Extended high-frequency hearing loss among Afro-Colombian adolescents from a rural area in Colombia: a cross-sectional study.

OBJECTIVES: Research trends concerning hearing loss within teen rural populations are limited and current evidence suggests that extended high-frequency audiometry can be a sensitive tool to detect subclinical hearing loss. Moreover, current research emphasises the importance of representing different ethnic populations in science. This study aimed to determine the prevalence of acquired hearing loss through conventional pure-tone (0.25-8 kHz) and extended high frequency (EHF) (9-20 kHz) audiometry in Afro-Colombian adolescents from a rural area in Colombia. DESIGN: Observational, cross-sectional study. PARTICIPANTS: 230 Afro-Colombian adolescents aged 13-17 years who attended high school in a rural population from Cartagena, Colombia. INTERVENTIONS: Otoscopic examination, conventional (0.25-8 kHz) and EHF (9-20 kHz) audiometry tests were performed during February-March 2021. Sociodemographic and associated factor questionnaires were also applied to assess probable factors associated with EHF hearing loss. MAIN OUTCOME MEASURES: Prevalence of acquired hearing loss using conventional and EHF audiometry, and factors associated with hearing loss. RESULTS: Of 230 adolescents who met the eligibility criteria, 133 (57.82%) were female. The mean age was 15.22 years (SD: 1.62). The prevalence of hearing loss in at least one ear assessed with conventional audiometry was 21.30% and with EHF audiometry 14.78%. The main abnormal otoscopic findings included: neotympanum (1.30%), myringosclerosis (0.87%) and monomeric scars (0.43%). Factors associated with a higher probability of EHF hearing loss found through logistic regression were older age (prevalence ratio (PR): 1.45; 95% CI 1.16 to 1.80), attending the 'Picó' four or more times a month (PR: 6.63; 95% CI 2.16 to 20.30), attending bars more than three times a month (PR: 1.14; 95% CI 1.03 to 1.59) and self-reported hearing difficulties (PR: 1.24; 95% CI 1.22 to 4.05). CONCLUSIONS: Our results suggest that acquired hearing loss is already widespread among this young rural population.

Refining the phenotype of SINO syndrome: A comprehensive cohort report of 14 novel cases.

BACKGROUND: SINO syndrome (Spastic paraplegia, Intellectual disability, Nystagmus and Obesity) is a rare autosomal dominant condition caused by heterozygous variants in KIDINS220. A total of 12 individuals are reported, comprising eight with SINO and four with an autosomal recessive condition attributed to bi-allelic KIDINS220 variants. METHODS: In our international cohort, we have comprised 14 individuals, carrying 13 novel pathogenic KIDINS220 variants in heterozygous form. We assessed clinical and molecular data of our cohort and previously reported individuals and based on functional experiments reached a better understanding of the pathogenesis behind KIDINS220-related disease. RESULTS: Using fetal tissue and in vitro assays, we demonstrate that the variants generate KIDINS220 truncated forms that mislocalize in punctate intracellular structures, with decreased levels of the full-length protein, suggesting a trans-dominant negative effect. 92% had their diagnosis within three years, with symptoms of developmental delay, spasticity, hypotonia, lack of eye contact and nystagmus. We identified a KIDINS220 variant associated with fetal hydrocephalus and show that 58% of examined individuals present brain ventricular dilatation. We extend the phenotypic spectrum of SINO syndrome to behavioral manifestations not previously highlighted. CONCLUSION: Our study provides further insights into the clinical spectrum, etiology and predicted functional impact of KIDINS220 variants.

Evaluating the Usability and Safety of Virtual Reality Application Combined with the SWalker for Functional Gait Rehabilitation.

Objective: This research evaluates from a usability point of view the combination of a developed fully immersive virtual reality (VR) solution with the SWalker robotic device. It aims to contribute to research in the exploration of immersive experiences overground with a functional gait recovery device. Materials and Methods: We evaluated the system in a pilot study with 20 healthy participants aged 85.1 (SD: 6.29). Participants used the SWalker-VR platform while testing one VR application focused on walking and the other on balance practice. Afterward, the participants answered three usability questionnaires. Results: The platform was validated in terms of safety using the Simulator Sickness Questionnaire, obtaining less than 20 points for all subscales: nausea (4.29 ± 14.47), oculomotor (0.38 ± 14.18), and disorientation (1.39 ± 14.52). For usability evaluation, the System Usability Scale provided an overall score of 70.63 ± 11.64, and the Post-Study System Usability Questionnaire (PSSUQ) rated 1.61 ± 0.54. The usability scores reported by both questionnaires were moderate and good, respectively. These results were similar in overall scores for both groups: participants with low cognitive level and participants with high cognitive level. Finally, the possible causes for the "no answered" responses on the PSSUQ were discussed. Conclusion: It is concluded that the SWalker-VR platform is reported to have adequate usability and high security by older adults. The potential interest of studying the effects of the long-term use of this platform by older adults with gait impairment is expressed. Clinical Trials reference: NCT06025981.

eIF2α phosphorylation evokes dystonia-like movements with D2-receptor and cholinergic origin and abnormal neuronal connectivity.

Dystonia is the 3rd most common movement disorder. Dystonia is acquired through either injury or genetic mutations, with poorly understood molecular and cellular mechanisms. Eukaryotic initiation factor alpha (eIF2α) controls cell state including neuronal plasticity via protein translation control and expression of ATF4. Dysregulated eIF2α phosphorylation (eIF2α-P) occurs in dystonia patients and models including DYT1, but the consequences are unknown. We increased/decreased eIF2α-P and tested motor control and neuronal properties in a Drosophila model. Bidirectionally altering eIF2α-P produced dystonia-like abnormal posturing and dyskinetic movements in flies. These movements were also observed with expression of the DYT1 risk allele. We identified cholinergic and D2-receptor neuroanatomical origins of these dyskinetic movements caused by genetic manipulations to dystonia molecular candidates eIF2α-P, ATF4, or DYT1, with evidence for decreased cholinergic release. In vivo, increased and decreased eIF2α-P increase synaptic connectivity at the NMJ with increased terminal size and bouton synaptic release sites. Long-term treatment of elevated eIF2α-P with ISRIB restored adult longevity, but not performance in a motor assay. Disrupted eIF2α-P signaling may alter neuronal connectivity, change synaptic release, and drive motor circuit changes in dystonia.

Mosquito Microbiomes of Rwanda: Characterizing Mosquito Host and Microbial Communities in the Land of a Thousand Hills.

Mosquitoes are a complex nuisance around the world and tropical countries bear the brunt of the burden of mosquito-borne diseases. Rwanda has had success in reducing malaria and some arboviral diseases over the last few years, but still faces challenges to elimination. By building our understanding of in situ mosquito communities in Rwanda at a disturbed, human-occupied site and at a natural, preserved site, we can build our understanding of natural mosquito microbiomes toward the goal of implementing novel microbial control methods. Here, we examined the composition of collected mosquitoes and their microbiomes at two diverse sites using Cytochrome c Oxidase I sequencing and 16S V4 high-throughput sequencing. The majority (36 of 40 species) of mosquitoes captured and characterized in this study are the first-known record of their species for Rwanda but have been characterized in other nations in East Africa. We found significant differences among mosquito genera and among species, but not between mosquito sexes or catch method. Bacteria of interest for arbovirus control, Asaia, Serratia, and Wolbachia, were found in abundance at both sites and varied greatly by species.

Exposure to environmental pollutants and genetic variants related to oxidative stress and xenobiotic metabolism-Association with prostate cancer.

This study assessed whether genetic variants coding for certain enzymes involved in xenobiotic detoxification, antioxidant defences and DNA repair, along with exposure to environmental chemicals, were associated with an increased prostate cancer (PCa) risk. The study population consisted of 300 men (150 PCa cases and 150 controls) which underwent prostate biopsy as their serum prostate specific antigen (PSA) levels were greater than 4 ng/ml. Genetic variants in GSTM1, GSTP1, SOD2, CAT, GPX1, XRCC1 were determined and data for chemical exposures was obtained through a structured questionnaire and by biomonitoring in a subsample of cases and controls. High serum PSA levels were associated with a greater risk of PCa, while physical exercise appears to exert a protective effect against its development. In addition, elevated urinary levels of certain organic pollutants, such as benzo(a)pyrene (BaP), bisphenol A (BPA), and ethyl-paraben (EPB), were associated with an increased risk of PCa.

Novel Titanocene Y derivative with albumin affinity exhibits improved anticancer activity against platinum resistant cells.

The antitumor activity of Ti(IV)-based compounds put them in the spotlight for cancer treatment in the past, but their lack of stability in vivo due to a high rate of hydrolysis has hindered their development as antitumor drugs. As a possible solution for this problem, we have reported a synthesis strategy through which we combined a titanocene fragment, a tridentate ligand, and a long aliphatic chain. This strategy allowed us to generate a titanium compound (Myr-Ti) capable of interacting with albumin, highly stable in water and with cytotoxic activity in tumor cells[1]. Following a similar strategy, now we report the synthesis of a new compound (Myr-TiY) derived from titanocene Y that shows antitumoral activity in a cisplatin resistant model with a 50% inhibitory concentration (IC50) of 41-76 µM. This new compound shows high stability and a strong interaction with human serum albumin. Myr-TiY has a significant antiproliferative and proapoptotic effect on the tested cancer cells and shows potential tumor selectivity when assayed in non-tumor human epithelial cells being more selective (1.3-3.8 times) for tumor cells than cisplatin. These results lead us to think that the described synthesis strategy could be useful to generate compounds for the treatment of both cisplatin-sensitive and cisplatin-resistant cancers.

Self-perception of mental health, COVID-19 and associated sociodemographic-contextual factors in Latin America.

This study aimed to estimate the prevalence of alterations in self-perceived mental health during the COVID-19 pandemic and their associated factors in four Latin American countries. This is a cross-sectional study based on data collected from adults in 2021 through the Collaborative Response COVID-19 Survey by the MacDonnell Academy at Washington University in St. Louis (United States). The sample was composed of 8,125 individuals from Brazil, Colombia, Mexico, and Chile. A generalized linear model for a binary outcome variable with a logistic link and fixed country effects was used. There were 2,336 (28.75%) individuals who considered having suffered alterations in self-perceived mental health. Unemployed individuals (OR = 1.40; 95%CI: 1.24-1.58), those with bad/regular quality of life (OR = 5.03; 95%CI: 4.01-6.31), and those with high socioeconomic status (OR = 1.66; 95%CI: 1.41-1.96) had a higher risk of self-perceived mental health alterations than those with full-time employment, excellent quality, and low socioeconomic status. According to the fixed-effects model, Brazilians living in the country during the pandemic, who disagreed with their government's decisions (OR = 2.05; 95%CI: 1.74-2.42) and lacked trust in their government (OR = 2.10; 95%CI: 1.74-2.42) had a higher risk of having self-perceived mental health alterations. Nearly 30% of respondents indicated that the COVID-19 pandemic altered their self-perceived mental health. This outcome was associated with political, sociodemographic, and health risk factors. These findings should help policymakers develop post-pandemic community interventions.

Expansion of the neurodevelopmental phenotype of individuals with EEF1A2 variants and genotype-phenotype study.

Translation elongation factor eEF1A2 constitutes the alpha subunit of the elongation factor-1 complex, responsible for the enzymatic binding of aminoacyl-tRNA to the ribosome. Since 2012, 21 pathogenic missense variants affecting EEF1A2 have been described in 42 individuals with a severe neurodevelopmental phenotype including epileptic encephalopathy and moderate to profound intellectual disability (ID), with neurological regression in some patients. Through international collaborative call, we collected 26 patients with EEF1A2 variants and compared them to the literature. Our cohort shows a significantly milder phenotype. 83% of the patients are walking (vs. 29% in the literature), and 84% of the patients have language skills (vs. 15%). Three of our patients do not have ID. Epilepsy is present in 63% (vs. 93%). Neurological examination shows a less severe phenotype with significantly less hypotonia (58% vs. 96%), and pyramidal signs (24% vs. 68%). Cognitive regression was noted in 4% (vs. 56% in the literature). Among individuals over 10 years, 56% disclosed neurocognitive regression, with a mean age of onset at 2 years. We describe 8 novel missense variants of EEF1A2. Modeling of the different amino-acid sites shows that the variants associated with a severe phenotype, and the majority of those associated with a moderate phenotype, cluster within the switch II region of the protein and thus may affect GTP exchange. In contrast, variants associated with milder phenotypes may impact secondary functions such as actin binding. We report the largest cohort of individuals with EEF1A2 variants thus far, allowing us to expand the phenotype spectrum and reveal genotype-phenotype correlations.

Analysis of Spatial Offensive Performance in Handball: Differences between Men's and Women's Senior World Championships.

The aim of this study was to carry out a descriptive analysis of the main performance variables of national teams that competed in the Men's (Germany-Denmark 2019) and Women's (Germany 2017) senior handball World Cups, and to compare the spatial offensive performance indices of laterality and depth according to the gender of players, considering for this purpose the total number of throws made according to the finishing area. A documentary study was carried out based on the total number of throws made in 192 male and 154 female games of 48 national teams belonging to 33 countries, which participated in previous World Cups. The data were collected from the International Handball Federation (IHF) statistics. The results showed that the areas from which the highest number of shots were taken in both World Cups were the central and shallow areas of the field. Several gender differences were observed. More specifically, male teams made much more attempts from the left side area than female teams (data), who finished from the right side (data). The depth index reflected that, although the dominant execution by gender was from deep offensive zones, men's teams finished more often from the 1st offensive line, while female teams finished from the 2nd offensive line. This information will be useful for coaches in designing training tasks and for players in improving decision making.

Venoarterial extracorporeal membrane oxygenation for vasoplegic shock after treprostinil refill of an implanted intravenous pump: a case report.

Introduction: Venoarterial extracorporeal membrane oxygenation (ECMO) is a rescue therapy that can stabilize patients with hemodynamic compromise. Indications continue to evolve, including drug overdose. However, the indication merely for vasoplegic shock following drug overdose is controversial. Case summary: We report a case of a 57-year-old male with high-risk idiopathic pulmonary arterial hypertension treated with upfront triple combination therapy (sildenafil, bosentan, and intravenous treprostinil infusion via subcutaneous abdominal implantable pump). In one of the refills of the drug reservoir, accidental administration of 1 months's supply of treprostinil (200 mg) into the subcutaneous tissue occurred, causing refractory vasoplegic shock. He required urgent VA-ECMO for 96 h, surviving to discharge 28 days later. Discussion: Treprostinil poisoning is rare due to its less frequent use but is life-threatening. ECMO may be considered in vasoplegic shock due to overdose of vasodilatory medication. It allows organ perfusion to be maintained, with the knowledge that recovery is as rapid as drug elimination.

On the pixel selection criterion for the calculation of the Pearson's correlation coefficient in fluorescence microscopy.

Colocalisation microscopy analysis provides an intuitive and straightforward way of determining if two biomolecules occupy the same diffraction-limited volume. A popular colocalisation coefficient, the Pearson's correlation coefficient (PCC), can be calculated using different pixel selection criteria: PCCALL includes all image pixels, PCCOR only pixels exceeding the intensity thresholds for either one of the detection channels, and PCCAND only pixels exceeding the intensity thresholds for both detection channels. Our results show that PCCALL depends on the foreground to background ratio, producing values influenced by factors unrelated to biomolecular association. PCCAND focuses on areas with the highest intensities in both channels, which allows it to detect low levels of colocalisation, but makes it inappropriate for evaluating spatial cooccurrence between the signals. PCCOR produces values influenced both by signal proportionality and spatial cooccurrence but can sometimes overemphasise the lack of the latter. Overall, PCCAND excels at detecting low levels of colocalisation, PCCOR provides a balanced quantification of signal proportionality and spatial coincidence, and PCCALL risks misinterpretation yet avoids segmentation challenges. Awareness of their distinct properties should inform their appropriate application with the aim of accurately representing the underlying biology.

Prospective, comparative, pilot study of maintenance treatment in comorbid bipolar disorders with post-traumatic stress disorder.

There is limited real-world evidence that evaluates the impact of monotherapy vs. combination therapy as a maintenance treatment in comorbid post-traumatic stress disorder (PTSD) in bipolar disorder (BD). Our aim was to compare lithium vs. lithium plus quetiapine in maintenance treatment in a sample of comorbid BD with PTSD. An exploratory, comparative pilot study over a 28-week period in 34 comorbid BD with PTSD patients was performed to compare monotherapy (n = 18) vs. combination therapy (n = 16) during maintenance treatment. The primary outcome was the time to event of recurrence of any mood episode. The secondary outcomes were regarding change from the baseline to endpoint in the Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). A Cox regression, Kaplan-Meir survival, and mixed-effects model for repeated measures analyses were performed. Lithium plus quetiapine reduces the risk of recurrence of any mood episode. There are significant differences between baseline and endpoint for YMRS, MADRS, and CGI-BP scales in the sample. In this pilot, exploratory analysis, combination therapy during maintenance treatment for comorbid BD with PTSD may be effective in preventing recurrences of any type of mood episode.

O-glycosylation of the transcription factor SPATULA promotes style development in Arabidopsis.

O-linked ß-N-acetylglucosamine (O-GlcNAc) and O-fucose are two sugar-based post-translational modifications whose mechanistic role in plant signalling and transcriptional regulation is still largely unknown. Here we investigated how two O-glycosyltransferase enzymes of Arabidopsis thaliana, SPINDLY (SPY) and SECRET AGENT (SEC), promote the activity of the basic helix-loop-helix transcription factor SPATULA (SPT) during morphogenesis of the plant female reproductive organ apex, the style. SPY and SEC modify amino-terminal residues of SPT in vivo and in vitro by attaching O-fucose and O-GlcNAc, respectively. This post-translational regulation does not impact SPT homo- and heterodimerization events, although it enhances the affinity of SPT for the kinase PINOID gene locus and its transcriptional repression. Our findings offer a mechanistic example of the effect of O-GlcNAc and O-fucose on the activity of a plant transcription factor and reveal previously unrecognized roles for SEC and SPY in orchestrating style elongation and shape.

Knowing is half the battle: Regulating and appraising emotions co-protect from suicidal ideation.

College students, particularly those in healthcare fields, face an elevated risk of suicidal ideation and depression. Therefore, it is essential to explore how both actual and perceived emotional resources may play a role in suicide prevention within this age group. This study examined (1) whether actual self-focused emotion-regulation ability diminishes suicidal ideation through a decrease in depressive symptoms, and (2) whether perceived self-emotion appraisal moderates this relationship. In 312 healthcare students (209 women) actual self-focused emotion-regulation ability was negatively related to suicidal ideation through depressive symptoms. Furthermore, perceived self-emotion appraisal buffered the relationship between depressive symptoms and suicidal ideation. Findings suggest that perceived self-emotion appraisal may reinforce the adaptiveness of actual self-focused emotion-regulation ability as a protective factor for psychological maladjustment. The results indicate the collaborative ability to regulate one's emotions coupled with the self-perception of emotion appraisal could effectively alleviate the potential progression of emotional difficulties among healthcare students.

Dizziness in adults with chronic otitis media at two otology referral centres in Colombia: a cross-sectional study in a middle-income country.

OBJECTIVE: This study aimed to determine the prevalence of dizziness and its associated factors in patients with COM at two otologic referral centres in a middle-income country. DESIGN: Cross-sectional study. Adults with and without COM diagnosis from two otology-referral centres in Bogotá (Colombia) were included. Dizziness and quality of life were assessed using the "Chronic Suppurative Otitis Media Questionnaire-12" (COMQ-12), and sociodemographic questionnaires were applied. Otoscopic evaluation and audiometric data were collected. STUDY SAMPLE: A total of 231 adults. RESULTS: Of the 231 participants, up to 64.5% (n = 149) reported at least mild inconvenience due to dizziness. Factors associated with dizziness included female sex (aPR: 1.23; 95% CI: 1.04-1.46), chronic suppurative otitis media (aPR: 3.02; 95% CI: 1.21-7.52), and severe tinnitus (aPR: 1.75; 95% CI: 1.24-2.48). An interaction was found between socioeconomic status and educational level, with more frequent reports of dizziness in the middle/high economic status and secondary education (aPR: 3.09; 95% CI: 0.52-18.55; p < 0.001). Differences of 14 points in symptom severity and 18.5 points in the total score of the COMQ-12 were found between the groups with dizziness and without dizziness. CONCLUSIONS: Dizziness was frequent in patients with COM and was associated with severe tinnitus and quality of life deterioration.