Amantadine use in the French prospective NS-Park cohort.

OBJECTIVE: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD). BACKGROUND: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres. METHODS: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis). RESULTS: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users. CONCLUSIONS: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs.

Genotype-phenotype correlation in PRKN-associated Parkinson's disease.

Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson's disease (PD). 647 patients with PRKN-PD were included in this international study. The pathogenic variants present were characterised and investigated for their effect on phenotype. Clinical features and progression of PRKN-PD was also assessed. Among 133 variants in index cases (n = 582), there were 58 (43.6%) structural variants, 34 (25.6%) missense, 20 (15%) frameshift, 10 splice site (7.5%%), 9 (6.8%) nonsense and 2 (1.5%) indels. The most frequent variant overall was an exon 3 deletion (n = 145, 12.3%), followed by the p.R275W substitution (n = 117, 10%). Exon3, RING0 protein domain and the ubiquitin-like protein domain were mutational hotspots with 31%, 35.4% and 31.7% of index cases presenting mutations in these regions respectively. The presence of a frameshift or structural variant was associated with a 3.4 ± 1.6 years or a 4.7 ± 1.6 years earlier age at onset of PRKN-PD respectively (p < 0.05). Furthermore, variants located in the N-terminus of the protein, a region enriched with frameshift variants, were associated with an earlier age at onset. The phenotype of PRKN-PD was characterised by slow motor progression, preserved cognition, an excellent motor response to levodopa therapy and later development of motor complications compared to early-onset PD. Non-motor symptoms were however common in PRKN-PD. Our findings on the relationship between the type of variant in PRKN and the phenotype of the disease may have implications for both genetic counselling and the design of precision clinical trials.

In-depth transcriptomic analysis of Anopheles gambiae hemocytes uncovers novel genes and the oenocytoid developmental lineage.

BACKGROUND: Hemocytes are immune cells that patrol the mosquito hemocoel and mediate critical cellular defense responses against pathogens. However, despite their importance, a comprehensive transcriptome of these cells was lacking because they constitute a very small fraction of the total cells in the insect, limiting the study of hemocyte differentiation and immune function. RESULTS: In this study, an in-depth hemocyte transcriptome was built by extensive bulk RNA sequencing and assembly of hemocyte RNAs from adult A. gambiae female mosquitoes, based on approximately 2.4 billion short Illumina and about 9.4 million long PacBio high-quality reads that mapped to the A. gambiae PEST genome (P4.14 version). A total of 34,939 transcripts were annotated including 4,020 transcripts from novel genes and 20,008 novel isoforms that result from extensive differential splicing of transcripts from previously annotated genes. Most hemocyte transcripts identified (89.8%) are protein-coding while 10.2% are non-coding RNAs. The number of transcripts identified in the novel hemocyte transcriptome is twice the number in the current annotation of the A. gambiae genome (P4.14 version). Furthermore, we were able to refine the analysis of a previously published single-cell transcriptome (scRNAseq) data set by using the novel hemocyte transcriptome as a reference to re-define the hemocyte clusters and determine the path of hemocyte differentiation. Unsupervised pseudo-temporal ordering using the Tools for Single Cell Analysis software uncovered a novel putative prohemocyte precursor cell type that gives rise to prohemocytes. Pseudo-temporal ordering with the Monocle 3 software, which analyses changes in gene expression during dynamic biological processes, determined that oenocytoids derive from prohemocytes, a cell population that also gives rise to the granulocyte lineage. CONCLUSION: A high number of mRNA splice variants are expressed in hemocytes, and they may account for the plasticity required to mount efficient responses to many different pathogens. This study highlights the importance of a comprehensive set of reference transcripts to perform robust single-cell transcriptomic data analysis of cells present in low abundance. The detailed annotation of the hemocyte transcriptome will uncover new facets of hemocyte development and function in adult dipterans and is a valuable community resource for future studies on mosquito cellular immunity.

Redox imbalance induces remodeling of glucose metabolism in Rhipicephalus microplus embryonic cell line.

Carbohydrate metabolism not only functions in supplying cellular energy but also has an important role in maintaining physiological homeostasis and in preventing oxidative damage caused by reactive oxygen species. Previously, we showed that arthropod embryonic cell lines have high tolerance to H2O2 exposure. Here, we describe that Rhipicephalus microplus tick embryonic cell line (BME26) employs an adaptive glucose metabolism mechanism that confers tolerance to hydrogen peroxide at concentrations too high for other organisms. This adaptive mechanism sustained by glucose metabolism remodeling promotes cell survival and redox balance in BME26 cell line after millimolar H2O2 exposure. The present work shows that this tick cell line could tolerate high H2O2 concentrations by initiating a carbohydrate-related adaptive response. We demonstrate that gluconeogenesis was induced as a compensation strategy that involved, among other molecules, the metabolic enzymes NADP-ICDH, G6PDH, and PEPCK. We also found that this phenomenon was coupled to glycogen accumulation and glucose uptake, supporting the pentose phosphate pathway to sustain NADPH production and leading to cell survival and proliferation. Our findings suggest that the described response is not atypical, being also observed in cancer cells, which highlights the importance of this model to all proliferative cells. We propose that these results will be useful in generating basic biological information to support the development of new strategies for disease treatment and parasite control.

Aedes fluviatilis cell lines as new tools to study metabolic and immune interactions in mosquito-Wolbachia symbiosis.

In the present work, we established two novel embryonic cell lines from the mosquito Aedes fluviatilis containing or not the naturally occurring symbiont bacteria Wolbachia, which were called wAflu1 and Aflu2, respectively. We also obtained wAflu1 without Wolbachia after tetracycline treatment, named wAflu1.tet. Morphofunctional characterization was performed to help elucidate the symbiont-host interaction in the context of energy metabolism regulation and molecular mechanisms of the immune responses involved. The presence of Wolbachia pipientis improves energy performance in A. fluviatilis cells; it affects the regulation of key energy sources such as lipids, proteins, and carbohydrates, making the distribution of actin more peripheral and with extensions that come into contact with neighboring cells. Additionally, innate immunity mechanisms were activated, showing that the wAflu1 and wAflu1.tet cells are responsive after the stimulus using Gram negative bacteria. Therefore, this work confirms the natural, mutually co-regulating symbiotic relationship between W. pipientis and A. fluviatilis, modulating the host metabolism and immune pathway activation. The results presented here add important resources to the current knowledge of Wolbachia-arthropod interactions.

The wide spectrum of COVID-19 neuropsychiatric complications within a multidisciplinary centre.

A variety of neuropsychiatric complications has been described in association with COVID-19 infection. Large scale studies presenting a wider picture of these complications and their relative frequency are lacking. The objective of our study was to describe the spectrum of neurological and psychiatric complications in patients with COVID-19 seen in a multidisciplinary hospital centre over 6 months. We conducted a retrospective, observational study of all patients showing neurological or psychiatric symptoms in the context of COVID-19 seen in the medical and university neuroscience department of Assistance Publique Hopitaux de Paris-Sorbonne University. We collected demographic data, comorbidities, symptoms and severity of COVID-19 infection, neurological and psychiatric symptoms, neurological and psychiatric examination data and, when available, results from CSF analysis, MRI, EEG and EMG. A total of 249 COVID-19 patients with a de novo neurological or psychiatric manifestation were included in the database and 245 were included in the final analyses. One-hundred fourteen patients (47%) were admitted to the intensive care unit and 10 (4%) died. The most frequent neuropsychiatric complications diagnosed were encephalopathy (43%), critical illness polyneuropathy and myopathy (26%), isolated psychiatric disturbance (18%) and cerebrovascular disorders (16%). No patients showed CSF evidence of SARS-CoV-2. Encephalopathy was associated with older age and higher risk of death. Critical illness neuromyopathy was associated with an extended stay in the intensive care unit. The majority of these neuropsychiatric complications could be imputed to critical illness, intensive care and systemic inflammation, which contrasts with the paucity of more direct SARS-CoV-2-related complications or post-infection disorders.

Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease.

OBJECTIVE: Decreased amyloid beta (Aß) 42 together with increased tau and phospho-tau in cerebrospinal fluid (CSF) is indicative of Alzheimer's disease (AD). However, the molecular pathophysiology underlying the slowly progressive cognitive decline observed in AD is not fully understood and it is not known what other CSF biomarkers may be altered in early disease stages. METHODS: We utilized an antibody-based suspension bead array to analyze levels of 216 proteins in CSF from AD patients, patients with mild cognitive impairment (MCI), and controls from two independent cohorts collected within the AETIONOMY consortium. Two additional cohorts from Sweden were used for biological verification. RESULTS: Six proteins, amphiphysin (AMPH), aquaporin 4 (AQP4), cAMP-regulated phosphoprotein 21 (ARPP21), growth-associated protein 43 (GAP43), neurofilament medium polypeptide (NEFM), and synuclein beta (SNCB) were found at increased levels in CSF from AD patients compared with controls. Next, we used CSF levels of Aß42 and tau for the stratification of the MCI patients and observed increased levels of AMPH, AQP4, ARPP21, GAP43, and SNCB in the MCI subgroups with abnormal tau levels compared with controls. Further characterization revealed strong to moderate correlations between these five proteins and tau concentrations. INTERPRETATION: In conclusion, we report six extensively replicated candidate biomarkers with the potential to reflect disease development. Continued evaluation of these proteins will determine to what extent they can aid in the discrimination of MCI patients with and without an underlying AD etiology, and if they have the potential to contribute to a better understanding of the AD continuum.

Mechanical Permeabilization as a New Method for Assessment of Mitochondrial Function in Insect Tissues.

Respirometry analysis is an effective technique to assess mitochondrial physiology. Insects are valuable biochemical models to understand metabolism and human diseases. Insect flight muscle and brain have been extensively used to explore mitochondrial function due to dissection feasibility and the low sample effort to allow oxygen consumption measurements. However, adequate plasma membrane permeabilization is required for substrates/modulators to reach mitochondria. Here, we describe a new method for study of mitochondrial physiology in insect tissues based on mechanical permeabilization as a fast and reliable method that do not require the use of detergents for chemical permeabilization of plasma membrane, while preserves mitochondrial integrity.

Comprehensive Quantitative Proteome Analysis of Aedes aegypti Identifies Proteins and Pathways Involved in Wolbachia pipientis and Zika Virus Interference Phenomenon.

Zika virus (ZIKV) is a global public health emergency due to its association with microcephaly, Guillain-Barré syndrome, neuropathy, and myelitis in children and adults. A total of 87 countries have had evidence of autochthonous mosquito-borne transmission of ZIKV, distributed across four continents, and no antivirus therapy or vaccines are available. Therefore, several strategies have been developed to target the main mosquito vector, Aedes aegypti, to reduce the burden of different arboviruses. Among such strategies, the use of the maternally-inherited endosymbiont Wolbachia pipientis has been applied successfully to reduce virus susceptibility and decrease transmission. However, the mechanisms by which Wolbachia orchestrate resistance to ZIKV infection remain to be elucidated. In this study, we apply isobaric labeling quantitative mass spectrometry (MS)-based proteomics to quantify proteins and identify pathways altered during ZIKV infection; Wolbachia infection; co-infection with Wolbachia/ZIKV in the A. aegypti heads and salivary glands. We show that Wolbachia regulates proteins involved in reactive oxygen species production, regulates humoral immune response, and antioxidant production. The reduction of ZIKV polyprotein in the presence of Wolbachia in mosquitoes was determined by MS and corroborates the idea that Wolbachia helps to block ZIKV infections in A. aegypti. The present study offers a rich resource of data that may help to elucidate mechanisms by which Wolbachia orchestrate resistance to ZIKV infection in A. aegypti, and represents a step further on the development of new targeted methods to detect and quantify ZIKV and Wolbachia directly in complex tissues.

Aedes aegypti post-emergence transcriptome: Unveiling the molecular basis for the hematophagic and gonotrophic capacitation.

The adult females of Aedes aegypti mosquitoes are facultative hematophagous insects but they are unable to feed on blood right after pupae emergence. The maturation process that takes place during the first post-emergence days, hereafter named hematophagic and gonotrophic capacitation, comprises a set of molecular and physiological changes that prepare the females for the first gonotrophic cycle. Notwithstanding, the molecular bases underlying mosquito hematophagic and gonotrophic capacitation remain obscure. Here, we investigated the molecular and biochemical changes in adult Ae. aegypti along the first four days post-emergence, prior to a blood meal. We performed a RNA-Seq analysis of the head and body, comparing male and female gene expression time courses. A total of 811 and 203 genes were differentially expressed, respectively in the body and head, and both body parts showed early, mid, and late female-specific expression profiles. Female-specific up-regulation of genes involved in muscle development and the oxidative phosphorylation pathway were remarkable features observed in the head. Functional assessment of mitochondrial oxygen consumption in heads showed a gradual increase in respiratory capacity and ATP-linked respiration as a consequence of induced mitochondrial biogenesis and content over time. This pattern strongly suggests that boosting oxidative phosphorylation in heads is a required step towards blood sucking habit. Several salivary gland genes, proteases, and genes involved in DNA replication and repair, ribosome biogenesis, and juvenile hormone signaling were up-regulated specifically in the female body, which may reflect the gonotrophic capacitation. This comprehensive description of molecular and biochemical mechanisms of the hematophagic and gonotrophic capacitation in mosquitoes unravels potentially new targets for vector control.

Cerebrospinal Fluid Levels of Kininogen-1 Indicate Early Cognitive Impairment in Parkinson's Disease.

BACKGROUND: Cognitive impairment is common in patients with PD. Core markers of Alzheimer's dementia have been related also to PD dementia, but no disease-specific signature to predict PD dementia exists to date. OBJECTIVES: The aim of this study was to investigate CSF markers associated with cognition in early PD. METHODS: A high-throughput suspension bead array examined 216 proteins in CSF of 74 PD patients in the AETIONOMY project. Cognitive function was assessed with Repeatable Battery for the Assessment of the Neuropsychological Status, Montreal Cognitive Assessment, and Mini-Mental State Examination. RESULTS: Of 69 patients with complete data, 34 had high (≥90) and 35 had low Repeatable Battery for the Assessment of the Neuropsychological Status total score (<90). Of 14 proteins in CSF that differed in levels between groups, increased kininogen-1, validated with several antibodies, was independently associated with lower Repeatable Battery for the Assessment of the Neuropsychological Status and Montreal Cognitive Assessment scores after adjustment for confounders. CONCLUSIONS: Kininogen-1 levels in CSF may serve as a marker of cognitive impairment in PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Description of Referrals for Colposcopy in a Hospital in Brazil.

OBJECTIVE: To describe the referral for colposcopy in a Hospital in Brazil and the relative frequency of patients who benefited from it, considering the correct indications for the examination and its final diagnoses. METHODS: A retrospective study was performed in the colposcopy service database of the Hospital Universitário de Taubaté, Taubaté, state of São Paulo, Brazil. The frequency validated in the analysis of the medical records of women referred for clinical indication or cytological alteration, attended from March 2015 to March 2017. The population selected and analyzed included 256 results that were correlated to the cytological, clinical data and the result of the colposcopy. RESULTS: Of the women referred, 45% presented out of the age of screening according to the guidelines of cervical cancer screening, 8.6% being adolescents and young adults < 25 years old, and 36.4% of the patients being ≥ 65 years old. A total of 50% of the patients had no indication of colposcopy, that is, normal cytologies, benign changes, ectopia, cervicitis, atypical squamous cells of indeterminate significance (ASC-US) and low-grade intraepithelial lesion (LSIL) without persistence and normal clinical appearance. A total of 39.84% who underwent colposcopy had high-grade lesion or cancer results, thus benefiting from the adequate referral. CONCLUSION: Most (60.16%) of the patients referred to the colposcopy service did not benefit from the referral for results without changes, such as negative colposcopies, histologies with no cervical intraepithelial neoplasm (CIN) or only CIN 1, or were out of the age for screening. These findings therefore demonstrate a significant number of unnecessary and inadequate referrals.

OBJETIVO: Descrever os encaminhamentos para colposcopia em um hospital no Brasil e a frequência relativa dos pacientes que foram beneficiados, considerando as indicações corretas para o exame e seus diagnósticos finais. MéTODOS: Foi realizado um estudo retrospectivo no banco de dados do serviço de colposcopia do Hospital Universitário de Taubaté, Taubaté, SP, Brasil. A frequência validou em análise de prontuários de mulheres encaminhadas por indicação clínica ou alteração citológica, atendidas no período de março de 2015 a março de 2017. A população selecionada e analisada incluiu 256 resultados que estavam correlacionadas aos dados citológicos, clínicos e com o resultado da colposcopia. RESULTADOS: Das mulheres encaminhadas, 45% apresentaram-se fora da idade de rastreamento conforme as diretrizes de rastreio de câncer de colo uterino, sendo que 8,6% eram adolescentes e adultas jovens < 25 anos de idade e 36,4% das pacientes tinham idade ≥ 65 anos. Um total de 50% das pacientes não possuía indicação de colposcopia, ou seja, citologias normais, de alterações benignas, ectopia, cervicite, células escamosas atípicas de significado indeterminado (ASC-US) e lesão intraepitelial escamosa de baixo grau (LSIL) sem persistência e aspecto clínico normal. Um total de 39,84% das pacientes que realizaram a colposcopia tiveram resultados de lesão de alto grau ou câncer e, dessa forma, se beneficiaram com o encaminhamento adequado. CONCLUSãO: A maioria (60,16%) das pacientes encaminhadas para o serviço de colposcopia não se beneficiou com o encaminhamento, por resultados sem alterações como colposcopias negativas, histologias com ausência de neoplasia intraepitelial cervical (NIC) ou apenas NIC 1, ou estavam fora da idade de rastreamento. Esses achados demonstram, portanto, significativo número de encaminhamentos desnecessários e inadequados.

Description of referrals for colposcopy in a hospital in Brazil / Descrição dos encaminhamentos para colposcopia em um hospital no Brasil

Abstract Objective To describe the referral for colposcopy in a Hospital in Brazil and the relative frequency of patients who benefited from it, considering the correct indications for the examination and its final diagnoses. Methods A retrospective study was performed in the colposcopy service database of the Hospital Universitário de Taubaté, Taubaté, state of São Paulo, Brazil. The frequency validated in the analysis of the medical records of women referred for clinical indication or cytological alteration, attended from March 2015 to March 2017. The population selected and analyzed included 256 results that were correlated to the cytological, clinical data and the result of the colposcopy. Results Of the women referred, 45% presented out of the age of screening according to the guidelines of cervical cancer screening, 8.6% being adolescents and young adults < 25 years old, and 36.4% of the patients being ≥ 65 years old. A total of 50% of the patients had no indication of colposcopy, that is, normal cytologies, benign changes, ectopia, cervicitis, atypical squamous cells of indeterminate significance (ASC-US) and low-grade intraepithelial lesion (LSIL) without persistence and normal clinical appearance. A total of 39.84% who underwent colposcopy had high-grade lesion or cancer results, thus benefiting from the adequate referral. Conclusion Most (60.16%) of the patients referred to the colposcopy service did not benefit from the referral for results without changes, such as negative colposcopies, histologies with no cervical intraepithelial neoplasm (CIN) or only CIN 1, or were out of the age for screening. These findings therefore demonstrate a significant number of unnecessary and inadequate referrals.

Resumo Objetivo Descrever os encaminhamentos para colposcopia em um hospital no Brasil e a frequência relativa dos pacientes que foram beneficiados, considerando as indicações corretas para o exame e seus diagnósticos finais. Métodos Foi realizado um estudo retrospectivo no banco de dados do serviço de colposcopia do Hospital Universitário de Taubaté, Taubaté, SP, Brasil. A frequência validou em análise de prontuários de mulheres encaminhadas por indicação clínica ou alteração citológica, atendidas no período de março de 2015 a março de 2017. A população selecionada e analisada incluiu 256 resultados que estavam correlacionadas aos dados citológicos, clínicos e com o resultado da colposcopia. Resultados Das mulheres encaminhadas, 45% apresentaram-se fora da idade de rastreamento conforme as diretrizes de rastreio de câncer de colo uterino, sendo que 8,6% eram adolescentes e adultas jovens < 25 anos de idade e 36,4% das pacientes tinham idade ≥ 65 anos. Um total de 50% das pacientes não possuía indicação de colposcopia, ou seja, citologias normais, de alterações benignas, ectopia, cervicite, células escamosas atípicas de significado indeterminado (ASC-US) e lesão intraepitelial escamosa de baixo grau (LSIL) sem persistência e aspecto clínico normal. Um total de 39,84% das pacientes que realizaram a colposcopia tiveram resultados de lesão de alto grau ou câncer e, dessa forma, se beneficiaram com o encaminhamento adequado. Conclusão A maioria (60,16%) das pacientes encaminhadas para o serviço de colposcopia não se beneficiou com o encaminhamento, por resultados sem alterações como colposcopias negativas, histologias com ausência de neoplasia intraepitelial cervical (NIC) ou apenas NIC 1, ou estavam fora da idade de rastreamento. Esses achados demonstram, portanto, significativo número de encaminhamentos desnecessários e inadequados.

Concordância entre cintura hipertrigliceridêmica e cintura estatura hipertrigliceridêmica em trabalhadores em turnos alternantes / Agreement between hypertriglyceridic waist and hypertriplyceridemic waist height in rotation shift workers

Objetivos: Avaliar a concordância entre fenótipo de cintura hipertrigliceridêmica e fenótipo cintura estatura hipertrigliceridêmica, e a associação desses fenótipos com alterações antropométricas, bioquímicas e clínicas em homens adultos com risco metabólico aumentado pela exposição ao turno alternante. Métodos: Estudo transversal realizado com 678 trabalhadores do sexo masculino. O fenótipo de cintura hipertrigliceridêmica foi definido pelo perímetro da cintura ≥ 94 cm e triglicérides ≥ 150 mg/dL; o fenótipo cintura estatura hipertrigliceridêmica pela razão cintura estatura ≥ 0,5; e triglicérides ≥ 150mg/dL. Foram avaliados o índice de massa corporal, pressão arterial, colesterol total, high-density lipoprotein colesterol, low-density lipoprotein colesterol, triglicérides e glicemia de jejum. O teste Kappa foi utilizado para avaliar a concordância entre os fenótipos e o teste Qui-quadrado de Pearson, para verificar a associação entre os fenótipos e os componentes de risco para doenças cardiovasculares. Para todos os testes, o nível de significância adotado foi de 5%. Resultados: A concordância entre o fenótipo de cintura hipertrigliceridêmica e o fenótipo cintura estatura hipertrigliceridêmica foi significativa e substancial. Ambos fenótipos foram relacionados significativamente com índice de massa corporal, colesterol total, high-density lipoprotein colesterol e pressão arterial aumentados. Conclusões: Sugere-se o uso do fenótipo cintura estatura hipertrigliceridemica, já que demonstrou associações que se mantiveram independentemente da faixa etária e identificou maior proporção de trabalhadores em turnos alternantes com componentes de risco cardiovascular. (AU)

Objective: This study evaluated the agreement between hypertriglyceridemic waist and hypertriglyceridemic waist height phenotypes and the association of these phenotypes with anthropometric, biochemical, and clinical alterations in adult men with increased metabolic risk due to rotating shift exposure. Methods: The cross-sectional study included 678 male workers. The hypertriglyceridemic waist phenotype was defined as waist circumference ≥ 94 cm and triglyceride concentration ≥150 mg/dL; the hypertriglyceridemic waist height phenotype was defined as a height-waist ratio ≥0.5 and triglyceride concentration ≥ 150mg/dL. Body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and glucose levels were evaluated. The Kappa test was used to assess the concordance between phenotypes, and the Pearson's chi-square tests were used to verify the association between phenotypes and risk components for cardiovascular diseases. For all tests, the significance level was 5%. Results: The agreement between the hypertriglyceridemic waist and the hypertriglyceridemic waist height phenotypes was significant and substantial. Both phenotypes were significantly related to increased body mass index, total cholesterol, high-density lipoprotein cholesterol, and blood pressure. Conclusion: We propose the use of hypertriglyceridemic waist-toheight ratio as it demonstrated associations that persisted regardless of the age group and also identified a higher proportion of rotating shift workers with cardiovascular risk components. (AU)

Multicenter Alzheimer's and Parkinson's disease immune biomarker verification study.

INTRODUCTION: Multiple immunity biomarkers have been suggested as tracers of neuroinflammation in neurodegeneration. This study aimed to verify findings in cerebrospinal fluid (CSF) samples of Alzheimer's disease (AD) and Parkinson's disease (PD) subjects from the network of the European, Innovative Medicines Initiative-funded project AETIONOMY. METHODS: A total of 227 samples from the studies/centres AETIONOMY, ICEBERG, and IDIBAPS were used to analyse 21 selected immunity biomarkers in CSF. Results were compared to data of an independent cohort of 399 subjects previously published. RESULTS: Immunity markers were predominantly and reproducibly associated with pathological levels of tau isoforms, but also with amyloid levels, aging, sex, APOE genotype, and center-specific factors. DISCUSSION: Immunity biomarker levels in CSF reflect molecular and cellular pathology rather than diagnosis in neurodegenerative disorders. Assay standardization and stratification for age and other covariates could improve the power of such markers in clinical applications or intervention studies targeting immune responses in neurodegeneration.

Use of extracorporeal bypass is associated with improved outcomes in open thoracic and thoracoabdominal aortic aneurysm repair.

OBJECTIVE: There is no consensus on the use or benefit of extracorporeal circulation (EC) during aneurysm repair of the descending thoracic aorta (DTA) or thoracoabdominal aorta (TAA). We evaluated the role of EC during DTA or TAA aneurysm repair using U.S. Medicare data. METHODS: Medicare (2004-2007) patients undergoing open repair of nonruptured DTA or TAA aneurysm were identified by International Classification of Diseases, Ninth Revision code. Specific exclusions included ascending aortic or arch repairs, concomitant cardiac procedures, and procedures employing deep hypothermic circulatory arrest. The impact of EC (code 3961) on early and late outcomes was analyzed using univariate analysis and multivariable regression. Survival was assessed using Kaplan-Meier analysis and Cox proportional hazards regression models. RESULTS: There were 4230 patients who had repair of intact DTA or TAA aneurysms, 2433 (57%) of which employed EC. Differences in baseline clinical features of EC and non-EC patients showed that patients undergoing aortic reconstruction with EC were older (73 ± 1 years vs 72 ± 1 years; P = .002), were more likely to be female (53% vs 47%; P < .001), and had more hypertension (56% vs 53%; P = .02); they had less chronic obstructive pulmonary disease (28% vs 34%; P < .0001), peripheral vascular disease (5.7% vs 11.3%; P < .001), and chronic kidney disease (7.7% vs 5.5%; P = .003). The 30-day mortality (9.7% for EC vs 12.2%; P = .02) and any major complication (49% for EC vs 58%; P < .001) were significantly reduced with EC use. EC use was associated with a shorter length of stay (13.5 ± 13 days vs 17.2 ± 18 days; P < .01) and lower total hospital charges ($151,000 ± 140,000 vs $180,000 ± 190,000; P < .01) compared with non-EC patients. EC patients were more likely to be discharged home instead of to an extended care facility (67% vs 56%; P < .01). Multivariable regression modeling to adjust for baseline clinical differences showed EC to independently reduce the risk of operative mortality (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.65-0.97; P = .02), any complication (OR, 0.67; 95% CI, 0.59-0.76; P < .01), pulmonary complications (OR, 0.68; 95% CI, 0.59-0.79; P < .01), and acute renal failure (OR, 0.52; 95% CI, 0.44-0.61; P < .01). Long-term survival was higher (log-rank, P < .01) in EC patients at 1 year (81% ± 0.8% vs 73% ± 1%) and 5 years (67% ± 1% vs 52% ± 1%). Risk-adjusted Cox proportional hazards regression also showed that EC was independently associated with improved long-term survival (hazard ratio, 0.69; 95% CI, 0.63-0.74; P < .01). CONCLUSIONS: Although important clinical variables such as DTA or TAA aneurysm extent and spinal cord ischemic complications cannot be assessed with the Medicare database, EC use during open DTA and TAA aneurysm repair is associated with improved late survival and a significant reduction in operative mortality, morbidity, and procedural costs. These data indicate that EC should be a more widely applied adjunct in open DTA or TAA aneurysm repair.

A Systematic Review of Integrated Care Interventions Addressing Perinatal Depression Care in Ambulatory Obstetric Care Settings.

This systematic review searched 4 databases (PubMed/MEDLINE, Scopus, CINAHL, and PsychINFO) and identified 21 articles eligible to evaluate the extent to which interventions that integrate depression care into outpatient obstetric practice are feasible, effective, acceptable, and sustainable. Despite limitations among the available studies including marked heterogeneity, there is evidence supporting feasibility, effectiveness, and acceptability. In general, this is an emerging field with promise that requires additional research. Critical to its real-world success will be consideration for practice workflow and logistics, and sustainability through novel reimbursement mechanisms.

Factors related to non-adherence to mammography in a city of the Brazilian Amazonian area: A population-based study.

OBJECTIVE: To assess the prevalence of mammography use and factors related to non-adherence in Boa Vista, capital of Roraima, Brazil. METHOD: A cross sectional study, quantitative analysis, based on household survey was performed between June and August 2013, using a face-to-face interview with a pre-tested form. Target population was women between 40 and 69 years. The sample size target was 240 participants, and the sampling method was random cluster sampling. The study was approved by the Institutional Review Board of Federal University of Roraima. RESULTS: 241 women were included without refusals. The prevalence of non-use of mammography in the past two years was 55.6% (95CI 49.1-61.9). In univariate analysis, the risk factors for non-adherence to mammography were having low educational level, family income below three minimum wages, receiving government assistance, not having consulted with a doctor and no health insurance. In multivariate analysis, only low educational level and receiving government assistance remained as risk factors. Medical consultation or health worker visiting were protective factors. CONCLUSION: Adherence to mammography is unsatisfactory in Boa Vista, Roraima, and has a predominantly opportunistic character. Low educational level is confirmed as an independent risk factor, but belonging to a family that receives government assistance can be interpreted as a social marker of families and/or areas lacking of government intervention to increase access to breast cancer control programs.

Factors related to non-adherence to mammography in a city of the Brazilian Amazonian area: A population-based study / Fatores relacionados à não utilização de mamografia em capital brasileira da região Norte: um estudo de base populacional

Summary Objective: To assess the prevalence of mammography use and factors related to non-adherence in Boa Vista, capital of Roraima, Brazil. Method: A cross sectional study, quantitative analysis, based on household survey was performed between June and August 2013, using a face-to-face interview with a pre-tested form. Target population was women between 40 and 69 years. The sample size target was 240 participants, and the sampling method was random cluster sampling. The study was approved by the Institutional Review Board of Federal University of Roraima. Results: 241 women were included without refusals. The prevalence of non-use of mammography in the past two years was 55.6% (95CI 49.1-61.9). In univariate analysis, the risk factors for non-adherence to mammography were having low educational level, family income below three minimum wages, receiving government assistance, not having consulted with a doctor and no health insurance. In multivariate analysis, only low educational level and receiving government assistance remained as risk factors. Medical consultation or health worker visiting were protective factors. Conclusion: Adherence to mammography is unsatisfactory in Boa Vista, Roraima, and has a predominantly opportunistic character. Low educational level is confirmed as an independent risk factor, but belonging to a family that receives government assistance can be interpreted as a social marker of families and/or areas lacking of government intervention to increase access to breast cancer control programs.

Resumo Objetivo: Avaliar a prevalência de utilização da mamografia e fatores relacionados à não adesão em Boa Vista, capital de Roraima, Brasil. Método: Trata-se de um estudo de corte transversal, de análise quantitativa, baseado em inquérito domiciliar, por entrevista face a face, utilizando formulário previamente testado. Foram incluídas mulheres entre 40 e 69 anos, entre junho e agosto de 2013. A meta amostral foram 240 participantes, e o método de amostragem foi aleatório por conglomerado. O estudo foi aprovado pelo Comitê de Ética em Pesquisa da Universidade Federal de Roraima. Resultados: 241 mulheres foram incluídas, sem recusas. A prevalência de não utilização de mamografia nos últimos dois anos foi 55,6% (IC95% 49.1-61.9). Em análise univariada, os fatores de risco para não adesão à mamografia foram baixa escolaridade, renda familiar inferior a três salários mínimos, receber auxílio governamental, não ter sido consultado por médico e não ter plano de saúde. Em análise multivariada, apenas baixa escolaridade e receber auxílio governamental se mantiveram como fatores de risco, enquanto consulta médica ou visita de agente de saúde, como fatores de proteção independentes. Conclusão: A adesão à mamografia é insatisfatória em Boa Vista e tem caráter predominantemente oportunista. Baixa escolaridade se confirma como fator de risco independente, mas pertencer a uma família que recebe auxílio governamental pode ser interpretado como marcador social das famílias e/ou áreas mais carentes de intervenção governamental para aumentar o acesso aos programas de controle do câncer de mama.