Functional lumen imaging probe use in a high-volume practice: Practical and technical implications.

BACKGROUND: The functional lumen imaging probe (FLIP) is a Food and Drug Administration approved tool to aid the diagnosis and management of esophageal disorders. However, widespread adoption of FLIP remains limited and its utility in high-volume practices remains unclear. AIM: To analyze large sample data on clinical use of FLIP and provide insight on several technical aspects when performing FLIP. METHODS: We conducted a retrospective comparative and descriptive analysis of FLIP procedures performed by a single provider at an academic medical center. There was a total of 398 FLIP procedures identified. Patient medical records were reviewed and data regarding demographics and procedural details were collected. Statistical tests, including chi-squared, t-test, and multivariable logistic and linear regression, were performed. RESULTS: There was an increase in FLIP cases with each successive time period of 13 months (n = 68, 146, 184, respectively) with notable rises specifically for indications of dysphagia and gastroesophageal reflux disease. There was a shift toward use of the longer FLIP balloon catheter for diagnostic purposes (overall 70.4% vs 29.6%, P < 0.01). Many cases (42.8%) were performed in conjunction with other diagnostics/interventions, such as dilation and wireless pH probe placement. Procedures were nearly equally performed with anesthesia vs moderate sedation (51.4% anesthesia), with no major complications. Patients who had anesthesia were less likely to have recurrent antegrade contractions [odds ratio (OR) = 0.4, 95%CI: 0.3-0.8] and were also more likely to have absent contractility (OR = 2.4, 95%CI: 1.3-4.4). CONCLUSION: FLIP cases have increased in our practice with expanding indications for its use. Given limited normative data, providers should be aware of several potential technical issues, including the possible impact of sedation choice when assessing esophageal motility patterns.

Gene Variants of the OAS/RNase L Pathway and Their Association with Severity of Symptoms and Outcome of SARS-CoV-2 Infection.

INTRODUCTION: The interferon pathway plays a critical role in triggering the immune response to SARS-CoV-2, and these gene variants may be involved in the severity of COVID-19. This study aimed to analyze the frequency of three gene variants of OAS and RNASEL with the occurrence of COVID-19 symptoms and disease outcome. METHODS: This cross-sectional study included 104 patients with SARS-CoV-2 infection, of which 34 were asymptomatic COVID-19, and 70 were symptomatic cases. The variants rs486907 (RNASEL), rs10774671 (OAS1), rs1293767 (OAS2), and rs2285932 (OAS3) were screened and discriminated using a predesigned 5'-nuclease assay with TaqMan probes. RESULTS: Patients with the allele C of the OAS2 gene rs1293767 (OR = 0.36, 95% CI: 0.15-0.83, p = 0.014) and allele T of the OAS3 gene rs2285932 (OR = 0.39, 95% CI: 0.2-0.023, p = 0.023) have lower susceptibility to developing symptomatic COVID-19. The genotype frequencies (G/G, G/C, and C/C) of rs1293767 for that comparison were 64.7%, 29.4%, and 5.9% in the asymptomatic group and 95.2%, 4.8%, and 0% in severe disease (p < 0.05). CONCLUSIONS: Our data indicate that individuals carrying the C allele of the OAS2 gene rs1293767 and the T allele of the OAS3 gene rs2285932 are less likely to develop symptomatic COVID-19, suggesting these genetic variations may confer a protective effect among the Mexican study population. Furthermore, the observed differences in genotype frequencies between asymptomatic individuals and those with severe disease emphasize the potential of these variants as markers for disease severity. These insights enhance our understanding of the genetic factors that may influence the course of COVID-19 and underscore the potential for genetic screening in identifying individuals at increased risk for severe disease outcomes.

Genetic Variant of DNAM-1 rs763361 C>T Is Associated with Ankylosing Spondylitis in a Mexican Population.

DNAM-1 (CD226) is an activating receptor expressed in CD8+ T cells, NK cells, and monocytes. It has been reported that two SNPs in the DNAM-1 gene, rs763361 C>T and rs727088 G>A, have been associated with different autoimmune diseases; however, the role of DNAM-1 in ankylosing spondylitis has been less studied. For this reason, we focused on the study of these two SNPs in association with ankylosing spondylitis. For this, 34 patients and 70 controls were analyzed using endpoint PCR with allele-specific primers. Our results suggest that rs763361 C>T is involved as a possible protective factor under the CT co-dominant model (OR = 0.34, 95% CI = 0.13-0.88, p = 0.022) and the CT + TT dominant model (OR = 0.39, 95% CI = 0.17-0.90, p = 0.025), while rs727088 G>A did not show an association with the disease in any of the inheritance models. When analyzing the relationships of the haplotypes, we found that the T + A haplotype (OR = 0.31, 95% CI = 0.13-0.73, p = 0.0083) is a protective factor for developing the disease. In conclusion, the CT and CT + TT variants of rs763361 C>T and the T + A haplotype were considered as protective factors for developing ankylosing spondylitis.

Myeloid cells in vascular dementia and Alzheimer's disease: Possible therapeutic targets?

Growing evidence supports the suggestion that the peripheral immune system plays a role in different pathologies associated with cognitive impairment, such as vascular dementia (VD) or Alzheimer's disease (AD). The aim of this review is to summarize, within the peripheral immune system, the implications of different types of myeloid cells in AD and VD, with a special focus on post-stroke cognitive impairment and dementia (PSCID). We will review the contributions of the myeloid lineage, from peripheral cells (neutrophils, platelets, monocytes and monocyte-derived macrophages) to central nervous system (CNS)-associated cells (perivascular macrophages and microglia). Finally, we will evaluate different potential strategies for pharmacological modulation of pathological processes mediated by myeloid cell subsets, with an emphasis on neutrophils, their interaction with platelets and the process of immunothrombosis that triggers neutrophil-dependent capillary stall and hypoperfusion, as possible effector mechanisms that may pave the way to novel therapeutic avenues to stop dementia, the epidemic of our time. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.

Ipsilesional Hippocampal GABA Is Elevated and Correlates With Cognitive Impairment and Maladaptive Neurogenesis After Cortical Stroke in Mice.

BACKGROUND: Cognitive dysfunction is a frequent stroke sequela, but its pathogenesis and treatment remain unresolved. Involvement of aberrant hippocampal neurogenesis and maladaptive circuitry remodeling has been proposed, but their mechanisms are unknown. Our aim was to evaluate potential underlying molecular/cellular events implicated. METHODS: Stroke was induced by permanent occlusion of the middle cerebral artery occlusion in 2-month-old C57BL/6 male mice. Hippocampal metabolites/neurotransmitters were analyzed longitudinally by in vivo magnetic resonance spectroscopy. Cognitive function was evaluated with the contextual fear conditioning test. Microglia, astrocytes, neuroblasts, interneurons, γ-aminobutyric acid (GABA), and c-fos were analyzed by immunofluorescence. RESULTS: Approximately 50% of mice exhibited progressive post-middle cerebral artery occlusion cognitive impairment. Notably, immature hippocampal neurons in the impaired group displayed more severe aberrant phenotypes than those from the nonimpaired group. Using magnetic resonance spectroscopy, significant bilateral changes in hippocampal metabolites, such as myo-inositol or N-acetylaspartic acid, were found that correlated, respectively, with numbers of glia and immature neuroblasts in the ischemic group. Importantly, some metabolites were specifically altered in the ipsilateral hippocampus suggesting its involvement in aberrant hippocampal neurogenesis and remodeling processes. Specifically, middle cerebral artery occlusion animals with higher hippocampal GABA levels displayed worse cognitive outcome. Implication of GABA in this setting was supported by the amelioration of ischemia-induced memory deficits and aberrant hippocampal neurogenesis after blocking pharmacologically GABAergic neurotransmission, an intervention which was ineffective when neurogenesis was inhibited. These data suggest that GABA exerts its detrimental effect, at least partly, by affecting morphology and integration of newborn neurons into the hippocampal circuits. CONCLUSIONS: Hippocampal GABAergic neurotransmission could be considered a novel diagnostic and therapeutic target for poststroke cognitive impairment.

Tick-Borne Pathogens Screening Using a Multiplex Real-Time Polymerase Chain Reaction-Based Method.

PURPOSE: This study aims to develop and evaluate a cost-effective, user-friendly multiplex quantitative real-time polymerase chain reaction (qPCR) method for detecting multiple tick-borne pathogens associated with human and veterinary diseases. METHODS: In silico PCR was performed to design and evaluate primer sequences reported for amplifying Rickettsia spp., Borrelia spp., and Ehrlichia spp. Single and multiplex qPCR assays were then standardized to detect individual pathogens and multiple pathogens in a single reaction. Positive controls were generated to determine the dynamic range of the methods. In the validation phase, a total of 800 samples were screened for the presence of tick-borne pathogens. RESULTS: Identification in a single qPCR reaction (multiplex) of Ehrlichia spp., and Borrelia spp. with a limit of detection of 10 copies and Rickettsia spp. with 100 copies, a PCR efficiency (E) of 90-100% and a coefficient of correlation (R2) of 0.998-0.996 for all pathogens. CONCLUSION: The ability to detect three significant pathogens (Ehrlichia spp., Rickettsia spp., and Borrelia spp.) in a single qPCR reaction offers a significant advantage in the field of molecular diagnostics for tick-borne diseases. This advancement has a profound impact on public health as it facilitates the selection of appropriate treatment protocols, thereby reducing complications associated with disease progression. The streamlined approach provided by this method simplifies the diagnostic process and enables timely intervention, ultimately improving patient outcomes and mitigating the potential risks associated with untreated or misdiagnosed tick-borne infections.

Maternal separation differentially modulates early pathology by sex in 5xFAD Alzheimer's disease-transgenic mice.

Alzheimer's disease (AD) is the most common neurodegenerative disease. Most cases of AD are considered idiopathic and likely due to a combination of genetic, environmental, and lifestyle-related risk factors. Despite occurring decades before the typical age of an AD diagnosis, early-life stress (ELS) has been suggested to have long-lasting effects that may contribute to AD risk and pathogenesis. Still, the mechanisms that underlie the role of ELS on AD risk remain largely unknown. Here, we used 5xFAD transgenic mice to study relatively short-term alterations related to ELS in an AD-like susceptible mouse model at 6 weeks of age. To model ELS, we separated pups from their dams for 3 h per day from postnatal day 2-14. Around 6 weeks of age, we found that maternally separated (MS) 5xFAD mice, particularly female mice, displayed increased amyloid-ß-immunoreactivity in the anterior cingulate cortex (ACC) and basolateral amygdala (BLA). In anterior cingulate cortex, we also noted significantly increased intraneuronal amyloid-ß-immunoreactivity associated with MS but only in female mice. Moreover, IBA1-positive DAPI density was significantly increased in relation to MS in ACC and BLA, and microglia in BLA of MS mice had significantly different morphology compared to microglia in non-MS 5xFAD mice. Cytokine analysis showed that male MS mice, specifically, had increased levels of neuroinflammatory markers CXCL1 and IL-10 in hippocampal extracts compared to non-MS counterparts. Additionally, hippocampal extracts from both male and female MS 5xFAD mice had decreased levels of synapse- and activity-related markers Bdnf, 5htr6, Cox2, and Syp in hippocampus. Lastly, we performed behavioral tests to evaluate anxiety- and depressive-like behavior and working memory but could not detect any significant differences between groups. Overall, we detected several sex-specific molecular and cellular alterations in 6-week-old adolescent 5xFAD mice associated with MS that may help explain the connection between ELS and AD risk.

Microglial Caspase-3 is essential for modulating hippocampal neurogenesis.

Adult hippocampal neurogenesis (AHN) is a process involved in numerous neurodegenerative diseases. Many researchers have described microglia as a key component in regulating the formation and migration of new neurons along the rostral migratory stream. Caspase-3 is a cysteine-aspartate-protease classically considered as one of the main effector caspases in the cell death program process. In addition to this classical function, we have identified the role of this protein as a modulator of microglial function; however, its action on neurogenic processes is unknown. The aim of the present study is to identify the role of Caspase-3 in neurogenesis-related microglial functions. To address this study, Caspase-3 conditional knockout mice in the microglia cell line were used. Using this tool, we wanted to elucidate the role of this protein in microglial function in the hippocampus, the main region in which adult neurogenesis takes place. After the reduction of Caspase-3 in microglia, mutant mice showed a reduction of microglia in the hippocampus, especially in the dentate gyrus region, a region inherently associated to neurogenesis. In addition, we found a reduction in doublecortin-positive neurons in conditional Caspase-3 knockout mice, which corresponds to a reduction in neurogenic neurons. Furthermore, using high-resolution image analysis, we also observed a reduction in the phagocytic capacity of microglia lacking Caspase-3. Behavioral analysis using object recognition and Y-maze tests showed altered memory and learning in the absence of Caspase-3. Finally, we identified specific microglia located specifically in neurogenic niche positive for Galectin 3 which colocalized with Cleaved-Caspase-3 in control mice. Taken together, these results showed the essential role of Caspase-3 in microglial function and highlight the relevant role of this specific microglial phenotype in the maintenance of AHN in the hippocampus.

Survival of patients with severe mental disorders: Influence of social functioning.

BACKGROUND: Patients with severe mental disorders have a high risk of premature death due to the interaction of various factors. Social functioning is a strategic functional factor in understanding the course of psychotic disorders. AIM: Analyze the relationship between social functioning and its various dimensions and survival during a 10-year follow-up. METHOD: The Social Functioning Scale (SFS) was administered to 163 close relatives of patients under treatment at a Community Mental Health Unit. Survival was described by Kaplan-Meier analysis and any differences in survival by level of social functioning were found by long-rank analysis. Finally, Cox regression was used to predict premature mortality. RESULTS: Significant differences in mortality were identified in the interpersonal behavior dimension of social functioning, while there were no significant gender or diagnostic differences in the rest of the dimensions. The interpersonal behavior dimension and age were found to be factors predicting premature death. CONCLUSION: These findings show the protective effect of social functioning retained by patients with psychotic disorders on their survival, and the need to apply evidence-based psychotherapy focused on recovery of social functioning in the early stages of the disorder.

Development of an Auxiliary Platform (Mentali) for the Primary Screening of Anxiety and Depression in Young Adults.

The current COVID-19 pandemic has completely changed people's daily routines. This has had a big impact on mental health. In Mexico, medical school authorities are interested in understanding the mental health status of the student population to be able to provide support to students who may need help from a mental health specialist. The aim of this study was to develop a platform comprised of a mobile and web application called Mentali, to be used as an auxiliary tool for the detection of conditions such as anxiety and depression, as well as variations in mood, by analysis of the results of validated inventories. Following the Scrum software development methodology, Python, Dart and PHP programming languages were used for development of the application. This platform was used prospectively with 155 first year students taking part in the human medicine program. After 22 weeks, Mentali enabled the identification of 40 users with positive primary screening for anxiety and/or depression (45% for anxiety, 32.5% for both anxiety and depression, and 22.5% for altered mood). These students were contacted and referred to a psychologist; however, only 26 (65%) accepted psychological support. For all of these students a mental health disorder was confirmed. The results support the use of Mentali for the primary screening of anxiety and depression in young adults, including medical students.

Usefulness of a Mobile Application (Mentali) for Anxiety and Depression Screening in Medical Students and Description of the Associated Triggering Factors.

The impact of the COVID-19 health crisis on the mental health of the population requires the implementation of new primary screening strategies of mental health disorders to intervene in a timelier manner, and technology may provide solutions. We aimed to evaluate the usefulness of the mobile app Mentali (version 1.1.2; creators: Jorge Alfonso Solís Galván Sodel Vázquez Reyes, Margarita de la Luz Martínez Fierro, Perla Velasco Elizondo, Idalia Garza Veloz, Alejandro Mauricio González and Claudia Caldera Villalobos, Zacatecas, México) as a primary screening tool for anxiety and depression disorders in medical students and to assess the triggering risk factors. This was a descriptive and longitudinal study and included 155 Mexican medical students. Participants interacted with Mentali for 6 months. The mobile app integrated the Beck anxiety and depression inventories together with a mood module. At the end of the interaction, the students received psychological and psychiatric interventions to confirm their primary diagnoses. Symptoms of moderate/severe anxiety and depression were present in 62.6% and 54.6% of the studied population. When corroborating the diagnoses, Mentali obtained a sensitivity of 100%, 95%, and 43% to classify a mental health disorder, anxiety, and depression, respectively. The most important triggers found were as follows: belonging to a dysfunctional family, being introverted, and having suffered from bullying. The proportion of users with excellent/good mood decreased from 78.7% to 34.4% at the end of the semester, and the proportion of users who claimed to have bad/very bad mood increased from 7.4% to 34.4% at the end of the semester (p < 0.05). Mentali was useful for identifying users with anxiety and/or depression, and as an auxiliary tool to coordinate the provision of specialized interventions, allowing us to increase the proportion of patients who needed psychological care and received it by 30%. The efficacy of Mentali in identifying activities through time with an impact on the mood and mental health of the users was confirmed. Our results support the use of Mentali for the primary screening of mental health disorders in young adults, including medical students.

Association of MIR3117 and MIR612 Genes Polymorphisms with Childhood Acute Lymphoblastic Leukemia in the Mexican Population.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer in the world, which is associated with a wide spectrum of factors that play an important role in epidemiology, risk stratification, and therapeutic intervention. Several studies have shown the role of microRNAs (miRNAs) in the development of the disease. Genetic variations such as single-nucleotide polymorphisms (SNPs) in miRNAs can alter their function and lead to alter the expression of their target genes. OBJECTIVE: The aim of this study was to evaluate the association of rs12402181 in MIR3117 and rs12803915 in MIR612 with the risk of childhood preB-ALL in Mexican population. MATERIAL AND METHODS: DNA from 148 children (<18 years old) diagnosed with preB-ALL and 172 samples from participants in control group were included in the present study. Genotyping of the rs12402181 and rs12803915 polymorphisms was carried out by Real-Time PCR. To estimate the risk factor, the multiple genetic models co-dominant, dominant, and recessive were determined in both polymorphisms. RESULTS: In dominant genetic model from rs12402181, a high risk of susceptibility to ALL was observed (OR = 2.03, 95% CI = 1.27-3.22, p = 0.003). In the analysis adjusted for gender, a significant increase in the risk of ALL was maintained (OR = 2.03, 95% CI = 1.28-3.24, p = 0.003). The rs12803915 polymorphism was no associated with the risk of susceptibility to preB-ALL in any of the genetic models using in this study. CONCLUSIONS: Our data indicated that the A allele of the rs12402181 polymorphism may be considered as a genetic biomarker of preB-ALL susceptibility. Likewise, it was identified that the A allele of the rs12402181 polymorphism is an independent risk factor for ALL.

Deleted genes associated with obesity in Mexican patients diagnosed with nonalcoholic fatty liver disease.

AIM: Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic condition in which both lifestyle and genetic factors have a pathogenic role. The LEP gene encodes leptin, which regulates appetite, body weight, and several metabolic functions. Proopiomelanocortin (POMC), regulates food intake and energy balance. The aim of the study was to determine partial or complete deletions of genes associated with obesity in patients diagnosed with NAFLD. MATERIAL AND METHODS: Blood samples and DNA from 43 individuals diagnosed with NAFLD by ultrasonographic technique (Fibroscan) were obtained. The partial or complete deletions of genes were determined by MLPA (Multiplex Ligation-dependent Probe Amplification) using the SALSA probemix P220-B2 Obesity only on 43 individuals. Fifty blood samples from healthy individuals were included. RESULTS: Eleven out of 43 individuals analyzed by MLPA presented some deletion of the genes analyzed: six were female and five were male. The partial or complete deletion of the LEPR and POMC genes was observed in eight patients (18.6%), SIM1 in six patients (13.9%), GRIK2 and SH2B1 in two patients (4.7%), SEZGL2 in four patients (9.3%), and MCR4 in one patient (2.3%). CONCLUSION: Partial deletion was observed in LEPR, POMC, SIM1, GRIK2, SH2B1, SEZGL2, and MCR4 genes in 26% of the cases, and we suggest that these alterations probably has a potential relationship for the development of NAFLD.

Anxiety, depression, and academic stress among medical students during the COVID-19 pandemic.

Background: The social distancing policies implemented by the health authorities during the COVID-19 pandemic in Mexico and elsewhere led to major changes in teaching strategies for college undergraduates. So far, there is limited data regarding the impact of the lockdown on the academic stress and mental health of these students. Objective: To assess the occurrence of academic difficulties, anxiety, depression, and academic stressors resulting in somatization with subsequent coping strategies linked to the pandemic. Materials and methods: A cross-sectional study was conducted with 728 medical students (years 1-5). A purposely designed questionnaire to assess academic difficulties associated with the pandemic was administered electronically. The validated Goldberg anxiety and depression scale was also used, as well as the SISCO-II inventory on academic stress. Results: Screening for anxiety and depression led to a prevalence of 67.9 and 81.3%, respectively. Most relevant stressors, reported always or nearly always, included professors' evaluations (63.9%), and reading overload of academic papers (50.6%). Factorial analyses showed that women were more prone to stress than men (p < 0.001). Somatization symptomatology included drowsiness or increased need of sleep, anxiety, anguish, desperation, chronic fatigue, and sleep disorders. Common coping strategies included practicing a hobby, done always or nearly always by 65% of students with high stress, and 34% of those with low stress (p < 0.001). Conclusion: There was a relevant impact of the mandatory lockdown during COVID-19 pandemic on the mental health of medical students reflected in the high prevalence rates of anxiety, depression, and stressors in the studied population pointing to the need for designing and implementing preventive strategies to deal with the effects of lockdowns.

Ten-year follow-up of social functioning and behaviour problems in people with schizophrenia and related disorders.

BACKGROUND: In recent years, several variables in the course of schizophrenia and related psychotic disorders have been studied. However, an instrumental analysis of the evolution of social functioning and behaviour problems has scarcely been explored. AIM: To analyse the evolution of social functioning and behaviour problems and find any diagnosis or gender differences. METHOD: The Social Functioning Scale (SFS) and the Behaviour Problems Inventory (BPI) were administered in Stages I (2003-2007) and II (2014-2017) to 100 close relatives of patients under treatment at a Community Mental Health Unit. A related samples t-test, analysis of variance and multivariate analysis of variance were performed to study the evolution and differences in social functioning and behaviour problems. Then a stepwise multiple linear regression analysis was done to predict the evolution of social functioning. RESULTS: No deterioration in the evolution of social functioning or behaviour problems was observed, and schizophrenia patient scores were lower. Women scored higher in withdrawal/social engagement, interpersonal behaviour, independence-performance, independence-competence and total social functioning, with no significant differences in behaviour problems. Previous social functioning, underactivity/social withdrawal and education are predictive factors in the evolution of social functioning. Conclusion: The results show the need for implementing psychosocial intervention programs that promote functional recovery and keep problems from becoming chronic.

The influence of the -94 Ins/Del ATTG polymorphism of NFkB on the anti-CCP antibody levels in patients with rheumatoid arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an inflammatory process that affects mainly synovial tissue in joints, and by the production of cyclic citrullinated peptides (anti-CCP) antibodies. In the inflammatory process the regulation of the nuclear factor kappa B (NFkB) transcription factor activation is a key point in the production of inflammatory cytokines. On the other hand, polymorphisms in several genes could contribute to the promotion of the inflammatory process observed in RA, and the association of the rs28362491 polymorphism in the NFkB gene with RA has been studied in different population. Therefore, it could be one of the interest targets to analyze their association with RA in a Mexican population.This is a case-control study to determine the influence of rs28362491 in the NFkB gene on RA and on clinical features of this disease, such as anti-CCP antibody levels, Disease Activity Score, and Health Assessment Questionnaire-Disability Index.The genotype of rs28362491 in the NFkB gene was determined in 140 RA patients and 135 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism method with the enzyme PflMI. The following clinical variables were also determined: anti-CCP levels, Disease Activity Score, and Spanish version of the Health Assessment Questionnaire Disability-Index.Although no association of the polymorphism as a risk/protection factor with RA was found, the RA patients who carried the Ins/Ins genotype showed higher anti-CCP levels, while those with the Del/Del genotype showed higher Spanish version of the Health Assessment Questionnaire-Disability Index levels, compared to the other genotypes.The NFkB -94 Ins/Del ATTG (rs28362491) polymorphism is, therefore, associated with higher levels of anti-CCP antibodies, though no significant association as a risk or protection factor in RA cases was identified.

Gender influence on severe mental disorders: relationship between behavior problems and family burden / Influencia del género en trastornos mentales graves: relación entre problemas de comportamiento y carga familiar

Gender differences in behavior problems and their relationship with family burden in severe mental disorders were analyzed. The Behavior Problems Inventory (BPI) and two items related to family burden (FB 1: "Do you feel able to endure the illness or disorder and the problems it causes?" and FB 2: "How often are you overwhelmed by these behavior/illness problems?") were administered to 235 key informants under treatment in a community mental health unit. The results show that men presented more behavior problems and family burden, with significant differences in impulse dyscontrol and severe behavior problems. A positive correlation was found between behavior problems and family burden, where the inactivity/social withdrawal dimension was the best predictor of family load for men and women. We conclude that men have more behavior problems and that the inactivity/social withdrawal dimension has the most explanatory power for family burden in both men and women. (AU)

Se analizan las diferencias de género en problemas de conducta y su relación con la carga familiar en trastornos mentales graves. El Inventario de Problemas de Conducta (BPI) y dos ítems relativos a la carga familiar ("¿Se siente usted capaz de sobrellevar la enfermedad o trastorno y los problemas que ocasiona?" y "¿Con qué frecuencia se ve usted desbordado/a por estos problemas de comportamiento/enfermedad?") se administraron a 235 informantes clave de pacientes en tratamiento en una unidad de Salud Mental Comunitaria. Los hombres presentaban mayores problemas de conducta y carga familiar, existiendo diferencias significativas en descontrol de impulsos y en problemas de comportamiento graves. Se halla una correlación positiva entre problemas de comportamiento y carga familiar, siendo la dimensión inactividad/aislamiento social la mejor predictora de carga familiar. Respecto a la carga familiar, es la dimensión inactividad/aislamiento social la que posee mayor capacidad explicativa en hombres y mujeres. (AU)

A Fluorescence Dequenching-based Liposome Leakage Assay to Measure Membrane Permeabilization by Pore-forming Proteins.

Pore-forming toxins (PFTs) have been discovered in a wide range of organisms. Their functions are essential to the survival or virulence of many species. PFTs often interact with lipid membranes. Large unilamellar vesicles (LUV), also known as liposomes, have been commonly used as reliable membrane models for testing PFTs activity. Liposomes have great adaptability in size, lipid composition, and loading cargo. Incorporating the fluorescent dye/quencher pair, 8-Aminonaphthalene-1,3,6-Trisulfonic Acid (ANTS) and p-Xylene-Bis-Pyridinium Bromide (DPX), in liposomes is an effective approach for measuring membrane leakage. When ANTS and DPX are encapsulated in a liposome, the fluorescence of ANTS is quenched by DPX. However, disruption of liposome integrity and subsequent leakage result in measurable fluorescence emitted by ANTS. Here, we report our protocol for optimal liposome preparation for measuring liposome leakage by fluorescence dequenching.

Post-stroke Neurogenesis: Friend or Foe?

The substantial clinical burden and disability after stroke injury urges the need to explore therapeutic solutions. Recent compelling evidence supports that neurogenesis persists in the adult mammalian brain and is amenable to regulation in both physiological and pathological situations. Its ability to generate new neurons implies a potential to contribute to recovery after brain injury. However, post-stroke neurogenic response may have different functional consequences. On the one hand, the capacity of newborn neurons to replenish the damaged tissue may be limited. In addition, aberrant forms of neurogenesis have been identified in several insult settings. All these data suggest that adult neurogenesis is at a crossroads between the physiological and the pathological regulation of the neurological function in the injured central nervous system (CNS). Given the complexity of the CNS together with its interaction with the periphery, we ultimately lack in-depth understanding of the key cell types, cell-cell interactions, and molecular pathways involved in the neurogenic response after brain damage and their positive or otherwise deleterious impact. Here we will review the evidence on the stroke-induced neurogenic response and on its potential repercussions on functional outcome. First, we will briefly describe subventricular zone (SVZ) neurogenesis after stroke beside the main evidence supporting its positive role on functional restoration after stroke. Then, we will focus on hippocampal subgranular zone (SGZ) neurogenesis due to the relevance of hippocampus in cognitive functions; we will outline compelling evidence that supports that, after stroke, SGZ neurogenesis may adopt a maladaptive plasticity response further contributing to the development of post-stroke cognitive impairment and dementia. Finally, we will discuss the therapeutic potential of specific steps in the neurogenic cascade that might ameliorate brain malfunctioning and the development of post-stroke cognitive impairment in the chronic phase.