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Since its emergence in 2019, coronavirus disease (COVID-19) has spread worldwide and consumed public health resources. However, the world still has to address the burdens of other infectious diseases that continue to thrive. Countries in the tropics and neotropics, including Brazil, are affected by annual, cyclic dengue epidemics. Little is known about the impact of subsequent infections between DENV and SARS-CoV-2. Our study was performed on 400 serum samples collected from laboratory-confirmed COVID-19 patients between January and June 2021, months historically known for DENV outbreaks in Brazil. The samples were tested by serology and molecular assays for the presence of DENV and other arboviruses. While no DENV PCR results were detected, 6% were DENV IgM-positive, and 0.25% were DENV NS1-positive according to ELISA. IgM antibodies were isolated by chromatography, and 62.5% of the samples were positive for neutralizing antibodies (FRNT 80 ) against DENV IgM, suggesting a recent infection. We also observed increased IL-10, TNF-α, and IL-1β levels in patients with overlapping SARS-CoV-2/DENV infections. Intriguingly, diabetes was the only relevant comorbidity (p=0.046). High rates of hospitalization (94.9%) and mortality (50%) were found, with a significant increase in invasive mechanical ventilatory support (86.96%) in SARS-CoV-2/DENV- infected patients, suggesting an impact on patient clinical outcomes. When analyzing previous exposure to DENV, secondary dengue patients infected with SARS-CoV-2 more frequently presented with dyspnea and respiratory distress, longer hospital and intensive care unit (ICU) stays (4 and 20.29 days, respectively) and a higher mortality rate (60%). However, a greater proportion of patients with primary DENV infection had fever and cough than patients with secondary dengue (87.50% vs. 33.33%, p=0.027 for fever). Our data demonstrate that differentiating between the two diseases is a great concern for tropical countries and should be explored to improve patient management.

Myoclonus dystonia (DYT11) is a movement disorder caused by loss-of-function mutations in SGCE and characterized by involuntary jerking and dystonia that frequently improve after drinking alcohol. Existing transgenic mouse models of DYT11 exhibit only mild motor symptoms, possibly due to rodent-specific developmental compensation mechanisms, which have limited the study of neural mechanisms underlying DYT11. To circumvent potential compensation, we used short hairpin RNA (shRNA) to acutely knock down Sgce in the adult mouse and found that this approach produced dystonia and repetitive, myoclonic-like, jerking movements in mice that improved after administration of ethanol. Acute knockdown of Sgce in the cerebellum, but not the basal ganglia, produced motor symptoms, likely due to aberrant cerebellar activity. The acute knockdown model described here reproduces the salient features of DYT11 and provides a platform to study the mechanisms underlying symptoms of the disorder, and to explore potential therapeutic options.

Abstract Disclosure: C.M. Ramos Moreno: None. V.F. Moore Reyes: None. B.V. Prieto Castillo: None. P.S. Duron Medina: None. E. Mendez: None. N.H. Shaaban: None. Background: Nonclassical congenital adrenal hyperplasia (NCCAH) is a milder form of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency. It presents later in life with signs of hyperandrogenism, such as irregular menses, hirsutism, and infertility. Due to clinical overlap with polycystic ovary syndrome (PCOS), it is often misdiagnosed, especially when initial laboratory evaluation is limited to ovarian-focused studies without assessing adrenal function. When standard PCOS treatments fail, NCCAH should be considered, as its management and follow-up differ significantly. Clinical Case: A 32-year-old woman with a history of prediabetes and oligomenorrhea presented for endocrine evaluation after one year of infertility and elevated androgen levels. She had previously been diagnosed with PCOS based on irregular cycles and mild hirsutism. Initial labs revealed elevated DHEA-S, mildly elevated total and free testosterone, and elevated 17-OHP level (698 ng/dL). A dexamethasone suppression test showed persistent cortisol and DHEA-S elevation. Due to suspicion of NCCAH, a cosyntropin stimulation test was performed, confirming the diagnosis with 17-OHP levels of 1051 ng/dL. She was started on hydrocortisone 15 mg daily, leading to spontaneous conception within weeks. After pregnancy confirmation, her therapy was transitioned to a physiologic dose of prednisone 7.5 mg daily. The plan included monitoring pregnancy progression, testing the newborn for 21-hydroxylase deficiency, and adjusting therapy postpartum. Conclusion: This case emphasized the importance of thorough endocrine evaluation in women with infertility and hyperandrogenism. Early differentiation between PCOS and NCCAH is critical, as management strategies and reproductive outcomes differ. Adrenal-focused testing in the initial workup of atypical PCOS presentations can prevent delayed diagnosis and improve fertility outcomes. Presentation: Saturday, July 12, 2025

Myoclonus dystonia (DYT11) is a movement disorder caused by loss-of-function mutations in SGCE and characterized by involuntary jerking and dystonia that frequently improve after drinking alcohol. Existing transgenic mouse models of DYT11 exhibit only mild motor symptoms, possibly due to rodent-specific developmental compensation mechanisms, which have limited the study of neural mechanisms underlying DYT11. To circumvent potential compensation, we used short hairpin RNA (shRNA) to acutely knock down Sgce in the adult mouse and found that this approach produced dystonia and repetitive, myoclonic-like movements in mice that improved after administration of ethanol. Acute knockdown of Sgce in the cerebellum, but not the basal ganglia, produced motor symptoms, likely due to aberrant cerebellar activity. The acute knockdown model described here reproduces the salient features of DYT11 and provides a platform to study the mechanisms underlying symptoms of the disorder, and to explore potential therapeutic options.

IntroductionA successful extubation process is critical for the future health outcomes of paediatric patients, as it tests the functioning of the respiratory system without the support of mechanical ventilation. However, extubation can cause stress, pain, anxiety or discomfort in patients, which may sometimes lead to an increased likelihood of reintubation. Music-based interventions and therapies have been shown to be effective in reducing anxiety and stress levels in ventilated patients in the paediatric intensive care unit (PICU), but studies evaluating the effect of music therapy during the extubation process in the PICU are scarce.Methods and analysisThis is a pragmatic multicentre randomised clinical trial with two parallel arms. The intervention group will receive standard care + music therapy during the extubation process, and the control group will receive standard care alone. The main outcome measure is heart rate, which will be measured every minute for 5 min pre-extubation, during the extubation process and up to 10 min postextubation. Secondary outcome measures are: oxygen saturation, respiratory rate, blood pressure and heart rate variability. A total of 82 patients will be randomised.Ethics and disseminationThis study was approved by the Research Ethics Committee of the Fundación Universitaria Sanitas (CEIFUS 1356-24, date of approval: 3 May 2024). All parents or legal guardians of patients will sign a written informed consent, and if applicable, assent from participants will be sought. The results will be disseminated through publications in peer-reviewed journals, conferences and presentations at the hospitals’ clinical committees.Protocol versionVersion 1.0, 18 December 2024.Trial registration numberNCT06591533, trial registration date: 10 September 2024.

Coronavirus disease 2019 (COVID-19) is currently a worldwide emergency caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In observational clinical studies, statins have been identified as beneficial to hospitalized patients with COVID-19. However, experimental evidence of underlying statins protection against SARS-CoV-2 remains elusive. Here we reported for the first-time experimental evidence of the protective effects of simvastatin treatment both in vitro and in vivo . We found that treatment with simvastatin significantly reduced the viral replication and lung damage in vivo , delaying SARS-CoV-2-associated physiopathology and mortality in the K18-hACE2-transgenic mice model. Moreover, simvastatin also downregulated the inflammation triggered by SARS-CoV-2 infection in pulmonary tissue and in human neutrophils, peripheral blood monocytes, and lung epithelial Calu-3 cells in vitro , showing its potential to modulate the inflammatory response both at the site of infection and systemically. Additionally, we also observed that simvastatin affected the course of SARS-CoV-2 infection through displacing ACE2 on cell membrane lipid rafts. In conclusion, our results show that simvastatin exhibits early protective effects on SARS-CoV-2 infection by inhibiting virus cell entry and inflammatory cytokine production, through mechanisms at least in part dependent on lipid rafts disruption.

We describe in vivo follow-up PET imaging and postmortem findings from an autosomal dominant Alzheimer’s disease (ADAD) PSEN1 E280A carrier who was also homozygous for the APOE3 Christchurch (APOE3ch) variant and was protected against Alzheimer’s symptoms for almost three decades beyond the expected age of onset. We identified a distinct anatomical pattern of tau pathology with atypical accumulation in vivo and unusual postmortem regional distribution characterized by sparing in the frontal cortex and severe pathology in the occipital cortex. The frontal cortex and the hippocampus, less affected than the occipital cortex by tau pathology, contained Related Orphan Receptor B (RORB) positive neurons, homeostatic astrocytes and higher APOE expression. The occipital cortex, the only cortical region showing cerebral amyloid angiopathy (CAA), exhibited a distinctive chronic inflammatory microglial profile and lower APOE expression. Thus, the Christchurch variant may impact the distribution of tau pathology, modulate age at onset, severity, progression, and clinical presentation of ADAD, suggesting possible therapeutic strategies.

Disorders of sex development (DSDs) are congenital conditions in which the external appearance of the individual does not coincide with the chromosomal constitution or the gonadal sex. In other words, there is an ambiguous or intermediate condition between the male and female phenotypes of the anatomical sex. These atypical conditions are manifested in several ways, ranging from genital ambiguity to phenotypes that are so attenuated that they can go unnoticed or appear normal. Currently, there is a lack of understanding of the factors responsible for these outcomes; however, they are likely to be conditioned by genetic, hormonal and environmental factors during prenatal and postnatal development. The present study determined the genetic etiology of DSDs in Colombian patients by conventional cytogenetic analysis, FISH and MLPA (for SF1, DAX1, SOX9, SRY and WNT4). A cohort of 43 patients with clinical phenotypes of sex development disorder was used in the present study. Using this multistep experimental approach, a diagnostic percentage of 25.58% was obtained: 17 patients (39.53%) were classified as having gonadal development disorders, the majority of which were ovotesticular disorders with numerical and/or structural alterations of the sex chromosomes, 9 patients (20.93%) were classified as having testicular DSD with a 46,XY karyotype, and 3 patients (6.98%) as having ovarian DSD with a 46,XX karyotype. The remaining 14 patients (32.56%) were classified as 'other' since they could not be grouped into a specific class of gonadal development, corresponding to hypospadias and multiple congenital anomalies. These findings highlight the importance of histological and cytogenetic studies in a gonadal biopsy. In 11/43 cases, the multistep experimental protocol presented in the present study yielded etiological or histological findings that could be used to define the medical management of patients with DSDs. In conclusion, for the etiological diagnosis of DSDs, a broad-spectrum approach that includes endocrinological tests, conventional karyotyping, molecular karyotyping by FISH and, molecular tests is required, in addition to gonadal tissue analyses, to identify genetic alterations.

Tomatoes are the major dietary source of lycopene, a carotenoid that crosses the blood–brain barrier and exerts antioxidant and anti-inflammatory effects. However, the impact of tomato consumption on cognitive function in healthy adults remains unclear. This study assessed the effects of concentrated tomato paste on cognitive performance and explored potential mechanisms, including brain-derived neurotrophic factor (BDNF) and functional brain connectivity. A randomized, two-period crossover trial (ClinicalTrials.gov: NCT05891977) was conducted in 47 healthy adults aged 40–55 years assigned to two 3-month interventions separated by a 1-month washout: (a) daily consumption of concentrated tomato paste (0.5 g/kg body weight) and (b) a lycopene-restricted control diet. Cognitive performance was evaluated using validated neuropsychological tests (d2-R, Face-Name Associative Memory Exam, Modified Wisconsin Card Sorting Test), alongside plasma lycopene and BDNF, and resting-state functional magnetic resonance imaging (fMRI). Forty-two participants completed the study. Tomato intake improved selective attention (concentration performance: +7.2 points; processing speed: +8.3 points) and associative memory (face-name matching: +0.8 points). Plasma BDNF showed a borderline increase with tomato intake (mean difference 15.2 ng/mL). Resting-state fMRI revealed changes in brain networks, including reduced connectivity in frontoparietal and auditory networks, contrasting with reductions in the dorsal attention network during the control period. These findings provide evidence that tomato consumption may support cognitive function and modulate brain connectivity in healthy middle-aged adults.

Background Bioremediation faces several compounds to recover oil spilled ecosystem. The BTEX (benzene, toluene, ethylbenzene, and xylene) are toxic hydrocarbons requiring efficient microbial degradation for bioremediation. Pseudomonas aeruginosa can degrade hydrocarbons through emulsification ( rhl genes) and tolerance ( mla genes). However, genomic organization of these systems in environmental P. aeruginosa strains remains unclear. This study aimed to investigate the rhl and mla systems in six strains isolated from hydrocarbon-contaminated sites in Peru. Methods Six Pseudomonas aeruginosa strains were evaluated in this study. Each strain were able to degrade hydrocarbon and tolerate heavy metals. DNA extraction, sequencing, and quality-controlled assembly, functional genome annotation was performed using BAKTA. Comparative analysis included high-quality Pseudomonas genomes from RefSeq, with ANI metrics. A phylogenetic tree was built from core gene alignment, revealed evolutionary connections and was visualized with iTOL. Results The assembled genomes ranged from 5.6 to 6.0 Mbp with ~66% GC content. All the strains were confirmed as P. aeruginosa by ANI; placing them within Clade 1 alongside environmental and clinical strains. Pangenome analysis identified 3,544 core genes and a diverse accessory genome. All strains had rhlABRI genes in a conserved 3′-5′ orientation. Most of them contained duplicated rhlB gene, except C1BHIC5 strain. However, rhlG varied in position and orientation, it was often near rhlC, with C1BHIC5 also displaying an exception in rhlG orientation.100% of strains presented mla system, associated with toluene tolerance, with two copies of mlaA, mlaFEDC, and mlaEFD genes arranged with high synteny but variable orientations. In comparison to Pseudomonas putida, where mla genes are positioned between murA and ppcD with an additional toluene tolerance gene ( ttg2D). Conclusions In conclusion, the presence of the rhlABC genes and the BTEX tolerance genes in all of the analyzed strains allowed us to understand the great ability of P. aeruginosa to survive in polluted environments.