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1.
BMJ Open ; 14(2): e074680, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38355174

ABSTRACT

INTRODUCTION: Lung cancer (LC) is the most common cause of cancer-related deaths worldwide. Its early detection can be achieved with a CT scan. Two large randomised trials proved the efficacy of low-dose CT (LDCT)-based lung cancer screening (LCS) in high-risk populations. The decrease in specific mortality is 20%-25%.Nonetheless, implementing LCS on a large scale faces obstacles due to the low number of thoracic radiologists and CT scans available for the eligible population and the high frequency of false-positive screening results and the long period of indeterminacy of nodules that can reach up to 24 months, which is a source of prolonged anxiety and multiple costly examinations with possible side effects.Deep learning, an artificial intelligence solution has shown promising results in retrospective trials detecting lung nodules and characterising them. However, until now no prospective studies have demonstrated their importance in a real-life setting. METHODS AND ANALYSIS: This open-label randomised controlled study focuses on LCS for patients aged 50-80 years, who smoked more than 20 pack-years, whether active or quit smoking less than 15 years ago. Its objective is to determine whether assisting a multidisciplinary team (MDT) with a 3D convolutional network-based analysis of screening chest CT scans accelerates the definitive classification of nodules into malignant or benign. 2722 patients will be included with the aim to demonstrate a 3-month reduction in the delay between lung nodule detection and its definitive classification into benign or malignant. ETHICS AND DISSEMINATION: The sponsor of this study is the University Hospital of Nice. The study was approved for France by the ethical committee CPP (Comités de Protection des Personnes) Sud-Ouest et outre-mer III (No. 2022-A01543-40) and the Agence Nationale du Medicament et des produits de Santé (Ministry of Health) in December 2023. The findings of the trial will be disseminated through peer-reviewed journals and national and international conference presentations. TRIAL REGISTRATION NUMBER: NCT05704920.


Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/epidemiology , Artificial Intelligence , Early Detection of Cancer/methods , Retrospective Studies , Tomography, X-Ray Computed/methods , Randomized Controlled Trials as Topic
2.
Respir Med ; 224: 107564, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38360190

ABSTRACT

BACKGROUND: Impulse oscillometry (IOS) is an effective tool for assessing airway mechanics and diagnosing obstructive airway disease (OAD) in children with sickle cell disease (C-SCD). Obesity is known to be associated with OAD, and untreated OAD often leads to hypoxia-related complications in C-SCD. Considering the increasing prevalence of obesity in C-SCD, it is important to explore the influence of body mass index (BMI) on OAD in this disease population. METHODS: A longitudinal retrospective chart review was conducted on 55 C-SCD (161 IOS observations) and 35 non-SCD asthmatic children (C-Asthma) (58 observations), primarily to investigate the association between BMI and airway resistance in C-SCD and C-Asthma. We conducted generalized linear mixed models (GLMM), adjusted for pharmacotherapies, to demonstrate the influence of BMI on total (R5), central (R20), and peripheral (R5-20) airway resistance and reactance (X5, resonant frequency (Fres)). We further compared age, BMI, and IOS indices between C-SCD and C-Asthma using the Mann-Whitney test. RESULTS: Age and BMI were not statistically different between the two groups. In C-SCD, BMI was associated with R5 (GLMM t-statistics:3.75, 95%CI:1.01,3.27, p-value<0.001*) and R20 (t-statistics:4.01, 95%CI:1.04,1.15, p-value<0.001*), but not with R5-20 or airway reactance. In asthmatics, BMI was not associated with IOS estimates except Fres (t-statistics: 3.93, 95%CI: -0.06, -0.02, p-value<0.001*). C-SCD demonstrated higher airway resistances (R5 and R20) and reactance (Fres) compared to C-Asthma (Mann-Whitney: p-values<0.05). CONCLUSION: BMI significantly influenced total and central airway resistance in C-SCD. While higher airway resistances reflected increased OAD in C-SCD than asthmatics, higher Fres perhaps indicated progressive pulmonary involvement in C-SCD.


Subject(s)
Anemia, Sickle Cell , Asthma , Child , Humans , Airway Resistance , Body Mass Index , Retrospective Studies , Longitudinal Studies , Oscillometry , Spirometry , Lung , Asthma/drug therapy , Anemia, Sickle Cell/complications , Obesity
3.
Rev. esp. nutr. comunitaria ; 29(4): 1-12, Octubre-Diciembre, 2023. tab
Article in Spanish | IBECS | ID: ibc-229075

ABSTRACT

Fundamentos: las semillas ancestrales se establecen como un elemento importante, dado que todo su proceso productivo conlleva un simbolismo de riqueza y conocimiento de los saberes ancestrales como un legado de la población, por tanto, se pretende describir las prácticas productivas semillas ancestrales del Resguardo Indígena Quillasinga "Refugio del Sol del corregimiento El Encano, Nariño 2022. Métodos: estudio cualitativo, descriptivo con la participación de 23 personas entre 50 y 70 años conocedores de los modelos productivos de las semillas, la información se recolecto por medio de entrevistas semiestructuradas. Resultados: se categorizaron 65 especies de semillas, ubicación y nombre, de igual manera, las principales características de sus modelos de producción, conservación y comercialización. Conclusiones: las prácticas productivas de las semillas muestran la relevancia e importancia de la soberanía alimentaria de los territorios indígenas y como se contribuye a la preservación y rescate de los saberes ancestrales de las comunidades en pro de sus legados. (AU)


Background: ancestral seeds are based as an important element, given that their entire productive process carries a symbolism of wealth and knowledge of ancestral knowledge as a legacy of the population, therefore, it is intended to describe the productive practices of ancestral seeds of the Indigenous Reservation Quillasinga "Shelter from the Sun of the corregimiento El Encano, Nariño 2022. Methods: qualitative, descriptive study with the participation of 23 people between 50 and 70 years old, familiar with the productive models of the seeds, the information is collected through semi-structured interviews. Results: 65 species of seeds, location and name were categorized, in the same way, the main characteristics of their production, conservation and commercialization models. Conclusions: the productive practices of the seeds show the relevance and importance of the food sovereignty of the indigenous territories and how they contribute to the have made and rescue of the ancestral knowledge of the communities in favor of their legacies. (AU)


Subject(s)
Seeds , Seed Bank , Food Preservation , Commerce , Food Production , Crop Production , Surveys and Questionnaires , Colombia
4.
NPJ Clim Atmos Sci ; 5(1): 79, 2022.
Article in English | MEDLINE | ID: mdl-36281291

ABSTRACT

Early career (EC) Earth system scientists in the Latin America and the Caribbean region (LAC) have been facing several issues, such as limited funding opportunities, substandard scientific facilities, lack of security of tenure, and unrepresented groups equality issues. On top of this, the worsening regional environmental and climatic crises call for the need for this new generation of scientists to help to tackle these crises by increasing public awareness and research. Realizing the need to converge and step up in making a collective action to be a part of the solution, the Latin America Early Career Earth System Scientist Network (LAECESS) was created in 2016. LAECESS's primary goals are to promote regional networking, foster integrated and interdisciplinary science, organize soft skills courses and workshops, and empower Latin American EC researchers. This article is an initial step towards letting the global science community grasp the current situation and hear the early career LAC science community's perspectives. The paper also presents a series of future steps needed for better scientific and social development in the LAC region.

5.
Article in English | MEDLINE | ID: mdl-37214276

ABSTRACT

Various neurological diseases affect the morphology of myelinated axons. Quantitative analysis of these structures and changes occurring due to neurodegeneration or neuroregeneration is of great importance for characterization of disease state and treatment response. This paper proposes a robust, meta-learning based pipeline for segmentation of axons and surrounding myelin sheaths in electron microscopy images. This is the first step towards computation of electron microscopy related bio-markers of hypoglossal nerve degeneration/regeneration. This segmentation task is challenging due to large variations in morphology and texture of myelinated axons at different levels of degeneration and very limited availability of annotated data. To overcome these difficulties, the proposed pipeline uses a meta learning-based training strategy and a U-net like encoder decoder deep neural network. Experiments on unseen test data collected at different magnification levels (i.e, trained on 500X and 1200X images, and tested on 250X and 2500X images) showed improved segmentation performance by 5% to 7% compared to a regularly trained, comparable deep learning network.

7.
Front Public Health ; 8: 575946, 2020.
Article in English | MEDLINE | ID: mdl-33072714

ABSTRACT

The benefits of walking in older age include improved cognitive health (e.g., mental alertness, improved memory functioning) and a reduced risk of stress, depression and dementia. However, research capturing the benefits of walking among older people in real-time as they navigate their world is currently very limited. This study explores cognitive health and well-being outcomes in older people as they walk in their local neighborhood environment. Residents from an independent living facility for older people (mean age 65, n = 11) walked from their home in two dichotomous settings, selected on the basis of significantly different infrastructure, varying levels of noise, traffic and percentage of green space. Employing a repeated-measures, cross over design, participants were randomly allocated to one of two groups, and walked on different days in an urban busy "gray" district (a busy, built up commercial street) vs. an urban quiet "green" district (a quiet residential area with front gardens and street trees). Our study captured real-time air quality and noise data using hand-held Airbeam sensors and physiologic health data using a smart watch to capture heart rate variability (a biomarker of stress). Cognitive health outcome measures were a pre- and post-walk short cognitive reaction time (SRT) test and memory recall of the route walked (captured via a drawn mental map). Emotional well-being outcomes were a pre- and post-walk mood scale capturing perceived stress, happiness and arousal levels. Findings showed significant positive health benefits from walking in the urban green district on emotional well-being (happiness levels) and stress physiology (p < 0.05), accompanied by faster cognitive reaction times post-walk, albeit not statistically significant in this small sample. Cognitive recall of the route varied between urban gray and urban green conditions, as participants were more likely to rely on natural features to define their routes when present. The environmental and physiologic data sets were converged to show a significant effect of ambient noise and urban conditions on stress activation as measured by heart rate variability. Findings are discussed in relation to the complexity of combining real-time environmental and physiologic data and the implications for follow-on studies. Overall, our study demonstrates the viability of using older people as citizen scientists in the capture of environmental and physiologic stress data and establishes a new protocol for exploring relationships between the built environment and cognitive health in older people.


Subject(s)
Built Environment , Walking , Aged , Aged, 80 and over , Environment Design , Humans , Outcome Assessment, Health Care , Pilot Projects
8.
Urban Clim ; 34: 100674, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32834965

ABSTRACT

The negative effects on human health, along with the fatalities caused by the new coronavirus, have led governments worldwide to take strict measures. However, a reduction in air pollution has been found in many regions on a global scale. This study is focused on how the COVID-19 pandemic is impacting on the air quality in Ecuador, one of the most alarming cases of COVID-19 contagion in Latin America, occupying the first place as regards deaths per capita. The spatio-temporal variations in NO2 concentrations in 12 highly populated cities were evaluated by comparing the NO2 tropospheric concentrations before (2019) and after (2020) the COVID-19 lockdown. The atmospheric data was collected from the TROPOMI on the Sentinel-5P satellite of the European Space Agency. A reduction in NO2 concentrations (-13%) was observed as a consequence of the COVID-19 lockdown in Ecuador. However, this reduction occurred to the greatest extent in the cases of Guayaquil (-23.4%) and Quito (-22.4%), the two most highly populated cities. Linking NO2 levels to confirmed cases/deaths of COVID-19, a strong correlation between air NO2 concentrations and the cases/mortality caused by coronavirus (r = 0.91; p<0.001) was observed. This work highlights the crucial role played by air quality as regards human health.

9.
J Chem Ecol ; 46(8): 649-658, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32206946

ABSTRACT

Many pollinator species are declining due to a variety of interacting stressors including pathogens, sparking interest in understanding factors that could mitigate these outcomes. Diet can affect host-pathogen interactions by changing nutritional reserves or providing bioactive secondary chemicals. Recent work found that sunflower pollen (Helianthus annuus) dramatically reduced cell counts of the gut pathogen Crithidia bombi in bumble bee workers (Bombus impatiens), but the mechanism underlying this effect is unknown. Here we analyzed methanolic extracts of sunflower pollen by LC-MS and identified triscoumaroyl spermidines as the major secondary metabolite components, along with a flavonoid quercetin-3-O-hexoside and a quercetin-3-O-(6-O-malonyl)-hexoside. We then tested the effect of triscoumaroyl spermidine and rutin (as a proxy for quercetin glycosides) on Crithidia infection in B. impatiens, compared to buckwheat pollen (Fagopyrum esculentum) as a negative control and sunflower pollen as a positive control. In addition, we tested the effect of nine fatty acids from sunflower pollen individually and in combination using similar methods. Although sunflower pollen consistently reduced Crithidia relative to control pollen, none of the compounds we tested had significant effects. In addition, diet treatments did not affect mortality, or sucrose or pollen consumption. Thus, the mechanisms underlying the medicinal effect of sunflower are still unknown; future work could use bioactivity-guided fractionation to more efficiently target compounds of interest, and explore non-chemical mechanisms. Ultimately, identifying the mechanism underlying the effect of sunflower pollen on pathogens will open up new avenues for managing bee health.


Subject(s)
Bees/microbiology , Crithidia/physiology , Glycosides/chemistry , Helianthus/chemistry , Host-Pathogen Interactions , Pollen/chemistry , Animals , Crithidia/drug effects , Fagopyrum/chemistry , Gastrointestinal Microbiome/drug effects , Plant Extracts/chemistry , Secondary Metabolism
10.
Biotechnol Biofuels ; 11: 90, 2018.
Article in English | MEDLINE | ID: mdl-29619086

ABSTRACT

BACKGROUND: Yeast-based chemical production is an environmentally friendly alternative to petroleum-based production or processes that involve harsh chemicals. However, many potential alcohol biofuels, such as n-butanol, isobutanol and n-hexanol, are toxic to production organisms, lowering the efficiency and cost-effectiveness of these processes. We set out to improve the tolerance of Saccharomyces cerevisiae toward these alcohols. RESULTS: We evolved the laboratory strain of S. cerevisiae BY4741 to be more tolerant toward n-hexanol and show that the mutations which confer tolerance occur in proteins of the translation initiation complex. We found that n-hexanol inhibits initiation of translation and evolved mutations in the α subunit of eIF2 and the γ subunit of its guanine exchange factor eIF2B rescue this inhibition. We further demonstrate that translation initiation is affected by other alcohols such as n-pentanol and n-heptanol, and that mutations in the eIF2 and eIF2B complexes greatly improve tolerance to these medium-chain alcohols. CONCLUSIONS: We successfully generated S. cerevisiae strains that have improved tolerance toward medium-chain alcohols and have demonstrated that the causative mutations overcome inhibition of translation initiation by these alcohols.

11.
JAMA Intern Med ; 178(3): 383-389, 2018 03 01.
Article in English | MEDLINE | ID: mdl-29404572

ABSTRACT

Importance: Transportation barriers contribute to missed primary care appointments for patients with Medicaid. Rideshare services have been proposed as alternatives to nonemergency medical transportation programs because of convenience and lower costs. Objective: To evaluate the association between rideshare-based medical transportation and missed primary care appointments among Medicaid patients. Design, Setting, and Participants: In a prospective clinical trial, 786 Medicaid beneficiaries who resided in West Philadelphia and were established primary care patients at 1 of 2 academic internal medicine practices located within the same building were included. Participants were allocated to being offered complimentary ride-sharing services (intervention arm) or usual care (control arm) based on the prescheduled day of their primary care appointment reminder. Those scheduled on even-numbered weekdays were in the intervention arm and on odd-numbered weekdays, the control arm. The primary study outcome was the rate of missed appointments, estimated using an intent-to-treat approach. All individuals receiving a phone call reminder were included in the study sample, regardless of whether they answered their phone. The study was conducted between October 24, 2016, and April 20, 2017. Interventions: A model of providing rideshare-based transportation was designed. As part of usual care, patients assigned to both arms received automated appointment phone call reminders. As part of the study protocol, patients assigned to both arms received up to 3 additional appointment reminder phone calls from research staff 2 days before their scheduled appointment. During these calls, patients in the intervention arm were offered a complimentary ridesharing service. Research staff prescheduled rides for those interested in the service. After their appointment, patients phoned research staff to initiate a return trip home. Main Outcomes and Measures: Missed appointment rate (no shows and same-day cancellations) in the intervention compared with control arm. Results: Of the 786 patients allocated to the intervention or control arm, 566 (72.0%) were women; mean (SD) age was 46.0. (12.5) years. Within the intervention arm, 85 among 288 (26.0%) participants who answered the phone call used ridesharing. The missed appointment rate was 36.5% (144 of 394) for the intervention arm and 36.7% (144 of 392) for the control arm (P = .96). Conclusions and Relevance: The uptake of ridesharing was low and did not decrease missed primary care appointments. Future studies trying to reduce missed appointments should explore alternative delivery models or targeting populations with stronger transportation needs. Trial Registration: clinicaltrials.gov Identifier: NCT02955433.


Subject(s)
Appointments and Schedules , No-Show Patients/statistics & numerical data , Patient Compliance/statistics & numerical data , Primary Health Care/organization & administration , Reminder Systems/statistics & numerical data , Transportation of Patients/organization & administration , Adult , Female , Humans , Male , Middle Aged , Philadelphia , Prospective Studies
13.
Rev. Fac. Nac. Salud Pública ; 34(2): 175-183, ago. 2016. ilus, tab
Article in Spanish | LILACS | ID: biblio-957168

ABSTRACT

Objetivo: presentar un Estado del Arte sobre el contenido de las políticas públicas de salud mental vigentes en Suramérica, con el propósito de establecer un panorama de los alcances y limitaciones de la normatividad sobre el tema en la región. Metodología:Estudio documental de enfoque hermenéutico mediante el cual se interpretó y explicó las relaciones entre los contenidos de las políticas públicas de salud mental y el contexto de los países suramericanos. Para el análisis se incluyeron documentos normativos de los países, tales como Acuerdos, Resoluciones y Leyes. Igualmente, se utilizaron publicaciones académicas en el periodo comprendido entre 2003 a 2013, que posibilitaron la descripción y el análisis del tema de investigación. Resultados: países como Colombia, Argentina, Paraguay, Brasil, Perú, Ecuador y Uruguay cuentan con disposiciones normativas vigentes (acuerdos, resoluciones y leyes) que sustentan el contenido de las políticas públicas en materia de salud mental. Por otra parte, Chile, Bolivia y Venezuela fundamentan sus políticas en mecanismos administrativos (programas, planes y proyectos) sin apelar a la norma de obligatorio cumplimiento. Conclusión: la noción de salud mental que subyace a cada Política Nacional hace énfasis en la promoción de la salud y la prevención de la enfermedad, desde una concepción positiva del bienestar que resalta el papel activo de los sujetos y poblaciones, las capacidades y libertades disponibles; sin embargo, los recursos, estrategias, acciones y metas están orientados sobre la base de un modelo biomédico que prioriza el diagnóstico y el tratamiento de trastornos mentales


Objective: to present the state of the art regarding the content of the public mental health policies currently in force in South America in order to establish an overview of the scope and limitations of the regulations on the subject in the region. Methodology: a documentary study with a hermeneutic approach explaining the relationships between the contents of the public policies for mental health and the context of the South American countries. For the analysis, we included normative documents of the countries, e.g. agreements, resolutions and acts. Similarly, academic papers from the period between 2003 and 2013 were included. These made it possible to describe and analyze the research subject. Results: countries such as Colombia, Argentina, Paraguay, Brazil, Peru, Ecuador and Uruguay have current regulations (agreements, resolutions and acts) supporting the content of public policies in regards to mental health. On the other hand, Chile, Bolivia and Venezuela base their policies on administrative mechanisms (programs, plans and projects) without enforcing mandatory compliance. Conclusion: the notion of mental health underlying each national policy emphasizes health promotion and prevention equally, and is based on a positive conception of well-being that highlights the active role of subjects and populations as well as the capabilities and liberties available. Nevertheless, their resources, strategies, actions and goals are based on a biomedical model that prioritizes the diagnosis and treatment of mental disorders.


Objetivo: apresenta um Estado da Arte sobre o conteúdo das políticas públicas de saúde mental em vigor na América do Sul, com o objetivo de estabelecer o panorama da abrangência e das limitações das normas sobre esta temática, na região. Metodologia: estudo documental de abordagem hermenêutica que foi interpretado e explicou as relações entre o conteúdo das políticas públicas de saúde mental e do contexto dos países da América do Sul. Para a análise foram incluídos documentos normativos dos países, tais como acordos, resoluções e leis. Da mesma forma, publicações acadêmicas foram utilizados no período de 2003 a 2013, que permitiu a descrição e análise do tema de pesquisa. Resultados: países como a Colômbia, a Argentina, o Paraguai, o Brasil, o Peru, o Equador e o Uruguai têm disposições regulamentares em vigor (acordos, resoluções e leis) que suportam o conteúdo das políticas públicas relacionadas com a saúde mental. Por outro lado, o Chile, a Bolívia e a Venezuela fundamentam as suas políticas em mecanismos administrativos (programas, planos e projetos), sem ter uma regra de cumprimento obrigatório. Conclusão: a noção de saúde mental que que subjaz cada Política Nacional enfatiza na promoção da saúde e da prevenção da doença, partindo de uma concepção positiva do bem-estar, ressaltando a função ativa dos sujeitos e das populações, as capacidades e as liberdades disponíveis. Porém, os recursos, as estratégias, as ações e as metas estão orientadas sobre a base de um modelo biomédico, priorizando o diagnóstico e tratamento de transtornos mentais.

14.
Metab Eng ; 33: 130-137, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26656942

ABSTRACT

Microorganisms can be engineered to produce a variety of biofuels and commodity chemicals. The accumulation of these products, however, is often toxic to the cells and subsequently lowers production yields. Efflux pumps are a natural mechanism for alleviating toxicity through secretion of the product; unfortunately, pump overexpression also often inhibits growth. Tuning expression levels with inducible promoters is time-consuming and the reliance on small-molecule inducers is cost-prohibitive in industry. We design an expression regulation system utilizing a native Escherichia coli stress promoter, PgntK, to provide negative feedback to regulate transporter expression levels. We test the promoter in the context of the efflux pump AcrB and its butanol-secreting variant, AcrBv2. PgntK-driven AcrBv2 confers increased tolerance to n-butanol and increased titers of n-butanol in production. Furthermore, the system is responsive to stress from toxic overexpression of other membrane-associated proteins. Our results suggest a use for feedback regulation networks in membrane protein expression.


Subject(s)
1-Butanol/metabolism , Drug Resistance/genetics , Escherichia coli Proteins/metabolism , Escherichia coli/physiology , Genetic Enhancement/methods , Multidrug Resistance-Associated Proteins/metabolism , Transcription, Genetic/physiology , 1-Butanol/isolation & purification , Cell Survival/genetics , Escherichia coli/cytology , Escherichia coli Proteins/genetics , Feedback, Physiological/physiology , Metabolic Engineering/methods , Multidrug Resistance-Associated Proteins/genetics , Promoter Regions, Genetic/genetics
15.
J Clin Endocrinol Metab ; 100(6): E926-35, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25853793

ABSTRACT

CONTEXT: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of primary adrenal Cushing's syndrome (CS). ARMC5 germline mutations have been identified recently in PBMAH. OBJECTIVE: To determine the prevalence of ARMC5 mutations and analyze genotype-phenotype correlation in a large cohort of unrelated PBMAH patients with subclinical or clinical CS. PATIENTS AND METHODS: ARMC5 was sequenced in 98 unrelated PBMAH index cases. PBMAH was identified by bilateral adrenal nodular enlargement on computed tomography scan. The effect on apoptosis of ARMC5 missense mutants was tested in H295R and HeLa cells. Clinical and hormonal data were collected including midnight and urinary free cortisol levels, ACTH, androgens, renin/aldosterone ratio, cortisol after overnight dexamethasone suppression test, cortisol and 17-hydroxyprogesterone after ACTH 1-24 stimulation and illegitimate receptor responses. Computed tomography and histological reports were analyzed. RESULTS: ARMC5-damaging mutations were identified in 24 patients (26%). The missense mutants and the p.F700del deletion were unable to induce apoptosis in both H295R and HeLa cell lines, unlike the wild-type gene. ARMC5-mutated patients showed an overt CS more frequently, compared to wild-type patients: lower ACTH, higher midnight plasma cortisol, urinary free cortisol, and cortisol after dexamethasone suppression test (P = .003, .019, .006, and <.001, respectively). Adrenals of patients with mutations were bigger and had a higher number of nodules (P = .001 and <.001, respectively). CONCLUSIONS: ARMC5 germline mutations are common in PBMAH. Index cases of mutation carriers show a more severe hypercortisolism and larger adrenals. ARMC5 genotyping may help to identify clinical forms of PBMAH better and may also allow earlier diagnosis of this disease.


Subject(s)
Adrenal Cortex Diseases/genetics , Adrenal Glands/pathology , Mutation, Missense , Tumor Suppressor Proteins/genetics , Adrenal Cortex Diseases/epidemiology , Adult , Aged , Armadillo Domain Proteins , Cells, Cultured , Cohort Studies , Cushing Syndrome/epidemiology , Cushing Syndrome/genetics , DNA Mutational Analysis , Female , Genetic Association Studies , HeLa Cells , Humans , Hyperplasia/genetics , Hyperplasia/pathology , Male , Middle Aged
16.
Eur J Hum Genet ; 22(2): 283-5, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23778871

ABSTRACT

Germline mutations of the MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterized by tumors of the parathyroids, the pancreas, and the anterior pituitary. Paraganglioma (PGL) is a rare endocrine tumor, which can be sporadic or genetically determined. To date, PGL has never been reported as a feature of MEN1.We report here a patient presenting three features of MEN1 syndrome (hyperparathyroidism, pancreatic neuroendocrine tumor, and adrenocortical adenoma) associated with PGL. Genetic analysis of MEN1 gene revealed a new missense mutation in exon 5 (AGGAAG), causing the substitution of arginine by lysine at codon 275. Screening for other genetic disorders (SDHx, TMEM127, MAX, CDKN1B) causing PGL was negative. Immunohistochemical analyses showed normal levels of succinate dehydrogenase (SDH)A and SDHB in the PGL. The proband's sister, bearing the mutation, had primary hyperparathyroidism. It was the first typical MEN1 syndrome reported with an extra-adrenal PGL.


Subject(s)
Abnormalities, Multiple/diagnosis , Adrenal Cortex Neoplasms/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Paraganglioma/diagnostic imaging , Proto-Oncogene Proteins/genetics , Abnormalities, Multiple/genetics , Adrenal Cortex Neoplasms/genetics , DNA Mutational Analysis , Female , Humans , Mutation, Missense , Pancreatic Neoplasms/genetics , Paraganglioma/genetics , Pedigree , Radiography , Syndrome
17.
J R Soc Interface ; 9(76): 2781-90, 2012 Nov 07.
Article in English | MEDLINE | ID: mdl-22696482

ABSTRACT

Gecko toe pads show strong adhesion on various surfaces yet remain remarkably clean around everyday contaminants. An understanding of how geckos clean their toe pads while being in motion is essential for the elucidation of animal behaviours as well as the design of biomimetic devices with optimal performance. Here, we test the self-cleaning of geckos during locomotion. We provide, to our knowledge, the first evidence that geckos clean their feet through a unique dynamic self-cleaning mechanism via digital hyperextension. When walking naturally with hyperextension, geckos shed dirt from their toes twice as fast as they would if walking without hyperextension, returning their feet to nearly 80 per cent of their original stickiness in only four steps. Our dynamic model predicts that when setae suddenly release from the attached substrate, they generate enough inertial force to dislodge dirt particles from the attached spatulae. The predicted cleaning force on dirt particles significantly increases when the dynamic effect is included. The extraordinary design of gecko toe pads perfectly combines dynamic self-cleaning with repeated attachment/detachment, making gecko feet sticky yet clean. This work thus provides a new mechanism to be considered for biomimetic design of highly reuseable and reliable dry adhesives and devices.


Subject(s)
Extremities/anatomy & histology , Extremities/physiology , Grooming/physiology , Lizards/physiology , Adhesiveness , Animals , Locomotion/physiology , Models, Biological
18.
Investig. andin ; 13(23): 268-280, sept. 2011.
Article in English, Spanish | LILACS | ID: lil-595417

ABSTRACT

Objetivo: caracterizar el riesgo suicida y depresión en internos de una cárcel deldepartamento del Quindío (Colombia). Metodología: se utilizó una metodología descriptiva-relacional y un diseño no experimental; se seleccionó una muestra de 34 reclusos entre los 18-51 años de acuerdo a criterios de inclusión y exclusión a quienes se les suministraron los cuestionarios ISO 30 e IDB. Resultados: más del 75% de los internos presentan riesgo suicida moderado o alto; el 56% reporta sintomatología depresiva grave y moderada. Se halló importante correlación entre estas dos variables. En la sub escala de afrontamiento de la ISO-30 se encontró una media de 8,81, lo que la ubica con resultados significativos; las medias restantes están en valores medios. Conclusión: es significativo determinar factores de riesgo en esta población y fortalecer la investigación en este campo desde un enfoque interdisciplinario, lo cual facilitará la identificación precoz y prevención de la conducta suicida.


Introduction: characterize the risk of suicide and depression among a group ofinmates in a jail in the state of Quindio (Colombia). Methods: a relational-descriptive methodology was used along with a non experimental design; ISO-30 and IDB surveys were distributed among a sample of 34 inmates between the ages of 18 – 51, who were selected according to inclusion and exclusion criteria. Results: more than 75% of the inmates presented a moderate to high risk of suicide; 56% reported depressive symptoms in a moderate to high degree. An important correlation among these two variables was found. The confrontation sub scale of the ISO-30 yielded a mean of 8.81, which places it with significant results; the remaining results are among median values. Conclusion: it is significant to determine risk factors in this population andstrengthen the investigation in this field, from an interdisciplinary focus, which willfacilitate an early detection and prevention of suicidal contact.


Subject(s)
Humans , Depression , Prisons , Suicide
19.
PLoS One ; 3(5): e2192, 2008 May 14.
Article in English | MEDLINE | ID: mdl-18478106

ABSTRACT

Gecko adhesion is expected to be temperature insensitive over the range of temperatures typically experienced by geckos. Previous work is limited and equivocal on whether this expectation holds. We tested the temperature dependence of adhesion in Tokay and Day geckos and found that clinging ability at 12 degrees C was nearly double the clinging ability at 32 degrees C. However, rather than confirming a simple temperature effect, our data reveal a complex interaction between temperature and humidity that can drive differences in adhesion by as much as two-fold. Our findings have important implications for inferences about the mechanisms underlying the exceptional clinging capabilities of geckos, including whether performance of free-ranging animals is based solely on a dry adhesive model. An understanding of the relative contributions of van der Waals interactions and how humidity and temperature variation affects clinging capacities will be required to test hypotheses about the evolution of gecko toepads and is relevant to the design and manufacture of synthetic mimics.


Subject(s)
Adhesives , Humidity , Lizards/physiology , Temperature , Animals
20.
J Clin Microbiol ; 46(3): 1026-36, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18216214

ABSTRACT

The Shigella genus has historically been separated into four species, based on biochemical assays. The classification within each species relies on serotyping. Recently, genome sequencing and DNA assays, in particular the multilocus sequence typing (MLST) approach, greatly improved the current knowledge of the origin and phylogenetic evolution of Shigella spp. The Shigella and Escherichia genera are now considered to belong to a unique genomospecies. Multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) provides valuable polymorphic markers for genotyping and performing phylogenetic analyses of highly homogeneous bacterial pathogens. Here, we assess the capability of MLVA for Shigella typing. Thirty-two potentially polymorphic VNTRs were selected by analyzing in silico five Shigella genomic sequences and subsequently evaluated. Eventually, a panel of 15 VNTRs was selected (i.e., MLVA15 analysis). MLVA15 analysis of 78 strains or genome sequences of Shigella spp. and 11 strains or genome sequences of Escherichia coli distinguished 83 genotypes. Shigella population cluster analysis gave consistent results compared to MLST. MLVA15 analysis showed capabilities for E. coli typing, providing classification among pathogenic and nonpathogenic E. coli strains included in the study. The resulting data can be queried on our genotyping webpage (http://mlva.u-psud.fr). The MLVA15 assay is rapid, highly discriminatory, and reproducible for Shigella and Escherichia strains, suggesting that it could significantly contribute to epidemiological trace-back analysis of Shigella infections and pathogenic Escherichia outbreaks. Typing was performed on strains obtained mostly from collections. Further studies should include strains of much more diverse origins, including all pathogenic E. coli types.


Subject(s)
Bacterial Typing Techniques , Minisatellite Repeats/genetics , Shigella/classification , Shigella/genetics , DNA, Bacterial/analysis , Dysentery, Bacillary/microbiology , Genome, Bacterial , Humans , Sequence Analysis, DNA
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