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OBJECTIVE: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) distinguish multiple sclerosis (MS) from MOG-associated disease in most cases. However, studies analyzing MOG-Ab at the time of a first demyelinating event suggestive of MS in adults are lacking. We aimed to (1) evaluate the prevalence of MOG-Ab in a first demyelinating event suggestive of MS and (2) compare clinical and paraclinical features between seropositive (MOG-Ab+) and seronegative (MOG-Ab-) patients. METHODS: Six hundred thirty adult patients with available serum samples obtained within 6 months from the first event were included. MOG-Ab were analyzed using a live cell-based assay. Statistical analyses included parametric and nonparametric tests, logistic regression, and survival models. RESULTS: MOG-Ab were positive in 17 of 630 (2.7%). Fourteen out of 17 (82.4%) MOG-Ab+ patients presented with optic neuritis (ON) compared to 227of 613 (37.0%) MOG-Ab- patients (p = 0.009). Cerebrospinal fluid-restricted oligoclonal bands (CSF-OBs) were found in 2 of 16 (12.5%) MOG-Ab+ versus 371 of 601 (61.7%) MOG-Ab- subjects (p < 0.001). Baseline brain magnetic resonance imaging (MRI) was normal in 9 of 17 (52.9%) MOG-Ab+ versus 153 of 585 (26.2%) MOG-Ab- patients (p = 0.029). Absence of CSF-OBs and ON at onset were independently associated with MOG-Ab positivity (odds ratio [OR] = 9.03, 95% confidence interval [CI] = 2.04-53.6, p = 0.009; and OR = 4.17, 95% CI = 1.15-19.8, p = 0.042, respectively). Of MOG-Ab+ patients, 22.9% (95% CI = 0.0-42.7) compared to 67.6% (95% CI = 63.3-71.3) of MOG-Ab- patients fulfilled McDonald 2017 criteria at 5 years (log-rank p = 0.003). INTERPRETATION: MOG-Ab are infrequent in adults with a first demyelinating event suggestive of MS. However, based on our results, we suggest to determine these antibodies in those patients with ON and absence of CSF-OBs, as long as the brain MRI is not suggestive of MS. ANN NEUROL 2023.
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BACKGROUND: Respiratory syncytial virus (RSV) is a highly infectious disease that poses a significant clinical and medical burden, as well as social disruption and economic costs, recognized by the World Health Organization as a public health issue. After several failed attempts to find preventive candidates (compounds, products, including vaccines), new alternatives might be available, one being nirsevimab, the first and only option approved for RSV prevention in neonates and infants during their first RSV season. The objective of this study was to develop a novel multi-criteria decision analysis (MCDA) framework for RSV antibody-based preventive alternatives and to use it to assess the value of nirsevimab vs. placebo as a systematic immunization approach to prevent RSV in neonates and infants during their first RSV season in Spain. METHODS: Based on a pre-established model called Vaccinex, an ad-hoc MCDA framework was created to reflect relevant attributes for the assessment of current and future antibody-based preventive measures for RSV. The estimated value of nirsevimab was obtained by means of an additive linear model combining weights and scores assigned by a multidisciplinary committee of 9 experts. A retest and three sensitivity analyses were conducted. RESULTS: Nirsevimab was evaluated through a novel framework with 26 criteria by the committee as a measure that adds value (positive final estimated value: 0.56 ± 0.11) to the current RSV scenario in Spain, by providing a high efficacy for prevention of neonates and infants. In addition, its implementation might generate cost savings in hospitalizations and to the healthcare system and increase the level of public health awareness among the general population, while reducing health inequities. CONCLUSIONS: Under a methodology with increasing use in the health field, nirsevimab has been evaluated as a measure which adds value for RSV prevention in neonates and infants during their first RSV season in Spain.
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Anticorpos Monoclonais Humanizados , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Recém-Nascido , Lactente , Humanos , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Antivirais , Espanha , Técnicas de Apoio para a DecisãoRESUMO
Milk yield and composition phenotypes are systematically recorded across several lactations in goats, but the majority of genome-wide association studies (GWAS) performed so far have rather ignored the longitudinal nature of such data. Here, we have used two different GWAS approaches to analyse data from three lactations recorded in Murciano-Granadina goats. In Analysis 1, independent GWAS have been carried out for each trait and lactation, while a single longitudinal GWAS, jointly considering all data, has been performed in Analysis 2. In both analyses, genome-wide significant QTL for lactose percentage on chromosome 2 (129.77-131.01 Mb) and for milk protein percentage on the chromosome 6 (74.8-94.6 Mb) casein gene cluster region were detected. In Analysis 1, several QTL were not replicated in all three lactations, possibly due to the existence of lactation-specific genetic determinants. In Analysis 2, we identified several genome-wide significant QTL related to milk yield and protein content that were not uncovered in Analysis 1. The increased number of QTL identified in Analysis 2 suggests that the longitudinal GWAS is particularly well suited for the genetic analysis of dairy traits. Moreover, our data confirm that variability within or close to the casein complex is the main genetic determinant of milk protein percentage in Murciano-Granadina goats.
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Caseínas , Estudo de Associação Genômica Ampla , Feminino , Animais , Estudo de Associação Genômica Ampla/veterinária , Caseínas/genética , Cabras/genética , Lactação/genética , Fenótipo , Proteínas do Leite/genéticaRESUMO
Intergenic transcription is a common feature of eukaryotic genomes and performs important and diverse cellular functions. Here, we investigate the iab-8 ncRNA from the Drosophila Bithorax Complex and show that this RNA is able to repress the transcription of genes located at its 3' end by a sequence-independent, transcriptional interference mechanism. Although this RNA is expressed in the early epidermis and CNS, we find that its repressive activity is limited to the CNS, where, in wild-type embryos, it acts on the Hox gene, abd-A, located immediately downstream of it. The CNS specificity is achieved through a 3' extension of the transcript, mediated by the neuronal-specific, RNA-binding protein, ELAV. Loss of ELAV activity eliminates the 3' extension and results in the ectopic activation of abd-A. Thus, a tissue-specific change in the length of a ncRNA is used to generate a precise pattern of gene expression in a higher eukaryote.
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Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Proteínas ELAV/genética , Genes Homeobox , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Transcrição Gênica , Animais , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Drosophila melanogaster/embriologia , Genes Reporter , MicroRNAs/genética , RNA Longo não Codificante/genética , Deleção de SequênciaRESUMO
Nonsense variants can inactivate gene function by causing the synthesis of truncated proteins or by inducing nonsense mediated decay of messenger RNAs. The occurrence of such variants in the genomes of livestock species is modulated by multiple demographic and selective factors. Even though nonsense variants can have causal effects on embryo lethality, abortions, and disease, their genomic distribution and segregation in domestic goats have not been characterized in depth yet. In this work, we have sequenced the genomes of 15 Murciano-Granadina bucks with an average coverage of 32.92 × ± 1.45 × . Bioinformatic analysis revealed 947 nonsense variants consistently detected with SnpEff and Ensembl-VEP. These variants were especially abundant in the 3'end of the protein-coding regions. Genes related to olfactory perception, ATPase activity coupled to transmembrane movement of substances, defense to virus, hormonal response, and sensory perception of taste were particularly enriched in nonsense variants. Seventeen nonsense variants expected to have harmful effects on fitness were genotyped in parent-offspring trios. We observed that several nonsense variants predicted to be lethal based on mouse knockout data did not have such effect, a finding that could be explained by the existence of multiple mechanisms counteracting lethality. These findings demonstrate that predicting the effects of putative nonsense variants on fitness is extremely challenging. As a matter of fact, such a goal could only be achieved by generating a high quality telomere-to-telomere goat reference genome combined with carefully curated annotation and functional testing of promising candidate variants.
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PURPOSE: To evaluate the predictive value of serum AMH for clinical pregnancy in non-infertile population undergoing intrauterine insemination with donor sperm (ds-IUI). METHODS: This multicenter prospective study (ClinicalTrials.gov ID: NCT06263192) recruited all non-infertile women undergoing ds-IUI from June 2020 to December 2022 in three different fertility clinics in Spain and Chile. Indications for ds-IUI included severe oligoasthenoteratozoospermia, female partner, or single status. Clinical pregnancy rates were compared between women with AMH ≥ 1.1 and < 1.1 ng/mL. The main outcome measure was the cumulative clinical pregnancy rate after up to 4 ds-IUI cycles. RESULTS: A total of 458 ds-IUI cycles were performed among 245 patients, of whom 108 (44.08%) achieved clinical pregnancy within 4 cycles, 60.2% of these occurring in the first attempt and 84.2% after two attempts. We found no significant differences in AMH levels or other parameters (such as age, BMI, FSH, AFC) between women who became pregnant and those who did not. Cumulative pregnancy rates and logistic regression analysis revealed that AMH ≥ 1.1 ng/mL was not predictive of ds-IUI success. While a high positive correlation was observed between AFC and AMH (r = 0.67, p < 0.001), ROC curve analyses indicated that neither of these ovarian reserve markers accurately forecasts cumulative ds-IUI outcomes in non-infertile women. CONCLUSIONS: The findings of this multicenter study suggest that AMH is not a reliable predictor of pregnancy in non-infertile women undergoing ds-IUI. Even women with low AMH levels can achieve successful pregnancy outcomes, supporting the notion that diminished ovarian reserve should not restrict access to ds-IUI treatments in eligible non-infertile women.
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There are few studies exploring intake diagnostic characteristics as predictors of change in integrative naturalistic settings. The aim of this study is to explore baseline variables at the intake process and establish the predictive value of the individual trajectories of the patients. We recruited 259 patients undergoing an integrative psychotherapy network of psychotherapists from Buenos Aires, Argentina. Every therapist completed the intake form of each patient involved in the routine outcome monitoring. Thereafter step-wise regressions based on forward selection strategies were used, in order to identify meaningful baseline predictors of patients' clinical evolution, derived from the intake process. The selected predictors were social support network, subjective distress, the initial measure of clinical distress, unemployment, sociocultural status and reactance. When including those six variables in a multilevel model, the results indicate that social support network, subjective distress, and the initial measure of clinical distress were significant predictors of the trajectories of OQ-30, whereas unemployment, sociocultural status and reactance were not significant. The results regarding social support network are in line with the literature, while results of socioeconomic status (unemployment and sociocultural level) move in an opposite direction in comparison to the available evidence. Moreover, the mental health findings (initial OQ-30 and subjective distress) confirm the contradictory body of literature produced in this domain. Finally, reactance seems to be a significant predictor in previous study in contradiction of our results. Overall, this endeavor constitutes important but preliminary evidence to enhance the production of bottom-up science within practice research networks in the global south.
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There has been a growing emphasis on dissemination of empirically supported treatments. Dissemination, however, should not be restricted to treatment. It can and, in the spirit of the scientific-practitioner model, should also involve research. Because it focuses on the investigation of clinical routine as it takes place in local settings and because it can involve the collaboration of several stakeholders, practice-oriented research (POR) can be viewed as an optimal research method to be disseminated. POR has the potential of addressing particularly relevant gaps of knowledge and action when implemented in regions of the world that have limited resources for or experiences with empirical research, and/or in clinical settings that are serving clinical populations who are not typically receiving optimal mental care services - specifically, individuals in rural and inner cities that have limited economic and social resources. The establishment and maintenance of POR in such regions and/or settings, however, come with specific obstacles and challenges. Integrating the experiences acquired from research conducted in various continents (Africa, Europe, Latin America, and North America), the goal of this paper is to describe some of these challenges, strategies that have been implemented to address them, as well as new possible directions to facilitate the creation and growth of POR. It also describes how these challenges and ways to deal with them can provide helpful lessons for already existing POR infrastructures.
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Serviços de Saúde Mental , Populações Vulneráveis , Humanos , Serviços de Saúde Mental/organização & administração , Pesquisa sobre Serviços de Saúde/organização & administraçãoRESUMO
Ecological momentary assessment (EMA) allows measuring intra-individual processes moment by moment, identifying and modeling, in a naturalistic way, individual levels and changes in different psychological processes. However, active EMA requires a high degree of adherence, as it implies a significant burden for patients. Moreover, there is still no consensus on standardized procedures for implementation. There have been few results in detecting desirable characteristics for the design and implementation of an EMA device. Studies that address these issues from the perspectives of participants in psychotherapeutic processes are needed. To analyze the perspectives of patients, therapists and supervisors on the implementation of an EMA device in a psychotherapeutic treatment for depression. The sample will include eight patients, eleven therapists and five supervisors, taken from a research project that implemented an EMA system for monitoring the dynamics of affectivity at the beginning of psychotherapies for depression. Semi-structured interviews specific to each group are being conducted and analyzed from a qualitative approach based on consensual qualitative research (CQR). Participants reported having a positive evaluation of the study's informational resources and implementation. Difficulties were expressed in responding in the morning hours and the importance of having a customized EMA that is tailored to the needs of the patients was expressed. Furthermore, patients and therapists agreed that the impact of the use of the monitoring system on treatment was neutral or positive. In contrast, patients considered the EMA to be positive for their daily life.
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Avaliação Momentânea Ecológica , Psicoterapia , Pesquisa Qualitativa , Humanos , Psicoterapia/métodos , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Atitude do Pessoal de Saúde , Depressão/terapiaRESUMO
Hematological traits are important indicators of health status, and they are frequently used as criteria for clinical diagnosis. In humans, the genomic architecture of blood traits has been investigated in depth and thousands of associations with genetic variants have been found. In contrast, the association between marker genotypes and the variation of hematological traits has not been investigated in goats yet. Herewith, we have recorded 12 hematological parameters in 882 Murciano-Granadina goats that were also genotyped with the Goat SNP50 BeadChip (Illumina). Performance of a univariate genome-wide association study (GWAS) made it possible to detect one genomic region on goat chromosome (CHI) 21 (19.2-19.5 Mb) associated, at the genome-wide level of significance, with 4 red blood cell traits. The three markers displaying the highest significances were rs268272996 (CHI21: 19225290 bp), rs268273004 (CHI21: 19565629 bp) and rs268239059 (CHI13: 9615190 bp). Consistently, a multivariate GWAS indicated that the rs268273004 marker on chromosome 21 is associated with seven blood cell traits. Interestingly, this marker maps close to the FA Complementation Group I (FANCI) gene (CHI21: 20021947-20077025 bp), which is functionally related to Fanconi anemia, a syndrome characterized by bone marrow failure, aplastic anemia, and congenital disorders. We have also uncovered additional chromosome-wide significant associations between genetic markers and erythrocyte and leukocyte traits in the univariate GWAS. These findings evidence that the phenotypic variation of hematological traits in goats is regulated, at least to some extent, by polygenic determinants distributed in multiple chromosomes.
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Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Humanos , Animais , Estudo de Associação Genômica Ampla/veterinária , Cabras/genética , Fenótipo , GenótipoRESUMO
Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pneumonia that emerged in 2012. There is limited information on MERS-CoV pathogenesis, as data from patients are scarce and the generation of animal models reproducing MERS clinical manifestations has been challenging. Human dipeptidyl peptidase 4 knock-in (hDPP4-KI) mice and a mouse-adapted MERS-CoV strain (MERSMA-6-1-2) were recently described. hDPP4-KI mice infected with MERSMA-6-1-2 show pathological signs of respiratory disease, high viral titers in the lung, and death. In this work, a mouse-adapted MERS-CoV infectious cDNA was engineered by introducing nonsynonymous mutations contained in the MERSMA-6-1-2 genome into a MERS-CoV infectious cDNA, leading to a recombinant mouse-adapted virus (rMERS-MA) that was virulent in hDDP4-KI mice. MERS-CoV adaptation to cell culture or mouse lungs led to mutations and deletions in genus-specific gene 5 that prevented full-length protein expression. In contrast, analysis of 476 MERS-CoV field isolates showed that gene 5 is highly stable in vivo in both humans and camels. To study the role of protein 5, two additional viruses were engineered expressing a full-length gene 5 (rMERS-MA-5FL) or containing a complete gene 5 deletion (rMERS-MA-Δ5). rMERS-MA-5FL virus was unstable, as deletions appeared during passage in different tissue culture cells, highlighting MERS-CoV instability. The virulence of rMERS-MA-Δ5 was analyzed in a sublethal hDPP4-KI mouse model. Unexpectedly, all mice died after infection with rMERS-MA-Δ5, in contrast to those infected with the parental virus, which contains a 17-nucleotide (nt) deletion and a stop codon in protein 5 at position 108. Expression of interferon and proinflammatory cytokines was delayed and dysregulated in the lungs of rMERS-MA-Δ5-infected mice. Overall, these data indicated that the rMERS-MA-Δ5 virus was more virulent than the parental one and suggest that the residual gene 5 sequence present in the mouse-adapted parental virus had a function in ameliorating severe MERS-CoV pathogenesis.IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus causing human infections with high mortality rate (â¼35%). Animal models together with reverse-genetics systems are essential to understand MERS-CoV pathogenesis. We developed a reverse-genetics system for a mouse-adapted MERS-CoV that reproduces the virus behavior observed in humans. This system is highly useful to investigate the role of specific viral genes in pathogenesis. In addition, we described a virus lacking gene 5 expression that is more virulent than the parental one. The data provide novel functions in IFN modulation for gene 5 in the context of viral infection and will help to develop novel antiviral strategies.
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Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Proteínas não Estruturais Virais/metabolismo , Animais , Linhagem Celular , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Citocinas/metabolismo , DNA Complementar/genética , Dipeptidil Peptidase 4/genética , Genoma Viral/genética , Humanos , Imunidade Inata , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Transgênicos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Mutação , Carga Viral , Proteínas não Estruturais Virais/genética , Virulência/genéticaRESUMO
Objective: To determine the relative risk of a lethal outcome associated with chronic degenerative conditions in patients with COVID-19. Methods: A cohort study was conducted using electronic medical records belonging to patients who tested positive for COVID-19 on RT-PCR while receiving care as outpatients or inpatients in a social security system facility between March 2020 and March 2021. Two study groups were formed. The exposed group was divided into four subgroups, each of which was diagnosed with one and only one chronic condition (diabetes, hypertension, obesity, or chronic kidney disease); the unexposed group was obtained from the medical records of patients without comorbidities. A total of 1 114 medical records were examined using simple random sampling. Once the minimum sample size was reached, the relative risk was calculated for each chronic condition. Combinations of two, three, and four conditions were created, and each of them was included in the analysis. Results: In the absence of a chronic degenerative condition, the prevalence of a lethal outcome from COVID-19 is 3.8%; in the presence of type 2 diabetes mellitus, 15.8%; in the presence of arterial hypertension, 15.6%; and in the presence of obesity, 15.0%. For diabetes and hypertension combined, the prevalence of a lethal outcome is 54.1%; for diabetes and obesity combined, 36.8%, and for obesity and hypertension combined, 28.1%. Conclusion: In patients with COVID-19, the relative risk of a lethal outcome is 4.17 for those with diabetes, 4.13 for those with hypertension, and 3.96 for those with obesity. For two chronic conditions combined, the relative risk doubles or triples. The relative risk of a lethal outcome is 14.27 for diabetes plus hypertension; 9.73 for diabetes plus obesity, and 7.43 for obesity plus hypertension. Chronic conditions do not present alone; they generally occur together, hence the significance of the relative risks for lethal outcomes presented in this paper.
Objetivo: Determinar o risco de letalidade conferido por doenças crônicas degenerativas em pacientes com COVID-19. Métodos: Foi realizado um estudo de coorte em prontuários eletrônicos de pacientes com RT-PCR positivo para COVID-19 em atendimento ambulatorial ou hospitalar em uma instituição de previdência social, no período de março de 2020 a março de 2021. Foram constituídos dois grupos de estudo. O grupo exposto foi dividido em quatro subgrupos, cada um com diagnóstico único e exclusivo de uma doença crônica (diabetes, hipertensão, obesidade ou doença renal crônica). O grupo não exposto foi constituído por prontuários de pacientes sem comorbidades. Foram revisados 1.114 prontuários no total, utilizando técnica de amostragem aleatória simples. Uma vez obtido o tamanho mínimo da amostra, foi calculado o risco relativo para cada doença crônica. Foram realizadas combinações de 2, 3 e 4, tendo sido feita a análise com cada uma delas. Resultados: Na ausência de doença crônica degenerativa, a prevalência de letalidade na COVID-19 é de 3,8%; na presença de diabetes mellitus tipo 2, a letalidade é de 15,8%; na presença de hipertensão arterial, 15,6%; e na presença de obesidade, 15%. Quando tanto diabetes como hipertensão estão presentes, a letalidade é de 54,1%; com diabetes e obesidade, 36,8%; e obesidade com hipertensão, 28,1%. Conclusões: Em pacientes com COVID-19, o risco relativo de letalidade é de 4,17 naqueles com diabetes; 4,13 naqueles com hipertensão; e 3,96 naqueles com obesidade. Quando duas doenças crônicas são combinadas, o risco relativo dobra ou triplica. Para diabetes e hipertensão, o risco relativo de letalidade é 14,27; para diabetes e obesidade, 9,73; e para obesidade e hipertensão, 7,43. As doenças crônicas não ocorrem sozinhas (geralmente estão associadas), e nessa perspectiva os riscos relativos de letalidade apresentados neste artigo tornam-se relevantes.
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This work presents a case study in which Cognitive-Integrative psychotherapy was used to treat a patient with obsessive-compulsive disorder with the implementation of routine outcome monitoring (ROM) at Aiglé Foundation in Argentina. The patient, a 34-year-old female with a university degree reports having obsessive ideas about dirt or pollution, causing harm to others, and religious and superstitious topics on a daily basis. The therapeutic process carried out during the first 17 psychotherapy sessions is described: construction of the therapeutic alliance, psychoeducation, and main interventions. The purpose of the article is to describe a case in which the measures' results did not show clinically relevant improvement even though the clinical indicators assessed by the therapist and the patient's subjective evaluation were positive. The article, shows the application of ROM during the supervision process, proposes interpretations of these results, and discusses decision-making processes in the light of this discrepancy.
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Terapia Cognitivo-Comportamental , Transtorno Obsessivo-Compulsivo , Adulto , Argentina , Terapia Cognitivo-Comportamental/métodos , Feminino , Humanos , Transtorno Obsessivo-Compulsivo/terapia , Psicoterapia , Resultado do TratamentoRESUMO
The aim of this study was to evaluate the effect of non-genetic factors on the variability of milk production and composition using Bayesian linear regression. We analyzed 2594 milk records from 159 dairy goats from the breeding nucleus of the Murciano-Granadina breed. Bayesian linear regression was used to determine the effects of non-genetic factors on the phenomics for quality-related milk nutrients and yield. Multivariate regression model significantly explained 21.5%, 40.0%, 41.5%, 44.3%, 44.6%, and 47.5% of the variability in somatic cell count (SCC, sc/mL), lactose (%), protein (%), milk yield (kg), fat (%), and dry matter (%), respectively. Although the aforementioned factor combination significantly conditions milk production and composition, SCC may be particularly affected by collateral factors. Milking routine and drying period factors are reference predictors to be considered in the evaluation of milk production and composition progression. Drying period extensions positively repercussed on milk yield and lactose content, but negatively affected fat, protein, dry matter contents, and somatic cell count. Variability across drying years may depend on the drying season rather than the drying month course, except for milk yield, for which an increasing trend was reported from winter to summer. Including drying period-related non-genetic factors in genetic evaluations improves the accuracy of the regression models and permits to boost the commercial possibilities and profitability of local breeds.
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Cabras , Leite , Feminino , Animais , Cabras/genética , Leite/metabolismo , Lactose/metabolismo , Lactação/genética , Fenômica , Proteínas do Leite , Teorema de Bayes , NutrientesRESUMO
The foraging (for) gene has been extensively studied in many species for its functions in development, physiology, and behavior. It is common for genes that influence behavior and development to be essential genes, and for has been found to be an essential gene in both fruit flies and mammals, with for mutants dying before reaching the adult stage. However, the biological process underlying the lethality associated with this gene is not known. Here, we show that in Drosophila melanogaster, some but not all gene products of for are essential for survival. Specifically, we show that promoter 3 of for, but not promoters 1, 2, and 4 are required for survival past pupal stage. We use full and partial genetic deletions of for, and temperature-restricted knock-down of the gene to further investigate the stage of lethality. While deletion analysis shows that flies lacking for die at the end of pupal development, as pharate adults, temperature-restricted knock-down shows that for is only required at the start of pupal development, for normal adult emergence (AE) and viability. We further show that the inability of these mutants to emerge from their pupal cases is linked to deficiencies in emergence behaviors, caused by a possible energy deficiency, and finally, that the lethality of for mutants seems to be linked to protein isoform P3, transcribed from for promoter 3.
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Proteínas Quinases Dependentes de GMP Cíclico/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Metamorfose Biológica/genética , AnimaisRESUMO
BACKGROUND AND PURPOSE: Anti-IgLON5 disease is a rare disorder characterized by a heterogeneous myriad of symptoms that may include sleep disorders, bulbar dysfunction, gait problems, movement disorders, cognitive impairment, oculomotor abnormalities, and nervous system hyperexcitability. Its physiopathology remains unknown, with a combination of both autoimmune and neurodegenerative findings. METHODS: We describe clinical, cerebrospinal fluid (CSF), and ioflupane single-photon emission computed tomography (SPECT) findings of a positive case of anti-IgLON5 disease mimicking probable progressive supranuclear palsy (PSP). We performed a literature review of previous publications reporting on anti-IgLON5 disease and ioflupane SPECT. RESULTS: We report the case of a 66-year-old male who met clinical criteria for probable PSP, in whom ioflupane SPECT showed an alteration of the left presynaptic dopaminergic pathway. However, the presence of atypical neurological symptoms for PSP led to further complementary tests, and IgLON5 antibodies were detected in CSF. According to our literature review, ioflupane SPECT findings have been previously described in only three other patients with anti-IgLON5 disease, with a reduced uptake in the striatum in two of them. CONCLUSIONS: Ioflupane SPECT abnormalities, though scarcely described, are not uncommon in anti-IgLON5 disease. They could be related to nigrostriatal dopaminergic degeneration in the context of the tauopathy component of the disease, but further case descriptions are necessary.
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Encefalite , Nortropanos , Paralisia Supranuclear Progressiva , Idoso , Moléculas de Adesão Celular Neuronais , Humanos , Masculino , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Transmission ratio distortion (TRD) is the preferential transmission of one specific allele to offspring at the expense of the other. The existence of TRD is mostly explained by the segregation of genetic variants with deleterious effects on the developmental processes that go from the formation of gametes to fecundation and birth. A few years ago, a statistical methodology was implemented in order to detect TRD signals on a genome-wide scale as a first step toward uncovering the biological basis of TRD and reproductive success in domestic species. In the current work, we have analyzed the impact of SNP calling quality on the detection of TRD signals in a population of Murciano-Granadina goats. Seventeen bucks and their offspring (N = 288) were typed with the Goat SNP50 BeadChip, whereas the genotypes of the dams were lacking. Performance of a genome-wide scan revealed the existence of 36 SNPs showing significant evidence of TRD. When we calculated GenTrain scores for each of the SNPs, we observed that 25 SNPs showed scores below 0.8. The allele frequencies of these SNPs in the offspring were not correlated with the allele frequencies estimated in the dams with statistical methods, providing evidence that flawed SNP calling quality might lead to the detection of spurious TRD signals. We conclude that, when performing TRD scans, the GenTrain scores of markers should be taken into account to discriminate SNPs that are truly under TRD from those yielding spurious signals owing to technical problems.
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Cabras/genética , Padrões de Herança , Modelos Genéticos , Alelos , Animais , Frequência do Gene , Marcadores Genéticos , Genótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Emotional disorders (EDs) are among the most prevalent mental disorders. Existing evidence-based psychological treatments are not sufficient to reduce the disease burden of mental disorders. It is therefore essential to implement innovative solutions to achieve a successful dissemination of psychological treatment protocols, and in this regard, the use of information and communication technologies such as the internet can be very useful. Furthermore, the literature suggests that not everyone with an ED receives the appropriate treatment. This situation has led to the development of new intervention proposals based on the transdiagnostic perspective, which attempts to address the underlying processes common to EDs. Most of these transdiagnostic interventions focus primarily on downregulating negative affectivity (NA), and less attention has been paid to strengths and the upregulation of positive affectivity, despite its importance for well-being and mental health. OBJECTIVE: This study aims to evaluate the efficacy of a transdiagnostic internet-based treatment for EDs in a community sample. METHODS: A 3-armed randomized controlled trial was conducted. A total of 216 participants were randomly assigned to a transdiagnostic internet-based protocol (TIBP), a TIBP+ positive affect (PA) component, or a waiting list (WL) control group. The treatment protocol contained core components mainly addressed to downregulate NA (ie, present-focused emotional awareness and acceptance, cognitive flexibility, behavioral and emotional avoidance patterns, and interoceptive and situational exposure) as well as a PA regulation component to promote psychological strengths and enhance well-being. Data on depression, anxiety, quality of life, neuroticism and extraversion, and PA/NA before and after treatment were analyzed. Expectations and opinions of treatment were also analyzed. RESULTS: Within-group comparisons indicated significant pre-post reductions in the two experimental conditions. In the TIBP+PA condition, the effect sizes were large for all primary outcomes (d=1.42, Beck Depression Inventory [BDI-II]; d=0.91, Beck Anxiety Inventory [BAI]; d=1.27, Positive and Negative Affect Schedule-Positive [PANAS-P]; d=1.26, Positive and Negative Affect Schedule-Negative [PANAS-N]), whereas the TIBP condition yielded large effect sizes for BDI-II (d=1.19) and PANAS-N (d=1.28) and medium effect sizes for BAI (d=0.63) and PANAS-P (d=0.69). Between-group comparisons revealed that participants who received one of the two active treatments scored better at posttreatment than WL participants. Although there were no statistically significant differences between the two intervention groups on the PA measure, effect sizes were consistently larger in the TIBP+PA condition than in the standard transdiagnostic protocol. CONCLUSIONS: Overall, the findings indicate that EDs can be effectively treated with a transdiagnostic intervention via the internet, as significant improvements in depression, anxiety, and quality of life measures were observed. Regarding PA measures, promising effects were found, but more research is needed to study the role of PA as a therapeutic component. TRIAL REGISTRATION: ClinicalTrials.gov NCT02578758; https://clinicaltrials.gov/ct2/show/NCT02578758. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12888-017-1297-z.
Assuntos
Emoções/fisiologia , Intervenção Baseada em Internet/tendências , Transtornos Mentais/terapia , Qualidade de Vida/psicologia , Telemedicina/métodos , Adolescente , Adulto , Afeto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: In insects, continuous growth requires the periodic replacement of the exoskeleton. Once the remains of the exoskeleton from the previous stage have been shed during ecdysis, the new one is rapidly sclerotized (hardened) and melanized (pigmented), a process collectively known as tanning. The rapid tanning that occurs after ecdysis is critical for insect survival, as it reduces desiccation, and gives the exoskeleton the rigidity needed to support the internal organs and to provide a solid anchor for the muscles. This rapid postecdysial tanning is triggered by the "tanning hormone", bursicon. Since bursicon is released into the hemolymph, it has naturally been assumed that it would act on the epidermal cells to cause the tanning of the overlying exoskeleton. RESULTS: Here we investigated the site of bursicon action in Drosophila by examining the consequences on tanning of disabling the bursicon receptor (encoded by the rickets gene) in different tissues. To our surprise, we found that rapid tanning does not require rickets function in the epidermis but requires it instead in peptidergic neurons of the ventral nervous system (VNS). Although we were unable to identify the signal that is transmitted from the VNS to the epidermis, we show that neurons that express the Drosophila insulin-like peptide ILP7, but not the ILP7 peptide itself, are involved. In addition, we found that some of the bursicon targets involved in melanization are different from those that cause sclerotization. CONCLUSIONS: Our findings show that bursicon does not act directly on the epidermis to cause the tanning of the overlying exoskeleton but instead requires an intermediary messenger produced by peptidergic neurons within the central nervous system. Thus, this work has uncovered an unexpected layer of control in a process that is critical for insect survival, which will significantly alter the direction of future research aimed at understanding how rapid postecdysial tanning occurs.
Assuntos
Exoesqueleto/fisiologia , Drosophila/fisiologia , Hormônios de Inseto/metabolismo , Hormônios de Invertebrado/metabolismo , Animais , Proteínas de Drosophila/metabolismo , Epiderme/fisiologia , Feminino , Masculino , Neuropeptídeos/metabolismoRESUMO
The use of virtual reality (VR) and mixed reality (MR) technology in clinical psychology is growing. Efficacious VR-based treatments for a variety of disorders have been developed. However, the field of technology-assisted psychotherapy is constantly changing with the advancement in technology. Factors such as interdisciplinary collaboration, consumer familiarity and adoption of VR products, and progress in clinical science all need to be taken into consideration when integrating virtual technologies into psychotherapies. We aim to present an overview of current expert opinions on the use of virtual technologies in the treatment of anxiety and stress-related disorders. An anonymous survey was distributed to a select group of researchers and clinicians, using an analytic framework known as Strengths, Weaknesses, Opportunities, and Threats (SWOT). Overall, the respondents had an optimistic outlook regarding the current use as well as future development and implementation of technology-assisted interventions. VR and MR psychotherapies offer distinct advantages that can overcome shortcomings associated with traditional therapy. The respondents acknowledged and discussed current limitations of VR and MR psychotherapies. They recommended consolidation of existing knowledge and encouraged standardisation in both theory and practice. Continued research is needed to leverage the strengths of VR and MR to develop better treatments.Abbreviations: AR: Augmented Reality; MR: Mixed Reality; RCT: Randomised Controlled Trial; SWOT: Strengths, Weaknesses, Opportunities, and Threats; VR: Virtual Reality; VR-EBT: Virtual Reality Exposure-Based Therapy.