Pseudomonas aeruginosa epidemic high-risk clones and their association with multidrug-resistant.

BACKGROUND: In Ecuador, data on molecular epidemiology, as well as circulating clones, are limited. Therefore, this study aims to know the population structure of Pseudomonas aeruginosa by identifying clones in clinical samples in Quito-Ecuador. METHODS: A significant set (45) clinical Pseudomonas aeruginosa isolates were selected, including multidrug and non-multidrug resistant isolates, which were assigned to sequence types (STs) and compared with their antibiotic susceptibility profile. The genetic diversity was assessed by applying the multilocus sequence typing (MLST) scheme and the genetic relationships between different STs were corroborated by phylogenetic networks. RESULTS: The MLST analysis identified 24 different STs and the most prevalent STs were ST-3750 and ST-253. The majority of the multidrug-resistance (MDR) isolates were included in ST-3750 and ST-253, also 3 singleton STs were identified as MDR isolates. The 21 different STs were found in non-multidrug resistance (non-MDR) isolates, and only 3 STs were found in more the one isolate. CONCLUSIONS: The population structure of clinical P. aeruginosa present in these isolates indicates a significant association between MDR isolates and the clonal types: all ST-3750 and ST-253 isolates were MDR. ST-3750 is a closely related strain to the clonal complex ST111 (CC111). ST-253 and ST111 are a group of successful high-risk clones widely distributed worldwide. The multiresistant isolates studied are grouped in the most prevalent sequence types found, and the susceptible isolates correspond mainly to singleton sequence types. Therefore, these high-risk clones and their association with multidrug-resistance phenotypes are contributing to the spread of MDR in Quito-Ecuador.

Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.

Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific mechanism-based treatment. We used Mendelian randomization to combine a unique cerebrospinal fluid (CSF) and plasma pQTL resource with the latest European-ancestry GWAS of MRI-markers of cSVD (white matter hyperintensities, perivascular spaces). We describe a new biological fingerprint of 49 protein-cSVD associations, predominantly in the CSF. We implemented a multipronged follow-up, across fluids, platforms, and ancestries (Europeans and East-Asian), including testing associations of direct plasma protein measurements with MRI-cSVD. We highlight 16 proteins robustly associated in both CSF and plasma, with 24/4 proteins identified in CSF/plasma only. cSVD-proteins were enriched in extracellular matrix and immune response pathways, and in genes enriched in microglia and specific microglial states (integration with single-nucleus RNA sequencing). Immune-related proteins were associated with MRI-cSVD already at age twenty. Half of cSVD-proteins were associated with stroke, dementia, or both, and seven cSVD-proteins are targets for known drugs (used for other indications in directions compatible with beneficial therapeutic effects. This first cSVD proteogenomic signature opens new avenues for biomarker and therapeutic developments.

Asymptomatic herpes simplex virus brain infection elicits cellular senescence phenotypes in the central nervous system of mice suffering multiple sclerosis-like disease.

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease affecting the central nervous system (CNS) in animals that parallels several clinical and molecular traits of multiple sclerosis in humans. Herpes simplex virus type 1 (HSV-1) infection mainly causes cold sores and eye diseases, yet eventually, it can also reach the CNS, leading to acute encephalitis. Notably, a significant proportion of healthy individuals are likely to have asymptomatic HSV-1 brain infection with chronic brain inflammation due to persistent latent infection in neurons. Because cellular senescence is suggested as a potential factor contributing to the development of various neurodegenerative disorders, including multiple sclerosis, and viral infections may induce a premature senescence state in the CNS, potentially increasing susceptibility to such disorders, here we examine the presence of senescence-related markers in the brains and spinal cords of mice with asymptomatic HSV-1 brain infection, EAE, and both conditions. Across all scenarios, we find a significant increases of senescence biomarkers in the CNS with some differences depending on the analyzed group. Notably, some senescence biomarkers are exclusively observed in mice with the combined conditions. These results indicate that asymptomatic HSV-1 brain infection and EAE associate with a significant expression of senescence biomarkers in the CNS.

Predicting functional movement capacity in adults: the effect of range of motion and isometric strength.

The aim of the study was to determine the role of isometric strength and range of motion in predicting Functional Movement Screen (FMS) scores of adults. A total of 120 participants (age = 34.62 ± 11.82 years; height = 170.56 ± 9.63 cm; weight = 73.62 ± 15.39 kg) volunteered to participate in the study. Anthropometric measurements were performed, including height, body weight, muscle mass, and body fat. Following this, the ranges of motion of the shoulder, hip, knee, and ankle joints were measured sequentially. Isometric strength and FMS tests were then performed. Hip extension isometric strength explained 23% of the variation in FMStotal. The common effect of knee flexion, shoulder flexion, and dorsiflexion joint range of motion explained 34% of the change in FMStotal (F (3-116) = 20.375, p < 0.001). A significant relationship (R = 0.658, R2 = 0.413) was found between hip extension isometric strength, knee flexion, shoulder flexion, and dorsiflexion range of motion and FMStotal (F (4-115) = 21.952, p < 0.001). The common effect of all these variables explains 43% of the change in FMStotal. The results indicate that the FMS test scores, which are utilized to evaluate the risk of injury in sedentary adults, can be significantly predicted by the effect of hip extension isometric strength and parameters related to knee flexion, shoulder flexion, and dorsiflexion joint range of motion. At this time, it is advised that range of motion and isometric strength be taken into account when determining a person's functional movement capacity.

Clinical and radiological differences between patients diagnosed with acute ischemic stroke and chameleons at the emergency room: insights from a single center observational study.

BACKGROUND: Scarce data exist about clinical/radiological differences between acute ischemic strokes diagnosed in the emergency room (AISER) and stroke chameleons (SC). We aimed at describing the differences observed in a comprehensive stroke center in Chile. METHODS: Prospective observational study of patients with ischemic stroke syndromes admitted to the ER of Clínica Alemana between December 2014 and October 2023. RESULTS: 1197 patients were included; of these 63 (5.2%, 95%CI 4.1-6.6) were SC; these were younger (p<0.001), less frequently hypertensive (p=0.03) and they also had lower systolic (SBP) (p<0.001), diastolic blood pressures (DBP) (p=0.011), and NIHSS (p<0.001). Clinically they presented less frequently gaze (p=0.008) and campimetry alterations (p=0.03), facial (p<0.001) and limb weakness (left arm (p=0.004), right arm (p=0,041), left leg (p=0.001), right leg P=0.0029), sensory abnormalities (p<0.001), and dysarthria (p<0.001). Neuro-radiological evaluations included less frequently large vessel occlusions (p=0.01), and stroke locations (p=0.005); they also differed in their etiologies (p<0.001). Brainstem strokes (p<0.001) and extinction/inattention symptoms (p<0.001) were only seen in AISER. In multivariate analysis, younger age (OR: 0.945; 95% CI 0.93 - 0.96), DBP (OR: 0.97; 95% CI, 0.95-0.99), facial weakness (OR: 0.39; CI 95% 0.19-0.78), sensory abnormities (OR: 0.16.18; 95% CI, 0.05-0.4), infratentorial location (OR: 0.36; 95% CI, 0.15-0.78), posterior circulation involvement (OR: 3.02; 95% CI, 1.45-6.3), cardioembolic (OR: 3.5; 95% CI, 1.56-7.99) and undetermined (OR: 2.42; 95% CI, 1.22-4.7; 95%) etiologies, remained statistically significant. A stepwise analysis including only clinical elements present on the patient's arrival to the ER, demonstrates that age (OR: 0.95; 95% CI 0.94 - 0.97), DBP (OR: 0.97; 95% CI, 0.95-0.99), the presence of atrial fibrillation (OR: 2.22; 95% CI, 1.04-4.75, NIHSS (OR: 0.88; 95% CI, 0.71-0.89) and the presence in NIHSS of 1.a Level of consciousness (OR: 5.66; CI 95% 1.8-16.9), 1.b Level of consciousness questions (OR: 3.023; 95% CI, 1.35-6.8), facial weakness (OR: 0.3; CI 95% 0.17-0.8) and sensitive abnormalities (OR: 0.27; 95% CI, 0.1-0.72) remained statistically significant. CONCLUSIONS: SC had clinical and radiological differences compared to AISER. An additional relevant finding is that any neurological symptom in a patient with atrial fibrillation, even in the presence of a negative DWI should be considered an episode of stroke until this is satisfactorily ruled out.

New insights into the pathogenesis of SARS-CoV-2 during and after the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects several physiological systems, including the gastrointestinal, renal, and central nervous (CNS) systems, significantly influencing the patient's overall quality of life. Additionally, numerous risk factors have been suggested, including gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, and inflammatory conditions. Despite advances in understanding the genome and pathophysiological ramifications of COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme 2 (ACE2). This receptor is expressed in various organs of different species, including humans, with different abundance. Although COVID-19 has multiorgan manifestations, the main pathologies occur in the lung, including pulmonary fibrosis, respiratory failure, pulmonary embolism, and secondary bacterial pneumonia. In the post-COVID-19 period, different sequelae may occur, which may have various causes, including the direct action of the virus, alteration of the immune response, and metabolic alterations during infection, among others. Recognizing the serious adverse health effects associated with COVID-19, it becomes imperative to comprehensively elucidate and discuss the existing evidence surrounding this viral infection, including those related to the pathophysiological effects of the disease and the subsequent consequences. This review aims to contribute to a comprehensive understanding of the impact of COVID-19 and its long-term effects on human health.

Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia.

Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10-12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10-12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10-8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.

Differences in knee flexor and extensor force and kinematic variables in rural versus urban area female students in Romania.

The study aimed to identify and explain the typical differences in low-intensity high-volume resistance training (LIHV-RT) performances for major muscle groups between rural versus urban young female students to establish the relevant set of quantitative and qualitative resistance training parameters. The study sample included 46 recreational active female students at the Transilvania University of Brașov, (mean ± SD age, 20 ± 1 year; body mass, 60 ± 3 kg; height, 160 ± 4 cm) grouped urban vs. rural. The study used modified resistance exercise machines for the hamstring- and quadricep-group muscles, equipped with a dynamometer and sensors for identifying developed forces and accelerations. A number of 368 tests were performed, representing two attempts for each subject, for knee flexion and knee extension exercises, with two different loads. For the performance analysis some variables were considered: the maximum number of repetition until failure, maximum force developed, maximum acceleration, the duration of the set and the mean time per repetition. The maximum number of repetition to failure shows a significant higher value for rural than urban in case of knee flexion (d = 0.98 [0.32, 1.54] for load 1(L1) and d = 0.65 [0.03, 1.21] for load 2(L2)) and in case of knee extension (d = 1.89 [1.11, 2.48] for L1 and d = 1.67 [0.92, 2.25] for L2). The total duration of the sets shows a significant higher value for rural than urban in case of knee flexion (d = 0.84 [0.19, 1.39] for L2) and in case of knee extension (d = 1.46 [0.74, 2.03] for L1 and d = 1.56 [0.98, 2.14] for L2). Additionally we found differences in the quality of the relevant repetitions execution and in the impulse developed during the LIHV- MNRF sets. The study's main finding was that there are differences in LIHV-RT performances knee flexion and knee extension antagonistic exercises, between rural and urban female students. We concluded that the obtained results allow teachers to understand the optimal design of RT programs for the different groups of participants, in order to adapt their teaching techniques so that their final objectives are achieved, insisting on particular aspects of the theoretical or practical contents.

Genetic associations with psychosis and affective disturbance in Alzheimer's disease.

INTRODUCTION: Individuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes. METHODS: Genome-wide association meta-analysis of 9988 AD participants from six source studies with participants characterized for AD+P AD+A, and a joint phenotype (AD+A+P). RESULTS: AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms. AD+A was positively correlated with anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereas AD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations. DISCUSSION: AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development. Highlights: It has long been known that psychotic and affective symptoms are often comorbid in individuals diagnosed with Alzheimer's disease. Here we examined for the first time the genetic architecture underlying this clinical observation, determining that psychotic and affective phenotypes in Alzheimer's disease are genetically correlated.Nevertheless, psychotic and affective phenotypes in Alzheimer's disease diverged in their genetic correlations with psychiatric phenotypes assessed in individuals without Alzheimer's disease. Psychosis in Alzheimer's disease was negatively genetically correlated with bipolar disorder and positively with depressive symptoms, whereas the affective phenotypes in Alzheimer's disease were positively correlated with anxiety disorder and more strongly correlated than psychosis with depressive symptoms.Psychosis in Alzheimer's disease, and the joint psychotic and affective phenotype, had significant estimated heritability, whereas the affective in AD did not.Examination of the loci most strongly associated with the psychotic, affective, or joint phenotypes revealed overlapping and unique associations.

Immune responses during COVID-19 breakthrough cases in vaccinated children and adolescents.

Background: Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus. Methods: Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay. Results: 2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects. Conclusion: SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease. Clinical Trial Registration: clinicaltrials.gov #NCT04992260.

Gestational hypothyroxinemia induces ASD-like phenotypes in behavior, proinflammatory markers, and glutamatergic protein expression in mouse offspring of both sexes.

Background: The prevalence of autism spectrum disorder (ASD) has significantly risen in the past three decades, prompting researchers to explore the potential contributions of environmental factors during pregnancy to ASD development. One such factor of interest is gestational hypothyroxinemia (HTX), a frequent condition in pregnancy associated with cognitive impairments in the offspring. While retrospective human studies have linked gestational HTX to autistic traits, the cellular and molecular mechanisms underlying the development of ASD-like phenotypes remain poorly understood. This study used a mouse model of gestational HTX to evaluate ASD-like phenotypes in the offspring. Methods: To induce gestational HTX, pregnant mice were treated with 2-mercapto-1-methylimidazole (MMI), a thyroid hormones synthesis inhibitor, in the tap-drinking water from embryonic days (E) 10 to E14. A separate group received MMI along with a daily subcutaneous injection of T4, while the control group received regular tap water during the entire pregnancy. Female and male offspring underwent assessments for repetitive, anxious, and social behaviors from postnatal day (P) 55 to P64. On P65, mice were euthanized for the evaluation of ASD-related inflammatory markers in blood, spleen, and specific brain regions. Additionally, the expression of glutamatergic proteins (NLGN3 and HOMER1) was analyzed in the prefrontal cortex and hippocampus. Results: The HTX-offspring exhibited anxious-like behavior, a subordinate state, and impaired social interactions. Subsequently, both female and male HTX-offspring displayed elevated proinflammatory cytokines in blood, including IL-1ß, IL-6, IL-17A, and TNF-α, while only males showed reduced levels of IL-10. The spleen of HTX-offspring of both sexes showed increased Th17/Treg ratio and M1-like macrophages. In the prefrontal cortex and hippocampus of male HTX-offspring, elevated levels of IL-17A and reduced IL-10 were observed, accompanied by increased expression of hippocampal NLGN3 and HOMER1. All these observations were compared to those observed in the Control-offspring. Notably, the supplementation with T4 during the MMI treatment prevents the development of the observed phenotypes. Correlation analysis revealed an association between maternal T4 levels and specific ASD-like outcomes. Discussion: This study validates human observations, demonstrating for the first time that gestational HTX induces ASD-like phenotypes in the offspring, highlighting the need of monitoring thyroid function during pregnancy.

Haemoglobinopathies and other rare anemias in Spain: ten years of a nationwide registry (REHem-AR).

REHem-AR was created in 2013. The progressive implementation of neonatal screening for haemoglobinopathies in Spanish autonomous communities where the registry had not been implemented, as well as the addition of new centres during this period, has considerably increased the sample of patients covered. In this study, we update our previous publication in this area, after a follow-up of more than 5 years. An observational, descriptive, multicentre and ambispective study of adult and paediatric patients with haemoglobinopathies and rare anaemias registered in REHem was performed. The data are from a cross-sectional analysis performed on 1 June, 2023. The study population comprised 1,756 patients, of whom 1,317 had SCD, 214 had thalassaemia and 224 were diagnosed with another condition. Slightly more than one third of SCD patients (37%) were diagnosed based on neonatal bloodspot screening, and the mean age at diagnosis was 2.5 years; 71% of thalassaemia patients were diagnosed based on the presence of anaemia. Vaso-occlusive crisis and acute chest syndrome continue to be the most frequent complications in SCD. HSCT was performed in 83 patients with SCD and in 50 patients with thalassaemia. Since the previous publication, REHem-AR has grown in size by more than 500 cases. SCD and TM are less frequent in Spain than in other European countries, although the data show that rare anaemias are frequent within rare diseases. REHem-AR constitutes an important structure for following the natural history of rare anaemias and enables us to calculate investment needs for current and future treatments.

HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study.

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.

Open clinical trial evaluating the efficacy of a novel eyelash growth enhancer with peptides and glycosaminoglycans.

BACKGROUND: Eyelashes play a crucial role in self-image and ocular protection. Enhancements to their structure are of both cosmetic and clinical interest. AIMS: To assess the efficacy of a peptide and glycosaminoglycan-based eyelash enhancer serum in improving eyelash structure. PATIENTS/METHODS: This open-label clinical trial involved 30 females aged 25-65. Eyelashes were assessed at baseline (D0), 4 weeks (D28), and 12 weeks (D84) using specialized software and high-resolution imagery. Measurements included lash number, width, length, volume, arc, and angle. RESULTS: At 12 weeks, significant increases were observed in lash length (+8.3%), number (+5%), width (+10.1%), volume (+14.1%), arc (+13.4%), and angle (+28.3%) compared to baseline. Global Eyelash Assessment (GEA) scores significantly improved, and patient treatment satisfaction increased from 73.34% at D28 to 84.33% at D84. No adverse effects were reported. CONCLUSIONS: The eyelash growth enhancer serum demonstrated significant efficacy in improving eyelash structure by Week 12, with early signs of improvement evident by Week 4. The high patient satisfaction levels underscore the perceived effectiveness of the product.

Cost-effectiveness of intraoperative radiation therapy versus intensity-modulated radiation therapy for the treatment of early breast cancer: a disinvestment analysis.

BACKGROUND: Adjuvant radiotherapy represents a key component in curative-intent treatment for early-stage breast cancer patients. In recent years, two accelerated partial breast irradiation (APBI) techniques are preferred for this population in our organization: electron-based Intraoperative radiation therapy (IORT) and Linac-based External Beam Radiotherapy, particularly Intensity-modulated radiation therapy (IMRT). Recently published long-term follow-up data evaluating these technologies have motivated a health technology reassessment of IORT compared to IMRT. METHODS: We developed a Markov model to simulate health-state transitions from a cohort of women with early-stage breast cancer, after lumpectomy and adjuvant APBI using either IORT or IMRT techniques. The cost-effectiveness from a private health provider perspective was assessed from a disinvestment point of view, using life-years (LYs) and recurrence-free life-years (RFLYs) as measure of benefits, along with their respective quality adjustments. Expected costs and benefits, and the incremental cost-effectiveness ratio (ICER) were reported. Finally, a sensitivity and scenario analyses were performed to evaluate the cost-effectiveness using lower IORT local recurrence and metastasis rates in IORT patients, and if equipment maintenance costs are removed. RESULTS: IORT technology was dominated by IMRT in all cases (i.e., fewer benefits with greater costs). Despite small differences were found regarding benefits, especially for LYs, costs were considerably higher for IORT. For sensitivity analyses with lower recurrence and metastasis rates for IORT, and scenario analyses without equipment maintenance costs, IORT was still dominated by IMRT. CONCLUSIONS: For this cohort of patients, IMRT was, at least, non-inferior to IORT in terms of expected benefits, with considerably lower costs. As a result, IORT disinvestment should be considered, favoring the use of IMRT in these patients.

[Lights and shadows in the implementation of community action for health]. / Luces y sombras en la implementación de la acción comunitaria para la salud.

OBJECTIVE: To explore the experiences of individuals who develop projects and interventions where community participation-action constitutes a strategic tool for reducing health inequalities. METHOD: Qualitative study based on semi-structured, in-depth online interviews with individuals considered experts in the development of health promotion strategies involving community participation. A total of 12 individuals from the healthcare, social healthcare, academic, and associative backgrounds were selected. The texts were analyzed following the thematic content analysis approach. RESULTS: The prominent strength of the processes involving the interviewed individuals is their participatory approach. However, there is no genuine commitment to promoting community participation from primary healthcare, and precarity has been identified as a significant weakness in the development of participatory health promotion projects. The sustainability of participatory processes relies on the transfer of knowledge to the community and their empowerment. CONCLUSIONS: Participatory processes have demonstrated their ability to reposition the community as an essential part of the healthcare system. It would be interesting to use a measurement tool for participation in all community health actions, both to guide their design and planning and to assess the depth of participation and its impact on the process. Enhancing community action expectations for health in the near future involves promoting a community-oriented approach in primary care and intersectoral collaboration, which requires a significant institutional and policy commitment.

Phospho-KNL-1 recognition by a TPR domain targets the BUB-1-BUB-3 complex to C. elegans kinetochores.

During mitosis, the Bub1-Bub3 complex concentrates at kinetochores, the microtubule-coupling interfaces on chromosomes, where it contributes to spindle checkpoint activation, kinetochore-spindle microtubule interactions, and protection of centromeric cohesion. Bub1 has a conserved N-terminal tetratricopeptide repeat (TPR) domain followed by a binding motif for its conserved interactor Bub3. The current model for Bub1-Bub3 localization to kinetochores is that Bub3, along with its bound motif from Bub1, recognizes phosphorylated "MELT" motifs in the kinetochore scaffold protein Knl1. Motivated by the greater phenotypic severity of BUB-1 versus BUB-3 loss in C. elegans, we show that the BUB-1 TPR domain directly recognizes a distinct class of phosphorylated motifs in KNL-1 and that this interaction is essential for BUB-1-BUB-3 localization and function. BUB-3 recognition of phospho-MELT motifs additively contributes to drive super-stoichiometric accumulation of BUB-1-BUB-3 on its KNL-1 scaffold during mitotic entry. Bub1's TPR domain interacts with Knl1 in other species, suggesting that collaboration of TPR-dependent and Bub3-dependent interfaces in Bub1-Bub3 localization and functions may be conserved.

Smartphone app-based interventions on physical activity behaviors and psychological correlates in healthy young adults: A systematic review.

BACKGROUND: The issue of low physical activity (PA) levels among the youth is a longstanding concern. Smartphone applications offer a promising avenue for delivering interventions that are both accessible and engaging. Up to now, there appears to be a gap in the literature, with no systematic reviews assessing the efficacy of smartphone apps in encouraging increased physical activity among healthy young adults. OBJECTIVE: To synthesize the effects of a smartphone app-based intervention on PA and PA-related psychological correlates in healthy young adults (18-35 years old). METHODS: A search was conducted on eighteen databases: PubMed, Medline, Web of Science, SPORTDiscus, Scopus, Academic Search Premier, Communication and Mass Media Complete, Article First, Biomed Central, BioOne, EBSCOHost, JSTOR, ProQuest, SAGE Reference Online, ScienceDirect, SpringerLink, Taylor&Francis, and Wiley Online. The search covered the period up until December 2023. This research included all randomized controlled trials (RCTs) that evaluated the effectiveness of smartphone app-based interventions on PA and PA related psychological outcomes in healthy young adults. The overall impact was determined by vote counting based on the direction of effect and aggregating p values. The quality of the evidence was evaluated using an 8-item scale. This study has been registered in the PROSPERO database with the identification number CRD42023390033. RESULTS: A total of 8403 articles were retrieved, and based on the predefined inclusion and exclusion criteria, seven articles were selected for inclusion. Among these articles, four high-quality RCTs were identified, and the results of vote counting and combining p values methods suggested that smartphone-based app interventions did not demonstrate significant effectiveness in improving PA and PA-related psychological outcomes. However, some improvements were observed. The analysis results, which were categorized into fitness apps and health apps based on the characteristics of the interventions, also failed to demonstrate significant intervention effects. CONCLUSION: The findings indicate that, currently, there are no significant effects of smartphone app interventions on improving PA and PA-related psychological outcomes in healthy young adults aged 18-35 years. It is important to note that these findings should be interpreted with caution due to the limited number of included studies. Future research should focus on employing high-quality study designs to determine the true effects of interventions and analyze various smartphone app interventions. These analyses should encompass different app characteristics (e.g., fitness app and health app), various combinations (e.g., fitness app alone and fitness app in combination with other interventions), diverse intervention goals (e.g., PA and PA along with other outcomes), and multiple intervention characteristics (e.g., frequency and duration).

Emotional and Social Outcomes of the Teaching Personal and Social Responsibility Model in Physical Education: A Systematic Review and Meta-Analysis.

CONTEXT: In today's ever-changing world, fostering personal and social responsibility is essential for building strong and compassionate communities. This study aimed to provide a quantitative synthesis focusing on the emotional and social outcomes of Teaching Personal and Social Responsibility (TPSR) model-based Physical Education (PE) programs. METHODS: A comprehensive literature review covering the period from November 2022 to September 2023 identified 637 articles published between 2005 and 2023. Of these, 20 met the inclusion criteria. Data from these articles were coded, and a comprehensive meta-analysis was conducted, incorporating 28 effect sizes. Methodological quality was assessed using the Medical Education Research Study Quality Instrument. Hedge's g served as the effect size measure and emotional and social outcomes subgroups were consolidated. Heterogeneity was evaluated with Cochran's Q and I2. Meta-regression and ANOVA-like models addressed categorical moderators, whereas publication bias was assessed through funnel plot, failsafe number, and Egger's linear regression. RESULTS: A significant and positive effect of the TPSR model on product outcomes (Hedge's g = 0.337, 95% CI = 0.199 to 0.476) was found. Despite considerable heterogeneity (I2 = 83.830), a random effects model was justified. Assessment of publication bias indicated a low likelihood. Moderator analyses revealed that publication countries significantly influenced the effect, with stronger effects in Turkey. Publication type (article vs. thesis) also played roles in moderation. The meta-regression analyses did not reveal significant effects for the grade level, duration of intervention, publication year or sample size on the TPSR model's impact on product outcomes. The TPSR model positively impacts emotional and social outcomes in PE, enhancing children' skills and behaviour. However, variations across cultures highlight the need for further research, considering limitations like language constraints and potential biases in study selection and data extraction.