Enhancing nursing care through technology and standardized nursing language: The TEC-MED multilingual platform.

PURPOSE: This study describes the design, integration, and semantic interoperability process of a minimum data set using standardized nursing language in the caring module of the TEC-MED care platform. METHODS: The caring module was developed in three phases (2020-2022): platform concept, functional design and construction, and testing and evaluation. Phases involved collaboration among academics, information technology developers, and social/healthcare professionals. Nursing taxonomies (NANDA-I, NOC, NIC) were integrated to support the nursing process. The platform was piloted in six Mediterranean countries. FINDINGS: The final platform features an assessment module with eight dimensions for data collection on older adults and their caregivers. A clinical decision support system links assessment data with nursing diagnoses, outcomes, and interventions. The platform is available in six languages (English, Spanish, French, Italian, Greek, and Arabic). Usability testing identified the need for improved Arabic language support. CONCLUSIONS: The TEC-MED platform is a pioneering tool using standardized nursing language to improve care for older adults in the Mediterranean. The platform's multilingualism promotes accessibility. Limitations include offline use and mobile app functionality. Pilot testing is underway to evaluate effectiveness and facilitate cross-cultural validation of nursing taxonomies. IMPLICATIONS FOR NURSING PRACTICE: The TEC-MED platform offers standardized nursing care for older adults across the Mediterranean, promoting consistent communication and evidence-based practice. This approach has the potential to improve care quality and accessibility for a vulnerable population.

OBJETIVO: Este estudio describe el diseño, la integración y el proceso de interoperabilidad semántica de un conjunto mínimo de datos utilizando un lenguaje estandarizado de enfermería en el módulo de atención de la plataforma de cuidados TEC­MED. MÉTODOS: El módulo de atención se desarrolló en tres fases (2020­2022): concepto de la plataforma, diseño y construcción funcional, y pruebas y evaluación. Las fases involucraron la colaboración entre académicos, desarrolladores de tecnología de la información y profesionales sociales/sanitarios. Se integraron taxonomías de enfermería (NANDA­I, NOC, NIC) para apoyar el proceso de enfermería. La plataforma se pilotó en seis países mediterráneos. RESULTADOS: La plataforma final presenta un módulo de evaluación con ocho dimensiones para la recopilación de datos sobre adultos mayores y sus cuidadores. Un Sistema de Apoyo a la Decisión Clínica (CDSS) vincula los datos de evaluación con diagnósticos, resultados e intervenciones de enfermería. La plataforma está disponible en seis idiomas (inglés, español, francés, italiano, griego, árabe). Las pruebas de usabilidad identificaron la necesidad de mejorar el soporte en idioma árabe. CONCLUSIONES: La plataforma TEC­MED es una herramienta pionera que utiliza un lenguaje estandarizado de enfermería para mejorar la atención a los adultos mayores en el Mediterráneo. La disponibilidad en varios idiomas de la plataforma promueve la accesibilidad a la misma. Las limitaciones incluyen el uso sin conexión y la funcionalidad de la aplicación móvil. Se están realizando pruebas piloto para evaluar la efectividad y facilitar la validación intercultural de las taxonomías de enfermería. IMPLICACIONES PARA LA PRÁCTICA DE ENFERMERÍA: La plataforma TEC­MED ofrece atención de enfermería estandarizada para los adultos mayores en todo el Mediterráneo, promoviendo la comunicación consistente y la práctica basada en evidencia. Este enfoque tiene el potencial de mejorar la calidad y accesibilidad de la atención para una población vulnerable.

Hyperparathyroidism in patients with low bone mineral density treated with zoledronic acid or denosumab. / Hiperparatiroidismo en pacientes con baja densidad mineral ósea tratados con ácido zoledrónico o denosumab.

OBJECTIVE: To analyze the prevalence of hyperparathyroidism in patients treated with zoledronic acid (ZA) or denosumab, its relationship with other parameters and how it affects on bone mineral density (BMD) evolution. METHODS: Retrospective observational study in patients with osteoporosis or osteopenia and high risk of fracture, who have received denosumab or ZA for at least two years. Patients diagnosed with hyperparathyroidism or glomerular filtration rate <30ml/min at baseline visit were excluded from the study. RESULTS: Ninety patients (ZA: 54.44%) were included. 18.36% of ZA-treated patients had elevated PTH levels at some time compared to 36.58% denosumab-treated patients (p>0.05). Patients with persistently elevated PTH were 6.13% in the AZ group and 19.51% in the denosumab group (p<0.04). We found a statistically significant inverse association between elevated PTH levels, glomerular filtration rate (p=0.007), and albumin-corrected calcium (p <0.001). We did not find an association between hyperparathyroidism and BMD evolution. CONCLUSIONS: A high incidence of hyperparathyroidism was observed in patients treated with AZ and especially denosumab. Hyperparathyroidism correlated inversely with glomerular filtration rate and albumin-corrected calcium. Elevated PTH does not appear to affect short-term bone mineral density evolution.

Impact of an SMS intervention to support type 2 diabetes self-management: DiabeText clinical trial.

BACKGROUND: Complications arising from uncontrolled Type 2 Diabetes Mellitus (T2DM) pose a significant burden on individuals' well-being and healthcare resources. Digital interventions may play a key role in mitigating such complications by supporting patients to adequately self-manage their condition. AIM: To assess the impact of DiabeText, a new theory-based, patient-centered, mobile health intervention integrated with electronic health records to send tailored short text messages to support T2DM self-management. DESIGN AND SETTING: Pragmatic, Phase III, 12-month, two-arm randomized clinical trial with T2DM primary care patients in Spain. METHOD: 742 participants with suboptimal glycemic control (HbA1c>7.5) were randomly allocated to a control (usual care) or intervention (DiabeText) group. The DiabeText group received, in addition to usual care, 165 messages focused on healthy lifestyle and medication adherence. PRIMARY OUTCOME: glycated hemoglobin (HbA1c). SECONDARY OUTCOMES: medication possession ratio, quality of life (EQ-5D-5L), diabetes self-efficacy (DSES); and self-reported adherence to medication, Mediterranean diet (MEDAS-14), and physical activity (IPAQ). RESULTS: Over the 12-month period, we observed no significant differences in HbA1c between the intervention and the control groups (Beta=-0.025 (-0.198 to 0.147; p=0.772)). In comparison with the control group, the DiabeText group showed significant (p<0.05) improvements in self-reported medication adherence (OR=1.4; 95%CI: 1.0 to 1.9), DSES (Cohen's d=0.35), and EQ5D-5L (Cohen's d=0.18) scores; but not in the rest of secondary outcomes. CONCLUSION: DiabeText successfully improved quality of life, diabetes self-management, and self-reported medication adherence in primary care patients with T2DM. Further research is needed to enhance its effects on physiological outcomes.

Priorities and challenges in social and healthcare policies for older people living in the Mediterranean basin: A Delphi panel study.

BACKGROUND: Recently, the countries in the Mediterranean basin (which share cultural ties) have been showing a common trend of declining social support for the elderly, with deficiencies in social care models for this demographic. Thus, this Delphi panel study analyzed the gaps in social and integrated care among the participating countries in a European research project. METHODS: This three-round Delphi panel study focused on the European countries of Greece and Spain and the non-European countries of Egypt, Lebanon, and Tunisia. In this project, experts were identified according to their level of expertise in the subject matter, their gender, and their membership in different social groups. Subsequently, they were asked to identify the current situation of social care, set future goals, and locate the gaps regarding the social and healthcare models for older people in the participating countries. The median score (Mdn) and interquartile range (IQR) were calculated to assess the degree of consensus on the different priorities. RESULTS: Among the participating countries, there was a lack of state agreements to maintain social care models, a lack of coordination between public and private institutions to provide social care services, territorial inequalities in terms of access and coverage of rights, and job insecurity for professionals. The desired situation was to integrate social and healthcare services with a person-centered social care model, thus promoting autonomy and empowering users and families in participation and decision-making. CONCLUSIONS: This Delphi study reveals significant disparities in social and healthcare policies for older adults across Mediterranean countries, highlighting shared challenges and specific national needs. European nations like Greece and Spain face fragmented systems, while non-European countries such as Lebanon, Egypt, and Tunisia lack specialized geriatric services and social security. All countries urgently need better professional training, social and economic empowerment of older adults, and integrated national strategies. These findings offer key insights for policymakers to develop equitable, sustainable solutions for aging populations.

TGF-ß1 overexpression in severe COVID-19 survivors and its implications for early-phase fibrotic abnormalities and long-term functional impairment.

Introduction: In post-COVID survivors, transforming growth factor-beta-1 (TGF-ß1) might mediate fibroblast activation, resulting in persistent fibrosis. Methods: In this study, 82 survivors of COVID-19-associated ARDS were examined at 6- and 24-months post-ICU discharge. At 6-months, quantitative CT analysis of lung attenuation was performed and active TGF-ß1 was measured in blood and exhaled breath condensate (EBC). Results: At 6-months of ICU-discharge, patients with reduced DmCO/alveolar volume ratio exhibited higher plasma and EBC levels of active TGF-ß1. Plasma TGF-ß1 levels were elevated in dyspneic survivors and directly related to the high-attenuation lung volume. In vitro, plasma and EBC from survivors induced profibrotic changes in human primary fibroblasts in a TGF-ß receptor-dependent manner. Finally, at 6-months, plasma and EBC active TGF-ß1 levels discriminated patients who, 24-months post-ICU-discharge, developed gas exchange impairment. Discussion: TGF-ß1 pathway plays a pivotal role in the early-phase fibrotic abnormalities in COVID-19-induced ARDS survivors, with significant implications for long-term functional impairment.

Harnessing sustainable nanoclusters for sensitive optical detection of tetracyclines and the underlying mechanism.

Simple and rapid sensing methods for the detection of antibiotics in drinks and foods are highly desirable due to the presence of these drugs in food products, as a consequence of extensive abuse of antibiotics in livestock production. In this study, we report a facile synthesis strategy of gold nanoclusters (AuNCs) passivated with N-acetyl-l-cysteine (AuNC@NAC). This nanocluster exhibits a fluorescence emission peak at 700 nm, which gradually decreases at increasing concentrations of antibiotics, such as tetracyclines. The limit of detection (LOD) was determined to be 0.8 ppm with a linear range of 0.1-140 µM (0.04-62 ppm). This method showcased exceptional selectivity in the detection of tetracyclines compared to anions, metallic cations and amino acids. The underlying mechanism has been elucidated, and the fluorescence quenching was found to be a combination of dynamic and static quenching mechanisms, with photoinduced electron transfer (PET) identified as the primary process for dynamic quenching.

Online peer assessment in Galenic Pharmacy: enhancing evaluative judgement in higher education.

Assessment influences how students define their priorities and their commitment to the learning process. Assessment strategies can empower students to actively engage in metacognitive processes, fostering cross-curricular competencies. Mastery of these competencies not only enhances deep and meaningful learning but also prepares learners for the challenges of the ever-evolving knowledge field. However, developing evaluative judgement, the ability to critically and autonomously judge the quality of one's own work and that of others, is essential but challenging. The purpose of this study was to design and assess an online educational experience for Galenic Pharmacy students (N = 339) during the 2021-2022 academic year of the Degree of Pharmacy. Beyond content acquisition, the primary goal was to foster evaluative judgement as a pivotal component of the 'learning to learn' competence. A complex task with iterative deliverables was proposed, using peer assessment as the central tool for the development of evaluative judgement. Students were required to give presentations on methods of administering medicines and had iterative deliverables. They underwent multiple rounds of peer feedback. The task as well as peer assessment process were compulsory for all the students. The participating students voluntarily answered an ad hoc online questionnaire in relation to their perception of the overall experience of peer assessment. The outcomes showcased the positive impacts of peer assessment based on the roles of assessor and assessed. An improvement in feedback quality was observed from one iteration to another, and an enhancement of critical judgement was evident. Enhancing assessment literacy might be essential for both educators and students. For educators, this would allow them to set criteria more aligned with competencies, whereas students might place higher value on these practices and actively engage with the learning process. Such engagement is crucial for promoting lifelong autonomous and self-regulated learning.

Retinal ganglion cell vulnerability to pathogenic tau in Alzheimer's disease.

Accumulation of pathological tau isoforms, especially hyperphosphorylated tau at serine 396 (pS396-tau) and tau oligomers, has been demonstrated in the retinas of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Previous studies have noted a decrease in retinal ganglion cells (RGCs) in AD patients, but the presence and impact of pathological tau isoforms in RGCs and RGC integrity, particularly in early AD stages, have not been explored. To investigate this, we examined retinal superior temporal cross-sections from 25 patients with MCI (due to AD) or AD dementia and 16 cognitively normal (CN) controls, matched for age and gender. We utilized the RGC marker ribonucleic acid binding protein with multiple splicing (RBPMS) and Nissl staining to assess neuronal density in the ganglion cell layer (GCL). Our study found that hypertrophic RGCs containing pS396-tau and T22-positive tau oligomers were more frequently observed in MCI and AD patients compared to CN subjects. Quantitative analyses indicated a decline in RGC integrity, with 46-55% and 55-56% reductions of RBPMS+ RGCs (P<0.01) and Nissl+ GCL neurons (P<0.01-0.001), respectively, in MCI and AD patients. This decrease in RGC count was accompanied by increases in necroptotic-like morphology and the cleaved caspase-3 apoptotic marker in RGCs of AD patients. Furthermore, there was a 2.1 to 3.1-fold increase (P<0.05-0.0001) in pS396-tau-laden RGCs in MCI and AD patients, with a greater abundance observed in individuals with higher Braak stages (V-VI), more severe clinical dementia ratings (CDR=3), and lower mini-mental state examination (MMSE) scores. Strong correlations were noted between the decline in RGCs and the total amount of retinal pS396-tau and pS396-tau+ RGCs, with pS396-tau+ RGC counts correlating significantly with brain neurofibrillary tangle scores (r= 0.71, P= 0.0001), Braak stage (r= 0.65, P= 0.0009), and MMSE scores (r= -0.76, P= 0.0004). These findings suggest that retinal tauopathy, characterized by pS396-tau and oligomeric tau in hypertrophic RGCs, is associated with and may contribute to RGC degeneration in AD. Future research should validate these findings in larger cohorts and explore noninvasive retinal imaging techniques that target tau pathology in RGCs to improve AD detection and monitor disease progression.

Comparative analysis of the efficacy and complications of mid-urethral slings when inserted either in isolation or in conjunction with pelvic organ prolapse surgery.

INTRODUCTION: Stress urinary incontinence (SUI) is a highly prevalent condition that affects between 20 and 50% of the female population. Pelvic organ prolapse (POP) can coexist with SUI and both can be addressed through a vaginal approach. However, it is unclear whether simultaneous surgery for these two conditions can influence the outcome of incontinence treatment. OBJECTIVE: To evaluate the objective and subjective effectiveness of the transobturator suburethral (TO) band by comparing two groups: group A, of patients undergoing surgery for stress urinary incontinence (SUI) by insertion of TO mesh, and group B, formed for patients requiring simultaneous correction of pelvic organ prolapse (POP) in addition to TO mesh insertion. MATERIALS AND METHODS: This is an observational, descriptive and retrospective study in which 91 patients participated: 33 (group A) underwent surgery for SUI and 58 (group B) underwent corrective surgery for pelvic organ prolapse (POP) and TO band simultaneously. Variables included: total urinary continence, objective urinary continence, subjective urinary continence (satisfaction levels and two validated questionnaires (PGI-1 and ICIQ-SF)) and complications. RESULTS: Regarding total continence, from the seventh to the ninth year, statistically significant differences were observed, with total continence being higher in group A. Objective continence decreased in both groups during the follow-up period. No significant differences were found between the two groups regarding subjective urinary continence (ICIQ-SF) and the degree of improvement after surgical treatment (PGI-1). The level of satisfaction after surgery was high in both groups. Regarding complications, there were no statistically significant differences. CONCLUSIONS: Isolated surgery for SUI could be considered more effective in achieving total and objective continence. However, the insertion of the TO band in both cases improves subjective urinary continence and quality of life with great safety and without differences regarding complications.

Web-based objective and structured assessment of point-of-care lung ultrasound skills in resource-limited settings.

BACKGROUND: Objective assessment of skills after training is essential for safe implementation of lung point-of-care ultrasound (POCUS). In low-and middle-income countries (LMIC) there is a need for assessment tools without onsite experts to scale up POCUS access. Our objective is to develop a web-based assessment tool and evaluate trainees across different countries and at different time points after initial lung POCUS training. METHODS: We adapted the objective and validated lung ultrasound score (LUS-OSAUS) to a web-based tool with quiz and practical skills test. Trainees were evaluated after a short (4-day) standardized lung POCUS training and were classified in distinct groups according to (i) their geographical location (Benin vs. South-Africa) and (ii) time elapsed since training (Benin 0 months vs. Benin 6 months). The Benin 6 months group had minimal continuous education. Skills test images were read by two blinded experts. We report the overall success rates and then compare these rates based on location and timing since training, using the Fischer's exact test. RESULTS: A total of 35 out of 43 participants completed the online LUS-OSAUS quiz and skills test. The overall success rate was 0.84 (95%CI 0.80-0.88), with lower success rates for "correct depth" 0.54 (0.37-0.71), "correct assessment of pleura" 0.63 (0.45-0.79) and "conclusion" 0.71 (0.54-0.85). There were no differences based on location, with respective rates of 0.86 (0.80-0.92) and 0.83 (0.75-0.91) (p-value = 0.125) for Benin and South Africa at 0 months, respectively. Similarly, there were no differences according to timing with success rates of 0.86 (0.80-0.92) and 0.82 (0.72-0.93) (p-value = 0.563) for Benin at 0 months and 6 months, respectively. CONCLUSION: Web-based objective and structured assessment of lung POCUS skills in LMIC following a short-standardized training is feasible and has a good overall success rate with consistent results across regions and up to 6 months after training given minimal continuous education. Overall, technical and POCUS-based clinical conclusion skills are the most difficult to acquire.

Age-Related Retinal Layer Thickness Changes Measured by OCT in APPNL-F/NL-F Mice: Implications for Alzheimer's Disease.

In Alzheimer's disease (AD), transgenic mouse models have established links between abnormalities in the retina and those in the brain. APPNL-F/NL-F is a murine, humanized AD model that replicates several pathological features observed in patients with AD. Research has focused on obtaining quantitative parameters from optical coherence tomography (OCT) in AD. The aim of this study was to analyze, in a transversal case-control study using manual retinal segmentation via SD-OCT, the changes occurring in the retinal layers of the APPNL/F-NF/L AD model in comparison to C57BL/6J mice (WT) at 6, 9, 12, 15, 17, and 20 months of age. The analysis focused on retinal thickness in RNFL-GCL, IPL, INL, OPL, and ONL based on the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Both APPNL-F/NL-F-model and WT animals exhibited thickness changes at the time points studied. While WT showed significant changes in INL, OPL, and ONL, the AD model showed changes in all retinal layers analyzed. The APPNL-F/NL-F displayed significant thickness variations in the analyzed layers except for the IPL compared to related WT. These thickness changes closely resembled those found in humans during preclinical stages, as well as during mild and moderate AD stages, making this AD model behave more similarly to the disease in humans.

Effect of physical activity in lymphocytes senescence burden in patients with COPD.

Chronic obstructive pulmonary disease (COPD) is regarded as an accelerated-age disease in which chronic inflammation, maladaptive immune responses, and senescence cell burden coexist. Accordingly, cellular senescence has emerged as a potential mechanism involved in COPD pathophysiology. In this study, 25 stable patients with COPD underwent a daily physical activity promotion program for 6 mo. We reported that increase of physical activity was related to a reduction of the senescent cell burden in circulating lymphocytes of patients with COPD. Senescent T-lymphocyte population, characterized by absence of surface expression of CD28, was reduced after physical activity intervention, and the reduction was associated to the increase of physical activity level. In addition, the mRNA expression of cyclin-dependent kinase inhibitors, a hallmark of cell senescence, was reduced and, in accordance, the proliferative capacity of lymphocytes was improved postintervention. Moreover, we observed an increase in functionality in T cells from patients after intervention, including improved markers of activation, enhanced cytotoxicity, and altered cytokine secretions in response to viral challenge. Lastly, physical activity intervention reduced the potential of lymphocytes' secretome to induce senescence in human primary fibroblasts. In conclusion, our study provides, for the first time, evidence of the potential of physical activity intervention in patients with COPD to reduce the senescent burden in circulating immune cells.NEW & NOTEWORTHY For the first time, we identified in patients with COPD a relation between physical activity intervention with respiratory function improvement and cellular senescence burden in lymphocytes that improved the T cell functionality and proliferative capacity of patients. In addition, our experiments highlight the possible impact of T-cell senescence in other cell types which could be related to some of the clinical lung complications observed in COPD.

Predictors of outcomes after internal fixation of periprosthetic femoral hip fractures Subgroup analysis of the peri-implant and peri-prosthetic fractures Spanish registry (PIPPAS).

PURPOSE: To identify risk factors predisposing patients to poor outcomes after fixation of periprosthetic hip fractures around femoral stems. METHODS: Prospective multicentre cohort study of fractures around a hip replacement stem managed by internal fixation. The primary outcome was one-year mortality, while secondary outcomes were local complications and healthcare burden-related outcomes (nursing facility utilization and hospital length of stay). RESULTS: One-year mortality was 16.2%. Age-adjusted Charlson Comorbidity Index score (OR=1.17; 95%CI=1.03-1.33)), Pfeiffer Short Portable Mental Status Questionnaire (SPMSQ) score (OR=1.16; 1.06-1.28), prosthetic dysfunction (OR=1.90; 1.00-3.61), and postoperative medical complications (OR=1.97; 1.06-3.68) were predictors of mortality. Patients with prior prosthetic dysfunction, lower Pfeiffer SPMSQ scores, Vancouver A fractures, and fractures fixed only using cerclages were at higher risk of local complications, which occurred in 9.3% of cases. Medical (OR=1.81; 1.05-3.13) and local complications (OR=5.56; 2.42-3.13) emerged as consistent risk factors for new institutionalization. Average hospitalization time was 13.9±9.2 days. Each day of fixation delay led to an average 1.4-day increase in total hospitalization. CONCLUSION: Frail periprosthetic hip-fracture patients with poorer functional status, dysfunctional replacements, and postoperative complications are at increased risk of mortality. Postoperative complications are more common in patients with dysfunctional arthroplasties, Vancouver A fractures, and fixation using cerclages alone. Postoperative complications were the most consistent predictor of higher healthcare resource utilization.

The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice.

Cholinergic striatal interneurons (ChIs) express the vesicular glutamate transporter 3 (VGLUT3) which allows them to regulate the striatal network with glutamate and acetylcholine (ACh). In addition, VGLUT3-dependent glutamate increases ACh vesicular stores through vesicular synergy. A missense polymorphism, VGLUT3-p.T8I, was identified in patients with substance use disorders (SUDs) and eating disorders (EDs). A mouse line was generated to understand the neurochemical and behavioral impact of the p.T8I variant. In VGLUT3T8I/T8I male mice, glutamate signaling was unchanged but vesicular synergy and ACh release were blunted. Mutant male mice exhibited a reduced DA release in the dorsomedial striatum but not in the dorsolateral striatum, facilitating habit formation and exacerbating maladaptive use of drug or food. Increasing ACh tone with donepezil reversed the self-starvation phenotype observed in VGLUT3T8I/T8I male mice. Our study suggests that unbalanced dopaminergic transmission in the dorsal striatum could be a common mechanism between SUDs and EDs.

Retinal Vascular and Structural Changes in the Murine Alzheimer's APPNL-F/NL-F Model from 6 to 20 Months.

Alzheimer's disease (AD) may manifest retinal changes preceding brain pathology. A transversal case-control study utilized spectral-domain OCT angiography (SD-OCTA) and Angio-Tool software 0.6a to assess retinal vascular structures and OCT for inner and outer retina thickness in the APPNL-F/NL-F AD model at 6, 9, 12, 15, 17, and 20 months old. Comparisons to age-matched wild type (WT) were performed. The analysis focused on the three vascular plexuses using AngiooTool and on retinal thickness, which was represented with the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Compared to WT, the APPNL-F/NL-F group exhibited both vascular and structural changes as early as 6 months persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, principally in the superficial vascular complex (SVC), were observed. There was a significant decrease in the vessel area and the total vessel length in SVC, intermediate, and deep capillary plexus. The inner retina in the APPNL-F/NL-F group predominantly decreased in thickness while the outer retina showed increased thickness in most analyzed time points compared to the control group. There are early vascular and structural retinal changes that precede the cognitive changes, which appear at later stages. Therefore, the natural history of the APPNL-F/NL-F model may be more similar to human AD than other transgenic models.

A mild increase in nutrient signaling to mTORC1 in mice leads to parenchymal damage, myeloid inflammation and shortened lifespan.

The mechanistic target of rapamycin complex 1 controls cellular anabolism in response to growth factor signaling and to nutrient sufficiency signaled through the Rag GTPases. Inhibition of mTOR reproducibly extends longevity across eukaryotes. Here we report that mice that endogenously express active mutant variants of RagC exhibit multiple features of parenchymal damage that include senescence, expression of inflammatory molecules, increased myeloid inflammation with extensive features of inflammaging and a ~30% reduction in lifespan. Through bone marrow transplantation experiments, we show that myeloid cells are abnormally activated by signals emanating from dysfunctional RagC-mutant parenchyma, causing neutrophil extravasation that inflicts additional inflammatory damage. Therapeutic suppression of myeloid inflammation in aged RagC-mutant mice attenuates parenchymal damage and extends survival. Together, our findings link mildly increased nutrient signaling to limited lifespan in mammals, and support a two-component process of parenchymal damage and myeloid inflammation that together precipitate a time-dependent organ deterioration that limits longevity.

Medium-Term Disability and Long-Term Functional Impairment Persistence in Survivors of Severe COVID-19 ARDS: Clinical and Physiological Insights.

BACKGROUND: Although the medium- and long-term sequelae of survivor of acute respiratory distress syndrome (ARDS) of any cause have been documented, little is known about the way in which COVID-19-induced ARDS affects functional disability and exercise components. Our aims were to examine the medium-term disability in severe COVID-19-associated ARDS survivors, delineate pathophysiological changes contributing to their exercise intolerance, and explore its utility in predicting long-term functional impairment persistence. METHODS: We studied 108 consecutive subjects with severe COVID-19 ARDS who remained alive 6 months after intensive care unit (ICU) discharge. Lung morphology was assessed with chest non-contrast CT scans and CT angiography. Functional evaluation included spirometry, plethysmography, muscle strength, and diffusion capacity, with assessment of gas exchange components through diffusing capacity of nitric oxide. Disability was assessed through an incremental exercise test, and measurements were repeated 12 and 24 months later in patients with functional impairments. RESULTS: At 6 months after ICU discharge, a notable dissociation between morphological and clinical-functional sequelae was identified. Moderate-severe disability was present in 47% of patients and these subjects had greater limitation of ventilatory mechanics and gas exchange, as well as greater symptomatic perception during exercise and a probable associated cardiac limitation. Female sex, hypothyroidism, reduced membrane diffusion component, lower functional residual capacity, and high-attenuation lung volume were independently associated with the presence of moderate-severe functional disability, which in turn was related to higher frequency and greater intensity of dyspnea and worse quality of life. Out of the 71 patients with reduced lung volumes or diffusion capacity at 6 months post-ICU discharge, only 19 maintained a restrictive disorder associated with gas exchange impairment at 24 months post-discharge. In these patients, 6-month values for diffusion membrane component, maximal oxygen uptake, ventilatory equivalent for CO2, and dead space to tidal volume ratio were identified as independent risk factors for persistence of long-term functional sequelae. CONCLUSIONS: Less than half of survivors of COVID-19 ARDS have moderate-severe disability in the medium term, identifying several risk factors. In turn, diffusion membrane component and exercise tolerance at 6-month ICU discharge are independently associated with the persistence of long-term functional sequelae.

Gut microbiota signatures of vulnerability to food addiction in mice and humans.

OBJECTIVE: Food addiction is a multifactorial disorder characterised by a loss of control over food intake that may promote obesity and alter gut microbiota composition. We have investigated the potential involvement of the gut microbiota in the mechanisms underlying food addiction. DESIGN: We used the Yale Food Addiction Scale (YFAS) 2.0 criteria to classify extreme food addiction in mouse and human subpopulations to identify gut microbiota signatures associated with vulnerability to this disorder. RESULTS: Both animal and human cohorts showed important similarities in the gut microbiota signatures linked to food addiction. The signatures suggested possible non-beneficial effects of bacteria belonging to the Proteobacteria phylum and potential protective effects of Actinobacteria against the development of food addiction in both cohorts of humans and mice. A decreased relative abundance of the species Blautia wexlerae was observed in addicted humans and of Blautia genus in addicted mice. Administration of the non-digestible carbohydrates, lactulose and rhamnose, known to favour Blautia growth, led to increased relative abundance of Blautia in mice faeces in parallel with dramatic improvements in food addiction. A similar improvement was revealed after oral administration of Blautia wexlerae as a beneficial microbe. CONCLUSION: By understanding the crosstalk between this behavioural alteration and gut microbiota, these findings constitute a step forward to future treatments for food addiction and related eating disorders.