Resilience, achievement motivation and level of satisfaction with degree programs in university students of Mechanical Physics

En este trabajo se analiza el grado de resiliencia, de motivación de logro y de satisfacción con la carrera elegida que presentaron los estudiantes de la asignatura Física I de las carreras de Bioquímica y Farmacia de la Facultad de Ciencias Exactas, Químicas y Naturales de la Universidad Nacional de Misiones. Para la recolección de datos se utilizaron encuestas anónimas a través de la plataforma Google, que luego fueron analizados estadísticamente. Los resultados obtenidos dan cuenta que los estudiantes se perciben altamente resilientes y poseen un alto grado de satisfacción con la carrera que eligieron. El análisis de la variable motivación de logros demostró que existe una gran brecha entre sus expectativas respecto a las calificaciones y los resultados de las instancias evaluativas.This paper analyzes the degree of resilience, achievement motivation and satisfaction with the career they have chosen, presented by Biochemistry and Pharmacy students of the Facultad de Ciencias Exactas, Químicas y Naturales (Universidad Nacional de Misiones) studying Physics l. For data collection, anonymous surveys were used through the Google platform, which were then statistically analyzed. The results obtained show that students perceive themselves as highly resilient and have a high degree of satisfaction with the career they chose. The analysis of the achievement motivation variable showed that there is a large gap between their expectations regarding grades and the results of the evaluation instances.Fil: Sosa, María Angélica. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Benítez, Víctor Daniel. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales; ArgentinaFil: Espinosa, Teresa Genara. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales; ArgentinaFil: Rodríguez, María Daniela. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Sureda, Silvia Cristina. Universidad Nacional de Misiones. Facultad de Cs.económicas; ArgentinaFil: Sosa, Nora Mabel. Universidad Nacional de Misiones. Facultad de Cs.económicas; Argentin

Premature placental aging in term small-for-gestational-age and fetal-growth-restricted fetuses

Objective The aim of this study was to perform a comprehensive assessment of the placental aging process through senescence and apoptotic markers in late-onset small fetuses classified as SGA or FGR. Study Design A prospective nested case-control study in singleton pregnancies delivering at term including 21 normally grown fetuses and 36 small fetuses classified into SGA (if birthweight was between the 3rd and 9th centile and normal fetoplacental Doppler; n=18) and FGR (if birthweight <3rd centile and/or abnormal cerebroplacental ratio or uterine artery Doppler; n=18). Telomerase activity, telomere length and RNA expression of senescence (Sirtuin 1,3,6) and apoptotic markers (p53, p21, BAX, Caspase 3 and 9) were analyzed in placental samples collected at birth. Results Compared with normally grown fetuses, both SGA and FGR presented signs of accelerated placental aging including lower telomerase activity (controls mean±SD 12.8% ± 6.6 vs SGA 7.98% ± 4.2 vs FGR 7.79% ± 4.6, p=0.008), shorter telomeres (controls 1.20 T/S ± 0.6 vs SGA 1.08 T/S ± 0.9 vs FGR 0.66 T/S ± 0.5, p=0.017), and reduced Sirtuin1 RNA expression (controls 1.55 2-' ' Ct ± 0.8 vs SGA 0.91 2-' ' Ct ± 0.8vs FGR 0.63 2-' ' Ct ± 0.5, p<0.001) together with increased p53 RNA expression (controls median(IQR) 1.072-' ' Ct (3.2) vs SGA 5.39 2-' ' Ct (15) vs FGR 3.75 2-' ' Ct (7.8), p=0.040), with a significant linear tendency across severity stages. In addition, FGR cases presented signs of apoptosis with increased RNA levels of Caspase 3 (controls 0.94 2-' ' Ct (1.1) vs FGR 3.98 2-' ' Ct (30), p=0.031) and Caspase 9 (controls 1.21 2-' ' Ct (4.0) vs FGR 3.87 2-' ' Ct (8.7), p=0.037) as compared to controls

Evaluation of aminoglycoside and non-aminoglycoside compounds for stop-codon readthrough therapy in four lysosomal storage diseases

Nonsense mutations are quite prevalent in inherited diseases. Readthrough drugs could provide a therapeutic option for any disease caused by this type of mutation. Geneticin (G418) and gentamicin were among the first to be described. Novel compounds have been generated, but only a few have shown improved results. PTC124 is the only compound to have reached clinical trials. Here we first investigated the readthrough effects of gentamicin on fibroblasts from one patient with Sanfilippo B, one with Sanfilippo C, and one with Maro- teaux-Lamy. We found that ARSB activity (Maroteaux-Lamy case) resulted in an increase of 2 - 3 folds and that the amount of this enzyme within the lysosomes was also increased, after treatment. Since the other two cases (Sanfilippo B and Sanfilippo C) did not respond to gentamicin, the treatments were extended with the use of geneticin and five non-aminogly- coside (PTC124, RTC13, RTC14, BZ6 and BZ16) readthrough compounds (RTCs). No recovery was observed at the enzyme activity level. However, mRNA recovery was observed in both cases, nearly a two-fold increase for Sanfilippo B fibroblasts with G418 and around 1.5 fold increase for Sanfilippo C cells with RTC14 and PTC124. Afterwards, some of the products were assessed through in vitro analyses for seven mutations in genes responsible for those diseases and, also, for Niemann-Pick A/B. Using the coupled tran- scription/translation system (TNT), the best results were obtained for SMPD1 mutations with G418, reaching a 35% recovery at 0.25 μ g/ml, for the p.W168X mutation. The use of COS cells transfected with mutant cDNAs gave positive results for most of the mutations with some of the drugs, although to a different extent. The higher enzyme activity recovery, of around two-fold increase, was found for gentamicin on the ARSB p.W146X mutation. Our results are promising and consistent with those of other groups. Further studies of novelcompounds are necessary to find those with more consistent efficacy and fewer toxic effect

Intracellular Oxidant Activity, Antioxidant Enzyme Defense System, and Cell Senescence in Fibroblasts with Trisomy 21

Down’s syndrome (DS) is characterized by a complex phenotype associated with chronic oxidative stress and mitochondrial dysfunction. Overexpression of genes on chromosome-21 is thought to underlie the pathogenesis of the major phenotypic features of DS, such as premature aging. Using cultured fibroblasts with trisomy 21 (T21F), this study aimed to ascertain whether an imbalance exists in activities, mRNA, and protein expression of the antioxidant enzymes SOD1, SOD2, glutathione-peroxidase, and catalase during the cell replication process in vitro. T21F had high SOD1 expression and activity which led to an interenzymatic imbalance in the antioxidant defense system, accentuated with replicative senescence. Intracellular ROS production and oxidized protein levels were significantly higher in T21F compared with control cells; furthermore, a significant decline in intracellular ATP content was detected in T21F. Cell senescence was found to appear prematurely in DS cells as shown by SA-β-Gal assay and p21 assessment, though not apoptosis, as neither p53 nor the proapoptotic proteins cytochrome c and caspase 9 were altered in T21F. These novel findings would point to a deleterious role of oxidatively modified molecules in early cell senescence of T21F, thereby linking replicative and stress-induced senescence in cultured cells to premature aging in DS

Premature placental aging in term small-for-gestational-age and fetal-growth-restricted fetuses

Objective The aim of this study was to perform a comprehensive assessment of the placental aging process through senescence and apoptotic markers in late-onset small fetuses classified as SGA or FGR. Study Design A prospective nested case-control study in singleton pregnancies delivering at term including 21 normally grown fetuses and 36 small fetuses classified into SGA (if birthweight was between the 3rd and 9th centile and normal fetoplacental Doppler; n=18) and FGR (if birthweight <3rd centile and/or abnormal cerebroplacental ratio or uterine artery Doppler; n=18). Telomerase activity, telomere length and RNA expression of senescence (Sirtuin 1,3,6) and apoptotic markers (p53, p21, BAX, Caspase 3 and 9) were analyzed in placental samples collected at birth. Results Compared with normally grown fetuses, both SGA and FGR presented signs of accelerated placental aging including lower telomerase activity (controls mean±SD 12.8% ± 6.6 vs SGA 7.98% ± 4.2 vs FGR 7.79% ± 4.6, p=0.008), shorter telomeres (controls 1.20 T/S ± 0.6 vs SGA 1.08 T/S ± 0.9 vs FGR 0.66 T/S ± 0.5, p=0.017), and reduced Sirtuin1 RNA expression (controls 1.55 2-' ' Ct ± 0.8 vs SGA 0.91 2-' ' Ct ± 0.8vs FGR 0.63 2-' ' Ct ± 0.5, p<0.001) together with increased p53 RNA expression (controls median(IQR) 1.072-' ' Ct (3.2) vs SGA 5.39 2-' ' Ct (15) vs FGR 3.75 2-' ' Ct (7.8), p=0.040), with a significant linear tendency across severity stages. In addition, FGR cases presented signs of apoptosis with increased RNA levels of Caspase 3 (controls 0.94 2-' ' Ct (1.1) vs FGR 3.98 2-' ' Ct (30), p=0.031) and Caspase 9 (controls 1.21 2-' ' Ct (4.0) vs FGR 3.87 2-' ' Ct (8.7), p=0.037) as compared to controls

Evaluation of aminoglycoside and non-aminoglycoside compounds for stop-codon readthrough therapy in four lysosomal storage diseases

Nonsense mutations are quite prevalent in inherited diseases. Readthrough drugs could provide a therapeutic option for any disease caused by this type of mutation. Geneticin (G418) and gentamicin were among the first to be described. Novel compounds have been generated, but only a few have shown improved results. PTC124 is the only compound to have reached clinical trials. Here we first investigated the readthrough effects of gentamicin on fibroblasts from one patient with Sanfilippo B, one with Sanfilippo C, and one with Maro- teaux-Lamy. We found that ARSB activity (Maroteaux-Lamy case) resulted in an increase of 2 - 3 folds and that the amount of this enzyme within the lysosomes was also increased, after treatment. Since the other two cases (Sanfilippo B and Sanfilippo C) did not respond to gentamicin, the treatments were extended with the use of geneticin and five non-aminogly- coside (PTC124, RTC13, RTC14, BZ6 and BZ16) readthrough compounds (RTCs). No recovery was observed at the enzyme activity level. However, mRNA recovery was observed in both cases, nearly a two-fold increase for Sanfilippo B fibroblasts with G418 and around 1.5 fold increase for Sanfilippo C cells with RTC14 and PTC124. Afterwards, some of the products were assessed through in vitro analyses for seven mutations in genes responsible for those diseases and, also, for Niemann-Pick A/B. Using the coupled tran- scription/translation system (TNT), the best results were obtained for SMPD1 mutations with G418, reaching a 35% recovery at 0.25 μ g/ml, for the p.W168X mutation. The use of COS cells transfected with mutant cDNAs gave positive results for most of the mutations with some of the drugs, although to a different extent. The higher enzyme activity recovery, of around two-fold increase, was found for gentamicin on the ARSB p.W146X mutation. Our results are promising and consistent with those of other groups. Further studies of novelcompounds are necessary to find those with more consistent efficacy and fewer toxic effect

Cord Blood Cardiovascular Biomarkers in Left-Sided Congenital Heart Disease

Fetal echocardiography has limited prognostic ability in the evaluation of left-sided congenital heart defects (left heart defects). Cord blood cardiovascular biomarkers could improve the prognostic evaluation of left heart defects. A multicenter prospective cohort (2013–2019) including fetuses with left heart defects (aortic coarctation, aortic stenosis, hypoplastic left heart, and multilevel obstruction (complex left heart defects) subdivided according to their outcome (favorable vs. poor), and control fetuses were evaluated in the third trimester of pregnancy at three referral centers in Spain. Poor outcome was defined as univentricular palliation, heart transplant, or death. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factor β, placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. A total of 45 fetuses with left heart defects (29 favorable and 16 poor outcomes) and 35 normal fetuses were included, with a median follow-up of 3.1 years (interquartile range 1.4–3.9). Left heart defects with favorable outcome showed markedly increased cord blood transforming growth factor β (normal heart median 15.5 ng/mL (6.8–21.4) vs. favorable outcome 51.7 ng/mL (13.8–73.9) vs. poor outcome 25.1 ng/mL (6.9–39.0), p = 0.001) and decreased placental growth factor concentrations (normal heart 17.9 pg/mL (13.8–23.9) vs. favorable outcome 12.8 pg/mL (11.7–13.6) vs. poor outcome 11.0 pg/mL (8.8–15.4), p p = 0.001) and drastically reduced soluble fms-like tyrosine kinase-1 concentrations (normal heart 1929.7 pg/mL (1364.3–2715.8) vs. favorable outcome (1848.3 pg/mL (646.9–2313.6) vs. poor outcome 259.0 pg/mL (182.0–606.0), p < 0.001). Results showed that fetuses with left heart defects present a distinct cord blood biomarker profile according to their outcome

Defective thermoregulation, impaired lipid metabolism, but preserved adrenergic induction of gene expression in brown fat of mice lacking C/EBPβ

C/EBPβ (CCAAT/enhancer-binding protein β) is a transcriptional regulator of the UCP1 (uncoupling protein-1) gene, the specific marker gene of brown adipocytes that is responsible for their thermogenic capacity. To investigate the role of C/EBPβ in brown fat, we studied the C/EBPβ-null mice. When placed in the cold, C/EBPβ(−/−) mice did not maintain body temperature. This cold-sensitive phenotype occurred, although UCP1 and PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) gene expression was unaltered in brown fat of C/EBPβ(−/−) mice. The UCP1 gene promoter was repressed by the truncated inhibitory C/EBPβ isoform LIP (liver-enriched transcriptional inhibitory protein, the truncated inhibitory C/EBPβ isoform). Since C/EBPβ-null mice lack both C/EBPβ isoforms, active LAP (liver-enriched transcriptional activatory protein, the active C/EBPβ isoform) and LIP, the absence of LIP may have a stronger effect than the absence of LAP upon UCP1 gene expression. Gene expression for UCP2 and UCP3 was not impaired in all tissues analysed. In primary brown adipocytes from C/EBPβ(−/−) mice, induction of gene expression by noradrenaline was preserved. In contrast, the expression of genes related to lipid storage was impaired, as was the amount of triacylglycerol mobilized after acute cold exposure in brown fat from C/EBPβ(−/−) mice. LPL (lipoprotein lipase) activity was also impaired in brown fat, but not in other tissues of C/EBPβ(−/−) mice. LPL protein levels were also diminished, but this effect was independent of changes in LPL mRNA, suggesting that C/EBPβ is involved in the post-transcriptional regulation of LPL gene expression in brown fat. In summary, defective thermoregulation owing to the lack of C/EBPβ is associated with the reduced capacity to supply fatty acids as fuels to sustain brown fat thermogenesis

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C : A prospective observational study

Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with ≥2 clinical signs/symptoms of NP-C were considered 'suspected NP-C' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI ≥70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 [4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores ≥70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis