Transplacental transmission of dengue infection.

We specifically addressed the persistent challenge of dengue in endemic regions, highlighting the potential seriousness of dengue infection through vertical transmission. Vertical dengue transmission has been well documented, particularly in hyper-endemic regions, including Ecuador. Herein, we present a neonate diagnosed with congenital dengue and review similar cases from previously published reports. Although congenital dengue is commonly infected with severe serotypes of DENV (DENV-1 and DENV-2) infections, favorable outcomes are generally observed.

Association between glaucoma susceptibility with combined defects in mitochondrial oxidative phosphorylation and fatty acid beta oxidation.

Glaucoma is one of the leading causes of visual impairment and blindness worldwide, and is characterized by the progressive damage of retinal ganglion cells (RGCs) and the atrophy of the optic nerve head (ONH). The exact cause of RGC loss and optic nerve damage in glaucoma is not fully understood. The high energy demands of these cells imply a higher sensitivity to mitochondrial defects. Moreover, it has been postulated that the optic nerve is vulnerable towards damage from oxidative stress and mitochondrial dysfunction. To investigate this further, we conducted a pooled analysis of mitochondrial variants related to energy production, specifically focusing on oxidative phosphorylation (OXPHOS) and fatty acid ß-oxidation (FAO). Our findings revealed that patients carrying non-synonymous (NS) mitochondrial DNA (mtDNA) variants within the OXPHOS complexes had an almost two-fold increased risk of developing glaucoma. Regarding FAO, our results demonstrated that longer-chain acylcarnitines (AC) tended to decrease, while shorter-chain AC tended to increase in patients with glaucoma. Furthermore, we observed that the knocking down cpt1a (a key rate-limiting enzyme involved in FAO) in zebrafish induced a degenerative process in the optic nerve and RGC, which resembled the characteristics observed in glaucoma. In conclusion, our study provides evidence that genes encoding mitochondrial proteins involved in energy metabolisms, such as OXPHOS and FAO, are associated with glaucoma. These findings contribute to a better understanding of the molecular mechanisms underlying glaucoma pathogenesis and may offer potential targets for therapeutic interventions in the future.

A systematic proteomic profiling and pathway analysis of protein biomarkers in diabetic retinopathy with subsequent validation of the IL-6 upstream regulator.

Purpose: Diabetic retinopathy (DR) is a leading cause of irreversible blindness worldwide. Identifying risk factors associated with DR development and progression is crucial for improving treatment efficacy. Although proteomic changes in DR have been extensively studied, the results remain equivocal. Hence, this study aims to summarize and identify potential diagnostic or prognostic markers for DR. In addition, the upstream regulator responsible for protein deregulation of this disease was also validated. Methods: We systematically analyzed the current literature on proteomic profile changes in DR, followed by pathway analysis identification. To validate the protein level changes, ELISA was performed from serum samples collected from 27 patients with DR and 25 healthy controls. Results: Our analysis revealed that 1 candidate marker (afamin [AFM]) distinguished non-proliferative diabetic retinopathy (NPDR) from type 2 diabetic patients with no diabetic retinopathy/controls, 65 candidate markers distinguished proliferative diabetic retinopathy (PDR) from NPDR, 1 candidate marker (thyroid receptor-interacting protein 11 [TRIP11]) distinguished PDR from PDR-DME/DME, and 3 candidate markers for therapeutic evaluation of PDR. Our results pinpoint that inflammatory response, which IL-6 mainly modulated, is responsible for the changes of proteomic profiles identified in DR. This was also validated by ELISA analysis, indicating that IL-6 could be potentially useful for diagnosing DR. Conclusion: We report a comprehensive patient-based proteomic approach to identify potential biomarkers for DR diagnosis, prognosis, and treatment evaluation. Supplementary information: The online version contains supplementary material available at 10.1007/s40200-023-01204-6.

SF3B4 Frameshift Variants Represented a More Severe Clinical Manifestation in Nager Syndrome.

Nager syndrome (NS) is a rare disease marked with craniofacial and preaxial limb anomalies. In this report, we summarized the current evidence to determine a possible genotype-phenotype association among NS individuals. Twenty-four articles comprising of 84 NS (including 9 patients with a severe form of NS [Rodriguez syndrome]) patients were examined, of which 76% were caused by variants in SF3B4 (OMIM *605593, Splicing Factor 3B, Subunit 4). Within the SF3B4 gene, variants located in exon 3 commonly occurred (20%) from a total identified variant, while hotspot location was identified in exon 1 (12%), and primarily occurred as frameshift variants (64%). Thirty-five distinct pathogenic variants within SF3B4 gene were identified with two common sites, c.1A > G and c.1060dupC in exons 1 and 5, respectively. Although no significant genotype-phenotype association was found, it is notable that patients with frameshift SF3B4 variants and predicted to lead to nonsense-mediated RNA decay (NMD) of the transcripts tended to have a more severe clinical manifestation. Additionally, patients harboring variants in exons 2 and 3 displayed a higher proportion of cardiac malformations. Taken together, this article summarizes the pathogenic variants observed in SF3B4 and provides a possible genotype-phenotype relationship in this disease.

A systematic review on Treacher Collins syndrome: Correlation between molecular genetic findings and clinical severity.

Treacher Collins syndrome (TCS, OMIM: 154500) is a rare congenital craniofacial disorder that is caused by variants in the genes TCOF1, POLR1D, POLR1C, and POLR1B. Studies on the association between phenotypic variability and their relative variants are very limited. This systematic review summarized the 53 literatures from PubMed and Scopus to explore the potential TCS genotype-phenotype correlations with statistical analysis. Studies reporting both complete molecular genetics and clinical data were included. We identified that the molecular anomaly within TCOF1 (88.71%) accounted for most TCS cases. The only true hot spot for TCOF1 was detected in exon 24, with recurrent c.4369_4373delAAGAA variant is identified. While the hot spot for POLR1D, POLR1C, and POLR1B were identified in exons 3, 8, and 15, respectively. Our result suggested that the higher severity level was likely to be observed in Asian patients harboring TCOF1 variants rather than POLR1. Moreover, common 5-bp deletions tended to have a higher severity degree in comparison to any variants within exon 24 of TCOF1. In summary, this report suggested the relationship between genetic and clinical data in TCS. Our findings could be used as a reference for clinical diagnosis and further biological studies.

The Impact of Online vs Blended Clinical Skill Laboratory Learning on Student Academic Performance: A Case Study in Indonesia.

Objective: Online and blended learning methods have experienced rapid growth in higher education due to the COVID-19 pandemic. Our study aimed to compare students' academic performance between online and blended Clinical Skill Laboratories (CSL) learning in undergraduate medical students. Methods: A total of 101 undergraduate medical students at Maulana Malik Ibrahim State Islamic University, Malang, Indonesia, were enrolled (50 students from the academic year 2020 [group 1: online CSL]; 51 students from the academic year 2020 [group 2: blended CSL]). The main outcome was students' academic performance collected from the Objective Structured Clinical Examination (OSCE) score. Additionally, students also completed an evaluation questionnaire to assess the quality of the learning scheme. Results: Both groups agreed that CSL is an important subject and clinical video demonstration is useful for their OSCE preparation. However, students who received online learning felt that online CSL was ineffective and scored lower in the OSCE compared to the blended CSL. Qualitative data also supported these findings. Conclusion: Blended learning provides more value than online learning in terms of teaching clinical skills for undergraduate medical students. Additionally, online CSL may not be sufficient for medical students to attain critical skills.

A Brief Analysis on Clinical Severity of Mandibulofacial Dysostosis Guion-Almeida Type.

OBJECTIVE: Genetic variants in EFTUD2 were proven to influence variable phenotypic expressivity in mandibulofacial dysostosis Guion-Almeida type (MFDGA) or mandibulofacial dysostosis with microcephaly (MFDM). Yet, the association between the severity of clinical findings with variants within the EFTUD2 gene has not been established. Thus, we aim to elucidate a possible genotype-phenotype correlation in MFDM. METHODS: Forty articles comprising 156 patients were evaluated. The genotype-phenotype correlation was analyzed using a chi-square or Fisher's exact test. RESULTS: The proportion of patients with MFDM was higher in Caucasian relative to Asian populations. Although, in general, there was no apparent genotype-phenotype correlation in patients with MFDM, Asians tended to have more severe clinical manifestations than Caucasians. In addition, cardiac abnormality presented in patients with intronic variants located in canonical splice sites was a predisposing factor in affecting MFDM severity. CONCLUSION: Altogether, this article provides the pathogenic variants observed in EFTUD2 and possible genotype-phenotype relationships in this disease.