Glenolabral Articular Disruption (GLAD) Is Not Associated with Worse Outcomes or Higher Instability Recurrence after Arthroscopic Bankart Repair-A Matched-Pair Analysis.

Background: This study aimed to compare clinical outcomes and recurrence of instability after arthroscopic Bankart repair (ABR) in patients with anterior shoulder instability, with and without a GLAD lesion, while distinguishing between primary and recurrent instability. Methods: Consecutive patients who underwent isolated ABR between January 2012 and December 2021 were included. Patients with a concomitant GLAD lesion were matched in with patients without a GLAD lesion according to the following criteria: age, sex, BMI, follow-up time, and primary versus recurrent instability. At minimum two-year follow-up, the clinical outcome (Rowe score, redislocation rate) and the functional outcome, including the American Shoulder and Elbow Surgeons (ASES) score, Western Ontario Shoulder Instability Index (WOSI), Oxford Shoulder Instability Score (OSIS), satisfaction (1-10 scale, 0 = unsatisfied, 10 = very satisfied), and Visual Analogue Scale (VAS), were compared between groups. Results: In total, 28 patients (14 GLAD vs. 14 Bankart; age: 32.5 ± 13.0 years; sex: 92.9% male; BMI: 24.6 ± 2.2) were included 6.9 ± 2.8 (2-11) years after isolated ABR (follow-up rate 63.6%). Clinical and functional outcome did not differ significantly between patients with versus without GLAD lesions (ASES score: 100 [96.5-100] vs. 97.5 [93.3-100], p = 0.27); WOSI (%): 9.0 [3.7-24.5] vs. 3.8 [0.8-8.9], p = 0.22; Rowe score: 90.0 [75.0-100] vs. 95.0 [78.8-100], p = 0.57; OSIS: 46 [44.7-48] vs. 46 [43.0-48], p = 0.54; satisfaction: 8.9 ± 1.4 vs. 8.0 ± 1.4, p = 0.78; VAS 0 [0-1.3] vs. 0 [0-1.0]. In both groups, two patients (14.3%) reported a redislocation during the observation period. Conclusions: At short- to mid-term follow-up, ABR showed favorable outcomes, low dislocation rates, and high patient satisfaction, regardless of the presence of a GLAD lesion or primary versus recurrent instability. However, follow-up time was heterogeneous, and the follow-up rate was marginal.

A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease.

Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD ,estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m2 and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks treatment with standard of care plus subcutaneous cotadutide up-titrated to100, 300, or 600 µg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once-weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m2, geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 µg (-43.9% [95%confidence interval -54.7 to -30.6]) and 600 µg (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 µg were comparable to semaglutide. Thus, our study shows that in patients with T2Dand CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study.

Effect of Primary Cable Position on Accuracy in Non-Toroidal-Shaped Pass-Through Current Transformer.

Non-toroidal-shaped primary pass-through protection current transformers (CTs) are used to measure high currents. Their design provides them with a big airgap that allow the passing of several cables per phase though them, which is the main advantage versus toroidal types, as the number of CTs required to measure the whole phase current is drastically reduced. The cables passed through the transformer window can be in several positions. As the isolines of the magnetic field generated by the primary currents are centered in the cables, if these cables are not centered in the transformer window, then the magnetic field will be non-uniform along the transformer core. Consequently, local saturations can appear if the cables are not properly disposed, causing the malfunction of the CT. In this paper, the performance of a non-toroidal-shaped protection CT is studied. This research is focused on the influence of the cable position on possible partial saturations of the CT when it is operating near to its accuracy limit. Depending on the cable position, the ratio of the primary and secondary currents can depart from the assigned ratio. The validation of this phenomenon was carried out via finite element analysis (FEA), showing that partial transformer core saturations appear in areas of the magnetic core close to the cable. By applying FEA, the admissible accuracy region for cable positioning inside the CT is also delimited. Finally, the simulation results are ratified with experimental tests performed in non-toroidal protection CTs, varying the primary cables' positions, which are subjected to currents up to 5 kA, achieving satisfactory results. From this analysis, installation recommendations are given.

Extremely thin but very robust: Surprising cryptogam trait combinations at the end of the leaf economics spectrum.

Leaf economics spectrum (LES) describes the fundamental trade-offs between leaf structural, chemical, and physiological investments. Generally, structurally robust thick leaves with high leaf dry mass per unit area (LMA) exhibit lower photosynthetic capacity per dry mass (A mass). Paradoxically, "soft and thin-leaved" mosses and spikemosses have very low A mass, but due to minute-size foliage elements, their LMA and its components, leaf thickness (LT) and density (LD), have not been systematically estimated. Here, we characterized LES and associated traits in cryptogams in unprecedented details, covering five evolutionarily different lineages. We found that mosses and spikemosses had the lowest LMA and LT values ever measured for terrestrial plants. Across a broad range of species from different lineages, A mass and LD were negatively correlated. In contrast, A mass was only related to LMA when LMA was greater than 14 g cm- 2. In fact, low A mass reflected high LD and cell wall thickness in the studied cryptogams. We conclude that evolutionarily old plant lineages attained poorly differentiated, ultrathin mesophyll by increasing LD. Across plant lineages, LD, not LMA, is the trait that represents the trade-off between leaf robustness and physiology in the LES.

Validation of a Clinical Scale for Early Detection of Infections at the Exit Site of Central Venous Catheters for Hemodialysis.

Introduction: Exit-site infections (ESI) of central venous catheters for hemodialysis (CVC-HD) has been associated with early catheter removal and an increased risk of CVC-HD related bacteremia. No specific clinical scales to predict ESI have previously been validated. Methods: A multicenter prospective cohort study was performed to validate the proposed scale, which is based on the following 5 signs and symptoms: (i) pain at exit site during interdialytic period; (ii) hyperemia or erythema ≥2 cm from exit site; (iii) inflammation, induration, or swelling at exit site; (iv) fever ≥38 °C not attributable to other causes, and (v) obvious abscess or purulent exudate at the exit site. Adult patients with a tunneled CVC-HD for at least 1 month after insertion has been included. During each hemodialysis session, the exit site was assessed with the proposed scale by nurses. If any item was present, a pericatheter skin swab culture was collected: positive results were gold standard. The scale was validated using receiver operating characteristic (ROC) curves and logistic regression analysis. For this purpose, the logit function was applied, and the ESI probability calculated, as elogit ESI/1 + elogit ESI. Results: Three hundred thirty-seven CVC-HDs from 310 patients were analyzed, producing 515 cultures (117 infected and 398 healthy). The final version of the scale includes the following 3 signs and symptoms, which present the greatest predictive capacity: (i) pain at exit site during interdialytic period, (ii) hyperemia or erythema ≥2 cm from exit site, and (iii) abscess or purulent exudate at the exit site. The final version generated an area under the ROC curve (AUC) of 88.3% (95% confidence interval [CI]: 85.2%-91%; P < 0.001), Youden index 0.7557 ≈ 1, sensitivity 80.34% (95% CI: 71.36%-87.71%) and specificity 95.23% (95% CI: 92.73%-97%). Conclusions: The validation shows that the scale has good predictive properties, detecting approximately 90% of ESI with very acceptable validity parameters.

Genome-wide association analysis and admixture mapping in a Puerto Rican cohort supports an Alzheimer disease risk locus on chromosome 12.

Introduction: Hispanic/Latino populations are underrepresented in Alzheimer Disease (AD) genetic studies. Puerto Ricans (PR), a three-way admixed (European, African, and Amerindian) population is the second-largest Hispanic group in the continental US. We aimed to conduct a genome-wide association study (GWAS) and comprehensive analyses to identify novel AD susceptibility loci and characterize known AD genetic risk loci in the PR population. Materials and methods: Our study included Whole Genome Sequencing (WGS) and phenotype data from 648 PR individuals (345 AD, 303 cognitively unimpaired). We used a generalized linear-mixed model adjusting for sex, age, population substructure, and genetic relationship matrix. To infer local ancestry, we merged the dataset with the HGDP/1000G reference panel. Subsequently, we conducted univariate admixture mapping (AM) analysis. Results: We identified suggestive signals within the SLC38A1 and SCN8A genes on chromosome 12q13. This region overlaps with an area of linkage of AD in previous studies (12q13) in independent data sets further supporting. Univariate African AM analysis identified one suggestive ancestral block (p = 7.2×10-6) located in the same region. The ancestry-aware approach showed that this region has both European and African ancestral backgrounds and both contributing to the risk in this region. We also replicated 11 different known AD loci -including APOE- identified in mostly European studies, which is likely due to the high European background of the PR population. Conclusion: PR GWAS and AM analysis identified a suggestive AD risk locus on chromosome 12, which includes the SLC38A1 and SCN8A genes. Our findings demonstrate the importance of designing GWAS and ancestry-aware approaches and including underrepresented populations in genetic studies of AD.

Influence of the kinesiophobia and its pain intensity relationship in subjects with onychocryptosis.

Background: Onychocryptosis is a nail deformity that occurs when the side of the nail grows into soft tissue, which causes pain, sepsis and the formation of granulation. The aim of the study was to evaluate and compare different levels of kinesiophobia in subjects with onychocryptosis before and after surgery to eliminate this condition. Methods: A descriptive and observational study was conducted with a total sample size of 25 subjects with a mean age of 40.96 ± 18.25 years. The pretest sample was composed of the 25 subjects before the surgical treatment of onychocryptosis and the posttest sample was composed of the same 25 subjects after the surgical treatment of onychocryptosis. Kinesiophobia levels and total scores were self-reported using the Spanish version of the Tampa Scale for Kinesiophobia (TSK-11). Results: The Wilcoxon test for related samples and the Mann-Whitney U test for independent samples were used to compare the results before and after the surgical treatment. It was observed that in all the items as well as in the total score, there were significant changes in the levels of kinesiophobia, after the surgical intervention for onychocryptosis (P < 0.05) compared to the levels before surgery, except for items 4 and 11 in which there were no significant differences (P > 0.05). Before surgery, 0% of the subjects with onychocryptosis reported not being afraid of movement, 16% reported mild fear of movement, 8% reported moderate fear of movement and 76% of the subjects with onychocryptosis reported severe and maximum fear of movement. On the other hand, 100% of the subjects did not report kinesiophobia after surgical treatment (P < 0.01). Conclusions: The levels of kinesiophobia were higher in the subjects with onychocryptosis compared to the subjects after having undergone surgery to eliminate onychocryptosis.

Recompensation after TIPS reduces the incidence of hepatocellular carcinoma and increases survival in patients with cirrhosis.

BACKGROUND AND AIMS: It has been described that recompensation can improve prognosis in patients with cirrhosis. However, recompensation after transjugular intrahepatic portosystemic shunt (TIPS) has not been studied. We evaluated the impact of recompensation after TIPS on the risk of hepatocellular carcinoma (HCC) and death, and we compared it with compensated cirrhosis patients. METHODS: An observational study of consecutive patients with cirrhosis undergoing TIPS between 2008 and 2022 was performed. Baveno VII definition of recompensation was used including patients with or without diuretics/Hepatic encephalopathy prophylaxis. A prospective cohort of consecutive compensated cirrhosis patients was used for comparison. RESULTS: Overall, 208 patients with cirrhosis were included, 92 compensated and 116 decompensated who underwent TIPS. After 1 year, 24% achieved recompensation. Liver function (MELD 12 ± 5 vs. 15 ± 6; p = .049), LDL-cholesterol (97 mg/dL vs. 76 mg/dL, p = .018), white cell count (7.96 × 109/dL vs. 6.24 × 109/dL, p = .039) and platelets (129 × 109/dL vs. 101 × 109/dL, p = .039) were associated with recompensation. Recompensation was associated with a reduction in the risk of HCC (p = .020). Multivariable analysis showed that this risk was significantly higher in non-recompensated patients (p = .003) but no differences were observed in recompensated compared with compensated patients (p = .816). Similarly, decompensated patients presented lower survival rates (p = .011), while no differences were observed between recompensated and compensated patients (p = .677). CONCLUSIONS: Recompensation after TIPS has a clear impact on the incidence of HCC and death, with a similar prognosis than patients with compensated cirrhosis. Liver function is associated with recompensation, suggesting the importance of considering early TIPS in patients with indication.

Morbidity burden of imported chronic schistosomiasis among West African migrants.

BACKGROUND: Past exposure to schistosomiasis is frequent among migrants from endemic countries, and chronic untreated infection may lead to long-term morbidities. METHODS: We carried out a prospective population-based cross-sectional study among migrants from endemic Sub-Saharan countries living in Barcelona, Spain. Participants had not been previously diagnosed or treated for schistosomiasis. Clinical signs and symptoms were scrutinised through a systematic revision of electronic medical records and an on-site standardised questionnaire, and blood and urine samples were screened for Schistosoma. FINDINGS: We recruited 522 eligible participants, 74.3% males, mean age 42.7 years (SD=11.5, range 18-76), Overall, 46.4% were from Senegal and 23.6% from Gambia. They had lived in the European Union for a median of 16 years (IQR 10-21). The prevalence of a Schistosoma-positive serology was 35.8%. S. haematobium eggs were observed in urine samples in 6 (1.2%) participants. The most prevalent symptoms among Schistosoma-positive participants were chronic abdominal pain (68.8%, OR=1.79; 95%CI 1.2-2.6), eosinophilia (44.9%, OR=2.69; 95%CI 1.8-4.0) and specific symptoms associated with urinary schistosomiasis, like self-reported episodes of haematuria (37.2%; OR=2.47; 95%CI 1.6-3.8), dysuria (47.9%, OR=1.84; 95%CI=1.3-2.7) and current renal insufficiency (13.4%; OR=2.35; 95%CI=1.3-4.3). We found a significant prevalence of gender-specific genital signs and symptoms among females (mainly menstrual disorders) and males (erectile dysfunction and pelvic pain). Individuals typically presented with a multitude of interconnected symptoms, most commonly chronic abdominal pain, which are often disregarded. CONCLUSIONS: Despite the lack of urine parasite identification, the high incidence of clinical signs and symptoms strongly correlated with a positive schistosomiasis serology suggests the existence of a heavy clinical burden among long-term West African migrants living for years/decades in the study region. More research is urgently required to determine whether these symptoms are the result of long-term sequelae or a persistent active Schistosoma infection.

Untargeted metabolic analysis of Epaltes mexicana by LC-QTOF-MS: Terpenes with activity against human cancer cell lines.

Epaltes mexicana is a plant widely used in traditional medicine and as a food in Mexico; however, its phytochemical and pharmacological studies are limited. This study aimed to identify the active secondary metabolites of Epaltes mexicana and determine its cytotoxic activity on cancer cell lines. Three organic extracts were obtained by maceration using n-hexane, dichloromethane, and methanol. The n-hexane extract was fractioned by simple column chromatography. Eight terpenes were annotated in collection 6 (C6) by LC-QTOF-MS using a gradient elution and Electrospray Ionization (ESI) in positive ion mode: 1) Gibberellin A15, 2) farfugin A, 3) dehydromyodesmone, 4) eremopetasitenin A1, 5) hydroxyisonobilin, 6) anhydrocinnzeylanine, 7) nigakilactone H and 8) taxodione. On the other hand, C6 showed a concentration-dependent cytotoxic effect on cancer cell lines MCF-7 (Emax = 74.69 ± 6.19 % and IC50 = 6.31 µg/mL), MDA-MB-231 (Emax = 79.28 ± 12.12 % and IC50 = 124.21 µg/mL), and SiHa (Emax = 82.96 ± 6.02 % and IC50 = 124.31 µg/mL). The C6 did not show a cytotoxic effect against DU-145 and non-cancerous cells from the mammary glands MCF-10A. These results indicate cytotoxic specificity on cancer cell lines and support the hypothesis that terpenes identified in E. mexicana must be investigated and developed for non-clinical and clinical trials as potential anti-cancer drugs.

Thriving of Older People Assessment Scale (TOPAS): Transcultural adaptation, psychometric evaluation, and refinement in a Spanish sample.

The objective of this study was to culturally adapt the Thriving of Older People Assessment Scale (TOPAS) instrument and evaluate its psychometric properties. The study was carried out in two phases: cross-cultural adaptation and psychometric validation and refinement through a cross-sectional study conducted between 2018 and 2020 with 314 participants. The refinement resulted in an abbreviated version of TOPAS, maintaining the original 5 factors with 16 items. Cronbach alpha was 0.91. Composite reliability (0.72-0.89) and average variance extracted (0.57-0.81), supporting discriminant validity. Maximum shared variance for the factors (0.22-0.50) and average shared variance (0.16-0.31), demonstrating discriminant validity. The abbreviated version of TOPAS showed evidence of being a valid and reliable instrument for measuring the adaptability of elderly residents in institutions. Implementing this instrument in Spanish nursing homes allows for a continuous evaluation of residents' well-being in relation to their environment, a construct not previously assessed with available scales.

Production of hypernuclei from antiproton capture within a relativistic transport model.

Production yields of single- Λ  hypernuclei from simulated peripheral annihilations of antiprotons after capture on various target nuclei are reported. The initial annihilation process and the production of excited hypernuclei are estimated within the GiBUU transport framework, while their deexcitation process is treated with the ABLA++ code. The yield of excited hypernuclei range from ∼ 0.3 % for 16 O to ∼ 1.2 % for 132 Xe per annihilation, consistent with previous measurements at LEAR, CERN. The yield of specific ground state hypernuclei after deexcitation reaches up to a few 10 - 4 per annihilation. The hypernuclei are produced in strangeness exchange reactions occuring between a nucleon of the target and the kaons originating from the annihilation in ∼ 80 % of the cases, while the strangeness pair production in secondary pion-nucleon collision contributes to the remaining ∼ 20 %. The simulations indicate that antiproton annihilations at rest on different nuclei could populate a wide range of so-far unexplored hypernuclei.

Influence of the Culture Conditions on Camellia sinensis Cell Cultures.

Since the last century, it has been shown that dedifferentiated cells of Camellia sinensis can produce catechins and other secondary metabolites under in vitro conditions, with potential applications in the cosmetic, pharmaceutical and food industries. In this work, cell suspension cultures of a C. sinensis cell line (LSC-5Y) were established in a liquid medium in order to optimize the biomass productivity, catechin monomer (GC, EGC, C, EC, CG, and ECG) and alkaloid (TB and CAF) productivity. The following factors were evaluated: concentration of growth regulators (BA and IBA), inoculum size, age of the cell line, light exposure, and effect of biotic elicitors (MeJA and extracts of Ciborinia camelliae). GC, EGC, and ECG increased approximately 1.80-fold when the auxin IBA concentration was increased from 0.1 to 2.0 mg/L. In addition, better productivity of EGC, C, EC, and CAF was achieved by using inoculum densities between 50 and 100 g/L. Although lower inoculum densities (25 g/L) showed a higher growth rate (0.20 d-1), the use of inoculum densities higher than 25 g/L favors a 2-4-fold increase in total catechin (TC) productivity, with maximum productivity being reached after 21 days of culture. However, the cell line showed instability in TC productivity: in the short term (in three successive subcultures), the coefficient of variation was 32.80%, and catechin production capacity was 2.5 years with maximum productivity at 0.5 years. Finally, it was observed that ethanol, used as an elicitor solvent, has a strong elicitor effect capable of increasing the accumulation of catechins up to 5.24 times compared to the treatment without an elicitor.

Assessment of oral toxicity of Moringa oleifera Lam aqueous extract and its effect on gout induced in a murine model.

Background and Aim: Although widely employed in traditional remedies globally, the safety and efficacy of Moringa oleifera remain inadequately documented through scientific research. This study evaluated the oral toxicity of M. oleifera leaf aqueous extract (MoAE) and its impact on gout-induced rats. Materials and Methods: 2000 mg/kg was given in a single dose during the acute oral toxicity test, while 100 mg/kg, 250 mg/kg, and 500 mg/kg were given daily for 28 days in the repeated dose toxicity test. 100 mg/kg, 250 mg/kg, and 500 mg/kg MoAE doses were administered during the assessment of its impact on gout caused by monosodium urate. In the hyperuricemia model induced by oxonic acid, serum uric acid levels were assessed and pain response was measured through acetic acid-induced writhing. Results: In acute oral and 28-day repeated dose tests, no indications of toxicity were detected, while MoAE alleviated ankle joint swelling and reduced serum uric acid concentrations in arthritic rats, causing a significant reduction in acetic acid-induced contortions. Conclusion: No acute oral toxicity or toxicity in 28-day repeated doses was found for MoAE, while it exhibited antiarthritic, antihyperuricemic, and pain-relieving effects in the murine model.

Impact of a comprehensive geriatric assessment to manage elderly patients with locally advanced non-small-cell lung cancers: a multicenter prospective study.

PURPOSE: Concurrent chemoradiotherapy (cCRT) is the standard treatment for locally advanced and unresectable non-small-cell lung cancer. Population is aging, and Geriatric assessment (GA) has demonstrated its paper to select fit patients for active treatment and vulnerable, frail patients for interventions and/or palliative care in many histologies. Its role in locally advanced, unresectable non-small-cell lung cancer has been less explored. METHODS: To assess the capability of GA to detect frail patients not suitable for active treatment, we developed this exploratory non-interventional prospective study. All patients ≥ 70 years diagnosed with stage locally advanced and unresectable non-small-cell lung cancer were invited to undergo geriatric assessment. Secondary aims were description of population, exploring GA as prognostic factor, determination of toxicity profile and look for a frailty biomarker. RESULTS: From June 2017 to June 2020, 51 patients were included, of whom 35% (n:18) were classified as frail. Frail patients had less overall survival and more grade 3-4 toxicity. Exploratory results for frailty phenotype are described in the text. CONCLUSIONS: With the results of our study, we confirm that GA can detect frail patients unsuitable for treatment, with a higher risk of toxicity and less overall survival. A trend toward blood-test results for phenotype frailty can be hypothesis generation.

A novel TAp73-inhibitory compound counteracts stemness features of glioblastoma stem cells.

Glioblastoma (GB) is the most common and fatal type of primary malignant brain tumor for which effective therapeutics are still lacking. GB stem cells, with tumor-initiating and self-renewal capacity, are mostly responsible for GB malignancy, representing a crucial target for therapies. The TP73 gene, which is highly expressed in GB, gives rise to the TAp73 isoform, a pleiotropic protein that regulates neural stem cell biology; however, its role in cancer has been highly controversial. We inactivated TP73 in human GB stem cells and revealed that TAp73 is required for their stemness potential, acting as a regulator of the transcriptional stemness signatures, highlighting TAp73 as a possible therapeutic target. As proof of concept, we identified a novel natural compound with TAp73-inhibitory capacity, which was highly effective against GB stem cells. The treatment reduced GB stem cell-invasion capacity and stem features, at least in part by TAp73 repression. Our data are consistent with a novel paradigm in which hijacking of p73-regulated neurodevelopmental programs, including neural stemness, might sustain tumor progression, pointing out TAp73 as a therapeutic strategy for GB.

Schwann cell JUN expression worsens motor performance in an amyotrophic lateral sclerosis mouse model.

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by motor neuron death and distal axonopathy. Despite its clinical severity and profound impact in the patients and their families, many questions about its pathogenesis remain still unclear, including the role of Schwann cells and axon-glial signaling in disease progression. Upon axonal injury, upregulation of JUN transcription factor promotes Schwann cell reprogramming into a repair phenotype that favors axon regrowth and neuronal survival. To study the potential role of repair Schwann cells on motoneuron survival in amyotrophic lateral sclerosis, we generated a mouse line that over-expresses JUN in the Schwann cells of the SOD1G93A mutant, a mouse model of this disease. Then, we explored disease progression by evaluating survival, motor performance and histology of peripheral nerves and spinal cord of these mice. We found that Schwann cell JUN overexpression does not prevent axon degeneration neither motor neuron death in the SOD1G93A mice. Instead, it induces a partial demyelination of medium and large size axons, worsening motor performance and resulting in more aggressive disease phenotype.

Immunoinformatic approach for multi-epitope vaccine design against Staphylococcus aureus based on hemolysin proteins.

Staphylococcus aureus is a common bacterium that causes a variety of infections in humans. This microorganism produces several virulence factors, including hemolysins, which contribute to its disease-causing ability. The treatment of S. aureus infections typically involves the use of antibiotics. However, the emergence of antibiotic-resistant strains has become a major concern. Therefore, vaccination against S. aureus has gained attention as an alternative approach. Vaccination has the advantage of stimulating the immune system to produce specific antibodies that can neutralize bacteria and prevent infection. However, developing an effective vaccine against S. aureus has proven to be challenging. This study aimed to use in silico methods to design a multi-epitope vaccine against S. aureus infection based on hemolysin proteins. The designed vaccine contained four B-cell epitopes, four CTL epitopes, and four HTL epitopes, as well as the ribosomal protein L7/L12 and pan-HLA DR-binding epitope, included as adjuvants. Furthermore, the vaccine was non-allergenic and non-toxic with the potential to stimulate the TLR2-, TLR-4, and TLR-6 receptors. The predicted vaccine exhibited a high degree of antigenicity and stability, suggesting potential for further development as a viable vaccine candidate. The population coverage of the vaccine was 94.4 %, indicating potential widespread protection against S. aureus. Overall, these findings provide valuable insights into the design of an effective multi-epitope vaccine against S. aureus infection and pave the way for future experimental validations.