Advancements in Artificial Intelligence for Precision Diagnosis and Treatment of Myocardial Infarction: A Comprehensive Review of Clinical Trials and Randomized Controlled Trials.

Coronary artery disease (CAD) is still a serious global health issue that has a substantial impact on death and illness rates. The goal of primary prevention strategies is to lower the risk of developing CAD. Nevertheless, current methods usually rely on simple risk assessment instruments that might overlook significant individual risk factors. This limitation highlights the need for innovative methods that can accurately assess cardiovascular risk and offer personalized preventive care. Recent advances in machine learning and artificial intelligence (AI) have opened up interesting new avenues for optimizing primary preventive efforts for CAD and improving risk prediction models. By leveraging large-scale databases and advanced computational techniques, AI has the potential to fundamentally alter how cardiovascular risk is evaluated and managed. This review looks at current randomized controlled studies and clinical trials that explore the application of AI and machine learning to improve primary preventive measures for CAD. The emphasis is on their ability to recognize and include a range of risk elements in sophisticated risk assessment models.

The Role of Nicotinic Receptors on Ca2+ Signaling in Bovine Chromaffin Cells.

Chromaffin cells have been used as a physiological model to understand neurosecretion in mammals for many years. Nicotinic receptors located in the cells' membrane are stimulated by acetylcholine, and they participate in the exocytosis of chromaffin granules, releasing catecholamines in response to stress. In this work, we discuss how the participation of nicotinic receptors and the localization of active zones in the borders of the cytoskeleton can generate local calcium signals leading to secretion. We use a computational model of a cytoskeleton cage to simulate Ca2+ levels in response to voltage and acetylcholine pulses. We find that nicotinic receptors are able to enhance the differences between local and average calcium values, as well as the heterogeneous distributions around the active zones, producing a non-linear, highly localized Ca2+ entry that, although consisting of a few ions, is able to improve secretion responses in chromaffin cells. Our findings emphasize the intricate interplay among nicotinic receptors, the cytoskeleton, and active zones within chromaffin cells as an example of Ca2+-dependent neurosecretion in mammals.

α3ß4 Acetylcholine Nicotinic Receptors Are Components of the Secretory Machinery Clusters in Chromaffin Cells.

The heteromeric assembly of α3 and ß4 subunits of acetylcholine nicotinic receptors (nAChRs) seems to mediate the secretory response in bovine chromaffin cells. However, there is no information about the localization of these nAChRs in relationship with the secretory active zones in this cellular model. The present work presents the first evidence that, in fact, a population of these receptors is associated through the F-actin cytoskeleton with exocytotic machinery components, as detected by SNAP-25 labeling. Furthermore, we also prove that, upon stimulation, the probability to find α3ß4 nAChRs very close to exocytotic events increases with randomized distributions, thus substantiating the clear dynamic behavior of these receptors during the secretory process. Modeling on secretory dynamics and secretory component distributions supports the idea that α3ß4 nAChR cluster mobility could help with improving the efficiency of the secretory response of chromaffin cells. Our study is limited by the use of conventional confocal microscopy; in this sense, a strengthening to our conclusions could come from the use of super-resolution microscopy techniques in the near future.

Development of the hypersecretory phenotype in the population of adrenal chromaffin cells from prehypertensive SHRs.

The hypersecretory phenotype of adrenal chromaffin cells (CCs) from early spontaneously hypertensive rats (SHRs) mainly results from enhanced Ca2+-induced Ca2+-release (CICR). A key question is if these abnormalities can be traced to the prehypertensive stage. Spontaneous and stimulus-induced catecholamine exocytosis, intracellular Ca2+ signals, and dense-core granule size and density were examined in CCs from prehypertensive and hypertensive SHRs and compared with age-matched Wistar-Kyoto rats (WKY). During the prehypertensive stage, the depolarization-elicited catecholamine exocytosis was ~ 2.9-fold greater in SHR than in WKY CCs. Interestingly, in half of CCs the exocytosis was indistinguishable from WKY CCs, while it was between 3- and sixfold larger in the other half. Likewise, caffeine-induced exocytosis was ~ twofold larger in prehypertensive SHR. Accordingly, depolarization and caffeine application elicited [Ca2+]i rises ~ 1.5-fold larger in prehypertensive SHR than in WKY CCs. Ryanodine reduced the depolarization-induced secretion in prehypertensive SHR by 57%, compared to 14% in WKY CCs, suggesting a greater contribution of intracellular Ca2+ release to exocytosis. In SHR CCs, the mean spike amplitude and charge per spike were significantly larger than in WKY CCs, regardless of age and stimulus type. This difference in granule content could explain in part the enhanced exocytosis in SHR CCs. However, electron microscopy did not reveal significant differences in granule size between SHRs and WKY rats' adrenal medulla. Nonetheless, preSHR and hypSHR display 63% and 82% more granules than WKY, which could explain in part the enhanced catecholamine secretion. The mechanism responsible for the heterogeneous population of prehypertensive SHR CCs and the bias towards secreting more medium and large granules remains unexplained.

Pollutant emissions released during sewage sludge combustion in a bubbling fluidized bed reactor.

The combustion of dry sewage sludge particles in a bubbling fluidized bed was studied in detail, analyzing the composition of the exhaust gases by means of a FTIR equipment. The operating conditions of the fluidized bed, i.e., the bed temperature and mass flow rate of fluidizing air, were varied to quantify their effect on the exhaust gas composition. The bed material was also varied, using sepiolite, silica sand and braunite particles, to evaluate the effect of different bed densities on the pollutant emissions. The results obtained for the combustion of sewage sludge particles in the different fluidized beds tested were compared to combustion tests run for the same operating conditions and bed materials using Cynara cardunculus L. as a fuel. Pollutant emissions derived from sludge combustion are much higher than those obtained from combustion of Cynara. The operating conditions also affect the emissions, e.g., the concentration of CO in the exhaust fumes decreased substantially when increasing bed temperature and air flow rate. The bed density has an effect on the combustion efficiency of sludge, obtaining higher efficiencies in low-density beds for high temperature and air flow rates, while the efficiency was increased in high-density beds for low bed temperature and fluidizing air flow rate. The effects of ash accumulation and agglomerates formation were also analyzed.

Factores sociodemográficos y clínicos asociados a la supervivencia de dientes tratados endodónticamente por estudiantes de pregrado. Medellín (Colombia) / Sociodemographic and clinical factors associated to survival of endodontically treated teeth conducted by undergraduate dentistry students. Medellin (Colombia)

Resumen Objetivo: Determinar los factores sociodemográficos y clínicos asociados con la supervivencia de dientes tratados endodónticamente por estudiantes de pregrado de la Facultad de Odontología-Universidad de Antioquia (Medellín, Colombia), durante el periodo 2007-2011. Material y métodos: Estudio longitudinal retrospectivo con análisis de supervivencia por medio de las historias clínicas según los criterios de inclusión y posteriormente se examinaron a los pacientes. La supervivencia global se calculó utilizando el análisis de Kaplan-Meier, y las curvas se compararon a través del log rank test. Para el análisis multivariado se realizó el modelo de riesgos proporcionales de Cox, obteniendo la medida de asociación HR ajustada, con su intervalo de confianza al 95%. Resultados: Las variables sociodemográficas y clínicas con asociación estadísticamente significativa fueron nivel de educación, tipo de afiliación a salud, diagnóstico inicial y tipo de restauración. Los dientes que permanecen después de un tratamiento endodóntico durante los primeros tres años es del 78% y los que sobreviven por más de seis años es del 57%. La media de sobrevida de los dientes en los pacientes atendidos es de 1,959 días (error estándar de 66.9 días). El modelo multivariado mostró que la velocidad de pérdida del diente fue mayor en multirradiculares (HR 2.38; IC 95% 1.23-4.60) y en aquellos con diagnóstico inicial de absceso apical agudo (HR 27.96; IC 95% 1.84-423.09). Conclusión: Se identificaron factores sociodemográficos y clínicos asociados con la supervivencia de los dientes tratados endodónticamente, lo que permite establecer sistemas de vigilancia epidemiológica para evaluar la calidad de la atención odontológica.

Abstract Objective: To determine clinical and sociodemographic factors associated to survival of endodontically treated teeth. The present study was conducted by undergraduate students of the Faculty of Dentistry (Medellin, Colombia) during the period 2007-2011. Material and methods: Retrospective, longitudinal study with survival analysis through consultation with clinical histories according to inclusion criteria, and, further ahead, patient examination. Global survival was calculated with the use of Kaplan-Meier analysis, and curves were compared with log rank test. Cox proportional risk model was used for multivariate analysis, adjusted HR association was obtained with a 95% confidence interval. Results: Sociodemographic and clinical variables with statistically significant association were: education level, type of health affiliation, initial diagnosis and restoration type. Teeth remaining for three years after endodontic treatment were 78%, whereas 57% survived for over six years. Tooth survival mean in treated patients was 1,959 days (standard error: 66.9 days). Multivariate model showed that tooth loss speed was greater in multi-rooted teeth (HR 2.38, CI 95% 1.23-4.60) as well as in teeth with initial diagnosis of acute apical abscess (HR 27.96, CI 95%, 1.84-423.09). Conclusion: Clinical and sociodemographic factors were identified, associated to survival of endodontically treated teeth, this allowed to establish epidemiological monitoring systems in order to assess dental care quality.

A theoretical study of factors influencing calcium-secretion coupling in a presynaptic active zone model.

A theoretical analysis of some of the relevant factors influencing the calcium time course and the strength and timing of release probabilities of vesicles evoked by an action potential in a calyx-type active zone is presented in this paper. In particular, our study focus on the comparison of cooperative vs non-cooperative calcium binding by the release site and the effect of the number of Ca(2+) binding sites on the calcium sensitivity for release. Regarding the comparison of cooperative and non-cooperative kinetic schemes, our simulations show that quite different results are obtained when considering one or another: a reduction in the release probability of more than a 50% is obtained when considering the cooperative kinetic scheme. Also, a delay in the average time for release appears when using this model for the calcium sensor. Our study also shows that a non-cooperative kinetic binding scheme gives rise to a well defined average calcium level for release assuming that the same kinetic constants are considered for all the sites. Our results also suggest that the central value of the calcium sensitivity for release depends on the number of binding sites N and the dissociation constant KD with a scaling law depending on NKD.

Prevalence and incidence rates of dementia and cognitive impairment no dementia in the Mexican population: data from the Mexican Health and Aging Study.

OBJECTIVE: To estimate the prevalence and incidence of dementia and cognitive impairment without dementia (CIND) in the Mexican population. METHOD: The MHAS study is a prospective panel study of health and aging in Mexico with 7,000 elders that represent eight million participants nationally. Using measurements of cognition and activities of daily living of dementia cases and CIND were identified at baseline and follow-up. Overall incidence rates and specific rates for sex, age, and education were calculated. RESULTS: Prevalence was 6.1% and 28.7% for dementia and CIND, respectively. Incidence rates were 27.3 per 1,000 person-years for dementia and 223 per 1,000 persons-year for CIND. Rates of dementia and CIND increased with advancing age and decreased with higher educational level; sex had a differential effect depending on the age strata. Hypertension, diabetes, and depression were risk factors for dementia but not for CIND. DISCUSSION: These data provide estimates of prevalence and incidence of dementia and cognitive impairment in the Mexican population for projection of future burden.

P2X7 receptors trigger ATP exocytosis and modify secretory vesicle dynamics in neuroblastoma cells.

Previously, we reported that purinergic ionotropic P2X7 receptors negatively regulate neurite formation in Neuro-2a (N2a) mouse neuroblastoma cells through a Ca(2+)/calmodulin-dependent kinase II-related mechanism. In the present study we used this cell line to investigate a parallel though faster P2X7 receptor-mediated signaling pathway, namely Ca(2+)-regulated exocytosis. Selective activation of P2X7 receptors evoked exocytosis as assayed by high resolution membrane capacitance measurements. Using dual-wavelength total internal reflection microscopy, we have observed both the increase in near-membrane Ca(2+) concentration and the exocytosis of fluorescently labeled vesicles in response to P2X7 receptor stimulation. Moreover, activation of P2X7 receptors also affects vesicle motion in the vertical and horizontal directions, thus, involving this receptor type in the control of early steps (docking and priming) of the secretory pathway. Immunocytochemical and RT-PCR experiments evidenced that N2a cells express the three neuronal SNAREs as well as vesicular nucleotide and monoamine (VMAT-1 and VMAT-2) transporters. Biochemical measurements indicated that ionomycin induced a significant release of ATP from N2a cells. Finally, P2X7 receptor stimulation and ionomycin increased the incidence of small transient inward currents, reminiscent of postsynaptic quantal events observed at synapses. Small transient inward currents were dependent on extracellular Ca(2+) and were abolished by Brilliant Blue G, suggesting they were mediated by P2X7 receptors. Altogether, these results suggest the existence of a positive feedback mechanism mediated by P2X7 receptor-stimulated exocytotic release of ATP that would act on P2X7 receptors on the same or neighbor cells to further stimulate its own release and negatively control N2a cell differentiation.

Determining the influence of telomere dysfunction and DNA damage on stem and progenitor cell aging: what markers can we use?

The decline in organ maintenance and function is one of the major problems limiting quality of life during aging. The accumulation of telomere dysfunction and DNA damage appears to be one of the underlying causes. Uncapping of chromosome ends in response to critical telomere shortening limits the proliferative capacity of human cells by activation of DNA damage checkpoints inducing senescence or apoptosis. Telomere shortening occurs in the vast majority of human tissues during aging and in chronic diseases that increase the rate of cell turnover. There is emerging evidence that telomere shortening can limit the maintenance and function of adult stem cells -- a cell type of utmost importance for organ maintenance and regeneration. In mouse models, telomere dysfunction leads to a depletion of adult stem cell compartments suggesting that stem cells are very sensitive to DNA damage. Both the rarity of stem and progenitor cells in adult organs and their removal in response to damage make it difficult to assess the impact of telomere dysfunction and DNA damage on stem and progenitor cell aging. Such approaches require the development of sensitive biomarkers recognizing low levels of telomere dysfunction and DNA damage in stem and progenitor cells. Here, we review experimental data on the prevalence of telomere dysfunction and DNA damage during aging and its possible impact on stem and progenitor cell aging.

Comparative analysis of cognitive impairment among Mexicans and Spanish-speaking immigrant's elders.

OBJECTIVE: This study aims to compare the prevalence of cognitive impairment among older Mexicans and Spanish-speaking U.S. immigrants. METHODS: The relationship of cognitive impairment with social and demographic variables was explored using data from five different population based survey studies. RESULTS: Prevalence rates increased with age, with low educational level, didn't show a clear association with gender and decreased in married subjects. Estimates of cognitive and functional impairment combined are greater in the immigrant samples than those for Mexican residents. Primary memory measures are the least discriminative for cognitive impairment, whereas orientation, attention, and secondary verbal memory measures discriminate better. DISCUSSION: Mexicans and Spanish-speaking USA immigrants have similar prevalence estimates of cognitive impairment. However, prevalence of functional impairment differs between Mexicans and immigrants because of measurement issues and cultural factors.

Cognition, functional status, education, and the diagnosis of dementia and mild cognitive impairment in Spanish-speaking elderly.

A group of 314 Spanish-speaking elders were classified in 55 participants with mild to moderate dementia, 74 participants with mild cognitive impairment (MCI), and 185 control participants, according to clinical evaluation derived. Sensitivity, specificity, and detection characteristics of frequently cognitive and functional tests were calculated in comparison with the clinical evaluation: Minimental State Examination, Brief Neuropsychological Test Battery, Short Blessed test, Pfeffer Functional Activities Questionnaire, and Blessed Dementia Scale. Influence of education on sensitivity and specificity values varied along the tests. For all the cognitive and functional measures, a great number of MCI participants who fulfilled Mayo's (Mayo's Clinical School) clinical criteria (Petersen et al., 1999) were misclassified as controls and a few were misclassified as demented. Level of education plays a very important role in both cognitive and functional assessment. The cognitive tests that are commonly used to screen demented patients may fail to detect MCI particularly in high-functioning individuals as well as those who are well educated.