Microglial Modulation of Synaptic Maturation, Activity, and Plasticity.

Microglia, which are the resident immune cells of the CNS, also have important functions in physiological conditions. In this chapter, we review the experimental evidence that microglia modulate neuronal and synaptic activity during normal development and in adults. We show that microglia can regulate the maturation and function of both inhibitory and excitatory synapses that can be stimulated or repressed. We further review the fact that these regulations occur in various brain regions, through soluble and membrane molecules, directly or through other cell partners. This review emphasizes the fact that microglia are genuine and highly context-dependent and thus adaptable regulators of neuronal activity.

Effects of a Multifactorial Program with Case Management for Falls Prevention on Functional Outcomes in Community-Dwelling Older People: A Randomized Clinical Study.

Falls are among the top 10 causes of years lived with disability in people aged 75 and over. Preventive programs like case management (CM) are crucial. OBJECTIVES: To evaluate the effects of a multifactorial fall prevention program based on CM on physical performance, the presence of pain, and the risk of falls and fractures in older people who have suffered falls. METHODS: This randomized, single-blind clinical trial with parallel groups, Intervention Group (IG) and Control Group (CG), was composed of 55 older people with a history of falling, living in the community. All participants underwent an initial assessment via video call (containing anamnesis, timed up-and-go test, falls risk score, short physical performance battery, and clinical frax). The IG underwent CM, the physical exercise protocol, and the cognitive stimulation protocol. The CG was monitored through telephone calls and received general health and fall guidance. RESULTS: No significant results were found in the physical capacity, the presence of pain, the risk of falls, or the fractures between the Intervention and Control Groups and between assessments. CONCLUSION: This program was not effective in improving functional performance, but it was important for characterizing pain and the probability of fracture in the next 10 years in this population.

Using Digital Technology to Promote Patient Participation in the Rehabilitation Process in Hip Replacement: A Scoping Review.

The purpose of this scoping review was to identify and summarize how technology can promote patient participation in the rehabilitation process in hip replacement. We conducted a scoping review following the steps outlined by the Joanna Briggs Institute. The PRISMA Checklist (Preferred Reporting Items for Systematic reviews and Meta-Analyses) was utilized to systematically organize the gathered information. A thorough search of articles was performed on PubMed, Scopus, and CINAHL databases for all publications up to December 2022. Twenty articles were included in this study. Various technologies, such as mobile applications, Web sites, and platforms, offer interactive approaches to facilitate total hip replacement rehabilitation. The analyzed studies were based on the rehabilitation of total hip arthroplasty, which in most of them was developed in mobile applications and Web sites. The studies identified reflect trends in the application of digital health technologies to promote patient engagement in the rehabilitation process and provide risk monitoring and patient education.

Effects of a case management-based intervention on non-motor risk factors for falls in older people with history of falls: a randomised clinical trial.

BACKGROUND: Falls are directly related to morbidity and mortality of older people. Multifactorial approaches that are individualised and based on fall risk factors are necessary. This study aims to verify the effects of a case management-based intervention on non-motor risk factors for falls in community-dwelling older people with a history of falls. METHODS: The intervention applied a multidimensional assessment of risk factors for falls, a discussion about the identified risk factors, the preparation of an individualised plan with the participant, and the application, monitoring and review of the plan. RESULTS: There was a significant interaction between groups and assessments only in the visuospatial domain (P = 0.031). After simple main effects analysis, differences between groups and assessments were not significant, although there was a tendency of worse visuospatial performance in the control group in the follow-up assessment (P = 0.099). There were no significant differences between groups or between assessments in other variables. CONCLUSION: The intervention has the potential to maintain non-motor risk factors for falls in community-dwelling older people with a history of falls. However, more clinical trials are needed to prove its effects.

RehabApp to promote patient participation in the rehabilitation process after HIP replacement: Development and usability study.

OBJECTIVE: This study aims to present the developmental stages of a Mobile App Prototype designed to enhance patient participation in the rehabilitation process after hip replacement. METHODS: To ensure effective interaction between the system and the end user, a User-Centered Design methodology was followed, encompassing three phases: Requirements gathering, Prototyping, and Evaluation. Usability tests were conducted to assess the usability of the developed system. RESULTS: The RehabApp for mobile devices was created, and the testing results were positive. Users expressed satisfaction with the outcome, deeming it a valuable tool for their recovery. This outcome demonstrates the high receptiveness of these technologies in the healthcare sector, making it a project that can readily be expanded into other areas of rehabilitation. CONCLUSION: This study demonstrated the potential of the RehabApp in the rehabilitation process after hip replacement surgery. This accomplishment was realized by ensuring the active participation of patients, potential users, and healthcare professionals throughout the app's development. INNOVATION: The RehabApp is a mobile application to provide users with all the necessary knowledge, enabling them to undergo a smoother and safer rehabilitation. Feedback from both patients and healthcare professionals played a crucial role in refining the app's features and addressing usability concerns.

Frequency of low-dose dexamethasone suppression test (LDDST) response patterns and their correlation with clinicopathologic signs in dogs suspected of having Cushing's syndrome: A retrospective study.

A retrospective cross-sectional study was conducted to assess the frequency of low-dose dexamethasone suppression test (LDDST) patterns in canine patients that had clinicopathologic signs consistent with Cushing's syndrome (CS). Medical records for patients of interest (N = 128) were reviewed between January 2014 and December 2020 to analyse and classify LDDST results based upon the following patterns: lack of suppression, partial suppression, complete suppression, escape, or inverse. Complete suppression, lack of suppression, partial suppression, escape, and inverse patterns were identified in 39.1%, 31.2%, 14.1%, 10.1% and 5.5% of cases respectively. LDDST results were also evaluated with respect to clinical signs, serum alkaline phosphatase (ALP) activity, urine specific gravity (USG) and adrenal ultrasonographic findings. There was no association between LDDST patterns and clinical signs (p = 0.11), increased ALP (p = 0.32), USG (p = 0.33) or adrenal ultrasonographic findings (p = 0.19). In all dogs that demonstrated complete suppression or an inverse pattern, CS was excluded by the attending clinician. The diagnosis of CS was also excluded without further exploration in 23.1%, 7.5% and 5.6% of dogs that demonstrated an escape pattern, lack of suppression and partial suppression pattern, respectively. These results suggest that the clinical significance of LDDST patterns, particularly escape and inverse patterns, are misunderstood by some clinicians, leading them to prematurely exclude the diagnosis of CS.

Resistance to KRAS inhibition in advanced non-small cell lung cancer.

Lung cancer remains the leading cause of cancer death globally. More than 50% of new cases are diagnosed in an advanced or metastatic stage, thus contributing to the poor survival of such patients. Mutations in the KRAS (Kirsten rat sarcoma virus) gene occur in nearly a third of lung adenocarcinoma and have for decades been deemed an 'undruggable' target. Yet, in recent years, a growing number of small molecules, such as the GTPase inhibitors, has been investigated in clinical trials of lung cancer patients harboring KRAS mutations, yielding promising results with improved outcomes. Currently, there are only two approved targeted therapies (adagrasib and sotorasib) for advanced or metastatic KRAS-mutated NSCLC from the second-line setting onwards. In this narrative review, we will focus on KRAS, its molecular basis, the role of its co-mutations, clinical evidence for its inhibition, putative mutation to resistance, and future strategies to overcome resistance to KRAS inhibition.

Development and Validation of the Serious Educational Game in Nursing Appraisal Scale.

OBJECTIVES: This study aims to develop and validate the Serious Educational Game in Nursing Appraisal Scale (SEGiNAS), a tool designed to evaluate the implementation of serious games within nurse education contexts of quantity of process, quality of process, and learning outcomes. METHODS AND MATERIALS: This methodological and psychometric study aimed to develop and validate a scale. The item generation phase was based on the cognitive theory of multimedia learning, resulting in a 20-item scale. The validation phase involved evaluating the psychometric scale by surveying 160 Portuguese nurses. RESULTS: A factor analysis revealed a three-factor structure corresponding to the scale's designed dimensions, explaining a total variance of 64.5%. The scale demonstrated high internal consistency for all factors, including engagement and teaching effectiveness (0.925), learning impact and practical application (0.883), and content relevance and clarity (0.848). The dimensions were engagement and teaching effectiveness, learning impact and practical application, and content relevance and clarity. CONCLUSIONS: The SEGiNAS scale represents a valid and reliable tool for evaluating serious games in nursing education. Its development fills an existing gap in assessing the teaching-learning process with serious games. This study was not registered.

Repeated human leukocyte antigens eplets, importance of typing the partner.

INTRODUCTION: Antibody-mediated rejection (AMR) is the most common cause of immune-mediated allograft failure after kidney transplant and impacts allograft survival. Previous sensitization is a major risk factor for development of donor specific antibodies (DSA). AMR can have a wide range of clinical features such as impaired kidney function, proteinuria/hypertension or can be subclinical. HLA molecules have specific regions of antigens binding antibodies called epitopes and eplets are considered essential components responsible for immune recognition. We present a patient with subclinical AMR 1 week post transplantation. CASE REPORT: A 48-year-old, caucasian woman with end-stage kidney disease (ESKD) secondary to autosomal dominant polycystic kidney disease (ADPKD) on peritoneal dialysis was registered in deceased donor waitlist. She was a hypersensitized patient from 3 prior pregnancies with a calculated panel reactive antibody of 93,48%. She was transplanted through kidney paired exchange donation with no evidence of DSA pre transplantation. Surgery and post-op were unremarkable with excellent and immediate graft function. Per protocol DSA levels on the 5th day was DR1 of 3300 MFI, with an increase in MFI by day 13 with 7820 MFI and a new B41 1979MFI. Allograft kidney biopsy findings were diagnostic of AMR and she was treated with immunoglobulin and plasmapheresis. As early onset AMR post transplantation was observed an anamnestic response was hypothesized from a previous exposure to allo-HLA. We decided to type her husband, her son's father, which was presented with DSA. Mismatch eplet analysis revealed a shared 41 T and 67LQ eplets between the donor and husband, responsible for the reactivity and new HLA class I B41 and HLA class II DR1 DSA, respectively. DISCUSSION: Shared eplets between the patient husband and donor was responsible for the alloimmune response and early development of DSAs. This case highlights the importance of early monitoring DSA levels in highly sensitized patients after transplant in order to promptly address and lower inflammatory damage. Mismatch eplet analysis can provide a thorough and precise evaluation of immune compatibility providing a useful technique to immune risk stratification, donor selection and post-transplant immunosuppressive therapy and monitoring.

Microglial TNFα controls daily changes in synaptic GABAARs and sleep slow waves.

Microglia sense the changes in their environment. How microglia actively translate these changes into suitable cues to adapt brain physiology is unknown. We reveal an activity-dependent regulation of cortical inhibitory synapses by microglia, driven by purinergic signaling acting on P2RX7 and mediated by microglia-derived TNFα. We demonstrate that sleep induces microglia-dependent synaptic enrichment of GABAARs in a manner dependent on microglial TNFα and P2RX7. We further show that microglia-specific depletion of TNFα alters slow waves during NREM sleep and blunt memory consolidation in sleep-dependent learning tasks. Together, our results reveal that microglia orchestrate sleep-intrinsic plasticity of synaptic GABAARs, sculpt sleep slow waves, and support memory consolidation.

Family Nursing Care during the Transition to Parenthood: A Scoping Review.

BACKGROUND: Family-centered care places the family at the core of care, with family nurses playing a pivotal role in supporting and guiding members through pregnancy and the transition to parenthood and acknowledging the significant adjustments during these phases. AIM: To map the evidence concerning family nurses' care for families during the transition to parenthood. METHOD: The scoping review followed the Joanna Briggs Institute (JBI) methodology, focusing on family-centered care during pregnancy adaptation and the initial months of parenthood. Using a PCC (population, concept, and context) strategy, the research covered various databases: Scopus; Web of Science; and CINAHL Complete, MedLine Complete, and MedicLatina by EBSCOhost. RESULTS: A Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) flow diagram was used to present the results. Eighteen articles were included, mainly from the Middle East and Europe, including cross-sectional studies and reviews. Key findings addressed the transitioning process to parenthood, the impact of family characteristics, and the role of family nurses in enhancing these processes. CONCLUSION: Home care is considered vital during this transition. Family nursing should concentrate on both individuals and the parental subsystem, addressing social determinants equitably. Through these efforts, they empower families to establish an optimal environment for children's development.

Multiple basal infusion rates in open-loop insulin delivery systems: is there a metabolic benefit?

Objective: To evaluate glycemic control according to the number of daily basal rates (BRs) in type 1 diabetes patients using continuous subcutaneous insulin infusion (CSII). Subjects and methods: Cross-sectional study of patients treated with an open-loop CSII for at least 6 months and using a flash glucose monitoring system. Patients were divided into 2 groups: group 1 (G1) and group 2 (G2), with ≤4 and >4 BRs/24h, respectively. The groups were compared regarding HbA1c, time in range (TIR), time above range (TAR), time below range (TBR), glucose management indicator (GMI), glucose variability and data related to hypoglycemia. Regression models were performed. Results: The study included 99 patients (n = 55 in G1; n = 44 in G2). Median (Interquartile range) overall age was 30 (17) years, with 19.5 (48) and 51 (77) months of CSII use, respectively. The median number of different BRs was 3 (2) for G1 and 6 (2) for G2. There were no differences concerning age, sex, educational stage, weight, and insulin analog used. G2 had longer disease duration, longer CSII use, and higher total basal daily dose/kg. No significant differences regarding HbA1c, median glucose, GMI, TIR, TAR, and CV were found. G2 patients had more hypoglycemia, more asymptomatic hypoglycemia, and higher TBR. After adjusting for potential confounders, G1 maintained a lower risk of asymptomatic hypoglycemia. Conclusion: Programming open-loop CSII devices with more than 4 BRs does not improve metabolic control. Additionally, it seems to be a risk factor for hypoglycemia and was an independent predictor for asymptomatic hypoglycemia.

ERS International Congress 2023: highlights from the Thoracic Oncology Assembly.

Lung cancer is the leading cause of cancer mortality in the world. It greatly affects the patients' quality of life, and is thus a challenge for the daily practice in respiratory medicine. Advances in the genetic knowledge of thoracic tumours' mutational landscape, and the development of targeted therapies and immune checkpoint inhibitors, have led to a paradigm shift in the treatment of lung cancer and pleural mesothelioma. During the 2023 European Respiratory Society Congress in Milan, Italy, experts from all over the world presented their high-quality research and reviewed best clinical practices. Lung cancer screening, management of early stages of lung cancer, application of artificial intelligence and biomarkers were discussed and they will be summarised here.

On the potential role of naturally occurring carboxylic organic acids as anti-infective agents: opportunities and challenges.

Carboxylic organic acids are intermediates of central carbon metabolic pathways (e.g. acetic, propionic, citric, and lactic acid) long known to have potent antimicrobial potential, mainly at acidic pHs. The food industry has been leveraging those properties for years, using many of these acids as preservatives to inhibit the growth of pathogenic and/or spoilage fungal and bacterial species. A few of these molecules (the most prominent being acetic acid) have been used as antiseptics since Hippocratic medicine, mainly to treat infected wounds in patients with burns. With the growth of antibiotic therapy, the use of carboxylic acids (and other chemical antiseptics) in clinical settings lost relevance; however, with the continuous emergence of multi-antibiotic/antifungal resistant strains, the search for alternatives has intensified. This prospective article raises awareness of the potential of carboxylic acids to control infections in clinical settings, considering not only their previous exploitation in this context (which we overview) but also the positive experience of their safe use in food preservation. At a time of great concern with antimicrobial resistance and the slow arrival of new antimicrobial therapeutics to the market, further exploration of organic acids as anti-infective molecules may pave the way to more sustainable prophylactic and therapeutic approaches.

Multiple myeloma in dogs: Use of the cell block technique as a new diagnostic tool.

BACKGROUND: The diagnosis of multiple myeloma (MM) in dogs may be challenging and complex. The cell blocks are a diagnostic technique that allows the characterization of neoplastic cells and, therefore, might help in the diagnosis of atypical MM. OBJECTIVE: The objective of the present work is to describe three clinical cases in which the cell blocks and immunohistochemistry contributed to the definitive diagnosis of canine MM. METHODS: Three dogs, one female and two males, with different clinical signs, were presented for consultation with anemia, hyperproteinemia with monoclonal gammopathy, and the presence of plasmacytosis in the bone marrow. Cytologic analysis of the spleen was performed in two dogs and was suggestive of the presence of lymphocytes or plasma cells of a neoplastic nature in one of the cases and plasma cell hyperplasia associated with extramedullary hematopoiesis in the other. Given the hypotheses of lymphoid neoplasms with a plasma cell phenotype, cell blocks from aspiration punctures were performed for immunohistochemical analysis with anti-CD3, CD20, CD79αcy, PAX5, and MUM1 antibodies. RESULTS: The results revealed positive staining for MUM1 in 80% of the cells in the spleen cell block and for CD20 and MUM1 in 70% of the cells in the bone marrow cell blocks, with negative staining for the other antibodies. The immunophenotyping results allowed the diagnosis of MM in the three cases and excluded other lymphoid neoplasms. CONCLUSIONS: This work reinforces the importance of using cell blocks in the diagnosis of neoplasms by demonstrating their potential to aid the diagnosis of MM.

Multiple basal infusion rates in open-loop insulin delivery systems: is there a metabolic benefit?

ABSTRACT Objective: To evaluate glycemic control according to the number of daily basal rates (BRs) in type 1 diabetes patients using continuous subcutaneous insulin infusion (CSII). Subjects and methods: Cross-sectional study of patients treated with an open-loop CSII for at least 6 months and using a flash glucose monitoring system. Patients were divided into 2 groups: group 1 (G1) and group 2 (G2), with ≤4 and >4 BRs/24h, respectively. The groups were compared regarding HbA1c, time in range (TIR), time above range (TAR), time below range (TBR), glucose management indicator (GMI), glucose variability and data related to hypoglycemia. Regression models were performed. Results: The study included 99 patients (n = 55 in G1; n = 44 in G2). Median (Interquartile range) overall age was 30 (17) years, with 19.5 (48) and 51 (77) months of CSII use, respectively. The median number of different BRs was 3 (2) for G1 and 6 (2) for G2. There were no differences concerning age, sex, educational stage, weight, and insulin analog used. G2 had longer disease duration, longer CSII use, and higher total basal daily dose/kg. No significant differences regarding HbA1c, median glucose, GMI, TIR, TAR, and CV were found. G2 patients had more hypoglycemia, more asymptomatic hypoglycemia, and higher TBR. After adjusting for potential confounders, G1 maintained a lower risk of asymptomatic hypoglycemia. Conclusion: Programming open-loop CSII devices with more than 4 BRs does not improve metabolic control. Additionally, it seems to be a risk factor for hypoglycemia and was an independent predictor for asymptomatic hypoglycemia.

The potential of games for vulnerable groups like refugees: a scoping review.

OBJECTIVE: To map existing studies on the development of games for refugees, identifying the developed games, characteristics and possible application to health care. METHOD: A scoping review study, carried out in July 2022, using the MEDLINE® (Medical Literature Analysis and Retrieval System Online), CINAHL® (Cumulative Index to Nursing and Allied Health Literature), SPORTDiscus, Scopus, SciELO (Scientific Electronic Library Online), Psychology and Behavioral Sciences Collection, Cochrane Central Register of Controlled Trials databases. RESULTS: 8 studies were identified, with 8 different types of games published between 2016 and 2022. The characteristics of the games found essentially fall on their use to increase empathy towards refugees. CONCLUSION: This study identifies opportunities to strengthen the current body of knowledge in nursing, using games as ways of welcoming, training and integrating populations in situations of social vulnerability in which refugees find themselves.

The first Miocene fossils from coastal woodlands in the southern East African Rift.

The Miocene was a key time in the evolution of African ecosystems witnessing the origin of the African apes and the isolation of eastern coastal forests through an expanding arid corridor. Until recently, however, Miocene sites from the southeastern regions of the continent were unknown. Here, we report the first Miocene fossil teeth from the shoulders of the Urema Rift in Gorongosa National Park, Mozambique. We provide the first 1) radiometric ages of the Mazamba Formation, 2) reconstructions of paleovegetation in the region based on pedogenic carbonates and fossil wood, and 3) descriptions of fossil teeth. Gorongosa is unique in the East African Rift in combining marine invertebrates, marine vertebrates, reptiles, terrestrial mammals, and fossil woods in coastal paleoenvironments. The Gorongosa fossil sites offer the first evidence of woodlands and forests on the coastal margins of southeastern Africa during the Miocene, and an exceptional assemblage of fossils including new species.

Clinical findings and prognostic factors for mortality in hospitalized dogs with leishmaniosis: aretrospective study.

This retrospective study evaluated factors responsible for mortality of dogs hospitalized for Canine Leishmaniosis. Medical records of 31 dogs with leishmaniosis from a Portuguese Veterinary Teaching Hospital were examined between August 2018 and January 2022. Females (n = 18) and pure breed dogs (n = 27) were overrepresented, with higher frequency of Labrador Retriever (n = 4). Median age was 7 years (interquartile range=7). Most had historical findings of lethargy (n = 26) and the commonest clinicopathological abnormality was hypoalbuminemia (n = 26). Eleven dogs were classified as LeishVet stage II, 10 stage III and 10 stage IV. Fourteen dogs (45.2%) died or were euthanized, with azotemia, leukocytosis, stage IV, absence of diagnosis before hospitalization and lack of leishmaniosis specific treatment during hospitalization contributing to mortality. Absence of hypoalbuminemia and stages II/III increased survival. Mean hospitalization length prior to discharge was 5.41days ( ± 1.84) and diarrhea prolonged hospital stay.

ERS International Congress 2022: highlights from the Thoracic Oncology Assembly.

Thoracic malignancies are associated with a substantial public health burden. Lung cancer is the leading cause of cancer-related mortality worldwide, with significant impact on patients' quality of life. Following 2 years of virtual European Respiratory Society (ERS) Congresses due to the COVID-19 pandemic, the 2022 hybrid ERS Congress in Barcelona, Spain allowed peers from all over the world to meet again and present their work. Thoracic oncology experts presented best practices and latest developments in lung cancer screening, lung cancer diagnosis and management. Early lung cancer diagnosis, subsequent pros and cons of aggressive management, identification and management of systemic treatments' side-effects, and the application of artificial intelligence and biomarkers across all aspects of the thoracic oncology pathway were among the areas that triggered specific interest and will be summarised here.