Low-molecular-weight chitosan relieves enterotoxigenic Escherichia coli-induced growth retardation in weaned pigs.

The objective of the present study was to evaluate the effects of low-molecular-weight chitosan (LMWC) on the growth performance, immune responses and intestinal health of weaned pigs challenged by enterotoxigenic Escherichia coli (ETEC). A total of 32 weaned pigs were randomly allocated to four treatments: non-challenged (fed with basal diet), ETEC-challenged (fed with basal diet) and ETEC-challenged plus 50 or 100 mg/kg LMWC supplementation, respectively. After 11 days feeding, the non-challenged pigs were infused with sterilised Luria-Bertani culture, while the remaining pigs were infused with 2.6 × 1011 colony-forming units of ETEC. At 3 days post-challenge, all pigs were administered d-xylose at 0.1 g/kg body weight. One hour later, blood samples were obtained, and the pigs then euthanised to collect intestinal samples. Data showed that only 100 mg/kg LMWC supplementation attenuated (P < 0.05) the average daily gain reduction caused by ETEC. Furthermore, besides the decreased (P < 0.05) serum tumour necrosis factor-α and immunoglobulin (Ig) G concentrations detected in ETEC-challenged pigs supplemented with LMWC at 50 or 100 mg/kg, the higher dose (100 mg/kg) also decreased (P < 0.05) the serum IgM concentration and increased (P < 0.05) the villus height and villus height-to-crypt depth ratio in both the jejunum and ileum, and the sucrase activity in the ileal mucosa. Moreover, LMWC supplementation (50 or 100 mg/kg) in ETEC-challenged pigs elevated (P < 0.05) the mRNA levels of jejunal mucosal peptide transporter 1 and ileal mucosal peptide transporter 1, divalent metal transporter 1 and zinc transporter 1, and decreased (P < 0.05) the ileal and caecal E. coli abundances, while 100 mg/kg LMWC additionally elevated (P < 0.05) the ileal Bacillus abundance, and caecal and colonic Bifidobacterium abundances. These results suggest that LMWC helps alleviate ETEC-induced growth retardation in weaned pigs, which could be associated with the inhibition of the immune responses and improved intestinal health.

Abnormal glucose metabolism and galactose-deficient immunoglobulin A1 (IgA1) synthesis: a possible mechanism of IgA nephropathy.

BACKGROUND/AIMS: It is widely accepted that a possible etiopathogenic factor associated with IgA nephropathy is the glycosylation of IgA1 molecule O-glycans. The present study aimed to determine if galactose-deficient IgA1 is related to glucose metabolism. METHODS: IgA nephropathy was identified from the renal biopsies of 108 adult patients enrolled in our study with 60 healthy controls. The concentration of serum lactose, galactose, and lactase was measured. The relationship between glucose metabolism, proteinuria, and renal pathological changes was studied. RESULTS: The circulating lactose level was higher in IgAN patients compared to that in the healthy controls [143.9 (93.9-225.6) vs. 77.9 (54.9 - 209.6); p < 0.001]. The circulating lactase level was lower in IgAN patients than that in the healthy controls (229.9 ± 57.56 vs. 270.0 ± 69.30; p < 0.001). Serum galactose level of IgAN patients was lower than that of healthy controls but without significant differences. Lactose levels showed a significant positive correlation with 24-h proteinuria (r = 0.222; p = 0.021). CONCLUSION: The differences in lactose and lactase from the IgAN patients and healthy controls may be an indicator of the possible pathogenesis of IgAN. The level of serum lactose was correlated with the level of 24-h urinary protein during the same period, suggesting that it plays a role in IgA kidney disease progression. Future studies are required to validate our findings during the follow-up and investigate the underlying mechanisms.

Experience of combined use of a Bakri uterine balloon and a non-pneumatic anti-shock garment in a university hospital in Colombia.

OBJECTIVE: To compare the outcomes of women with postpartum hemorrhage (PPH) refractory to initial management and in a state of hypoperfusion between management with a non-pneumatic anti-shock garment (NASG) and Bakri balloon and management with other surgical interventions. METHODS: A retrospective observational descriptive study of women with PPH and hemorrhagic shock who were treated at a high complexity obstetric unit in Columbia between 2011 and 2017. Clinical records were reviewed and women were divided in two groups by clinical management. Group 1 women were managed with surgical interventions; group 2 women were managed with NASG plus a Bakri balloon. RESULTS: Overall, 142 women were treated for PPH, with 69 in group 1 and 73 in group 2). There were differences between group 1 and group 2 in the degree of hypovolemic shock (shock index: 1.1 vs 0.9, P=0.02), indicators associated with hypoperfusion (lactic acid, 2.9 vs 1.9 mmol/L, P=0.001), and frequency of transfusion of blood components (68% vs 44%, P<0.05). CONCLUSIONS: The joint use of NASG and Bakri balloon in PPH management seemed to improve hypoperfusion-related markers such as lactic acid and shock index, and reduce the frequency of additional blood transfusion.

Association between increased plasma levels of homocysteine and depression observed in individuals with primary lactose malabsorption.

BACKGROUND: Current literature proposes associations between homocysteine (HCY), folic acid (FA), vitamin B12 metabolism and depression. However, the exact underlying biological mechanisms remain unclear. This study aimed at evaluating a possible link between primary adult-type lactose malabsorption (PALM), HCY, FA and vitamin B12 metabolism and depressive disorder. METHODS: Plasma levels of HCY, FA and vitamin B12 were determined in 78 patients with PALM and 160 individuals with lactase persistence sub-grouped by the presence or absence of major depression. RESULTS: In 78 patients with PALM, the subgroup of 22 individuals with major depression showed significantly higher median (interquartile range) HCY (10.10 [8.46-12.03] vs. 8.9 [7.54-9.86] µmol/L, p = 0.029) and lower plasma FA levels (5.7 [4.68-9.14] vs. 6.95 [5.24-10.56] µmol/L, p = 0.272) compared to the subgroup of 56 individuals without depression, respectively. No such associations could be observed for those 160 individuals without PALM (i.e., lactase persistence) Plasma HCY levels were positively correlated with depressive symptoms (p = 0.052), and showed negative correlations with FA (p = < 0.001) and vitamin B12 (p = 0.029), respectively. CONCLUSION: Depressed individuals with PALM were found with significantly higher HCY and lower FA levels compared to non-depressed individuals with PALM, however, this association was absent in the subgroup of lactase persistent individuals. These findings suggest an association between increased HCY levels, lactose malabsorption and depression.

Functional Status Change Among Children With Extracorporeal Membrane Oxygenation to Support Cardiopulmonary Resuscitation in a Pediatric Cardiac ICU: A Single Institution Report.

OBJECTIVES: The purpose of this study is to describe the functional status of survivors from extracorporeal cardiopulmonary resuscitation instituted during in-hospital cardiac arrest using the Functional Status Scale. We aimed to determine risk factors leading to the development of new morbidity and unfavorable functional outcomes. DESIGN: This was a single-center retrospective chart review abstracting patient characteristics/demographic data, duration of cardiopulmonary resuscitation, duration of extracorporeal membrane oxygenation support, as well as maximum lactate levels within 2 hours before and after extracorporeal cardiopulmonary resuscitation. Cardiac arrest was defined as the administration of chest compressions for a nonperfusing cardiac rhythm. Extracorporeal cardiopulmonary resuscitation was defined by instituting extracorporeal membrane oxygenation during active chest compressions. Functional Status Scale scores were calculated at admission and on hospital discharge for patients who survived. SETTING: Patients admitted in the pediatric cardiac ICU at C.S. Mott Children's Hospital from January 1, 2005, to December 31, 2015. PATIENTS: Children less than 18 years who underwent extracorporeal cardiopulmonary resuscitation. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Of 608 extracorporeal membrane oxygenation events during the study period, 80 were extracorporeal cardiopulmonary resuscitation (14%). There were 40 female patients (50%). Median age was 40 days (interquartile range, 9-342 d). Survival to hospital discharge was 48% (38/80). Median Functional Status Scale score at admission was 6 (interquartile range, 6-6) and at hospital discharge 9 (interquartile range, 8-11). Out of 38 survivors, 19 (50%) had a change of Functional Status Scale score greater than or equal to 3, that is consistent with new morbidity, and 26 (68%) had favorable functional outcomes with a change in Functional Status Scale score of less than 5. CONCLUSIONS: This is the first extracorporeal cardiopulmonary resuscitation report to examine changes in Functional Status Scale from admission (baseline) to discharge as a measure of overall functional outcome. Half of surviving patients (19/38) had new morbidity, while 68% (26/38) had favorable outcomes. Lactate levels, duration of cardiopulmonary resuscitation, and duration of extracorporeal membrane oxygenation were not found to be risk factors for the development of new morbidity and poor functional outcomes. Functional Status Scale may be used as a metric to monitor improvement of extracorporeal cardiopulmonary resuscitation outcomes and help guide research initiatives to decrease morbidity in this patient population.

Lactase persistence, milk intake, hip fracture and bone mineral density: a study of 97 811 Danish individuals and a meta-analysis.

BACKGROUND: Whether a causal relationship exists between milk intake and reduced risk of fractures is unclear. OBJECTIVES: We tested the hypothesis that genetically determined milk intake reduces the risk of fractures and increases bone mineral density (BMD). METHODS: We investigated the association between milk intake, LCT-13910 C/T (rs4988235), which is associated with lactase persistence (TT/TC) in Northern Europeans, and hip fractures in three Danish prospective studies (N = 97 811, age ≥20 years). We added meta-analyses of LCT-13910 and fractures and BMD from five published Northern European population studies. RESULTS: In the Danish studies, the adjusted hazard ratio (HR) for hip fracture per one glass per week higher milk intake was 1.00 (95% CI: 0.99-1.01). The per T-allele milk intake was 0.58 (0.49-0.68) glasses per week, but HR was 1.01 (0.94-1.09) for hip fracture. In meta-analyses of Danish studies with published Northern European population studies, the random effects odds ratio for any fracture was 0.86 (0.61-1.21; I2 = 73%) for TT vs. CC and 0.90 (0.68-1.21; I2 = 63%) for TC vs. CC. The standardized mean difference in femoral neck BMD was 0.10 (0.02-0.18; I2 = 0%) g cm-2 for TT vs. CC and 0.06 (-0.04 to 0.17; I2 = 17%) g cm-2 for TC vs. CC. There were no differences in lumbar spine or total hip BMD comparing TT or TC with CC. CONCLUSION: Genetically lifelong lactase persistence with high milk intake was not associated with hip fracture in Danish population-based cohorts. A meta-analysis combining Danish studies with published Northern European population studies also showed that lactase persistence was not associated with fracture risk. Genetic lactase persistence was associated with a higher femoral neck BMD, but not lumbar spine or total hip BMD.

A retrospective comparison of survivors and non-survivors of massive pulmonary embolism receiving veno-arterial extracorporeal membrane oxygenation support.

INTRODUCTION: While the optimal care of patients with massive pulmonary embolism (PE) is unclear, the general goal of therapy is to rapidly correct the physiologic derangements propagated by obstructive clot. Extracorporeal membrane oxygenation (ECMO) in this setting is promising, however the paucity of data limits its routine use. Our institution expanded the role of ECMO as an advanced therapy option in the initial management of massive PE. The purpose of this project was to evaluate ECMO-treated patients with massive PE at an academic medical center and report shortterm mortality outcomes. METHODS: Thirty-two patients placed on ECMO for confirmed, massive PE from January 2012 to December 2015 were retrospectively analyzed. All patients had PE confirmed by computerized tomography and/or invasive pulmonary angiography. RESULTS: In our population of patients managed with ECMO, 21 (65.6%) patients survived to decannulation and 17 (53.1%) survived index hospitalization. Baseline characteristics and clinical variables showed no difference in age, gender, right ventricular-to-left ventricular ratios, or peak troponin-T between survivors and non-survivors. Non-survivors tended to have a previous history of malignancy. Cardiac arrest prior to ECMO cannulation was associated with worse outcomes. All 5 patients who received concomitant systemic thrombolysis died, while 11 of 15 patients who received catheter-directed thrombolysis survived. A lactic acid level ≤6mmol/L had an 82.4% sensitivity and 84.6% specificity for predicting survival to discharge. CONCLUSION: The practical approach of utilizing ECMO for massive PE is to reserve it for those who would receive the greatest benefit. Patients with poor perfusion, for example from cardiac arrest, may gain less benefit from ECMO. Our findings indicate that a serum lactate >6mmol/L may be an indicator of worse prognosis. Finally, in our patient population, catheter-directed thrombolytics was effectively combined with ECMO.

Assessment of tryptophan metabolism and signs of depression in individuals with carbohydrate malabsorption.

This prospective cross-sectional study aimed to investigate the potential association between primary-adult lactose malabsorption, fructose malabsorption, tryptophan (TRP) metabolism and the presence of depressive signs. Overall 251 patients, who were referred for lactase gene C/T-13910 polymorphism genotyping and fructose hydrogen/methane breath testing, were included. All participants filled out the Beck Depression Inventory (BDI II). Serum concentrations of tryptophan (TRP), kynurenine (KYN), kynuric acid (KYNA), and TRP competing amino acids (leucine, isoleucine, valine, phenylalanine, tyrosine) were measured by high-pressure liquid-chromatography. Logistic regression analysis was performed with lactose malabsorption, fructose malabsorption and all potential biomarkers of TRP metabolism to assess the effect on signs of depression, defined as a BDI II score > 13. Primary-adult lactose malabsorption and fructose malabsorption was detected in 65 (25.90%) and 65 (25.90%) patients, respectively. Fructose malabsorption was significantly associated with BDI II score, whereas no such relationship was found for lactose malabsorption. Serum levels of TRP and TRP metabolites were no predictors of depression. The authors suggest to conduct further prospective longitudinal studies in order to get further insight of associations between carbohydrate malabsorption, biomarkers and mood disorders.

Demographic, lifestyle, and genetic determinants of circulating concentrations of 25-hydroxyvitamin D and vitamin D-binding protein in African American and European American women.

Background: Vitamin D may have anticancer activities. The high prevalence of vitamin D deficiency in African Americans (AAs) may be a contributing factor to the cancer health disparities between AAs and European Americans (EAs).Objectives: We compared concentrations of 25(OH)D and vitamin D-binding protein (VDBP) in AA and EA women and investigated determinants of the vitamin D-biomarker concentrations in both populations.Design: We used data and biospecimens from 909 AA and 847 EA healthy control subjects from the Carolina Breast Cancer Study (CBCS) and the Women's Circle of Health Study (WCHS) in the African American Breast Cancer Epidemiology and Risk Consortium. We measured plasma 25(OH)D and VDBP concentrations in all participants and genotyped 67 vitamin D-related genes in AA women only.Results: AA women had lower 25(OH)D concentrations than did EA women (mean ± SD: 14.2 ± 8.1 compared with 21.1 ± 11.5 ng/mL, respectively; P < 0.0001) but similar concentrations of VDBP (mean ± SD: 344 ± 133 compared with 336 ± 124 µg/mL, respectively; P = 0.25). With VDBP and other factors controlled for, the observed racial difference in 25(OH)D concentrations did not diminish. Relations of demographic and lifestyle factors with 25(OH)D were similar between AA and EA women. Although none of the genetic variants that have been identified in previous genome-wide association studies of 25(OH)D concentrations in EAs were significant (P > 0.05) in AAs, AA women who carried the allele of a functional single nucleotide polymorphism rs4988235, which has been previously associated with lactase expression and lactose tolerance, had higher dietary vitamin D intake and higher measured 25(OH)D concentrations.Conclusions: AA women have lower concentrations of total 25(OH)D than EA women do, but both groups have similar VDBP concentrations, suggesting that there are lower concentrations of free 25(OH)D in AAs. Although demographic and lifestyle determinants of 25(OH)D concentrations are similar between the 2 groups, genetic determinants may be ethnicity specific. Larger studies in AAs will be needed to fully elucidate the underlying determinants of low vitamin D concentrations in AA populations.

Assessment of vitamin D status and serum CrossLaps levels in adults with primary lactose malabsorption.

BACKGROUND/OBJECTIVES: Primary adult-type lactose malabsorption (PALM) is a widespread inherited autosomal recessive condition, which is considered to be associated with osteoporosis. This prospective study aimed at assessing the 25-hydroxy-vitamin D (25(OH)D) status and serum CrossLaps levels in individuals with PALM and normal controls. SUBJECTS/METHODS: All participants (n=210) underwent genotyping for the LCT C/T-13910 polymorphism, 25(OH)D and CrossLaps measurements and clinical examinations. In addition, the anthropometric data (that is, height, weight and body mass index) were determined. RESULTS: Fifty-five individuals with PALM (that is, LCT C/C-13910 homozygotes) showed lower 25(OH)D (mean: 24.95±10.04 vs 28.59±9.56 ng/ml, P=0.018) and higher CrossLaps serum levels (mean: 0.46±0.31 vs 0.43±0.49 ng/ml, P=0.251) compared with 155 normal controls (that is, LCT C/T-13910 hetero- or T/T-13910 homozygotes). Anthropometric data were similar between PALM probands and controls. CONCLUSIONS: Individuals with PALM were found to have lower 25(OH)D and higher CrossLaps serum levels compared with normal controls. In order to preserve life-long bone health, routine 25(OH)D and CrossLaps serum measurements should be performed in individuals with PALM.

Reliable analysis of the single nucleotide polymorphism of lactase persistence LPH(-13910) C/T from saliva derived DNA: validation of a standardized saliva collection system.

BACKGROUND: The purpose of this study was to investigate the applicability of the Greiner Saliva Collection System (SCS) to obtain human genomic DNA for the analysis of single nucleotide polymorphisms (SNP) in the clinical routine laboratory. METHODS: Saliva and EDTA-blood were collected pair-wise from 112 participants. DNA was prepared by two automated procedures (MagNA Pure LC or MagNa Pure compact) and analyzed by UV-spectrophotometry and real-time PCR. RESULTS: Mean saliva derived DNA concentration was 52.7 ng/µL ± 36.4 (1000 µL, MagNA Pure LC) and 9.2 ng/µL ± 5.6 (200 µL, MagNA Pure compact) with A260/A280 ratios of 1.9 ± 0.1 and 2.1 ± 0.3 for MagNA Pure LC and MagNA Pure compact, respectively. SNP analysis for caucasian adult type lactase persistence showed a 100% success rate from saliva derived DNA and as reference from blood derived DNA. Matching genotypes were obtained in each sample pair. CONCLUSIONS: Saliva obtained with the standardized SCS yielded sufficient amounts of DNA in high purity and was found to represent a suitable and reliable source of human DNA for SNP analysis in the clinical routine laboratory.

Lactase deficiency: a potential novel aetiological factor in chronic pruritus of unknown origin.

Chronic pruritus, which is associated with a wide variety of underlying diseases, represents a challenge in diagnostics and treatment in dermatology and general medicine. The cause of pruritus remains unknown in up to 45% of patients. In this study, 718 patients with chronic pruritus were analysed concerning lactase deficiency, demographic data, aetiology, duration and intensity of pruritus. A total of 154 patients were tested positive for lactase deficiency and 38.3% showed a significant anti-pruritic response to a lactose-free diet (minimum 4 weeks). The best results were observed in patients with pruritus of mixed or unknown origin (n = 91; 64% response). Age, sex, localization or duration had no significant influence on the anti-pruritic effect of a lactose-free diet. Lactase deficiency might be an independent causal factor in the elicitation of chronic pruritus. Thus, screening for lactase deficiency represents a rational step in the diagnostic work-up of chronic pruritus. In case of a positive test result, a lactose-free diet offers a low-cost, efficient and specific therapy in patients with chronic pruritus.

Associations between lactase persistence and the metabolic syndrome in a cross-sectional study in the Canary Islands.

BACKGROUND: The single nucleotide polymorphism (SNP) LCT -13910 C>T, associated with genetically determined phenotypes of lactase persistence (LP) or non-persistence (LNP), was studied in relation to the metabolic syndrome (MS). AIM OF THE STUDY: The aim was to determine if milk intake and MS are associated. We applied Mendelian randomization (MR). The SNP, LCT -13910 C>T, with the genotypes LP (TT/CT) and LNP (CC), was taken as a proxy for milk consumption. METHODS: A representative sample of adults belonging to the Canary Islands Nutrition Survey (ENCA) in Spain aged 18-75 years (n = 551) was genotyped for the LCT -13910 C>T polymorphism. We used the International Diabetes Federation (IDF) criteria to define MS. RESULTS: 60% of the population was LP and 40% LNP. One hundred seven LP subjects (35.0%) and 53 LNP subjects (25.6%) showed MS (chi (2) = 5.04, p = 0.025). LP subjects showed a significantly higher odds ratio (OR) for MS than LNP subjects computed for the whole population: both the crude OR (1.56; 95% CI 1.06-2.31) and adjusted OR for sex, age, daily energy intake, physical activity and educational level (1.57; 95% CI 1.02-2.43). Adjusted OR for women with LP was 1.93; 95% CI 1.06-3.52. CONCLUSIONS: The T allele of the SNP might constitute a nutrigenetic factor increasing the susceptibility of LP subjects, especially women, to develop MS in the Canary Islands.

Decay of heat acclimation during exercise in cold and exposure to cold environment.

Sixteen male students exercised for 14 days (1 h/day) in the heat for heat acclimation (HA). During deacclimation (DA) one group exercised in the cold (EXG, n=8) for 60 min/day (morning) and was exposed to the cold for another hour (afternoon) for 14 days. The other group was exposed to the cold (EPG, n=8) for 1 h each in the morning and afternoon (Ta: 18.0 degrees C, RH: 58%) over the same period. All returned to exercise in the heat for reacclimation (RA) for 10 days. Subjects were tested on days 1, 16, 21, 32, 36 and 44 on a bicycle ergometer for 60 min at 60% of VO(2max) in the heat (Ta: 31.1 degrees C, RH: 70%). Rectal temperature (T (re)) and heart rate (HR) at 40 min of exercise were used to determine the decay/gain of HA, which was calculated using the formula described by Pandolf et al. (Ergonomics, 20:399-408, 1977). After HA (day 16) T (re) and HR decreased significantly. During DA, EXG showed decay in T (re) of 24 and 35% and HR of 29 and 35% on days 21 and 32, respectively. For EPG the corresponding decay was of 2 and 9% for T (re) and 17 and 17% for HR. After 10 days of RA, EXG showed gains of 11% in T (re) and 12% in HR, while EPG showed gains of 47% in T (re) and 38% in HR. In conclusion, EXG had greater decay during DA and lower gains in RA compared to EPG. However, the differences between groups were significant only for T (re) after 4 days of DA.

A novel method for diagnosis of adult hypolactasia by genotyping of the -13910 C/T polymorphism with Pyrosequencing technology.

The lactose-loading test and other functional tests that have been the most widely used clinically in the diagnosis of adult hypolactasia up to now are labour intensive and costly, and suffer from low sensitivity as well as low specificity. In addition, lactose-loading tests may be painful to the patient. Here, a new genotyping method for the diagnosis of adult hypolactasia is described. The method utilizes Pyrosequencing technology, which gives the DNA sequence around the recently identified C/T polymorphic site in the MCM6 gene. Among the advantages compared to the other genotyping methods published are less staff hands-on time than for example RFLP analyses, and the avoidance of radioactivity, as in the originally described isotope-minisequencing. Most importantly, Pyrosequencing, which is a direct DNA sequencing technique, gives unambiguous genotyping results as well as some redundant sequence information beyond the SNP position, which serves as a valuable internal control, obtained for each sample.

The genetic variant of lactase persistence C (-13910) T as a risk factor for type I and II diabetes in the Finnish population.

OBJECTIVE: Lactase persistence (LP), the ability to maintain a high lactase activity throughout life, has been suggested to be a possible risk factor for diabetes. Recently, a single nucleotide polymorphism C (-13910) T, residing 14 kb from the 5' end of the lactase (LCT) gene was shown to be associated with LP. Here we have studied the relationship between C (13910) T polymorphism and diabetes in the Finnish population. PATIENTS AND DESIGN: In all, 1455 patients with type I and 615 with type II diabetes and 446 nondiabetic controls in the Finnish population were genotyped for the C (-13910) T polymorphism by PCR minisequencing. RESULTS: No differences were detected in the LP genotype frequencies (CT&TT) between diabetic and nondiabetic subjects. CONCLUSIONS: We conclude that the C (-13910) T polymorphism associated with lifelong LP is not a risk factor for type I or type II diabetes in the Finnish population.