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Lissencephaly is a neurodevelopmental disorder characterized by a loss of brain surface convolutions caused by genetic variants that disrupt neuronal migration. However, the genetic origins of the disorder remain unidentified in nearly one-fifth of people with lissencephaly. Using whole-exome sequencing, we identified a de novo BAIAP2 variant, p.Arg29Trp, in an individual with lissencephaly with a posterior more severe than anterior (P>A) gradient, implicating BAIAP2 as a potential lissencephaly gene. Spatial transcriptome analysis in the developing mouse cortex revealed that Baiap2 is expressed in the cortical plate and intermediate zone in an anterior low to posterior high gradient. We next used in utero electroporation to explore the effects of the Baiap2 variant in the developing mouse cortex. We found that Baiap2 knockdown caused abnormalities in neuronal migration, morphogenesis and differentiation. Expression of the p.Arg29Trp variant failed to rescue the migration defect, suggesting a loss-of-function effect. Mechanistically, the variant interfered with the ability of BAIAP2 to localize to the cell membrane. These results suggest that the functions of BAIAP2 in the cytoskeleton, cell morphogenesis and migration are important for cortical development and for the pathogenesis of lissencephaly in humans.
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Lisencefalia , Animais , Humanos , Camundongos , Encéfalo/metabolismo , Movimento Celular/genética , Citoesqueleto/metabolismo , Lisencefalia/genética , Lisencefalia/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismoRESUMO
Naja atra, the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated N. atra venom. Following confirmation of the immune response in the alpaca, we amplified VHH genes from isolated peripheral blood mononuclear cells and constructed a phage display VHH library of 1.0 × 107 transformants. After four rounds of biopanning, the enriched phages exhibited increased binding activity to N. atra venom. Four nanobody clones with high binding affinities were selected: aNAH1, aNAH6, aNAH7, and aNAH9. Specificity testing against venom from various snake species, including two Southeast Asian cobra species, revealed nanobodies specific to the genus Naja. An in vivo mouse venom neutralization assay demonstrated that all nanobodies prolonged mouse survival and aNAH6 protected 66.6% of the mice from the lethal dosage. These findings highlight the potential of phage display-derived nanobodies as valuable antidotes for N. atra venom, laying the groundwork for future applications in snakebite treatment.IMPORTANCEChinese cobra venom bites present a formidable medical challenge, and current serum treatments face unresolved issues. Our research applied microbial phage display technology to obtain a new, effective, and cost-efficient treatment approach. Despite interest among scientists in utilizing this technology to screen alpaca antibodies against toxins, the available literature is limited. This study makes a significant contribution by introducing neutralizing antibodies that are specifically tailored to Chinese cobra venom. We provide a comprehensive and unbiased account of the antibody construction process, accompanied by thorough testing of various nanobodies and an assessment of cross-reactivity with diverse snake venoms. These nanobodies represent a promising avenue for targeted antivenom development that bridges microbiology and biotechnology to address critical health needs.
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Antivenenos , Camelídeos Americanos , Venenos Elapídicos , Anticorpos de Domínio Único , Mordeduras de Serpentes , Animais , Anticorpos de Domínio Único/imunologia , Camundongos , Mordeduras de Serpentes/terapia , Mordeduras de Serpentes/imunologia , Antivenenos/imunologia , Venenos Elapídicos/imunologia , Técnicas de Visualização da Superfície Celular , Naja naja , Biblioteca de PeptídeosRESUMO
Reactive oxygen species (ROS) play a crucial role in regulating numerous functions in organisms. Among the key regulators of ROS production are NADPH oxidases, primarily referred to as respiratory burst oxidase homologues (RBOHs). However, our understanding of whether and how pathogens directly target RBOHs has been limited. In this study, we revealed that the effector protein RipBJ, originating from the phytopathogenic bacterium Ralstonia solanacearum, was present in low- to medium-virulence strains but absent in high-virulence strains. Functional genetic assays demonstrated that the expression of ripBJ led to a reduction in bacterial infection. In the plant, RipBJ expression triggered plant cell death and the accumulation of H2O2, while also enhancing host defence against R. solanacearum by modulating multiple defence signalling pathways. Through protein interaction and functional studies, we demonstrated that RipBJ was associated with the plant's plasma membrane and interacted with the tomato RBOH known as SlWfi1, which contributed positively to RipBJ's effects on plants. Importantly, SlWfi1 expression was induced during the early stages following R. solanacearum infection and played a key role in defence against this bacterium. This research uncovers the plant RBOH as an interacting target of a pathogen's effector, providing valuable insights into the mechanisms of plant defence.
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OBJECTIVES: Few reports have indicated the secular trend in the sudden cardiac death (SCD) incidence and pre-arrest comorbidities. This study aimed to comprehensively analyze the trend of SCD incidence and its association with pre-arrest comorbidities. METHODS: This population-based cohort study analyzed Taiwan's National Health Insurance (NHI) research database and identified SCD incidents by inspecting data from all emergency department visits from 2011 to 2018. The inclusion criteria were ICD-9:427.5 or 427.41, or ICD-10:I46.9, I46.8, or I46.2. Pre-existing comorbidities were confirmed based on medication use. Multivariable logistic regression was adopted with covariates age, sex, and pre-existing comorbidities. RESULTS: This study reviewed a total of 184,164,969 person-year records, and identified 92,138 SCD incidents. From 2011 to 2018, the SCD incidence rate increased from 36.3 to 55.4 per 100,000 enrollees in Taiwan. The top five pre-arrest comorbidities were stable, while the prevalence of chronic kidney disease rose significantly. Compared to those aged 20-29, enrollees aged >65 years had significantly higher odds of SCD (aOR:27.30, 95% CI:26.05-28.61). Higher odds of SCD were noted in the enrollees who had a seizure (aOR:2.24, 95% CI:2.12-2.38), parkinsonism (aOR:1.81, 95% CI:1.73-1.89), psychological disorders (aOR:1.59, 95% CI:1.56-1.62), diabetes mellitus (aOR:1.44, 95% CI:1.41-1.46), heart diseases (aOR:1.41, 95% CI:1.38-1.44). CONCLUSIONS: The incidence of SCD steadily increased in Taiwan from 2011 to 2018. Hypertension, diabetes mellitus, heart disease, psychological disorders, and arthritis were major pre-arrest comorbidities. Age is the most important risk factor for SCD. Further large-scaled population-based study that investigated in diverse ethnicities from countries in addition to Asians would be warranted.
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The hematophagous insect Mepraia spinolai (Hemiptera: Reduviidae: Triatominae) is naturally infected with the protozoan parasite Trypanosoma cruzi, the agent of Chagas disease in humans. In this study, we compared the demographic parameters of M. spinolai with and without T. cruzi infection. We collected the immature life table data of 479 M. spinolai individuals of control cohort (reared on mice without T. cruzi infection) and 563 M. spinolai individuals of treatment cohort (reared on mice with T. cruzi infection). Nymphs were maintained in individual compartments inside a growth chamber (26°C; 65-75%) until adult emergence; moulting and survival were recorded daily. For the adult life table study of the control, we used 24 pairs of adults from the control cohort. For the adult life table study of T. cruzi-infected cohort, 25 infected females were paired with 25 males from the control cohort. Life table data were analysed using bootstrap-match technique based on the age-stage, two-sex life table. The preadult survival rate (0.5282) of the control cohort was significantly higher than that of the infected cohort (0.2913). However, the mean fecundity of reproductive females (Fr = 22.29 eggs/â) and net reproductive rate of population (R0 = 5.07 offspring/individual) of the 0.5th percentile bootstrap-match control cohort were not significantly different from those of the infected cohort (Fr = 23.35 eggs/â, R0 = 3.77 offspring/individual). Due to the shorter total preoviposition period and higher proportion of reproductive female, the intrinsic rate of increase (r = 0.0053 d-1 ) and finite rate of increase (λ = 1.0053 d-1 ) of control cohort of M. spinolai were significantly higher than those of the T. cruzi-infected cohort (r = 0.0035 d-1 , λ = 1.0035 d-1 ). These results suggest that T. cruzi infection reduces the population fitness of the Chagas disease vector M. spinolai.
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Doença de Chagas , Doenças dos Roedores , Triatominae , Trypanosoma cruzi , Humanos , Masculino , Feminino , Animais , Camundongos , Aptidão Genética , Insetos Vetores/parasitologia , Doença de Chagas/veterinária , Triatominae/parasitologiaRESUMO
BACKGROUND: Entrustable Professional Activities (EPA)-based assessment is easily and intuitively used in evaluating the learning outcomes of competency-based medical education (CBME). This study aimed to develop an EPA for occupational therapy focused on providing health education and consultation (TP-EPA3) and examine its validity. METHODS: Nineteen occupational therapists who had completed online training on the EQual rubric evaluation participated in this study. An expert committee identified six core EPAs for pediatric occupational therapy. TP-EPA3 was developed following the EPA template and refined through consensus meetings. The EQual rubric, a 14-item, five-point criterion-based anchor system, encompassing discrete units of work (DU), entrustable, essential, and important tasks of the profession (EEIT), and curricular role (CR), was used to evaluate the quality of TP-EPA3. Overall scores below 4.07, or scores for DU, EEIT, and CR domains below 4.17. 4.00, and 4.00, respectively, indicate the need for modifications. RESULTS: The TP-EPA3 demonstrated good validity, surpassing the required cut-off score with an average overall EQual score of 4.21 (SD = 0.41). Specific domain scores for DU, EEIT, and CR were 3.90 (SD = 0.69), 4.46 (SD = 0.44), and 4.42 (SD = 0.45), respectively. Subsequent revisions clarified observation contexts, enhancing specificity and focus. Further validation of the revised TP-EPA3 and a thorough examination of its reliability and validity are needed. CONCLUSION: The successful validation of TP-EPA3 suggests its potential as a valid assessment tool in occupational therapy education, offering a structured approach for developing competency in providing health education and consultation. This process model for EPA development and validation can guide occupational therapists in creating tailored EPAs for diverse specialties and settings.
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Competência Clínica , Educação Baseada em Competências , Terapia Ocupacional , Humanos , Terapia Ocupacional/educação , Competência Clínica/normas , Reprodutibilidade dos Testes , Avaliação Educacional , Educação em Saúde , Encaminhamento e Consulta/normas , Currículo , Masculino , FemininoRESUMO
BACKGROUND: Computed tomography (CT) is frequently performed in the patients who admitted to the emergency department (ED), discharged but returned to ED within 72 h. It is unknown whether the main complaints of patients assist physicians to use CT effectively. This study aimed to find the association between chief complaints and the CT results. METHODS: This three-year retrospective cohort study was conducted in the ED of a tertiary medical center. Adult patients who returned to the ED after the index visit were included from 2019 to 2021. Demographics, pre-existing diseases, chief complaints, and CT region were recorded by independent ED physicians. A logistic regression model with an odds ratio (OR) and 95% confidence interval (CI) was used to determine the relationship between chief complaints and positive CT results. RESULTS: In total, 7,699 patients revisited ED after the index visit; 1,202 (15.6%) received CT. The top chief complaints in patients who received CT were abdominal pain, dizziness, and muscle weakness. Patients with abdominal pain or gastrointestinal symptoms had a significantly higher rate of positive abdominopelvic CT than those without it (OR 2.83, 95% CI 1.98-4.05, p < 0.001), while the central nervous system and cardiopulmonary chief complaints were not associated (or negatively associated) with new positive CT findings. CONCLUSION: Chief complaints of patients on revisit to the ED are associated with different yields of new findings when CT scans of the chest, abdomen and head are performed. Physicians should consider these differential likelihoods of new positive findings based on these data.
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Dor Abdominal , Serviço Hospitalar de Emergência , Tomografia Computadorizada por Raios X , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Dor Abdominal/diagnóstico por imagem , Dor Abdominal/etiologia , Idoso , Tontura , Gastroenteropatias/diagnóstico por imagemRESUMO
Among genetically engineered mouse models of breast cancer, MMTV-PyVT is a mouse strain in which the oncogenic polyoma virus middle T antigen is driven by the mouse mammary tumor virus promoter. The aim of the present study was to perform morphologic and genetic analyses of mammary tumors arising from MMTV-PyVT mice. To this end, mammary tumors were obtained at 6, 9, 12, and 16 weeks of age for histology and whole-mount analyses. We conducted whole-exome sequencing to identify constitutional and tumor-specific mutations, and genetic variants were identified using the GRCm38/mm10 mouse reference genome. Using hematoxylin and eosin analysis and whole-mount carmine alum staining, we demonstrated the progressive proliferation and invasion of mammary tumors. Frameshift insertions/deletions (indels) were noted in the Muc4. Mammary tumors showed small indels and nonsynonymous single-nucleotide variants but no somatic structural alterations or copy number variations. In summary, we validated MMTV-PyVT transgenic mice as a multistage model for mammary carcinoma development and progression. Our characterization may be used as a reference for guidance in future research.
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BACKGROUND: The increased frequency of heavy rains in recent years has led to submergence stress in rice paddies, severely affecting rice production. Submergence causes not only hypoxic stress from excess water in the surrounding environment but also osmotic stress in plant cells. We assessed physiological responses and Ethylene-Response AP2/ERF Factor regulation under submergence conditions alone and with ionic or nonionic osmotic stress in submergence-sensitive IR64 and submergence-tolerant IR64-Sub1 Indica rice cultivars. RESULTS: Our results indicate that both IR64 and IR64-Sub1 exhibited shorter plant heights and root lengths under submergence with nonionic osmotic stress than normal condition and submergence alone. IR64-Sub1 seedlings exhibited a significantly lower plant height under submergence conditions alone and with ionic or nonionic osmotic stress than IR64 cultivars. IR64-Sub1 seedlings also presented lower malondialdehyde (MDA) concentration and higher survival rates than did IR64 seedlings after submergence with ionic or nonionic osmotic stress treatment. Sub1A-1 affects reactive oxygen species (ROS) accumulation and antioxidant enzyme activity in rice. The results also show that hypoxia-inducible ethylene response factors (ERF)-VII group and alcohol dehydrogenase 1 (ADH1) and lactate dehydrogenase 1 (LDH1) genes exhibited different expression levels under nonionic or ionic osmotic stress during submergence on rice. CONCLUSIONS: Together, these results demonstrate that complex regulatory mechanisms are involved in responses to the aforementioned forms of stress and offer new insights into the effects of submergence and osmotic stress on rice.
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Oryza , Estresse Fisiológico , Etilenos , Regulação da Expressão Gênica de Plantas , Oryza/fisiologia , Pressão Osmótica , Álcool Desidrogenase/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
BACKGROUND: Data about changes in the characteristics of ED return visits before and after the COVID-19 outbreak are limited. This study aimed to report the differences on utility in ED return visits after the COVID-19 outbreak. METHODS: This retrospective cohort study was conducted from 2019 to 2020. Adult patients with ED return visits were included in the analysis. Variables including demographic characteristics, pre-comorbidities, triage levels, vital signs, chief complaints, management, and diagnosis were recorded and confirmed via a manual assessment. RESULTS: The proportion of patients with ED visits decreased by 23%. Hence, that of patients with ED return visits also reduced from 2580 to 2020 patients (22%) after the COVID-19 outbreak. The average age (60-57.8 years) of patients with return visits was significantly younger, and the proportion of female patients decreased remarkably. Further, the proportion of patients with chronic pre-existing diseases at the return visit significantly differed after the COVID-19 outbreak. The proportion of patients with chief complaints including dizziness, dyspnea, cough, vomiting, diarrhea, and chills during the return visits significantly differed before and after the COVID-19 pandemic. In the multivariable logistic regression model, age, high triage level were significantly associated with unfavorable outcome return visit. CONCLUSION: The use of services in the ED has changed since the COVID-19 outbreak. Hence, the proportion of patients with unplanned return visits within 72 h decreased. After the COVID-19 outbreak, people are now cautious whether they should return to the ED, as in the pre-pandemic situation, or just treat conservatively at home.
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COVID-19 , Humanos , Adulto , Feminino , COVID-19/epidemiologia , Readmissão do Paciente , Estudos Retrospectivos , Pandemias , Serviço Hospitalar de Emergência , Surtos de DoençasRESUMO
BACKGROUND: Water pollution due to uncontrolled release of chemical pollutants is an important global problem. Its effect on medically important insects, especially mosquitoes, is a critical issue in the epidemiology of mosquito-borne diseases. METHODS: In order to understand the effect of water pollutants on the demography of Anopheles stephensi, colonies were reared in clean, moderately and highly polluted water for three consecutive generations at 27 °C, 75% RH, and a photoperiod of 12:12 h (L:D). The demographic data of the 4th generation of An. stephensi were collected and analysed using the age-stage, two-sex life table. RESULTS: The intrinsic rate of increase (r), finite rate of increase (λ), mean fecundity (F) and net reproductive rate (R0) of An. stephensi in clean water were 0.2568 d-1, 1.2927 d-1, 251.72 eggs, and 109.08 offspring, respectively. These values were significantly higher than those obtained in moderately polluted water (r = 0.2302 d-1, λ = 1.2589 d-1, 196.04 eggs, and R0 = 65.35 offspring) and highly polluted water (r = 0.2282 d-1, λ = 1.2564 d-1, 182.45 eggs, and R0 = 62.03 offspring). Female adult longevity in moderately polluted (9.38 days) and highly polluted water (9.88 days) were significantly shorter than those reared in clean water (12.43 days), while no significant difference in the male adult longevity was observed among treatments. CONCLUSIONS: The results of this study showed that An. stephensi can partially adapt to water pollution and this may be sufficient to extend the range of mosquito-borne diseases.
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Anopheles , Doenças Transmissíveis , Malária , Poluentes da Água , Adaptação Psicológica , Animais , Feminino , Tábuas de Vida , Masculino , Mosquitos Vetores , Poluentes da Água/farmacologia , Qualidade da ÁguaRESUMO
Children's everyday learning environment is semantically structured. For example, semantically related things (e.g., fork and spoon) usually co-occur in the same contexts. The current study examines the effects of semantically structured contexts on preschool-age children's (N = 65, 33 girls, age range: 52-68 months) use of statistical information to learn novel word-object mappings. Children were assigned into one of two conditions, in which objects from the same semantic category repeatedly co-occurred in the same trials (Same-category condition) or objects from different categories repeatedly co-occurred in the same trials (Different-categories condition). Children's word learning performance in the two conditions were comparable. However, their errors at test suggested that information extracted by children in the two conditions differed. Importantly, children in the Same-category condition extracted both statistical and semantic relationships from the stimuli.
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Aprendizagem , Aprendizagem Verbal , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Extratos Vegetais , Instituições Acadêmicas , SemânticaRESUMO
A healthy and safe public health environment is a fundamental responsibility of government; achieving it requires collaboration across multiple sectors. Public health services include, for example, vaccination and quarantine for infectious diseases; health promotion, such as anti-smoking campaigns for noncommunicable diseases; and health insurance for universal health coverage. All these services require intersectoral actions in which the government must play a fundamental role, either partially or totally. The Taiwanese outlook on governmental public health infrastructure and professionalization of public health is given in this paper. It also describes the national governmental public health measures that were employed during the Covid-19 pandemic and discusses the challenges ahead for the country's governmental public health. Governmental public health is essential and should not be affected by changes in political forms or socioeconomic development. Instead, effective governmental public health will promote these developments while protecting citizens' right to health.
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COVID-19 , Saúde Pública , Humanos , Taiwan , Pandemias , GovernoRESUMO
BACKGROUND: Mycoplasma pneumoniae is a pathogen that causes respiratory diseases in children. Infections caused by M. pneumoniae are usually self-limited but occasionally can be severe. We observed emerging cases of severe mycoplasma infection requiring extracorporeal membrane oxygenation (ECMO). Thus, we investigated chronological changes in the molecular features of the M. pneumoniae and its clinical impacts among the pediatric population. METHODS: From 2011 to 2019, respiratory samples were collected from patients younger than 18 years old with pneumonia in a tertiary children's hospital. Focused multiple-locus variable number of tandem repeats analysis (MLVA) typing was performed on samples positive for M. pneumoniae in 2016 and 2019. Clinical data from the patients' electronic medical records were collected. We described the annual trend of macrolide resistance and MLVA type and analyzed the associations between clinical manifestations and MLVA types. RESULTS: The percentage of macrolide-resistant (MLR) M. pneumoniae gradually increased from 22% (27/122) in 2015 to 70% (82/117) in 2019. Among the MLRM. pneumoniae, the predominant strain shifted from type P (31% [13/42]) to type A (40% [19/46]). The demographics, initial presentations, and clinical courses of the subjects with MLRM. pneumoniae did not differ significantly between 2011 and 2019. However, in 2019, two fulminant cases requiring venovenous ECMO were observed, which indicates that more attention to the clinical severity of MLRM. pneumoniae infections is warranted. CONCLUSION: Obtaining accurate information on macrolide susceptibility is crucial for physicians to initiate appropriate antibiotic treatment in a timely fashion. Although we could not identify significant differences among mycoplasma pneumonias caused by different MLVAs over a span of 9 years, the emergence of severe mycoplasma infections requiring ECMO was clinically significant, and further monitoring was required.
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Pneumonia por Mycoplasma , Adolescente , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Farmacorresistência Bacteriana , Humanos , Macrolídeos/uso terapêutico , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/epidemiologia , TaiwanRESUMO
BACKGROUND/PURPOSE: Acute gastroenteritis (AGE) remains a significant health issue in children. The worldwide evolution of pediatric AGE pathogens had been recorded since the introduction of rotavirus vaccine. Ten years after the rotavirus vaccine was introduced to the private sectors in Taiwan, a nationwide study was conducted to elucidate the epidemiological changes among major AGE pathogens. METHODS: From January 2014 to December 2017, children younger than 5 years old, hospitalized with AGE at 10 hospitals across Taiwan were enrolled. Stool specimens were tested for Salmonella spp., Campylobacter spp., Clostridiodes difficile, norovirus, and rotavirus by polymerase chain reaction (PCR). The epidemiological and clinical information was collected. RESULTS: Enteric pathogen were detected in 1983 (42.2%) of 4700 subjects, with Salmonella spp. (12.5%) being the leading cause of AGE, followed by norovirus (11.2%), rotavirus (8.7%), C. difficile (4.2%), Campylobacter spp. (1.0%), and a mixture of at least 2 of 5 above-mentioned pathogens (4.6%). The case distributions varied across different regions. In eastern Taiwan, rotavirus (21/131, 16.0%) remained the most common pathogen detected. The rotavirus vaccine uptake rate is significantly lower in patients with rotavirus AGE. Besides, rotavirus AGE frequently occurred in children with foreign parent(s), Taiwanese indigenous people, and those with the household monthly income < NT$ 60,000. CONCLUSION: Salmonella spp. and norovirus were two major pathogens of pediatric AGE in Taiwan during 2014-17. Providing low-to middle-income households with free rotavirus vaccine nationwide and an industry-led act to reduce salmonellosis should be considered by the authorities.
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Clostridioides difficile , Gastroenterite , Infecções por Rotavirus , Rotavirus , Criança , Pré-Escolar , Fezes , Gastroenterite/epidemiologia , Humanos , Lactente , Infecções por Rotavirus/epidemiologia , Taiwan/epidemiologiaRESUMO
The COVID-19 pandemic has evolved to immune escape and threatened small children and the elderly with a higher severity and fatality of non-pulmonary diseases. These life-threatening non-pulmonary COVID-19 diseases such as acute necrotizing encephalopathies (ANE) and multisystem inflammatory syndrome in children (MIS-C) are more prevalent in children. However, the mortality of multisystem inflammatory syndrome in adults (MIS-A) is much higher than that of MIS-C although the incidence of MIS-A is lower. Clarification of immunopathogenesis and genetic susceptibility of inflammatory non-pulmonary COVID-19 diseases would provide an appropriate guide for the crisis management and prevention of morbidity and fatality in the ongoing pandemic. This review article described three inflammatory non-pulmonary COVID-19 diseases including (1) meningoencephalitis (ME), (2) acute necrotizing encephalopathies (ANE), and (3) post-infectious multisystem inflammatory syndrome in children (MIS-C) and in adults (MIS-A). To prevent these life-threatening non-pulmonary COVID-19 diseases, hosts carrying susceptible genetic variants should receive prophylactic vaccines, avoid febrile respiratory tract infection, and institute immunomodulators and mitochondrial cocktails as early as possible.
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Encefalopatias , COVID-19 , Adulto , Criança , Idoso , Humanos , PandemiasRESUMO
Enterovirus 71 (EV71) is the major etiological agent contributing to the development of hand-foot-mouth disease (HFMD). There are not any global available vaccines or antibody drugs against EV71 released yet. In this study, we perform the virus immunization in a cost-effective and convenient approach by preparing virus particles from size exclusion and immunization of chicken. Polyclonal yolk-immunoglobulin (IgY) was simply purified from egg yolk and monoclonal single-chain variable fragments (scFv) were selected via phage display technology with two scFv libraries containing 6.0 × 106 and 1.3 × 107 transformants. Specific clones were enriched after 5 rounds of bio-panning and four identical genes were classified after the sequence analysis. Moreover, the higher mutation rates were revealed in the CDR regions, especially in the CDR3. IgY showed specific binding activities to both EV71-infected and Coxsackievirus 16-infected cell lysates and high infectivity inhibitory activity of EV71. However, while IgY detected a 37 kDa protein, the selected scFv seemingly detected higher size proteins which could be cell protein instead of EV71 proteins. Despite the highly effective chicken antibody generation, the purity of virus particles prepared by size exclusion is the limitation of this study, and further characterization should be carried out rigorously.
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Enterovirus Humano A , Enterovirus , Doença de Mão, Pé e Boca , Anticorpos de Cadeia Única , Animais , Vírion/genética , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/metabolismo , Gema de Ovo , GalinhasRESUMO
IMPORTANCE: The Objective Structured Clinical Examination (OSCE) is a highly valued measure of students' clinical competencies in medical education. However, few studies have reported on the administration of the OSCE in pediatric occupational therapy education. OBJECTIVE: To describe the development of a pediatric occupational therapy OSCE station to evaluate students' use of a standardized assessment and examine its standard setting, failure rates, and psychometric properties. DESIGN: Prospective, cross-sectional, observational study design. SETTING: Three OSCE stations in a university clinical skills center. PARTICIPANTS: Five experienced occupational therapists, 60 examinees, 44 child standardized patients, 44 chaperones, and 15 examiners. MEASURES: The sum of the rating scale and the global performance scores were used. The rating scale measured the examinee's clinical competences in administering a standardized assessment. The 5-point global performance score was used to evaluate the examinee's whole performance. RESULTS: The OCSE station's expert validity was acceptable (item-level content validity index [CVI] = 0.8-1.0; scale-level CVI = 0.98). Passing scores according to the Angoff method (passing score = 14) and the contrasting-groups M-SD method (passing score = 13) were similar. Failure rates were high (61.7%-73.3%). Internal consistency was acceptable (Cronbach's α = .78). No significant examiner effect was found (p = .554), and interexaminer reliability was acceptable (item score = 0.58-1.00; sum of the rating scale score = 0.97; global performance score = 0.79). CONCLUSIONS AND RELEVANCE: The OSCE station for using a standardized assessment is a reliable and valid measure of students' interpersonal communication skills and assessment skills. What This Article Adds: The OSCE for education in pediatric occupational therapy is both effective and rigorous.
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Terapia Ocupacional , Criança , Competência Clínica , Estudos Transversais , Avaliação Educacional , Humanos , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
IMPORTANCE: The Mini-Clinical Evaluation Exercise (Mini-CEX) is highly recommended for assessing interns' performance. OBJECTIVE: To develop a pediatric occupational therapy-specific Mini-CEX and examine its psychometrics. DESIGN: Stage 1 had a retrospective design; Stage 2 had a prospective design. SETTING: Pediatric occupational therapy unit in a hospital in Taiwan. PARTICIPANTS: Thirty-four occupational therapy interns were evaluated with the Mini-CEX (physician version), and 57 were evaluated with the occupational therapy-specific Mini-CEX. OUTCOMES AND MEASURES: The occupational therapy-specific Mini-CEX was developed with seven items on a 9-point scale categorized into three levels (unsatisfactory, satisfactory, highly satisfactory). RESULTS: In Stage 1, the frequency of Mini-CEX (physician version) items receiving a rating of not applicable ranged from 1.9% to 88.1%. In Stage 2, the frequency of occupational therapy-specific Mini-CEX items receiving a rating of not applicable ranged from 3.5% to 31.6%. With the theme of evaluation taken into consideration, the frequency of not-applicable ratings was 0% to 8.8%. For the occupational therapy-specific Mini-CEX, content validity (item-level content validity index = 1, scale-level content validity index = 1) and internal consistency (Cronbach's α = .93) were excellent. The interns' scores on the second evaluation were significantly higher than those on their first evaluation, indicating good discriminant validity. CONCLUSIONS AND RELEVANCE: The occupational therapy-specific Mini-CEX appears to be reliable and valid, and it is appropriate for evaluating interns' skills and attitudes in pediatric occupational therapy practice. What This Article Adds: The results support the development of the occupational therapy-specific Mini-CEX and its application in pediatric internship training.
Assuntos
Internato e Residência , Terapia Ocupacional , Criança , Competência Clínica , Avaliação Educacional , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: In 2016 in Taiwan, inoculation with the Bacillus Calmette-Guérin (BCG) Tokyo-172 vaccine was postponed from 24 hours after birth to 5-8 months of age. We reviewed BCG-induced adverse reactions reported to the Vaccine Injury Compensation Program (VICP) to identify differences between early and delayed BCG inoculation. METHODS: Clinical presentations of BCG-related adverse reactions reported to VICP for the 2012-2017 birth cohort were reviewed until the end of 2019. The correlations between inoculation age and complications were evaluated. RESULTS: We analyzed 233 BCG adverse reactions, including regional lymphadenitis (33.9%), injection site reactions (35.2%), osteitis/osteomyelitis (27.9%), and distant soft tissue infections (3.0%). The incidence of osteitis/osteomyelitis was lower when vaccination was done after 5 months of age (relative risk [RR], 0.32; 95% confidence interval [CI], .16-.64). Injection site reactions (RR, 8.82; 95% CI, 5.04-15.44) and lymphadenitis (RR, 2.24; 95% CI, 1.44-3.45) were significantly more common in vaccinees older than 5 months. Shorter onset durations of mild adverse reactions (lymphadenitis and injection site reactions) were reported in vaccinees older than 5 months, while no statistical significance was found regarding osteitis/osteomyelitis. CONCLUSIONS: Osteomyelitis and distant soft tissue infection may occur less frequently when BCG inoculation occurs after 5 months of age, although mild adverse reactions can be more frequent, symptom onset times can be shortened. As few severe reactions might occur more than 2 years after BCG inoculation and the policy of delayed BCG inoculation was implemented in 2016, a longer observational period is needed to clarify the exact severe complications decrement.