Role of palmitoylation on the neuronal glycine transporter GlyT2.

The neuronal glycine transporter GlyT2 removes glycine from the synaptic cleft through active Na+, Cl-, and glycine cotransport contributing to the termination of the glycinergic signal as well as supplying substrate to the presynaptic terminal for the maintenance of the neurotransmitter content in synaptic vesicles. Patients with mutations in the human GlyT2 gene (SLC6A5), develop hyperekplexia or startle disease (OMIM 149400), characterized by hypertonia and exaggerated startle responses to trivial stimuli that may have lethal consequences in the neonates as a result of apnea episodes. Post-translational modifications in cysteine residues of GlyT2 are an aspect of structural interest we analyzed. Our study is compatible with a reversible and short-lived S-acylation in spinal cord membranes, detectable by biochemical and proteomics methods (acyl-Rac binding and IP-ABE) confirmed with positive and negative controls (palmitoylated and non-palmitoylated proteins). According to a short-lived modification, direct labeling using click chemistry was faint but mostly consistent. We have analyzed the physiological properties of a GlyT2 mutant lacking the cysteines with high prediction of palmitoylation and the mutant is less prone to be included in lipid rafts, an effect also observed upon treatment with the palmitoylation inhibitor 2-bromopalmitate. This work demonstrates there are determinants of lipid raft inclusion associated with the GlyT2 mutated cysteines, which are presumably modified by palmitoylation.

Interplay between drought and plant viruses co-infecting melon plants.

Drought affects crops directly, and indirectly by affecting the activity of insect pests and the transmitted pathogens. Here, we established an experiment with well-watered or water-stressed melon plants, later single infected with either cucumber mosaic virus (CMV: non-persistent), or cucurbit aphid-borne yellow virus (CABYV: persistent), or both CMV and CABYV, and mock-inoculated control. We tested whether i) the relation between CMV and CABYV is additive, and ii) the relationship between water stress and virus infection is antagonistic, i.e., water stress primes plants for enhanced tolerance to virus infection. Water stress increased leaf greenness and temperature, and reduced leaf water potential, shoot biomass, stem dimensions, rate of flowering, CABYV symptom severity, and marketable fruit yield. Virus infection reduced leaf water potential transiently in single infected plants and persistently until harvest in double-infected plants. Double-virus infection caused the largest and synergistic reduction of marketable fruit yield. The relationship between water regime and virus treatment was additive in 12 out of 15 traits at harvest, with interactions for leaf water content, leaf:stem ratio, and fruit set. We conclude that both virus-virus relations in double infection and virus-drought relations cannot be generalized because they vary with virus, trait, and plant ontogeny.

[Translated article] Fractures of the peroneal malleolus: Current concepts.

Ankle fractures represent up to 9% of all fractures, with an increased incidence in the elderly population. Among these fractures, isolated fractures of the lateral malleolus are the most common, representing 65-70% of all cases. The therapeutic decision-making primarily relies on the stability of the ankle ring, considering it stable if affected at one point and unstable if two or more points are affected. Surgical treatment focuses on restoring the length of the fibula, joint reconstruction, stabilising the syndesmosis, and providing a stable fixation. It is crucial to rule out associated injuries that may influence therapeutic management. This article reviews the evaluation and management of lateral malleolus fractures, proposes a decision-making algorithm, and examines several fibular fixation options.

Boosting the Electrolysis of Monosaccharide-Based Streams in an Anion-Exchange Membrane Cell.

A systematic study on the electrochemical reforming of monosaccharides (fructose, glucose, and xylose) using Pt-based anodic electrocatalysts is here presented for the first time to completely optimize the anodic catalyst and electrolyzer operating conditions. First, the electro-oxidation of each molecule was studied using a monometallic (Pt) and two bimetallic (PtNi and PtCo) anodic electrocatalysts supported on graphene nanoplatelets (GNPs). Tests in a three-electrode cell showed superior electrochemical activity and durability of PtNi/GNPs, especially at potentials higher than 1.2 V vs RHE, with the highest electrocatalytic activity in d-xylose electro-oxidation. Then, monometallic (Pt and Ni) and bimetallic electrocatalysts with different Pt:Ni mass ratios (1:1 and 2:1) were studied for d-xylose electro-oxidation, with the 2:1 mass ratio presenting the best results. This electrocatalyst was selected as the most suitable for scale-up to an anion-exchange membrane electrolyzer, where the optimal operating potential was determined. Additionally, stable operating conditions of the electrolyzer were achieved by cyclic H2 production and cathodic regeneration polarization steps. This led to suitable and reproducible H2 production rates throughout the production cycles for renewable hydrogen production from biomass-derived streams.

Fractures of the peroneal malleolus: Current concepts. / Fracturas del maléolo peroneo: conceptos actuales.

Ankle fractures represent up to 9% of all fractures, with an increased incidence in the elderly population. Among these fractures, isolated fractures of the lateral malleolus are the most common, representing 65-70% of all cases. The therapeutic decision-making primarily relies on the stability of the ankle ring, considering it stable if affected at one point and unstable if two or more points are affected. Surgical treatment focuses on restoring the length of the fibula, joint reconstruction, stabilizing the syndesmosis, and providing a stable fixation. It is crucial to rule out associated injuries that may influence therapeutic management. This article reviews the evaluation and management of lateral malleolus fractures, proposes a decision-making algorithm, and examines several fibular fixation options.

The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: implications for deep space missions, female crews, and potential antioxidant countermeasures.

Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment is lacking. Here we asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received the antioxidant CDDO-EA (400 µg/g of food) or a control diet (vehicle, Veh) for 5 days and either Sham-irradiation (IRR) or whole-body 33-GCR (0.75Gy) on the 4th day. Three-months post-IRR, mice underwent two touchscreen-platform tests: 1) location discrimination reversal (which tests behavior pattern separation and cognitive flexibility, two abilities reliant on the dentate gyrus) and 2) stimulus-response learning/extinction. Mice then underwent arena-based behavior tests (e.g. open field, 3-chamber social interaction). At the experiment end (14.25-month post-IRR), neurogenesis was assessed (doublecortin-immunoreactive [DCX+] dentate gyrus neurons). Female mice exposed to Veh/Sham vs. Veh/33-GCR had similar pattern separation (% correct to 1st reversal). There were two effects of diet: CDDO-EA/Sham and CDDO-EA/33-GCR mice had better pattern separation vs. their respective control groups (Veh/Sham, Veh/33-GCR), and CDDO-EA/33-GCR mice had better cognitive flexibility (reversal number) vs. Veh/33-GCR mice. Notably, one radiation effect/CDDO-EA countereffect also emerged: Veh/33-GCR mice had worse stimulus-response learning (days to completion) vs. all other groups, including CDDO-EA/33-GCR mice. In general, all mice show normal anxiety-like behavior, exploration, and habituation to novel environments. There was also a change in neurogenesis: Veh/33-GCR mice had fewer DCX+ dentate gyrus immature neurons vs. Veh/Sham mice. Our study implies space radiation is a risk to a female crew's longitudinal mission-relevant cognitive processes and CDDO-EA is a potential dietary countermeasure for space-radiation CNS risks.

The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

Prevalence and prognostic meaning of interstitial lung abnormalities in remote CT scans of patients with interstitial lung disease treated with antifibrotic therapy.

OBJECTIVES: To describe the prevalence and characteristics of interstitial lung abnormalities (ILA) in CT scans performed prior to the initiation of antifibrotics in a series of patients with interstitial lung disease (ILD), and to identify characteristics apparent on early CT scans that could help to predict outcomes. METHODS: We conducted a retrospective observational study. The original cohort consisted of 101 patients diagnosed with ILD and treated with antifibrotics in a tertiary hospital. Patients were included if they had a thoracic CT scan performed at least one year before initiation of therapy. They were classified radiologically in three groups: without ILA, with radiological ILA and extensive abnormalities. ILA were classified as subpleural fibrotic, subpleural non-fibrotic and non-subpleural. The initial scan and the latest CT scan performed before treatment were read for assessing progression. The relationship between CT findings of fibrosis and the radiological progression rate and mortality were analyzed. RESULTS: We included 50 patients. Only 1 (2%) had a normal CT scan, 25 (50%) had extensive alterations and 24 (48%) had radiological criteria for ILA, a median of 98.2 months before initiation of antifibrotics, of them 18 (75%) had a subpleural fibrotic pattern. Significant bronchiectasis and obvious honeycombing in the lower zones were associated with shorter survival (p = 0.04). Obvious honeycombing in the lower zones was also significantly (p < 0.05) associated with a faster progression rate. CONCLUSIONS: Fibrotic ILAs are frequent in remote scans of patients with clinically relevant ILD, long before they require antifibrotics. Findings of traction bronchiectasis and honeycombing in the earliest scans, even in asymptomatic patients, are related to mortality and progression later on.

Organophosphate ester additives and microplastics in benthic compartments from the Loire estuary (French Atlantic coast).

We report the first empirical confirmation of the co-occurrence of organophosphate esters (OPEs) additives and microplastics (MPs) in benthic compartments from the Loire estuary. Higher median concentrations of MPs (3387 items/kg dw), ∑13tri-OPEs (12.0 ng/g dw) and ∑4di-OPEs (0.7 ng/g dw) were measured in intertidal sediments with predominance of fine particles, and under higher anthropogenic pressures, with a general lack of seasonality. Contrarily, Scrobicularia plana showed up to 4-fold higher ∑tri-OPE concentrations in summer (reaching 37.0 ng/g dw), and similar spatial distribution. Polyethylene predominated in both compartments. Tris(2-ethylhexyl) phosphate (TEHP), its degradation metabolite (BEHP) and tris-(2-chloro, 1-methylethyl) phosphate (TCIPP) were the most abundant OPEs in sediments, while TCIPP predominated in S. plana. The biota-sediment accumulation factors suggest bioaccumulation potential for chlorinated-OPEs, with higher exposure in summer. No significant correlations were generally found between OPEs and MPs in sediments suggesting a limited role of MPs as in-situ source of OPEs.

Modulation of myeloid-derived suppressor cell functions by oral inflammatory diseases and important oral pathogens.

The oral cavity presents a diverse microbiota in a dynamic balance with the host. Disruption of the microbial community can promote dysregulation of local immune response which could generate oral diseases. Additionally, alterations in host immune system can result in inflammatory disorders. Different microorganisms have been associated with establishment and progression of the oral diseases. Oral cavity pathogens/diseases can modulate components of the inflammatory response. Myeloid-derived suppressor cells (MDSCs) own immunoregulatory functions and have been involved in different inflammatory conditions such as infectious processes, autoimmune diseases, and cancer. The aim of this review is to provide a comprehensive overview of generation, phenotypes, and biological functions of the MDSCs in oral inflammatory diseases. Also, it is addressed the biological aspects of MDSCs in presence of major oral pathogens. MDSCs have been mainly analyzed in periodontal disease and Sjögren's syndrome and could be involved in the outcome of these diseases. Studies including the participation of MDSCs in other important oral diseases are very scarce. Major oral bacterial and fungal pathogens can modulate expansion, subpopulations, recruitment, metabolism, immunosuppressive activity and osteoclastogenic potential of MDSCs. Moreover, MDSC plasticity is exhibited in presence of oral inflammatory diseases/oral pathogens and appears to be relevant in the disease progression and potentially useful in the searching of possible treatments. Further analyses of MDSCs in oral cavity context could allow to understand the contribution of these cells in the fine-tuned balance between host immune system and microorganism of the oral biofilm, as well as their involvement in the development of oral diseases when this balance is altered.

A cathodoluminescence study of InP/InGaP axially heterostructured NWs for tandem solar cells.

Axially heterostructured nanowires (NWs) constitute a promising platform for advanced electronic and optoelectronic nanodevices. The presence of different materials in these NWs introduces a mismatch resulting in complex strain distributions susceptible of changing the band gap and carrier mobility. The growth of these NWs presents challenges related to the reservoir effect in the catalysts droplet that affect to the junction abruptness, and the occurrence of undesired lateral growth creating core-shell heterostructures that introduce additional strain. We present herein a cathodoluminescence (CL) analysis on axially heterostructured InP/InGaP NWs with tandem solar cell structure. The CL is complemented with micro Raman, micro photoluminescence (PL), and high resolution transmission electron microscopy measurements. The results reveal the zinc blende structure of the NWs, the presence of a thin InGaP shell around the InP bottom cell, along with its associated strain, and the doping distribution.

Development of a Questionnaire on Knowledge, Habits, and Attitudes on Sexually Transmitted Infections in Teenagers and Young Adults. / [Artículo traducido] Generación de un cuestionario sobre conocimientos, hábitos y actitudes sobre infecciones de transmisión sexual en adolescentes y adultos jóvenes.

Communication with teenagers who are significantly affected by sexually transmitted infections (STIs) is essential for the sake of prevention. The aim of this study is to develop a specific questionnaire for surveying the degree of knowledge, behavior, and attitudes of current teenagers and young adults on STIs to come up with the proper training tools. We conducted the study following the Delphi method, a 2-round critical assessment score (from 1 to 9) of all domains and items. Only domains and items with median scores ≥8 were selected. A total of 8 panelists were involved in this survey. After establishing a median score ≥8, a total of 14 domains and 40 items were eventually selected. This is the first questionnaire ever conducted to study the knowledge, habits, and attitudes of contemporary teenagers and young adults on STIs, and stands as a valuable tool for future training on STI prevention in teenagers and young adults.

Spinal gunshot wounds: A retrospective, multicenter, cohort study. / [Artículo traducido] Lesiones vertebrales por proyectil de arma de fuego: estudio de cohorte retrospectivo, multicéntrico.

INTRODUCTION AND OBJECTIVE: To describe the demographic and clinical characteristics and treatment of patients with spinal gunshot wounds across Latin America. MATERIAL AND METHODS: Retrospective, multicenter cohort study of patients treated for gunshot wounds to the spine spanning 12 institutions across Latin America between January 2015 and January 2022. Demographic and clinical data were recorded, including the time of injury, initial assessment, characteristics of the vertebral gunshot injury, and treatment. RESULTS: Data on 423 patients with spinal gunshot injuries were extracted from institutions in Mexico (82%), Argentina, Brazil, Colombia, and Venezuela. Patients were predominantly male civilians in low-risk-of-violence professions, and of lower/middle social status, and a sizeable majority of gunshots were from low-energy firearms. Vertebral injuries mainly affected the thoracic and lumbar spine. Neurological injury was documented in 320 (76%) patients, with spinal cord injuries in 269 (63%). Treatment was largely conservative, with just 90 (21%) patients treated surgically, principally using posterior open midline approach to the spine (79; 87%). Injury features distinguishing surgical from non-surgical cases were neurological compromise (P = 0.004), canal compromise (P < 0.001), dirty wounds (P < 0.001), bullet or bone fragment remains in the spinal canal (P < 0.001) and injury pattern (P < 0.001). After a multivariate analysis through a binary logistic regression model, the aforementioned variables remained statistically significant except neurological compromise. CONCLUSIONS: In this multicenter study of spinal gunshot victims, most were treated non-surgically, despite neurological injury in 76% and spinal injury in 63% of patients.

Changes in benign prostatic hyperplasia management in Valencia: a real-world evidence analysis.

INTRODUCTION AND OBJECTIVES: A training program was developed to increase general practitioners' engagement in the optimal management of Benign Prostatic Hyperplasia (BPH). The goal of this study was to evaluate changes in BPH management after the implementation of a training program. MATERIAL AND METHODS: This observational retrospective cohort study was conducted between 2019 and 2020. Aggregated data were analyzed in three evaluation periods (2010, 2012 and 2015), addressing quality indicators for diagnosis, treatment, and treatment outcomes. RESULTS: Overall, 118 795 patients who presented any data points were included. All quality indicators (number of IPSS and PSA determinations) increased between the first period and the last. Combination (α-blocker + 5-ARI) therapy was increasingly prescribed during the study periods whereas the proportion of prescriptions for single-agent α-blocker showed no significant differences among the periods analyzed. However, the total number of patients eligible for combination therapy who actually received this treatment was low in all periods (7.5%, 17.9%, and 20.1%, in 2010, 2012, and 2015, respectively). The outcome indicators revealed a decrease in referrals to the urology unit mostly among newly diagnosed patients. Even though the proportion of patients who underwent BPH-related surgeries increased significantly from the first to the second period, the number of surgeries remained stable between the second and third periods. CONCLUSIONS: The training program had a generally positive impact on the management of BPH patients in PC, but the overall study period may be insufficient to show an effect on some outcome indicators such as the number of surgeries.

Exploring the physiological benefits of carrying a suspended backpack versus a traditional backpack.

This study investigates the differences in metabolic energy cost and physiological adaptations between carrying a suspended backpack and a traditional backpack during exercise. For that, 30 males completed the Bruce test while carrying a loaded backpack. Researchers used a metabolic system to obtain variables, analysed muscle oxygen saturation, and used a 2-way RM ANOVA. As results, a significant fatigue interaction was found, but the interaction between fatigue and backpack was non-significant. Using a suspended backpack resulted in energetic advantages in oxygen consumption, muscle oxygen saturation, and performance compared to a traditional backpack. In conclusion, this study offers insights into the physiological implications of using a suspended backpack, suggesting it may reduce the risk of musculoskeletal issues and improve performance for those carrying heavy loads.Practitioner summary: The suspended-load backpacks have been proposed as an alternative to traditional backpacks. This study highlighted that the use of a suspended backpack provided some energetical advantages adaptation compared to the traditional backpack in terms of oxygen consumption, muscle oxygen saturation and performance during a multistage treadmill test walking-running test.

Is low back pain a risk/prognostic factor for the development and/or progression of temporomandibular disorders? A systematic review with meta-analysis.

OBJECTIVES: To evaluate the association between low back pain (LBP) and painful temporomandibular disorders (TMDs). METHODS: Systematic review of observational studies. Searches were conducted using OVID MEDLINE, CINHAL, Web of Science and PUBMED databases up to 21 October 2022. Qualitative and quantitative analyses were performed. Risk of bias (RoB) was assessed using the Quality in Prognosis Studies tool (QUIPS). RESULTS: Eight studies were included in the present review with meta-analysis. The first onset of TMDs was more likely in patients with previous chronic LBP (hazard ratio (HR) 1.53 [95% confidence interval (CI): 1.28; 1.83, p < .00001]). In addition, patients with chronic LBP had 3.25 times the odds (OR) [95% CI: 1.94; 5.43, p < .00001] of having chronic TMDs than those who did not have chronic LBP. In addition, the higher the exposure to chronic LBP, the higher the risk of developing a first onset of TMDs. CONCLUSIONS: Chronic LBP can be considered a risk/contributing factor for painful TMDs. Although there is a high certainty in the evidence linking chronic LBP with the risk of a first onset of TMDs, there are insufficient studies to draw definitive conclusions. Furthermore, while an association between chronic LBP and chronic TMDs and a dose-effect was observed between these two conditions, a limited number of studies and evidence exist to support these findings. Future studies are needed to increase the body of evidence.

[Analysis of notifications of drug-induced skin ulcers in Spain]. / Análisis de las notificaciones de úlceras cutáneas inducidas por medicamentos en España.

Skin ulcers are a serious health problem with significant socioeconomic and labour repercussions and a high tendency to chronicity and recurrence; approximately, up to 50% remain active between six months to one year. AIM: To study the role of drugs in the aetiology of skin ulcers. MATERIAL AND METHOD: A comprehensive study of all spontaneous reports related to skin ulcers that appear in the Spanish Pharmacovigilance System of Medicines for Human Use database. RESULTS: A total of 292 reports were identified containing suspected adverse drug reactions (ADRs) of ulcer lesion type. Three hundred sixty-nine medications with 427 active ingredients were identified. The ulcers appeared mainly in women with a mean age of 56.6 years. The most frequently reported suspected drugs were SGLT-2, vaccines against COVID-19, methotrexate, hydroxycarbamide, trimethoprim-sulfamethoxazole, foscarnet trisodium hexahydrate, ribavirin, docetaxel, acenocumarol and imiquimod, and the combination of lidocaine Hcl-pentosan polysulfate sodium-triamcinolone acetonide. DISCUSSION: Numerous medications may cause ulcers as an adverse reaction. This possibility should not be ruled out when a new skin lesion appears after the administration of new drugs since 25% of the ADRs were unknown at the time of their notification, as were the cases of ulcers associated with i-SGLT2 and vaccines against COVID at the beginning of their commercialization. However, informative health alerts can be generated by continuously notifying suspected ADRs, so we strongly advise reporting any suspected ADRs to the regional pharmacovigilance system.

Development of a Questionnaire on Knowledge, Habits, and Attitudes on Sexually Transmitted Infections in Teenagers and Young Adults.

Communication with teenagers who are significantly affected by sexually transmitted infections (STIs) is essential for the sake of prevention. The aim of this study is to develop a specific questionnaire for surveying the degree of knowledge, behavior, and attitudes of current teenagers and young adults on STIs to come up with the proper training tools. We conducted the study following the Delphi method, a 2-round critical assessment score (from 1 to 9) of all domains and items. Only domains and items with median scores ≥8 were selected. A total of 8 panelists were involved in this survey. After establishing a median score ≥8, a total of 14 domains and 40 items were eventually selected. This is the first questionnaire ever conducted to study the knowledge, habits, and attitudes of contemporary teenagers and young adults on STIs, and stands as a valuable tool for future training on STI prevention in teenagers and young adults.