Elderly hypertensive patients: Silent white matter lesions, blood pressure variability, baroreflex impairment and cognitive deterioration

Introduction: Hypertension may increase the risk for stroke and is frequently associated with subcortical and periventricular white matter lesions (WML). This is considered a prognostic factor for the development of stroke and cognitive impairment, particularly in attention processes. Additionally, in elderly subjects, it is known the implications of alterations in the neural cardiovascular regulation and the cardiovascular risk. Aims: To evaluate, in asymptomatic elderly hypertensives, the association of ambulatory blood pressure values and autonomic activity with neurocognitive impairment and WML. In addition, we also evaluated the role of the autonomic nervous system particularly the vagal component, in the pathogenesis of white matter lesions. Methods: We studied 22 elderly essential hypertensive patients (69±1.1y) and as control group, 16 normotensive elderly subjects (age 67±3.2y) were also enrolled. To each one of them, a cerebral MRI was performed to classify them, by a neuro-radiologist blinded of the subject clinical status, using a 0 to 9 scale where 0 denoted no WML and 9 the most severe lesions. Twenty four hours arterial blood pressure monitoring was performed to each one of the subjects under study. Office blood pressure was measured 3 times and the mean value reported. Beat to beat finger arterial pressure monitoring (Finapres) was performed for a 2h period. During the first hour the patient remained lying supine in a quiet darkened room and during the second hour four manoeuvres: stand-up, cold pressor test, handgrip and quiet activity were randomly performed. Mean blood pressure and pulse interval values, from the two periods, and their respective variabilities, baroreflex sensitivity and power spectral analysis were calculated. Regarding neuropsychological assessment: Minimental test, attention evaluation, RAVLT, visual memory, language and executive function, geriatric depression scale, cognitive deficit rate tests were performed in all subject. Results: We found a closer correlation of WML with 24hs ABPM than with office BP readings being more evident with systolic blood pressure during the night time period. WML failed to show any correlation with SBP average values derived from the Finapres recordings in either the supine or the upright position, while it was positively and significantly related to PP in both conditions. However, beat to beat SBP variability, either in the supine or in the upright position, showed a positive and significant correlation with WML. During the resting period, BRS calculated through the sequence method (Time Domain) was similar in HT and NT subjects. However when BRS was assessed in the frequency domain a significant reduction was observed in HT compared with NT. In addition, At the time of laboratory manoeuvres implying sympathetic activation, BRS was significantly reduced as compared to the resting values being particularly evident for the HF values. In hypertensive subjects, only semantic fluency showed a significant difference (p=0.01), when compared to normotensives. When the patients were divided in older and younger than 75 years, a significant difference was observed in the delayed analysis of words, and in the phonological fluency showing a significant higher rate of pathological results in the group of patients older than 75 years. Conclusions: As previously shown, incidental WML, suggestive of silent cerebrovascular disease, is a frequent finding in elderly hypertensives. Night-time BP mean values and SBP variability in upright position seems to be the best predictor on silent cerebral WML. The vagal component of the autonomic nervous system seems to be involved in the pathogenesis of these lesions. Finally, the neurocognitive alterations are multifactorial in origin where the aging process seems to be the principal component.Fil: Ramírez, Agustín José. Fundación Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Parati, Gianfranco. San Gerardo Hospital; Italia. University of Milan-Bicocca; ItaliaFil: Castiglioni, Paolo. Fondazione Don Gnocchi; ItaliaFil: Consalvo, Damian. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Solis, Patricia Cristina Lourdes. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Risk, Marcelo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Waissman, Paola. Fundación Favaloro; ArgentinaFil: di Rienzo, Marco. Fondazione Don Gnocchi; ItaliaFil: Mancia, Giusepe. San Gerardo Hospital; Italia. University of Milan-Bicocca; ItaliaFil: Sanchez, Ramiro A.. Fundación Favaloro; Argentin

Targeting of Slc25a21 is associated with orofacial defects and otitis media due to disrupted expression of a neighbouring gene.

Homozygosity for Slc25a21(tm1a(KOMP)Wtsi) results in mice exhibiting orofacial abnormalities, alterations in carpal and rugae structures, hearing impairment and inflammation in the middle ear. In humans it has been hypothesised that the 2-oxoadipate mitochondrial carrier coded by SLC25A21 may be involved in the disease 2-oxoadipate acidaemia. Unexpectedly, no 2-oxoadipate acidaemia-like symptoms were observed in animals homozygous for Slc25a21(tm1a(KOMP)Wtsi) despite confirmation that this allele reduces Slc25a21 expression by 71.3%. To study the complete knockout, an allelic series was generated using the loxP and FRT sites typical of a Knockout Mouse Project allele. After removal of the critical exon and neomycin selection cassette, Slc25a21 knockout mice homozygous for the Slc25a21(tm1b(KOMP)Wtsi) and Slc25a21(tm1d(KOMP)Wtsi) alleles were phenotypically indistinguishable from wild-type. This led us to explore the genomic environment of Slc25a21 and to discover that expression of Pax9, located 3' of the target gene, was reduced in homozygous Slc25a21(tm1a(KOMP)Wtsi) mice. We hypothesize that the presence of the selection cassette is the cause of the down regulation of Pax9 observed. The phenotypes we observed in homozygous Slc25a21(tm1a(KOMP)Wtsi) mice were broadly consistent with a hypomorphic Pax9 allele with the exception of otitis media and hearing impairment which may be a novel consequence of Pax9 down regulation. We explore the ramifications associated with this particular targeted mutation and emphasise the need to interpret phenotypes taking into consideration all potential underlying genetic mechanisms

Optimising experimental design for high-throughput phenotyping in mice: a case study

To further the functional annotation of the mammalian genome, the Sanger Mouse Genetics Programme aims to generate and characterise knockout mice in a high-throughput manner. Annually, approximately 200 lines of knockout mice will be characterised using a standardised battery of phenotyping tests covering key disease indications ranging from obesity to sensory acuity. From these findings secondary centres will select putative mutants of interest for more in-depth, confirmatory experiments. Optimising experimental design and data analysis is essential to maximise output using the resources with greatest efficiency, thereby attaining our biological objective of understanding the role of genes in normal development and disease. This study uses the example of the noninvasive blood pressure test to demonstrate how statistical investigation is important for generating meaningful, reliable results and assessing the design for the defined research objectives. The analysis adjusts for the multiple-testing problem by applying the false discovery rate, which controls the number of false calls within those highlighted as significant. A variance analysis finds that the variation between mice dominates this assay. These variance measures were used to examine the interplay between days, readings, and number of mice on power, the ability to detect change. If an experiment is underpowered, we cannot conclude whether failure to detect a biological difference arises from low power or lack of a distinct phenotype, hence the mice are subjected to testing without gain. Consequently, in confirmatory studies, a power analysis along with the 3Rs can provide justification to increase the number of mice used

A large targeted deletion of Hoxb1-Hoxb9 produces a series single-segment anterior homeotic transformations

Hox genes regulate axial regional specification during animal embryonic development and are grouped into four clusters. The mouse HoxB cluster contains 10 genes, Hoxb to Hoxb9 and Hoxb13, which are transcribed in the same direction. We have generated a mouse strain with a targeted 90-kb deletion within the HoxB cluster from Hoxb1 to Hoxb9. Surprisingly, heterozygous mice show no detectable abnormalities. Homozygous mutant embryos survive to term and exhibit an ordered series of one-segment anterior homeotic transformations along the cervical and thoracic vertebral column and defects in sternum morphogenesis. Neurofilament staining indicates abnormalities in the IXth cranial nerve. Notably, simultaneous deletion of Hoxb1 to Hoxb9 resulted in the sum of phenotypes of single HoxB gene mutants. Although a higher penetrance is observed, no synergistic or new phenotypes were observed, except for the loss of ventral curvature at the cervicothoracic boundary of the vertebral column. Although Hoxb13, the most 5′ gene, is separated from the rest by 70 kb, it has been suggested to be expressed with temporal and spatial colinearity. Here, we show that the expression pattern of Hoxb13 is not affected by the targeted deletion of the other 9 genes Thus, Hoxb13 expression seems to be independent of the deleted region, suggesting that its expression pattern could be achieved independent of the colinear pattern of the cluster or by a regulatory element located 5′ of Hoxb9

Proceso de enseñanza – aprendizaje significativo y comunidad en el área de la salud

Relacionar el aprendizaje activo y la responsabilidad social universitaria, resaltando la importancia de actividades académicas con valores para sentar las bases de atención primaria de salud. Diseño observacional, descriptivo y multidisciplinario con participación de profesores y estudiantes universitarios de las carreras de Medicina, Nutrición y Odontología, de 2o-4o semestres para brindar atención primaria de salud. Mediante consentimiento informado se atendió a más de 300 pobladores de diferentes comunidades incluyendo, niños, adolescentes y adultos. Los estudiantes educaron en salud con talleres de concientización y dinámicas grupales en temas relacionados al bienestar social como cuidado de mascotas, lavado de manos, toxoplasmosis, COVID-19, parasitosis alimentaria, plato del buen comer y salud bucal; se tomaron muestras de sangre para determinación de glicemia, colesterol, triglicéridos, grupo sanguíneo y antígeno prostático. Con este trabajo comunitario de atención a la salud, en escenarios reales, se logró el aprendizaje significativo en las áreas de bioquímica, histología, fisiología, nutrición, patología especial, patología y medicina bucal con trato digno al paciente

Evaluation of Cooking Quality, Nutritional and Texture Characteristics of Pasta Added with Oat Bran and Apple Flour

This study reports the effect of the addition of oat bran and apple flour on the cooking quality, digestibility, antioxidant, nutritional and texture characteristics of a spaghetti-type pasta. Pasta samples were prepared by substituting 50% of durum wheat semolina with oat bran (OBP) or apple flour (AFP). AFP presented higher cooking loss and water absorption index than the control pasta prepared with 100% durum wheat semolina (WSP). The supplementation of pasta with oat bran increased the total dietary fiber content (16.43% w/w, dw), while apple flour decreased the protein content (11.16% w/w, dw). There was no significant difference in the resistant starch content among all pasta samples. The pasta samples made with 50/50 durum wheat semolina/oat bran and 50/50 durum wheat semolina/apple flour increased the antioxidant activity by ≈46% and ≈97%, respectively. The OBP and AFP samples had a similar texture to the control pasta. A 50% replacement of durum wheat semolina with oat bran in a pasta formulation decreased the caloric content and digestibility of its starch components. These attributes found in the oat bran pasta and apple flour pasta make them a healthy choice for the diet of people with specific nutritional needs