The schizophrenia risk gene C4 induces pathological synaptic loss by impairing AMPAR trafficking.

Neuroimmune interactions play a significant role in regulating synaptic plasticity in both the healthy and diseased brain. The complement pathway, an extracellular proteolytic cascade, exemplifies these interactions. Its activation triggers microglia-dependent synaptic elimination via the complement receptor 3 (CR3). Current models of pathological complement activity in the brain propose that accelerated synaptic loss resulting from overexpression of C4 (C4-OE), a gene associated with schizophrenia, follows this pathway. Here, we report that C4-mediated cortical hypoconnectivity is CR3-independent. Instead, C4-OE triggers impaired GluR1 trafficking through an intracellular mechanism involving the endosomal protein SNX27, resulting in pathological synaptic loss. Moreover, C4 circuit alterations in the prefrontal cortex, a brain region associated with neuropsychiatric disorders, were rescued by increasing neuronal levels of SNX27, which we identify as an interacting partner of this neuroimmune protein. Our results link excessive complement activity to an intracellular endo-lysosomal trafficking pathway altering synaptic plasticity.

Effects of a Resistance Exercise Program in Patients with Colorectal Cancer Undergoing Chemotherapy Treatment: A Randomized Controlled Trial Study Protocol.

Background: Colorectal cancer is a leading cause of morbidity and mortality worldwide, with chemotherapy being a crucial treatment despite its significant side effects, such as chemotherapy-induced peripheral neuropathy (CIPN). Physical exercise has shown potential benefits in mitigating these side effects and improving patients' overall well-being. Objective: This study aims to evaluate the efficacy of a strength exercise program in reducing CIPN in patients with colorectal cancer undergoing chemotherapy, along with secondary objectives including impacts on quality of life, body mass index, oxygen consumption, anxiety and depression, fatigue, sleep quality, and various analytical parameters. Methods: A double-blind randomized controlled trial was conducted with 44 participants, divided into an intervention group (supervised resistance training twice a week and home exercises) and a control group (home exercises only). The primary outcome measure was CIPN, assessed using the EORTC QLQ-CIPN20 questionnaire. Secondary outcomes included assessments using the EORTC QLQ-C30, the 6-minute walk test, HADS, FACT-F, and MISS, along with various blood parameters. Results and Conclusions: The study will provide insights into the effectiveness of physical exercise in managing CIPN and improving various health parameters in colorectal cancer patients. By developing tailored exercise protocols, this research aims to enhance patient quality of life, optimize treatment outcomes, and reduce the incidence of debilitating side effects, thereby supporting the integration of physical exercise into standard oncological care.

FAM72A degrades UNG2 through the GID/CTLH complex to promote mutagenic repair during antibody maturation.

A diverse antibody repertoire is essential for humoral immunity. Antibody diversification requires the introduction of deoxyuridine (dU) mutations within immunoglobulin genes to initiate somatic hypermutation (SHM) and class switch recombination (CSR). dUs are normally recognized and excised by the base excision repair (BER) protein uracil-DNA glycosylase 2 (UNG2). However, FAM72A downregulates UNG2 permitting dUs to persist and trigger SHM and CSR. How FAM72A promotes UNG2 degradation is unknown. Here, we show that FAM72A recruits a C-terminal to LisH (CTLH) E3 ligase complex to target UNG2 for proteasomal degradation. Deficiency in CTLH complex components result in elevated UNG2 and reduced SHM and CSR. Cryo-EM structural analysis reveals FAM72A directly binds to MKLN1 within the CTLH complex to recruit and ubiquitinate UNG2. Our study further suggests that FAM72A hijacks the CTLH complex to promote mutagenesis in cancer. These findings show that FAM72A is an E3 ligase substrate adaptor critical for humoral immunity and cancer development.

Descriptive Study on the Relationship between Dyspnea, Physical Performance, and Functionality in Oncology Patients.

BACKGROUND: Cancer is a leading cause of morbidity and mortality globally. Dyspnea, affecting up to 60% of cancer patients, exacerbates physical and psychological distress, reducing quality of life. This study aims to explore the relationship between dyspnea and factors such as age, sex, clinical diagnosis, and treatment lines in cancer patients, with the goal of improving understanding and management of this debilitating symptom to enhance patient care and quality of life. METHODS: This study employed an observational, cross-sectional, and descriptive approach to investigate patients with oncological disease at the University Hospital of Salamanca between March 2021 and April 2024. A convenience sample was selected, including patients over 18 years old with a pathological diagnosis of cancer, experiencing any degree of dyspnea, and who consented to participate by signing the informed consent. Exclusion criteria included lack of consent and clinical conditions that prevented an interview. The studied variables encompass sociodemographic (age, gender, diagnosis, tumor stage, number of treatment lines) and clinical aspects (daily activities, degree of dyspnea, functional capacity, physical performance), evaluated using the Barthel Index, the mMRC Dyspnea Scale, the ECOG Scale, and the Short Physical Performance Battery (SPPB). Data were collected through semistructured interviews and medical records, and analyzed using specialized software. This research has ethical approval CEiM Code 2023 12 1472, Reference 2024/01. RESULTS: The mean age was 66.82 years. Lung cancer was predominant (60.2%), with most patients in stage 3 (65.7%) and receiving three treatment lines (68.7%). Higher age, advanced disease stage, and more treatment lines correlated with lower Barthel and SPPB scores, and higher ECOG and mMRC scores, indicating worse functionality, physical performance, and greater dyspnea. No significant correlations were found between gender or pathological diagnosis and the studied variables. CONCLUSIONS: Advanced age, higher disease stage, and more treatment lines are associated with decreased functionality, poorer physical performance, and increased dyspnea in cancer patients. Gender and specific cancer diagnosis do not significantly affect these relationships. Addressing dyspnea is crucial to improving the quality of life and physical performance in this population. Future studies should explore additional factors like treatment types and nutritional status.

Impact of Simulated Human Gastrointestinal Digestion on the Functional Properties of Dietary Fibres Obtained from Broccoli Leaves, Grape Stems, Pomegranate and Tomato Peels.

This study aimed to analyse the impact of a simulated human digestion process on the composition and functional properties of dietary fibres derived from pomegranate-peel, tomato-peel, broccoli-stem and grape-stem by-products. For this purpose, a computer-controlled simulated digestion system consisting of three bioreactors (simulating the stomach, small intestine and colon) was utilised. Non-extractable phenols associated with dietary fibre and their influence on antioxidant capacity and antiproliferative activity were investigated throughout the simulated digestive phases. Additionally, the modifications in oligosaccharide composition, the microbiological population and short-chain fatty acids produced within the digestion media were examined. The type and composition of each dietary fibre significantly influenced its functional properties and behaviour during intestinal transit. Notably, the dietary fibre from the pomegranate peel retained its high phenol content throughout colon digestion, potentially enhancing intestinal health due to its strong antioxidant activity. Similarly, the dietary fibre from broccoli stems and pomegranate peel demonstrated anti-proliferative effects in both the small and the large intestines, prompting significant modifications in colonic microbiology. Moreover, these fibre types promoted the growth of bifidobacteria over lactic acid bacteria. Thus, these results suggest that the dietary fibre from pomegranate peel seems to be a promising functional food ingredient for improving human health.

Study on the additional financial burden of breast cancer disease on cancer patients and their families. Financial toxicity in cancer.

Introduction: Breast cancer is among the most frequently diagnosed cancers worldwide, with 2.3 million new cases reported annually. The condition causes a social and economic impact known as financial toxicity of cancer. The study aims to explore the extra expenses borne by patients and their families on being diagnosed with breast cancer. Methodology: An observational, descriptive, cross-sectional study was conducted. The data was collected between November 2021 and March 2022 at the Medical Oncology Service in Complejo Asistencial Universitario de Salamanca, Spain. The variables under investigation were additional economic costs, physical disability (as measured by the Barthel Index), instrumental activities of daily living (as measured by the Lawton-Brody Scale), and caregiver burden (measured using the ZARIT scale). Results: The final sample size was N = 107. The study yielded the following outcomes: the median age was 55 years old and the majority of participants were female, with a proportion of 99.1%. The incidence rates for stage I and II were 31.8 and 35.5%, respectively. The median Barthel score was 100 points, while the Lawton and Brody score were 8 points and the ECOG score was 2 points. The analysis of primary caregiver burden resulted in a median ZARIT score of 15 points. The expenses related solely to the cancer diagnosis totaled 1511.22 euros per year (316.82 euros for pharmaceuticals; 487.85 euros for orthopedic equipment; 140.19 euros for home help; and 566.36 euros for housing adaptation or transfer to a hospital). The average annual income before diagnosis was 19962.62 euros. However, after being diagnosed with breast cancer, there is a significant income decrease of 15.91%, resulting in a reduced average annual income of 16785.98 euros. Additionally, a significant correlation was found between total expenditure and the level of dependency (p = 0.032) and functional status (p = 0.045). Conclusion: These findings indicate that breast cancer patients experience a considerable economic burden, which worsens as their functional status deteriorates. Therefore, we believe policies should be implemented to help control this economic deterioration resulting from a serious health condition.

Identification of master regulator genes controlling pathogenic CD4+ T cell fate in inflammatory bowel disease through transcriptional network analysis.

Inflammatory bowel diseases (IBD) are a group of chronic inflammatory conditions of the gastrointestinal tract associated with multiple pathogenic factors, including dysregulation of the immune response. Effector CD4+ T cells and regulatory CD4+ T cells (Treg) are central players in maintaining the balance between tolerance and inflammation. Interestingly, genetic modifications in these cells have been implicated in regulating the commitment of specific phenotypes and immune functions. However, the transcriptional program controlling the pathogenic behavior of T helper cells in IBD progression is still unknown. In this study, we aimed to find master transcription regulators controlling the pathogenic behavior of effector CD4+ T cells upon gut inflammation. To achieve this goal, we used an animal model of IBD induced by the transfer of naïve CD4+ T cells into recombination-activating gene 1 (Rag1) deficient mice, which are devoid of lymphocytes. As a control, a group of Rag1-/- mice received the transfer of the whole CD4+ T cells population, which includes both effector T cells and Treg. When gut inflammation progressed, we isolated CD4+ T cells from the colonic lamina propria and spleen tissue, and performed bulk RNA-seq. We identified differentially up- and down-regulated genes by comparing samples from both experimental groups. We found 532 differentially expressed genes (DEGs) in the colon and 30 DEGs in the spleen, mostly related to Th1 response, leukocyte migration, and response to cytokines in lamina propria T-cells. We integrated these data into Gene Regulatory Networks to identify Master Regulators, identifying four up-regulated master gene regulators (Lef1, Dnmt1, Mybl2, and Jup) and only one down-regulated master regulator (Foxo3). The altered expression of master regulators observed in the transcriptomic analysis was confirmed by qRT-PCR analysis and found an up-regulation of Lef1 and Mybl2, but without differences on Dnmt1, Jup, and Foxo3. These two master regulators have been involved in T cells function and cell cycle progression, respectively. We identified two master regulator genes associated with the pathogenic behavior of effector CD4+ T cells in an animal model of IBD. These findings provide two new potential molecular targets for treating IBD.

Sex differences in strength, functional capacity and mobility in patients with multiple sclerosis: An exploratory analysis.

BACKGROUND: Physical exercise programs are commonly designed without consideration for sex differences. Nevertheless, disease progression exhibits sex-specific patterns, resulting in different functionality and strength performances. OBJECTIVES: To analyze sex differences in strength, functional capacity, and mobility, and to evaluate sex-dependent differences in leg strength in multiple sclerosis (MS) patients. METHODS: A cross-sectional study was conducted with 35 participants (female: n = 19; Expanded Disability Status Scale (EDSS)= 3.0 ± 1.2, male: n = 16; EDSS= 3.3 ± 1.2). Body composition, maximal voluntary isometric contraction (MVIC), explosive strength (rate of force development, RFD), central activation ratio (CAR), functional capacity, and mobility were assessed. RESULTS: Differences were observed between males and females (p = 0.001) in height, lean body mass and MVIC. No differences were observed in the other variables. Regarding the leg asymmetry, men showed higher values in the stronger leg for both MVIC (p < 0.001, d=large) and RFD, whereas women showed higher values only in RFD. Men with MS demonstrated a greater capacity to produce maximal strength than women with this disease. CONCLUSIONS: The results found suggest that maximum strength differs between men and women in our sample of patients with multiple sclerosis. Furthermore, the weaker leg, regardless of sex, exhibits poorer results in explosive strength compared to the stronger leg. However, maximum strength only shows differences in men and not in women. Therefore, these findings should serve as a basis for rehabilitation professionals when planning training programs for this population.

Genetic polymorphisms of CYP2C19 in ecuadorian population: An interethnic approach.

Introduction: CYP2C19 is a highly polymorphic gene responsible for metabolizing commonly used drugs. CYP2C19*2,*3 (loss of activity alleles) and *17 (increased activity allele) are the principal alleles included in clinical guidelines, however their prevalence varies among different ethnicities. Ecuadorian population is formed by Mestizos, Afrodescendants and Native Americans and frequency of CYP2C19 alleles could be different among them. The objective of this study was to establish the frequency of these variants in the different populations of Ecuador and to compare them with other populations. Materials and methods: DNA from 105 Afrodescendants, 75 Native Americans of the Kichwa ethnicity, and 33 Mestizos Ecuadorians was analyzed by nested-PCR to identify CYP2C19*17 carriers. CYP2C19*2 allele was analyzed in DNA from 78 Afrodescendants, 29 Native Americans of the Kichwa, and 16 Mestizos by TaqMan Allelic Discrimination Assay. CYP2C19*3 was analyzed in 33 Afrodescendants by nested-PCR. Results: The global frequencies of the alternate alleles were 14.22% (CYP2C19*2) and 2.10% (CYP2C19*17). No differences (p > 0.05) were observed among the subgroups. No CYP2C19*3 carrier was identified. CYP2C19*2 frequencies in Ecuador were similar to the ones reported in Europe, Africa and Middle East countries and to some American populations. Low CYP2C19*17 frequencies, like the ones in our population, were also observed in East and South Asia and in Native American groups. Discussion: Absence of differences in the ethnic groups in Ecuador for CYP2C19*2 and *17 could be due to either a bias in sample selection (ethnic group was assed by self-identification) or to a high interethnic admixture in the Ecuadorian population that would had diluted genetic differences. In addition, CYP2C19*2, *3, and *17 alleles frequencies in our study suggest that Ecuadorians ancestry is mostly of Native American origin.

Comparison of ddRADseq and EUChip60K SNP genotyping systems for population genetics and genomic selection in Eucalyptus dunnii (Maiden).

Eucalyptus dunnii is one of the most important Eucalyptus species for short-fiber pulp production in regions where other species of the genus are affected by poor soil and climatic conditions. In this context, E. dunnii holds promise as a resource to address and adapt to the challenges of climate change. Despite its rapid growth and favorable wood properties for solid wood products, the advancement of its improvement remains in its early stages. In this work, we evaluated the performance of two single nucleotide polymorphism, (SNP), genotyping methods for population genetics analysis and Genomic Selection in E. dunnii. Double digest restriction-site associated DNA sequencing (ddRADseq) was compared with the EUChip60K array in 308 individuals from a provenance-progeny trial. The compared SNP set included 8,011 and 19,008 informative SNPs distributed along the 11 chromosomes, respectively. Although the two datasets differed in the percentage of missing data, genome coverage, minor allele frequency and estimated genetic diversity parameters, they revealed a similar genetic structure, showing two subpopulations with little differentiation between them, and low linkage disequilibrium. GS analyses were performed for eleven traits using Genomic Best Linear Unbiased Prediction (GBLUP) and a conventional pedigree-based model (ABLUP). Regardless of the SNP dataset, the predictive ability (PA) of GBLUP was better than that of ABLUP for six traits (Cellulose content, Total and Ethanolic extractives, Total and Klason lignin content and Syringyl and Guaiacyl lignin monomer ratio). When contrasting the SNP datasets used to estimate PAs, the GBLUP-EUChip60K model gave higher and significant PA values for six traits, meanwhile, the values estimated using ddRADseq gave higher values for three other traits. The PAs correlated positively with narrow sense heritabilities, with the highest correlations shown by the ABLUP and GBLUP-EUChip60K. The two genotyping methods, ddRADseq and EUChip60K, are generally comparable for population genetics and genomic prediction, demonstrating the utility of the former when subjected to rigorous SNP filtering. The results of this study provide a basis for future whole-genome studies using ddRADseq in non-model forest species for which SNP arrays have not yet been developed.

Acidithiobacillia class members originating at sites within the Pacific Ring of Fire and other tectonically active locations and description of the novel genus 'Igneacidithiobacillus'.

Recent studies have expanded the genomic contours of the Acidithiobacillia, highlighting important lacunae in our comprehension of the phylogenetic space occupied by certain lineages of the class. One such lineage is 'Igneacidithiobacillus', a novel genus-level taxon, represented by 'Igneacidithiobacillus copahuensis' VAN18-1T as its type species, along with two other uncultivated metagenome-assembled genomes (MAGs) originating from geothermally active sites across the Pacific Ring of Fire. In this study, we investigate the genetic and genomic diversity, and the distribution patterns of several uncharacterized Acidithiobacillia class strains and sequence clones, which are ascribed to the same 16S rRNA gene sequence clade. By digging deeper into this data and contributing to novel MAGs emerging from environmental studies in tectonically active locations, the description of this novel genus has been consolidated. Using state-of-the-art genomic taxonomy methods, we added to already recognized taxa, an additional four novel Candidate (Ca.) species, including 'Ca. Igneacidithiobacillus chanchocoensis' (mCHCt20-1TS), 'Igneacidithiobacillus siniensis' (S30A2T), 'Ca. Igneacidithiobacillus taupoensis' (TVZ-G3 TS), and 'Ca. Igneacidithiobacillus waiarikiensis' (TVZ-G4 TS). Analysis of published data on the isolation, enrichment, cultivation, and preliminary microbiological characterization of several of these unassigned or misassigned strains, along with the type species of the genus, plus the recoverable environmental data from metagenomic studies, allowed us to identify habitat preferences of these taxa. Commonalities and lineage-specific adaptations of the seven species of the genus were derived from pangenome analysis and comparative genomic metabolic reconstruction. The findings emerging from this study lay the groundwork for further research on the ecology, evolution, and biotechnological potential of the novel genus 'Igneacidithiobacillus'.

Characterization of carboxylated cellulose nanofibrils and oligosaccharides from Kraft pulp fibers and their potential elicitor effect on the gene expression of Capsicum annuum.

Biomass-derived oligo- and polysaccharides may act as elicitors, i.e., bioactive molecules that trigger plant immune responses. This is particularly important to increase the resistance of plants to abiotic and biotic stresses. In this study, cellulose nanofibrils (CNF) gels were obtained by TEMPO-mediated oxidation of unbleached and bleached kraft pulps. The molecular structures were characterized with ESI and MALDI MS. Analysis of the fine sequences was achieved by MS and MS/MS of the water-soluble oligosaccharides obtained by acid hydrolysis of the CNF gels. The analysis revealed the presence of two families: one corresponding to homoglucuronic acid sequences and the other composed by alternating glucose and glucuronic acid units. The CNF gels, alone or with the addition of the water-soluble oligosaccharides, were tested on Chili pepper (Capsicum annuum). Based on the characterization of the gene expression with Next Generation Sequencing (NGS) of the C. annuum's total messenger RNA, the differences in growth of the C. annuum seeds correlated well with the downregulation of the pathways regulating photosynthesis. A downregulation of the response to abiotic factors was detected, suggesting that these gels would improve the resistance of the C. annuum plants to abiotic stress due to, e.g., water deprivation and cold temperatures.

Study protocol for a randomized controlled trial: Effect of an everyday cognition training program on cognitive function, emotional state, frailty and functioning in older adults without cognitive impairment.

BACKGROUND: Ageing entails changes in complex cognitive functions that lead to a decrease in autonomy and quality of life. Everyday cognition is the ability to solve cognitively complex problems in the everyday world, enabling instrumental activities of life. Benefits have been found in studies using everyday cognition-based assessment and intervention, as the results predict improvements in everyday performance, not just in specific cognitive functions. A study protocol is presented based on assessment and training in everyday cognition versus traditional cognitive stimulation for the improvement of functionality, emotional state, frailty and cognitive function. METHODS: A parallel randomised controlled clinical trial with two arms will be conducted. It will be carried out by the University of Salamanca (Spain) in eleven centres and associations for the elderly of the City Council of Salamanca. People aged 60 years or older without cognitive impairment will be recruited. Participants will be randomly distributed into two groups: the experimental group will undergo a training programme in everyday cognition and the control group a programme of traditional cognitive stimulation, completing 25 sessions over 7 months. All participants will be assessed at the beginning and at the end of the intervention, where socio-demographic data and the following scales will be collected: The Medical Outcomes Study (MOS), Questionnaire ARMS-e, Everyday Cognition Test (PECC), Scale Yesavage, Test Montreal Cognitive Assessment (MoCA), The Functional Independence Measure (FIM), Fragility Index and Lawton y Brody Scale. DISCUSSION: The present study aims to improve conventional clinical practice on cognitive function training by proposing a specific assessment and intervention of everyday cognition based on the importance of actual cognitive functioning during the resolution of complex tasks of daily life, giving priority to the improvement of autonomy. TRIAL REGISTRATION: ClinicalTrials.gov; ID: NCT05688163. Registered on: January 18, 2023.

Using metabolic networks to predict cross-feeding and competition interactions between microorganisms.

Understanding the interactions between microorganisms and their impact on bacterial behavior at the community level is a key research topic in microbiology. Different methods, relying on experimental or mathematical approaches based on the diverse properties of bacteria, are currently employed to study these interactions. Recently, the use of metabolic networks to understand the interactions between bacterial pairs has increased, highlighting the relevance of this approach in characterizing bacteria. In this study, we leverage the representation of bacteria through their metabolic networks to build a predictive model aimed at reducing the number of experimental assays required for designing bacterial consortia with specific behaviors. Our novel method for predicting cross-feeding or competition interactions between pairs of microorganisms utilizes metabolic network features. Machine learning classifiers are employed to determine the type of interaction from automatically reconstructed metabolic networks. Several algorithms were assessed and selected based on comprehensive testing and careful separation of manually compiled data sets obtained from literature sources. We used different classification algorithms, including K Nearest Neighbors, XGBoost, Support Vector Machine, and Random Forest, tested different parameter values, and implemented several data curation approaches to reduce the biological bias associated with our data set, ultimately achieving an accuracy of over 0.9. Our method holds substantial potential to advance the understanding of community behavior and contribute to the development of more effective approaches for consortia design.IMPORTANCEUnderstanding bacterial interactions at the community level is critical for microbiology, and leveraging metabolic networks presents an efficient and effective approach. The introduction of this novel method for predicting interactions through machine learning classifiers has the potential to advance the field by reducing the number of experimental assays required and contributing to the development of more effective bacterial consortia.

Daily Consumption of Golden Berry (Physalis peruviana) Has Been Shown to Halt the Progression of Insulin Resistance and Obesity in Obese Rats with Metabolic Syndrome.

In a study addressing the high risk of chronic diseases in people with diabetes and obesity linked to metabolic syndrome, the impact of a Golden Berry diet was investigated using a diabetic animal model. Obese rats with diabetic characteristics were fed a diet containing five percent Golden Berry for 16 days. This study focused on various parameters including organ weights, expression of metabolic genes, and urinary biomarkers. Post-Golden Berry intake, there was a notable decrease in the body, liver, pancreas, visceral, and subcutaneous adipose tissue weights in these obese, hyperglycemic rats. In contrast, an increase in brown adipose tissue (BAT) cell mass was observed. This diet also resulted in reduced blood glucose levels and normalized plasma biochemical profiles, including cholesterol, triglycerides, LDL, and HDL levels. Additionally, it modulated specific urinary biomarkers, particularly pipe-colic acid, a primary marker for type 2 diabetes. Bioinformatics analysis linked these dietary effects to improved insulin signaling and adipogenesis. Regular consumption of Golden Berry effectively prevented insulin resistance and obesity in rats, underscoring its significant health benefits and the protective role of an antioxidant-rich diet against metabolic syndrome. These findings offer promising insights for future therapeutic strategies to manage and prevent obesity and related chronic diseases.

Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction.

Fast-spiking parvalbumin (PV)-positive cells are key players in orchestrating pyramidal neuron activity, and their dysfunction is consistently observed in myriad brain diseases. To understand how immune complement dysregulation - a prevalent locus of brain disease etiology - in PV cells may drive disease pathogenesis, we have developed a transgenic mouse line that permits cell-type specific overexpression of the schizophrenia-associated complement component 4 (C4) gene. We found that overexpression of mouse C4 (mC4) in PV cells causes sex-specific behavioral alterations and concomitant deficits in synaptic connectivity and excitability of PV cells of the prefrontal cortex. Using a computational network, we demonstrated that these microcircuit deficits led to hyperactivity and disrupted neural communication. Finally, pan-neuronal overexpression of mC4 failed to evoke the same deficits in behavior as PV-specific mC4 overexpression, suggesting that C4 perturbations in fast-spiking neurons are more harmful to brain function than pan-neuronal alterations. Together, these results provide a causative link between C4 and the vulnerability of PV cells in brain disease.

Effectiveness of Different Neurocognitive Intervention Approaches on Functionality in Healthy Older Adults: A Systematic Review.

Subtle loss of functionality in healthy older adults is considered one of the most important predictors of cognitive decline. Neurocognitive interventions are increasingly being used, from a preventive maintenance approach to functional capacity. This study evaluates the effectiveness of different neurocognitive approaches on the functionality of healthy older adults. In this systematic review (CRD42023473944), an extensive search was conducted for articles published in the last 10 years (2013-2023) in the following databases: Medline, Scopus, and Web of Science. A total of 809 trials were identified, of which 18 were considered to be eligible for inclusion in the review. The data revealed heterogeneity in sample size, measures of functional assessment, neurocognitive interventions used, number of sessions, session duration, and time. Traditional cognitive stimulation is shown to have no significant functional benefit, while other less commonly used neurocognitive interventions, such as those based on everyday cognition, are associated with more significant benefits. Moreover, it is demonstrated that although the Instrumental Activities of Daily Living scale (IADL) is the most used test in similar studies, it is not sensitive enough to detect changes in functionality in healthy elderly individuals, with other tests such as the Timed Instrumental Activities of Daily Living (TIADL) being more advantageous. Therefore, a new guideline is proposed for its use in clinical practice and research, using homogeneous study protocols and neurocognitive interventions that allow for the transfer and generalization of results in daily life.

Correction: Vicencio et al. Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis. Int. J. Mol. Sci. 2023, 24, 14835.

In the original publication [...].