Stratification of rheumatoid arthritis cohort using Ayurveda based deep phenotyping approach identifies novel genes in a GWAS.

BACKGROUND AND AIM: Genome wide association studies have scaled up both in terms of sample size and range of complex disorders investigated, but these have explained relatively little phenotypic variance. Of the several reasons, phenotypic heterogeneity seems to be a likely contributor for missing out genetic associations of large effects. Ayurveda, the traditional Indian system of medicine is one such tool which adopts a holistic deep phenotyping approach and classifies individuals based on their body constitution/prakriti. We hypothesized that Ayurveda based phenotypic stratification of healthy and diseased individuals will allow us to achieve much desired homogeneous cohorts which would facilitate detection of genetic association of large effects. In this proof of concept study, we performed a genome wide association testing of clinically diagnosed rheumatoid arthritis patients and healthy controls, who were re-phenotyped into Vata, Pitta and Kapha predominant prakriti sub-groups. EXPERIMENTAL PROCEDURE: Genotypes of rheumatoid arthritis cases (Vata = 49; Pitta = 117; Kapha = 78) and controls (Vata = 33; Pitta = 175; Kapha = 85) were retrieved from the total genotype data, used in a recent genome-wide association study performed in our laboratory. A total of 528461 SNPs were included after quality control. Prakriti-wise genome-wide association analysis was employed. RESULTS AND CONCLUSION: This study identified (i) prakriti-specific novel disease risk genes of high effect sizes; (ii) putative candidates of novel therapeutic potential; and (iii) a good correlation between genetic findings and clinical knowledge in Ayurveda. Adopting Ayurveda based deep phenotyping may facilitate explaining hitherto undiscovered heritability in complex traits and may propel much needed progress in personalized medicine.

Protocol for Outcome Evaluation of Ayahuasca-Assisted Addiction Treatment: The Case of Takiwasi Center.

The present study describes the protocol for the Ayahuasca Treatment Outcome Project (ATOP) with a special focus on the evaluation of addiction treatment services provided through Takiwasi Center, the first ATOP study site. The goal of the project is to assess treatment outcomes and understand the therapeutic mechanisms of an Ayahuasca-assisted, integrative treatment model for addiction rehabilitation in the Peruvian Amazon. The proposed intervention protocol highlights the significance of treatment setting in the design, delivery, and efficacy of an addiction rehabilitation program that involves the potent psychedelic tea known as Ayahuasca. After describing the context of the study, we put forth details about our mixed-methods approach to data collection and analysis, with which we seek to gain an understanding of why, how, and for whom this specific ayahuasca-assisted treatment program is effective across a range of outcomes. The ATOP protocol employs qualitative research methods as a means to determine which aspects of the setting are meaningful to clients and practitioners, and how this may correlate with outcome measures. This paper delineates the core principles, methods, and measures of the overall ATOP umbrella, then discusses the role of ATOP in the context of the literature on long-term residential programs. To conclude, we discuss the strengths and limitations of the protocol and the intended future of the project.

Environmental consequences of wheat-based crop rotation in potato farming systems in galicia, Spain.

Intensive agricultural farming systems have negative impacts on the ecosystem. Therefore, the use of crop rotation emerges as an opportunity to improve the environmental sustainability of agricultural systems. In the region of Galicia in north-western Spain, potato and wheat are important commodities and essential foods in the diet. Hence, it is interesting to investigate the environmental profile of these crops to improve the understanding of local agrosystems. This study evaluated three agricultural crops managed under a crop rotation system and following a conventional arable farming: the main rotation crop, which is the potato in the first year (cP), followed by a second year of commercial wheat (cW) and autochthonous Galician wheat (GcW) in the third year. The Life Cycle Assessment (LCA) methodology was performed using four types of functional units: in terms of productivity (kg-1); land management (ha-1∙year-1); a financial function (euros €-1 of income from sales) and energetic value (MJ-1). The environmental indicators selected are Climate Change (CC), Particulate Matter (PM), Terrestrial Acidification (TA), Freshwater Eutrophication (FE), Marine Eutrophication (ME), Human Toxicity (HT), Land Use (LU) and Fossil Depletion (FD). The figures show that the GcW has the lowest environmental impact when the functional units refer to land management, financial function and energetic value. However, if analysed in terms of productivity, cP is presented as the best crop due to its comparatively higher yield, reaching a production ratio 10 times higher than wheat. In the specific case of wheat, compared to a previous study in the same region, the environmental impacts are lower when grown in a crop rotation system in contrast to monoculture. This article demonstrates the relevance of using LCA for diverse stakeholders (e.g., farmers, consumers and researchers) to understand the environmental impacts of regional agricultural systems. In addition, it serves as a basis for future work aimed at comparing rotational agricultural systems in this region, integrating economic and social aspects.

Contribution of phosphorus and PTH to the development of cardiac hypertrophy and fibrosis in an experimental model of chronic renal failure.

BACKGROUND AND OBJECTIVE: Adequate serum phosphorus levels in patients with chronic kidney disease is essential for their clinical management. However, the control of hyperphosphatemia is difficult because is normally associated with increases in serum PTH. In the present study, the effects of hyperphosphatemia, in the presence of elevated and normal PTH, on cardiac inflammation, hypertrophy and fibrosis in an experimental renal failure model were analyzed. MATERIALS AND METHODS: 4 groups of rats were formed. Two groups underwent total parathyroidectomy (PTx). Rats with Ca <7.5 mg/dL and PTH < 50 pg/mL underwent 7/8 nephrectomy (CRF) and a subcutaneous pellet was placed that releases PTH 1-34 (5 µg/kg/day). One group received a diet with normal P (NP) (CRF + PTx + rPTH + NP group) and another with a high P diet (0.9% - HP) (CRF + PTx + rPTH + HP group). Other 2 groups that only had CRF received NP (CRF + NP) and HP (CRF + HP) diet. A SHAM group for nephrectomy and parathyroidectomy was also added. After 14 weeks the rats were sacrificed. RESULTS: The groups with a diet high in phosphorus (CRF + H A and CRF + PTx + rPTH + HP) had a significant reduction in creatinine clearance and also in body weight with an increase in serum phosphorus regardless of parathyroidectomy, but not serum levels of calcium, FGF23 and calcitriol that were 2-3 times higher in the group with secondary hyperparathyroidism (CRF + HP). The diameter of the cardiomyocytes was greater in the CRF + HP group, while parathyroidectomy (CRF + PTx + rPTH + HP) significantly reduced them, despite the high and similar serum phosphorus values. TNF-α, Adam17 and cardiac fibrosis at the histological and molecular level showed a similar pattern with increases in the group with severe secondary hyperparathyroidism (CRF + HP). CONCLUSIONS: Hyperphosphatemia confirmed its importance in the genesis of secondary hyperparathyroidism, but also of kidney damage that was independent of PTH levels. However, inflammation, fibrosis, and cardiomyocyte growth were more closely related to PTH levels, since in the presence of similar severe hyperphosphatemia, parathyroidectomy reduced the values ​​of inflammatory parameters, cardiac hypertrophy, and fibrosis.

Long-Term Weight Loss Results, Remission of Comorbidities and Nutritional Deficiencies of Sleeve Gastrectomy (SG), Roux-En-Y Gastric Bypass (RYGB) and One-Anastomosis Gastric Bypass (OAGB) on Type 2 Diabetic (T2D) Patients.

This study aimed to compare the long-term weight loss results, remission of comorbidities and nutritional deficiencies of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) and One-Anastomosis gastric bypass (OAGB) on type 2 diabetic (T2D) patients. PATIENTS AND METHODS: A retrospective analysis of all the morbidly obese and diabetic patients undergoing SG, RYGB, and OAGB as primary bariatric procedures between February 2010 and June 2015 was performed. Anthropometric parameters, remission of comorbidities, nutritional deficiencies and supplementation requirements at 1, 2 and 5 years' follow-up were monitored. Patients lost to follow-up 5 years after surgery were excluded from the analysis. RESULTS: 358 patients were included. The follow-up rate was 84.8%. Finally, 83 SG, 152 RYGB, and 123 OAGB patients were included in the analysis. OAGB obtained significantly greater weight loss and remission of dyslipidemia than the other techniques. There was a trend towards greater T2D and hypertension remission rate after OAGB, while fasting glucose and glycated hemoglobin levels were significantly lower after OAGB. There were no significant differences in hemoglobin or protein levels between groups. SG obtained lower iron deficiencies than the other techniques, while there were no significant differences in other nutritional deficiencies between groups. CONCLUSION: OAGB obtained greater weight loss and remission of dyslipidemia than RYGB or SG. Excluding lower iron deficiency rates after SG, there were no significant differences in the development of nutritional deficiencies between groups.

Regular insulin added to total parenteral nutrition vs subcutaneous glargine in non-critically ill diabetic inpatients, a multicenter randomized clinical trial: INSUPAR trial.

BACKGROUND: There is no established insulin regimen in T2DM patients receiving parenteral nutrition. AIMS: To compare the effectiveness (metabolic control) and safety of two insulin regimens in patients with diabetes receiving TPN. DESIGN: Prospective, open-label, multicenter, clinical trial on adult inpatients with type 2 diabetes on a non-critical setting with indication for TPN. Patients were randomized on one of these two regimens: 100% of RI on TPN or 50% of Regular insulin added to TPN bag and 50% subcutaneous GI. Data were analyzed according to intention-to-treat principle. RESULTS: 81 patients were on RI and 80 on GI. No differences were observed in neither average total daily dose of insulin, programmed or correction, nor in capillary mean blood glucose during TPN infusion (165.3 ± 35.4 in RI vs 172.5 ± 43.6 mg/dL in GI; p = 0.25). Mean capillary glucose was significantly lower in the GI group within two days after TPN interruption (160.3 ± 45.1 in RI vs 141.7 ± 43.8 mg/dL in GI; p = 0.024). The percentage of capillary glucose above 180 mg/dL was similar in both groups. The rate of capillary glucose ≤70 mg/dL, the number of hypoglycemic episodes per 100 days of TPN, and the percentage of patients with non-severe hypoglycemia were significantly higher on GI group. No severe hypoglycemia was detected. No differences were observed in length of stay, infectious complications, or hospital mortality. CONCLUSION: Effectiveness of both regimens was similar. GI group achieved better metabolic control after TPN interruption but non-severe hypoglycemia rate was higher in the GI group. CLINICAL TRIAL REGISTRY: This trial is registered at clinicaltrials.gov as NCT02706119.

Metachronous Signet Ring Cell Bladder Metastasis as First Sing of Cancer Recurrence.

We describe the case of a 74-year-old woman with previous history of gastric signet cell carcinoma who develops bladder metastasis as first sign of recurrence 6 years later. Bladder metastasis due to signet cell carcinoma is extremely rare with only 19 cases reported. Treatment includes radical cystectomy or chemotherapy.

Efecto terapéutico homeopático en la giardiasis de la edad pediátrica / Homeopathic therapeutic effect in giardiasis of pediatric age

Introducción: la giardiasis es causa frecuente de enfermedad diarreica aguda en menores de cinco años y de dolor abdominal recurrente en el niño mayor. Inicialmente se tratada con mercuriales, productos arsenicales y bismuto. En la actualidad se cuenta con numerosas alternativas terapéuticas.Objetivo: evaluar el efecto terapéutico del tratamiento homeopático en la giardiasis.Método: se realizó un ensayo clínico fase IV, controlado y aleatorizado, con enfermos de edad pediátrica diagnosticados en el Hospital General Provincial Docente de Ciego de Ávila en el trienio 2014-2016. Se constituyeron dos grupos de tratamiento: control, tratado con secnidazol, y experimental, tratado con giardinum 30 CH (tratamiento homeopático). Se realizó seguimiento de la evolución, clínica y de laboratorio, de forma prospectiva a los 15 días, al mes, dos y tres meses.Resultados: el grupo de edades de mayor incidencia fue entre uno y cinco años (42,22 por ciento), el síntoma principal en ambos grupos fue el dolor abdominal: 52,22 por ciento en el control y 40,00 por ciento en el experimental. Luego de 15 días el efecto terapéutico favorable fue superior en el grupo experimental (51,11 por ciento), respecto al control (34,44 por ciento), con significación estadística (p=0,04), sin embargo, el resultado no fue igual a los 30 días, dos y tres meses.Conclusiones: el tratamiento homeopático con giardinum 30 CH fue efectivo desde el punto de vista clínico al reducir el tiempo de resolución de los síntomas y signos, y la negativización de quistes o trofozoítos en las heces fecales a los 15 días del tratamiento(AU)

Introduction: giardiasis is a frequent cause of acute diarrheal disease in children under five years of age and recurrent abdominal pain in the older child. Initially it was treated with mercurials, arsenical products and bismuth. Currently there are numerous therapeutic alternatives.Objective: to evaluate the therapeutic effect of homeopathic treatment in giardiasis.Method: a phase IV clinical trial, controlled and randomized, was carried out with pediatric patients diagnosed in the General Provincial Teaching Hospital of Ciego de Ávila in the triennium 2014-2016. Two treatment groups were established: control, treated with secnidazole, and experimental, treated with giardinum 30 CH (homeopathic treatment). Clinical and laboratory evolution were carried out prospectively at 15 days, a month, two and three months later.Results: the age group with the highest incidence was between one and five years (42,22 percent), the main symptom in both groups was abdominal pain, 52,22 percent in the control group and 40,00 percent in the experimental group. After 15 days the favorable therapeutic effect was higher in the experimental group (51,11 percent), compared to the control group (34,44 percent), with statistical significance (p=0,04), however, the result was not the same after 30 days, two and three months.Conclusions: the homeopathic treatment with giardinum 30 CH was effective from the clinical point of view, reducing the time of resolution of the symptoms and signs, and the negativization of cysts or trophozoites in the feces 15 days after the treatment, being shown statistically(AU)

Self-treatment with herbal products for weight-loss among overweight and obese subjects from central Mexico.

ETHNOPHARMACOLOGICAL RELEVANCE: Mexico ranks second in the world for obesity prevalence. In Mexico, obese and overweight subjects commonly seek alternative treatments for weight-loss, including the use of herbal products. AIM OF THE STUDY: The main objective of this study was to evaluate the prevalence of self-medication with herbal products for weight-loss among overweight and obese subjects residing in four states (Guanajuato, San Luis Potosi, State of Mexico, and Mexico City) from central Mexico. In addition, the factors related to self-medication among patients were studied. MATERIALS AND METHODS: A total of 1404 overweight and obese subjects were interviewed. A chi-square test examined associations between socio-demographic and socio-economic information, and self-medication with herbal products for weight-loss. RESULTS: The prevalence of self-medication was 42.9% among the participants who used herbal products for weight-loss. The female gender was the strongest factor (OR: 2.20 (1.75-2.77) associated with self-medication for weight-loss, followed by a low educational level (elementary and middle school) [OR: 1.80 (1.31-2.44)], and a middle-socioeconomic status [OR: 1.75 (1.21-2.52)]. The main herbal products used for weight-loss were based on: i) green tea, Camellia sinensis (12.7% of frequency), ii) aceitilla, Bidens odorata (6.6%), and iii) soybean, Glycine max (5.3%). In addition, 65% of the respondents considered herbal products ineffective for weight-loss after 6 months of use. CONCLUSION: Due to the high incidence of overweight and obesity in Mexico, there is a high prevalence (42.9%) of self-medication using natural products for weight-loss, particularly in women from Central Mexico. This study indicates the important need to educate patients about the harmful effects of consuming these products.

Ventromedial medulla inhibitory neuron inactivation induces REM sleep without atonia and REM sleep behavior disorder.

Despite decades of research, there is a persistent debate regarding the localization of GABA/glycine neurons responsible for hyperpolarizing somatic motoneurons during paradoxical (or REM) sleep (PS), resulting in the loss of muscle tone during this sleep state. Combining complementary neuroanatomical approaches in rats, we first show that these inhibitory neurons are localized within the ventromedial medulla (vmM) rather than within the spinal cord. We then demonstrate their functional role in PS expression through local injections of adeno-associated virus carrying specific short-hairpin RNA in order to chronically impair inhibitory neurotransmission from vmM. After such selective genetic inactivation, rats display PS without atonia associated with abnormal and violent motor activity, concomitant with a small reduction of daily PS quantity. These symptoms closely mimic human REM sleep behavior disorder (RBD), a prodromal parasomnia of synucleinopathies. Our findings demonstrate the crucial role of GABA/glycine inhibitory vmM neurons in muscle atonia during PS and highlight a candidate brain region that can be susceptible to α-synuclein-dependent degeneration in RBD patients.

Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts.

OBJECTIVES: To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. DESIGN: Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa. SETTING: Multiple institutions that were members of international PRACTICAL consortium. PARTICIPANTS: All consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men. MAIN OUTCOME MEASURES: Prediction with hazard score of age of onset of aggressive cancer in validation set. RESULTS: In the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10-16). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score. CONCLUSIONS: Polygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.

Hypophonia as a sign of thalamus lesion: a case report.

Hypophonia is a neurological sign usually seen after brainstem or peripheral damage, either at the recurrent laryngeal nerve or vocal cord level. However, it has been described as a sign of supratentorial strokes in a few studies, specifically when anterior and ventral thalamic involvement is reported. In addition, it is a prominent sign of other neurological disorders such as Parkinson disease and other extrapyramidal conditions. We describe a case of hypophonia secondary to a left thalamic hemorrhage, after a careful search of other potential causes of this deficit, and we discuss the underlying neuroanatomical circuits.

Life cycle assessment of gasoline production and use in Chile.

Gasoline is the second most consumed fuel in Chile, accounting for 34% of the total fuel consumption in transportation related activities in 2012. Chilean refineries process more than 97% of the total gasoline commercialized in the national market. When it comes to evaluating the environmental profile of a Chilean process or product, the analysis should consider the characteristics of the Chilean scenario for fuel production and use. Therefore, the identification of the environmental impacts of gasoline production turns to be very relevant for the determination of the associated environmental impacts. For this purpose, Life Cycle Assessment has been selected as a useful methodology to assess the ecological burdens derived from fuel-based systems. In this case study, five subsystems were considered under a "well-to-wheel" analysis: crude oil extraction, gasoline importation, refinery, gasoline storage and distribution/use. The distance of 1 km driven by a middle size passenger car was chosen as functional unit. Moreover, volume, economic and energy-based allocations were also considered in a further sensitivity analysis. According to the results, the main hotspots were the refining activities as well as the tailpipe emissions from car use. When detailing by impact category, climate change was mainly affected by the combustion emissions derived from the gasoline use and refining activities. Refinery was also remarkable in toxicity related categories due to heavy metals emissions. In ozone layer and mineral depletion, transport activities played an important role. Refinery was also predominant in photochemical oxidation and water depletion. In terms of terrestrial acidification and marine eutrophication, the combustion emissions from gasoline use accounted for large contributions. This study provides real inventory data for the Chilean case study and the environmental results give insight into their influence of the assessment of products and processes in the country. Moreover, they could be compared with production and distribution schemes in other regions.

New aspects in the pathophysiology of rapid eye movement sleep behavior disorder: the potential role of glutamate, gamma-aminobutyric acid, and glycine.

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by the occurrence of intense movements during rapid eye movement (REM) sleep, also named paradoxical sleep. The neuronal dysfunctions at the origin of the loss of atonia in RBD patients are not known. One possibility is that RBD is due to the degeneration of neurons inducing the muscle atonia of REM sleep. Therefore, in our paper we review data on the populations of neurons responsible for the atonia of REM sleep before discussing their potential role in RBD. We first review evidence that motoneurons are tonically hyperpolarized by gamma-aminobutyric acid (GABA) and glycine and phasically excited by glutamate during REM sleep. Then, we review data indicating that the atonia of REM sleep is induced by glycinergic/GABAergic REM-on premotoneurons contained within the raphe magnus and the ventral and alpha gigantocellular reticular nuclei localized in the ventral medullary reticular formation. These neurons are excited during REM sleep by a direct projection from glutamatergic REM-on neurons localized in the pontine sublaterodorsal tegmental nucleus (SLD). From these results, we discuss the possibility that RBD is due to a specific degeneration of descending REM-on glutamatergic neurons localized in the caudal SLD or that of the REM-on GABA/glycinergic premotoneurons localized in the ventral medullary reticular formation. We then propose that movements of RBD are induced by descending projections of cortical motor neurons before discussing possible modes of action of clonazepam and melatonin.

Does smoking influence Crohn's disease in the biologic era? The TABACROHN study.

BACKGROUND: While most studies have found a negative effect of smoking on Crohn's disease (CD) phenotype, more recent data have failed to reproduce this association, which might be due to a current wider use of thiopurines and biologic therapy. The TABACROHN study aimed at defining the impact of smoking on CD in the largest published series. METHODS: This multicenter cross-sectional study included 1170 CD patients. Patients were classified as nonsmokers, current smokers, or former smokers according to their present smoking status. Clinical data regarding disease characteristics, treatment, and complications were collected. RESULTS: Smokers were more frequently under maintenance treatment when compared to nonsmokers. In addition, current smokers presented higher use of biologic drugs compared to nonsmokers. Tobacco exposure and a higher tobacco load were independent predictors of need for maintenance treatment and stenosing phenotype, respectively. CONCLUSIONS: In the era of early and widespread use of immunosuppressants and biologics, tobacco exposure is an independent predictor of need for maintenance treatment, specifically biologic therapy. The wider use of biologics and immunosuppressants could account for the existence of no major differences in disease behavior and complications between nonsmokers and current smokers.

Effects of milk enriched with omega-3 fatty acid, oleic acid and folic acid in patients with metabolic syndrome.

BACKGROUND & AIMS: Patients with metabolic syndrome (MS) have increased cardiovascular risk factors. Dietary modifications mainly polyunsatturated fatty acids intake, can improve them. The present study was performed to assess the effects of enriched milk with omega-3 and oleic fatty acids, folic acid and vitamin E, in these patients. METHODS: We performed a randomized, placebo-controlled and open clinical trial, among 72 patients with MS for 3 months. Thirty-six of them consumed 500 cm(3) per day of semi-skimmed milk (control group), and the others consumed 500 cm(3) per day of enriched milk (test group). Daily supplements in this group were 5.7 g of oleic acid, 0.2g of omega-3 fatty acid, 150 microg of folic acid and 7.5mg of vitamin E. Serum for total and HDL cholesterol, triglycerol, Apo B, glucose, insulin, hs-CRP, homocysteine and fatty acids contents in serum phospholipids, was obtained at the beginning and at the end of the study. LDL cholesterol was calculated by Friedewald formula. RESULTS: Four patients in the test group, and two in the control group dropped out. In the test group a decrease in serum total cholesterol (-6.2%, P=0.006), LDL cholesterol (-7.5%, P=0.032), triglycerol (-13.3%, P=0.016), Apo B (-5.7%, P=0.036), glucose (-5.3%, P=0.013), and homocysteine (-9.5%, P=0.00) was observed. Any of these parameters changed in the control group. CONCLUSIONS: Dietary supplementation with 500 cm(3) of enriched milk with omega-3 fatty acid, oleic acid and folic acid, reduces serum tryglicerides, total and LDL cholesterol, Apo B, glucose and homocysteine in patients with MS. This milk is well tolerated and accepted by the patients.