Glial progenitor cells of the adult human white and grey matter are contextually distinct.

Genomic analyses have revealed heterogeneity among glial progenitor cells (GPCs), but the compartment selectivity of human GPCs (hGPCs) is unclear. Here, we asked if GPCs of human grey and white brain matter are distinct in their architecture and associated gene expression. RNA profiling of NG2-defined hGPCs derived from adult human neocortex and white matter differed in their expression of genes involved in Wnt, NOTCH, BMP and TGFß signaling, suggesting compartment-selective biases in fate and self-renewal. White matter hGPCs over-expressed the BMP antagonists BAMBI and CHRDL1, suggesting their tonic suppression of astrocytic fate relative to cortical hGPCs, whose relative enrichment of cytoskeletal genes presaged their greater morphological complexity. In human glial chimeric mice, cortical hGPCs assumed larger and more complex morphologies than white matter hGPCs, and both were more complex than their mouse counterparts. These findings suggest that human grey and white matter GPCs comprise context-specific pools with distinct functional biases.

The importance of well protected forests for the conservation genetics of West African colobine monkeys.

In tropical forests, anthropogenic activities are major drivers of the destruction and degradation of natural habitats, causing severe biodiversity loss. African colobine monkeys (Colobinae) are mainly folivore and strictly arboreal primates that require large forests to subsist, being among the most vulnerable of all nonhuman primates. The Western red colobus Piliocolobus badius and the King colobus Colobus polykomos inhabit highly fragmented West African forests, including the Cantanhez Forests National Park (CFNP) in Guinea-Bissau. Both species are also found in the largest and best-preserved West African forest-the Taï National Park (TNP) in Ivory Coast. Colobine monkeys are hunted for bushmeat in both protected areas, but these exhibit contrasting levels of forest fragmentation, thus offering an excellent opportunity to investigate the importance of well-preserved forests for the maintenance of evolutionary potential in these arboreal primates. We estimated genetic diversity, population structure, and demographic history by using microsatellite loci and mitochondrial DNA. We then compared the genetic patterns of the colobines from TNP with the ones previously obtained for CFNP and found contrasting genetic patterns. Contrary to the colobines from CFNP that showed very low genetic diversity and a strong population decline, the populations in TNP still maintain high levels of genetic diversity and we found no clear signal of population decrease in Western red colobus and a limited decrease in King colobus. These results suggest larger and historically more stable populations in TNP compared to CFNP. We cannot exclude the possibility that the demographic effects resulting from the recent increase of bushmeat hunting are not yet detectable in TNP using genetic data. Nevertheless, the fact that the TNP colobus populations are highly genetically diverse and maintain large effective population sizes suggests that well-preserved forests are crucial for the maintenance of populations, species, and probably for the evolutionary potential in colobines.

Rapid scale-up of COVID-19 training for frontline health workers in 11 African countries.

BACKGROUND: The global spread of the SARS-CoV-2 virus highlights both the importance of frontline healthcare workers (HCW) in pandemic response and their heightened vulnerability during infectious disease outbreaks. Adequate preparation, including the development of human resources for health (HRH) is essential to an effective response. ICAP at Columbia University (ICAP) partnered with Resolve to Save Lives and MOHs to design an emergency training initiative for frontline HCW in 11 African countries, using a competency-based backward-design approach and tailoring training delivery and health facility selection based on country context, location and known COVID-19 community transmission. METHODS: Pre- and post-test assessments were conducted on participants completing the COVID-19 training. Parametric and non-parametric methods were used to examine average individual-level changes from pre- to post-test, and compare performance between countries, cadres, sex and facility types. A post-evaluation online training survey using Qualtrics was distributed to assess participants' satisfaction and explore training relevance and impact on their ability to address COVID-19 in their facilities and communities. RESULTS: A total of 8797 HCW at 945 health facilities were trained between June 2020 and October 2020. Training duration ranged from 1 to 8 days (median: 3 days) and consisted of in person, virtual or self guided training. Of the 8105 (92%) HCW working at health facilities, the majority (62%) worked at secondary level facilities as these were the HF targeted for COVID-19 patients. Paired pre- and post-test results were available for 2370 (25%) trainees, and 1768 (18%) participants completed the post-evaluation training survey. On average, participants increased their pre- to post-test scores by 15 percentage points (95% CI 0.14, 0.15). While confidence in their ability to manage COVID-19 was high following the training, respondents reported that lack of access to testing kits (55%) and PPE (50%), limited space in the facility to isolate patients (45%), and understaffing (39%) were major barriers. CONCLUSION: Ongoing investment in health systems and focused attention to health workforce capacity building is critical to outbreak response. Successful implementation of an emergency response training such as this short-term IPC training initiative in response to the COVID-19 pandemic, requires speed, rigor and flexibility of its design and delivery while building on pre-existing systems, resources, and partnerships.

Mesial temporal lobe epilepsy: Revisiting the relation of hippocampal volumetry with memory deficits.

OBJECTIVE: Neuropsychological tests can infer the lateralization of the epileptogenic focus, associating verbal memory to mesial structures in the left temporal lobe and visual or nonverbal memory to the right side. High-field magnetic resonance imaging (MRI) with high-resolution protocols allows acquisitions suitable for advanced postprocessing with precise volumetry of brain structures, and functional MRI demonstrates evidence that epilepsy should be seen as a network pathology, involving several structures in the brain. Since the literature showing associations between the volumetry of brain structures in left and right mesial temporal lobe epilepsy (MTLE) and verbal and visual memory performance on neuropsychological tests is conflicting, we revisited these relationships, considering the hippocampal volumetry of patients with unilateral MTLE. METHODS: Automatized hippocampal volumes were obtained using FreeSurfer software from MRI exams of 35 patients with unilateral MTLE and hippocampal atrophy and homolateral ictal onset zone defined by video electroencephalography concordant to the side of hippocampal volume reduction (15 on the left side). Verbal memory was assessed using the Rey Auditory-Verbal Learning Test (RAVLT), and visual memory tests employed the Rey-Osterrieth Complex Figure Test (ROCFT). The statistical analysis explored relationships between hippocampal volumetry, lateralization, and performance on memory tests. RESULTS: In general, we observed deficits in both verbal and visual memory for patients with left and right hippocampal volume reduction. Patients with left hippocampal volume reduction had poorer performance on verbal memory tests compared with those with right hippocampal atrophy (t = -3.813, p < 0.001). Visual memory deficits were seen on both left and right MTLE without a statistically significant difference (t = 0.074, p = 0.942). The correlation between the Hippocampal Asymmetry Index (HAI) and visual and verbal Z-scores was significant only for visual Z-score in right MTLE (R = -0.45, p = 0.048). CONCLUSIONS: Verbal memory deficit seems to be more consistent in patients with left hippocampal volume reduction. Although it had only a moderate correlation to HAI, visual memory deficit is suggested as a poorer indicator for right MTLE. Considering that verbal and visual memory deficits are seen on both right and left MTLE, MTLE should not be regarded as a unilateral, focal, or local insult but as a multifactorial and network pathology, possibly involving several brain structures.

Socioeconomic differences among resident, users and neighbour populations of a protected area in the Brazilian dry forest.

Protected areas are an important strategy to safeguard biodiversity. However, if social development is not considered, biological conservation targets may not be achieved. In this empirical study, we assess the relationship between poverty and conservation goals in dry forests within a 62,000-ha Brazilian National Park (Caatinga biome). We conducted 81 structured household interviews between January and July of 2016 to assess socioeconomic, resource management and land-use variables. We used non-parametric analysis of variance to test for differences in socioecological variables among families living inside and outside the Park and both (double dwelling). The majority of families (76%) residing inside the Park were living below the poverty line while less than 14% in outside and double dwelling residences faced the same issue. Families living inside the park had lower socioeconomic conditions such as limited water availability, poor house infrastructure, low income, and high dependence on firewood than outside and double dwelling families. They were also more dependent on external financial support and natural resources. We found that failures in protected areas inception and implementation have driven people towards a mutually reinforcing and declining situation in which negative socioeconomic outcomes are associated with nature degradation. Therefore, our results suggest that the future of dry forests, characterized worldwide by the presence of low-income populations, will be largely dependent on conservation strategies that address poverty alleviation and human well-being.

Tinea corporis by Microsporum audouinii in a female chimpanzee (Pan troglodytes) from Guinea-Bissau: A case report.

We report a Microsporum audouinii infection in a female juvenile chimpanzee (Pan troglodytes) presenting generalized dermatitis compatible with dermatophytosis. Dermatophyte was identified by macro- and microscopic characterization of skin and scales cultures in Mycosel Agar. The topical treatment applied was effective, having the potential for dermatophytosis treatment in immunocompetent primates.

Home-based step training using videogame technology in people with Parkinson's disease: a single-blinded randomised controlled trial.

OBJECTIVES: To determine whether 12-week home-based exergame step training can improve stepping performance, gait and complementary physical and neuropsychological measures associated with falls in Parkinson's disease. DESIGN: A single-blinded randomised controlled trial. SETTING: Community (experimental intervention), university laboratory (outcome measures). SUBJECTS: Sixty community-dwelling people with Parkinson's disease. INTERVENTIONS: Home-based step training using videogame technology. MAIN MEASURES: The primary outcomes were the choice stepping reaction time test and Functional Gait Assessment. Secondary outcomes included physical and neuropsychological measures associated with falls in Parkinson's disease, number of falls over six months and self-reported mobility and balance. RESULTS: Post intervention, there were no differences between the intervention ( n = 28) and control ( n = 25) groups in the primary or secondary outcomes except for the Timed Up and Go test, where there was a significant difference in favour of the control group ( P = 0.02). Intervention participants reported mobility improvement, whereas control participants reported mobility deterioration-between-group difference on an 11-point scale = 0.9 (95% confidence interval: -1.8 to -0.1, P = 0.03). Interaction effects between intervention and disease severity on physical function measures were observed ( P = 0.01 to P = 0.08) with seemingly positive effects for the low-severity group and potentially negative effects for the high-severity group. CONCLUSION: Overall, home-based exergame step training was not effective in improving the outcomes assessed. However, the improved physical function in the lower disease severity intervention participants as well as the self-reported improved mobility in the intervention group suggest home-based exergame step training may have benefits for some people with Parkinson's disease.

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.

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.

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.

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.

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.

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.

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.

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.

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.