Epidemiology of traumatic spinal cord injury in Spain: A ten-year analysis of trend of clinical and demographic characteristics.

CONTEXT: The study of epidemiological changes of traumatic spinal cord injury (TSCI) is needed due to its highly variable incidence. OBJECTIVE: To determine the incidence of TSCI in Spain and to describe the trend of clinical and demographic characteristics according to age group during a 10-year period. METHODS: A prospective cohort study was conducted. A multidisciplinary team evaluated all individuals with new TSCI. The data were recorded according to the International Spinal Cord Injury Core Data Sets. RESULTS: In a 10-year period, 933 new patients with TSCI were admitted to the hospital. The annual incidence of TSCI was 6.2 per million. The leading causes of injury were traffic accidents (38.5%), low-level falls (20.6%), and high-level falls (19.1%). Males, age group of 31-45 years, and cervical level of injury were the most common profiles of TSCI. In patients over 60 years,71.5% were injured following a fall, particularly low-level falls (47.2%). In patients under 60 years old, the leading cause of SCI was traffic accidents (46%). The proportion of tetraplegia in patients above 60 years was 68.3%, compared to 43.7% in patients under 60 years of age. Patients in the age group above 60 years were hospitalized with a shorter duration of rehabilitation compared to younger age group. CONCLUSIONS: Compared with globally estimated data reported in previous studies, this research demonstrated a low incidence of TSCI in Spain, suggesting a decrease in the last years. Falls and traffic accidents were the most common causes of TSCI in elderly and youth, respectively. Prevention programs should focus on these issues.

Metabolic profiling of single cells by exploiting NADH and FAD fluorescence via flow cytometry.

OBJECTIVE: The metabolism of different cells within the same microenvironment can differ and dictate physiological or pathological adaptions. Current single-cell analysis methods of metabolism are not label-free. METHODS: The study introduces a label-free, live-cell analysis method assessing endogenous fluorescence of NAD(P)H and FAD in surface-stained cells by flow cytometry. RESULTS: OxPhos inhibition, mitochondrial uncoupling, glucose exposure, genetic inactivation of glucose uptake and mitochondrial respiration alter the optical redox ratios of FAD and NAD(P)H as measured by flow cytometry. Those alterations correlate strongly with measurements obtained by extracellular flux analysis. Consequently, metabolically distinct live B-cell populations can be resolved, showing that human memory B-cells from peripheral blood exhibit a higher glycolytic flexibility than naïve B cells. Moreover, the comparison of blood-derived B- and T-lymphocytes from healthy donors and rheumatoid arthritis patients unleashes rheumatoid arthritis-associated metabolic traits in human naïve and memory B-lymphocytes. CONCLUSIONS: Taken together, these data show that the optical redox ratio can depict metabolic differences in distinct cell populations by flow cytometry.

Adequate control of seizures in a case of lead migration and neuromodulation of the posterior Sylvian junction: A case report.

Background: This report aims to describe the neuromodulation effect on seizure control in a patient with a left hippocampal migrated electrode to the Posterior Sylvian Junction (PSJ) during a follow-up of 17 years. Case Description: We report a case of a female patient with drug-resistant epilepsy who initiated at seven years old and underwent a stereotactic frame-based insertion of a left hippocampal electrode for deep brain stimulation (DBS). Posterior migration of the electrode was identified at PSJ by postoperative magnetic resonance imaging one month after surgery. A consistent seizure reduction (Engel IC) was obtained with 2v-120 uS-145 Hz, contacts 0-3 negative, casing positive DBS parameters and maintained to this day. Patient data were collected from electronic medical records preceded by obtaining an informed consent for research and publication purposes. Stimulation parameter adjustments were confirmed with the digital records of the local device provider (Medtronic). Results: PSJ is a connectivity confluence point of white matter pathways in the posterior quadrant of the hemispheres. White mater DBS could be considered for research as a potential complementary target for neuromodulation of refractory epilepsy.

Evaluating the impact of gypsum as a novel bedding material on broiler performance, foot pad health, and fear response.

Flue Gas Desulfurization (FGD) gypsum is a byproduct of the coal-fired power plant process commonly used to remove sulfur dioxide emissions from the flue gas. FGD gypsum has numerous industrial, agricultural, and environmental applications. This study aimed to explore a novel approach involving the use of FGD gypsum combined with different litter treatments as bedding for broiler production. It focused on performance metrics, including adjusted feed conversion ratio (AFCR) and average body weight (BW), foot pad dermatitis (FPD), and fear response over 5 consecutive flocks. A total of 1,800 one-day-old Ross 708 chicks were randomly assigned to 24 pens (75 birds/pen), divided into 6 treatment groups (4 pens/treatment), with 5 replications and raised until 42 d old (d). Treatments were gypsum that was decaked (D), rotovated (E), and rotovated then windrowed (F) between flocks. Control treatments using pine shavings were decaked (A), rotovated (B), and windrowed postrotovating (C). AFCR, average BW, and mortality were used as a measure of production. Foot pad dermatitis scores were taken on d42 using a scale of 0 (absence), 1 (mild), and 2 (severe). Response to observer and human approach test were used to measure fear response. Data were analyzed as a 2-way ANOVA (Proc Glimmix) for the main effects of bedding type and litter treatment. Means were identified using Tukey's HSD. No effect of bedding type or litter treatment was found for AFCR, BW, or mortality. FPD scores 2 and 1, were higher with pine shavings than gypsum (P = 0.01 and P = 0.01, respectively). While FPD scores 0 were higher for gypsum than the pine shaving (P = 0.01). No difference in fear response was found among birds raised on any of the gypsum litter treatments and any of the pine shaving litter treatments. Overall, the use of gypsum as bedding results in equivalent production and fear response to pine shavings, while increasing FPD quality when compared to pine shaving.

CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up.

BACKGROUND: Treatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission. METHODS: We evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology-European League against Rheumatism (ACR-EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded. RESULTS: The median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR-EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell-associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization. CONCLUSIONS: In this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.).

Use of electromyographic biofeedback in rehabilitation following anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

BACKGROUND: Rehabilitation following anterior cruciate ligament (ACL) reconstruction surgery is essential to regain functionality and return to previous activity level. Electromyographic biofeedback may be an effective intervention for rehabilitation of patients following ACL surgery. OBJECTIVE: To synthesize the available evidence on the effect of electromyographic biofeedback in the treatment of quadriceps strength following ACL surgery. DESIGN: Systematic review with meta-analysis. DATA SOURCES: PubMed, EMBASE, CENTRAL and Epistemonikos were searched. ELIGIBILITY CRITERIA: Randomized clinical trials with patients undergoing ACL reconstruction surgery comparing biofeedback with a standard rehabilitation control group. DATA EXTRACTION AND DATA SYNTHESIS: Two authors selected articles and performed data extraction. The analysed outcomes were strength, function, pain, knee extension and balance. The risk of bias of individual studies was assessed using the Cochrane Risk of Bias Tool. Results were combined through random-effects meta-analysis, reporting mean differences. RESULTS: Eight articles were included in the qualitative analysis, and four articles were included in the quantitative analysis. The interventions lasted between 4 and 12 weeks. Three studies evaluated the effect of biofeedback on quadriceps strength; of these, two studies showed a significant difference in favour of the biofeedback group. In addition, biofeedback was found to improve knee extension [standardized mean difference - 1.3, 95% confidence interval (CI) - 1.74 to -0.86] and balance (one study). There was no significant difference in Lysholm score (mean difference -6.21, 95% CI -17.51 to 5.08; I2 =59%) or pain between the biofeedback group and the control group. CONCLUSION: Electromyographic biofeedback in knee rehabilitation could be useful following ACL reconstruction surgery. KEY MESSAGES: SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO (CRD42020193768).

Sustained pacifier use is associated with smaller vocabulary sizes at 1 and 2 years of age: A cross-sectional study.

Pacifier use during childhood has been hypothesized to interfere with language processing, but, to date, there is limited evidence revealing detrimental effects of prolonged pacifier use on infant vocabulary learning. In the present study, parents of 12- and 24-month-old infants were recruited in Oslo (Norway). The sample included 1187 monolingual full-term born (without visual, auditory, or cognitive impairments) infants: 452 (230 girls; 222 boys) 12-month-olds and 735 (345 girls; 390 boys) 24-month-olds. Parents filled out an online Norwegian Communicative Development Inventory (CDI), which assesses the vocabulary in comprehension and production for 12-month-old infants and in production only for 24-month-old infants. CDI scores were transformed into age- and sex-adjusted percentiles using Norwegian norms. Additionally, parents retrospectively reported their child's daytime pacifier use, in hours, at 2-month intervals, from birth to the assessment date. Maternal education was used to control, in the analyses, for the socio-economic status. We found that greater pacifier use in an infant's lifespan was associated with lower vocabulary size. Pacifier use later in life was more negatively associated with vocabulary size than precocious use, and increased the odds of being a low language scorer. In sum, our study moves beyond the findings of momentary effects of experimentally induced "impairment" in articulators' movement on speech perception and suggests that, from 12 months of age, constraints on the infant's speech articulators (pacifier use) may be negatively associated with word comprehension and production. RESEARCH HIGHLIGHT: We examined the relationship between pacifier use and vocabulary sizes in production at 24 months of age and comprehension and production at 12 months of age. Lifespan Pacifier Use (LPU) was negatively correlated with vocabulary sizes in comprehension and production among 12-month-old infants and negatively correlated with production for 24-month-olds. Later pacifier use was found to be more negatively correlated with vocabulary size in infants, as compared to more precocious use. The amount of pacifier use in the 2 months prior to a child's second birthday was predictive of a higher prevalence of low vocabulary scores in 24-month-olds.

Preliminary data from a 4-year mirror-image and multicentre study of patients initiating paliperidone palmitate 6-monthly long-acting injectable antipsychotic: the Paliperidone 2 per Year study.

Background: Paliperidone palmitate 6-monthly (PP6M) is the first long-acting antipsychotic injectable (LAI) to allow for only two medication administrations per year, though there is presently limited insight into its effectiveness and potential added value in real clinical practice conditions. Objectives: To present our ongoing study and draw its preliminary data on patient characteristics initiating PP6M and adherence during the first year of treatment. Methods: The paliperidone 2 per year (P2Y) study is a 4-year, multicentre, prospective mirror-image pragmatic study taking place at over 20 different sites in Europe. The mirror period covers 2 years either side of the PP6M LAI initiation. Retrospective data for the previous 2 years are collected for each patient from the electronic health records. Prospective data are recorded at baseline, 6, 12, 18 and 24 months of drug administration and also cover information on concomitant psychiatric medication, relapses, hospital admissions, side effects, discontinuation and its reasons. Meanwhile, here we present preliminary data from the P2Y study at basal and 6-month period (first and second PP6M administration). Results: At the point of PP6M initiation, the most frequent diagnosis was schizophrenia (69%), the clinical global impression scale mean score was 3.5 (moderately markedly ill) and the rate of previous hospital admissions per patient and year was 0.21. PP6M was initiated after a median of 3-4 years on previous treatment: 146 (73%) from paliperidone palmitate 3-monthly, 37 (19%) from paliperidone palmitate 1-monthly and 17 (9%) from other antipsychotics. The mean dose of the first PP6M was 1098.9 mg. The retention rate at 6 months and 1 year of treatment on PP6M in our cohort was 94%. Conclusion: Patient and clinician preference for LAIs with longer dosing intervals was the main reason for PP6M initiation/switching resulting in high treatment persistence. Future data are needed to evaluate the full impact of PP6M in clinical practice.

The Molecular Role of Polyamines in Age-Related Diseases: An Update.

Polyamines (Pas) are short molecules that exhibit two or three amine groups that are positively charged at a physiological pH. These small molecules are present in high concentrations in a wide variety of organisms and tissues, suggesting that they play an important role in cellular physiology. Polyamines include spermine, spermidine, and putrescine, which play important roles in age-related diseases that have not been completely elucidated. Aging is a natural process, defined as the time-related deterioration of the physiological functions; it is considered a risk factor for degenerative diseases such as cardiovascular, neurodegenerative, and musculoskeletal diseases; arthritis; and even cancer. In this review, we provide a new perspective on the participation of Pas in the cellular and molecular processes related to age-related diseases, focusing our attention on important degenerative diseases such as Alzheimerߣs disease, Parkinsonߣs disease, osteoarthritis, sarcopenia, and osteoporosis. This new perspective leads us to propose that Pas function as novel biomarkers for age-related diseases, with the main purpose of achieving new molecular alternatives for healthier aging.

Buffering Capacity Comparison of Tris Phosphate Carbonate and Buffered Peptone Water Salmonella Pre-Enrichments for Manufactured Feed and Feed Ingredients.

Various culture-based methods to detect Salmonella in animal feed have been developed due to the impact of this bacterium on public and animal health. For this project, tris phosphate carbonate (TPC) and buffered peptone water (BPW) buffering capacities were compared as pre-enrichment mediums for the detection of Salmonella in feed ingredients. A total of 269 samples were collected from 6 feed mills and mixed with the pre-enrichments; pH was measured before and after a 24 h incubation. Differences were observed when comparing pH values by sample type; DDGS and poultry by-product meal presented lower initial pH values for TPC and BPW compared to the other samples. For both TPC and BPW, meat and bone meal presented higher final pH values, while soybean meal and peanut meal had lower final pH values. Furthermore, for BPW, post cooling, pellet loadout, and wheat middlings reported lower final pH values. Additionally, most feed ingredients presented significant differences in pH change after 24 h of incubation, except DDGS. From meat and bone meal samples, four Salmonella isolates were recovered and identified: three using BPW and one using TPC. TPC provided greater buffer capacity towards neutral pH compared to BPW, but BPW was more effective at recovering Salmonella.

Suppression of neutrophils by sodium exacerbates oxidative stress and arthritis.

Introduction: Typical Western diet, rich in salt, contributes to autoimmune disease development. However, conflicting reports exist about the effect of salt on neutrophil effector functions, also in the context of arthritis. Methods: We investigated the effect of sodium chloride (NaCl) on neutrophil viability and functions in vitro, and in vivo employing the murine K/BxN-serum transfer arthritis (STA) model. Results and discussion: The effects of NaCl and external reactive oxygen species (H2O2) were further examined on osteoclasts in vitro. Hypertonic sodium-rich media caused primary/secondary cell necrosis, altered the nuclear morphology, inhibited phagocytosis, degranulation, myeloperoxidase (MPO) peroxidation activity and neutrophil extracellular trap (NET) formation, while increasing total ROS production, mitochondrial ROS production, and neutrophil elastase (NE) activity. High salt diet (HSD) aggravated arthritis by increasing inflammation, bone erosion, and osteoclast differentiation, accompanied by increased NE expression and activity. Osteoclast differentiation was decreased with 25 mM NaCl or 100 nM H2O2 addition to isotonic media. In contrast to NaCl, external H2O2 had pro-resorptive effects in vitro. We postulate that in arthritis under HSD, increased bone erosion can be attributed to an enhanced oxidative milieu maintained by infiltrating neutrophils, rather than a direct effect of NaCl.

Attitudes and Beliefs of Mental Health Professionals towards Trans People: A Systematic Review of the Literature.

A systematic review was conducted to assess and synthesize recent research on mental health professionals' attitudes towards trans people. The main objectives of our research were (a) to identify, synthesize, and analyze the scientific evidence available so far about the attitudes of mental health professionals towards the trans community, and (b) to determine the factors related to these professionals' attitudes, paying special attention to psychosocial and cultural aspects. A systematic search was carried out in the following electronic databases: Pubmed, Web of Science, PsycINFO, PsycARTICLES, Gender Studies Database, and Lilacs. A total of 32 articles of quantitative (n = 19), qualitative (n = 11), and mixed (n = 2) design, published up to March 2023, were included. Most studies used a cross-sectional or qualitative design, limiting the possibility of generalizing the results. The studies reviewed indicated mostly positive attitudes among the professionals, depending on their psychosocial characteristics. In line with the results of our review, we recommend that the training of professionals is important to improve their positive attitudes towards transgender and gender diverse people.

Seizures regulate the cation-Cl- cotransporter NKCC1 in a hamster model of epilepsy: implications for GABA neurotransmission.

Background: The balance between the activity of the Na+/K+/Cl- cotransporter (NKCC1) that introduces Cl- into the cell and the K+/Cl- cotransporter (KCC2) that transports Cl- outside the cell is critical in determining the inhibitory or excitatory outcome of GABA release. Mounting evidence suggests that the impairment of GABAergic inhibitory neurotransmission plays a crucial role in the pathophysiology of epilepsy, both in patients and animal models. Previous studies indicate that decreased KCC2 expression is linked to audiogenic seizures in GASH/Sal hamsters, highlighting that Cl- imbalance can cause neuronal hyperexcitability. In this study, we aimed to investigate whether the Na+/K+/Cl- cotransporter NKCC1 is also affected by audiogenic seizures and could, therefore, play a role in neuronal hyperexcitability within the GASH/Sal epilepsy model. Methods: NKCC1 protein expression in both the GASH/Sal strain and wild type hamsters was analyzed by immunohistochemistry and Western blotting techniques. Brain regions examined included cortex, hippocampus, hypothalamus, inferior colliculus and pons-medulla oblongata, which were evaluated both at rest and after sound-inducing seizures in GASH/Sal hamsters. A complementary analysis of NKCC1 gene slc12a2 expression was conducted by real-time PCR. Finally, protein and mRNA levels of glutamate decarboxylase GAD67 were measured as an indicator of GABA release. Results: The induction of seizures caused significant changes in NKCC1 expression in epileptic GASH/Sal hamsters, despite the similar brain expression pattern of NKCC1 in GASH/Sal and wild type hamsters in the absence of seizures. Interestingly, the regulation of brain NKCC1 by seizures demonstrated regional specificity, as protein levels exclusively increased in the hippocampus and hypothalamus. Complementary real-time PCR analysis revealed that NKCC1 regulation was post-transcriptional only in the hypothalamus. In addition, seizures also modulated GAD67 mRNA levels in a brain region-specific manner. The increased GAD67 expression in the hippocampus and hypothalamus of the epileptic hamster brain suggests that NKCC1 upregulation overlaps with GABA release in these regions during seizures. Conclusions: Our results indicate that seizure induction causes dysregulation of NKCC1 expression in GASH/Sal animals, which overlaps with changes in GABA release. These observations provide evidence for the critical role of NKCC1 in how seizures affect neuronal excitability, and support NKCC1 contribution to the development of secondary foci of epileptogenic activity.

Effect of translucency and eggshell color on broiler breeder egg hatchability and hatch chick weight.

A successful hatch has a considerable economic impact on all poultry companies. The aim of the current study was to describe the possible effects of shell translucency (T score) and coloration lightness (L* value) on shell thickness, hatchability, and chick weight. A total of 4,320 eggs from 4 commercial Ross 708 breeder flocks (50-55-wk old) were used. Eggs were selected for T score and L* value. A 3-point subjective scoring system was used for T score (1 = low, 2 = medium, 3 = high), and an electronic colorimeter for L* value, sorting the eggs as light (avg. L* = 80.7) or dark (avg. L* = 76.0). Data were analyzed using the GLIMMIX procedure of SAS (V9.4) and Tukey's HSD test was performed to separate means, a significant difference was considered when P ≤ 0.05. Results suggest that the color of the eggshell was related to the egg weight on the day of collection (P = 0.0056) and at transfer (P = 0.0211), in both cases dark eggs were 0.6 g heavier than light eggs. Dark eggs had a 3.8% increased hatchability of egg set (P = 0.0481) and yielded 6 µm thicker shells (P = 0.0019) when compared to light eggs. Regarding translucency, egg weight at transfer was 0.8 g heavier for T score 1 eggs compared to T score 3 (P = 0.0358). The translucency score of 1 had a 6.9% higher hatchability of eggs set (P = 0.0127) and 0.7 g heavier chick weight (P = 0.0385) compared to T score 3. However, T score 1 eggs had shells 28 µm thinner than the T score 2 and 34 µm thinner than T score 3 (P < 0.0001). An interaction effect was observed for eggshell thickness, L* value, and T score, where eggs classified as light with T score 1 had thinner eggshells compared to those that were dark with T score 3 (P = 0.0292). These results suggest that eggshell translucency and coloration lightness can be good noninvasive indicators of eggshell thickness, hatchability, and chick weight in broiler breeder flocks.

IL-3 orchestrates ulcerative colitis pathogenesis by controlling the development and the recruitment of splenic reservoir neutrophils.

Inflammatory bowel diseases (IBDs) are a global health issue with an increasing incidence. Although the pathogenesis of IBDs has been investigated intensively, the etiology of IBDs remains enigmatic. Here, we report that interleukin-3 (Il-3)-deficient mice are more susceptible and exhibit increased intestinal inflammation during the early stage of experimental colitis. IL-3 is locally expressed in the colon by cells harboring a mesenchymal stem cell phenotype and protects by promoting the early recruitment of splenic neutrophils with high microbicidal capability into the colon. Mechanistically, IL-3-dependent neutrophil recruitment involves CCL5+ PD-1high LAG-3high T cells, STAT5, and CCL20 and is sustained by extramedullary splenic hematopoiesis. During acute colitis, Il-3-/- show, however, increased resistance to the disease as well as reduced intestinal inflammation. Altogether, this study deepens our understanding of IBD pathogenesis, identifies IL-3 as an orchestrator of intestinal inflammation, and reveals the spleen as an emergency reservoir for neutrophils during colonic inflammation.

Approaching the body of evidence: Key concepts of Overviews. / Abordando el cuerpo de evidencia: conceptos fundamentales de los overviews.

The increasing production of primary research and literature reviews in the last decades has made it necessary to develop a new methodological design to synthesize the evidence: the overviews. An overview is a type of evidence synthesis that uses systematic reviews as the unit of analysis, with the aim of extracting and analyzing the results for a new or broader research question, helping the shared decision-making processes. The aim of this article is to introduce the reader to this type of evidence summaries, highlighting the differences between overviews and other types of synthesis, the unique methodological aspects of overviews, and future challenges. This is the twelfth article from a collaborative methodological series of narrative reviews about biostatistics and clinical epidemiology.

El aumento de la producción de investigación primaria y de las revisiones de la literatura durante las últimas décadas ha hecho necesario el desarrollo de un nuevo diseño metodológico para sintetizar la evidencia: los overviews. Un overview es un diseño de síntesis de evidencia que toma como unidad de análisis a las revisiones sistemáticas, con el objetivo de extraer y analizar los resultados para una pregunta de interés nueva o más amplia, ayudando así a mejorar los procesos de toma de decisiones informadas. El objetivo de este artículo es introducir al lector a este tipo de resúmenes de evidencia, destacando las diferencias con los otros tipos de síntesis de evidencia, los aspectos metodológicos particulares de los overviews, y los desafíos pendientes. Este artículo es el duodécimo de una serie metodológica colaborativa de revisiones narrativas sobre temáticas de bioestadística y epidemiología clínica.

Butyrophilin 2a2 (Btn2a2) expression on thymic epithelial cells promotes central T cell tolerance and prevents autoimmune disease.

Butyrophilins are surface receptors belonging to the immunoglobulin superfamily. While several members of the butyrophilin family have been implicated in the development of unconventional T cells, butyrophilin 2a2 (Btn2a2) has been shown to inhibit conventional T cell activation. Here, we demonstrate that in steady state, the primary source of Btn2a2 are thymic epithelial cells (TEC). Absence of Btn2a2 alters thymic T cell maturation and bypasses central tolerance mechanisms. Furthermore, Btn2a2-/- mice develop spontaneous autoimmunity resembling human primary Sjögren's Syndrome (pSS), including formation of tertiary lymphoid structures (TLS) in target organs. Ligation of Btn2a2 on developing thymocytes is associated with reduced TCR signaling and CD5 levels, while absence of Btn2a2 results in increased TCR signaling and CD5 levels. These results define a novel role for Btn2a2 in promoting central tolerance by modulating TCR signaling strength and indicate a potential mechanism of pSS development.

Innovative perspectives in limbic surgery using deep brain stimulation.

Limbic surgery is one of the most attractive and retaken fields of functional neurosurgery in the last two decades. Psychiatric surgery emerged from the incipient work of Moniz and Lima lesioning the prefrontal cortex in agitated patients. Since the onset of stereotactic and functional neurosurgery with Spiegel and Wycis, the treatment of mental diseases gave attention to refractory illnesses mainly with the use of thalamotomies. Neurosis and some psychotic symptoms were treated by them. Several indications when lesioning the brain were included: obsessive-compulsive disorder, depression, and aggressiveness among others with a diversity of targets. The indiscriminately use of anatomical sites without enough scientific evidence, and uncertainly defined criteria for selecting patients merged with a deficiency in ethical aspects, brought a lack of procedures for a long time: only select clinics allowed this surgery around the world from 1950 to the 1990s. In 1999, Nuttin et al. began a new chapter in limbic surgery with the use of Deep Brain Stimulation, based on the experience of pain, Parkinson's disease, and epilepsy. The efforts were focused on different targets to treat depression and obsessive-compulsive disorders. Nevertheless, other diseases were added to use neuromodulation. The goal of this article is to show the new opportunities to treat neuropsychiatric diseases.

Abordando el cuerpo de evidencia: conceptos fundamentales de los overviews / Approaching the body of evidence: Key concepts of Overviews

El aumento de la producción de investigación primaria y de las revisiones de la literatura durante las últimas décadas ha hecho necesario el desarrollo de un nuevo diseño metodológico para sintetizar la evidencia: los overviews. Un overview es un diseño de síntesis de evidencia que toma como unidad de análisis a las revisiones sistemáticas, con el objetivo de extraer y analizar los resultados para una pregunta de interés nueva o más amplia, ayudando así a mejorar los procesos de toma de decisiones informadas. El objetivo de este artículo es introducir al lector a este tipo de resúmenes de evidencia, destacando las diferencias con los otros tipos de síntesis de evidencia, los aspectos metodológicos particulares de los overviews, y los desafíos pendientes. Este artículo es el duodécimo de una serie metodológica colaborativa de revisiones narrativas sobre temáticas de bioestadística y epidemiología clínica.

The increasing production of primary research and literature reviews in the last decades has made it necessary to develop a new methodological design to synthesize the evidence: the overviews. An overview is a type of evidence synthesis that uses systematic reviews as the unit of analysis, with the aim of extracting and analyzing the results for a new or broader research question, helping the shared decision-making processes. The aim of this article is to introduce the reader to this type of evidence summaries, highlighting the differences between overviews and other types of synthesis, the unique methodological aspects of overviews, and future challenges. This is the twelfth article from a collaborative methodological series of narrative reviews about biostatistics and clinical epidemiology.

Glutathione peroxidase 3 is a novel clinical diagnostic biomarker and potential therapeutic target for neutrophils in rheumatoid arthritis.

BACKGROUND: Neutrophils have a critical role in the pathogenesis of rheumatoid arthritis (RA) with immune system dysfunction. However, the molecular mechanisms of this process mediated by neutrophils still remain elusive. The purpose of the present study is to identify hub genes in neutrophils for diagnosis and treatment of RA utilizing publicly available datasets. METHODS: Gene expression profiles were downloaded from the Gene Expression Omnibus, and batch-corrected and normalized expression data were obtained using the ComBat package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were used to conduct significantly functional analysis and crucial pathways. The resulting co-expression genes modules and hub genes were generated based on the weighted gene co-expression network analysis and visualization by Cytoscape. Flow cytometry was conducted to detect reactive oxygen species (ROS) levels in neutrophils. RESULTS: Neutrophils underwent transcriptional changes in synovial fluid (SF) of RA patients, different from peripheral blood of healthy controls or patients with RA. Especially, glycolysis, HIF-1 signaling, NADH metabolism, and oxidative stress were affected. These hub genes were strongly linked with classical glycolysis-related genes (ENO1, GAPDH, and PKM) responsible for ROS production. The antioxidant enzyme glutathione peroxidase 3 (GPX3), a ROS scavenger, was first identified as a hub gene in RA neutrophils. Neutrophils from patients with autoinflammatory and autoimmune diseases had markedly enhanced ROS levels, most notably in RA SF. CONCLUSION: This research recognized hub genes and explored the characteristics of neutrophils in RA. Our findings suggest that the novel hub gene GPX3 is involved in the neutrophil-driven oxidative stress-mediated pathogenesis of RA. It has the potency to be a target for neutrophil-directed RA therapy.