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1.
Ann Dyslexia ; 74(1): 66-81, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38010579

RESUMO

Individuals with dyslexia have been shown to have an increased risk for developing internalizing problems. Various studies have revealed the powerful role that culture plays in determining the type of anxiety and coping strategies adopted by various groups of individuals. However, compared to the vast number of studies conducted in individualistic cultures, knowledge on collectivistic cultures with respect to this issue is still limited. This study examined anxiety and coping strategies of children with and without dyslexia in Ethiopia, where the majority of its cultural dimensions could be regarded as collectivistic. A total of 126 children with (n = 63) and without (n = 63) dyslexia, aged 8-11 (41 boys and 22 girls, in each group; and age: M = 9.43 years; SD = 1.14 and M = 9.46; SD =1.11), participated. Dyslexia was assessed using an Amharic dyslexia assessment battery, while anxiety level and coping strategy were respectively measured using the Spence Children's Anxiety Scales (SCAS) and the Children's Coping Questionnaire (CCQ), both translated into Amharic. Results indicated that dyslexia was associated with higher levels of anxiety (especially generalized anxiety) and lower levels of support-seeking coping strategies. We discuss these results in the light of the cultural and institutional context in Ethiopia.


Assuntos
Capacidades de Enfrentamento , Dislexia , Masculino , Criança , Feminino , Humanos , Etiópia , Leitura , Ansiedade
2.
Euro Surveill ; 28(39)2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37768562

RESUMO

BackgroundNeisseria meningitidis is a commensal bacterium which can cause invasive disease. Colonisation studies are important to guide vaccination strategies.AimThe study's aim was to determine the prevalence of meningococcal colonisation, duration of carriage and distribution of genogroups in Iceland.MethodsWe collected samples from 1 to 6-year-old children, 15-16-year-old adolescents and 18-20-year-old young adults. Carriers were sampled at regular intervals until the first negative swab. Conventional culture methods and qPCR were applied to detect meningococci and determine the genogroup. Whole genome sequencing was done on groupable meningococci.ResultsNo meningococci were detected among 460 children, while one of 197 (0.5%) adolescents and 34 of 525 young adults (6.5 %) carried meningococci. Non-groupable meningococci were most common (62/77 isolates from 26/35 carriers), followed by genogroup B (MenB) (12/77 isolates from 6/35 carriers). Genogroup Y was detected in two individuals and genogroup W in one. None carried genogroup C (MenC). The longest duration of carriage was at least 21 months. Serial samples from persistent carriers were closely related in WGS.ConclusionsCarriage of pathogenic meningococci is rare in young Icelanders. Non-groupable meningococci were the most common colonising meningococci in Iceland, followed by MenB. No MenC were found. Whole genome sequencing suggests prolonged carriage of the same strains in persistent carriers.


Assuntos
Neisseria meningitidis , Adolescente , Humanos , Criança , Adulto Jovem , Estudos Longitudinais , Estudos Transversais , Islândia/epidemiologia , Genótipo , Neisseria meningitidis/genética
3.
Vaccine ; 41(34): 4927-4932, 2023 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-37423800

RESUMO

Carriage of Neisseria meningitidisis an accepted endpoint in monitoring meningococcal vaccine effects. We applied molecular methods to assess the impact of menACWY vaccine implementation on meningococcal carriage and genogroup-specific prevalence in young adults in Fall of 2022, four years after the introduction of the tetravalent vaccine in the Netherlands. The overall carriage rate of genogroupable meningococci was not significantly different compared to a pre-menACWY cohort investigated in 2018 (20.8 % or 125 of 601 versus 17.4 % or 52 of 299 individuals, p = 0.25). Of 125 carriers of genogroupable meningococci, 122 (97.6 %) were positive for either vaccine-types menC, menW, menY or genogroups, menB, menE, and menX, which are not targeted by the menACWY vaccine. Compared with a pre-vaccine-implementation cohort, there was 3.8-fold reduction (p < 0.001) in vaccine-type carriage rates and 9.0-fold increase (p < 0.0001) in non-vaccine type menE prevalence. We observe a reduction in menW and menY and an increase in menE, which suggest that implementation of menACWY vaccine affected carriage.


Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis , Adulto Jovem , Humanos , Neisseria meningitidis/genética , Países Baixos/epidemiologia , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Genótipo , Vacinas Combinadas
4.
Front Psychiatry ; 13: 836807, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693963

RESUMO

Background: Phelan-McDermid syndrome (PMS) or 22q13.3 deletion syndrome is a rare genetic disorder characterized by developmental delay, hypotonia and severely delayed speech. Behavioral difficulties are often reported in PMS, although knowledge of behavioral profiles and the interpretation of reported behavior remains limited. Understanding the meaning of behavior requires considering the context as well as other domains of functioning, for example the individual's level of cognitive, social and emotional development. Combining structured direct in-person neurodevelopmental assessments with contextual assessments to enable meaningful interpretations of reported behavior on functional dimensions across multiple units of analysis, as proposed by the RDoc framework, is essential. Methods: In this article we present a structured multidisciplinary method of assessment through direct in-person neurodevelopmental assessments and assessment of contextual factors. Our study sample includes data of 33 children with an average age of 6.2 years (range 1.1 to 15.7) with PMS, obtained through individual in-person assessments in combination with parent informed questionnaires. We assessed developmental age using the Bayley-III, adaptive behavior was assessed with the Vineland screener, social-emotional development with the ESSEON-R and behavior by using the CBCL. Results: Our results show a great deal of variability in phenotypic presentation with regard to behavior, symptom expression and symptom severity in individuals with PMS. The data on behavior is interpreted in the context of the individual's level of cognitive, adaptive development and the (genetic) context. Behavioral data showed high levels of withdrawn behavior and attention problems. More than half of the children showed borderline or clinical symptoms related to Autism Spectrum Disorder (ASD). Conclusions: The interpretation of the meaning of certain behavior in PMS is often based on questionnaires and descriptions without taking the specific context of development into account. Combining questionnaires with direct in-person assessments measuring different domains of functioning should be considered a more accurate method to interpret the meaning of findings in order to understand behavior in rare genetic disorders associated with developmental delay such as PMS. Direct in-person assessment provides valuable and specific information relevant to understanding individual behavior and inform treatment as well as increase knowledge of the neurodevelopmental phenotype in individuals with PMS. More specific application of the proposed frameworks on behavior in PMS is desirable in making useful interpretations.

5.
Children (Basel) ; 9(4)2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35455556

RESUMO

There is growing demand for digital intelligence testing. In the current study, we evaluated the validity of an online version of the revised German Culture Fair Intelligence Test (CFT 20-R). A total of 4100 children from the third and fourth grades completed the online version using a smartphone or tablet. Subsequently, 220 of these children also completed the paper-pencil (PP) version. The internal consistency and construct validity of the online version appeared to be acceptable. The correlation between the raw scores and school grades in German and mathematics was slightly lower than expected. On average, the raw scores for the PP version were revealed to be higher, which was probably due to a learning effect. At the item level, the results show small differences for the subtests Series and Matrices, possibly caused by small differences in the presentation of the items. The correspondence between the versions did not depend on children's levels of impulsivity or intelligence. Altogether, the results support the hypothesis that the online version of the CFT 20-R is a valid measure of general fluid intelligence and highlight the need for separate norms.

6.
South Afr J HIV Med ; 23(1): 1322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399749

RESUMO

Background: South Africa's public antiretroviral treatment (ART) programme has undergone progressive changes since its introduction in 2004. The effect of this on the burden of the AIDS-defining opportunistic infection, cytomegalovirus retinitis (CMVR), in SA, has not been fully appreciated. Objectives: To determine the effect of ART availability in the public sector of SA on the trend in the number of cases of newly diagnosed CMVR over time. Methods: This is a retrospective study from 01 November 2002 to 31 August 2017 that took place at a tertiary hospital in the KwaZulu-Natal (KZN) province. Results: A total of 383 participants were included in the study, with 60.1% being female and 94% of black African origin. The mean age of patients was 34.08 years (SD ± 7.24). A linear trend model suggested an overall linear decrease in the number of new cases of CMVR per year (R 2 of 0.67). The average number of new cases of CMVR per year prior to ART being available to all persons living with HIV (PLWH) with a CD4+ ≤ 350 cells/µL and after was 34 and 13, respectively, and the difference (61.76%) between these values was statistically significant, P = 0.001. The median CD4+ count at diagnosis of CMVR was 22 (interquartile range: 9-51.25) cells/µL. An overall 51% of patients in this study were on ART at diagnosis of CMVR. There was a higher proportion of patients on ART ≤ 6 months (63.3%), compared with those on ART > 6 months (36.7%), and the difference was statistically significant, P < 0.01. Conclusion: ART has resulted in a decrease in the burden of CMVR on ophthalmic services for many in KZN, particularly following the introduction of ART for all PLWH with a CD4 ≤ 350 cells/µL.

7.
J Womens Health (Larchmt) ; 31(2): 219-230, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34077695

RESUMO

Background: Endometriosis stage is not directly related to the burden of symptoms, and recurrence of symptoms occurs frequently. It is suggested that symptoms are associated with psychological distress, as in depression and anxiety disorders. Our aim was to explore the strength of the associations between endometriosis and depression or anxiety and to review correlating factors. Materials and Methods: A literature search was carried out using the electronic databases Embase, PubMed, Web-of-science, and PsycINFO. Search terms related to depression, anxiety, and endometriosis were combined resulting in 1,837 records. Articles were included when describing an association between patients with endometriosis and symptoms of depression or anxiety assessed by validated tools, structured psychiatric interviews, or a documented diagnosis. With 47 articles a systematic qualitative review was performed. Seventeen studies were eligible for meta-analysis. Results: Endometriosis patients experienced significantly more symptoms of depression (standardized mean difference [SMD] of 0.71 (95% confidence interval [CI] 0.36-1.06)) and anxiety (SMD 0.60 (95% CI 0.35-0.84)) compared with healthy controls, but no differences were found comparing endometriosis patients with other chronic pelvic pain patients (SMD -0.01 [95% CI -0.17 to 0.15] for depression and SMD -0.02 [95% CI -0.22 to 0.18] for anxiety). Besides the effect of pain, other correlating factors included age, quality of life, quality of sleep, fatigue, sexual function, gastrointestinal symptoms, comorbidity, self-esteem, emotional self-efficacy, coping style, social adjustment, pain imagery, and pain sensitization. Conclusion: This systematic review supports the assumption that symptoms of depression and anxiety occur frequently in endometriosis patients and are related to chronic pain. Correlating factors should further be investigated.


Assuntos
Depressão , Endometriose , Ansiedade/epidemiologia , Transtornos de Ansiedade , Depressão/epidemiologia , Endometriose/complicações , Endometriose/epidemiologia , Feminino , Humanos , Qualidade de Vida
8.
Front Psychol ; 12: 725374, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759867

RESUMO

Introduction: DSM-5 presented a revised conceptualization of specific learning disorders (LD). Contrary to former versions, the various types of LD-i.e., mathematics disorder, reading disorder, and writing disorder-are not treated as distinct diagnostic entities but are integrated into one single LD category. In support of this new classification, it has been argued that the various types of LD overlap to a great extent in their cognitive functioning profiles and therefore do not exhibit a distinct set of cognitive causes. In contrast, ICD-11 still adheres to the idea of discrete categories and thus follows the specificity hypothesis of LD. Using latent profile analysis (LPA), we therefore tested the specificity of cognitive strengths and weaknesses in children with different types of LD. Secondly, we aimed at examining the extent to which observed LD characteristics (type and severity of LD as well as IQ-achievement discrepancy) were consistent with the membership of a given latent profile. Method: 302 German third-graders (134 girls; IQ ≥ 85; M age = 111.05 months; SD = 5.76) with single or comorbid types of LD in the domains of mathematics, reading, and spelling completed a wide range of domain-specific and domain-general cognitive functioning measures. Results: Five qualitative distinct profiles of cognitive strengths and weaknesses were identified. Profile 1 (23% of the sample) showed Comprehensive Cognitive Deficits, performing low in all measures except for naming speed, language, and inhibition. Profile 2 (21%) included children with a Double Deficit in Phonological Awareness and Phonological Short-term Memory. Profile 3 (20%) was characterized by a Double Deficit of Phonological Awareness and Naming Speed. Profile 4 (19%) included children with a Single Deficit in Attention, and profile 5 (17%) consisted of children without any cognitive deficits. Moreover, type and severity of LD as well as IQ-achievement discrepancy discriminated between the profiles, which is in line with the specificity hypothesis of LD. Discussion: Overall, the finding of specific associations between the LD types and the identified cognitive profiles supports the ICD-11 classification of LD. Yet, those inferences may not be valid for an individual child but need to be examined through comprehensive diagnostic.

9.
Ophthalmology ; 128(10): e51-e68, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34247850

RESUMO

PURPOSE: The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., anti-vascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system. DESIGN: Review of evidence-based literature, along with expert consensus opinion. PARTICIPANTS: International ROP expert committee assembled in March 2019 representing 17 countries and comprising 14 pediatric ophthalmologists and 20 retinal specialists, as well as 12 women and 22 men. METHODS: The committee was initially divided into 3 subcommittees-acute phase, regression or reactivation, and imaging-each of which used iterative videoconferences and an online message board to identify key challenges and approaches. Subsequently, the entire committee used iterative videoconferences, 2 in-person multiday meetings, and an online message board to develop consensus on classification. MAIN OUTCOME MEASURES: Consensus statement. RESULTS: The ICROP3 retains current definitions such as zone (location of disease), stage (appearance of disease at the avascular-vascular junction), and circumferential extent of disease. Major updates in the ICROP3 include refined classification metrics (e.g., posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. ROP regression and reactivation are described in detail, with additional description of long-term sequelae. CONCLUSIONS: These principles may improve the quality and standardization of ROP care worldwide and may provide a foundation to improve research and clinical care.


Assuntos
Retina/diagnóstico por imagem , Retinopatia da Prematuridade/classificação , Diagnóstico por Imagem , Progressão da Doença , Idade Gestacional , Humanos , Recém-Nascido , Retinopatia da Prematuridade/diagnóstico
10.
Prax Kinderpsychol Kinderpsychiatr ; 70(4): 282-297, 2021 May.
Artigo em Alemão | MEDLINE | ID: mdl-33977880

RESUMO

Differential Stability and Interrater-Dependencies in the Assessment of Psychopathological Symptoms: Longitudinal Analyses Based on the SDQ in Children with and without Specific Learning Disabilities A widely used open access instrument for screening of internalising and externalising problem behaviour is the Strengths and Difficulties Questionnaire (SDQ). For the use of the SDQ in clinical practice, information about its differential validity and applicability for follow-up assessments is relevant. Therefore, the aim was to study the SDQ regarding differential stability in the repeatedly collected child, parent and teacher reports. As the social context influences the perception of symptoms, we additionally explored the extent to which the child, parent and teacher reports influenced each other. Also, we studied differences in problem behaviour between children with and without specific learning disabilities and between girls and boys. To this end, 60 children from 5th and 6th grade with and without specific learning disabilities and their parents and teachers filled in the SDQ at three time points during secondary school. The results of the cross-lagged-panel-analyses showed substantial stability for almost all subscales. This shows that in their SDQ-reports, parents, children and teachers can separate the stable parts of problem behaviour from situational variations therein. Inter-rater dependencies between the different reports in the form of cross-delayed effects could be identified mainly from the adult to the child reports and clarify the caregiver's influence on the children's symptom perception. With respect to specific learning disabilities, the results showed differences only for the subscale related to hyperactivity: children with specific learning disabilities had more parent-reported, but less self-reported hyperactive symptoms than children without. Girls reported more emotional problems and boys more conduct problems and less prosocial behavior. Teacher and parents reported almost no differences between boys and girls. The results support the usefulness of the SDQ for repeated assessments in clinical practice.


Assuntos
Transtornos do Comportamento Infantil , Deficiências da Aprendizagem , Comportamento Problema , Criança , Transtornos do Comportamento Infantil/diagnóstico , Feminino , Humanos , Deficiências da Aprendizagem/diagnóstico , Masculino , Pais , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
11.
Ann Vasc Surg ; 76: 500-513, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33905851

RESUMO

BACKGROUND: Vascular surgery is considered a risk factor for the development of postoperative delirium (POD). In this systematic review we provide a report on the incidence and risk-factors of POD after vascular surgery. METHODS: A systematic literature search was conducted using Pubmed with the MeSH terms and key words "delirium" or "confusion", "vascular surgery procedures" and "risk factors or "risk assessment". Studies were selected for review after meeting the following inclusion criteria: vascular surgery, POD diagnosed using validated screening tools, and DSM-derived criteria to assess delirium. A meta-analysis was performed for each endpoint if at least two studies could be combined. RESULTS: Sixteen articles met the abovementioned criteria. The incidence of delirium ranged from 5% to 39%. Various preoperative risk factors were identified that is, age (Random MD 3.96, CI 2.57-5.35), hypertension (Fixed OR 1.30, CI 1.05-1.59), diabetes mellitus (Random OR 2.15, CI 1.30-3.56), hearing impairment (Fixed OR 1.89, CI 1.28-2.81), history of cerebrovascular incident or transient ischemic attack (Fixed OR 2.20, CI 1.68-2.88), renal failure (Fixed OR 1.61, CI 1.19-2.17), and pre-operative low haemoglobin level (fixed MD -0.76, CI -1.04 to -0.47). Intra-operative risk factors were duration of surgery (Random MD 15.68; CI 2.79-28.57), open aneurysm repair (Fixed OR 4.99, CI 3.10-8.03), aortic cross clamping time (fixed MD 7.99, CI 2.56-13.42), amputation surgery (random OR 3.77, CI 2.13-6.67), emergency surgery (Fixed OR 4.84, CI 2.81-8.32) and total blood loss (Random MD 496.5, CI 84.51-908.44) and need for blood transfusion (Random OR 3.72, CI 1.57-8.80). Regional anesthesia on the other hand, had a protective effect. Delirium was associated with longer ICU and hospital length of stay, and more frequent discharge to a care facility. CONCLUSIONS: POD after vascular surgery is a frequent complication and effect-size pooling supports the concept that delirium is a heterogeneous disorder. The risk factors identified can be used to either design a validated risk factor model or individual preventive strategies for high-risk patients.


Assuntos
Delírio/epidemiologia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Fatores Etários , Idoso , Comorbidade , Delírio/diagnóstico , Feminino , Humanos , Incidência , Masculino , Medição de Risco , Fatores de Risco , Resultado do Tratamento
12.
J Vasc Surg ; 73(6): 2132-2139.e2, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33387657

RESUMO

OBJECTIVE: Frailty has persistently been associated with unfavorable short-term outcomes after vascular surgery, including an increased complication risk, greater readmission rate, and greater short-term mortality. However, a knowledge gap remains concerning the association between preoperative frailty and long-term mortality. In the present study, we aimed to determine this association in elective vascular surgery patients. METHODS: The present study was a part of a large prospective cohort study initiated in 2010 in our tertiary referral teaching hospital to study frailty in elderly elective vascular surgery patients (Vascular Ageing Study). A total of 639 patients with a minimal follow-up of 5 years, who had been treated from 2010 to 2014, were included in the present study. The Groningen Frailty Indicator, a 15-item self-administered questionnaire, was used to determine the presence and degree of frailty. RESULTS: Of the 639 patients, 183 (28.6%) were considered frail preoperatively. For the frail patients, the actuarial survival after 1, 3, and 5 years was 81.4%, 66.7%, and 55.7%, respectively. For the nonfrail patients, the corresponding survival was 93.6%, 83.3%, and 75.2% (log-rank test, P < .001). Frail patients had a significantly greater risk of 5-year mortality (unadjusted hazard ratio, 2.09; 95% confidence interval, 1.572-2.771; P < .001). After adjusting for surgical- and patient-related risk factors, the hazard ratio was 1.68 (95% confidence interval, 1.231-2.286; P = .001). CONCLUSIONS: The results of our study have shown that preoperative frailty is associated with significantly increased long-term mortality after elective vascular surgery. Knowledge of a patient's preoperative frailty state could, therefore, be helpful in shared decision-making, because it provides more information about the procedural benefits and risks.


Assuntos
Idoso Fragilizado , Fragilidade/mortalidade , Doenças Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Eletivos , Feminino , Fragilidade/diagnóstico , Avaliação Geriátrica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/mortalidade , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade
13.
Eye (Lond) ; 35(4): 1066-1083, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33323984

RESUMO

Sub-Saharan Africa is home to 12% of the global population, and 4.3 million are blind and over 15 million are visually impaired. There are only 2.5 ophthalmologists per million people in SSA. Training of ophthalmologists is critical. We designed a systematic literature review protocol, searched MEDLINE Ovid and Embase OVID on 1 August 2019 and limited these searches to the year 2000 onwards. We also searched Google Scholar and websites of ophthalmic institutions for additional information. We include a total of 49 references in this review and used a narrative approach to synthesise the results. There are 56 training institutions for ophthalmologists in eleven Anglophone, eleven Francophone, and two Lusophone SSA countries. The median duration of ophthalmology training programmes was 4 years. Most curricula have been regionally standardised. National, regional and international collaborations are a key feature to ophthalmology training in more than half of ophthalmology training programmes. There is a drive, although perhaps not always evidence-based, for sub-specialisation in the region. Available published scientific data on ophthalmic medical and surgical training in SSA is sparse, especially for Francophone and Lusophone countries. However, through a broad scoping review strategy it has been possible to obtain a valuable and detailed view of ophthalmology training in SSA. Training of ophthalmologists is a complex and multi-faceted task. There are challenges in appropriate selection, capacity, and funding of available training institutions. Numerous learning outcomes demand curriculum, time, faculty, support, and appropriate assessment. There are opportunities provided by modern training approaches. Partnership is key.


Assuntos
Oftalmologia , África Subsaariana , Currículo , Humanos , Oftalmologia/educação , Revisões Sistemáticas como Assunto
14.
PLoS Pathog ; 16(7): e1008702, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32667958

RESUMO

The type I interferon response is an important innate antiviral pathway. Recognition of viral RNA by RIG-I-like receptors (RLRs) activates a signaling cascade that leads to type I interferon (IFN-α/ß) gene transcription. Multiple proteins in this signaling pathway (e.g. RIG-I, MDA5, MAVS, TBK1, IRF3) are regulated by (de)ubiquitination events. Most viruses have evolved mechanisms to counter this antiviral response. The leader protease (Lpro) of foot-and-mouth-disease virus (FMDV) has been recognized to reduce IFN-α/ß gene transcription; however, the exact mechanism is unknown. The proteolytic activity of Lpro is vital for releasing itself from the viral polyprotein and for cleaving and degrading specific host cell proteins, such as eIF4G and NF-κB. In addition, Lpro has been demonstrated to have deubiquitination/deISGylation activity. Lpro's deubiquitination/deISGylation activity and the cleavage/degradation of signaling proteins have both been postulated to be important for reduced IFN-α/ß gene transcription. Here, we demonstrate that TBK1, the kinase that phosphorylates and activates the transcription factor IRF3, is cleaved by Lpro in FMDV-infected cells as well as in cells infected with a recombinant EMCV expressing Lpro. In vitro cleavage experiments revealed that Lpro cleaves TBK1 at residues 692-694. We also observed cleavage of MAVS in HeLa cells infected with EMCV-Lpro, but only observed decreasing levels of MAVS in FMDV-infected porcine LFPK αVß6 cells. We set out to dissect Lpro's ability to cleave RLR signaling proteins from its deubiquitination/deISGylation activity to determine their relative contributions to the reduction of IFN-α/ß gene transcription. The introduction of specific mutations, of which several were based on the recently published structure of Lpro in complex with ISG15, allowed us to identify specific amino acid substitutions that separate the different proteolytic activities of Lpro. Characterization of the effects of these mutations revealed that Lpro's ability to cleave RLR signaling proteins but not its deubiquitination/deISGylation activity correlates with the reduced IFN-ß gene transcription.


Assuntos
Proteína DEAD-box 58/metabolismo , Endopeptidases/metabolismo , Vírus da Febre Aftosa/metabolismo , Interferon Tipo I/biossíntese , Animais , Linhagem Celular , Endopeptidases/genética , Febre Aftosa/imunologia , Febre Aftosa/metabolismo , Vírus da Febre Aftosa/imunologia , Humanos , Proteólise
15.
Indian J Ophthalmol ; 68(8): 1551-1554, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32709773

RESUMO

Purpose: The purpose was to identify and describe patients with new-onset vernal keratoconjunctivitis-like (VKC-like) disease after puberty. Methods: The study consisted of two parts: a prospective observational descriptive study of patients with new-onset VKC-like disease, and a case-control study to determine the relationship of a CD4 count with VKC-like disease in adults, in the setting of human immunodeficiency virus (HIV). Patients were recruited between January 2016 and November 2017 from a Provincial Eye hospital, one of two large referral hospitals in KwaZulu-Natal, South Africa. Patients presenting to the eye clinic were screened and diagnosed at the Primary Eye Care Unit. Inclusion criteria: age 15 years and older with signs and symptoms of new-onset VKC-like disease. Exclusion criteria: a history of childhood atopic diseases, atopic keratoconjunctivitis and patients who declined HIV testing. Data collected included HIV status, CD4 count, antinuclear antibodies and total serum immunoglobulin E. Results: Thirty-three patients were included; females n = 16 and males n = 17. The mean age at presentation was 32.45 ± 9.93 years, 95% CI = 28.94-35.97. Twenty-six patients (78.8%) were HIV positive, 95% CI (62-89). The proportion of HIV positive patients was statistically different from the HIV negative group, Chi-squared = 21.866, P value <0.0001. In the group of HIV positive patients, 72% were classified as immunodeficient according to their CD4 counts. An association was proven between severely immunodeficient patients and the risk of VKC-like disease (Chi-squared = 4.992, P value = 0.0255). Conclusion: In this cohort, a statistically significant association was found between VKC-like disease in adults and an HIV positive status. This association calls for more research on the subject.


Assuntos
Conjuntivite Alérgica , Infecções por HIV , Adolescente , Adulto , Estudos de Casos e Controles , Conjuntivite Alérgica/diagnóstico , Conjuntivite Alérgica/epidemiologia , Demografia , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Masculino , África do Sul/epidemiologia
16.
Nat Microbiol ; 5(11): 1361-1373, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32690955

RESUMO

Eukaryotic cells, when exposed to environmental or internal stress, activate the integrated stress response (ISR) to restore homeostasis and promote cell survival. Specific stress stimuli prompt dedicated stress kinases to phosphorylate eukaryotic initiation factor 2 (eIF2). Phosphorylated eIF2 (p-eIF2) in turn sequesters the eIF2-specific guanine exchange factor eIF2B to block eIF2 recycling, thereby halting translation initiation and reducing global protein synthesis. To circumvent stress-induced translational shutdown, viruses encode ISR antagonists. Those identified so far prevent or reverse eIF2 phosphorylation. We now describe two viral proteins-one from a coronavirus and the other from a picornavirus-that have independently acquired the ability to counteract the ISR at its very core by acting as a competitive inhibitor of p-eIF2-eIF2B interaction. This allows continued formation of the eIF2-GTP-Met-tRNAi ternary complex and unabated global translation at high p-eIF2 levels that would otherwise cause translational arrest. We conclude that eIF2 and p-eIF2 differ in their interaction with eIF2B to such effect that p-eIF2-eIF2B association can be selectively inhibited.


Assuntos
Fator de Iniciação 2B em Eucariotos/antagonistas & inibidores , Fator de Iniciação 2 em Eucariotos/antagonistas & inibidores , Estresse Fisiológico/fisiologia , Proteínas Virais/metabolismo , Animais , Sítios de Ligação , Chlorocebus aethiops , Células Eucarióticas/metabolismo , Fator de Iniciação 2 em Eucariotos/metabolismo , Fator de Iniciação 2B em Eucariotos/metabolismo , Técnicas de Inativação de Genes , Células HEK293 , Células HeLa , Humanos , Fosforilação , Picornaviridae/metabolismo , Ligação Proteica , Células Vero
18.
World J Surg ; 44(10): 3564-3572, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32494998

RESUMO

BACKGROUND: Frailty in the vascular surgical ward is common and predicts poor surgical outcomes. The aim of this study was to analyze transitions in frailty state in elderly patients after vascular surgery and to evaluate influence of patient characteristics on this transition. METHODS: Between 2014 and 2018, 310 patients, ≥65 years and scheduled for elective vascular surgery, were included in this cohort study. Transition in frailty state between preoperative and follow-up measurement was determined using the Groningen Frailty Indicator (GFI), a validated tool to measure frailty in vascular surgery patients. Frailty is defined as a GFI score ≥4. Patient characteristics leading to a transition in frailty state were analyzed using multivariable Cox regression analysis. RESULTS: Mean age was 72.7 ± 5.2 years, and 74.5% were male. Mean follow-up time was 22.7 ± 9.5 months. At baseline measurement, 79 patients (25.5%) were considered frail. In total, 64 non-frail patients (20.6%) shifted to frail and 29 frail patients (9.4%) to non-frail. Frail patients with a high Charlson Comorbidity Index (HR = 0.329 (CI: 0.133-0.812), p = 0.016) and that underwent a major vascular intervention (HR = 0.365 (CI: 0.154-0.865), p = 0.022) had a significantly higher risk to remain frail after the intervention. CONCLUSIONS: The results of this study, showing that after vascular surgery almost 21% of the non-frail patients become frail, may lead to a more effective shared decision-making process when considering treatment options, by providing more insight in the postoperative frailty course of patients.


Assuntos
Fragilidade , Procedimentos Cirúrgicos Vasculares , Idoso , Idoso de 80 Anos ou mais , Feminino , Idoso Fragilizado , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Procedimentos Cirúrgicos Vasculares/efeitos adversos
19.
Front Psychiatry ; 11: 292, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32411022

RESUMO

Children with reading and/or spelling disorders have increased rates of behavioral and emotional problems and combinations of these. Some studies also find increased rates of attention-deficit/hyperactivity disorder (ADHD), conduct disorder, anxiety disorder, and depression. However, the comorbidities of, e.g., arithmetic disorders with ADHD, anxiety disorder, and depression have been addressed only rarely. The current study explored the probability of children with specific learning disorders (SLD) in reading, spelling, and/or arithmetic to also have anxiety disorder, depression, ADHD, and/or conduct disorder. The sample consisted of 3,014 German children from grades 3 and 4 (mean age 9;9 years) who completed tests assessing reading, spelling as well as arithmetic achievement and intelligence via a web-based application. Psychopathology was assessed using questionnaires filled in by the parents. In children with a SLD we found high rates of anxiety disorder (21%), depression (28%), ADHD (28%), and conduct disorder (22%). Children with SLD in multiple learning domains had a higher risk for psychopathology and had a broader spectrum of psychopathology than children with an isolated SLD. The results highlight the importance of screening for and diagnosing psychiatric comorbidities in children with SLD.

20.
Res Dev Disabil ; 97: 103552, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31884314

RESUMO

BACKGROUND: Previous research results suggest that ADHD symptoms explain the relationship between specific learning disability and externalising psychopathology and between math disability and anxiety, but not between reading disability and anxiety. For depression, previous results are mixed. AIMS: The current study aims to clarify this role of ADHD symptoms in the relationship between various areas of academic achievement (reading, writing, and math skills) and psychopathological symptoms (anxiety, depression, and conduct disorder). METHODS AND PROCEDURES: We used linear regressions based on data from a general population sample (N = 3014) collected using online assessment of 3rd and 4th grade students in Germany, which included measures of academic achievement and parent-reported psychopathological symptoms. OUTCOMES AND RESULTS: ADHD symptoms completely account for the relationship between reading/writing achievement and anxiety and between writing/math achievement and conduct problems. The negative relationship between academic achievement and depression was strongest for children with average or high ADHD symptom scores. CONCLUSIONS AND IMPLICATIONS: ADHD symptoms play an important role in explaining the relationship between academic achievement and psychopathological symptoms in elementary school children. The nature and size of this role depend on the exact constructs under study. We discuss implications for the support of children with learning problems, ADHD, and/or psychopathological problems.


Assuntos
Desempenho Acadêmico , Ansiedade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno da Conduta/psicologia , Depressão/psicologia , Transtorno de Aprendizagem Específico/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Feminino , Humanos , Masculino , Matemática , Leitura , Transtorno de Aprendizagem Específico/psicologia , Redação
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