Developing an entrustable professional activity for providing health education and consultation in occupational therapy and examining its validity.

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.

Negative Regulatory Role of the Spring Viremia of Carp Virus Matrix Protein in the Host Interferon Response by Targeting the MAVS/TRAF3 Signaling Axis.

Spring viremia of carp virus (SVCV) is a severe infectious pathogen that causes high rates of mortality in cyprinids and other fish species. Despite numerous investigations of SVCV infection, the underlying molecular mechanisms remain poorly understood. In this study, we found that the SVCV matrix protein (SVCV-M) played an inhibitory role in the host interferon (IFN) response by targeting the MAVS/TRAF3 signaling axis, thereby uncovering a previously unrecognized mechanism of SVCV escape from host innate antiviral immunity. Mechanistically, SVCV-M was located at the mitochondria independent of MAVS, which allowed SVCV-M to build an arena for competition with the MAVS platform. A microscale thermophoresis assay showed that SVCV-M had a high affinity for TRAF3, as indicated by a lower equilibrium dissociation constant (KD) value than that of MAVS with TRAF3. Therefore, the association of MAVS with TRAF3 was competitively impaired by SVCV-M in a dose-dependent manner. Accordingly, SVCV-M showed a potent ability to inhibit the K63-linked polyubiquitination of TRAF3. This inhibition was accompanied by the impairment of the IFN response, as shown by the marked decline in IFN-φ1-promoter (pro) luciferase reporter activity. By constructing truncated TRAF3 and SVCV-M proteins, the RING finger, zinc finger, and coiled-coil domains of TRAF3 and the hydrophobic-pocket-like structure formed by the α2-, α3-, and α4-helices of SVCV-M may be the major target and antagonistic modules responsible for the protein-protein interaction between the TRAF3 and SVCV-M proteins. These findings highlighted the intervention of SVCV-M in host innate immunity, thereby providing new insights into the extensive participation of viral matrix proteins in multiple biological activities. IMPORTANCE The matrix protein of SVCV (SVCV-M) is an indispensable structural element for nucleocapsid condensation and virion formation during viral morphogenesis, and it connects the core nucleocapsid particle to the outer membrane within the mature virus. Previous studies have emphasized the architectural role of SVCV-M in viral construction; however, the potential nonstructural functions of SVCV-M in viral replication and virus-host interactions remain poorly understood. In this study, we identified the inhibitory role of the SVCV-M protein in host IFN production by competitively recruiting TRAF3 from the MAVS signaling complex and impairing TRAF3 activation via inhibition of K63-linked polyubiquitination. This finding provided new insights into the regulatory role of SVCV-M in host innate immunity, which highlighted the broader functionality of rhabdovirus matrix protein apart from being a structural protein. This study also revealed a previously unrecognized mechanism underlying SVCV immune evasion by inhibiting the IFN response by targeting the MAVS/TRAF3 signaling axis.

Novel stop-gain RNF170 variation detected in a Chinese family with adolescent-onset hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited neurodegenerative disease characterized by progressive lower limb spasticity. Recent studies revealed that biallelic variants in RNF170 gene cause autosomal recessive complicated HSP with infancy onset. Here, we report an adolescent-onset HSP patient from a consanguineous Chinese family, with lower extremity stiffness, spastic gait, and unstable straight-line walking as the main manifestations. Whole-exome sequencing identifies a novel RNF170 mutation c.190C>T (p.R64*), which co-segregates with the disease in this pedigree. Functional analysis, including quantitative real-time PCR (RT-qPCR) and Western blot, indicates that both the mRNA and protein levels of mutant RNF170 are significantly reduced, which confirms the loss-of-function mechanism. Our study expands the spectrum of RNF170-associated HSP, while the RNF170 protein-involved degradation of the inositol 1,4,5-trisphosphate receptor in neurodegenerative motor neuron disorders deserves further investigation.

Features Differ Between Paroxysmal Kinesigenic Dyskinesia Patients with PRRT2 and TMEM151A Variants.

BACKGROUND: Mutations in proline-rich transmembrane protein 2 (PRRT2) are the major cause of paroxysmal kinesigenic dyskinesia (PKD). We recently reported transmembrane protein 151A (TMEM151A) mutations caused PKD. Herein, we aimed to conduct phenotypic comparisons of patients with PKD carrying PRRT2 variants, carrying TMEM151A variants, and carrying neither the PRRT2 nor TMEM151A variant. METHODS: Sanger sequencing of PRRT2 and TMEM151A was performed, and phenotypic characteristics were analyzed. RESULTS: In a cohort of 131 PKD probands (108 without PRRT2 variants and 23 newly recruited), five novel TMEM151A variants were identified and one (c.647C > A) occurred de novo. Together with our previous studies, PRRT2 and TMEM151A variants accounted for 34.7% (85/245) and 6.9% (17/245) of PKD probands, respectively. Compared with patients carrying PRRT2 variants, those with TMEM151A variants tended to exbibit dystonia with shorter durations, have no history of benign infantile epilepsy, and have residual attacks/aura when treated with carbamazepine/oxcarbazepine. CONCLUSIONS: Patients with TMEM151A variants have different features from patients with PRRT2 variants. © 2022 International Parkinson and Movement Disorder Society.

Psychometric Properties of the Little Developmental Coordination Disorder Questionnaire-Taiwan.

IMPORTANCE: Early identification of young children at risk of developmental coordination disorder (DCD) can support early intervention and prevent secondary sequelae. OBJECTIVE: To examine the psychometric properties of a translated and cross-culturally adapted version of the Little Developmental Coordination Disorder Questionnaire-Taiwan (LDCDQ-TW). DESIGN: Prospective study. SETTING: Kindergartens and preschools in north, central, and south Taiwan. PARTICIPANTS: In Phase 1 the participants were 1,124 parents of typically developing children ages 36-71 mo. Children with confirmed developmental diagnoses were excluded. Participants in Phase 3 were 162 children who had been recruited in Phase 2. Outcomes and Measures: The LDCDQ-TW, a 15-item parent questionnaire for identifying children at risk for DCD, and the Movement Assessment Battery for Children (2nd ed.; MABC-2), were administered. RESULTS: The findings revealed excellent test-retest reliability (intraclass correlation coefficient [ICC] = .97) and poor interrater reliability (ICC = .47). On the basis of MABC-2 scores, the non-DCD group (≥15th percentile) scored significantly higher than the DCD and suspect-DCD groups on the LDCDQ-TW, but the latter two groups did not differ from one another. Using the 15th percentile as a cutoff for both the MABC-2 and the LDCDQ-TW, sensitivity was .96 and specificity was .68. CONCLUSIONS AND RELEVANCE: Although standardized performance-based assessments are required to confirm a diagnosis of DCD (typically after age 5 yr), the LDCDQ-TW demonstrated sound reliability and validity and can support the early identification of young children at risk of DCD in Taiwan. What This Article Adds: The LDCDQ-TW can facilitate early intervention for DCD and prevent secondary sequelae, improving outcomes for children with DCD.

Developing the Occupational Therapy-Specific Mini-Clinical Evaluation Exercise (Mini-CEX) for Evaluating Interns' Clinical Skills and Attitudes in Pediatric Occupational Therapy.

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.

[Application of extracorporeal membrane oxygenation in the treatment of persistent pulmonary hypertension of the newborn]. / 体外膜肺氧合技术在持续肺动脉高压新生儿救治中的临床应用.

OBJECTIVES: To study the clinical value of extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). METHODS: A retrospective analysis was performed on the medical data of 11 neonates with PPHN who were treated with ECMO in the Neonatal Intensive Care Unit of Zhongshan People's Hospital from January 2015 to December 2021, involving the neonates' general information, clinical diagnosis, laboratory results, duration of ECMO treatment, complications during ECMO treatment, length of hospital stay, and outcome. RESULTS: Of the 11 neonates, 10 (91%) had successful weaning from ECMO, and 8 (73%) survived. For the 11 neonates, the mean duration of ECMO treatment was (81±50) hours (range: 26 to 185 hours), the mean duration of ventilator use was (198±105) hours (range: 57 to 392 hours), and the mean length of hospital stay was (22±15) days (range: 2 to 49 days). The oxygenation index and blood lactate level were significantly improved after 24 hours of ECMO treatment among the 11 neonates (P<0.05). Ten neonates had significantly reduced pulmonary artery pressure after 24 hours of ECMO treatment (P<0.05). One neonate had a progressive increase in the pulmonary artery pressure during EMCO treatment, succumbing to death. This neonate was diagnosed with alveolar capillary dysplasia based on the histopathological findings of the lung tissue and whole-exome sequencing results. Among the 11 children, 5 had intracranial hemorrhage, 1 had disseminated intravascular coagulation, 1 had gastric hemorrhage, 2 had pulmonary hemorrhage, 1 had renal insufficiency, and 3 had bleeding at the puncture site during ECMO treatment. CONCLUSIONS: ECMO is effective for the treatment of PPHN, however, the high incidence of complications of ECMO treatment suggests that it is important to carefully assess the indications and timing of ECMO treatment and improve the management of ECMO, which can improve the weaning rate and survival rate.

Current state of technologies and recognition of anti-SSA/Ro antibodies in China: A multi-center study.

BACKGROUND: Previous studies have demonstrated that Ro60 and Ro52 have different clinical implications, and anti-Ro52 antibodies are an independent serum marker of systemic autoimmune diseases, including Sjögren's syndrome. Many different assays have been adopted to detect anti-Sjögren's syndrome antigen A (SSA)/Ro antibodies, while to date no specific approach has been recommended as optimal for anti-SSA/Ro antibody testing. Herein, we performed a multi-center study to explore the current clinical utility of different strategies for anti-SSA/Ro antibody testing in China. METHODS: Twenty-one tertiary care centers were included in this questionnaire-based study. The self-administered questionnaire mainly includes testing methods for anti-SSA/Ro antibodies, reporting system of results, and interpretation of results by clinicians. RESULTS: Six different methods were applied to detect anti-SSA/Ro antibodies in the 21 centers. Line immunoassay (eight different commercial kits) was the most frequently adopted method (21/21, 100%), with different cutoff values and strategies for intensity stratification. There were two reporting systems: One was reported as "anti-SSA antibodies" and "anti-Ro52 antibodies" (12/21, 57%), while the other was "anti-SSA/Ro60 antibodies" and "anti-SSA/Ro52 antibodies" (9/21, 43%). Notably, six centers (29%) considered either positive anti-Ro60 or anti-Ro52 antibodies as positive anti-SSA antibodies, all of which adopted the latter reporting system. CONCLUSION: Significant variabilities existed among anti-SSA/Ro assays. Nearly 30% of centers misinterpreted the definition of positive anti-SSA antibodies, which may be attributed to the confusing reporting systems of line immunoassay. Therefore, we advocate standardization of the nomenclature of anti-SSA/Ro antibodies, changing the "anti-SSA/Ro52" label in favor of the "anti-Ro52" antibodies for a clear designation.

[Application value of whole exome sequencing in critically ill neonates with inherited diseases].

OBJECTIVE: To study the application value of whole exome sequencing (WES) in critically ill neonates with inherited diseases. METHODS: A total of 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis who were admitted to the neonatal intensive care unit were enrolled as subjects. The clinical data of the neonates were collected, and venous blood samples were collected from the neonates and their parents for WES. The clinical manifestations of the neonates were observed to search for related pathogenic gene mutations. RESULTS: Among the 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis (34 boys and 32 girls), 14 (21%) were found to have gene mutations by WES. One neonate had no gene mutation detected by WES but was highly suspected of pigment incontinence based on clinical manifestations, and multiplex ligation-dependent probe amplification detected a heterozygous deletion mutation in exons 4-10 of the IKBKG gene. Among the 15 neonates with gene mutations, 10 (67%) had pathogenic gene mutation, 1 (7%) was suspected of pathogenic gene mutation, and 4 (27%) had gene mutations with unknown significance. Among the 15 neonates, 13 underwent chromosome examination, and only 1 neonate was found to have chromosome abnormality. CONCLUSIONS: Chromosome examination cannot be used as a diagnostic method for inherited diseases, and WES detection technology is an important tool to find inherited diseases in critically ill neonates with suspected inherited diseases or unclear clinical diagnosis; however WES technology has some limitation and it is thus necessary to combine with other sequencing methods to achieve an early diagnosis.

[mRNA expression of MDR3 gene in the blood of preterm infants with parenteral nutrition-associated cholestasis].

OBJECTIVE: To study the association between the expression of the MDR3 gene and the pathogenesis of parenteral nutrition-associated cholestasis (PNAC) in preterm infants. METHODS: Among the preterm infants who were admitted to the hospital from June 2011 to November 2017 and received parenteral nutrition for more than 14 days, 80 who did not develop PNAC were enrolled as non-PNAC group, and 76 who developed PNAC were enrolled as PNAC group. On days 1, 14, 30, 60 and 90 after birth, serum hepatobiliary biochemical parameters [alanine aminotransferase (ALT), total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA) and gamma-glutamyl transpeptidase (γ-GT)], fibrosis indices [hyaluronic acid, laminin, procollagen III N-terminal peptide and type IV collagen] and clinical manifestations were observed. Real-time quantitative PCR was used to measure the mRNA expression of MDR3 in both groups, and the correlation between the mRNA expression of MDR3 and serum hepatobiliary biochemical parameters was analyzed. RESULTS: In the PNAC group, serum levels of hepatobiliary biochemical parameters and fibrosis indices increased on day 14 after birth and reached the peak on day 30 after birth, followed by a reduction on day 60 after birth. On days 14, 30, 60 and 90 after birth, the PNAC group had significantly higher serum levels of hepatobiliary biochemical parameters and fibrosis indices than the non-PNAC group (P<0.05). The PNAC group had higher relative mRNA expression of MDR3 in peripheral blood cells than the non-PNAC group (P<0.05). In the PNAC group, the relative mRNA expression of MDR3 in peripheral blood cells was negatively correlated with serum levels of hepatobiliary biochemical parameters (ALT, TBil, DBil, TBA and γ-GT) (P<0.001). CONCLUSIONS: High mRNA expression of MDR3 in preterm infants may be associated with the development of PNAC, and further studies are needed to identify the mechanism.

A Novel Hypothesis on Excessive Activation of Residual B Lymphocytes in Common Variable Immunodeficiency Concurrent with Aseptic, Erosive Polyarthritis.

The aim of this study was to report aseptic, erosive polyarthritis in a patient with common variable immunodeficiency (CVID), which is quite different from the vastly more common nonerosive form. Peripheral blood mononuclear cells of the patient were isolated. Flow cytometry was used to analyze the proportion and function of lymphocytes. A Parker-Pearson needle biopsy was performed on the right knee. Four of her unaffected family members were enrolled as controls. A 21-year-old woman was admitted for recurrent polyarthritis of 3-year duration. The right knee, hip, wrist, proximal interphalangeal joints, and left elbow were involved, with progressive joint destruction. She was diagnosed as having CVID based on her recurrent infections, poor response to vaccines, and marked hypogammaglobulinemia. No bacterium or mycobacterium was detected in synovium or synovial fluid. The synovium was infiltrated by lymphocytes rather than neutrophils. Polyarthritis did not resolve by adequate intravenous immunoglobulin substitution and empirical antibiotic treatment, but resolved gradually after treatment with methylprednisolone and tacrolimus, supporting the diagnosis of aseptic polyarthritis. Further analyses showed that although only 0.5% of residual B lymphocytes were existent in peripheral blood of the patient, expressions of activation marker CD69 and production of IL-1ß, IL-6, and TNF-α were high. Marked infiltration with CD19+B lymphocytes (as well as CD4+ or CD8+ T lymphocytes) was detected in the synovium. The proportion of IL21+CD4+Th cells from peripheral blood of the patient was high. CD4+ Th cells from the patient secreted nearly 3 times more IL-21 than the same cell type analyzed from unaffected family members, perhaps due to excessive compensation to assist the function of residual B lymphocytes. A novel hypothesis in CVID concurrent with aseptic, erosive polyarthritis is that excessive activation of residual B lymphocytes infiltrate into the synovium of the involved joints and lead to polyarthritis and joint destruction.

Patients with Coexistence of Circulating Hepatitis B Surface Antigen and Its Antibody May Have a Strong Predisposition to Virus Reactivation During Immunosuppressive Therapy: A Hypothesis.

Hepatitis B virus (HBV) reactivation is a well-recognized complication in patients who undergo immunosuppressive drug therapy. Although the recommendation of antiviral prophylaxis made by the American Gastroenterological Association in 2015 focuses on the risk stratification of different immunosuppressive drugs, risk factors for HBV reactivation are also worth identifying in clinical practice. Recent studies have shown that the uncommon serological pattern of coexistent circulating HBV surface antigen (HBsAg) and its antibody (anti-HBs) was associated with double mutations (A1762T/G1764A) in the basal core promoter (BCP) region of the HBV genome, which is critical for HBV replication. Here, we depicted rheumatoid arthritis (RA) patients with coexistent HBsAg and anti-HBs in our medical center, who developed HBV reactivation during immunosuppressive drug therapy. DNA sequencing analysis of the HBV genome revealed triple mutations (A1762T, G1764A, and T1753V) in the BCP region, which could further enhance the ability of HBV replication. Hence, a novel hypothesis is advanced for the first time that patients with coexistent HBsAg and anti-HBs may have a strong predisposition to HBV reactivation due to specific BCP mutations. This hypothesis would, if correct, justify the concurrent detection of HBsAg and anti-HBs in HBV screening in patients with rheumatic diseases and quickly recognize patients with high risk of HBV reactivation. Further controlled studies are needed to confirm this hypothesis.

Using children as standardized patients in OSCE in pediatric occupational therapy.

BACKGROUND: Objective structured clinical examinations (OSCEs) have been administered in physical and psychiatric occupational therapy (OT) education, but not in pediatric OT education. The objectives were to examine the satisfaction and the influences of OSCE in pediatric OT on all participants. METHODS: The OSCE contained evaluation, intervention, and parent education stations. Sixty examinees, 44 child standardized patients (SPs), 44 chaperones, three playroom managers, 14 OSCE assistants, and 15 examiners participated in the OSCE. An OSCE video and three playrooms were prepared for child SPs. RESULTS: Ninety percent of the child SPs liked taking part in the OSCE and 75-85% expressed interest in participating in an OSCE the following year. Their parents appreciated the chaperones accompanying their children and giving them a memorable day. 88.3% of the examinees thought that the OSCE was helpful for their upcoming clinical training. 73.3% preferred the OSCE over the written exam. 60-93.4% considered the implementation appropriate. Most of the examiners thought that the content (80-100%) and the implementation (93.3-100%) were appropriate. Many chaperones reported having valuable experiences. CONCLUSIONS: It is practical using child SPs in OSCE in pediatric OT. The OSCE was beneficial to all participants. It is recommended that OSCEs be included in pediatric OT education.

Three cassava A20/AN1 family genes, Metip3 (5, and 7), can bestow on tolerance of plants to multiple abiotic stresses but show functional convergence and divergence.

A20/AN1 zinc-finger domain-containing genes are very promising candidates in improving plant tolerance to abiotic stresses, but considerably less is known about functions and mechanisms for many of them. In this study, Metip3 (5, and 7), cassava (Manihot esculenta) A20/AN1 genes carrying one A20 domain and one AN1 domain, were functionally characterized at different layers. Metip3 (5, and 7) proteins were all located in the nucleus. No interactions were found between these three proteins. Metip3 (5, and 7)-expressing Arabidopsis was more tolerant to multiple abiotic stresses by Na, Cd, Mn, Al, drought, high temperature, and low temperature. Metip3- and Metip5-expressing Arabidopsis was sensitive to Cu stress, while Metip7-expressing Arabidopsis was insensitive. The H2O2 production significantly decreased in all transgenic Arabidopsis, however, O2·- production significantly decreased in Metip3- and Metip5-expressing Arabidopsis but did not significantly changed in Metip7-expressing Arabidopsis under drought. Metip3 (5, and 7) expression-silenced cassava showed the decreased tolerance to drought and NaCl, presented significant decreases in superoxide dismutase and catalase activities and proline content, and displayed a significant increase in malondialdehyde content under drought. Taken together with transcriptome sequencing analysis, it is suggested that Metip5 gene can not only affect signal transduction related to plant hormone, mitogen activated protein kinases, and starch and sucrose metabolism, DRE-binding transcription factors, and antioxidants, conferring the drought tolerance, but also might deliver the signals from DREB2A INTERACTING PROTEIN1, E3 ubiquitin-protein ligases to proteasome, leading to the drought intolerance. The results are informative not only for further study on evolution of A20/AN1 genes but also for development of climate resilient crops.

Both gain- and loss-of-function variants of KCNA1 are associated with paroxysmal kinesigenic dyskinesia.

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channel α subunit. Three variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia (PKD), but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD cases. Using the whole exome sequencing followed by Sanger sequencing, we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese families. The proband of one family (c.496G>A, p.A166T) manifests as episodic ataxia type 1, and the other two (c.877G>A, p.V293I and c.1112C>A, p.T371A) manifest as PKD. The pathogenicity of these variants is confirmed by functional studies, suggesting that p.A166T and p.T371A cause a loss-of-function of the channel, while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic affected. By reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein, we find that these variants tend to cluster around the pore domain, which is similar to epilepsy. Thus, our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype-phenotype correlations of KCNA1 channelopathy.

[Spectrum of pathogens for community-acquired pneumonia in children].

OBJECTIVE: To investigate the spectrum of pathogens for community-acquired pneumonia (CAP) in children, and to provide a basis for the diagnosis and treatment of CAP. METHODS: Respiratory secretions and venous blood samples were collected from 1560 children with CAP aged from one month to 9 years within 2 hours after admission, for detection of multiple pathogens. Respiratory virus antigens in nasopharyngeal swab specimens were detected by immunofluorescence. Sputum was used for bacterial culture. Levels of Mycoplasma pneumoniae (MP)-IgM and Chlamydia pneumoniae (CP)-IgM in venous blood were measured by enzyme-linked immunosorbent assay. RESULTS: A total of 579 strains of bacteria were isolated from all respiratory secretions, including 213 (36.8%) Gram-positive strains and 366 (63.2%) Gram-negative strains. The five most common strains were Haemophilus influenzae (7.50%), Streptococcus pneumoniae (6.73%), Staphylococcus aureus (6.35%), Moraxella catarrhalis (5.19%), and Escherichia coli (3.46%), wherein the beta-lactamase-producing strains accounted for 3.3% of all strains. The non-bacterial pathogens mainly included respiratory syncytial virus (12.88%), MP (7.88%), and CP (8.91%). Mixed infection of pathogens was serious, and the mixed infection of respiratory syncytial virus with Haemophilus influenzae infections were the most common. For most pathogens, the infection rate was higher in children aged under one year than in those aged over one year. CONCLUSIONS: Haemophilus influenzae, respiratory syncytial virus, MP and CP are the main pathogens for children with CAP. For most pathogens, the infection rate is higher in children aged under one year than in those aged over one year. Mixed infection rate of pathogens is high.

Scurvy in a young man: a rare case report.

Scurvy, resulting from vitamin C deficiency, has nonspecific constitutional symptoms, including weakness, malaise, and fatigue. It is frequently misdiagnosed due to the lack of specific clinical manifestations. Although there are sporadic cases of scurvy currently reported in children, scurvy in young people is seldom encountered. Here, we report on a 25-year-old male patient without any underlying conditions who presented with severe pain and ecchymoses of both lower extremities. He was diagnosed with scurvy due to a long history of staying indoors and inadequate intake of fruits or vegetables.

Clinical significance of anti-rheumatoid arthritis 33 antibody in patients with systemic lupus erythematosus.

Although anti-rheumatoid arthritis (RA) 33 antibodies have been reported to be present in various connective tissue diseases (CTDs), the clinical significance of anti-RA33 in CTDs is still obscure. This study was performed to explore the clinical significance of anti-RA33 in CTDs, especially systemic lupus erythematosus (SLE). A total of 565 patients with positive anti-nuclear antibodies who had been tested for anti-RA33 were included in this study and were further classified into RA33-positive and RA33-negative groups. The association between anti-RA33 and the clinical features of CTDs was examined. Receiver operating characteristic (ROC) analysis was performed to explore the diagnostic value of anti-RA33 in SLE and SLE-related organ involvement. The results showed that SLE was the most common disease in CTD patients positive for anti-RA33 (48.8%). Compared with the RA33-negative group, higher proportions of SLE-associated antibodies and SLE patients with a high disease activity as well as lower levels of serum complement components were observed in the RA33-positive group (all p < 0.05). Furthermore, CTD patients with positive anti-RA33 were more likely to suffer from mucocutaneous and hematological involvement as well as interstitial lung disease (all p < 0.05). ROC analysis revealed an area under the curve value of 0.634 (95% confidence interval: 0.587-0.681) for anti-RA33 in the diagnosis of SLE, with a specificity and sensitivity of 92.9% and 13.5%, respectively. Taken together, this study reveals a significant association between anti-RA33 and the clinical features of CTDs, especially SLE, indicating a potential clinical significance of anti-RA33 in the management of SLE.

MeGATAs, functional generalists in interactions between cassava growth and development, and abiotic stresses.

The proteins with DNA-binding preference to the consensus DNA sequence (A/T) GATA (A/G) belong to a GATA transcription factor family, with a wide array of biological processes in plants. Cassava (Manihot esculenta) is an important food crop with high production of starch in storage roots. Little was however known about cassava GATA domain-containing genes (MeGATAs). Thirty-six MeGATAs, MeGATA1 to MeGATA36, were found in this study. Some MeGATAs showed a collinear relationship with orthologous genes of Arabidopsis, poplar and potato, rice, maize and sorghum. Eight MeGATA-encoded proteins (MeGATAs) analysed were all localized in the nucleus. Some MeGATAs had potentials of binding ligands and/or enzyme activity. One pair of tandem-duplicated MeGATA17-MeGATA18 and 30 pairs of whole genome-duplicated MeGATAs were found. Fourteen MeGATAs showed low or no expression in the tissues. Nine analysed MeGATAs showed expression responses to abiotic stresses and exogenous phytohormones. Three groups of MeGATA protein interactions were found. Fifty-three miRNAs which can target 18 MeGATAs were identified. Eight MeGATAs were found to target other 292 cassava genes, which were directed to radial pattern formation and phyllome development by gene ontology enrichment, and autophagy by Kyoto Encyclopaedia of Genes and Genomes enrichment. These data suggest that MeGATAs are functional generalists in interactions between cassava growth and development, abiotic stresses and starch metabolism.

Clinical characteristics, susceptibility profiles, and treatment of nocardiosis: a multicenter retrospective study in 2015-2021.

OBJECTIVES: This study aimed to investigate the microbiological characteristics, antimicrobial resistance profiles, antibiotic choice, and outcomes of Nocardia infection in various centers over a 7-year period (from 2015 to 2021). METHODS: We retrospectively analyzed the medical records of all hospitalized patients diagnosed with Nocardia between 2015 and 2021. The isolates were identified to the species level through the sequencing of 16S ribosomal RNA or secA1 or ropB genes. The susceptibility profiles were determined using the broth microdilution method. RESULTS: Of the 130 nocardiosis cases, 99 (76.2%) were established as pulmonary infection, of which the most common underlying disease was chronic lung disease (40.4%, 40/99), including bronchiectasis, chronic obstructive pulmonary disease, and chronic bronchitis. Among 130 isolates, 12 species were identified, with the most common species being Nocardia cyriacigeorgica (37.7%) and Nocardia farcinica (20.8%). All Nocardia strains were susceptible to linezolid and amikacin, and the susceptibility rate of trimethoprim-sulfamethoxazole (TMP-SMX) was 97.7%. Of the 130 patients, 86 (66.2%) received TMP-SMX monotherapy or multidrug regimen. Furthermore, 92.3% patients who were treated achieved clinical improvement. CONCLUSION: TMP-SMX was the treatment of choice for nocardiosis, and other combination drugs with TMP-SMX therapy yielded even better results.