Economic impact assessment from the use of a mobile app for the self-management of heart diseases by patients with heart failure in a Spanish region.

Currently, cardiovascular diseases are the deadliest diseases with a total of 17 million deaths worldwide. Hence, they are the focus of many mobile applications for smartphones and tablets. This paper will assess the ex-ante economic impact as well as will determine the cost-effectiveness analysis that the use of one of this app, CardioManager, by patients with heart failure will have in a Spanish community, Castile and Leon. For this, a cost-effectiveness analysis using the hidden Markov model were performed in a hypothetical cohort of patients diagnosed with heart failure, based on the information of epidemiological parameters and the costs derived from the management and care of heart failure patients by the Public Health Care System of Castile and Leon. The costs of patient care were estimated from the perspective of the Ministry of Health of Spain using a discount rate of 3 %. Finally, an estimation of the ex-ante impact that would suppose the introduction of CardioManager in the Health Care System is performed. It is concluded that the introduction of CardioManager may generate a 33 % reduction in the cost of management and treatment of the disease. This means that CardioManager may be able to save more than 9,000 € per patient to the local Health Care System of Castile and Leon, which can be translated in a saving of 0.31 % of the total health expenditure of the region.

Intrauterine and early-life malnutrition in rats disrupts the circadian rhythm programming of energy metabolites through adulthood.

Maternal malnutrition plays a crucial role in functional development, resulting in behavioral, cognitive, and metabolic abnormalities and disturbances. "Cafeteria diet" has been linked to obesity, metabolic syndrome, diabetes, and other metabolic disruptions in the mammalian lifespan. However, there are very few reports about the effect of intrauterine and early postnatal malnutrition on the circadian rhythm programming of energy metabolites. In mammals, circadian rhythm central control is fundamental for correct interaction with the environment and physiological regulation. Exposure to malnutrition during development imprints metabolic programming throughout life on the central nervous system and peripheral systems. Lifespan studies exploring the effect of high fat/low protein diet administered during critical periods of development are scarce. The present study explored the effect of intrauterine and perinatal malnutrition induced by a high fat/low protein diet (Cafeteria Diet) on circadian and peripheral oscillators controlling glucose, insulin, and triglycerides in rats at 40 and 90 days of age. We evaluated plasma glucose and triglyceride levels in 6 Zeitgeber times, in addition to an intraperitoneal glucose tolerance test (IpTGT) and homeostasis model assessment of insulin resistance (HOMA-IR) at two time-points over 24h. Our results show that offspring of malnourished dams fed cafeteria diet present alterations in circadian rhythmicity of glucose and triglycerides associated with a change in glucose tolerance and insulin sensibility differentially regulated at the development stage and time of day. Intrauterine and early malnutrition due to a cafeteria diet produces maladaptive responses and programs energetic metabolism at several developmental stages during the lifespan.

A Study in a Regional Hospital of a Mid-Sized Spanish City Indicates a Major Increase in Infection/Colonization by Carbapenem-Resistant Bacteria, Coinciding with the COVID-19 Pandemic.

Bacterial resistance to antibiotics has proven difficult to control over the past few decades. The large group of multidrug-resistant bacteria includes carbapenemase-producing bacteria (CPB), for which limited therapeutic options and infection control measures are available. Furthermore, carbapenemases associate with high-risk clones that are defined by the sequence type (ST) to which each bacterium belongs. The objectives of this cross-sectional and retrospective study were to describe the CPB population isolated in a third-level hospital in Southern Spain between 2015 and 2020 and to establish the relationship between the ST and the epidemiological situation defined by the hospital. CPB were microbiologically studied in all rectal and pharyngeal swabs and clinical samples received between January 2015 and December 2020, characterizing isolates using MicroScan and mass spectrometry. Carbapenemases were detected by PCR and Sanger sequencing, and STs were assigned by multilocus sequence typing (MLST). Isolates were genetically related by pulsed-field gel electrophoresis using Xbal, Spel, or Apal enzymes. The episodes in which each CPB was isolated were recorded and classified as involved or non-involved in an outbreak. There were 320 episodes with CPB during the study period: 18 with K. pneumoniae, 14 with Klebisella oxytoca, 9 with Citrobacter freundii, 11 with Escherichia coli, 46 with Enterobacter cloacae, 70 with Acinetobacter baumannii, and 52 with Pseudomonas aeruginosa. The carbapenemase groups detected were OXA, VIM, KPC, and NDM with various subgroups. Synchronous relationships were notified between episodes of K. pneumoniae and outbreaks for ST15, ST258, ST307, and ST45, but not for the other CPB. There was a major increase in infections with CPB over the years, most notably during 2020, coinciding with the COVID-19 pandemic. This study highlights the usefulness of gene sequencing techniques to control the spread of these microorganisms, especially in healthcare centers. These techniques offer faster results, and a reduction in their cost may make their real-time application more feasible. The combination of epidemiological data with real-time molecular sequencing techniques can provide a major advance in the transmission control of these CPB and in the management of infected patients. Real-time sequencing is essential to increase precision and thereby control outbreaks and target infection prevention measures in a more effective manner.

How Relevant Is the Place Where First-Year College Students Live in Relation to the Increase in Body Mass Index?

(1) Objective: This study analyzes the evolution of the body mass index (BMI) throughout the academic year associated with changes in the lifestyle associated with the place where students live during the course, lifestyle design, and health strategies for the university community. (2) Methods: A total of 93 first-year nursing students participated in this study. Data were collected throughout the course by administering self-reported questionnaires about eating habits and lifestyles, weight, and height to calculate their BMI and place of residence throughout the course. Data were analyzed using statistical analysis (Mann-Whitney, chi-square, Student's t-test, repeated-measures analysis of variance, and least significant difference tests). (3) Results: We found that the mean BMI increases significantly throughout the course among all students regardless of sex, age, eating habits, or where they live during the course. At the beginning of the course, the mean BMI was 22.10 ± 3.64. The mean difference between the beginning of the course and the middle has a value of p-value < 0.015 and between the middle of the course and the end a p-value < 0.009. The group that increased the most is found among students who continue to live in the family nucleus rather than those who live alone or in residence. Students significantly changed their eating and health habits, especially those who live alone or in residence. (4) Conclusions: There is an increase in BMI among students. It is necessary to carry out seminars or talks that can help students understand the importance of good eating practices and healthy habits to maintain their weight and, therefore, their health, in the short, medium, and long term and acquire a good quality of life.

Perinatal exposure to nicotine disrupts circadian locomotor and learning efficiency rhythms in juvenile mice.

The increased rates of nicotine exposure by electronic nicotine delivery systems (vaping), ingestion, or patches during pregnancy as an alternative to the smoking of tobacco arise concerns about the neurodevelopmental, cognitive, and behavioral long-term consequences in the juvenile offspring. Nowadays, the use of electronic cigarettes as supposed a safer smoking alternative has been increased mainly in young females at reproductive age, due to the "safety" misconception. However, previous studies suggest that exposure to nicotine during pregnancy and prenatal development may lead to detrimental effects in the postnatal lifespan. Nicotine, as an alkaloid, alters the reward system acting as acetylcholine (ACh) agonist on nicotinic cholinergic receptors (nAChRs). In early brain development, the cholinergic system is also involved in neurite outgrowth, cell survival, proliferation, differentiation, neurogenesis, and many other critical processes being considered as a developmental signal marker. The nicotine noxious effect at those early stages may impact the system programming and plasticity in the long-term postnatal life. In this study, we analyze the circadian locomotor activity and learning efficiency rhythms in the juvenile male offspring of mice exposed to nicotine through pregnancy and lactation. Attenuated rhythm amplitude and relative power of the circadian component were found in the nicotine exposed offspring (pN). The acrophase (the best performance during a 24-h cycle) of learning efficiency was delayed and the long-term memory consolidation task failed after 8 days of learning experience. The aforementioned results suggest nicotine exposure in uterus modifies the circadian modulation related to the memory consolidation and locomotor systems as well as its environmental temporal synchronization.

Fetal and Postnatal Nicotine Exposure Modifies Maturation of Gonocytes to Spermatogonia in Mice.

Studies in laboratory animals have shown that male offspring from dams, exposed to nicotine during pregnancy and postnatal periods, show alterations in fertility, although the origin of this is still uncertain. In this study, we examined in a mouse model if the process of gonocyte maturation to spermatogonia was affected in male offspring from dams with nicotine administration during pregnancy and postnatal periods. BALB/C mice, with and without nicotine administrations in pregnancy and postnatal periods, were studied. The animals were euthanized at 3, 7, 10, 16, and 35 days postpartum (dpp). Testicular tissue samples were processed for histological, ultrastructural, and immunohistochemical studies; and testicular lipoperoxidation was determined. It was observed that in the nicotine-exposed animals, there was increased apoptosis and a reduction in the number of gonocytes that matured to spermatogonia. This gonocyte-spermatogonia maturation reduction was associated with a greater immunoreactivity to nicotinic acetylcholine receptors in the germ cells. Lipoperoxidation was similar in both groups until 16 dpp, with significant reduction at 35 dpp. Our findings suggest that nicotine intake during pregnancy and postnatal periods can affect the process of maturation of gonocytes to spermatogonia and the pool of available spermatogonia for spermatogenesis.

Mice with hyper-long telomeres show less metabolic aging and longer lifespans.

Short telomeres trigger age-related pathologies and shorter lifespans in mice and humans. In the past, we generated mouse embryonic (ES) cells with longer telomeres than normal (hyper-long telomeres) in the absence of genetic manipulations, which contributed to all mouse tissues. To address whether hyper-long telomeres have deleterious effects, we generated mice in which 100% of their cells are derived from hyper-long telomere ES cells. We observe that these mice have longer telomeres and less DNA damage with aging. Hyper-long telomere mice are lean and show low cholesterol and LDL levels, as well as improved glucose and insulin tolerance. Hyper-long telomere mice also have less incidence of cancer and an increased longevity. These findings demonstrate that longer telomeres than normal in a given species are not deleterious but instead, show beneficial effects.

[Recommendations for the care of patients with community-acquired pneumonia in the Emergency Department]. / Recomendaciones para la atención del paciente con neumonía adquirida en la comunidad en los Servicios de Urgencias.

The incidence of community-acquired pneumonia (CAP) ranges from 2-15 cases / 1,000 inhabitants / year, being higher in those older than 65 years and in patients with high co-morbidity. Around 75% of all CAP diagnosed are treated in the Emergency Department (ED). The CAP represents the main cause for sepsis and septic shock in ED, and the most frequent cause of death and admission to the Intensive Care Unit (ICU) due to infectious disease. Overall mortality is 10-14% according to age and associated risk factors. Forty to 60% of CAP will require hospital admission, including observation units (with very variable ranges from 22-65% according to centers, seasonal of the year and patients´ characteristics). Between the admissions, 2-10% will be in the ICU. All of previously mentioned reflects the importance of the CAP in the ED, as well as the "impact of the emergency care on the patient with CAP", as it is the establishment where the initial, but key decisions, are made and could condition the outcome of the illness. It is known the great variability among physicians in the diagnostic and therapeutic management of CAP, which is one of the reasons that explains the great differences in the admission rates, achievement of the microbiological diagnosis, request for complementary studies, the choice of antimicrobial treatment, or the diversity of applied care. In this sense, the implementation of clinical practice guidelines with the use of the severity scores and the new tools available, such as biomarkers, can improve patient care with CAP in ED. Therefore, a multidisciplinary group of emergency professionals and specialists involved in the care process of CAP has designed a guideline with several recommendations for decisions-making during the key moments in patients with CAP attended in the ED.

Subchronic urinary bladder effects of muraglitazar in male rats.

Muraglitazar, a PPARalpha/gamma dual agonist, was dosed orally to rats once daily for 13 weeks to evaluate urinary and urothelial changes of potential relevance to urinary bladder tumorigenesis. Groups of 17 young or aged rats per sex were fed a normal or 1% NH4Cl-supplemented diet and were dosed with 0, 1, or 50 mg/kg muraglitazar. Lithogenic ions and sediment were profiled from freshly voided urine samples collected 24 h after dosing, and drug exposures were measured. Urinary citrate, oxalate, and epidermal growth factor (EGF) were assayed from 18-h urine collections. Urothelium was assessed by light microscopy, scanning electron microscopy, and BrdU and TUNEL immunohistochemistry. When fed a normal diet, urine pH was higher in males (above 6.5). Urine volume/body weight was greater in females. Urine soluble/total calcium and magnesium and phosphorus/creatinine ratios were lower in male rats fed a normal diet. Urine citrate levels were decreased and oxalate was increased in young male rats treated with 50 mg/kg muraglitazar compared to age/sex/diet-matched controls. No changes in urine sediment were detected 24 h after dosing. In young male rats treated with 50 mg/kg on normal diet, multifocal urothelial necrosis and proliferation were observed, whereas urothelial apoptosis and urine EGF levels were unchanged compared to age/sex/diet-matched controls. Urothelial necrosis and proliferation were not correlated to systemic or urinary drug exposures and were prevented by dietary acidification. These data suggest that muraglitazar-associated changes in urine composition predispose to urothelial cytotoxicity and proliferation in the urinary bladder of young male rats and that urine sediment must be profiled at multiple daily timepoints to fully qualify drug-induced changes in urine composition.

Effects of co-administration of antioxidants and arsenicals on the rat urinary bladder epithelium.

Oxidative stress has been increasingly recognized as a possible mechanism in the toxicity and carcinogenicity of various chemicals, including arsenic. Therefore, treatment with antioxidants may afford a protective effect against arsenic-induced cytotoxicity and carcinogenesis. Dimethylarsinic acid (DMAV) has been shown to be a bladder carcinogen in rats when administered at high doses (100 ppm) in the diet or in the drinking water. The main purpose of the present study was to evaluate the effects of co-administration of antioxidants with arsenicals on the rat urinary bladder epithelium in vitro and in vivo. In a previous experiment, treatment with 1000 ppm melatonin for two weeks did not inhibit cell proliferation induced in the rat urothelium by 100 ppm DMAV. In the current study, we examined the effects of five antioxidants that act via different mechanisms, on the in vitro cytotoxicity of various arsenicals, for the purpose of determining which antioxidants might have protective effects against arsenic-induced cytotoxicity. The antioxidants that inhibited cytotoxicity in vitro were then studied also in vivo. Melatonin showed slight inhibition of the cytotoxicity of arsenite, but had no effect on the other arsenicals. N-acetylcysteine (NAC) inhibited the cytotoxicity of monomethylarsonous acid (MMAIII), DMAV, dimethylarsinous acid (DMAIII), and trimethylarsine oxide (TMAO). Vitamin C inhibited cytotoxicity induced by arsenate, arsenite, MMAIII) and DMAIII. Tiron and Trolox had no effect on the cytotoxicity of any arsenical. The in vitro inhibitory effects of NAC and vitamin C on DMAV and on DMAIII, suggested that these antioxidants might afford preventive effects on DMAV-induced bladder cytotoxicity and carcinogenesis in rats. To test this hypothesis, a 10-week rat bioassay was conducted. Melatonin was also included to clarify the results of the previous two-week experiment. The sodium salt of vitamin C (Na-Asc), but not melatonin or NAC, inhibited the proliferative effects of DMAV on the bladder epithelium in rats. These results suggest that oxidative stress is at least in part involved in DMAV-induced rat bladder toxicity and proliferation, and therefore, vitamin C may afford inhibitory effects in DMAV-induced bladder carcinogenesis in rats. Microarray analysis of DMAV-responsive genes revealed that DMAV did not have a consistent modifying effect on gene expression in the rat bladder epithelium, suggesting that proteins and/or lipids may be the targets of damage by DMAV-induced oxidative stress.

Estado nutricional de una población escolar en España y su relación con hábitos de alimentación y actividad física / Nutritional status of a school population in Spain and its relationship to eating habits and physical activity

La obesidad infantil ha incrementado su prevalencia en España, y aunque se considera un problema multifactorial, es atribuible principalmente al aumento de la ingesta y la disminución de la actividad física por un ocio sedentario mayor. El objetivo de este estudio fue conocer la prevalencia de sobrepeso y obesidad infantil en la Zona Básica de Salud (ZBS) de Menasalbas (Toledo, España), y la influencia de los hábitos alimentarios, de actividad física y deporte, y de ocio sedentario. Se realizó un estudio transversal en la población escolarizada de 3 a 12 años de la ZBS de Menasalbas, tomando medidas de peso y talla a 725 menores, calculando su IMC y clasificando su estado ponderal según las tablas de Cole. También se recogieron datos referentes a sus hábitos alimentarios y cuestionario Kidmed de adherencia a la dieta mediterránea, y hábitos de actividad física y ocio sedentario, para estudiar su relación con el estado ponderal de los menores. La prevalencia de sobrecarga ponderal (suma de prevalencias de sobrepeso y obesidad) fue del 24,9%, con un 18,8% de sobrepeso y un 6,1% de obesidad, sin diferencias por edad y sexo. No se observaron diferencias respecto a los hábitos alimentarios, pero si una menor actividad física y un mayor ocio sedentario en aquellos con sobrecarga ponderal. La prevalencia de sobrepeso y obesidad en nuestra población es elevada, aunque menor a las de otros trabajos. La alimentación, la actividad física y el ocio sedentario influenciaron el sobrepeso y la obesidad infantil en este estudio(AU)

Childhood obesity has increased its prevalence in Spain, and although it´s considered a multifactorial problem, it is mainly attributable to increased intake and decreased physical activity due to increased sedentary leisure. The objective of this study was to know the prevalence of overweight and childhood obesity in the Basic Health Zone (ZBS) of Menasalbas (Toledo, Spain), and the influence of eating habits, physical activity and sport, and sedentary entertainment. A cross-sectional study was conducted in the school children of 3 to 12 years of age in the ZBS of Menasalbas, taking weight and height measurements for 725 minors, calculating their BMI and classifying their weight status according to Cole´s tables. Data regarding their eating habits and Kidmed questionnaire of adherence to the mediterranean diet, physical activity habits and sedentary leisure habits were also collected, to study its relationship with the weigh status of minors. The prevalence of weight overload (understood as the sum of the prevalence of overweight and obesity) was 24.9% , with 18.8% overweight and 6.1% of obesity, with no differences by age and sex. No differences were observed regarding eating habits, but less physical activity and a more sedentary leisure in those with weight overload was observed. The prevalence of overweight and obesity in our population is high, although lower than reported in other works. Diet, physical activity and sedentary leisure are confirmed as fundamental aspects in childhood overweight and obesity(AU)

Treatment compliance in chronic illness: Current situation and future perspectives. / Adherencia terapéutica en la enfermedad crónica: estado de la situación y perspectiva de futuro.

Long-term chronic diseases have a high mortality rate around the world, affecting both genders equally. Despite improvements in the diagnosis and treatment of various health problems, lack of treatment compliance remains an obstacle to improving health and patient quality of life, and it carries a high associated socio-healthcare cost. The objectives of this study were to develop the concept of «therapeutic adherence¼, which includes both pharmacological compliance as well as non-pharmacological (level of agreement and patient involvement, lifestyle changes, etc.) treatments. The study also aimed to establish the clinical and socio-health impact of non-compliance, the reasons for non-compliance, and methods and strategies to improve compliance. The results of this study support therapeutic adherence as an essential goal of the healthcare system that encompasses all stakeholders involved in patient health.

Detection of retained microbubbles in carotid arteries with real-time low mechanical index imaging in the setting of endothelial dysfunction.

OBJECTIVES: We sought to determine if intravenously injected microbubbles would be retained by the carotid arteries (CAs) in the setting of endothelial dysfunction (ED) using a linear transducer equipped with a low mechanical index pulse sequence scheme (PSS). BACKGROUND: Microbubbles normally pass freely through large and small vessels but are retained in regions with ED. New high-frequency low mechanical index PSS can potentially be utilized to image these retained microbubbles. METHODS: Intravenous albumin- and lipid-encapsulated microbubbles were administered in seven pigs while imaging the CAs before and after a 20% intralipid infusion to induce hypertriglyceridemia. The degree of microbubble retention was quantified by measuring endothelial acoustic intensity (AI) after clearance of free-flowing microbubbles. Microbubble adherence was also evaluated after selective balloon injury of the CAs. The CA diameter responses to acetylcholine were quantified. RESULTS: After induction of hypertriglyceridemia, adherence of albumin-encapsulated microbubbles was visually evident in all CAs, and endothelial AI increased significantly (p < 0.001 compared with baseline). The CA responses to acetylcholine went from vasodilation at baseline to vasoconstriction during hypertriglyceridemia. Endothelial AI also increased in the balloon-stretched vessels (p < 0.01 compared with uninjured vessels) after albumin-encapsulated microbubble injection, with a ring of microbubbles selectively adhering to the injured segment. This retention was not observed with lipid-encapsulated microbubbles. Scanning electron microscopy confirmed that albumin-coated microbubbles adhered to endothelial cells. CONCLUSIONS: Retention of intravenously injected albumin microbubbles occurs in the setting of both global and regional ED in large vessels and can be noninvasively imaged with high-frequency low mechanical index PSS.

Possible role of dimethylarsinous acid in dimethylarsinic acid-induced urothelial toxicity and regeneration in the rat.

Dimethylarsinic acid (DMA(V)) is carcinogenic to the rat urinary bladder when administered at high doses in the diet or drinking water. At a dietary dose of 100 ppm (microg/g), it produces cytotoxicity within 6 h and increased proliferation (hyperplasia) by 7 days of administration. We hypothesize that formation of the reactive organic intermediate dimethylarsinous acid (DMA(III)) is involved in the induction of the cytotoxicity. To evaluate the possibility that DMA(V) administration produces urothelial toxicity and regeneration by the formation of trivalent arsenicals, 2,3-dimercaptopropane-1-sulfonic acid (DMPS, 5600 ppm), a chelator of trivalent arsenicals, was co-administered with DMA(V) (100 ppm) for 2 weeks to groups of female Fischer F344 rats. Based on light and scanning electron microscopy, and bromodeoxyuridine labeling index, DMA(V) produced cytotoxicity and regenerative hyperplasia of the urothelium which was inhibited by co-administration with DMPS. The major forms of arsenic in the 24-h urine of rats administered DMA(V) were high concentrations of DMA(V) (66.4 +/- 2.7 microM) itself and the pentavalent organic arsenical trimethylarsine oxide (TMAO) (73.2 +/- 9.5 microM). Co-administration with DMPS led to an increase in DMA(V) (507 +/- 31 microM) with a decrease in TMAO (2.8 +/- 0.4 microM) excretion. The formation of TMAO from DMA(V) mechanistically suggests formation of the intermediate trivalent metabolite, DMA(III). In a second experiment evaluating fresh void urines collected on study days 1, 71, and 175, we detected DMA(III) in the urine of DMA(V) and DMA(V) plus DMPS-treated rats at approximately micromolar concentrations. Using rat (MYP3) and human (1T1) urothelial cells, cytotoxicity for trivalent arsenicals, sodium arsenite, monomethylarsonous acid (MMA(III)), and DMA(III) was demonstrated at 0.4-4.8 microM concentrations, whereas MMA(V), DMA(V), and TMAO were cytotoxic at millimolar concentrations. The presence of DMA(III) at micromolar concentrations in the urine of rats fed 100 ppm DMA(V) suggests that DMA(III) produced in vivo may be involved in the toxic effects in the rat urinary bladder after dietary administration of DMA(V).