The relative abundance of fecal bacterial species belonging to the Firmicutes and Bacteroidetes phyla is related to plasma levels of bile acids in young adults.

BACKGROUND: Gut bacteria play a crucial role in the metabolism of bile acids (BA). Whether an association exists between the fecal microbiota composition and circulating BA levels in humans is poorly understood. Here, we investigated the relationship between fecal microbiota diversity and composition with plasma levels of BA in young adults. METHODS: Fecal microbiota diversity/composition was analyzed with 16S rRNA sequencing in 80 young adults (74% women; 21.9 ± 2.2 years old). Plasma levels of BA were measured using liquid chromatography-tandem mass spectrometry. PERMANOVA and Spearman correlation analyses were used to investigate the association between fecal microbiota parameters and plasma levels of BA. RESULTS: Fecal microbiota beta (P = 0.025) and alpha diversity indexes of evenness (rho = 0.237, P = 0.033), Shannon (rho = 0.313, P = 0.004), and inverse Simpson (rho = 0.283, P = 0.010) were positively associated with plasma levels of the secondary BA glycolithocholic acid (GLCA). The relative abundance of genera belonging to the Firmicutes and Bacteroidetes phyla was positively correlated with plasma levels of GLCA (all rho ≥ 0.225, P ≤ 0.049). However, the relative abundance of species from Firmicutes and Bacteroidetes phyla were negatively correlated with plasma levels of primary and secondary BA (all rho ≤ - 0.220, P ≤ 0.045), except for the relative abundance of Bacteroides vulgatus, Alistipes onderdonkii, and Bacteroides xylanisolvens species (Bacteroidetes phylum) that were positively correlated with the plasma levels of GLCA. CONCLUSIONS: The relative abundance of specific fecal bacteria species is associated with plasma levels of BA in young adults. However, further investigations are required to validate whether the composition of the gut microbiota can regulate the plasma concentrations of BA in humans.

Intestinal stenosis developed after a complete response to chemotherapy in a patient with Crohn´s disease and lymphoma of the jejunum.

An increased risk of hematologic malignancies secondary to long-term immunomodulators and biologics has been described in patients with inflammatory bowel disease1. Here, we present a case of jejunal stricture after chemotherapy treatment in a patient with ileal Crohn´s disease (CD) and jejunal lymphoma. The patient was a 32-year-old male with ileal CD in remission presenting with abdominal pain and distension. Abdominal computed tomography (CT) showed a poorly defined mass in the proximal jejunum, and positron emission tomography (PET) - CT showed hypermetabolic activity at that level. An upper endoscopy evidenced an indurated, friable circumferential mass causing a significant reduction of the intestinal lumen. Histological and cytometry findings led to a diagnosis of large B cell lymphoma, for which the patient received standard treatment (R-CHOP and IPI), achieving complete response. Eight months later, the patient reported abdominal pain and distention. Abdominal CT showed a thickening of a short segment of the proximal jejunum. An upper endoscopy showed a punctiform stenosis, while multiple biopsies showed neither histological recurrence of lymphoma nor signs of IBD. The patient was diagnosed with a post-chemotherapy stricture and underwent progressive endoscopic balloon dilatation. He finally was scheduled for laparoscopic small bowel resection. An histological analysis of the surgical piece revealed a granulomatous reaction with multinucleated foreign body-like giant cells, without evidence of malignancy (recurrence of lymphoma) nor inflammatory infiltrate suggesting CD. The patient currently remains asymptomatic with no new episodes of abdominal pain.

Plasma isoprostanoids assessment as Alzheimer's disease progression biomarkers.

Alzheimer's Disease (AD) is the most common neurodegenerative disease worldwide. So, there is a need to identify AD early diagnosis and monitoring biomarkers in blood samples. The aim of this study was to analyse the utility of lipid peroxidation biomarkers in AD progression evaluation. Participants (n = 19) were diagnosed with AD at early stages (Time 0, T0), and they were re-evaluated 2 years later (Time 1, T1). Plasma biomarkers from AD patients were determined at both times. Some analytes, such as dihomo-isoprostanes (17-epi-17-F2t-dihomo-IsoP, 17-F2t-dihomo-IsoP, Ent-7(RS)-7-F2t-dihomo-IsoP), and neuroprostanes (10-epi-10-F4t-NeuroP) showed very high probability of showing an increasing trend over time. Baseline values allowed to develop an affordable preliminary regression model to predict long-term cognitive status. So, some lipid peroxidation biomarkers would deserve consideration as useful progression AD biomarkers. The developed prediction model would constitute an important minimally invasive approach in AD personalized prognosis and perhaps could have some interest also in experimental treatments evaluation.

Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults.

BACKGROUND: Succinate is produced by both host and microbiota, with a key role in the interplay of immunity and metabolism and an emerging role as a biomarker for inflammatory and metabolic disorders in middle-aged adults. The relationship between plasma succinate levels and cardiovascular disease (CVD) risk in young adults is unknown. METHODS: Cross-sectional study in 100 (65% women) individuals aged 18-25 years from the ACTIvating Brown Adipose Tissue through Exercise (ACTIBATE) study cohort. CVD risk factors, body composition, dietary intake, basal metabolic rate, and cardiorespiratory fitness were assessed by routine methods. Plasma succinate was measured with an enzyme-based assay. Brown adipose tissue (BAT) was evaluated by positron emission tomography, and circulating oxylipins were assessed by targeted metabolomics. Fecal microbiota composition was analyzed in a sub-sample. RESULTS: Individuals with higher succinate levels had higher levels of visceral adipose tissue (VAT) mass (+ 42.5%), triglycerides (+ 63.9%), C-reactive protein (+ 124.2%), diastolic blood pressure (+ 5.5%), and pro-inflammatory omega-6 oxylipins than individuals with lower succinate levels. Succinate levels were also higher in metabolically unhealthy individuals than in healthy overweight/obese peers. Succinate levels were not associated with BAT volume or activity or with fecal microbiota composition and diversity. CONCLUSIONS: Plasma succinate levels are linked to a specific pro-inflammatory omega-6 signature pattern and higher VAT levels, and seem to reflect the cardiovascular status of young adults.

Dermatologic Ultrasound in Primary Care: A New Modality of Teledermatology: A Prospective Multicenter Validation Study.

OBJECTIVES: This study aimed to validate dermatologic ultrasound as a complementary teledermatologic imaging modality in primary and tertiary care centers. METHODS: Six primary care centers and 1 tertiary care dermatology department collaborated in the program. Images were sent through the institutional teledermatologic platform to the tertiary care dermatology department. At the reference hospital, ultrasound images and clinical data were received and registered by a physician trained in dermatologic ultrasound. An in-person consultation was scheduled to confirm the teleultrasound diagnosis. The time of response by the tertiary center, quality and size of the teledermatologic image, and concordance with the in-person diagnosis were assessed for each dermatologic lesion. RESULTS: A total of 147 teleultrasound consultations with 143 patients (93 women and 50 men; mean age ± SD, 47 ± 23 years) were evaluated between June 2018 and January 2019. Nine teleultrasound consultations (6.1%) were not valid. Discordance between teleultrasound and the in-person diagnosis was evident in 6 of 138 cases (4.3%). Most cases corresponded to benign skin tumors (66.7%), followed by inflammatory skin lesions (15.9%), nonmelanoma skin lesions (13%), and other skin lesions (4.3%). All malignant tumors were detected (sensitivity, 100%), although 2 cases of benign lesions were telediagnosed as malignant (specificity, 97.8%). The positive and negative predictive values of a teleultrasound diagnosis of cutaneous malignancy were 90% and 100%, respectively. CONCLUSIONS: Asynchronous primary care teleultrasound combined with dermatologic ultrasound training at tertiary centers is an effective teledermatologic modality.

Higher Plasma Levels of Endocannabinoids and Analogues Correlate With a Worse Cardiometabolic Profile in Young Adults.

CONTEXT: The endocannabinoid system (ECS) is a signaling system composed of endocannabinoids (eCBs), their receptors, and the enzymes involved in their synthesis and metabolism. Alterations in the ECS are linked to the development of cardiometabolic diseases. OBJECTIVE: Here, we investigated the relationship between plasma levels of eCBs and their analogues with body composition and cardiometabolic risk factors. METHODS: The study included 133 young adults (age 22.1 ± 2.2 years, 67% women). Fasting plasma levels of eCBs and their analogues were measured using liquid chromatography-tandem mass spectrometry. Body composition, brown adipose tissue (BAT) volume, glucose uptake, and traditional cardiometabolic risk factors were measured. RESULTS: Plasma levels of eCBs and several eCB analogues were positively correlated with adiposity and traditional cardiometabolic risk factors (eg, serum insulin and triacylglyceride levels, all r ≥ 0.17 and P ≤ .045). Plasma levels of 2-arachidonoyl glycerol and N-pentadecenoylethanolamine were negatively correlated with BAT volume and glucose uptake (all r ≤ -0.17 and P ≤ .047). We observed that the plasma levels of eCBs and their analogues were higher in metabolically unhealthy overweight-obese participants than in metabolically healthy overweight-obese participants. CONCLUSION: Our findings show that the plasma levels of eCBs and their analogues are related to higher levels of adiposity and worse cardiometabolic profile.

Protective effects of iodine on rat prostate inflammation induced by sex hormones and on the DU145 prostate cancer cell line treated with TNF.

Molecular iodine (I2) prevents oxidative stress and prostate hyperplasia induced by hyperandrogenism and reduces cell viability in prostate cancer cell lines. Here, we aimed to evaluate the protective effect of I2 and testosterone (T) on hyperestrogenism-induced prostate inflammation. Additionally, the effects of I2 and/or tumor necrosis factor (TNF) on cell viability and interleukin 6 (IL6) secretion were evaluated in a prostate cancer cell line (DU145). We also investigated whether the effects of I2 on viability are peroxisome proliferator-activated receptor gamma (PPARG)-dependent. Castrated (Cx) rats received pellets of either 17ß estradiol (E2) or E2 and T and were treated with I2 (0.05%) in the drinking water for four weeks. The experimental groups were sham, Cx, Cx + E2, Cx + E2+I2, Cx + E2+T, and Cx + E2+T + I2. As expected, inflammation was triggered in the Cx + E2 group (high inflammation score; increase in TNF and transcriptional activity of RELA [nuclear factor-kappa B p65 subunit]), and this effect was diminished in the Cx + E2+T group (medium inflammation score and decrease in TNF). The lowest inflammation score (decrease of TNF and RELA and increase of PPARG) was obtained in the Cx + E2+T + I2 group. In DU145 cells, I2 (400 µM) and TNF (10 ng/ml) additively reduced cell viability, and I2 reduced the production of TNF-stimulated IL6. The PPARG antagonist (GW9662) did not inhibit the effects of I2 on the loss of cell viability. In summary, our data suggest that I2 and T exert a synergistic anti-inflammatory action on the normal prostate, and the interrelationship between I2 and TNF leads to anti-proliferative effects in DU145 cells. PPARG does not seem to participate in the I2-induced cell viability loss in the prostate.

Neuroprotective Efficacy of Betulinic Acid Hydroxamate, a B55α/PP2A Activator, in Acute Hypoxia-Ischemia-Induced Brain Damage in Newborn Rats.

There is an increasing evidence of the neuroprotective effects of hypoxia inducing factor prolyl-hydroxylase inhibitors (HIF-PHDi) after hypoxic-ischemic (HI) brain damage (HIBD). We studied the neuroprotective effects of betulinic hydroxamate (BAH), a novel B55α/PP2A activator that dephosphorylates and inhibits PHD2 activity, in a rat model of neonatal HIBD. Seven-day-old (P7) Wistar rats were exposed to hypoxia after left carotid artery electrocoagulation and then received vehicle (HI + VEH) or BAH 3 mg/kg i.p. 30 min post-insult. Brain damage was assessed by magnetic resonance imaging (MRI) and neurobehavioral studies testing motor and cognitive performance at P14 and P37, as well as immunohistochemical studies (TUNEL and myelin basic protein (MBP) signal) at P37. Mechanisms of damage were assessed at P14 determining excitotoxicity (glutamate/N-acetylaspartate ratio by H+-magnetic resonance spectroscopy), oxidative stress (protein nitrosylation by Oxyblot), and inflammation (cytokine and chemokine concentration). BAH reduced brain damage volume and cell death, preventing the development of motor and working memory deficits. BAH showed a robust protective effect on myelination, restoring MBP expression at P37. BAH modulated excitotoxicity, oxidative stress, and inflammation. Most neuroprotective effects were still present despite BAH administration was delayed for 12 h, whereas beneficial effects on motor strength at P14 and on cell death and myelination at P37 were preserved even when BAH administration was delayed for 24 h. In conclusion, BAH appears as an effective neuroprotective treatment for neonatal HIBD in a manner associated with the modulation of excitotoxicity, oxidative stress, and inflammation, showing a broad therapeutic window.

Plasma Levels of Omega-3 and Omega-6 Derived Oxylipins Are Associated with Fecal Microbiota Composition in Young Adults.

Pre-clinical studies suggest that circulating oxylipins, i.e., the oxidation products of polyunsaturated fatty acids (PUFAs), modulate gut microbiota composition in mice, but there is no information available in humans. Therefore, this study aimed to investigate the relationship between omega-3 and omega-6 derived oxylipins plasma levels and fecal microbiota composition in a cohort of young adults. 80 young adults (74% women; 21.9 ± 2.2 years old) were included in this cross-sectional study. Plasma levels of oxylipins were measured using liquid chromatography-tandem mass spectrometry. Fecal microbiota composition was analyzed by V3-V4 16S rRNA gene sequencing. We observed that plasma levels of omega-3 derived oxylipins were positively associated with the relative abundance of Clostridium cluster IV genus (Firmicutes phylum; rho ≥ 0.415, p ≤ 0.009) and negatively associated with the relative abundance of Sutterella genus (Proteobacteria phylum; rho ≥ -0.270, p ≤ 0.041), respectively. Moreover, plasma levels of omega-6 derived oxylipins were negatively associated with the relative abundance of Acidaminococcus and Phascolarctobacterium genera (Firmicutes phylum; all rho ≥ -0.263, p ≤ 0.024), as well as Sutterella, Succinivibrio, and Gemmiger genera (Proteobacteria phylum; all rho ≥ -0.263, p ≤ 0.024). Lastly, the ratio between omega-6 and omega-3 oxylipins plasma levels was negatively associated with the relative abundance of Clostridium cluster IV genus (Firmicutes phylum; rho = -0.334, p = 0.004) and Butyricimonas genus (Bacteroidetes phylum; rho = -0.292, p = 0.014). In conclusion, our results show that the plasma levels of omega-3 and omega-6 derived oxylipins are associated with the relative abundance of specific fecal bacteria genera.

Acute and long-term exercise differently modulate plasma levels of oxylipins, endocannabinoids, and their analogues in young sedentary adults: A sub-study and secondary analyses from the ACTIBATE randomized controlled-trial.

BACKGROUND: Fatty acid-derived lipid mediators including oxylipins, endocannabinoids (eCBs), and their analogues, have emerged as key metabolites in the inflammatory and immune response to physiological stressors. METHODS: This report was based on a sub-study and secondary analyses the ACTIBATE single-center unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129). The study was performed in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada. Eligible participants were young, sedentary adults with no chronic diseases. Here, we performed both an acute endurance and resistance exercise sub-studies (n.ß=.ß14 and 17 respectively), and a 24-week supervised exercise intervention, combining endurance and resistance exercise training at moderate-intensity (MOD-EX) or vigorous-intensity (VIG-EX) exercise groups, in young sedentary adults. Randomization was performed by unrestricted randomization. Plasma levels of oxylipins, eCBs, and their analogues were measured using liquid chromatography-tandem mass spectrometry. FINDINGS: Both endurance and resistance exercise increased by.ß+50% the plasma levels of dihomo-..-linolenic acid and arachidonic acid (AA) omega-6 derived oxylipins, as well as eicosapentaenoic acid and docosahexaenoic acid omega-3 derived after 3 and 120.ßmin of the bout of exercise (all ..2.ß....ß0.219 and P.ß..±.ß0.039). These exercise modalities also increased the levels of anandamide and eCBs analogues (+25%). 145 young sedentary adults were assigned to a control (CON, n.ß=.ß54), a MOD-EX (n.ß=.ß48) or a VIG-EX (n.ß=.ß43). 102 participants were included in the final long-term analyses (CON, n.ß=.ß36; MOD-EX, n.ß=.ß33; and VIG-EX, n.ß=.ß33) of the trial. After 24-week of supervised exercise, MOD-EX decreased plasma levels of omega-6 oxylipins, concretely linoleic acid (LA) and adrenic acid derived oxylipins, and the eCBs analogues OEA and LEA in comparison to the CON (all P.ß..±.ß0.021). VIG-EX decreased LA-derived oxylipins and LEA compared to CON. No relevant adverse events were recorded. INTERPRETATION: Endurance and resistance exercises acutely increased plasma levels of oxylipins, eCBs, and their analogues, whereas 24 weeks of exercise training decreased fasting plasma levels of omega-6 oxylipins, and eCBs analogues in young, sedentary adults. FUNDING: See Acknowledgments section.

Plasma Levels of Endocannabinoids and Their Analogues Are Related to Specific Fecal Bacterial Genera in Young Adults: Role in Gut Barrier Integrity.

OBJECTIVE: To investigate the association of plasma levels of endocannabinoids with fecal microbiota. METHODS: Plasma levels of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), as well as their eleven analogues, and arachidonic acid (AA), were measured using liquid chromatography-tandem mass spectrometry in 92 young adults. DNA extracted from stool samples was analyzed using 16S rRNA gene sequencing. Lipopolysaccharide levels were measured in plasma samples. RESULTS: Plasma levels of endocannabinoids and their analogues were not related to beta or alpha diversity indexes. Plasma levels of AEA and related N-acylethanolamines correlated positively with the relative abundance of Faecalibacterium genus (all rho ≥ 0.26, p ≤ 0.012) and Akkermansia genus (all rho ≥ 0.22, p ≤ 0.036), and negatively with the relative abundance of Bilophila genus (all rho ≤ -0.23, p ≤ 0.031). Moreover, plasma levels of 2-AG and other acylglycerols correlated positively with the relative abundance of Parasutterella (all rho ≥ 0.24, p ≤ 0.020) and Odoribacter genera (all rho ≥ 0.27, p ≤ 0.011), and negatively with the relative abundance of Prevotella genus (all rho ≤ -0.24, p ≤ 0.023). In participants with high lipopolysaccharide values, the plasma levels of AEA and related N-acylethanolamines, as well as AA and 2-AG, were negatively correlated with plasma levels of lipopolysaccharide (all rho ≤ -0.24, p ≤ 0.020). CONCLUSION: Plasma levels of endocannabinoids and their analogues are correlated to specific fecal bacterial genera involved in maintaining gut barrier integrity in young adults. This suggests that plasma levels of endocannabinoids and their analogues may play a role in the gut barrier integrity in young adults.

No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial.

Exercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n = 31, and VIG-EX; n = 31). We observed no changes in BAT volume (Δ Control: -22.2 ± 52.6 ml; Δ MOD-EX: -15.5 ± 62.1 ml, Δ VIG-EX: -6.8 ± 66.4 ml; P = 0.771) or 18F-fluorodeoxyglucose uptake (SUVpeak Δ Control: -2.6 ± 3.1 ml; Δ MOD-EX: -1.2 ± 4.8, Δ VIG-EX: -2.2 ± 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.

No Solid Colloidal Carriers: Aspects Thermodynamic the Immobilization Chitinase and Laminarinase in Liposome.

The present review describes the basic properties of colloidal and vesicular vehicles that can be used for immobilization of enzymes. The thermodynamic aspects of the immobilization of enzymes (laminarinase and chitinase) in liposomes are discussed. These systems protect enzymes against environmental stress and allow for a controlled and targeted release. The diversity of colloidal and vesicular carriers allows the use of enzymes for different purposes, such as mycolytic enzymes used to control phytopathogenic fungi.

Association between dietary factors and brown adipose tissue volume/18F-FDG uptake in young adults.

OBJECTIVE: To study the association between usual dietary factors (dietary energy density, nutrient intake, food group consumption, and dietary pattern) and brown adipose tissue (BAT) volume/18F-fluorodeoxyglucose (18F-FDG) uptake after personalized cold exposure in young healthy adults. METHODS: A total of 122 young adults (n = 82 women; 22.0 ± 2.1 years old; 24.8 ± 4.8 kg/m2) took part in this cross-sectional study. Dietary factors were measured via a food frequency questionnaire and three non-consecutive 24 h recalls. Dietary energy density (foods and caloric beverages included) and macronutrient intakes were subsequently estimated using EvalFINUT® software, food group consumption was estimated from the food frequency questionnaire, and different dietary patterns and quality indices were determined according to the reference methods. BAT volume, BAT 18F-FDG uptake, and skeletal muscle 18F-FDG uptake were assessed by static 18F-FDG positron-emission tomography and computed tomography (PET-CT) scans after a 2 h personalized exposure to cold. RESULTS: A direct association was detected between dietary energy density and BAT Standardized Uptake Value (SUV)mean (ß = 0.215; R2 = 0.044; P = 0.022), and between ethanol consumption and BAT volume (ß = 0.215; R2 = 0.044; P = 0.022). The a priori Mediterranean dietary pattern was inversely associated with BAT SUVmean and SUVpeak (ß = -0.273; R2 = 0.075; P = 0.003 and ß = -0.255; R2 = 0.066; P = 0.005 respectively). In addition, the diet quality index for a Mediterranean diet and a pro-inflammatory dietary pattern (as determined via the dietary inflammatory index) were directly associated with BAT SUVmean and SUVpeak (SUVmean: ß = 0.238; R2 = 0.053; P = 0.013 and ß = 0.256; R2 = 0.052; P = 0.012 respectively; SUVpeak: ß = 0.278; R2 = 0.073; P = 0.003 and ß = 0.248; R2 = 0.049; P = 0.016 respectively). After controlling for multiplicity and possible confounders (sex, the evaluation wave and BMI), all the detected associations persisted. CONCLUSION: Dietary factors are slightly associated with BAT volume and/or 18F-FDG uptake after a personalized cold exposure in young adults. Our results provide an overall picture of the potential relationships between dietary factors and BAT-related variables in humans.

Influence of Exercise on the Human Gut Microbiota of Healthy Adults: A Systematic Review.

OBJECTIVES: To summarize the literature on the influence of exercise on the gut microbiota of healthy adults. METHODS: A systematic and comprehensive search in electronic database, including SciELO, Scopus, PubMed, and Web of Science up to July 5, 2019. Eligibility criterion was original studies conducted on healthy humans including exercise interventions or interventions involving any type of physical activity. RESULTS: The initial search retrieved 619 articles of which 18 met the inclusion criteria, 9 were observational, 4 reported very short-term exercise interventions, and 5 reported medium/long-term exercise interventions. Higher levels of physical activity or cardiorespiratory fitness were positively associated with fecal bacterial alpha diversity. Contrasting associations were detected between both the level of physical activity and cardiorespiratory fitness and fecal counts for the phyla Firmicutes, Bacteroidetes, and Proteobacteria. Higher levels of physical activity and cardiorespiratory fitness were positively associated with the fecal concentration of short-chain fatty acids. Reports on the effects of very short-term and medium/long-term exercise interventions on the composition of the gut microbiota were inconsistent. DISCUSSION: Higher levels of physical activity and cardiorespiratory fitness are associated with higher fecal bacterial alpha diversity and with the increased representation of some phyla and certain short-chain fatty acids in the feces of healthy adults. Very short-term and medium/long-term exercise interventions seem to influence the fecal counts of some phyla. However, the heterogeneity between studies hampers any strong conclusions from being drawn. Better-designed studies are needed to unravel the possible mechanisms through which exercise might influence the composition and activity of the human gut microbiota.

Clinical Utility of Plasma Lipid Peroxidation Biomarkers in Alzheimer's Disease Differential Diagnosis.

BACKGROUND: Differential diagnosis of Alzheimer's disease (AD) is a complex task due to the clinical similarity among neurodegenerative diseases. Previous studies showed the role of lipid peroxidation in early AD development. However, the clinical validation of potential specific biomarkers in minimally invasive samples constitutes a great challenge in early AD diagnosis. METHODS: Plasma samples from participants classified into AD (n = 138), non-AD (including MCI and other dementias not due to AD) (n = 70) and healthy (n = 50) were analysed. Lipid peroxidation compounds (isoprostanes, isofurans, neuroprostanes, neurofurans) were determined by ultra-performance liquid chromatography coupled with tandem mass spectrometry. Statistical analysis for biomarkers' clinical validation was based on Elastic Net. RESULTS: A two-step diagnosis model was developed from plasma lipid peroxidation products to diagnose early AD specifically, and a bootstrap validated AUC of 0.74 was obtained. CONCLUSION: A promising AD differential diagnosis model was developed. It was clinically validated as a screening test. However, further external validation is required before clinical application.

A rise in T3/T4 ratio reduces the growth of prostate tumors in a murine model.

Thyroxine (T4) promotes cell proliferation and tumor growth in prostate cancer models, but it is unknown if the increase in the triiodothyronine (T3)/T4 ratio could attenuate prostate tumor development. We assessed T3 effects on thyroid response, histology, proliferation, and apoptosis in the prostate of wild-type (WT) and TRAMP (transgenic adenocarcinoma of the mouse prostate) mice. Physiological doses of T3 were administered in the drinking water (2.5, 5 and 15 µg/100 g body weight) for 6 weeks. None of the doses modified the body weight or serum levels of testosterone, but all of them reduced serum T4 levels by 50%, and the highest dose increased the T3/T4 ratio in TRAMP. In WT, the highest dose of T3 decreased cyclin D1 levels (immunohistochemistry) but did not modify prostate weight or alter the epithelial morphology. In TRAMP, this dose reduced tumor growth by antiproliferative mechanisms independent of apoptosis, but it did not modify the intraluminal or fibromuscular invasion of tumors. In vitro, in the LNCaP prostate cancer cell line, we found that both T3 and T4 increased the number of viable cells (Trypan blue assay), and only T4 response was fully blocked in the presence of an integrin-binding inhibitor peptide (RGD, arginine-glycine-aspartate). In summary, our data show that the prostate was highly sensitive to physiological T3 doses and suggest that in vivo, an increase in the T3/T4 ratio could be associated with the reduced weight of prostate tumors. Longitudinal studies are required to understand the role of thyroid hormones in prostate cancer progression.

Economic evaluation of surgical treatment of obesity. / Evaluación económica del tratamiento quirúrgico de la obesidad.

INTRODUCTION: Obesity surgery is the best treatment for extreme obesity, with demonstrated long-term positive outcomes. The potential cost-savings generated by the improvement of comorbidities after surgery can justify the allocation of more resources in the surgical treatment of obesity. METHODS: This was an observational, descriptive, longitudinal and retrospective study. Eligible patients underwent Roux-en-Y gastric bypass surgery at the Hospital Universitario Central de Asturias between 2003 and 2012. The established minimum follow-up period was two years. We calculated the individualized cost per patient treated (bottom-up) as well as per Diagnosis-Related Group (DRG) codes (top-down). RESULTS: Our study included 307 patients. The average cost per hospitalization calculated by DRG codes was €6,545.90, and the average cost per patient was €10,572.20. DRG 288 represented 91% of the series, with a value of €4,631. The number of medications also decreased during this period, from 2.86 to 0.78 per medically treated patient, representing a cost reduction of €4,433 per patient with all the obesity-related comorbidities analyzed. CONCLUSIONS: Two years after Roux-en-Y gastric bypass conducted at Hospital Universitario Central de Asturias, the savings in drug costs for patients with multiple pathologies would compensate the inherent costs of the surgical treatment itself. Our results showed that DRG-related costs was insufficient to make a correct economic evaluation, so we recommend an individualized cost calculating method.

Prospective Analysis Regarding Health-Related Quality of Life (HR-QOL) between Morbid Obese Patients Following Bariatric Surgery Versus on a Waiting List.

BACKGROUND: Major impairment of health-related quality of life (HRQoL) is one of the main reasons why obese patients request surgical treatment. OBJECTIVE: To prospectively analyze the impact of HRQoL between obese patients who underwent surgery and those who were wait-listed. METHODS: Between April 2017 and March 2018, 70 surgical and 69 wait-listed patients were interviewed twice, at baseline and at the 12-month follow-up. Quality of life was measured by the SF-12v2 and the Impact of Weight on Quality of Life-Lite (IWQoL-Lite) questionnaires. Sociodemographic-, clinical-, and surgical-related variables were collected. RESULTS: One hundred thirty-nine patients were analyzed, showing similar baseline characteristics but differences in HRQoL. Performing more qualified work improved scores on some aspects of the SF-12 survey. In contrast, women scored worse on the self-esteem domain, and men scored worse on the mental health domain. By group, at the 12-month follow-up, statistically significant differences were found among all aspects of the questionnaires between both groups (P < 0.001) and between baseline and postoperative 12-month follow-up in the surgical group (P < 0.001). Furthermore, scores were lower in all domains in the evolution of wait-listed patients, with statistically significant differences among the Bodily Pain, Emotional Role, Mental Health, and Mental Component Summary Domains (P < 0.05). CONCLUSION: HRQoL is a multimodal concept that allows the identification of factors impacting obese patients' quality of life. It promotes the benefit of surgery against waiting list delays, which can take up to 4 years in our hospital. Therefore, HRQoL is an important pillar to justify more resources for reducing unacceptable surgical delays.

Cytospora elaeagnicola sp. nov. Associated with Narrow-leaved Oleaster Canker Disease in China.

Cytospora is a genus including important phytopathogens causing severe dieback and canker diseases distributed worldwide with a wide host range. However, identification of Cytospora species is difficult since the currently available DNA sequence data are insufficient. Aside the limited availability of ex-type sequence data, most of the genetic work is only based on the ITS region DNA marker which lacks the resolution to delineate to the species level in Cytospora. In this study, three fresh strains were isolated from the symptomatic branches of Elaeagnus angustifolia in Xinjiang Uygur Autonomous Region, China. Morphological observation and multi-locus phylogenetic analyses (ITS, LSU, ACT and RPB2) support these specimens are best accommodated as a distinct novel species of Cytospora. Cytospora elaeagnicola sp. nov. is introduced, having discoid, nearly flat, pycnidial conidiomata with hyaline, allantoid conidia, and differs from its relatives genetically and by host association.