Invasive disease caused simultaneously by two different serotypes of Streptococcus pneumoniae: a microbiological appreciation.

We report a clinical case of a child with an invasive pneumococcal disease caused by two different pneumococcal serotypes that belonged to different sequence types. She was a 15-month-old girl with pneumonia and pleural effusion in which S. pneumoniae colonies with different morphologies grew, one from the blood culture (characteristic greyish appearance) and the other from the pleural fluid (mucoid appearance). The isolate from blood was serotype 22 F (ST698/CC698/GPSC61), while the isolate from the pleural fluid was serotype 3 (ST180/CC180/GPSC12). The patient fully recovered after treatment with intravenous ampicillin followed by oral amoxicillin.

Developmental regulation of epithelial cell cuboidal-to-squamous transition in Drosophila follicle cells.

Epithelial cells form continuous membranous structures for organ formation, and these cells are classified into three major morphological categories: cuboidal, columnar, and squamous. It is crucial that cells transition between these shapes during the morphogenetic events of organogenesis, yet this process remains poorly understood. All three epithelial cell shapes can be found in the follicular epithelium of Drosophila egg chamber during oogenesis. Squamous cells (SCs) are initially restricted to the anterior terminus in cuboidal shape. They then rapidly become flattened to assume squamous shape by stretching and expansion in 12 â€‹h during midoogenesis. Previously, we reported that Notch signaling activated a zinc-finger transcription factor Broad (Br) at the end of early oogenesis. Here we report that ecdysone and JAK/STAT pathways subsequently converge on Br to serve as an important spatiotemporal regulator of this dramatic morphological change of SCs. The early uniform pattern of Br in the follicular epithelium is directly established by Notch signaling at stage 5 of oogenesis. Later, ecdysone and JAK/STAT signaling activities synergize to suppress Br in SCs from stage 8 to 10a, contributing to proper SC squamous shape. During this process, ecdysone signaling is essential for SC stretching, while JAK/STAT regulates SC clustering and cell fate determination. This study reveals an inhibitory role of ecdysone signaling in suppressing Br in epithelial cell remodeling. In this study we also used single-cell RNA sequencing data to highlight the shift in gene expression which occurs as Br is suppressed and cells become flattened.

Cross-Sectional Analysis of Risk Factors for Outbreak of COVID-19 in Nursing Homes for Older Adults in the Community of Madrid.

INTRODUCTION: Nursing homes for older adults have been hot spots for SARS-CoV-2 infections and mortality. Factors that facilitate COVID-19 outbreaks in these settings need to be assessed. METHODS: A retrospective cross-sectional study of a cohort of residents and workers in nursing homes taking occasion of a point seroprevalence survey was done in the Community of Madrid. Factors related to outbreaks in these facilities were analyzed. RESULTS: A total of 369 nursing homes for older adults, making a population of 23,756 residents and 20,795 staff members, were followed from July to December 2020. There were 54.2% SARS-CoV-2 IgG+ results in residents and in 32.2% of workers. Sixty-two nursing homes (16.8%) had an outbreak during the follow-up. Nursing homes with outbreaks had more residents than those without (median number of 81 [IQR, 74] vs. 50 [IQR, 56], p < 0.001). Seropositivity for SARS-CoV-2 was lower in facilities with versus without outbreaks, for residents (42.2% [IQR, 55.7] vs. 58.7% [IQR, 43.4], p = 0.002) and for workers (23.9% [IQR, 26.4] vs. 32.8% [IQR, 26.3], p = 0.01). For both residents and staff, the number of infections in outbreaks was larger in centers with lower, as compared with intermediate or high seroprevalence. The size of the facility did not correlate with the number of cases in the outbreak. Taking the incidence of cases in the community as a time-dependent variable (p = 0.03), a Cox analysis (HR [95% CI], p) showed that intermediate or high seroprevalence among residents in the facility was related to a reduction of 55% (0.45 [0.25-0.80], p = 0.007) and 78% (0.22 [0.10-0.48], p < 0.001) in the risk of outbreaks, respectively, as compared with low sero-prevalence. Also, as compared with smaller, medium (1.91 [1.00-3.65], p = 0.05) or large centers (4.57 [2.38-8.75], p < 0.001) had more respective risk of outbreaks. CONCLUSIONS: The size of the facility and the seroprevalence among residents in nursing homes, and the incidence of infections in the community, are associated with the risk of outbreaks of COVID-19. Facilities with greater proportion of seropositives had smaller number of cases. Monitoring of immunity in nursing homes may help detect those at a greater risk of future cases.

A Novel Localization of METTL7A in Bergmann Glial Cells in Human Cerebellum.

Methyltransferase-like protein 7A (METTL7A) is a member of the METTL family of methyltransferases.Little information is available regarding the cellular expression of METTL7A in the brain. METTL7A is commonly located in the endoplasmic reticulum and to a lesser extent, in the lipid droplets of some cells. Several studies have reported altered protein and RNA levels in different brain areas in schizophrenia. One of these studies found reduced protein levels of METTL7A in the cerebellar cortex in schizophrenia and stress murine models. Since there is limited information in the literature about METTL7A, we characterized its cellular and subcellular localizations in the human cerebellum using immunohistochemical analysis with laser confocal microscopy. Our study reveals a novel METTL7A localization in GFAP-positive cells, with higher expression in the end-feet of the Bergmann glia, which participate in the cerebrospinal fluid-brain parenchyma barrier. Further 3D reconstruction image analysis showed that METTL7A was expressed in the contacts between the Bergmann glia and Purkinje neurons. METTL7A was also detected in lipid droplets in some cells in the white matter. The localization of METTL7A in the human cerebellar glia limitans could suggest a putative role in maintaining the cerebellar parenchyma homeostasis and in the regulation of internal cerebellar circuits by modulating the synaptic activity of Purkinje neurons.

Inhibition of Prolyl Oligopeptidase Restores Prohibitin 2 Levels in Psychosis Models: Relationship to Cognitive Deficits in Schizophrenia.

Cognitive impairment represents one of the core features of schizophrenia. Prolyl Oligopeptidase (POP) inhibition is an emerging strategy for compensating cognitive deficits in hypoglutamatergic states such as schizophrenia, although little is known about how POP inhibitors exert their pharmacological activity. The mitochondrial and nuclear protein Prohibitin 2 (PHB2) could be dysregulated in schizophrenia. However, altered PHB2 levels in schizophrenia linked to N-methyl-D-aspartate receptor (NMDAR) activity and cognitive deficits are still unknown. To shed light on this, we measured the PHB2 levels by immunoblot in a postmortem dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects, in the frontal pole of mice treated with the NMDAR antagonists phencyclidine and dizocilpine, and in rat cortical astrocytes and neurons treated with dizocilpine. Mice and cells were treated in combination with the POP inhibitor IPR19. The PHB2 levels were also analyzed by immunocytochemistry in rat neurons. The PHB2 levels increased in DLPFC in cases of chronic schizophrenia and were associated with cognitive impairments. NMDAR antagonists increased PHB2 levels in the frontal pole of mice and in rat astrocytes and neurons. High levels of PHB2 were found in the nucleus and cytoplasm of neurons upon NMDAR inhibition. IPR19 restored PHB2 levels in the acute NMDAR inhibition. These results show that IPR19 restores the upregulation of PHB2 in an acute NMDAR hypoactivity stage suggesting that the modulation of PHB2 could compensate NMDAR-dependent cognitive impairments in schizophrenia.

A Pilot Study for the Evaluation of an Interferon Gamma Release Assay (IGRA) To Measure T-Cell Immune Responses after SARS-CoV-2 Infection or Vaccination in a Unique Cloistered Cohort.

Assessment of T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens may be of value to determine long-lasting protection to breakthrough infections or reinfections. Interferon gamma release assay is a validated method to test cellular immunity in mycobacterial infections and has been proposed for patients with SARS-CoV-2 infection or vaccination. Quantitative IgG to spike and qualitative IgG to nucleocapsid antigens were determined by chemiluminescence microparticle immunoassay using the Architect platform (Abbott), and interferon gamma release assays against two Qiagen proprietary mixes of SARS-CoV-2 spike protein (antigen 1 and antigen 2) were performed for a selected group of subjects. A total of 121 subjects in a cloistered institution after a COVID-19 outbreak was studied. IgG spike levels and interferon gamma concentrations were highest among subjects after two doses of vaccine, followed by patients with a longer history of past COVID-19 and no vaccination. The best cutoff for the interferon gamma assay was 25 IU/L for all subgroups of individuals and the two sets of SARS-CoV-2 antigens studied. Testing T-cell response may be of clinical utility to determine immunity after exposure to SARS-CoV-2 antigens, with the interferon gamma concentration of 25 IU/L as the best cutoff either after infection or vaccination.

Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology.

BACKGROUND: The cortico-cerebellar-thalamic-cortical circuit has been implicated in the emergence of psychotic symptoms in schizophrenia (SZ). The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA). METHODS: This work describes alterations in KP in the post-mortem prefrontal cortex (PFC) and cerebellum (CB) of 15 chronic SZ patients and 14 control subjects in PFC and 13 control subjects in CB using immunoblot for protein levels and ELISA for interleukins and QA and KYNA determinations. Monoamine metabolites were analysed by high-performance liquid chromatography and SZ symptomatology was assessed by Positive and Negative Syndrome Scale (PANSS). The association of KP with inflammatory mediators, monoamine metabolism and SZ symptomatology was explored. RESULTS: In the PFC, the presence of the anti-inflammatory cytokine IL-10 together with IDO2 and KATII enzymes decreased in SZ, while TDO and KMO enzyme expression increased. A network interaction analysis showed that in the PFC IL-10 was coupled to the QA branch of the kynurenine pathway (TDO-KMO-QA), whereas IL-10 associated with KMO in CB. KYNA in the CB inversely correlated with negative and general PANSS psychopathology. Although there were no changes in monoamine metabolite content in the PFC in SZ, a network interaction analysis showed associations between dopamine and methoxyhydroxyphenylglycol degradation metabolite. Direct correlations were found between general PANSS psychopathology and the serotonin degradation metabolite, 5-hydroxyindoleacetic acid. Interestingly, KYNA in the CB inversely correlated with 5-hydroxyindoleacetic acid in the PFC. CONCLUSIONS: Thus, this work found alterations in KP in two brain areas belonging to the cortico-cerebellar-thalamic-cortical circuit associated with SZ symptomatology, with a possible impact across areas in 5-HT degradation.

The demography and characteristics of SARS-CoV-2 seropositive residents and staff of nursing homes for older adults in the Community of Madrid: the SeroSOS study.

BACKGROUND: Nursing homes for older adults have concentrated large numbers of severe cases and deaths for coronavirus disease 2019 (COVID-19). METHODS: Point seroprevalence study of nursing homes to describe the demography and characteristic of severe acute respiratory syndrome by coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG)-positive residents and staff. RESULTS: Clinical information and blood samples were available for 9,332 residents (mean age 86.7 ± 8.1 years, 76.4% women) and 10,614 staff (mean age 45.6 ± 11.5, 86.2% women). Up to 84.4% of residents had frailty, 84.9% co-morbidity and 69.3% cognitive impairment; 65.2% of workers were health-aides.COVID-19 seroprevalence was 55.4% (95% confidence interval (CI), 54.4-56.4) for older adults and 31.5% (30.6-32.4) for staff. In multivariable analysis, frailty of residents was related with seropositivity (odds ratio (OR): 1.19, P = 0.02). In the case of staff, age > 50 years (2.10, P < 0.001), obesity (1.19, P = 0.01), being a health-aide (1.94, P < 0.001), working in a center with high seroprevalence in residents (3.49, P < 0.001) and contact with external cases of COVID-19 (1.52, P < 0.001) were factors associated with seropositivity. Past symptoms of COVID-19 were good predictors of seropositivity for residents (5.41, P < 0.001) and staff (2.52, P < 0.001). CONCLUSIONS: Level of dependency influences risk of COVID-19 among residents. Individual and work factors, contacts outside the nursing home are associated with COVID-19 exposure in staff members. It is key to strengthen control measures to prevent the introduction of COVID-19 into care facilities from the community.

Septal and posterior sliding plasty in tricuspid valve endocarditis.

The tricuspid valve can be affected in left-sided infective endocarditis. We present a new technique to repair anteroseptal tricuspid valve commissure. It was employed in a patient with left-sided infective endocarditis with intervalvular fibrous body abscess. A sliding plasty of septal and posterior leaflets was performed, reaching the anteroseptal commissure with the aid of De-Vega like annuloplasty.

Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models.

Despite the growing importance of the cerebellum as a region highly vulnerable to accumulating molecular errors in schizophrenia, limited information is available regarding altered molecular networks with potential therapeutic targets. To identify altered networks, we conducted one-shot liquid chromatography-tandem mass spectrometry in postmortem cerebellar cortex in schizophrenia and healthy individuals followed by bioinformatic analysis (PXD024937 identifier in ProteomeXchange repository). A total of 108 up-regulated proteins were enriched in stress-related proteins, half of which were also enriched in axonal cytoskeletal organization and vesicle-mediated transport. A total of 142 down-regulated proteins showed an enrichment in proteins involved in mitochondrial disease, most of which were also enriched in energy-related biological functions. Network analysis identified a mixed module of mainly axonal-related pathways for up-regulated proteins with a high number of interactions for stress-related proteins. Energy metabolism and neutrophil degranulation modules were found for down-regulated proteins. Further, two double-hit postnatal stress murine models based on maternal deprivation combined with social isolation or chronic restraint stress were used to investigate the most robust candidates of generated networks. CLASP1 from the axonal module in the model of maternal deprivation was combined with social isolation, while YWHAZ was not altered in either model. METTL7A from the degranulation pathway was reduced in both models and was identified as altered also in previous gene expression studies, while NDUFB9 from the energy network was reduced only in the model of maternal deprivation combined with social isolation. This work provides altered stress- and mitochondrial disease-related proteins involved in energy, immune and axonal networks in the cerebellum in schizophrenia as possible novel targets for therapeutic interventions and suggests that METTL7A is a possible relevant altered stress-related protein in this context.

Specificity proteins 1 and 4 in peripheral blood mononuclear cells in postmenopausal women with schizophrenia: a 24-week double-blind, randomized, parallel, placebo-controlled trial.

Accumulating evidence suggests that Specificity Protein 1 (SP1) and 4 (SP4) transcription factors are involved in the pathophysiology of schizophrenia. The therapeutic use of selective oestrogen modulators such as raloxifene added to antipsychotic drugs in the treatment of postmenopausal women with schizophrenia has been investigated in a few clinical trials, which reported an improvement in negative, positive, and general psychopathological symptoms. We aimed to investigate the possible association between peripheral SP protein levels and symptom improvement in postmenopausal women with schizophrenia treated with adjuvant raloxifene. In a subgroup of 14 postmenopausal women with schizophrenia from a 24-week, randomized, parallel, double-blind, placebo-controlled clinical trial (NCT015736370), we investigated changes in SP1 and SP4 protein levels in peripheral blood mononuclear cells. Participants were randomized to either 60 mg/day adjunctive raloxifene or placebo. Psychopathological symptoms were assessed at baseline and at week 24 with the Positive and Negative Syndrome Scale (PANSS). The expression of SP proteins was evaluated by immunoblot, and changes in PANSS scores and protein levels were compared at baseline and after 24 weeks of treatment. An improvement in symptoms was observed in the intervention group, but not in placebo group. Post-treatment protein levels of SP4, but not SP1, correlated with improvements in general and total PANSS subscales in the raloxifene intervention group. A reduction in SP4 levels was found after raloxifene treatment. These results suggest that SP4 may be involved in raloxifene symptom improvement in postmenopausal women and could be a potential candidate for future studies investigating blood-based biomarkers for raloxifene effectiveness.

Specificity proteins 1 and 4, hippocampal volume and first-episode psychosis.

We assessed specificity protein 1 (SP1) and 4 (SP4) transcription factor levels in peripheral blood mononuclear cells and conducted a voxel-based morphometry analysis on brain structural magnetic resonance images from 11 patients with first-episode psychosis and 14 healthy controls. We found lower SP1 and SP4 levels in patients, which correlated positively with right hippocampal volume. These results extend previous evidence showing that such transcription factors may constitute a molecular pathway to the development of psychosis.

[Population study of seroprevalence of antibodies against hepatitis A virus in the Community of Madrid, 2008-2009]. / Estudio poblacional de seroprevalencia de anticuerpos frente al virus de la hepatitis A en la Comunidad de Madrid, 2008-2009.

INTRODUCTION: Seroprevalence surveys enable the level of endemicity of hepatitis A (HAV) to be assessed. The aim of this study was to estimate the seroprevalence (SP) antibody against HAV by age group, and compare it with those obtained in previous surveys. METHODS: Observational cross-sectional study. The target population consists of residents from 2 to 60 years old in the Community of Madrid. Two-stage cluster sampling was performed with stratification of first stage units. After signing the informed consent, a serum sample was extracted from each participant and sociodemographic data were collected by a questionnaire. RESULTS: SP antibodies to hepatitis A is 46.8% (95% CI 44.6 to 49.0). The SP increases with age. It is higher in the population from more endemic countries and people with less education and lower social class. In relation to the previous survey, SP increased in the population under 30 years old, and a decline after that age is observed. If only the autochthonous population and from countries with very low endemicity is observed, the increase is statistically significant in the 2-5 years age group. CONCLUSIONS: Our region has a very low level of endemicity thus, following the recommendations of WHO, vaccination should be targeted at specific risk groups.

Correlation between serum levels of vascular endothelial growth factor-C and sentinel lymph node status in early breast cancer.

Axillary lymph nodes status is the most important prognosis factor in early breast cancer. This status is known by a selective sentinel lymph node biopsy (SLNB) and/or lymphadenectomy. Immunohistochemical studies of breast cancer tumour tissue have reported a relation between the increased expression of vascular endothelial growth factor-C (VEGF-C) and the risk of lymph node metastasis. We researched whether serum levels of VEGF-C could be a predictor factor of sentinel lymph node status in these patients. A prospective analysis was performed on serum from 174 patients with early breast cancer who underwent SLNB. The level of VEGF-C was determined by enzyme-linked immunosorbent assay. Clinical-pathologic variables were collected. Univariate analysis and multivariate logistic regression were conducted, taking SLNB positivity as the segmentation variable. The predictive value of VEGF-C was assessed using ROC curves. Of the sample group of 167 patients, 64 (38.3 %) had affected lymph node. Eighteen patients (28.1 %) presented micrometastasis; there were isolated tumour cells in 11 cases (17.2 %) and macrometastasis in 35 (54.6 %). The median value of VEGF-C was 6561.5 pg/ml. These values did not correlate with any clinical variables, and there was no association between the level of VEGF-C and SLNB status (p = 0.626). In the multivariate analysis, tumour size (p = 0.009) and the presence of vascular invasion (p < 0.001) were independently associated with sentinel lymph node affected. Serum levels of VEGF-C do not appear to predict sentinel lymph node status in patients with early breast cancer who undergo SLNB.

Phosphorylation of the transcription factor Sp4 is reduced by NMDA receptor signaling.

The regulation of transcription factor function in response to neuronal activity is important for development and function of the nervous system. The transcription factor Sp4 regulates the developmental patterning of dendrites, contributes to complex processes including learning and memory, and has been linked to psychiatric disorders such as schizophrenia and bipolar disorder. Despite its many roles in the nervous system, the molecular mechanisms regulating Sp4 activity are poorly understood. Here, we report a site of phosphorylation on Sp4 at serine 770 that is decreased in response to membrane depolarization. Inhibition of the voltage-dependent NMDA receptor increased Sp4 phosphorylation. Conversely, stimulation with NMDA reduced the levels of Sp4 phosphorylation, and this was dependent on the protein phosphatase 1/2A. A phosphomimetic substitution at S770 impaired the Sp4-dependent maturation of cerebellar granule neuron primary dendrites, whereas a non-phosphorylatable Sp4 mutant behaved like wild type. These data reveal that transcription factor Sp4 is regulated by NMDA receptor-dependent activation of a protein phosphatase 1/2A signaling pathway. Our findings also suggest that the regulated control of Sp4 activity is an important mechanism governing the developmental patterning of dendrites.

Probiotics in autism spectrum disorders: a systematic review of clinical studies and future directions.

CONTEXT: It is hypothesized that gut dysbiosis, a typical feature of patients with autism spectrum disorder (ASD), could be involved in the origin of this neurodevelopmental disorder. Therefore, the use of probiotics to restore gastrointestinal (GI) equilibrium might be a promising therapeutic strategy due to its capacity to balance the gut-brain axis and behavioral responses. OBJECTIVE: To summarize current knowledge on the use of probiotics to treat core clinical ASD symptoms and concomitant GI signs, compare the design of published studies with those of ongoing trials, assess the near future of this field, and provide recommendations for improving novel studies. DATA SOURCES: The literature search was conducted in February 2020 and updated in March 2021, using a broad range of bibliographic and clinical trial-specific databases. DATA EXTRACTION: Data were extracted using a standardized form, and articles reporting on 28 clinical studies (already published or still ongoing) were included. The risk of bias in clinical studies was evaluated using the Cochrane Collaboration Risk of Bias Assessment tool for randomized trials and the Risk of Bias in Nonrandomized Studies-Interventions tool for nonrandomized trials. RESULTS: The results suggest that probiotics improve ASD-like social deficits, GI symptoms, and gut microbiota profile. However, inconsistencies among studies and their methodological limitations make it difficult to draw any conclusions regarding the efficacy of probiotics in ASD. This review provides specific suggestions for future research to improve the quality of the studies. CONCLUSIONS: Although ongoing studies have improved designs, the available knowledge does not permit solid conclusions to be made regarding the efficacy of probiotics in ameliorating the symptoms (psychiatric and/or GI) associated with ASD. Thus, more high-quality research and new approaches are needed to design effective probiotic strategies for ASD.

Efficacy of the combination of water aerobics and metacognitive training on psychological and physical health variables and their relationship with SP1 and SP4 biomarkers in people with psychosis: a study protocol.

Background: Metacognitive Training (MCT) is widely used and effective in reducing positive symptoms in psychosis. Physical exercise, such as Water Aerobics (WA), improves general health, quality of life and symptoms as a low impact activity that allows social interactions. Preliminary results suggest a relationship between dopamine and psychotic symptoms, through SP transcription factors, SP1 and SP4 biomarkers. The aims of the project are to evaluate the efficacy of a combined intervention (WA and MCT) for psychosis to improve psychotic symptoms, physical health, and transcription levels of SP biomarkers. Materials and methods: This is a unicentric randomized controlled trial of three parallel intervention groups: MCT, WA and combined intervention. The estimated sample will be 48 patients with a psychotic spectrum disorder diagnosis. The assessment will be performed at baseline and at 2-months' follow-up. Instruments used in the assessment will include clinical, cognitive, metacognitive, social cognitive and psychosocial variables. Discussion: This will be the first study investigating the impact of the combination of MCT and WA in psychosis. Moreover, it will be the first study analyzing changes in the transcriptional biomarkers SP1 and SP4 after interventions. The results of this study may have clinical implications contributing to the improvement of treatment selection. Clinical trial registration: https://clinicaltrials.gov/, identifier: NCT05455593.

Analysis of networks in the dorsolateral prefrontal cortex in chronic schizophrenia: Relevance of altered immune response.

The dorsolateral prefrontal cortex (DLPFC) has a crucial role in cognitive functioning and negative symptoms in schizophrenia. However, limited information of altered protein networks is available in this region in schizophrenia. We performed a proteomic analysis using single-shot liquid chromatography-tandem mass spectrometry of grey matter of postmortem DLPFC in chronic schizophrenia subjects (n = 20) and unaffected subjects (n = 20) followed by bioinformatic analysis to identify altered protein networks in schizophrenia (PXD024939 identifier in ProteomeXchange repository). Our results displayed a proteome profile in the DLPFC of 1989 proteins. 43 proteins were found significantly altered in schizophrenia. Analysis of this panel showed an enrichment of biological processes implicated in vesicle-mediated transport, processing and antigen presentation via MHC class II, intracellular transport and selenium metabolism. The enriched identified pathways were MHC class II antigen presentation, vesicle-mediated transport, Golgi ER retrograde transport, Nef mediated CD8 downregulation and the immune system. All these enriched categories were found to be downregulated. Furthermore, our network analyses showed crosstalk between proteins involved in MHC class II antigen presentation, membrane trafficking, Golgi-to-ER retrograde transport, Nef-mediated CD8 downregulation and the immune system with only one module built by 13 proteins. RAB7A showed eight interactions with proteins of all these pathways. Our results provide an altered molecular network involved in immune response in the DLPFC in schizophrenia with a central role of RAB7A. These results suggest that RAB7A or other proteins of this network could be potential targets for novel pharmacological strategies in schizophrenia for improving cognitive and negative symptoms.

Evolution of Antimicrobial Susceptibility to Penicillin in Invasive Strains of Streptococcus pneumoniae during 2007-2021 in Madrid, Spain.

The use of pneumococcal conjugate vaccines has affected the epidemiology and distribution of Streptococcus pneumoniae serotypes causing Invasive Pneumococcal Disease (IPD). The aim of this study was to analyze the evolution of the phenotypical profiles of antimicrobial susceptibility to penicillin (PEN) in all IPD strains isolated in Madrid, Spain, during 2007-2021. In total, 7133 invasive clinical isolates were characterized between 2007 and 2021. Levels of PENR and PNSSDR were 2.0% and 24.2%, respectively. In addition, 94.4% of all the PENR belonged to four serotypes, including 11A (33.6%), 19A (30.8%), 14 (20.3%) and 9V (9.8%). All the strains of serotype 11A, which is a non-PCV13 serotype, were detected after the year 2011. Serotypes 6C, 15A, 23B, 24F, 35B, 19F, 16F, 6B, 23F, 24B, 24A, 15F and a limited number of strains of serogroups 16 and 24 (non-typed at serotype level) were associated with PNSSDR (p < 0.05). PNSSDR strains of non-PCV13 serotypes 11A, 24F, 23B, 24B, 23A and 16F were more frequent from 2014 to 2021. The changes in S. pneumoniae serotype distribution associated with the use of conjugate vaccines had caused in our region the emergence of non-PCV13 pneumococcal strains with different PENR or PNSSDR patterns. The emergence of serotype 11A resistant to penicillin as the most important non-PCV13 serotype is a worrisome event with marked relevance from the clinical and epidemiological perspective.

Distribution of Multidrug-Resistant Invasive Serotypes of Streptococcus pneumoniae during the Period 2007-2021 in Madrid, Spain.

After the systematic use of conjugate vaccines, the invasive pneumococcal disease (IPD) was included into the Madrid Notifiable Diseases Surveillance System through an Epidemiological Surveillance Network. Furthermore, Streptococcus pneumoniae was included in the Spanish Plan of Antibiotic Resistance. The aim of this study was to analyse the multidrug-resistant (MDR) phenotype distribution among invasive strains of Streptococcus pneumoniae isolated during 2007-2021 from usually sterile clinical samples in Madrid, Spain. A total number of 7133 invasive pneumococcal isolates were studied during the period from February 2007 to December 2021. Serotyping was characterised using the Pneumotest-Latex and by the Quellung reaction. Antibiotic susceptibility testing to penicillin (PEN), erythromycin (ERY), and levofloxacin (LVX) was performed using the E-test according to the EUCAST guidelines and breakpoints. Combination of non-susceptibility to PEN at standard dosing regimen (PNSSDR), resistance to ERY (ERYR) and to LVX (LVXR) was considered to be multidrug-resistant at standard dosing regimen of penicillin (MRPSDR), whereas the combination of resistance to PEN (PENR), ERYR, and LVXR was considered multidrug-resistant (MDR). The number of MDRPSDR and or MDR strains in the entire population (n = 7133) during the complete period (2007-2021) were 51 (0.7%) and 6 (0.1%), respectively. All MDRPSDR and/or MDR strains belonged to nine serotypes: 19A (n = 13), 15A (n = 12), 9V (n = 12), 14 (n = 7), 24F (n = 3), 15F (n = 1), 19F (n = 1), 6B (n = 1) and 6C (n = 1). Only two serotypes (9V and 19A) were found among MDR strains, and most of them (5/6) belonged to serotype 9V. Only 12.4% of the strains typified as serotype 9V were MDRPSDR and only 5.2% as MDR. The levels of pneumococcal MDRPSDR and/or MDR in this study were low and all six MDR strains were isolated between 2014 and 2018. These results reinforce the importance of monitoring the evolution of non-susceptible serotypes including those with MDR in the coming years, especially after the introduction of new conjugate vaccines of a broader spectrum.