To date, no instrument adapted and validated that measures engagement and disaffection in the physical education class has been found, which limits the generation of knowledge of this area in Mexico. ...The aims of this study were to translate and adapt the engagement and disaffection scale to the context of physical education in Mexico and to examine its reliability, structure (two and four factors), and factorial invariance by gender in Mexican fifth- and sixth-grade elementary school students. A total of 1470 students participated (50.6% boys) with ages between 10 and 14 years (mean (
) = 10.56; standard deviation (
) = 0.77) from federal (89.3%) and state (10.7%) elementary schools. Two factorial structures were tested (with four factors and two factors). The fit indexes of both models were satisfactory, and the factorial saturations were significant. The differences between the fit indexes of both models were irrelevant; therefore, the two-factor model was considered more suitable. The total strict invariance by gender was confirmed, and the reliabilities of the engagement and disaffection scale were acceptable. The Mexican version of the course engagement and disaffection scale in physical education is valid and useful to measure these constructs in the context of physical education in Mexico.
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Background: Patients with hormone receptor-positive early breast cancer (BC) can develop resistance to endocrine therapies (ET) and face a continuous risk of relapse, which can occur anywhere ...from a few months (m) to several decades after surgery. The causes of early vs late relapses are not well understood. Our research examines the presence of oncogenic drivers in circulating tumor DNA (ctDNA) at the time of relapse in patients with luminal BC who have either an early or late distant recurrence. Methods: We identified pts included in the GEICAM/2014-03 study (NCT02819882) with: 1) HR-positive BC, 2) metastatic relapse either <36m (early relapse, early-R) or >120m (late relapse, late-R) from diagnosis, and 3) ctDNA obtained before first line treatment for advanced disease. The AVENIO ctDNA assay was used for identifying genomic aberrations in 77 cancer-related genes. Results: Eighty-four pts, 36 in early-R and 48 in late-R groups, were selected. Median time to relapse was 24.97m in early-R vs 151.84m in late-R. Median time from last dose of adjuvant ET to relapse was 0.03m for early-R vs 74.06m for late-R. Median PFS to first line treatment was 7.62m in early-R and 35.15m in late-R. With a median follow-up of 32.08m, median OS after diagnosis of metastatic disease was 27.74m for early-R and not reached for late-R. ctDNA analysis detected at least 1 mutation (mut) in 71/84 (85%) pts (89% in early-R vs 81% in late-R). Early-R pts were enriched in mut in TP53 (44% vs 19%), ESR1 (11% vs 4%), MAPK_ERK pathway (14% vs 6%), and ERBB2 copy number alterations (CNA) (25% vs 2%). PI3K/AKT pathway alterations had similar frequency in both recurrence groups (38% vs 42%) and they were not associated with OS. Seven ESR1 mut were detected in 6 pts. In the early-R group there were 5 ESR1 mut (71% of total ESR1 mut), median mutant allele frequency (mMAF): 0.64%; while in the late-R, 2 ESR1 mut (29%), mMAF: 0.4%. ESR1 mut were associated with worse OS (median OS 48.48m vs 12.84m wild-type vs mutant; p=0.0025). There were 10 pts with E RBB2 CNA at metastatic relapse; 9 (25%) in the early-R and 1 pts (2%) in the late-R. Seven pts (70%) had HER2-positive. Pts with ctDNA ERBB2 CNA had worse OS (median OS 48.48m vs 20.52m wild-type vs mutant; p-adj=0.025). Conclusions: In luminal breast cancer (BC), early and late distant relapse differ at both the clinical and genomic levels. Early relapse is a highly aggressive form of the disease and is enriched in TP53 mutations and actionable genetic alterations, such as mutations in the ESR1 and CNA in ERBB2, as detected by ctDNA analysis at the time of metastatic relapse diagnosis. Clinical trial information: NCT02819882 . Table: see text
Background
Alzheimer’s disease (AD) is a common cause of dementia even in cases with very early onset, and implication of monogenic mutations in the PSEN1, PSEN2, and APP genes must be considered. ...Strong family history is the rule in autosomal dominant AD associated with mutations in these genes but, in rare cases, de novo mutations can occur.
Method
Case report of a sporadic AD case with onset in his twenties carrying the Pro436Gln mutation (exon 12, TM‐9 region) in PSEN1. Comparison with a previously reported familial case carrying the same mutation.
Result
A 32 years old male consulted for a 10 years‐long mild but slowly progressive learning difficulties, apathy and anxiety. There was no family history of neurologic diseases and both parents were cognitively preserved in their early 70s. The previous two years he had developed progressive visual disturbances including impaired reading, recognizing numbers, letters and faces and, more recently, he had experienced troubles with manual praxias. There were no specific complaints regarding episodic memory. Neuropsychological assessment showed severe visual agnosia and mild impairments in memory, speech, and executive functions. Neurologic examination showed brief distal myoclonus in upper limbs, markedly enhanced reflexes in lower limbs, as well as mild spasticiy. Blood tests, EEG, spinal MRI, and SSEP were normal. Brain MRI and FDG‐PET revealed severe parieto‐occipital atrophy/hypoperfusion (fig. 1‐4). AD CSF biomarkers showed decrease in Ab1‐42 and 1‐42/1‐40 ratio, increased pTau and normal total tau. Amyloid‐PET was positive, identifying a high burden of amyloid plaques in posterior cortex. The pathogenic PSEN1 mutation was found in the patient but was absent in his parents. It is remarkable that the phenotype of the previously reported case with this mutation was almost identical as regards onset in the late twenties and associated pyramidalism.
Conclusion
PSEN1 mutations should be considered in patients with sporadic very early onset dementia, as de novo mutations may occur. AD CSF biomarkers offer valuable diagnostic information in such cases. The specific mutation has a very strong impact in the clinical phenotype. Further, this case is another example that PSEN1 mutations affecting proline residues have the earliest age at onset.
El estrés laboral ha sido un factor determinante en la aparición de enfermedades en los docentes universitarios, lo cual ha generado absentismo, errores y accidentes en los ambientes de trabajo. El ...objetivo de esta investigación fue caracterizar el estrés laboral en personal docente universitario del área de la salud, con riesgo biológico. Se realizó una investigación descriptiva, transversal, de campo y prospectiva, con diseño no experimental, en 53 docentes de la Facultad de Ciencias de la Salud, de la Universidad Técnica de Manabí, Ecuador, desde junio de 2018 a junio de 2021, aplicándose el Instrumento de Estrés Laboral OIT-OMS y la estimación índice numérico de riesgo biológico para entornos académicos. Prevalecieron las mujeres (73,6%), mayores de cincuenta años (52,8%) con estrés nivel bajo. Todas las dimensiones del estrés en general mostraron niveles bajos (2,25 ± 1,05), no obstante, al discriminar según el cargo académico, los pocos casos de niveles altos fueron los Auxiliares Titulares, específicamente en las dimensiones: tecnología, clima organizacional y respaldo de grupo, el riesgo biológico ocurre en el 7,5% de los casos y 64,2% similar a la población en general. Se determinó que existen docentes con niveles de estrés que pudieran afectar su homeostasis psico-biológica, por lo cual se recomienda su intervención, independientemente de su escalafón académico o dedicación laboral
Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer (BC). Currently, however, most patients with BC are node negative at ...diagnosis. The only pure node-negative study (Spanish Breast Cancer Research Group 9805) reported so far showed a docetaxel benefit but significant toxicity. Here we tested the efficacy and safety of weekly paclitaxel (wP) in node-negative patients, which is yet to be established.
Patients with BC having T1-T3/N0 tumors and at least one high-risk factor for recurrence (according to St. Gallen 1998 criteria) were eligible. After primary surgery, 1,925 patients were randomly assigned to receive fluorouracil, doxorubicin, and cyclophosphamide (FAC) × 6 or FAC × 4 followed by wP × 8 (FAC-wP). The primary end point was disease-free survival (DFS) after a median follow-up of 5 years. Secondary end points included toxicity and overall survival.
After a median follow-up of 63.3 months, 93% and 90.3% of patients receiving FAC-wP or FAC regimens, respectively, remained disease free (hazard ratio HR, 0.73; 95% CI, 0.54 to 0.99; log-rank P = .04). Thirty-one patients receiving FAC-wP versus 40 patients receiving FAC died (one and seven from cardiovascular diseases, respectively; HR, 0.79; 95% CI, 0.49 to 1.26; log-rank P = .31). The most relevant grade 3 and 4 adverse events in the FAC-wP versus the FAC arm were febrile neutropenia (2.7% v 3.6%), fatigue (7.9% v 3.4%), and sensory neuropathy (5.5% v 0%).
For patients with high-risk node-negative BC, the adjuvant FAC-wP regimen was associated with a small but significant improvement in DFS compared with FAC therapy, in addition to manageable toxicity, especially regarding long-term cardiac effects.
The aggregation of α-synuclein (α-syn) is a major factor behind the onset of Parkinson's disease (PD). Sublocalization of this protein may be relevant for the formation of multimeric α-syn oligomeric ...configurations, insoluble aggregates that form Lewy bodies in PD brains. Processing of this protein aggregation is regulated by associations with distinct lipid classes. For instance, instability of lipid raft (LR) microdomains, membrane regions with a particular lipid composition, is an early event in the development of PD. However, the relevance of membrane microdomains in the regulation and trafficking of the distinct α-syn configurations associated with PD remains unexplored. In this study, using 6- and 14-month-old healthy and MPTP-treated animals as a model of PD, we have investigated the putative molecular alterations of raft membrane microstructures, and their impact on α-syn dynamics and conformation. A comparison of lipid analyses of LR microstructures and non-raft (NR) fractions showed alterations in gangliosides, cholesterol, polyunsaturated fatty acids (PUFA) and phospholipids in the midbrain and cortex of aged and MPTP-treated mice. In particular, the increase of PUFA and phosphatidylserine (PS) during aging correlated with α-syn multimeric formation in NR. In these aggregates, α-syn was phosphorylated in pSer129, the most abundant post-transductional modification of α-syn promoting toxic aggregation. Interestingly, similar variations in PUFA and PS content correlating with α-syn insoluble accumulation were also detected in membrane microstructures from the human cortex of incidental Parkinson Disease (iPD) and PD, as compared to healthy controls. Furthermore, structural changes in membrane lipid microenvironments may induce rearrangements in raft-interacting proteins involved in other neuropathologies. Therefore, we also investigated the dynamic of other protein markers involved in cognition and memory impairment such as metabotropic glutamate receptor 5 (mGluR5), ionotropic NMDA receptor (NMDAR2B), prion protein (PrPc) and amyloid precursor protein (APP), whose activity depends on membrane lipid organization. We observed a decline of these protein markers in LR fractions with the progression of aging and pathology. Overall, our findings demonstrate that lipid alterations in membranous compartments promoted by brain aging and PD-like injury may have an effect on α-syn aggregation and segregation in abnormal multimeric structures.
The authors sought to evaluate clinical outcomes of patients after an episode of acute heart failure (AHF) according to their adherence to the Mediterranean diet (MedDiet).
It has been proved that ...MedDiet is a useful tool in primary prevention of cardiovascular diseases. However, it is unknown whether adherence to MedDiet is associated with better outcomes in patients who have already experienced an episode of AHF.
We designed a prospective study that included consecutive patients diagnosed with AHF in 7 Spanish emergency departments (EDs). Patients were included if they or their relatives were able to answer a 14-point score of adherence to the MedDiet, which classified patients as adherents (≥9 points) or nonadherents (≤8 points). The primary endpoint was all-cause mortality at the end of follow-up, and secondary endpoints were 1-year ED revisit without hospitalization, rehospitalization, death, and a combined endpoint of all these variables for patients discharged after the index episode. Unadjusted and adjusted hazard ratios (HRs) were calculated.
We included 991 patients (mean age of 80 ± 10 years, 57.8% women); 523 (52.9%) of whom were adherent to the MedDiet. After a mean follow-up period of 2.1 ± 1.3 years, no differences were observed in survival between adherent and nonadherent patients (HR of adherents HR
= 0.86; 95% confidence interval CI: 0.73 to 1.02). The 1-year cumulative ED revisit for the whole cohort was 24.5% (HR
= 1.10; 95% CI: 0.84 to 1.42), hospitalization 43.7% (HR
= 0.74; 95% CI: 0.61 to 0.90), death 22.7% (HR
= 1.05; 95% CI: 0.8 to 1.38), and combined endpoint 66.8% (HR
= 0.89; 95% CI: 0.76 to 1.04). Adjustment by age, hypertension, peripheral arterial disease, previous episodes of AHF, treatment with statins, air-room pulsioxymetry, and need for ventilation support in the ED rendered similar results, with no statistically significant differences in mortality (HR
= 0.94; 95% CI: 0.80 to 1.13) and persistence of lower 1-year hospitalization for adherents (HR
= 0.76; 95% CI: 0.62 to 0.93).
Adherence to the MedDiet did not influence long-term mortality after an episode of AHF, but it was associated with decreased rates of rehospitalization during the next year.
Automated growth-based methods for sterility testing of cell-therapy products should be qualified to demonstrate that they are equivalent to, or better than, the conventional reference method. The ...aim of the present study was to assess the ability of the BACTEC FX40 system to detect low microbial contamination and to confirm the suitability of the method in the presence of seven different human mesenchymal cell–based products, according to Ph. Eur. 2.6.27. Additionally, a study to select the best vial to detect fungus contamination was performed.
Microorganisms representing Gram-negative, Gram-positive, aerobic, anaerobic, spore-forming, slow-growing bacteria, yeast and mold were prepared in either Dulbecco's PBS or seven biological matrices containing approximately 5, 10, and 15 colony-forming units (CFU) per sample. These preparations were inoculated to the specific media required for each test method: (i) BACTEC aerobic and anaerobic vials; (ii) aerobic and anaerobic media for direct inoculation; and (iii) Trypcase soy 3P or Brucella blood agar plates. Colonies from cultures were identified using MALDI-TOF mass spectrometry.
The BACTEC FX40 system, in both Dulbecco's PBS and the biological matrices with a 5-CFU inoculum, detected most of the microorganisms significantly faster than the conventional method, despite the presence of a matrix containing gentamicin and several matrices containing 10% DMSO. Conversely, it showed an extremely delayed detection of Candida albicans compared with the conventional method. The addition of a Mycosis IC/F (MYC) vial decreased radically the time to detection (TTD) of C. albicans (28.2 ± 1.8 h) compared with the conventional method (36 h).
When a MYC vial was added to the standard aerobic and anaerobic vials to test each sample, BACTEC FX40 was shown to be a superior alternative sterility method for cell-therapy products contaminated with low inocula, with a faster TTD for microbial growth compared with the conventional method (5 versus 14 days). The studies were carried out in different cell-based matrices with sensitivities and specificities of 100% for all the tested strains at 15-, 10- and 5-CFU inoculum, with the exception of Kocuria rhizophila at 5 CFU (90.48% sensitivity and 100% specificity).
Acinetobacter baumannii is one of the most important antibiotic-resistant nosocomial bacteria. We investigated changes in the clinical and molecular epidemiology of A. baumannii over a 10-year ...period. We compared the data from 2 prospective multicenter cohort studies in Spain, one performed in 2000 (183 patients) and one in 2010 (246 patients), which included consecutive patients infected or colonized by A. baumannii. Molecular typing was performed by repetitive extragenic palindromic polymerase chain reaction (REP-PCR), pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). The incidence density of A. baumannii colonization or infection increased significantly from 0.14 in 2000 to 0.52 in 2010 in medical services (p < 0.001). The number of non-nosocomial health care-associated cases increased from 1.2% to 14.2%, respectively (p < 0.001). Previous exposure to carbapenems increased in 2010 (16.9% in 2000 vs 27.3% in 2010, p = 0.03). The drugs most frequently used for definitive treatment of patients with infections were carbapenems in 2000 (45%) and colistin in 2010 (50.3%). There was molecular-typing evidence of an increase in the frequency of A. baumannii acquisition in non-intensive care unit wards in 2010 (7.6% in 2000 vs 19.2% in 2010, p = 0.01). By MSLT, the ST2 clonal group predominated and increased in 2010. This epidemic clonal group was more frequently resistant to imipenem and was associated with an increased risk of sepsis, although not with severe sepsis or mortality. Some significant changes were noted in the epidemiology of A. baumannii, which is increasingly affecting patients admitted to conventional wards and is also the cause of non-nosocomial health care-associated infections. Epidemic clones seem to combine antimicrobial resistance and the ability to spread, while maintaining their clinical virulence.
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