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The mosquito-borne alphavirus o’nyong-nyong virus (ONNV) has proven its potential to cause major human outbreaks. On the African continent, ONNV causes unspecific febrile illness and co-circulates with the close relative chikungunya virus (CHIKV). The true scale of ONNV burden is poorly understood in Africa, because of the scarce availability of molecular in-house and commercial assays, strong cross-reactivity between ONNV and CHIKV in serological assays and a lack of surveillance. We designed a new RT-qPCR assay targeting the E1 gene for the detection of ONNV that can be used in monoplex or in duplex format, combined with a previously published CHIKV monoplex assay targeting the nsp1. The lower limit of detection with 95% positivity rate was determined to be

Abstract Parkinson’s disease (PD) is a debilitating neurodegenerative disease characterized by the loss of midbrain dopaminergic neurons (DaNs) and the abnormal accumulation of α-Synuclein (α-Syn) protein. Currently, no treatment can slow nor halt the progression of PD. Multiplications and mutations of the α-Syn gene (SNCA) cause PD-associated syndromes and animal models that overexpress α-Syn replicate several features of PD. Decreasing total α-Syn levels, therefore, is an attractive approach to slow down neurodegeneration in patients with synucleinopathy. We previously performed a genetic screen for modifiers of α-Syn levels and identified CDK14, a kinase of largely unknown function as a regulator of α-Syn. To test the potential therapeutic effects of CDK14 reduction in PD, we ablated Cdk14 in the α-Syn preformed fibrils (PFF)-induced PD mouse model. We found that loss of Cdk14 mitigates the grip strength deficit of PFF-treated mice and ameliorates PFF-induced cortical α-Syn pathology, indicated by reduced numbers of pS129 α-Syn-containing cells. In primary neurons, we found that Cdk14 depletion protects against the propagation of toxic α-Syn species. We further validated these findings on pS129 α-Syn levels in PD patient neurons. Finally, we leveraged the recent discovery of a covalent inhibitor of CDK14 to determine whether this target is pharmacologically tractable in vitro and in vivo. We found that CDK14 inhibition decreases total and pathologically aggregated α-Syn in human neurons, in PFF-challenged rat neurons and in the brains of α-Syn-humanized mice. In summary, we suggest that CDK14 represents a novel therapeutic target for PD-associated synucleinopathy.

Probiotic bacteria are a recognized alternative to classical methods of disease prophylaxis and therapy. We tested the effects of their application on the immune reaction in juvenile turbot. To prevent digestion of the probiotics, rectal administration was applied to maximise colonization, by-passing digestion in the stomach. The application of Psychrobacter nivimaris and Psychrobacter faecalis showed beneficial effects on the inflammatory response and disease resistance after infection with the common pathogen Tenacibaculum maritimum. Treatment with P. nivimaris and P. faecalis resulted in 0% and 8% mortalities post-infection, while in the treatment control, an elevated mortality of 20% was observed. In the challenge controls (no infection), no mortalities were observed during the entire experimental period. After an experimental infection, mRNA expression of selected immune markers (mhc II α, il-1β, tcr, tgf β and tnf α) were determined by RT-QPCR at 0, 1 and 5 days post-infection (dpi). At 0 dpi, gene expression was comparable between the treatments and the treatment control, suggesting that probiotics did not act via immune stimulation of the host. At 1 dpi, all genes were up-regulated in the treatment control but not in the probiotic groups, indicating that the infection in probiotic-treated fish developed at a less severe level. At 5 dpi, mRNA expression returned to baseline levels. As a conclusion, the native probiotic candidates P. nivimaris and P. faecalis improved survival, whereas, in the control, mortality increased and expression of the immune markers was up-regulated post infection. This highlights a potential application of P. nivimaris and P. faecalis in disease prophylaxis, but further research is needed.

This study aims to identify the epidemiology and effects of facial fractures on return to play (RTP) in Major League Soccer (MLS) and the English Premier League (EPL). A total of 39 MLS players and 40 EPL players who sustained facial fractures from 2007 to 2019 were identified. Data on player demographics, the injury, and the impact of their injury on RTP were collected. Elbow-to-head was the most common mechanism of injury (20.3%). The most common fracture involved the nasal bone (48.3%). Most players (90%) RTP the same season. Players who sustained nasal fractures missed significantly fewer games (p

Degeneration of dopaminergic neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinson's disease. In idiopathic cases, high levels of mitochondrial DNA alterations, leading to mitochondrial dysfunction, are a central feature of these vulnerable neurons. Here we present a mouse model expressing the K320E variant of the mitochondrial helicase Twinkle in dopaminergic neurons, leading to accelerated mitochondrial DNA mutations. These K320E-TwinkleDaN mice showed normal motor function at 20 months of age, although ∼70% of nigral dopaminergic neurons had perished. Remaining neurons still preserved ∼75% of axon terminals in the dorsal striatum and enabled normal dopamine release. Transcriptome analysis and viral tracing confirmed compensatory axonal sprouting of the surviving neurons. We conclude that a small population of substantia nigra dopaminergic neurons is able to adapt to the accumulation of mitochondrial DNA mutations and maintain motor control. [ABSTRACT FROM AUTHOR]

The Quality of Life Assessment in Spina bifida for Teenagers (QUALAS-T) is a tool used to evaluate health-related quality of life (HRQOL) in adolescents with spina bifida (SB). The purpose of this study was to translate the QUALAS-T into Korean and validate its Korean version (QUALAS-T-K). Translation and validation processes were carried out in accordance with a specified protocol, including forward and back translation, a content validity study, and a main study. The tool's reliability was evaluated based on its internal consistency and stability. Factor analysis was conducted, and convergent validity was confirmed using the KIDSCREEN-27. Of the 59 participants, 35 had lipomyelomeningoceles. Confirmatory factor analysis confirmed that QUALAS-T-K had the same structure as QUALAS-T. The QUALAS-T-K showed excellent internal consistency (α: 0.872–0.893, ω: 0.875–0.885), test–retest reliability (ICC:0.84–0.92), and weak to strong correlations with the KIDSCREEN-27. The QUALAS-T-K, developed by reflecting on the characteristics of SB and considering the applicability of Korean cultural characteristics and clinical practice, is a convenient and reliable tool with excellent internal consistency and stability. This could be a useful tool in clinical and research settings for HRQOL evaluation of adolescents with SB. Optimizing health-related quality of life (HRQOL) is one of the goals of individuals with spina bifida (SB), and HRQOL measures that reflect the condition specificity of SB should be performed. The QUAlity of Life Assessment in Spina bifida for Teenagers (QUALAS-T), developed in the USA, is a self-reported HRQOL questionnaire used in research and clinical practice for adolescents with SB. This study revealed that the QUALAS-T, translated into Korean, is a valid, convenient, and reliable tool. The Korean version of the QUALAS-T is a useful tool that can be used in clinical and research settings to optimize HRQOL in adolescents with SB. [ABSTRACT FROM AUTHOR]

This study aimed to translate and cross-culturally adapt the QUAlity of Life Assessment in Spina bifida for Children (QUALAS-C) and validate the Korean version of the QUALAS-C (QUALAS-C-K). Three urologists translated the QUALAS-C into Korean. Facial and content validity were assessed in the pilot study. Back-translation into English was performed. In the main study, the QUALAS-C-K and Korean version of KIDSCREEN-27 were administered simultaneously. Test-retest reliability was confirmed by re-administering the QUALAS-C-K. Internal consistency was verified using Cronbach's alpha. Factor analysis was performed, and convergent and divergent validity were demonstrated using the Korean version of KIDSCREEN-27. A total of 53 children with spina bifida participated in the main study. Cronbach's alpha for the overall instrument determined good internal consistency (0.72–0.85), the intraclass correlation coefficient showed good stability (0.74–0.77), and the factor analysis converged to the same two-factor structure as in the original version. Construct validity revealed weak-to-moderate associations (r ≤ 0.57) between QUALAS-C-K and K-KIDSCREEN-27, indicating that QUALAS-C-K measures different aspects of the HRQOL than K-KIDSCEEN-27. The QUALAS-C-K is a reliable and valid instrument for assessing the health-related quality of life of children with SB in Korea. Health-related quality of life (HRQOL) is an important patient-reported outcome among children with spina bifida (SB). The QUAlity of Life Assessment of Spina bifida for Children (QUALAS-C) is a self-reported, age-appropriate, and condition-specific HRQOL questionnaire for children with SB, developed in the United States. Our study demonstrated that the Korean version of the QUAlity of Life Assessment of Spina bifida for Children (QUALAS-C-K) is a valid and reliable tool. The QUALAS-C-K is a succinct and valuable questionnaire that can be used to assess HRQOL of children with SB, particularly focusing on bladder and bowel problems in clinical practice and research. [ABSTRACT FROM AUTHOR]