We quantified how different roles (supervisors, health professionals, administrators, peers, schoolteachers, and clients) contributed to the students' learning in each of the four domains. We used exponential random graph models (ERGMs) to test which relational processes contributed to the structure of the observed learning networks. RESULTS: Data was available from a complete cohort of 10 students on placement in a network of 69 members, thus providing information on 680 potential learning relations. Students engaged in similar ways in the domains of clinical knowledge, procedural skills, and professional development. Learning relations with academic supervisors were significantly more likely. Also students reported reciprocal learning relations with peers - i.e. they formed learning pairs. This effect was absent in learning networks about complex determinants of health (including socio-economic and cultural factors). Instead, local administrative staff were significantly more often the source of learning about the local contextual factors. CONCLUSIONS: Understanding the structure of student learning networks through social network analysis helps identify targeted strategies to enhance learning in community-based service-learning programs. Our findings suggest students recognised important learning from each other and from administrative personnel that is unrelated to the content of their placement. Based on this insight clinical educators could prepare students to become agentic learners, learning with each other and from sources outside their program.
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Pessoal Técnico de Saúde/educação , Serviços de Saúde Comunitária/normas , Atenção à Saúde/normas , Educação Baseada em Competências , Pesquisa sobre Serviços de Saúde , Humanos , Avaliação de Programas e Projetos de Saúde , Rede Social , Estudantes de Ciências da SaúdeRESUMO
INTRODUCTION: Phyllodes tumours are rare, accounting for 0.3-1.0% of all primary breast tumours. According to biological behaviour, they are divided into three categories: benign, borderline and malignant. Due to the rare incidence, the requirements for the radicality of surgical treatment are not well known. According to respected foreign recommendations, resection with a free margin of 10 mm or more is desirable. METHODS: A retrospective review of patients, who underwent surgical treatment due to phyllodes tumour in the Masaryk Memorial Cancer lnstitute in 2003-2014. RESULTS: 83 patients were evaluated with a median follow-up of 68.0 months. Benign tumours accounted for 62.3%, borderline tumours accounted for 16.9% and malignant accounted for 20.8% of all tumours. Malignant phyllodes tumours reached a bigger average size (84.9 mm) than borderline (41.4 mm) and benign tumours (33.3 mm) and occurred in older patients (mean 56.4 years) than benign (mean 42.5 years). Results from preoperative core-cut biopsy were often inaccurate. In 70 cases, the primary resection was breast preserving, but the free margin above 1 mm was achieved only in 13 cases. The width of the resection edge never exceeded the recommended 10 mm. Nevertheless, there was a relapse in benign tumours in two cases and in the borderline tumours only in one case. Malignant tumours recurred more frequently, even after total mastectomy. Four patients with malignant tumours experienced distant metastases. There has never been a death caused by benign or borderline tumour. CONCLUSION: The 10 mm resection margin is unachievable in our conditions. However, it seems that such radicality is not necessary in benign tumours, because they rarely recur even with close margins. Conversely, neither total mastectomy of the malignant phyllodes tumours will protect against local progression or distant metastasis.
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Tumor Filoide , Idoso , Neoplasias da Mama , Humanos , Mastectomia , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
Farber disease (FD) is a debilitating lysosomal storage disorder (LSD) caused by a deficiency of acid ceramidase (ACDase) activity due to mutations in the gene ASAH1. Patients with ACDase deficiency may develop a spectrum of clinical phenotypes. Severe cases of FD are frequently associated with neurological involvement, failure to thrive, and respiratory complications. Mice homozygous ( Asah1P361R/P361R) for an orthologous patient mutation in Asah1 recapitulate human FD. In this study, we show significant impairment in lung function, including low compliance and increased airway resistance in a mouse model of ACDase deficiency. Impaired lung mechanics in Farber mice resulted in decreased blood oxygenation and increased red blood cell production. Inflammatory cells were recruited to both perivascular and peribronchial areas of the lung. We observed large vacuolated foamy histiocytes that were full of storage material. An increase in vascular permeability led to protein leakage, edema, and impacted surfactant homeostasis in the lungs of Asah1P361R/P361R mice. Bronchial alveolar lavage fluid (BALF) extraction and analysis revealed accumulation of a highly turbid lipoprotein-like substance that was composed in part of surfactants, phospholipids, and ceramides. The phospholipid composition of BALF from Asah1P361R/P361R mice was severely altered, with an increase in both phosphatidylethanolamine (PE) and sphingomyelin (SM). Ceramides were also found at significantly higher levels in both BALF and lung tissue from Asah1P361R/P361R mice when compared with levels from wild-type animals. We demonstrate that a deficiency in ACDase leads to sphingolipid and phospholipid imbalance, chronic lung injury caused by significant inflammation, and increased vascular permeability, leading to impaired lung function.
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Ceramidase Ácida/fisiologia , Modelos Animais de Doenças , Lesão Pulmonar/etiologia , Pulmão/patologia , Animais , Líquido da Lavagem Broncoalveolar , Ceramidas/metabolismo , Homozigoto , Pulmão/metabolismo , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Camundongos , Camundongos Knockout , Fenótipo , Fosfolipídeos/metabolismo , Testes de Função RespiratóriaRESUMO
OBJECTIVES: To quantify public and academic interest in the urological field using a novel new media-based methodology. METHODS: We systematically measured public and academic interest in 56 urological keywords and combined in nine subspecialties. Public interest was quantified as video views on YouTube. Academic interest was quantified as article citations using Microsoft Academic Search. The public-to-academic interest ratio was calculated for a comparison of subspecialties as well as for diseases and treatments. RESULTS: For the selected 56 urological keywords, we found 226 617 591 video views on YouTube and 2 146 287 citations in the academic literature. The public-to-academic interest ratio was highest for the subspecialties robotic urology (ratio 6.3) and andrological urology (ratio 4.6). Prostate cancer was the central urological disease combining both a high public (20% of all video views) and academic interest (26% of all citations, ratio 0.8). Further diseases/treatments of high public interest were premature ejaculation (ratio 54.4), testicular cancer (ratio 11.4), erectile dysfunction (ratio 5.5) and kidney transplant (ratio 3.7). Urological treatments had a higher public-to-academic interest ratio (median ratio 0.25) than diseases (median ratio 0.05; P = 0.029). CONCLUSIONS: A quantification of academic and public interest in the urological field is feasible using a novel new media-based methodology. We found several mismatches in public versus academic interest in urological diseases and treatments, which has implications for research strategies, conference planning and patient information projects. Regular re-assessments of the public and academic interest landscape can contribute to detecting and proving trends in the field of urology.
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Pesquisa Biomédica/métodos , Sociedades Médicas , Urologia , Estudos Transversais , Internet , Meios de Comunicação de Massa , Informática em Saúde Pública , Doenças Urológicas/terapiaRESUMO
INTRODUCTION: No consensus exists as yet regarding the optimal extent of surgery on the lymph nodes in breast cancer patients after neoadjuvant treatment. In addition to axillary dissection and sentinel lymph node biopsy (SLNB), a new approach called Targeted Axillary Dissection (TAD) was introduced. It requires the marking of metastatic nodes before the neoadjuvant treatment. METHOD: A retrospective observational study on patients with breast cancer and neoadjuvant chemotherapy treated surgically at a single institution in 2017. RESULTS: The analysis included 121 cancers in 120 patients. Clinical regression of lymphadenopathy occurred in 29 out of 74 cases. Axillary dissection was performed 34x, SLNB 52x and TAD 35x. In TAD procedures, the marked lymph node was found 30x and was among the sentinel nodes in 19 cases. No case occurred in which the marked node was assessed as negative with a metastasis found in the other nodes. On the contrary, there were 3 cases with negative sentinel nodes whereas the marked node was positive. Out of 74 cases with initially pathologic nodes, 23 patients were spared axillary dissection. CONCLUSION: Clinical assessment of the lymph node status is rather inaccurate. In cases with initially pathologic nodes we recommend marking of the most explicit metastatic node to enable TAD. The marked node is likely to reflect the status of the lymph nodes after neoadjuvant treatment more accurately than common sentinel nodes. A considerable proportion of patients can be spared axillary dissection in this way. However, the long-term oncologic safety of TAD still needs to be verified. Key words: breast cancer - neoadjuvant treatment - axillary dissection - sentinel lymph node biopsy - targeted axillary dissection.
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Neoplasias da Mama , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Humanos , Linfonodos , Metástase Linfática , Terapia Neoadjuvante , Estudos RetrospectivosRESUMO
BACKGROUND: A great deal of consumer data, collected actively through consumer reporting or passively through sensors, is shared among apps. Developers increasingly allow their programs to communicate with other apps, sensors, and Web-based services, which are promoted as features to potential users. However, health apps also routinely pose risks related to information leaks, information manipulation, and loss of information. There has been less investigation into the kinds of user data that developers are likely to collect, and who might have access to it. OBJECTIVE: We sought to describe how consumer data generated from mobile health apps might be distributed and reused. We also aimed to outline risks to individual privacy and security presented by this potential for aggregating and combining user data across apps. METHODS: We purposively sampled prominent health and fitness apps available in the United States, Canada, and Australia Google Play and iTunes app stores in November 2015. Two independent coders extracted data from app promotional materials on app and developer characteristics, and the developer-reported collection and sharing of user data. We conducted a descriptive analysis of app, developer, and user data collection characteristics. Using structural equivalence analysis, we conducted a network analysis of sampled apps' self-reported sharing of user-generated data. RESULTS: We included 297 unique apps published by 231 individual developers, which requested 58 different permissions (mean 7.95, SD 6.57). We grouped apps into 222 app families on the basis of shared ownership. Analysis of self-reported data sharing revealed a network of 359 app family nodes, with one connected central component of 210 app families (58.5%). Most (143/222, 64.4%) of the sampled app families did not report sharing any data and were therefore isolated from each other and from the core network. Fifteen app families assumed more central network positions as gatekeepers on the shortest paths that data would have to travel between other app families. CONCLUSIONS: This cross-sectional analysis highlights the possibilities for user data collection and potential paths that data is able to travel among a sample of prominent health and fitness apps. While individual apps may not collect personally identifiable information, app families and the partners with which they share data may be able to aggregate consumer data, thus achieving a much more comprehensive picture of the individual consumer. The organizations behind the centrally connected app families represent diverse industries, including apparel manufacturers and social media platforms that are not traditionally involved in health or fitness. This analysis highlights the potential for anticipated and voluntary but also possibly unanticipated and involuntary sharing of user data, validating privacy and security concerns in mobile health.