Miracle-dz/UniFAR-FTUs huggingface dataset:
Digestion and absorption of sorbitol, maltitol and isomalt from the small bowel. A study in ileostomy subjects.

OBJECTIVE To quantify small bowel digestion and absorption of sorbitol, isomalt and maltitol in ileostomy patients and estimate the metabolizable energy. SUBJECTS Study A: Nine ileostomy patients, under a constant controlled diet, ate during three consecutive days 2 milk chocolate bars per day, containing 2 x 15 g of polyol, each day with another polyol in random order. The first bar was taken 30 min after breakfast, and the second bar, 7 h after breakfast. Effluents were recovered during the whole study. Study B: 5, 10 or 20 g of sorbitol or isomalt were consumed each day in a drink during two 3-day periods by two ileostomy subjects. The recovery in the ileal effluent was measured over 24 h. RESULTS Study A: Carbohydrate recovery in ileostomy effluent was 26.8 +/- 2.8% (mean+SEM) for sorbitol, 24.8 + 5.7% for maltitol (2/3 as sorbitol) and 40.0 +/- 0.7% for isomalt (1/3 being sorbitol and mannitol). Ileal excretion, compared with a day without polyol, was compared in 4 subjects. The total volume excreted, as well as dry matter increased after polyol consumption. When taking this extra loss into account, the metabolizable energy value of the polyols for 2 x 15 g intake were: sorbitol, 12 kJ/g (2.8 kcal/g); maltitol, 13 kJ/g (3.1 kcal/g); isomalt, 9 kJ/g (2.1 kcal/g). Study B: The level of digestion and absorption of both sugar alcohols was dose dependent. CONCLUSIONS These results indicate that sorbitol, maltitol and isomalt are rather extensively absorbed, but the digestibility of the other nutrients is also reduced, due to the osmotic load caused by the polyols in the small intestine. There are evidences of a dose dependency of the energy value of the polyols.
Evoked Acetylcholine Release by Immortalized Brain Endothelial Cells Genetically Modified to Express Choline Acetyltransferase and/or the Vesicular Acetylcholine Transporter

Abstract : Immortalized rat brain endothelial RBE4 cells do not express choline acetyltransferase (ChAT), but they do express an endogenous machinery that enables them to release specifically acetylcholine (ACh) on calcium entry when they have been passively loaded with the neurotransmitter. Indeed, we have previously reported that these cells do not release glutamate or GABA after loading with these transmitters. The present study was set up to engineer stable cell lines producing ACh by transfecting them with an expression vector construct containing the rat ChAT. ChAT transfectants expressed a high level of ChAT activity and accumulated endogenous ACh. We examined evoked ACh release from RBE4 cells using two parallel approaches. First, Ca2+‐dependent ACh release induced by a calcium ionophore was followed with a chemiluminescent procedure. We showed that ChAT‐transfected cells released the transmitter they had synthesized and accumulated in the presence of an esterase inhibitor. Second, ACh released on an electrical depolarization was detected in real time by a whole‐cell voltageclamped Xenopus myocyte in contact with the cell. Whether cells synthesized ACh or whether they were passively loaded with ACh electrical stimulation elicited the release of ACh quanta detected as inward synaptic‐like currents in the myocyte. Repetitive stimulation elicited a continuous train of responses of decreasing amplitudes, with rare failures. Amplitude analysis showed that the currents peaked at preferential levels, as if they were multiples of an elementary component. Furthermore, we selected an RBE4 transgenic clone exhibiting a high level of ChAT activity to introduce the Torpedo vesicular ACh transporter (VAChT) gene. However, as the expression of ChAT was inactivated in stable VAChT transfectants, the potential influence of VAChT on evoked ACh release could only be studied on cells passively loaded with ACh. VAChT expression modified the pattern of ACh delivery on repetitive electrical stimulation. Stimulation trains evoked several groups of responses interupted by many failures. The total amount of released ACh and the mean quantal size were not modified. As brain endothelial cells are known as suitable cellular vectors for delivering gene products to the brain, the present results suggest that RBE4 cells genetically modified to produce ACh and intrinsically able to support evoked ACh release may provide a useful tool for improving altered cholinergic function in the CNS.
A Role for the MutL Mismatch Repair Mlh3 Protein in Immunoglobulin Class Switch DNA Recombination and Somatic Hypermutation1

Class switch DNA recombination (CSR) and somatic hypermutation (SHM) are central to the maturation of the Ab response. Both processes involve DNA mismatch repair (MMR). MMR proteins are recruited to dU:dG mispairs generated by activation-induced cytidine deaminase-mediated deamination of dC residues, thereby promoting S-S region synapses and introduction of mismatches (mutations). The MutL homolog Mlh3 is the last complement of the mammalian set of MMR proteins. It is highly conserved in evolution and is essential to meiosis and microsatellite stability. We used the recently generated knockout mlh3−/− mice to address the role of Mlh3 in CSR and SHM. We found that Mlh3 deficiency alters both CSR and SHM. mlh3−/− B cells switched in vitro to IgG and IgA but displayed preferential targeting of the RGYW/WRCY (R = A or G, Y = C or T, W = A or T) motif by Sγ1 and Sγ3 breakpoints and introduced more insertions and fewer donor/acceptor microhomologies in Sμ-Sγ1 and Sμ-Sγ3 DNA junctions, as compared with mlh3+/+ B cells. mlh3−/− mice showed only a slight decrease in the frequency of mutations in the intronic DNA downstream of the rearranged JH4 gene. However, the residual mutations were altered in spectrum. They comprised a decreased proportion of mutations at dA/dT and showed preferential RGYW/WRCY targeting by mutations at dC/dG. Thus, the MMR Mlh3 protein plays a role in both CSR and SHM.
[Health-related quality of life during a clinical behavior weight loss intervention therapy].

INTRODUCTION The aim of this study was to assess the effect of a multidisciplinary, behavioural obesity treatment program on weight management, physical improvements and health-related quality of life. MATERIAL AND METHODS The participants counted 47 women aged 20-60 years. The measurement period was from October 2007-July 2009 and a median time between measurements was six months. MEASUREMENTS height (cm), weight (kg), body mass index (BMI), waist circumference (WC), bioelectrical impedance analysis (BIA), cycle ergometer fitness test (w/kg), electrocardiogram, maximal oxygen uptake (VO2max), blood pressure (mmHg) and heart rate (bpm). Different dimensions of mental and physical health were assessed using validated questionnaires: SF-36v2TM of health-related quality of life, OP scale of psychosocial functioning in the obese, BAI anxiety inventory scale and BDI-II depression inventory scale. RESULTS BMI decreased on average by 3.9 kg/m2 (p<0.001). The total maximum output (watts) during the fitness test increased on average by 12% (p<0.001), fitness (w/kg) increased by 21% (p<0.001) and VO2max (ml/kg/min) by 18% (p<0.001). A decrease was noted in blood pressure as well as resting heart rate (p<0.05) at the end of the program. The results from the questionnaires showed improvements in quality of life and psychological well being (p<0.001). CONCLUSION These results highlight the importance of comprehensive weight management and emphasize the importance of permanent lifestyle changes for the patients. KEYWORDS Obesity, women, behavior therapy, ergometric.
Management, morbidity and mortality of COPD during an 11-year period: an observational retrospective epidemiological register study in Sweden (PATHOS)

Background: Chronic obstructive pulmonary disease (COPD) is one of the most common causes of mortality and a major contributor to morbidity. Longitudinal clinical practice data yielding information on the characteristics of the disease, its natural course, and management are limited. Aims: To investigate and describe the COPD population from a nationwide perspective during an 11-year period (1999–2009) with a focus on management, co-morbidity, and mortality. Methods: This observational retrospective epidemiological study linked electronic medical records data from patients with COPD in primary care to mandatory Swedish hospital, drug and Cause of Death registry data from 1999 to 2009 (PATHOS). Results: A total of 21,361 patients with a COPD diagnosis were included (mean age 68.0 years, 53% females). The proportion of patients diagnosed in primary care increased from 59% in 1999 to 81% in 2009 and the mean age at diagnosis decreased from 73 to 66 years. The number of exacerbations decreased from 3.0 to 1.3 and COPD-related hospitalisations decreased from 1.02 to 0.20 per patient per year. Prescriptions of long-acting muscarinic antagonists and fixed combinations of inhaled corticosteroid/long-acting β2-agonist inhalers increased from 0% to 36% and 37%, respectively. The most common co-morbidities were hypertension, heart failure, ischaemic heart disease, and diabetes. Overall life expectancy was 8.3±6.8 years shorter in patients with COPD than in the general population, and all-cause mortality was 3.5 times higher. Conclusions: Management of COPD in Sweden has improved during the 11-year study period. Despite this, patients with COPD have a substantially reduced life expectancy than the general population.
Maturation in Developing Permanent Porcine Enamel

Mineral content per tissue volume was investigated in developing permanent porcine enamel and contrasted with weight-related data. Levels of mineralization were correlated directly with the histological appearance of the overlying enamel organ. Magnesium concentrations were measured at different stages of enamel development. Mineral levels rose from ~30% per volume of tissue during the secretory stage to -60% in mature tissue. This is much lower than final mineral levels in enamel of other species. Enamel containing low mineral levels was adjacent to tall secretory ameloblasts which had reduced in height by -50% at a point corresponding to the beginning of the maturation stage. Magnesium concentrations remained relatively constant throughout the secretory stage, at 0.2% Mg by weight. These rose by 3-4 times in the enamel of the maturation stage. The low levels of mineralization in the mature porcine enamel did not appear to be due to enamel pathology, and the possibility of porcine teeth erupting in an immature, partially porous condition is discussed.
Reactivation of Ribonucleic Acid and Protein Synthesis During Germination of Blastocladiella Zoospores and the Role of the Ribosomal Nuclear Cap

Freshly harvested zoospores of Blastocladiella emersonii begin to germinate about 15 min after inoculation into a defined growth medium at a density of 106 zoospores per ml. Flagellum retraction accompanies encystment, and dispersal of the ribosomal nuclear cap takes place shortly thereafter. The primary rhizoid begins to emerge at 25 to 30 min and starts to branch at ca. 60 min. The first nuclear division occurs between 120 and 190 min. The dry weight per cell increases linearly after 60 min, whereas the deoxyribonucleic acid per cell doubles between 120 and 240 min. A linear increase in total ribonucleic acid (RNA) is detectable beginning at 40 to 45 min, and in total protein beginning at 80 min; neither process is interrupted during nuclear division. Encystment and nuclear cap disorganization are associated with a sharp rise in the rates of precursor incorporation into RNA and protein. Cycloheximide at 20 μg/ml prevents leucine incorporation at all stages and inhibits development beyond the earliest encystment stage. Actinomycin D at 25 μg to 50 μg/ml prevents uracil incorporation, but it has no effect on leucine incorporation or development until 40 to 45 min. At the latter stage, actinomycin D causes a sharp developmental arrest and begins to inhibit leucine incorporation. It is concluded that early protein synthesis must occur on the ribosomes formed during the prior growth phase and conserved through the zoospore stage in the nuclear cap. The results further indicate that this synthesis is dependent upon messenger RNA already present in the zoospore before germination.
Comparative Analysis of Retroviral and Native Promoters Driving Expression of β1,3-Galactosyltransferase β3Gal-T5 in Human and Mouse Tissues*

β1,3-Galactosyltransferase β3Gal-T5 is highly expressed in the colons of humans and certain primates due to a retroviral long terminal repeat (LTR) acting as a strong promoter. Because this promoter is inactive in other human tissues or mice, we attempted to understand how adoption of a retrotransposon allowed the gene to acquire tissue-specific expression. We identified three novel 5′-UTRs of β3Gal-T5 mRNA, types A, B, and C, and found widespread expression of the type A transcript at much lower levels than the LTR transcript, the expression of which is restricted to organs of the gastrointestinal tract. Expression of the type C 5′-UTR transcript was mostly restricted to the ileum, where it was expressed at high levels. We cloned the 5′-flanking regions of both types A and B 5′-UTRs, found deletion constructs functionally active as promoters, and identified CCAAT-binding factor (CBF) and hepatocyte nuclear factor 1 (HNF-1) as the principal nuclear factors controlling the promoters of types A and B 5′-UTR transcripts, respectively. The CCAAT-binding factor binding site and the entire downstream sequence driving the expression of type A transcripts in humans are structurally and functionally conserved in mice, where they constitute a uniqueβ3Gal-T5 promoter that appears to be the ancestral promoter of the gene. The HNF-1 binding motif of the second human promoter is identical to the HNF-1/Cdx binding motif of the LTR promoter but is in the antisense orientation, resulting in much lower binding affinity and promoter strength. These data may explain the successful insertion of the transposon during evolution.
Possible role of template-based lymphadenectomy in reducing the risk of regional node recurrence after nephroureterectomy in patients with renal pelvic cancer.

OBJECTIVE It remains unclear whether lymphadenectomy alters regional node recurrence after nephroureterectomy in patients with urothelial carcinoma of the renal pelvis. The predictive factors for regional node recurrence are still unclear. In this study, we retrospectively examined how the extent of lymphadenectomy influences regional node recurrence in patients with urothelial carcinoma of the renal pelvis. METHODS From January 1988 through July 2013, we performed nephroureterectomy in 180 patients with non-metastatic (cN0M0) urothelial carcinoma of the renal pelvis at two Japanese institutes. Regional nodes were determined according to our previous mapping study: complete lymphadenectomy designates that all regional sites were dissected; incomplete lymphadenectomy that all sites were not dissected. A third group included those without lymphadenectomy. RESULTS The 5-year cancer-specific and recurrence-free survival was significantly higher in the complete lymphadenectomy group than in the incomplete lymphadenectomy or without lymphadenectomy groups (P = 0.03). The incidence of regional node recurrence was significantly lower in the complete lymphadenectomy group at 2.9% (2/67) than in the incomplete lymphadenectomy at 18.1% (4/22) or without lymphadenectomy at 10.9% (10/91) groups (P = 0.03). In patients with incomplete lymphadenectomy, 75% of regional node recurrence occurred outside of the dissected sites. Complete lymphadenectomy is shown to be a likely predictive factor of reduced risk of recurrence at the regional nodes by multivariate analysis, after adjusting for patient age, pathological T stage, and pathological nodal metastases. CONCLUSIONS This study shows that template-based lymphadenectomy reduced the risk of regional node recurrence in patients with urothelial carcinoma of the renal pelvis and appears to result in improved survival.
Sickle cell disease: the Lebanese experience

Sickle cell disease (SCD), the commonest single gene disorder worldwide, is an inherited disease that has different clinical and hematological manifestations in different populations. The objective of this study is to describe the characteristics of the Lebanese SCD population. This was a retrospective study that included information on 387 patients with either sickle cell anemia (SS) or sickle beta‐thalassemia (ST). The mean (±SD) age was 17.9 years (±12.5), and the mean (±SD) follow‐up was 9.3 ± 6.9 years. Fifty percent of the patients were males and SS/ST distribution was 3 : 1. The disease was clustered in two geographic areas in North and South Lebanon. Nearly, all patients were Muslims and 56% were the offspring of consanguineous parents. The prevalence of splenomegaly beyond 6 years of age among SS patients was 28.9%. The prevalence rates of stroke, leg ulcers and priapism were 4.1%, 1.4%, and 0.8%, respectively. Comparing the SS and the ST patients, there were no statistically significant differences in the prevalence of all clinical manifestations except for splenomegaly (SS: 28.9%, ST: 54.9%, P‐value < 0.001) and splenectomy (SS: 16.1%, ST: 35.7%, P‐value < 0.001). In contrast to Northern American populations and similar to some Mediterranean populations, Lebanese SCD patients have a higher prevalence of persistent splenomegaly. The relatively low incidence of thrombotic complications deserves further investigation. The study’s limitations include those of any other retrospective study and the fact that not all Lebanese centers caring for inherited hemoglobin disorders were included. However, the results of this first large scale national survey indicate that preventive efforts should target the Northern and Southern regions of Lebanon to decrease the number of new off springs afflicted with this disease similar to what has been successfully achieved with Thalassemia, another hemoglobinopathy that is highly prevalent in the country.
Evidence for tissue factor phosphorylation and its correlation with protease‐activated receptor expression and the prognosis of primary breast cancer

Tissue factor (TF)‐mediated protease‐activated receptor (PAR)‐2 signaling is associated with a promigratory, invasive and proangiogenic phenotype in experimental models of breast cancer and has been mechanistically coupled to phosphorylation of the TF cytoplasmic domain (pTF). However, the clinical relevance of these findings is unknown. Here, we provide the first in vivo evidence of TF phosphorylation in experimental as well as clinical breast cancer tumors. pTF was demonstrated in MDA‐MB‐231 xenografts and in tumors from the MMTV‐PyMT transgene model of spontaneous murine breast adenocarcinoma. Tumors from PAR‐2–deficient transgenic mice were negative for pTF, thus linking pTF to PAR‐2 signaling. The clinical correlation between TF, pTF, PAR‐1, PAR‐2 and vascular endothelial growth factor (VEGF)‐A was determined by immunohistochemistry on tumors from a cohort of 172 consecutive primary breast cancer patients, with a median follow‐up time of 50 months. In 160 evaluable patient tumors, pTF was associated with TF (p = 0.01) and cancer cell expression of PAR‐1 (p = 0.001), PAR‐2 (p = 0.014) and VEGF‐A (p = 0.003) using χ2 test. PAR‐2 and VEGF‐A were coexpressed (p = 0.013) and associated with a more aggressive phenotype. Interestingly, all patients experiencing recurrences had tumors expressing pTF and PAR‐2, and pTF alone as well as coexpression of pTF and PAR‐2 were significantly correlated with shorter recurrence‐free survival (log rank test, p = 0.04 and p = 0.02, respectively). This study provides the first evidence to link PAR‐2 expression and TF phosphorylation to clinical data in human breast cancer. In conjunction with experimental tumor models, these data support an important role of TF‐PAR‐2 signaling in breast cancer recurrence.
The relationship between birth weight and blood pressure amplifies from childhood to adulthood.

OBJECTIVE To investigate relationships between birth characteristics and blood pressure at age 20 years and to assess whether effects of birth weight on blood pressure are amplified from childhood to adulthood. DESIGN A longitudinal study of 584 men and women from Adelaide, Australia, examined previously at 8 years and followed up at age 20 years. RESULTS Birth weight was negatively associated with systolic pressure at age 20 years in men (regression coefficient 2.6 mmHg per kg; 95% confidence interval 0.7, 4.4) and women (regression coefficient 4.6 mmHg per kg; 95% confidence interval 2.9, 6.4), after adjustment for current weight There was an interaction with current size (P = 0.05 for men and P = 0.09 for women), such that effects were enhanced among individuals with relatively high weight or weight for height. Shortness at birth, thinness at birth, and low birth weight relative to placental weight were also associated with elevated systolic pressure at age 20 years. Effects of birth weight on blood pressure were stronger at age 20 than at age 8 years (P < 0.01 for men and P = 0.03 for women). This was not due simply to increased variability of blood pressure in adulthood. There were greater rises in blood pressure with age among individuals of relatively low birth weight. CONCLUSIONS These findings are further evidence that poor fetal growth is associated with elevated blood pressure in later life. The results support the hypothesis that the relationship is amplified with increasing age.
Retinal Vessel Caliber, Choroidal Thickness and Ocular Pulse Amplitude Measurements in Essential Thrombocythemia

Purpose: The choroid and retina receive most of the blood that enter to the eye, and this uptake may be affected by essential thrombocythemia (ET) in which thrombosis and hemorrhage is common. This study compares choroidal thickness, retinal vascular caliber, and ocular pulse amplitude (OPA) measurements between patients with ET and healthy adults. Materials and Methods: Thirty.seven patients with ET and 37 age.sex. matched healthy adults were recruited in this cross.sectional and comparative study. Spectral.domain optical coherence tomography was used to measure the subfoveal choroidal thickness. (SFCT) and retinal vascular caliber measurements. The Pascal dynamic contour tonometer was used for OPA and intraocular pressure. (IOP) measurements. The independent samples t.test was used for comparison of measurements between the groups. Pearson's correlation coefficient analysis was used to detect correlations between the variables. A P< 0.05 was statistically significant. Results: SFCT, OPA, and IOP measurements were not statistically significant differences between the study group and the control group (P > 0.05, all comparisons). Blood platelet counts were not associated with choroidal thickness, OPA, and IOP (P > 0.05). Retinal arteriolar and venular calibers were statistically, significantly thicker in healthy controls when compared to the study group (P < 0.05). Conclusions: Our results indicate that choroidal thickness and pulsatile blood flow are not significantly affected in ET and under high blood platelet counts. Retinal arteriolar and venular calibers are thinner in ET when compared to age.sex matched healthy controls.