Search

"Abstract: The study aims at complementing the historical knowledge regarding the participation of Dr. Bucur (Hilarius) Mitrea and Dr. Ioan Arsenie within the Austrian volunteer corps in Mexico, using as sources the copies of their conduct lists preserved in the military archives of Vienna. The new data concern the battles they took part in, together with characterizations of their behavior and personality. The latter consolidate the image built by former biographers in the case of Dr. Mitrea and help to sketch a less known portrait in the case of Dr. Arsenie. Keywords: military physicians, 19th century, Transylvania, Mexico, Österreichisches Freiwilligenkorps in Mexiko"

Designed as a defensive system against the Ottoman Empire, the Austrian military border was doubled by a sanitary cordon, which served as a defense shield against epidemics. In order for this system to function adequately, the border patrol troops that served the House of Habsburg also needed protection against the diseases that threatened the empire. The present study brings into discussion the health problems that border guards from the Banat region experienced, a topic that remains largely unaddressed in the existing literature. By building on original archival research and the specialized work of the epoch, this article traces the main conditions, the means of tackling diseases, the remedies that were specifically local or those found within the European repertoire. It also sheds light on the support that the administrative apparatus offered to the troops, namely medical care in its material form (hospitals, quarantines, pharmacies, medicine, monetary assistance) and human form (the personnel hired at the borders: military doctors, surgeons, midwives, veterinarians). This article concludes that the entire correspondence from the center directed at the local authorities in Banat and vice versa reflects in a unique and subtle way the level of medical knowledge of the time.

"The study provides the documentation for the first public version of the database Digital Framework for the History of the Austrian Military Border in Transylvania by means of a detailed description and user manual. It includes: a short overview of the historical context of the establishment of the Austrian military border in this province, references to the international and Romanian state of the art, the detailing of primary sources issued by the military environment and starting from which the database was built and the main principles of construction and operation of the latter. The information in the database is extracted from the records of the military and administrative personnel of the Transylvanian border regiments between 1763 and 1850, including monthly staff records, information on salaries, enrollments, transfers, desertions, medical certificates, etc. The lists of conduct of the officers should also be mentioned, each of them including a detailed physical and psychological description of the respective person. The database serves two aims. On the one hand, to boost the use of and access to documents generated by the Austrian military and with this to bring the Romanian historical writing on the military border in Transylvania closer to the primary sources. On the other hand, to complement, for the territory of the former military border, the vital registration data provided by parish registers with social history data that can improve life course reconstruction and analysis. Keywords: Historical databases, Austrian Military Border, Transylvania, Habsburg Monarchy, Military history "

Designed as a defensive system against the Ottoman Empire, the Austrian military border was doubled by a sanitary cordon, which served as a defense shield against epidemics. In order for this system to function adequately, the border patrol troops that served the House of Habsburg also needed protection against the diseases that threatened the empire. The present study brings into discussion the health problems that border guards from the Banat region experienced, a topic that remains largely unaddressed in the existing literature. By building on original archival research and the specialized work of the epoch, this article traces the main conditions, the means of tackling diseases, the remedies that were specifically local or those found within the European repertoire. It also sheds light on the support that the administrative apparatus offered to the troops, namely medical care in its material form (hospitals, quarantines, pharmacies, medicine, monetary assistance) and human form (the personnel hired at the borders: military doctors, surgeons, midwives, veterinarians). This article concludes that the entire correspondence from the center directed at the local authorities in Banat and vice versa reflects in a unique and subtle way the level of medical knowledge of the time.

Der Einzug von Prinz Eugen von Savoyen in die osmanische Festung Temeswar (rum. Timişoara, ung. Temesvár, serb. Temišvar) am 18. Oktober 1716 markierte für die Stadt nicht nur einen Herrschaftswechsel, sondern auch den Anfang einer neuen Epoche. Die Stadt und das Land entfalteten sich nun nach den Regeln und Vorhaben der neuen Regierung und wurden damit Teil einer von oben geführten Planung.

An inexpensive and simple method to determine non-alcoholic fatty liver disease (NAFLD) is the abdominal ultrasound, but there are still doubts about its accuracy. We assessed the precision of a semi-quantitative ultrasound method to determine liver fat infiltration, using magnetic resonance spectroscopy (MRS) as the reference. The study was conducted in youths from an ongoing cohort study. Clinical validation was performed, using receiver operating characteristic analysis, in n = 60 participants (22.6y; 50% males). Abdominal ultrasound was carried out with liver brightness (score 0–3), diaphragm attenuation (0–2) and liver vessel blurring (0–1) scored by two observers. Liver fat was estimated using MRS. Then, analytical validation was conducted in the remaining participants (n = 555; 22.7y; 51% males) using effects size estimates. An ultrasound score ≥4.0 had the highest sensitivity (78%) and specificity (85%) for NAFLD diagnosis. An area under the curve of 86% denotes a good diagnostic performance of the test, whereas a Kappa of 0.63 suggests substantial agreement of ultrasound vs. MRS. The analytical validation showed that participants having NAFLD according to ultrasound had an unhealthier cardiometabolic profile than participants without the condition. Abdominal ultrasound, combined with a semi-quantitative score system, is a reliable method to determine liver fat infiltration in young adults and should be encouraged whenever MRS is unavailable.

Objectives International cutoff points for the diagnosis of sarcopenia are not applicable to the Chilean population due to previous evidence of a lower lean mass and strength in this population. Dual-energy x-ray absorptiometry is used to establish fat-free mass cutoff points to define sarcopenia in the Chilean population and analyze its association with handgrip strength in older adults. Methods Appendicular fat-free mass (AFFM) was calculated from 4062 dual-energy x-ray absorptiometries of healthy Chileans, ages 18 to 99 y. Possible cutoff points for sarcopenia were obtained using four methods: A) Normative, –2 standard deviation (SD) below mean AFFM/height2 (AFFMI) of adults age Results Using the normative method, sarcopenia was defined as an AFFMI Conclusions The AFFM of young Chileans is lower than that reported in Western countries but similar to Latin American data; therefore, the use of the traditional normative method would not be appropriate with –2 SD to establish cutoff points, and using –1 DS resulted in values that are higher than Baumgartner's. Stratification is advantageous because this method throws expected values of AFFM for each population; however, overdiagnosis of sarcopenia is a possibility and thus the method requires a representative sample. The percentage method is simple and showed the expected decrease of muscle mass with age, and also correlated well with handgrip strength in elderly women. Thus, this method represented our method of choice to detect sarcopenia.

Changes in DNA methylation, one of the most studied epigenetic mechanisms, are considered an initial marker for early cancer detection. We evaluated how availability of dietary factors (folates and vitamin B12) involved in one-carbon metabolism may contribute to DNA methylation changes of cancer-related genes in human subjects. We studied, by pyrosequencing, the methylation of tumor suppressor gene p16, DNA repair genes MLH1 and MGMT, and the repetitive element LINE-1 (as a surrogate for global DNA methylation), in blood of elderly individuals (n = 249) who had been exposed to folic acid (FA) through FA-fortified wheat flour during the last 12 years. We found that serum folate and to a lesser extent, vitamin B12 concentrations, were significantly correlated with DNA methylation of p16, MLH1, and MGMT, but not with LINE-1. High serum folate concentrations (>45.3 nmol/L) were present in 31.1% of the participants. Although the methylated fraction of CpG sites in p16, MLH1, and MGMT was low (1.17–3.8%), high folate concentrations were significantly associated with methylation at the 3rd tertile of specific CpG sites in all genes with OR between 1.97 and 4.17. This study shows that a public policy, like food fortification with FA that increases circulating serum folate levels, could affect methylation levels of specific genes linked to cancer risk. Our present results deserve additional studies to clarify the real impact of high FA levels for risk of cancer in a whole population chronically exposed to a fortified food such as wheat flour. ISRCTN 48153354 and ISRCTN 02694183

Background/Aims Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome characterized by a failure of the propulsion of intraluminal contents and recurrent symptoms of partial bowel obstruction in the absence of mechanical obstruction. Regional variations of the intestinal compromise have been described. Intestinal manometry can indicate the pathophysiology and prognosis. Our objective is to establish the demographic and clinical characteristics of group Chilean patients and analyze the motility of the small intestine and its prognostic value. Methods Patients with symptoms of intestinal pseudo-obstruction with dilated bowel loops were included, in all of whom a manometry of the small intestine was performed using perfused catheters. Results Of the 64 patients included, 51 women (average age 41.5 ± 17.6 years), 54 primary and 10 secondary CIPO were included. Dilatation of the small intestine was the only finding in 38 patients; in the remaining, the compromise was associated with other segments, primarily the colon. Forty-nine patients underwent 65 surgeries, mainly exploratory laparotomies and colectomies. Intestinal manometry was performed on all patients; 4 “patterns” were observed: neuropathic (n = 26), myopathic (n = 3), mixed (n = 24), and a group without motor activity (n = 11). The most relevant findings were the complex migrating motor disorders and decreased frequency and propagation of contractions. The 9 patients who died had a severe myopathic compromise. Conclusions In our series, isolated small bowel compromise was the most common disorder. Neuropathic motor compromise was observed in most of the patients. Mortality was associated with severe myopathic compromise. (J Neurogastroenterol Motil 2017;23:273-280)

Summary Problem Up to 35% of hospitalized patients may experience functional decline during or after hospitalization. Subjective Global Assessment (SGA) and handgrip strength at admission, have been proposed as simple and accessible tools to predict functional decline, but there are few studies in hospitalized patients to confirm these findings. Objective To assess the predictive value of handgrip strength at hospital admission, on functional decline after 30 days. Methods 125 non-critical patients hospitalized for medical and surgical conditions, were studied in El Pino hospital in Santiago, Chile. Upon admission, nutritional status was assessed by SGA, functional status through the Karnofsky index (KI), and handgrip strength by dynamometry. Change in functionality was assessed by the difference between KI at admission and 30 days later. Multivariate logistic regression models were used to establish associations between the variables at hospital admission, and subsequent functional decline. Results Thirty days post-hospital admission, 28.8% of the sample showed functional decline. In a multivariate analysis, only handgrip strength was associated with this decline (β = −0.025, OR = 0.974 (CI 0.956–0.992), p = 0.007). Conclusions Handgrip strength upon hospital admission can be a useful independent and early method to predict deterioration of functional status during hospitalization.

Objectives Predictive equations are frequently used to estimate resting energy expenditure (REE) because indirect calorimetry (IC) is not always available and is expensive. The aim of this study was to determine the concordance between the estimation of REE using predictive equations and its measurement by IC. Methods This was an analysis of the registry of indirect calorimetry performed in non-hospitalized participants. Harris–Benedict, FAO/WHO/UNU, Mifflin St. Jeor, and European Society for Clinical Nutrition and Metabolism (ESPEN) equations were used to estimate REE in these individuals. The concordance between measured and estimated REE using real, ideal, and adjusted weight was calculated using the concordance coefficient analysis of Lin and Bland– Altman plots in all participants and in subgroups separated according to their body mass index. Results We retrieved 680 measurements and discarded 247 that did not comply with the inclusion criteria. Thus, we studied 433 participants ages 36 y (29–48 y). Of the participants, 341 were women (79%) and the participants had a body mass index (BMI) of 30 kg/m2 (26.7–33.1 kg/m2). All predictive equations had concordance values 10% ranged from 36% to 87%. The ESPEN equation had the greater proportion of erroneous estimations of REE in all participants and BMI subgroups when real weight was used. Conclusions We observed a low level of concordance between REE estimated using predictive equations and measured by IC. These results should alert clinicians about the inaccuracy of predictive equations.

Objective Omega-3 fatty acids may reduce albuminuria and cardiovascular risk factors in patients with chronic kidney disease (CKD). We aimed to assess the effects of omega-3 fatty acid supplementation on albuminuria, blood pressure, pulse wave velocity, and inflammatory markers in patients with CKD. Methods Patients with CKD and a urine albumin excretion of at least 30 mg/g creatinine were supplemented for 3 months with 3,666 mg/day of docosahexaenoic and eicosapentaenoic acids or a corn oil supplement. The study was double blind. At baseline, 6 weeks, and 12 weeks, fasting blood and morning spot urine samples were obtained. Blood pressure, carotid intima media thickness, and pulse wave velocity were measured. The main outcome measure was a reduction of ≥20% in urine albumin. Results One hundred patients were randomized (50 received omega-3 fatty acids and 50 received corn oil). Four patients who received omega-3 fatty acids and 5 who received vegetable oil were lost to follow-up. In patients receiving omega-3 fatty acids, the omega-3 index increased from 3.08 (2.32-3.81) to 5.48 (3.045-7.04) percent. A 20% reduction in urine albumin excretion was observed in 13 participants of the control group and 19 participants of omega-3 group (Fisher's exact P = .274). However, the supplement had a significant and positive effect on pulse wave velocity and triglyceride level. Conclusion An omega-3 fatty acid supplement of 3,666 mg/day did not modify urine albumin excretion in patients with CKD but did improve pulse wave velocity and serum triglyceride levels.

espanolIntroduccion: la restriccion proteica es fundamental en el manejo de la enfermedad renal cronica. Objetivo: evaluamos la utilidad de la medicion de nitrogeno ureico urinario como marcador de restriccion proteica. Metodos: participantes jovenes sanos fueron divididos aleatoriamente en dos grupos. Un grupo recibio una dieta con 30 kcal/dia/kg peso corporal y 1 g/proteina/dia/kg peso corporal y el otro recibio una dieta con la misma cantidad de calorias pero con 0,6 g/kg peso corporal de proteina. Al inicio, a los siete y a los 14 dias, los participantes respondieron una encuesta dietaria de recordatorio de 24 horas. Ademas, recolectaron orina de 24 horas y se les tomo una muestra aislada de orina al comienzo y a los 14 dias de la intervencion para medir creatinina y nitrogeno ureico. Resultados: cuarenta y un participantes de 29 ± 5 anos completaron el estudio. El grupo que consumio 0,6 g/kg de proteinas redujo su ingesta proteica de 0,88 ± 0,06 a 0,59 ± 0,05 g/kg/dia durante la intervencion. En este grupo se observo una reduccion significativa en la excrecion urinaria de nitrogeno ureico en 24 horas. No se observo tal reduccion en el grupo que consumio 1 g/kg de proteinas. La tasa de probabilidad de detectar una reduccion en la ingesta proteica en las encuestas dietarias, cuando se observaba una disminucion en la excrecion urinaria de nitrogeno ureico/mg creatinina de 24 horas, fue de 5,75 (intervalos de confianza de 95% = 1,29-25,55, p = 0,02). No hubo cambios significativos en la excrecion de nitrogeno ureico en las muestras aisladas de orina. Conclusion: las mediciones repetidas de nitrogeno ureico urinario en 24 horas son un marcador de restriccion dietaria de proteinas. EnglishBackground: protein restriction is the mainstay of dietary management of chronic kidney disease. Aim: to assess the usefulness of urine urea nitrogen measurement as a marker of protein restriction. Methods: healthy young participants were randomly divided in two groups. During 14 days, one group received a diet containing 30 kcal/kg body weight and 1 g protein/kg body weight and the other group received a diet with the same amount of calories and 0.6 g/kg of proteins. At baseline, seven days and 14 days, 24 h dietary recalls were answered by the participants. They collected 24 hour urine and provided spot urine samples at baseline and at the end of the intervention, to measure creatinine and urea nitrogen. Results: forty-one participants aged 29 ± 5 years completed the follow-up. According to 24h dietary recalls, the group receiving 0.6 g/kg protein reduced significantly the protein intake during the intervention from 0.88 ± 0.06 to 0.59 ± 0.05 g/kg/day. A significant reduction in 24 h urea nitrogen excretion was also observed in this group. In the group receiving 1 g/kg of protein, no significant changes in 24 h urea nitrogen excretion were observed. Among all participants, the odds ratio of observing a reduction in protein intake in the dietary survey was 5.75 (95% confidence intervals 1.29-25.55, p = 0.02), when a reduction in 24 h urea nitrogen excretion corrected by creatinine was observed. No changes were observed in urea nitrogen excretion in spot urine samples. Conclusions: repeated urea nitrogen excretion measured in 24 h urine samples can be a reliable indicator of dietary protein restriction.

Introduction Muscle mass and function are among the most relevant factors that contribute to an optimal quality of life, and are strong predictors of mortality in the elderly. Loss of lean tissues and deterioration of muscle function have been described as one of the many complications of type 2 diabetes mellitus (DM2), but most studies do not isolate age as an intervening factor. Aim To study whether adult DM2 patients up to 60 years of age have decreased muscle mass and function compared with healthy non-diabetic (ND) subjects of similar age. Methodology Appendicular fat-free mass (ApFFM) by dual X-ray absorptiometry (DEXA), handgrip strength (HS), quadriceps strength (QS), 12 min walking capacity (12MW) and the Timed Up and Go test (TUG) were measured in 100 DM2 patients and 39 ND controls. Muscle quality, or the ratio between lean mass and muscle strength of upper and lower limbs, and the functional limitations associated with pain and stiffness assessed according to the Western Ontario and McMaster Universities Arthrosis Index (WOMAC) were also recorded. Specific tests were performed to rule out microvascular diabetic complications (retinal and peripheral nerves), metabolic control, kidney function and vitamin D status and examine their association with ApFFM and function. Results ApFFM was significantly higher among DM2 female patients and lower among diabetic men. However opposite results were obtained when individual values were corrected for body mass index (BMI), specifically among women, who were more likely to be obese. As for muscle strength and global functionality tests, significantly better performances in TUG, 12MW, QS and HS were observed among ND subjects of both sexes. These differences prevailed even after excluding diabetic patients with microvascular complications as well as those with more than 10 years of diabetes. Muscle quality was also significantly better among ND women. Higher scores of pain and stiffness in the WOMAC scale correlated with 12MW and TUG in both groups but did not correlate with ApFFM. Conclusions We found a clear deterioration of lean mass and muscle functions among adult DM2 patients of up to 60 years old, independent of length of disease, metabolic control, vitamin D status and presence of microvascular complications and pain.

Background Sedentariness may be an important risk factor for sarcopenia. The aim of this work was to assess the association between muscle mass and strength and markers of usual physical activity such as activity energy expenditure and peak oxygen uptake. Methods Young and old participants were assessed measuring body composition by DEXA (double beam X ray absorptiometry), handgrip strength, peak oxygen consumption and workload during an exercise calorimetry in a braked cycle ergometer and a 72 h activity energy expenditure using Actiheart actigraphs. A heart rate/energy expenditure curve derived from the exercise calorimetry was used to calibrate each actigraph. Sarcopenia was defined as having an appendicular fat free mass index below 7.5 kg/m2 and 5.6 kg/m2 in men and women respectively, or a handgrip strength z score below 1, using local normal data or having both parameters below the cutoff points. Results We analyzed data from 192 assessments performed in participants aged 22 to 88 years (106 women). Sarcopenic participants (as determined by muscle mass, strength or both) had a significantly lower peak oxygen uptake and work load and a significantly lower activity energy expenditure. When analyzing lean mass and strength as continuous variables, peak oxygen consumption was a significant predictor of fat free mass in men. Among women, the association was observed only when percentage of muscle mass was expressed as a z score. Conclusions Activity energy expenditure and peak oxygen consumption are associated with a lower muscle mass and the presence of sarcopenia and should be considered as risk factors for this condition.

Background: the prognostic value of maximal inspiratory and expiratory pressures on functional capacity and mortality of hospitalized patients are not well established. Aim: to evaluate the prognostic value of respiratory pressures in hospitalized patients. Methods: patients admitted to a general hospital in Santiago-Chile were prospectively studied. Within 48 hours of admission, handgrip strength and inspiratory and expiratory pressures were measured. Subjective global assessment of nutritional status (SGA) was determined and Apache II score was calculated. Functional status was assessed using the Karnofski index. Patients were followed for a period of 30 days. Mortality and decline in functional capacity, defined as a reduction in at least two stages of the Karnofski index were determined. Normal values for handgrip strength and respiratory pressures were obtained in 366 healthy subjects aged 20 to 89 years, thus the results obtained in patients were expressed as age and sex matched z-scores. Results: one hundred and eight patients were recruited and 18 had to be excluded. Thus, 90 patients aged 58 ± 16 years (46 females) were studied. During the observation period, six patients died and nine experienced a decline in functional status. Patients who died had significantly lower maximal inspiratory and expiratory pressures, hand grip strength and worse SGA. Logistic regression analysis only accepted maximal expiratory pressure expressed as z-score as a predictor of mortality. In addition, it was the only significant predictor of death or functional decline. Conclusions: maximal expiratory pressure on admission was a predictor of death or functional decline at 30 days.

OBJECTIVETo determine whether probiotic prophylaxes reduce the odds ofClostridium difficileinfection (CDI) in adults and children.DESIGNIndividual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.METHODSWe searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.RESULTSProbiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25–0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23–0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11–4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89–1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89–1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.CONCLUSIONSModerate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.TRIAL REGISTRATIONPROSPERO 2015 identifier: CRD42015015701Infect Control Hosp Epidemiol2018;771–781

Chronic renal disease (CRD) in its pre-dialysis stage is an important risk factor for mortality among adults. The aim of this study was to assess the effects of CRD on mortality among consultants in Chilean public primary care clinics. We obtained information about serum creatinine, urinary albumin excretion (UAE), blood pressure, and body mass index of 5224 consultants [3379 females aged 67 (59-75) years and 1845 males aged 68 (59-75) years] in three clinics of Metropolitan Santiago. Kaplan-Meier curves and Cox proportional hazard regression models were used to determine risk factors for mortality, determined 41 months after obtaining the blood samples. During the follow-up period, 262 patients died (33% due to circulatory causes and 29% due to tumors). Kaplan-Meier curves showed that there was a significant association between survival, estimated glomerular filtration rate, and UAE. Cox models showed that serum creatinine, UAE, a lower body mass index, and a history of diabetes were significant mortality predictors. A sensitivity analysis performed eliminating extreme ages (less than 50 and more than 80 years), included high diastolic pressure as a predictor of survival. We conclude that among patients with CRD in its pre-dialysis stage, UAE is an important predictor of survival, along with serum creatinine. A low body mass index was associated with a higher mortality.

Folic acid (FA) consumption at high levels has been associated with colon cancer risk. Several mechanisms have been proposed to explain this association. The Notch signal pathway has been implicated in the regulation of cellular proliferation. Our aim was to demonstrate that high concentrations of FA or its reduced form, 5-methyltetrahydrofolic acid (5-MTHF), increase colorectal carcinoma HT29 cell proliferation through an increase of Notch1 activation and to prove if the inhibition of Notch1 activation by gamma secretase inhibitor, reduce the effect of folic acid. HT29 cells were cultured in high (400 nM), low (20 nM), or 0 nM FA or 5-MTHF concentrations during 96 h with or without DAPT (gamma secretase inhibitor). Cell proliferation was determined by the methylthiazole tetrazolium method, and Notch1-intracellular domain (NICD) was analyzed by flow cytometry. HT29 cells exposed to 400 nM FA or 5-MTHF showed higher proliferation rate than those exposed to 20 nM of FA or 5-MTHF (P < 0.01) during 96 h. NICD expression increased at higher FA or 5-MTHF concentrations compared with lower concentrations (P < 0.01). This effect on proliferation was partially reversible when we blocked Notch1 activation with the inhibitor of γ-secretase (P < 0.05).These data suggest that high concentration of FA and 5-MTHF induce HT29 cell proliferation activating Notch1 pathway.

Introduction: Non-caloric artificial sweeteners (NAS) consumption may not be safe for health. Several cohort studies have found a positive association between consumption of artificially sweetened beverages (ASB) with weight gain chronic non-communicable diseases. Therefore, it is of interest to study the effect of the consumption of NAS on glucose and insulin response in different conditions.Aim: To determine the effect of acute NAS consumption on blood glucose and insulin curves in healthy people.Methods: A randomized double-blind clinical trial was conducted in 9 apparently healthy subjects who were randomly assigned to drink one can of ASB and one can of sugar sweetened beverages (SSB) and repeated under identical conditions for 3 times each beverage. Blood glucose and insulin levels were measured in the fasted state and during 180 min after the ingestion of the beverage. Areas Under the Curve (AUC) for glucose and insulin were calculated for the values above baseline for the 3 hour period following the drink intake. Within and between coefficients of variation were calculated.Results: The ASB beverage induced a significantly lower area under the curve (AUC) for plasma glucose (87 ± 182 mg* min/dl) and plasma insulin (36 ± 50 μ UI * min/ml) compared with the SSB drink (glucose 954 ± 669 mg * min/dl and insulin 1738 ± 887 μ UI * min/ml) p

Henriquez, S, Monsalves-Alvarez, M, Jimenez, T, Barrera, G, Hirsch, S, de la Maza, MP, Leiva, L, Rodriguez, JM, Silva, C, and Bunout, D. Effects of two training modalities on body fat and insulin resistance in postmenopausal women. J Strength Cond Res 31(11): 2955-2964, 2017-Our objective was to compare the effects of a low-load circuit resistance training protocol and usual aerobic training in postmenopausal women. Postmenopausal women with at least 1 feature of the metabolic syndrome were randomly allocated to a low-load circuit resistance training protocol or traditional aerobic training in a braked cycle ergometer. The intervention consisted in supervised sessions lasting 40 minutes, 3 times per week, during 6 months. At baseline and at the end of the intervention, fasting serum lipid levels, serum interleukin 6, C-reactive protein, 8 isoprostanes, and insulin resistance (assessed through QUICKI and HOMA-IR) were measured. Body fat was measured by double-beam X-ray absorptiometry and by computed tomography densitometric quantification at lumbar 3 vertebral level. Twenty-one women aged 58 (54-59) years were allocated to aerobic training and 21 women aged 55 (52-61) years were allocated to the low-load circuit resistance training protocol. Eighteen and 16 women in each group completed the 6 months training period. Women in both groups experienced significant reductions in blood pressure, total body, subcutaneous, and intraabdominal body fat. Reductions in total cholesterol and triacylglycerol levels were also observed. No changes in insulin resistance indexes, 8 isoprostanes, C-reactive protein, or interleukin 6 were observed in either group. No significant differences between treatment groups were observed in any of the measured parameters. We conclude that low-load circuit resistance training and aerobic training resulted in the same reductions in body fat and serum lipid levels.

Immunosenescence has been described as age-associated changes in the immune function which are thought to be responsible for the increased morbidity with age. Human Natural Killer (NK) cells are a specialized heterogeneous subpopulation of lymphocytes involved in immune defense against tumor and microbial diseases. Interestingly, aging-related NK cell dysfunction is associated with features of aging such as tumor incidence, reduced vaccination efficacy, and short survival due to infection. It is known that NK cell effector functions are critically dependent on cytokines and metabolic activity. Our aim was to determine whether there is a difference in purified human NK cell function in response to high concentration of IL-2 between young and elder donors. Here, we report that the stimulation of human NK cells with IL-2 (2000 U/mL) enhance NK cell cytotoxic activity from both young and elderly donors. However, while NK cells from young people responded to IL-2 signaling by increasing mitochondrial mass and mitochondrial membrane potential, no increase in these mitochondrial functional parameters was seen in purified NK cells from elderly subjects. Moreover, as purified NK cells from the young exhibited an almost three-fold increase in PGC-1α expression after IL-2 (2000 U/mL) stimulation, PGC-1α expression was inhibited in purified NK cells from elders. Furthermore, this response upon PGC-1α expression after IL-2 stimulation promoted an increase in ROS production in NK cells from elderly humans, while no increase in ROS production was observed in NK cells of young donors. Our data show that IL-2 stimulates NK cell effector function through a signaling pathway which involves a PGC-1α-dependent mitochondrial function in young NK cells, however it seems that NK cells from older donors exhibit an altered IL-2 signaling which affects mitochondrial function associated with an increased production of ROS which could represent a feature of NK cell senescence.

El aporte de folatos durante el embarazo es esencial para un desarrollo fetal y placentario adecuados y para la salud del individuo a largo plazo. Su deficiencia puede inducir alteraciones y patologías fetales como bajo peso al nacer, recién nacidos de pre término y defectos del tubo neural (DTN). Por ello, varios países han decidido implementar políticas públicas de fortificación de alimentos con ácido fólico (AF). Chile inició la fortificación de la harina de trigo con AF en el año 2000, logrando reducir en un 43% la prevalencia de DTN. Sin embargo, además de la elevada ingesta de pan de nuestra población (principal alimento fortificado con AF), muchas mujeres embarazadas consumen suplementos de AF, lo que podría estar superando las concentraciones máximas de AF recomendadas. Adicionalmente, si la dieta materna es reducida en vitamina B12 (vit B12), se alteraría la razón óptima folatos/vit B12 lo que modificaría la metilación de genes específicos y otras vías metabólicas pudiendo afectar el desarrollo fetal y la salud de los recién nacidos a largo plazo. Creemos que, transcurridos 17 años del inicio de la fortificación de la harina de trigo con AF, es necesario evaluar los posibles efectos secundarios de un alto consumo de AF, no solo durante el embarazo, sino también en la población general. Presentamos antecedentes acerca del mecanismo de acción de folatos y vit B12 a nivel celular, y conceptos actuales sobre las posibles consecuencias de un aporte materno elevado de AF sobre la descendencia.

Background: The Chilean Ministry of Health developed a healthy lifestyles intervention directed to adults with overweight and cardiovascular risk factors, called "Program on Healthy Eating and Physical Activity" (PASAF). Aim: To evaluate the impact of PASAF on nutritional status and metabolic parameters. Patients and Methods: We analyzed databases from three primary care centers belonging to a municipality of Metropolitan Santiago. We selected adults enrolled in the PASAF during three years (2007-2009). The program lasted four months and included an assessment of anthropometric and metabolic parameters at baseline and at the end, eight workshops with a nutritionist, seven with a psychologist and 32 sessions of physical activity. Result: We evaluated 526 subjects aged ≥ 18 years (93% females), of whom 85.6% attended the last appointment for assessment. Analyzing available data, attendance to workshops was < 50% of the scheduled sessions. Weight, body mass index and waist circumference decreased significantly (median: -1.4 kg, -0.6 kg/m² and -3 cm, respectively). The median weight loss was 1.8% of initial weight and 17.1% of participants experienced a decrease ≥ 5% of their initial weight. There were significant improvements in lipid levels and blood pressure among participants with lower initial excess weight. A reduction in fasting blood glucose was observed only among subjects who lost ≥ 5% of their initial weight. Conclusions: The PASAF modestly reduced nutritional parameters. Correction of metabolic parameters was especially effective in less obese subjects. The attendance to workshops was low.

Background Lack of weight gain throughout adult life could mimic the beneficial effects of energy restriction in humans. The present study aimed to assess the effects of weight stability or gain, over a period of 10 years, on telomere length, sirtuin 1 and 6 expression, and carotid intima media thickness. Methods We studied 148 healthy adults (age range 20–59 years; 101 females) who had an objective record of their weight 10 years before. They were classified as weight losers, weight maintainers, weight gainers and extreme weight gainers. A fasting blood sample was obtained for routine laboratory and isolation of peripheral blood mononuclear cells, to extract DNA and RNA, and to measure telomere length and sirtuin 1 and 6 expression, respectively. Carotid intima media thickness was measured by ultrasound. Body composition was measured by Dual-energy X-ray absorptiometry. Results In the 10-year period, 24 participants lost weight (17 females), 65 maintained weight (41 females), 25 gained weight (15 females) and 34 were extreme weight gainers (28 females). Female weight gainers had a higher body mass index, waist circumference, total body fat and homeostatic model assessment insulin resistance. Male weight gainers had a higher hip circumference and total body fat. No differences in telomere length, sirtuin 1 expression and carotid intima media thickness were observed between weight gainers and maintainers. Conclusions No effect of weight maintenance or gain was observed on metabolic and vascular markers of ageing.

Aim To explore the usefulness of carotid ultrasound examination as a marker of aging and predictor of disability among older people. Methods Carotid ultrasound, measuring carotid intima media thickness (CIMT) and recording the presence of plaques, was carried out in 152 adults aged 29–59 years (47 women) and in 107 older adults aged 61–88 years (86 women). In all, clinical routine laboratory parameters and lymphocyte telomere length as T/S ratio were measured. Among older adults, 12-min walk, timed up and go, hand grip and quadriceps strength were determined. Results CIMT was significantly higher among older people and T/S ratio was significantly higher in young women. Carotid plaques were found in one adult and 17 older people. A multiple regression analysis accepted age, systolic blood pressure and T/S ratios as independent predictors of CIMT (R2 = 0.51). Among older people, a logistic regression accepted age and the presence of carotid plaques as significant predictors of a 12-min walk speed below 1 m/s. Conclusions An abnormal 12-min walk as an indicator of functional decline among older people is associated with the presence of carotid artery plaques. CIMT is independently associated with age. Geriatr Gerontol Int 2014; 14: 710–715.

Folate deficiency during pregnancy has been related to low birth weight, preterm (PT) birth and other health risks in the offspring; however, it is unknown whether prematurity is related to low folate transport through the placenta due to altered expression of specific folate transporters. We determined placental expression (mRNA and protein concentrations by RT-qPCR and WB respectively) of specific folate transporters: RFC, PCFT/HCP1 and FOLR1 in chorionic (fetal) and basal (maternal) plates of placentas of PT pregnancies (PT, 32-36 weeks, n = 51). Term placentas were used as controls (T, 37-41 weeks, n = 47). Folates and vitamin B12 levels were measured by electrochemiluminescence in umbilical cord blood of newborns. FOLR1 mRNA expression was lower and protein concentration higher in PT placentas (both plates) relative to the control group (p

Folate intake during pregnancy is essential for an adequate fetal and placental development and for the long time health of the individual. Its deficiency may induce fetal pathologies, including neural tube disease (NTD). Therefore, several countries implemented public policies to fortify foods with folic acid (FA). Chile started the fortification of wheat flour with FA in the year 2000, decreasing a 43% the prevalence of NTD. However, despite the high consumption of bread (the main fortified food with FA) by our population, a high number of pregnant women consume FA supplements, thus, over passing the maximal recommended FA intake. Additionally, if the diet is reduced in vitamin B12, the optimal ratio folates/vit B12 may be altered, thus inducing changes in the methylation of specific genes and other metabolic pathways, affecting fetal development and the long-term health of the neonates. We think that, after 16 years of the initiation of the fortification of wheat flour with FA, it is necessary to evaluate the possible side effects of a high intake of FA in the pregnant population and their offspring. This article shows antecedents about mechanisms of folates and vit B12 at cellular level, and their possible consequences of an elevated FA maternal intake on the offspring.

Purpose: To determine if irisin plasma levels are associated with regular physical activity, body composition and metabolic parameters in women subjected to calorie restriction. Subjects and methods: We studied 42 women aged 34 ± 13 years with a body mass index of 27.7 ± 1.8 kg/m2, who were subjected to a calorie restriction for three months. At baseline and at the end of the study, weight, waist and hip circumference, laboratory parameters, body composition by DEXA, resting and activity energy expenditure by indirect calorimetry and 72 hours actigraphy were measured. Fasting serum irisin was quantified using an ELISA kit. Results: After the intervention period, participants lost 1.5 (0.4-3.4) kg and irisin levels did not change. Irisin baseline levels were positively but weakly correlated with the level of physical activity. This association was lost at the end of the intervention. No association was found between irisin levels and body composition or insulin sensitivity or their changes after calorie restriction. No association between serum irisin levels and PGC-1α expression in peripheral blood mononuclear cells and serum irisin was observed. Conclusions: Fasting serum irisin was weakly associated with usual physical activity and did not change after calorie restriction.

Summary Background & aims During the past few years, consumption of high amounts of folic acid and high serum levels of folate have been associated with cancer risk. Several mechanisms have been proposed to explain this association. One of them is that supraphysiological levels of folate may diminish natural killer (NK) cell cytotoxic activity and its action as an antitumoral barrier. To demonstrate this hypothesis, we studied the effect of serum folate levels on NK cell cytotoxic activity in healthy subjects. Methods We recruited 227 healthy subjects of both sexes and measured serum folate levels and NK cell cytotoxic activity. Serum folate was adjusted for sex, age and body mass index to look for an association between its levels and cytotoxic activity of NK cell. Results We found supraphysiological serum folate levels in 24% of studied subjects. NK cell cytotoxic activity was not associated with serum folate levels. There was no relation between NK cell activity and other variables such as age, sex and BMI. Conclusions In this study, NK cell cytotoxic activity was not associated with serum folate levels. It is necessary to search for other hypothesis in order to explain the observed association between folic acid and cancer.

BACKGROUND: Advanced glycation end-products (AGEs) are one of the mechanisms related to diabetic vascular complications. However, since AGEs are multiple and heterogeneous moieties, there is no universally accepted method to measure them for clinical purposes. The aim of this work was to study the utility of a simple fluorimetric assay as predictor of complications. METHODS: Blood samples from 102 type 2 diabetic patients were obtained to assess glucose, glycosylated haemoglobin, creatinine, lipoproteins and C Reactive Protein (CRP), fluorescent AGES by spectrophotofluorimetry and non-fluorescent AGEs by measurement of N(e)-carboxymethyl-Lysine (CML) using an ELISA kit in a subsample of 82 patients. Urinary fluorescent AGEs, albumin and creatinine were also measured in a morning urine sample. Microvascular complications were studied by ophthalmologic examination, albuminuria and peripheral nerve conduction velocity. RESULTS: Patients without microvascular complications had significantly lower levels of both serum and urinary AGEs. CML was associated with retinopathy. Multiple regression analysis confirmed that AGEs, length of diabetes and glycosylated haemoglobin were all variables associated with diabetic complications, in this sample. CONCLUSIONS: A simple fluorimetric assay to measure low molecular weight fluorescent AGEs, and CML could be employed as screening tools to predict diabetic complications, at a primary care setting. AGEs should probably be considered as another therapeutic target in diabetes management.

Background Exercise training during the dialytical procedure may have positive cardiovascular effects and prevent or revert muscle wasting in patients undergoing chronic hemodialysis. Aim To evaluate the effects of an exercise training program in patients undergoing chronic hemodialysis. Material and methods Fifteen patients on chronic hemodialysis aged 21 to 69 years (three females) were included in the study. Nine of these were included in an exercise training program. During 16 weeks, exercise sessions were carried out during each dialytical procedure that included a warm-up period, aerobic exercises done using standing cycles, and resistance exercises, performed using Thera-Band(®) elastic bands and loops. Borg scale was used to control the intensity of training. At baseline and at the end of the study, a blood sample prior and after the dialytical procedure was obtained to measure C reactive protein, tumor necrosis factor α and interleukin 6. Quadriceps muscle strength, six minutes' walk and quality of life using the SF-36 questionnaire, were also measured. Results Four experimental subjects did not complete the study period, two that withdrew before starting, one due to problems with the venous access and one that decided to withdraw after 1 month of training. Among the five patients that finished the training period, significant improvements in the six minutes' walk and quadriceps strength were observed in the experimental group. No significant changes were observed among controls. No changes were observed in either group in C reactive protein, tumor necrosis factor and interleukin 6 levels or quality of life. Conclusions Among patients undergoing chronic hemodialysis exercise training improves endurance and muscle strength.

Aim: To evaluate the association between loss of fat-free mass and mortality among older people. Methods: Information of healthy Chilean older people evaluated by dual energy X-ray absorptiometry was used, identifying those who died in a period of 12 years. A Cox proportional hazards model was used to identify mortality predictors. Life tables were constructed calculating survival using predictive variables. Results: Information from 1413 participants aged 74.3 ± 5.6 years (1001 women), was obtained. During the follow-up (median 1594 days), 221 participants died. The Cox model identified age and appendicular fat-free mass as predictors of death (hazard ratios 1.08 and 0.85, respectively). According to life tables, participants in the lower sex-specific quartile for appendicular fat-free mass/height had significantly higher mortality. This association was significant among participants aged over 73 years. Conclusion: A low fat-free mass was predictive of mortality in older people.

Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-κB expression – a transcription factor sensitive to inflammation and oxidative stress – suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

Introduction. The inhibition of angiotensin-converting enzyme could be useful to avoid sarcopenia in the elderly. Materials and methods. We compared in a prospective double blind trial, the effects of treatment with enalapril or nifedipine on muscle performance in hypertensive elderly subjects. Patients were followed for nine months, and at baseline, 4.5 months and the end of follow-up, quadriceps and hand grip muscle strength, walking capacity, timed up and go and the short physical performance test were measured. Results. During follow-up, more subjects on nifedipine than on enalapril discontinued the medication due to side-effects. No differences in the evolution of muscle strength, walking capacity or functional measures were observed. At nine months, plasma angiotensin-converting enzyme activity decreased by 6.0±2.5 U/L among patients on enalapril and increased by 8.5±4.2 U/L (p Conclusion. In this group of elderly subjects, enalapril was not superior to nifedipine with regard to the age-related decline of muscle performance.