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1.
PLoS Genet ; 18(8): e1010169, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35951639

RESUMO

2-deoxyglucose is a glucose analog that impacts many aspects of cellular physiology. After its uptake and its phosphorylation into 2-deoxyglucose-6-phosphate (2DG6P), it interferes with several metabolic pathways including glycolysis and protein N-glycosylation. Despite this systemic effect, resistance can arise through strategies that are only partially understood. In yeast, 2DG resistance is often associated with mutations causing increased activity of the yeast 5'-AMP activated protein kinase (AMPK), Snf1. Here we focus on the contribution of a Snf1 substrate in 2DG resistance, namely the alpha-arrestin Rod1 involved in nutrient transporter endocytosis. We report that 2DG triggers the endocytosis of many plasma membrane proteins, mostly in a Rod1-dependent manner. Rod1 participates in 2DG-induced endocytosis because 2DG, following its phosphorylation by hexokinase Hxk2, triggers changes in Rod1 post-translational modifications and promotes its function in endocytosis. Mechanistically, this is explained by a transient, 2DG-induced inactivation of Snf1/AMPK by protein phosphatase 1 (PP1). We show that 2DG-induced endocytosis is detrimental to cells, and the lack of Rod1 counteracts this process by stabilizing glucose transporters at the plasma membrane. This facilitates glucose uptake, which may help override the metabolic blockade caused by 2DG, and 2DG export-thus terminating the process of 2DG detoxification. Altogether, these results shed a new light on the regulation of AMPK signaling in yeast and highlight a remarkable strategy to bypass 2DG toxicity involving glucose transporter regulation.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Proteínas de Saccharomyces cerevisiae , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Desoxiglucose/farmacologia , Endocitose/genética , Glucose/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/genética , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Humanos , Redes e Vias Metabólicas , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
2.
Euro Surveill ; 29(5)2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38304951

RESUMO

Real-time PCR is one of the most widely used techniques to diagnose measles cases. Here we report measles virus variants with three genetic mutations in the reverse primer annealing site of a widely used PCR. The mutations result in a slight loss of the PCR sensitivity. Variants bearing the three mutations presently circulate in different countries since at least the end of 2021. Our findings highlight the usefulness of molecular surveillance in monitoring if oligonucleotides in diagnostic tests remain adequate.


Assuntos
Sarampo , Patologia Molecular , Humanos , Suíça , RNA Viral/genética , Sarampo/diagnóstico , Sarampo/epidemiologia , Vírus do Sarampo/genética , Mutação , Sensibilidade e Especificidade , Reação em Cadeia da Polimerase Via Transcriptase Reversa
3.
Euro Surveill ; 29(22)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38818746

RESUMO

A measles outbreak with 51 cases occurred in the canton of Vaud, Switzerland, between January and March 2024. The outbreak was triggered by an imported case, and 37 (72.5%) subsequent cases were previously vaccinated individuals. Epidemiological investigations showed that vaccinated measles cases were symptomatic and infectious. In a highly vaccinated population, it is important to raise awareness among healthcare professionals to suspect and test for measles virus when an outbreak is declared, irrespective of the vaccination status of the patients.


Assuntos
Surtos de Doenças , Vacina contra Sarampo , Vírus do Sarampo , Sarampo , Vacinação , Humanos , Sarampo/prevenção & controle , Sarampo/epidemiologia , Suíça/epidemiologia , Surtos de Doenças/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Vacinação/estatística & dados numéricos , Masculino , Feminino , Adulto , Adolescente , Criança , Vírus do Sarampo/imunologia , Vírus do Sarampo/isolamento & purificação , Pré-Escolar , Adulto Jovem , Lactente
4.
J Fish Biol ; 104(3): 723-736, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37961022

RESUMO

Body morphology is a valuable feature for distinguishing teleostean fishes. However, the utility of character variation in separate body regions has yet to be tested. The taxonomy of the Gerreidae family is controversial due to character overlapping among its fish species. This work aims to analyze and compare the body shape variation in three regions, cephalic, trunk, and caudal peduncle, using landmark data and geometric morphometric methods in 17 species and five genera of the family Gerreidae. The pattern of shape variation for the cephalic region consisted of well-defined character states exclusive of each species analyzed. Shape variation in the trunk and caudal peduncle regions does not distinguish all species in this study. This study showed that the dorsal cephalic profile is highly variable among the species, therefore, shape variation in this region is useful for distinguishing Gerreidae species. In contrast, some species within the same genus share similar shape states in the trunk and caudal peduncle regions, with the most shape variation in the dorsal profile and anal fin for the trunk and in the middle of the caudal peduncle.


Assuntos
Peixes , Animais
5.
J Fish Biol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978288

RESUMO

The genus Urotrygon comprises small- to medium-sized endemic round rays on the American continent and has undergone several synonymization processes. Here, we used an integrative taxonomic approach, including meristic, morphometric, and mtDNA analyses, to resolve the particularly intricate relationship among Urotrygon munda Gill, 1863, Urotrygon chilensis (Günther, 1872), and Urotrygon asterias (Jordan & Gilbert, 1883). The latter species is currently a synonym of U. munda but is also considered the U. chilensis "northern morphotype." These taxonomic entities have historically been confounded, mainly due to their phenotypical resemblance along their geographic distribution in the eastern Pacific. We assessed 78 specimens (43 "northern" and 30 "southern morphotypes" of U. chilensis, as well as 5 U. munda) using 19 external variables for taxonomic and morphometric analysis. Distinct meristic patterns, including pectoral and pelvic ceratotrichia, vertebrae number, and thorn distribution along the dorsal midline, were observed in the series-type specimens of the three taxonomic entities. Our multivariate morphometric analyses consistently differentiated the three groups as distinct taxonomic entities, with an overall classification accuracy of 66.7%. The meristic results also provided reliable information distinguishing the three entities. Based on the nicotinamide adenine dinucleotide (NADH2) and cytochrome oxidase subunit I (COI) genes, our phylogenetic analysis were consistent with the morphometric and meristic data, supporting these three entities as distinct species having their own evolutionary lineages. Our comprehensive approach confidently demonstrated that the northern U. chilensis morphotype matched and corresponded to the description of the Starry round ray, U. asterias, confirming its taxonomic resurrection as a valid species distinct from U. chilensis and U. munda. The geographic distribution of U. asterias spans from the tropical west coast of Mexico (including the Gulf of California) to Costa Rica, revealing that microevolutionary processes have well-defined population clades within this range. Furthermore, U. chilensis is unequivocally established as the sole Urotrygon species occurring south of the Guayaquil marine ecoregion. In addition, the public COI and NADH2 sequences available for Urotrygon hosted in the ad hoc online databases were found to be misidentified, emphasizing the need for rigorous taxonomic scrutiny in this group. Finally, our research underscores the significance of an integrative approach that combines morphometric, meristic, and molecular techniques with historical data to disentangle the complexities of closely related taxa.

6.
J Fish Dis ; 45(3): 395-409, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34871460

RESUMO

Although morphological abnormalities in several rays and skate species around the American continents have frequently mentioned, their numbers are unknown. The present work record morphological abnormalities in four Urotrygonidae species. Two anophthalmic specimens were detected (Urotrygon microphthalmum and Urobatis halleri). Two individuals lacked caudal fins (Urobatis maculatus and Urotrygon chilensis). Two round rays showed incomplete fusion of the pectoral fin to the head (U. microphthalmum and U. chilensis). Vertebral compression and fusion were found in a 6-year-old female Urotrygon rogersi. In addition, 118 abnormal batomorph specimens were gathered from the available bibliography, spanning the last six decades (1959-2021). Amblyraja doellojuradoi was the species with the highest number of abnormalities (18). The most common anomaly was an incomplete fusion of the pectoral fin with the head. Since 2010, at least 30 anomalous batomorphs have been recorded every 5 years. Sixty-nine abnormal specimens occurred in the Northern Hemisphere (1.00-60.00 N). The Cortezian (Pacific) and Southeastern Brazil (Atlantic) marine ecoregions stood out with the highest number of these specimens. Mexico recorded 58 anomalous specimens, followed by Brazil (n = 36). Biological, abiotic and anthropogenic factors are probably the leading causes. However, additional studies are necessary to elucidate these speculations.


Assuntos
Elasmobrânquios , Doenças dos Peixes , Rajidae , Animais , Brasil , Feminino , México
7.
J Sports Sci ; 40(14): 1558-1567, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35731706

RESUMO

Prolonged sitting has been shown to affect endothelial function. Strategies that promote interruption of sitting have shown varying results on the shear rate (SR), flow-mediated dilation (FMD) and blood flow (BF). Thus, we conducted a systematic review and meta-analysis to 1) increase the existing knowledge of the impact of sitting interruption in the prevention of endothelial dysfunction in adults and 2) determine the effect of the sitting interruption strategies on SR, FMD, BF. Literature search was carried out through 7 databases. A random effects model was used to provide the overall mean difference with a 95%CI, and forest plots were generated for pooled estimates of each study outcome. Assessment of biases was performed using ROB2 and considerations for crossover trials. Prolonged sitting interruption strategies showed a significant effect in increasing SR (MD: 7.58 s-1; 95% CI: 3.00 to 12.17), FMD (MD: 1.74%; 95% CI: 0.55 to 2.93) and BF (MD: 12.08 ml/min; 95% CI: 7.61 to 16.55) when compared with the uninterrupted prolonged sitting condition. Prolonged sitting interruption strategies significantly increase SR, FMD and BF, therefore, they represent a considerable effective preventive method on endothelial dysfunction caused by acute exposure to uninterrupted prolonged sitting.


Assuntos
Endotélio Vascular , Vasodilatação , Adulto , Estudos Cross-Over , Dilatação , Endotélio Vascular/fisiologia , Hemodinâmica , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fluxo Sanguíneo Regional/fisiologia , Vasodilatação/fisiologia
8.
J Insect Sci ; 22(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34942006

RESUMO

The carmine cochineal (Dactylopius coccus Costa) has high economic value as it is a natural source of carminic acid, an organic chromophore used in a wide range of sectors including pharmaceutics, food, and cosmetics. High demand is fuelling the search for innovative production techniques in order to move away from dependence on the prickly pear, which carries a number of limitations. The aim of this study was to establish cochineal colonies and breed and mass-produce the insects using two laboratory-scale production systems. The first system (STC-01) comprised a prismatic acrylic box with three compartments; synthetic matrices were placed vertically inside the box to provide support and a source of nutrients for the cochineal, and the system was lit artificially during fixed daylight periods. The second system (STC-02) comprised an automated micro-tunnel allowing the insects to move towards the sunlight, containing synthetic matrices arranged horizontally. There was a significant difference in yield between the two systems in a cochineal total life cycle of 120 d (80-90 d harvest period in both cases), with STC-01 being superior and producing a maximum yield of 4.86 ± 0.68 g fresh weight per day per square metre compared with 3.20 ± 0.14 g fresh weight per day per square metre production yield in STC-02. We conclude that cochineal production under controlled artificial conditions is feasible and sustainable, removing the need for natural and biological support and overcoming the environmental limitations posed by traditional production methods.


Assuntos
Carmim , Hemípteros , Animais , Hemípteros/crescimento & desenvolvimento , Peru
9.
Rev Med Chil ; 150(12): 1625-1632, 2022 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-37906784

RESUMO

BACKGROUND: The population of actively working older people is growing rapidly. The relationship between quality of life, levels of physical activity and functionality in this population is not entirely clear. AIM: To determine the association between quality of life, levels of physical activity and functional tests in actively working adults and older people. MATERIAL AND METHODS: Cross sectional assessment of 138 adults aged 40 to 50 years (53% women) and 119 older people aged 60 to 75 years (53% women) who were actively working in two public services. Quality of life was measured with the SF-36 questionnaire and usual physical activity was assessed with the International Physical Activity Questionnaire (IPAQ-short). Handgrip strength, the timed up and go (TUG) and chair stand test (CST) were used as functional tests. RESULTS: Compared to older people, adults had better physical functional tests (P < 0.01). Older people had better scores in the mental health component (MHC) of quality of life (p < 0.05). In adults, the physical health component of quality of life (CSF) had a positive association with physical activity (Spearman Rho (rs)= 0.270; p = 0.01), grip strength (rs = 0.330; p < 0.01) and the TUG (rs = -0.229; p < 0.01). In older patients, CSM and CST were positively correlated (rs = 0.201; P = 0.029). In both groups, a correlation was observed between CSM, grip strength (adults rs = 0.283; p < 0.01; older people rs = 0.211; P = 0.02) and with TUG (adults rs = -0.197; P = 0.021; older people rs = - 0.212; p = 0.02). CONCLUSIONS: There is a positive correlation between quality of life and level of physical activity in working adults, which is not observed in older people. Adequate performance in physical functional tests is positively correlated with better quality of life (CSF and CSM) in adults and only with the mental health component in older people.


Assuntos
Força da Mão , Qualidade de Vida , Humanos , Adulto , Feminino , Idoso , Masculino , Estudos Transversais , Exercício Físico , Saúde Mental
10.
Mol Biol Rep ; 48(10): 7007-7012, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34426903

RESUMO

BACKGROUND: Octopus hubbsorum Berry, 1953 is the most important species for commercial fishing in the Mexican Pacific. However, there is a lack of information regarding population structure that could have important management implications. We tested 44 microsatellite loci in O. hubbsorum by cross-amplification from O. bimaculatus. METHODS AND RESULTS: Genetic diversity and structure was tested over 30 octopus sampled from Santa Cruz de Miramar (Nayarit, México). A total of 11 loci were successfully amplified. All loci were polymorphic with the number of effective alleles ranging from 2.13 to 23.14, while three loci significantly deviated from Hardy-Weinberg equilibrium. No significant LD was observed between pairs of loci (P ≥ 0.05). The application of the new markers in a O. hubbsorum population from Santa Cruz de Miramar Nayarit, México, did not showed Wahlund or isolate breaking effects due to the mixing of distinct populations. CONCLUSIONS: The loci were useful to estimate levels of pairwise relatedness and to discard the presence of recent demographic bottlenecks in the population. We consider that eight microsatellites are adequate from the 11 amplified loci.


Assuntos
Variação Genética , Repetições de Microssatélites/genética , Octopodiformes/genética , Animais , Geografia , México
11.
Cell Mol Life Sci ; 77(22): 4631-4662, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31900623

RESUMO

Despite the experimental evidence pointing to a significant role of the Wnt family of proteins in physiological and pathological rodent spinal cord functioning, its potential relevance in the healthy and traumatically injured human spinal cord as well as its therapeutic potential in spinal cord injury (SCI) are still poorly understood. To get further insight into these interesting issues, we first demonstrated by quantitative Real-Time PCR and simple immunohistochemistry that detectable mRNA expression of most Wnt components, as well as protein expression of all known Wnt receptors, can be found in the healthy human spinal cord, supporting its potential involvement in human spinal cord physiology. Moreover, evaluation of Frizzled (Fz) 1 expression by double immunohistochemistry showed that its spatio-temporal and cellular expression pattern in the traumatically injured human spinal cord is equivalent to that observed in a clinically relevant model of rat SCI and suggests its potential involvement in SCI progression/outcome. Accordingly, we found that long-term lentiviral-mediated overexpression of the Fz1 ligand Wnt1 after rat SCI improves motor functional recovery, increases myelin preservation and neuronal survival, and reduces early astroglial reactivity and NG2+ cell accumulation, highlighting the therapeutic potential of Wnt1 in this neuropathological situation.


Assuntos
Receptores Frizzled/metabolismo , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Proteína Wnt1/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/metabolismo , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/fisiologia
12.
Int Arch Occup Environ Health ; 94(6): 1307-1315, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33730207

RESUMO

OBJECTIVE: To determine if there are differences in functional capacity and work ability between older and younger active workers in public institutions, and to relate functional capacity to work ability. METHODS: This cross-sectional study evaluated 360 subjects from two public institutions, a university and a high-complexity regional hospital. The participants were divided into 3 age ranges 40-49, 50-59 and ≥ 60 years. The following evaluations were applied: a multidimensional assessment questionnaire, work ability and functional capacity using physical tests (strength, flexibility and balance). RESULTS: There are no significant differences in work ability among the different age groups (P > 0.05). Significant differences were found according to age group in 30-s chair-stand test (30-s CST), 1 repetition maximum (1RM) extending the knee 90° (1RM-leg extension) and 1RM of handgrip strength (1RM-handgrip), upper body flexibility, lower body flexibility, static balance or dynamic balance (P < 0.05). Only the variables 30-s CST (rs = 0.13, P = 0.018), lower body flexibility (rs = 0.13, P = 0.012) and static balance (rs = 0.13, P = 0.012) were related to work ability. CONCLUSIONS: There are differences in functional capacity as the workers' ages increase. By contrast, work ability does not present any differences when comparing older and younger adults. Some physical tests of the lower extremities presented a small correlation with work ability.


Assuntos
Envelhecimento/fisiologia , Hospitais , Universidades , Avaliação da Capacidade de Trabalho , Adulto , Chile , Feminino , Força da Mão , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Equilíbrio Postural , Amplitude de Movimento Articular
13.
Sensors (Basel) ; 21(16)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34451090

RESUMO

Solar energy penetration has been on the rise worldwide during the past decade, attracting a growing interest in solar power forecasting over short time horizons. The increasing integration of these resources without accurate power forecasts hinders the grid operation and discourages the use of this renewable resource. To overcome this problem, Virtual Power Plants (VPPs) provide a solution to centralize the management of several installations to minimize the forecasting error. This paper introduces a method to efficiently produce intra-day accurate Photovoltaic (PV) power forecasts at different locations, by using free and available information. Prediction intervals, which are based on the Mean Absolute Error (MAE), account for the forecast uncertainty which provides additional information about the VPP node power generation. The performance of the forecasting strategy has been verified against the power generated by a real PV installation, and a set of ground-based meteorological stations in geographical proximity have been used to emulate a VPP. The forecasting approach is based on a Long Short-Term Memory (LSTM) network and shows similar errors to those obtained with other deep learning methods published in the literature, offering a MAE performance of 44.19 W/m2 under different lead times and launch times. By applying this technique to 8 VPP nodes, the global error is reduced by 12.37% in terms of the MAE, showing huge potential in this environment.


Assuntos
Redes Neurais de Computação , Energia Solar , Previsões , Centrais Elétricas , Luz Solar
14.
Adicciones ; 33(2): 121-136, 2021 Mar 31.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32677691

RESUMO

The objective was to evaluate the risk of presenting an alcohol use disorder (AUD) in outpatient psychiatric units and compare it with drug addiction outpatient units and with healthy controls in the same administrative health area. An observational, descriptive, multicenter study was carried out in which a total of 1054 participants were evaluated. Data were obtained by means of the camouflaged CAGE questionnaire, which consists of 4 basic questions camouflaged with 8 other questions about healthy lifestyle habits. Cut-off points 1 and 2 were considered.Of the total number of participants, 588 were psychiatric outpatients, 153 outpatients from addiction centers and 313 healthy individuals. The mean age of the total sample was 45.8 years and the percentage of men was 53.2%. Of the total sample, 38.3% scored ≥1, as did 34.2% of psychiatric patients, 72.5% of drug addicts and 29.4% of healthy people. The ≥2 cut-off was reached by 26.6% of the total sample, 22.6% of psychiatric patients, 64.7% of drug addicts and 15.3% of healthy subjects. The participants with the highest percentage of ≥1 scores were men (48.8%), those younger than 30 years (50%), those with a diagnosis of alcohol use disorder (95.9%) and ADHD (83.3%).Psychiatric patients are at a higher risk of having an AUD than the healthy subjects, although lower than those who are drug addicts, and the CAGE questionnaire is a simple and useful tool to detect the risk patients have to suffer the condition under study.


El objetivo fue evaluar el riesgo de presentar un trastorno por uso de alcohol (TUA) en las consultas psiquiátricas ambulatorias y compararlo con las consultas de drogodependencias y con individuos sanos de la misma zona de salud. Se realizó un estudio observacional, descriptivo, multicéntrico, en el que fueron incluidos un total de 1054 participantes. Se utilizó el cuestionario CAGE camuflado para la obtención de los datos, que consta de 4 preguntas básicas camufladas con otras 8 preguntas sobre hábitos de vida saludables. Se consideraron los puntos de corte de 1 y 2.Del total de participantes, 588 eran pacientes psiquiátricos ambulatorios, 153 de los centros de drogodependencias ambulatorios y 313 sanos. La edad media de la muestra fue de 45,8 años y el porcentaje de hombres fue del 53,2%. El 38,3% de los participantes presentaron una puntuación ≥1, el 34,2% en las consultas psiquiátricas, el 72,5% en las de drogodependencias y el 29,4% en sanos. El 26,6% presentaron una puntuación ≥2, el 22,6% en las consultas psiquiátricas, el 64,7% en las de drogodependencias y el 15,3% en sanos. Los que presentaron mayor porcentaje de puntuación ≥1 fueron los hombres (48,8%), los menores de 30 años (50%), y los que tenían un diagnóstico de trastorno por uso de alcohol (95,9%) y de TDAH (83,3%).Los pacientes psiquiátricos presentan un mayor riesgo de presentar un TUA que los individuos sanos, aunque menor que los drogodependientes, siendo el cuestionario CAGE una herramienta sencilla y útil para detectar el riesgo de presentarlos.


Assuntos
Alcoolismo , Usuários de Drogas , Transtornos Relacionados ao Uso de Substâncias , Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Populacionais , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e Questionários
15.
Ann Neurol ; 86(2): 293-303, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31125140

RESUMO

OBJECTIVE: Thymidine kinase 2, encoded by the nuclear gene TK2, is required for mitochondrial DNA maintenance. Autosomal recessive TK2 mutations cause depletion and multiple deletions of mtDNA that manifest predominantly as a myopathy usually beginning in childhood and progressing relentlessly. We investigated the safety and efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies. METHODS: We administered deoxynucleoside monophosphates and deoxynucleoside to 16 TK2-deficient patients under a compassionate use program. RESULTS: In 5 patients with early onset and severe disease, survival and motor functions were better than historically untreated patients. In 11 childhood and adult onset patients, clinical measures stabilized or improved. Three of 8 patients who were nonambulatory at baseline gained the ability to walk on therapy; 4 of 5 patients who required enteric nutrition were able to discontinue feeding tube use; and 1 of 9 patients who required mechanical ventilation became able to breathe independently. In motor functional scales, improvements were observed in the 6-minute walk test performance in 7 of 8 subjects, Egen Klassifikation in 2 of 3, and North Star Ambulatory Assessment in all 5 tested. Baseline elevated serum growth differentiation factor 15 levels decreased with treatment in all 7 patients tested. A side effect observed in 8 of the 16 patients was dose-dependent diarrhea, which did not require withdrawal of treatment. Among 12 other TK2 patients treated with deoxynucleoside, 2 adults developed elevated liver enzymes that normalized following discontinuation of therapy. INTERPRETATION: This open-label study indicates favorable side effect profiles and clinical efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies for TK2 deficiency. ANN NEUROL 2019;86:293-303.


Assuntos
Ensaios de Uso Compassivo/métodos , Desoxirribonucleosídeos/uso terapêutico , Doenças Musculares/tratamento farmacológico , Doenças Musculares/enzimologia , Timidina Quinase/deficiência , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Teste de Caminhada/métodos
16.
Cell Mol Neurobiol ; 40(7): 1087-1103, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31974907

RESUMO

Despite the emerging role of protein tyrosine kinase 7 (PTK7) as a Wnt co-receptor and the relevant functions of the Wnt family of proteins in spinal cord injury (SCI), the potential involvement of PTK7 in SCI is currently unknown. As a first essential step to shed light on this issue, we evaluated the spatio-temporal and cellular expression patterns of PTK7 in healthy and traumatically injured rat and human spinal cords. In the uninjured rats, PTK7 expression was observed in the ependymal epithelium, endothelial cells, meningeal fibronectin-expressing cells, and specific axonal tracts, but not in microglia, astrocytes, neurons, oligodendrocytes, or NG2+ cells. After rat SCI, the mRNA expression of PTK7 was significantly increased, while its spatio-temporal and cellular protein expression patterns also suffered evident changes in the injured region. Briefly, the expression of PTK7 in the affected areas was observed in axons, reactive astrocytes, NG2+ and fibronectin-expressing cells, and in a subpopulation of reactive microglia/macrophages and blood vessels. Finally, in both healthy and traumatically injured human spinal cords, PTK7 expression pattern was similar to that observed in the rat, although some specific differences were found. In conclusion, we demonstrate for the first time that PTK7 is constitutively expressed in the healthy adult rat and human spinal cord and that its expression pattern clearly varied after rat and human SCI which, to our knowledge, constitutes the first experimental evidence pointing to the potential involvement of this co-receptor in physiological and pathological spinal cord functioning.


Assuntos
Moléculas de Adesão Celular/metabolismo , Células Endoteliais/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Animais , Astrócitos/metabolismo , Axônios/metabolismo , Fibronectinas/metabolismo , Humanos , Macrófagos/metabolismo , Microglia/metabolismo , Neurônios/metabolismo , Oligodendroglia/metabolismo , Ratos
17.
Sensors (Basel) ; 20(10)2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32456050

RESUMO

In this work, we introduce an intelligent video sensor for the problem of Action Proposals (AP). AP consists of localizing temporal segments in untrimmed videos that are likely to contain actions. Solving this problem can accelerate several video action understanding tasks, such as detection, retrieval, or indexing. All previous AP approaches are supervised and offline, i.e. they need both the temporal annotations of the datasets during training and access to the whole video to effectively cast the proposals. We propose here a new approach which, unlike the rest of the state-of-the-art models, is unsupervised. This implies that we do not allow it to see any labeled data during learning nor to work with any pre-trained feature on the used dataset. Moreover, our approach also operates in an online manner, which can be beneficial for many real-world applications where the video has to be processed as soon as it arrives at the sensor, e.g., robotics or video monitoring. The core of our method is based on a Support Vector Classifier (SVC) module which produces candidate segments for AP by distinguishing between sets of contiguous video frames. We further propose a mechanism to refine and filter those candidate segments. This filter optimizes a learning-to-rank formulation over the dynamics of the segments. An extensive experimental evaluation is conducted on Thumos'14 and ActivityNet datasets, and, to the best of our knowledge, this work supposes the first unsupervised approach on these main AP benchmarks. Finally, we also provide a thorough comparison to the current state-of-the-art supervised AP approaches. We achieve 41% and 59% of the performance of the best-supervised model on ActivityNet and Thumos'14, respectively, confirming our unsupervised solution as a correct option to tackle the AP problem. The code to reproduce all our results will be publicly released upon acceptance of the paper.

18.
Sensors (Basel) ; 18(11)2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30441877

RESUMO

Bad data as a result of measurement errors in secondary substation (SS) monitoring equipment is difficult to detect and negatively affects power system state estimation performance by both increasing the computational burden and jeopardizing the state estimation accuracy. In this paper a short-term load forecasting (STLF) hybrid strategy based on singular spectrum analysis (SSA) in combination with artificial neural networks (ANN), is presented. This STLF approach is aimed at detecting, identifying and eliminating and/or correcting such bad data before it is provided to the state estimator. This approach is developed to improve the accuracy of the load forecasts and it is tested against real power load data provided by electricity suppliers. Depending on the week considered, mean absolute percentage error (MAPE) values which range from 1.6% to 3.4% are achieved for STLF. Different systematic errors, such as gain and offset error levels and outliers, are successfully detected with a hit rate of 98%, and the corresponding measurements are corrected before they are sent to the control center for state estimation purposes.

19.
RNA ; 21(9): 1544-53, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26150554

RESUMO

Genes coding for members of the Sm-like (LSm) protein family are conserved through evolution from prokaryotes to humans. These proteins have been described as forming homo- or heterocomplexes implicated in a broad range of RNA-related functions. To date, the nuclear LSm2-8 and the cytoplasmic LSm1-7 heteroheptamers are the best characterized complexes in eukaryotes. Through a comprehensive functional study of the LSm family members, we found that lsm-1 and lsm-3 are not essential for C. elegans viability, but their perturbation, by RNAi or mutations, produces defects in development, reproduction, and motility. We further investigated the function of lsm-1, which encodes the distinctive protein of the cytoplasmic complex. RNA-seq analysis of lsm-1 mutants suggests that they have impaired Insulin/IGF-1 signaling (IIS), which is conserved in metazoans and involved in the response to various types of stress through the action of the FOXO transcription factor DAF-16. Further analysis using a DAF-16::GFP reporter indicated that heat stress-induced translocation of DAF-16 to the nuclei is dependent on lsm-1. Consistent with this, we observed that lsm-1 mutants display heightened sensitivity to thermal stress and starvation, while overexpression of lsm-1 has the opposite effect. We also observed that under stress, cytoplasmic LSm proteins aggregate into granules in an LSM-1-dependent manner. Moreover, we found that lsm-1 and lsm-3 are required for other processes regulated by the IIS pathway, such as aging and pathogen resistance.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Citoplasma/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Animais , Sequência de Bases , Caenorhabditis elegans/genética , Sequência Conservada , Fatores de Transcrição Forkhead/metabolismo , Genes Essenciais , Temperatura Alta , Humanos , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Mutação , Transdução de Sinais , Estresse Fisiológico
20.
Nurs Ethics ; 24(8): 962-966, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27162134

RESUMO

This article will explore a clinical case study of a home visit carried out by the case manager nurse. In this case, we will discuss the dilemma of finding the balance between autonomy and beneficence from the perspective of principlist ethics, virtue ethics and the 'ethics of care'. The main conflict in this case study deals with all proposals are unsuitable and it is not necessary for a nurse to pay him a home visit, whereas for the healthcare system it is considered necessary. We could conclude that, during the home visit, the case manager aspires to achieve excellence, and throughout his clinical relationship with Francesc, searches for a series of virtues, respecting certain fundamental principles. In this way, the case managers ensure that Jaume's care is more humanised. The case has been anonymised and confidentiality maintained.


Assuntos
Gerentes de Casos/ética , Serviços de Assistência Domiciliar/ética , Beneficência , Ética em Enfermagem , Humanos , Atenção Primária à Saúde/métodos , Autonomia Profissional , Recursos Humanos
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