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1.
Nat Methods ; 20(5): 761-769, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37024651

RESUMO

Neuronal computation is achieved through connections of individual neurons into a larger network. To expand the repertoire of endogenous cellular communication, we developed a synthetic, photon-assisted synaptic transmission (PhAST) system. PhAST is based on luciferases and channelrhodopsins that enable the transmission of a neuronal state across space, using photons as neurotransmitters. PhAST overcomes synaptic barriers and rescues the behavioral deficit of a glutamate mutant with conditional, calcium-triggered photon emission between two neurons of the Caenorhabditis elegans nociceptive avoidance circuit. To demonstrate versatility and flexibility, we generated de novo synaptic transmission between two unconnected cells in a sexually dimorphic neuronal circuit, suppressed endogenous nocifensive response through activation of an anion channelrhodopsin and switched attractive to aversive behavior in an olfactory circuit. Finally, we applied PhAST to dissect the calcium dynamics of the temporal pattern generator in a motor circuit for ovipositioning. In summary, we established photon-based synaptic transmission that facilitates the modification of animal behavior.


Assuntos
Cálcio , Fótons , Animais , Neurônios/fisiologia , Transmissão Sináptica , Caenorhabditis elegans/fisiologia
2.
Proc Natl Acad Sci U S A ; 120(6): e2209967120, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36719921

RESUMO

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by the lack of dystrophin. Heart failure, driven by cardiomyocyte death, fibrosis, and the development of dilated cardiomyopathy, is the leading cause of death in DMD patients. Current treatments decrease the mechanical load on the heart but do not address the root cause of dilated cardiomyopathy: cardiomyocyte death. Previously, we showed that telomere shortening is a hallmark of DMD cardiomyocytes. Here, we test whether prevention of telomere attrition is possible in cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPSC-CMs) and if preventing telomere shortening impacts cardiomyocyte function. We observe reduced cell size, nuclear size, and sarcomere density in DMD iPSC-CMs compared with healthy isogenic controls. We find that expression of just one telomere-binding protein, telomeric repeat-binding factor 2 (TRF2), a core component of the shelterin complex, prevents telomere attrition and rescues deficiencies in cell size as well as sarcomere density. We employ a bioengineered platform to micropattern cardiomyocytes for calcium imaging and perform Southern blots of telomere restriction fragments, the gold standard for telomere length assessments. Importantly, preservation of telomere lengths in DMD cardiomyocytes improves their viability. These data provide evidence that preventing telomere attrition ameliorates deficits in cell morphology, activation of the DNA damage response, and premature cell death, suggesting that TRF2 is a key player in DMD-associated cardiac failure.


Assuntos
Cardiomiopatia Dilatada , Insuficiência Cardíaca , Células-Tronco Pluripotentes Induzidas , Distrofia Muscular de Duchenne , Humanos , Cardiomiopatia Dilatada/genética , Sobrevivência Celular , Distrofina/genética , Insuficiência Cardíaca/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Distrofia Muscular de Duchenne/metabolismo , Miócitos Cardíacos/metabolismo , Telômero/genética , Telômero/metabolismo
3.
BMC Public Health ; 24(1): 1082, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38637782

RESUMO

BACKGROUND: Much evidence-based physical activity (PA) interventions have been tested and implemented in urban contexts. However, studies that adapt, implement, and evaluate the effectiveness of these interventions in micropolitan rural contexts are needed. The study aimed to evaluate the effectiveness of the Active Ottumwa intervention to promote PA in a micropolitan community. METHODS: Between 2013 - 2019, we implemented Active Ottumwa in a micropolitan setting, and subsequently implemented and evaluated its effectiveness using a Hybrid Type I design. In this paper, we describe the intervention's effectiveness in promoting PA. We collected PA data over 24 months from a cohort of community residents using accelerometers and PA data from two cross-sectional community surveys administered in 2013 and 2018, using the Global Physical Activity Questionnaire. RESULTS: From the cohort, we found significant change in PA over 24 months (P = 0.03) corresponding to a 45-min daily decrease in sedentary activity, a daily increase of 35-min in light PA and 9 min in moderate-to-vigorous PA. There was a statistically significant (P = 0.01) increasing trend at the population-level in the moderate-to-vigorous composition of 7 min between the two cross-sectional assessments (95% CI: 0.1%-1.34%). CONCLUSIONS: The study demonstrates that the adapted evidence-based PA interventions in a micropolitan context is effective.


Assuntos
Exercício Físico , População Rural , Humanos , Estudos Transversais
4.
J Minim Invasive Gynecol ; 31(2): 71-83.e17, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37931893

RESUMO

OBJECTIVE: No consensus currently exists regarding patient-reported outcome measure (PROM) instruments. This structured review was conducted to identify the PROMs used by randomized controlled trials (RCTs) that evaluated surgical treatment in patients with endometriosis. DATA SOURCES: Two parallel searches were conducted by a medical librarian using Ovid MEDLINE, Ovid Embase, and Cochrane Library for RCTs published from 2000 to July 2022. One search focused on studies reporting quality of life (QoL), and the second search focused on studies reporting pain and sexual, bowel, and bladder function. METHOD OF STUDY SELECTION: During the title and abstract screening and reference check, 600 results were identified on PROMs relating to QoL and 465 studies on PROMs relating to pain and sexual, bowel, and/or bladder function and an evaluation of 17 and 12 studies conducted, respectively. The inclusion criteria involved selecting RCTs that focused on surgical intervention and assessing QoL, pain, and sexual, bowel, and/or bladder function using PROMs. TABULATION, INTEGRATION, AND RESULTS: Covidence software was used to organize and identify duplicate articles through screening. We developed a data extraction form to collect key information about each included study, as well as the pertinent PROMs used in the study. Assessment of the risk of bias of each study was also performed. A total of 19 studies were identified involving 2089 participants and a total of 16 PROMs used across the studies; 9 of 19 studies (47%) were rated as having a low risk of bias. There were no high-risk studies identified in this review. CONCLUSION: This study identified a large number of RCTs in surgical treatment of endometriosis that used various PROMs to assess QoL, pain, and bladder, bowel, and sexual function. The PROMs used by high-quality RCTs for QoL include Endometriosis Health Profile-30, Endometriosis Health Profile-5, Short-Form 36, Short-Form 12, and EQ-5D; for bowel-related symptoms Knowles-Eccersley-Scott-Symptom Questionnaire, Gastrointestinal Quality of Life Index, and Cleveland Clinic Fecal Incontinence Severity Scoring System/Wexner; for bladder-related function Bristol Female Lower Urinary Tract Symptoms, International Prostate Symptom Score, Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire, and Urinary Symptom Profile; and finally for sexual function Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire and Sexual Activity Questionnaire. Unlike other domains, only one tool (visual analog scale) was the dominant PROM used for the assessment of pain. In addition, the use of more than one PROM in each study to assess different aspects of patient's health and pain symptoms did not become prevalent until after 2015.


Assuntos
Endometriose , Prolapso de Órgão Pélvico , Incontinência Urinária , Masculino , Feminino , Humanos , Endometriose/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Dor , Qualidade de Vida , Medidas de Resultados Relatados pelo Paciente
5.
Genet Mol Biol ; 47(1): e20220263, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38593425

RESUMO

The infection process of the hemibiotrophic fungus Colletotrichum lindemuthianum has been independently studied at the microscopic and genomic levels. However, the relationship between the morphological changes and the pathogenicity mechanisms of the fungus at the early stages of the infection remains uncharacterized. Therefore, this study attempts to bridge this gap by integrating microscopic and transcriptional approaches to understand the infection process of C. lindemuthianum. Fungal structures were followed by fluorescence microscopy for 120 hours. Simultaneously, the transcriptomic profile was made using RNAseq. Morphological characterization shows that appressoria, infective vesicles, and secondary hypha formation occur before 72 hours. Additionally, we assembled 38,206 transcripts with lengths between 201 and 3,548 bp. The secretome annotation revealed the expression of 1,204 CAZymes, of which 17 exhibited secretion domains and were identified as chitinases and ß-1,3-glucanases, 27 were effector candidates, and 30 were transport proteins mostly associated with ABC-type. Finally, we confirmed the presence and expression of CAC1 role during the appressoria formation of Clr7. This result represents the first report of adenylate cyclase expression evaluated under three different approaches. In conclusion, C. lindemuthianum colonizes the host through different infection structures complemented with the expression of multiple enzymes, where CAC1 favors disease development.

6.
BMC Womens Health ; 23(1): 503, 2023 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-37735400

RESUMO

BACKGROUND: Induced abortion in Costa Rica is illegal in all cases except to save the life of the pregnant person. Despite severe restrictions to legal abortion, individuals in Costa Rica still induce abortions outside of the formal healthcare system. These individuals and those with spontaneous abortions, also known as miscarriages, occasionally need medical care for complications. In Costa Rica, an estimated 41% of unintended pregnancies end in abortion, yet there is very little published literature exploring the perspectives of healthcare providers on abortion in Costa Rica. METHODS: We interviewed ten obstetrician-gynecologist clinicians and five obstetrician-gynecologist medical residents in San José, Costa Rica about their beliefs and practices related to extra-legal abortion and post-abortion care (PAC) using a Spanish language in-depth semi-structured interview guide. After transcription and translation into English, analysis team pairs used a combination of deductive and inductive coding to identify themes and sub-themes within the data. RESULTS: Obstetrician-gynecologist clinicians and medical residents were aware of the presence of extra-legal abortion, and particularly, medication abortion, in their communities, but less familiar with dosing for induction. They expressed the desire to provide non-judgmental care and support their patients through extra-legal abortion and PAC journeys. Study participants were most familiar with providing care to individuals with spontaneous abortions. When discussing PAC, they often spoke about a policy of reporting individuals who seek PAC following an extra-legal abortion, without commenting on whether or not they followed the guidance. CONCLUSIONS: This study contributes to a gap in research about the knowledge, attitudes, and practices of Costa Rican obstetrician-gynecologist clinicians and medical residents around extra-legal abortion and PAC. The results reveal an opportunity to train these healthcare providers as harm reduction experts, who are able to accurately counsel individuals who are seeking abortion services outside of the healthcare system, and to provide training to improve care for individuals needing PAC.


Assuntos
Aborto Espontâneo , Internato e Residência , Feminino , Gravidez , Humanos , Aborto Legal , Costa Rica , Ginecologista , Conhecimentos, Atitudes e Prática em Saúde , Obstetra , Pessoal de Saúde
7.
Int J Mol Sci ; 24(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37047093

RESUMO

ADAM10 is the main α-secretase acting in the non-amyloidogenic processing of APP. We hypothesized that certain rare ADAM10 variants could increase the risk for AD by conferring the age-related downregulation of α-secretase. The ADAM10 gene was sequenced in 103 AD cases (82% familial) and 96 cognitively preserved nonagenarians. We examined rare variants (MAF < 0.01) and determined their potential association in the AD group with lower CSF protein levels, as analyzed by means of ELISA, and Western blot (species of 50 kDa, 55 kDa, and 80 kDa). Rare variants were found in 15.5% of AD cases (23% early-onset, 8% late-onset) and in 12.5% of nonagenarians, and some were group-specific. All were intronic variants except Q170H, found in three AD cases and one nonagenarian. The 3'UTR rs74016945 (MAF = 0.01) was found in 6% of the nonagenarians (OR 0.146, p = 0.057). Altogether, ADAM10 total levels or specific species were not significantly different when comparing AD with controls or carriers of rare variants versus non-carriers (except a Q170H carrier exhibiting low levels of all species), and did not differ according to the age at onset or APOE genotype. We conclude that ADAM10 exonic variants are uncommon in AD cases, and the presence of rare intronic variants (more frequent in early-onset cases) is not associated with decreased protein levels in CSF.


Assuntos
Doença de Alzheimer , Idoso de 80 Anos ou mais , Humanos , Proteínas ADAM/metabolismo , Proteína ADAM10/genética , Proteína ADAM10/metabolismo , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas do Líquido Cefalorraquidiano/análise , Proteínas do Líquido Cefalorraquidiano/metabolismo
8.
Sante Publique ; 35(4): 417-422, 2023 12 11.
Artigo em Francês | MEDLINE | ID: mdl-38078636

RESUMO

In 2020, food shortages occurred at the beginning of the confinement period that was supposed to curb the COVID-19 pandemic. In French Guiana, where a major part of the population lives under the poverty line, health workers voiced major concerns. Alongside massive food aid distributions, a first transversal study was carried out in August 2020 targeting poor neighborhoods in Cayenne. The results were particularly worrying. More than 80% of households had been suffering from hunger during that month, with a median decrease of 46% in revenue. Two other investigations followed in February and then in August of 2021. With the relaxing of the health measures, the situation improved in the Cayenne region, but two out of three were still affected, showing signs of quantitative deficiencies and insufficient food diversity. The situation seemed particularly grave for children. In light of this situation, we propose to create an observatory of food insecurity in Guiana, while maintaining this topic as a health priority. In addition, the fight against food insecurity cannot be limited to multi-sectorial material and strategic aide. It must be thought about in a more global manner, including health and social questions, territorial management policies, access to land and water, access to rights and social inclusion. Targeted actions helping the most exposed and vulnerable people is also an important stake, independent of the administrative situation and residency rights of the concerned people.


En 2020, des pénuries alimentaires sont survenues dès l'entrée en vigueur du confinement destiné à contrôler la pandémie de COVID-19. En Guyane Française, où une forte proportion de la population vivait déjà sous le seuil de pauvreté, des alertes préoccupantes ont émané d'acteurs de santé. En parallèle du déploiement d'une aide alimentaire massive, une première enquête transversale a été menée en août 2020, ciblant les quartiers précaires des environs de Cayenne. Les résultats étaient particulièrement inquiétants : plus de 80 % des ménages avaient souffert de la faim dans le mois, avec une baisse médiane de revenus de 46 %. Deux autres enquêtes ont suivi, en février, puis en août 2021. Avec l'allègement des mesures sanitaires, la situation s'était sensiblement améliorée dans la région de Cayenne, mais deux ménages sur trois restaient impactés, avec des carences quantitatives et une diversité alimentaire insuffisante. La situation semblait particulièrement critique parmi les enfants. Au vu de cette situation, nous proposons de créer un observatoire de l'insécurité alimentaire en Guyane, tout en maintenant ce sujet en tête des priorités sanitaires. En outre, la lutte contre l'insécurité alimentaire ne peut se limiter à l'aide matérielle : la stratégie, multisectorielle, doit être pensée en globalité, intégrant les problématiques sanitaires et sociales, les enjeux de l'aménagement du territoire, de l'accès à la terre et à l'eau, de l'accès aux droits et à l'insertion sociale. Un ciblage juste des actions vers les publics les plus exposés et vulnérables est également un enjeu important, indépendamment de la situation administrative et du droit au séjour des personnes concernées.


Assuntos
COVID-19 , Abastecimento de Alimentos , Fome , Criança , Humanos , COVID-19/epidemiologia , Abastecimento de Alimentos/estatística & dados numéricos , Guiana Francesa/epidemiologia , Pandemias/estatística & dados numéricos
9.
Curr Psychol ; : 1-16, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37359653

RESUMO

The current systematic review sought to identify quantitative empirical studies that focused on the transdiagnostic factors of intolerance of uncertainty, emotional dysregulation and rumination, and their relation with depression and post-traumatic stress disorder (PTSD). The overall research aim was to examine the relationship between these transdiagnostic factors and their relation with depression and PTSD symptoms. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Out of the 768 articles initially identified, 55 met the inclusion criteria for the current review. The results determined that intolerance of uncertainty is indirectly related to depression and PTSD symptoms, mainly through other factors including emotion dysregulation and rumination. Additionally, emotional dysregulation is a significant predictor of both depression and PTSD symptoms. Rumination is a robust factor related to depression and PTSD symptoms, this relationship was significant in cross-sectional and longitudinal studies. This review provides evidence on the transdiagnostic factors of intolerance of uncertainty, emotional dysregulation and rumination in the relationship with depression and PTSD symptoms.

10.
J Biol Chem ; 296: 100152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33288674

RESUMO

Phospholipase D3 (PLD3) and phospholipase D4 (PLD4), the most recently described lysosomal nucleases, are associated with Alzheimer's disease, spinocerebellar ataxia, and systemic lupus erythematosus. They exhibit 5' exonuclease activity on single-stranded DNA, hydrolyzing it at the acidic pH associated with the lysosome. However, their full cellular function is inadequately understood. To examine these enzymes, we developed a robust and automatable cell-based assay based on fluorophore- and fluorescence-quencher-coupled oligonucleotides for the quantitative determination of acidic 5' exonuclease activity. We validated the assay under knockout and PLD-overexpression conditions and then applied it to characterize PLD3 and PLD4 biochemically. Our experiments revealed PLD3 as the principal acid 5' exonuclease in HeLa cells, where it showed a markedly higher specific activity compared with PLD4. We further used our newly developed assay to determine the substrate specificity and inhibitory profile of PLD3 and found that proteolytic processing of PLD3 is dispensable for its hydrolytic activity. We followed the expression, proteolytic processing, and intracellular distribution of genetic PLD3 variants previously associated with Alzheimer's disease and investigated each variant's effect on the 5' nuclease activity of PLD3, finding that some variants lead to reduced activity, but others not. The development of a PLD3/4-specific biochemical assay will be instrumental in understanding better both nucleases and their incompletely understood roles in vitro and in vivo.


Assuntos
Bioensaio/métodos , Exonucleases/metabolismo , Fosfolipase D/metabolismo , Proteólise , Células HeLa , Humanos , Mutagênese Sítio-Dirigida , Mutação , Fosfolipase D/genética
11.
Scand J Immunol ; 95(4): e13143, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35067952

RESUMO

INTRODUCTION: For many patients with primary immune deficiency (PID), stem-cell transplantation (SCT) may be life-saving. OBJECTIVE: To review our experience of 11 years transplanting children with PID in Mexico. METHODS: Chart review of patients who underwent SCT from 2008 to 2018, to describe their diagnoses, time to transplant, conditioning regime, survival rate and outcomes. All patients received post-transplant cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis. RESULTS: 19 patients with combined, phagocytic or syndromic PID from 5 states. Twelve of them were male (58%) and 14 survive (79%). Mean age at HSCT was 41.9 months; mean time from diagnosis was 31.2 months. Seven grafts were umbilical cord and 12 haploidentical. The conditioning regime was myeloablative, with five primary graft failures. Two patients had partial and 10 full chimerism. Five patients died within 2 months after transplant. Immune reconstitution was complete in 11 of 19 patients. We found a prevalence of 21% GVHD. DISCUSSION: We describe 19 patients from Mexico with 8 PID diagnoses who underwent allogenic HSCT over a period of 11 years. Survival rate and other outcomes compare well with industrialized countries. We recommend the use of post-transplant cyclophosphamide to prevent GVHD in scenarios of resource scarcity and a lack of HLA-identical donors.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doenças da Imunodeficiência Primária , Criança , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , México , Doenças da Imunodeficiência Primária/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante
12.
BMC Psychiatry ; 22(1): 392, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35689188

RESUMO

OBJECTIVES: To assess the impact of a short psychoeducation intervention for antisocial personality disorder on offending after randomization to treatment. DESIGN: Multicentre, superiority, non-blinded randomized controlled trial. Random assignment was conducted in blocks of varying sizes at a central randomization centre. Participants were followed using national register data until 365 days after randomization, migration, or death, whichever occurred first. SETTING: Thirteen outpatient uptake areas in Denmark. PARTICIPANTS: Patients with antisocial personality disorder in treatment for substance use disorders were randomized to treatment as usual (TAU, n = 80) or Impulsive Lifestyle Counselling (ILC, n = 96). A total of 165 patients could be linked to criminal records (TAU, n = 74; ILC, n = 91). INTERVENTION: ILC is a brief psychoeducational program targeting antisocial behavior. The trial was conducted between January 2012 and June 2014. OUTCOMES: Number of criminal offences leading to convictions based on national registers. RESULTS: The mean number of offences was 2.76 in the TAU group (95% Poisson confidence interval [CI] = 2.39, 3.16) and 1.87 in the ILC group (95% CI = 0.97, 1.43). Negative binomial regression was used to assess total number of convictions, as well as convictions for violent, property, driving under the influence, and drug-related crimes. In both adjusted and unadjusted analyses, random assignment to ILC was associated with a lower number of total offences (incidence rate risk ratio [IRR] = 0.43, p = .013; adjusted IRR = 0.45, p < .001) and convictions related to violence (IRR = 0.19, p = .001 adjusted IRR = 0.19, p = .007) and property offences (unadjusted IRR = 0.30, p = 0.003, adjusted IRR = 0.42, p = 0.010). Differences between conditions were not significant for driving under the influence (unadjusted IRR = 0.49, p = .370; adjusted IRR = 0.53, p = .417) or drug offences (unadjusted IRR = 1.06, p = .907; adjusted IRR = 0.55, p = .223). CONCLUSIONS: The ILC program shows promise in reducing offending behavior in people with comorbid substance use and antisocial personality disorder. TRIAL REGISTRATION: ISRCTN registry, ISRCTN67266318 , 15/10/2012.


Assuntos
Transtorno da Personalidade Antissocial , Transtornos Relacionados ao Uso de Substâncias , Transtorno da Personalidade Antissocial/complicações , Transtorno da Personalidade Antissocial/terapia , Aconselhamento , Humanos , Comportamento Impulsivo , Estilo de Vida , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/terapia
13.
Sensors (Basel) ; 22(10)2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35632193

RESUMO

Stress has become a common condition and is one of the chief causes of university course disenrollment. Most of the studies and tests on academic stress have been conducted in research labs or controlled environments, but these tests can not be extended to a real academic environment due to their complexity. Academic stress presents different associated symptoms, anxiety being one of the most common. This study focuses on anxiety derived from academic activities. This study aims to validate the following hypothesis: by using a non-contact method based on the use of remote photoplethysmography (rPPG), it is possible to identify academic stress levels with an accuracy greater than or equal to that of previous works which used contact methods. rPPG signals from 56 first-year engineering undergraduate students were recorded during an experimental task. The results show that the rPPG signals combined with students' demographic data and psychological scales (the State-Trait Anxiety Inventory) improve the accuracy of different classification methods. Moreover, the results demonstrate that the proposed method provides 96% accuracy by using K-nearest neighbors, J48, and random forest classifiers. The performance metrics show better or equal accuracy compared to other contact methods. In general, this study demonstrates that it is possible to implement a low-cost method for identifying academic stress levels in educational environments.


Assuntos
Fotopletismografia , Estudantes , Ansiedade , Análise por Conglomerados , Humanos , Fotopletismografia/métodos , Estudantes/psicologia
14.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36362034

RESUMO

A computational protocol aimed to design new antioxidants with versatile behavior is presented. It is called Computer-Assisted Design of Multifunctional Antioxidants and is based on chemical properties (CADMA-Chem). The desired multi-functionality consists of in different methods of antioxidant protection combined with neuroprotection, although the protocol can also be used to pursue other health benefits. The dM38 melatonin derivative is used as a study case to illustrate the protocol in detail. This was found to be a highly promising candidate for the treatment of neurodegeneration, in particular Parkinson's and Alzheimer's diseases. This also has the desired properties of an oral-drug, which is significantly better than Trolox for scavenging free radicals, and has chelates redox metals, prevents the ●OH production, via Fenton-like reactions, repairs oxidative damage in biomolecules (lipids, proteins, and DNA), and acts as a polygenic neuroprotector by inhibiting catechol-O-methyl transferase (COMT), acetylcholinesterase (AChE) and monoamine oxidase B (MAOB). To the best of our best knowledge, CADMA-Chem is currently the only protocol that simultaneously involves the analyses of drug-like behavior, toxicity, manufacturability, versatile antioxidant protection, and receptor-ligand binding affinities. It is expected to provide a starting point that helps to accelerate the discovery of oral drugs with the potential to prevent, or slow down, multifactorial human health disorders.


Assuntos
Antioxidantes , Química Computacional , Humanos , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Antioxidantes/química , Catecol O-Metiltransferase/metabolismo , Inibidores da Colinesterase/farmacologia , Estresse Oxidativo , Química Computacional/métodos
15.
J Neurooncol ; 155(1): 53-61, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34505229

RESUMO

BACKGROUND: Many studies have demonstrated in the last years that once medulloblastoma has recurred, the probability of regaining tumor control is poor despite salvage therapy. Although re-irradiation has an emerging role in other relapsed brain tumors, there is a lack of strong data on re-irradiation for medulloblastoma. METHODS: This is a retrospective cohort study of patients aged 18 years or under, treated at least by a second course of external beam for recurrence medulloblastoma at Garrahan Hospital between 2009 and 2020. Twenty-four patients met eligibility criteria for inclusion. All patients received upfront radiotherapy as part of the curative-intent first radiotherapy, either craniospinal irradiation (CSI) followed by posterior fossa boost in 20 patients or focal posterior fossa radiation in 4 infants. The second course of radiation consisted of CSI in 15 and focal in 9. The 3-year post first failure OS (50% vs. 0%; p = 0.0010) was significantly better for children who received re-CSI compared to children who received focal re-irradiation. Similarly, the 3-year post-re-RT PFS (31% vs. 0%; p = 0.0005) and OS (25% vs. 0%; p = 0.0003) was significantly improved for patients who received re-CSI compared to patients who received focal re-irradiation. No symptomatic intratumoral haemorrhagic events or symptomatic radionecrosis were observed. Survivors fell within mild to moderate intellectual disability range, with a median IQ at last assessment of 58 (range 43-69). CONCLUSIONS: Re-irradiation with CSI is a safe and effective treatment for children with relapsed medulloblastoma; improves disease control and survival compared with focal re-irradiation. However this approach carries a high neurocognitive cost.


Assuntos
Neoplasias Cerebelares , Radiação Cranioespinal , Meduloblastoma , Reirradiação , Neoplasias Encefálicas , Neoplasias Cerebelares/radioterapia , Criança , Seguimentos , Humanos , Lactente , Meduloblastoma/radioterapia , Recidiva Local de Neoplasia/radioterapia , Dosagem Radioterapêutica , Estudos Retrospectivos
16.
Sensors (Basel) ; 21(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34502617

RESUMO

Today, computer vision algorithms are very important for different fields and applications, such as closed-circuit television security, health status monitoring, and recognizing a specific person or object and robotics. Regarding this topic, the present paper deals with a recent review of the literature on computer vision algorithms (recognition and tracking of faces, bodies, and objects) oriented towards socially assistive robot applications. The performance, frames per second (FPS) processing speed, and hardware implemented to run the algorithms are highlighted by comparing the available solutions. Moreover, this paper provides general information for researchers interested in knowing which vision algorithms are available, enabling them to select the one that is most suitable to include in their robotic system applications.


Assuntos
Robótica , Algoritmos , Humanos , Visão Ocular
17.
Nord J Psychiatry ; 75(8): 633-640, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34154520

RESUMO

PURPOSE: The aim of the study was to investigate the effectiveness of the Partners for Change Outcome Management System (PCOMS) in improving the retention rate and reducing drug use in a clinic for drug use treatment. MATERIAL AND METHODS: One-hundred outpatients with cannabis use as the primary presenting problem were randomized to either the PCOMS (n = 51) or treatment as usual (TAU; n = 49). Eight weekly psychotherapy sessions were planned in both conditions. The primary outcome was treatment retention measured as the rate of attendance to planned treatment sessions and dropout. The secondary outcomes were current cannabis and other drug use assessed with the European Addiction Severity Index (EuropASI). Several explorative outcomes were analyzed. Blind assessments of drug use were conducted three and six months after baseline. Outcome analyses were conducted on both the treated sample with at least one psychotherapy session (n = 82) and the intention-to-treat sample (n = 100). RESULTS: The results showed no incremental effect of the PCOMS compared to the TAU condition, for neither treatment retention, drug use, or therapeutic alliance. CONCLUSION: The main findings align with previous studies that have found no effect of the PCOMS when employing outcome measures independent from the PCOMS intervention. The results are interpreted with caution due to implementation difficulties, which at the same time suggest challenges when employing the PCOMS in large outpatient clinics for drug use treatment.


Assuntos
Cannabis , Transtornos Relacionados ao Uso de Substâncias , Humanos , Pacientes Ambulatoriais , Psicoterapia , Resultado do Tratamento
18.
Gac Med Mex ; 157(6): 566-573, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35108247

RESUMO

INTRODUCTION: The fear of COVID-19 scale (FCV-19S) is used to screen for symptoms of anxiety and depression related to COVID-19 in the general population; it consists of seven questions with Likert-type answers (1-5). Our objective was to validate FCV-19S Spanish version in the Mexican general population. MATERIAL AND METHODS: Analytical, cross-sectional design. Three-hundred and six subjects from the general population were included during 2020 after having signed informed consent. Barlett and Kaiser-Meyer-Olkin (KMO) sphericity tests were applied. Reliability was calculated with Cronbach's alpha, and external validity, using the Hospital Anxiety and Depression Scale and Pearson's correlation coefficient for retest. RESULTS: The general population sample included 306 participants; 64.4 % were women (n = 197), mean age was 32 years (18-68). We obtained a KMO = 0.848, internal consistency with Cronbach's alpha = 0.870 (95% CI: 0.848-0.891), a rho coefficient of 0.508 (p < 0.001) and external validity of 0.151 (p = 0.008). Confirmatory analysis showed: χ2 = 22.802 (df = 13) with CMIN-DF = 1.900 (p ≤ 0.001), GFI = 0.972, CFI = 0.901, RMSEA = 0.062 (90% CI: 0.019-0.100) and TLI = 0.827. CONCLUSIONS: According to our findings, the scale shows adequate psychometric properties: reliability, internal consistency, correlation with subsequent measurements and convergence validity, for initial screening of the Mexican general population.


INTRODUCCIÓN: La Escala de temor a la COVID-19 (FCV-19S) se usa en el tamizaje de síntomas de ansiedad y depresión relacionados con la COVID-19 en población general; consta de siete preguntas con respuestas tipo Likert (1-5). Nuestro objetivo fue validar la versión del FCV-19S en la población general mexicana. MATERIAL Y MÉTODOS: Diseño transversal analítico. Se incluyeron 306 sujetos de la población general durante 2020 con firma previa de consentimiento informado. Se aplicaron pruebas de esfericidad de Barlett y Kaiser-Meyer-Olkin (KMO). Se calculó la confiabilidad con el alfa de Cronbach, la validez externa utilizando la Escala hospitalaria de ansiedad y depresión y el coeficiente de correlación de Pearson para retest. RESULTADOS: La muestra de la población general incluyó a 306 participantes, el 64.4% mujeres (n = 197), edad media 32 años (18-68). Obtuvimos un KMO = 0.848, consistencia interna con alfa de Cronbach = 0.870 (IC 95%: 0.848-0.891), coeficiente rho de 0.508 (p < 0.001) y validez externa de 0.151 (p = 0.008). El análisis confirmatorio mostró: χ2 = 22.802 (df = 13) con CMIN-DF= 1.900, p ≤ 0.001, GFI = 0.972, CFI = 0.901, RMSEA = 0.062 (IC 90%: 0.019-0.100) y TLI = 0.827. CONCLUSIONES: La FCV-19S demuestra propiedades psicométricas adecuadas (confiabilidad, consistencia interna, correlación con mediciones subsecuentes y validez de convergencia) para su aplicación en la población general mexicana.


Assuntos
COVID-19 , Adulto , Estudos Transversais , Medo , Feminino , Humanos , Reprodutibilidade dos Testes , SARS-CoV-2 , Inquéritos e Questionários
19.
Mol Microbiol ; 111(3): 825-843, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30582883

RESUMO

Surface properties, such as adhesion and hydrophobicity, constrain dispersal of bacterial spores in the environment. In Bacillus subtilis, these properties are influenced by the outermost layer of the spore, the crust. Previous work has shown that two clusters, cotVWXYZ and cgeAB, encode the protein components of the crust. Here, we characterize the respective roles of these genes in surface properties using Bacterial Adherence to Hydrocarbons assays, negative staining of polysaccharides by India ink and Transmission Electron Microscopy. We showed that inactivation of crust genes caused increases in spore relative hydrophobicity, disrupted the spore polysaccharide layer, and impaired crust structure and attachment to the rest of the coat. We also found that cotO, previously identified for its role in outer coat formation, is necessary for proper encasement of the spore by the crust. In parallel, we conducted fluorescence microscopy experiments to determine the full network of genetic dependencies for subcellular localization of crust proteins. We determined that CotZ is required for the localization of most crust proteins, while CgeA is at the bottom of the genetic interaction hierarchy.


Assuntos
Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Membrana/metabolismo , Esporos/metabolismo , Propriedades de Superfície , Bacillus subtilis/fisiologia , Bacillus subtilis/ultraestrutura , Aderência Bacteriana , Microscopia Eletrônica de Transmissão , Esporos/fisiologia , Esporos/ultraestrutura
20.
Memory ; 28(4): 516-527, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32148184

RESUMO

Intrusive involuntary memories and images are a cardinal phenomenon in a range of psychological disorders, but not systematically examined in social anxiety. We examined potential biases upon generating involuntary versus voluntary memories and future projections in individuals with high and low levels of social anxiety. Participants recorded involuntary and voluntary autobiographical events, and their associated emotional response in a structured mental time travel diary. High social anxiety was associated with more intense anxiety and embarrassment and greater use of a range of emotion regulation strategies upon generating all types of autobiographical events. Involuntary (versus voluntary) memories and future events were associated with a heightened emotional response independent of social anxiety, and memories were associated with more embarrassment than imagined future events. The effects of high versus low social anxiety and involuntary versus voluntary generation process were independent from each other. The findings have implications for affective and cognitive models of involuntary memories and future projections in emotional disorders.


Assuntos
Ansiedade/psicologia , Previsões , Memória Episódica , Rememoração Mental/fisiologia , Adulto , Sinais (Psicologia) , Diários como Assunto , Regulação Emocional , Feminino , Humanos , Masculino , Tempo , Adulto Jovem
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