Serum lipidomic profiling of dairy calves fed milk replacers containing animal or vegetable fats.

Vegetable fat blends are commonly used as fat sources in milk replacers (MR) for calves, but their composition differs considerably from that of bovine milk fat. The aim of this study was to investigate the serum lipid profile of pre-weaned calves fed twice-daily MR containing 30% fat (% DM). Upon arrival, 30 male Holstein-Friesian calves (BW = 45.6 ± 4.0 kg, age = 2.29 ± 0.8 d) were randomly assigned to 2 experimental diets (n = 15 per treatment): one MR was derived from either vegetable fats (VG; 80% rapeseed and 20% coconut fats) or animal fats (AN; 65% Packer's lard and 35% dairy cream). The 2 MR formulas contained 30% fat, 24% CP, and 36% lactose. Calves were housed indoors in individual pens with ad libitum access to chopped straw and water. Daily milk allowances were 6.0 L from d 1 to 5, 7.0 L from d 6 to 9, and 8.0 L from d 10 to 35, divided into 2 equal meals and prepared at 13.5% solids. An untargeted liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) method was employed to analyze the lipid profiles in the serum of calves sampled from the jugular vein at 35 d of age. In total, 594 lipids were characterized, comprising 25 different lipid classes. Principal component analysis (PCA) showed significant separation between VG and AN, indicating different lipid profiles in the serum. An orthogonal partial least squares discriminant analysis (OPLS-DA) classification model was used to further validate the distinction between the 2 treatment groups. The model exhibited a robust class separation and high predictive accuracy. Using a Volcano plot (fold change threshold ≥1.5 and false discovery rate ≤0.05), it was observed that calves fed AN had higher levels of 39 lipid species in serum than calves fed VG, whereas 171 lipid species were lower in the AN group. Lipid classes, such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), triglycerides (TG), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE), were different. In particular, PC and PE were observed at lower levels in calves fed AN, possibly indicating shifts in cell membrane characteristics, intracellular signaling, and liver functions. In addition, a decrease in certain triglyceride (TG) species was observed in calves fed AN, including a decrease in TG species such as TG 36:0 and TG 38:0, possibly related to variations in the content of certain fatty acids (FA) within the AN MR, such as C10:0, C12:0, C14:0, and C18:0 compared with the VG MR. Calves fed AN had lower levels of LPC and LPE, and lyso-phosphatidylinositol (LPI), SM, and phosphatidylinositol (PI) species than calves fed VG, suggesting shifts in lipoprotein and lipid metabolic pathways. In conclusion, these results deepen the understanding of how lipid sources in MR can modulate the serum lipidome profiles of dairy calves.

Regulatory mechanisms of the early phase of white adipocyte differentiation: an overview.

The adipose organ comprises two main fat depots termed white and brown adipose tissues. Adipogenesis is a process leading to newly differentiated adipocytes starting from precursor cells, which requires the contribution of many cellular activities at the genome, transcriptome, proteome, and metabolome levels. The adipogenic program is accomplished through two sequential phases; the first includes events favoring the commitment of adipose tissue stem cells/precursors to preadipocytes, while the second involves mechanisms that allow the achievement of full adipocyte differentiation. While there is a very large literature about the mechanisms involved in terminal adipogenesis, little is known about the first stage of this process. Growing interest in this field is due to the recent identification of adipose tissue precursors, which include a heterogenous cell population within different types of adipose tissue as well as within the same fat depot. In addition, the alteration of the heterogeneity of adipose tissue stem cells and of the mechanisms involved in their commitment have been linked to adipose tissue development defects and hence to the onset/progression of metabolic diseases, such as obesity. For this reason, the characterization of early adipogenic events is crucial to understand the etiology and the evolution of adipogenesis-related pathologies, and to explore the adipose tissue precursors' potential as future tools for precision medicine.

The untargeted lipidomic profile of quarter milk from dairy cows with subclinical intramammary infection by non-aureus staphylococci.

This observational study determined the lipidome of cow milk during subclinical intramammary infection (IMI) by non-aureus staphylococci (NAS), also defined as coagulase-negative staphylococci, using an untargeted approach. Among the pathogens causing bovine IMI, NAS have become the most frequently isolated bacteria from milk samples. Although the application of system biology approaches to mastitis has provided pivotal information by investigating the transcriptome, proteome, peptidome, and metabolome, the milk lipidome during mammary gland inflammation remains undisclosed. To cover this gap, we determined the milk lipidome of 17 dairy cows with IMI caused by NAS (NAS-IMI), and we compared the results with those of healthy quarter milk from 11 cows. The lipidome was determined following a liquid chromatography-quadrupole time-of-flight mass spectrometry approach. Sixteen subclasses of lipids were identified in both groups of animals. From 2,556 measured lipids, the abundance of 597 changed more than 10-fold in quarter milk with NAS-IMI compared with healthy quarters. The results demonstrate the influence of NAS-IMI on the milk lipidome, implying significant changes in lipid species belonging to the family of triacylglycerols and sphingomyelins, and contribute to the understanding of inflammatory processes in the bovine udder, highlighting potential novel biomarkers for improving mastitis diagnostics.

Neuroactive steroids and diabetic complications in the nervous system.

Important complications of diabetes mellitus in the nervous system are represented by diabetic peripheral neuropathy and diabetic encephalopathy. In this context, an important link is represented by neuroactive steroids (i.e., steroids coming from peripheral glands and affecting nervous functionality as well as directly synthesized in the nervous system). Indeed, diabetes does not only affect the reproductive axis and consequently the levels of sex steroid hormones, but also those of neuroactive steroids. Indeed, as will be here summarized, the levels of these neuromodulators present in the central and peripheral nervous system are affected by the pathology in a sex-dimorphic way. In addition, some of these neuroactive steroids, such as the metabolites of progesterone or testosterone, as well as pharmacological tools able to increase their levels have been demonstrated, in experimental models, to be promising protective agents against diabetic peripheral neuropathy and diabetic encephalopathy.

Relevance of TSH evaluation in elderly in-patients with non-thyroidal illness.

BACKGROUND: Non-thyroidal illness (NTI) is frequent in hospitalized patients. Its recovery is characterized by a raise in TSH levels. However, the clinical significance of high TSH levels at admission in hospitalized elderly patients with NTI remains uncertain. AIM: To explore the relevance of baseline TSH evaluation in hospitalized elderly patients with NTI. METHODS: We examined the participants with NTI (n = 123) from our previous study (Sforza, 2017). NTI was defined as: low T3 (< 80 ng/dL) and normal or low total T4 in the presence of TSH values between 0.1 and 6.0 mU/L. Thyroid function tests were performed on day 1 and day 8 of the hospital stay. Positive TSH changes (+ ΔTSH) were considered when the day-8 TSH value increased more than the reference change value for TSH (+ 78%). Multiple logistic regression was used to evaluate the independent association of baseline TSH, sex, clinical comorbidities (by ACE-27) and medications with + ΔTSH. RESULTS: Out of 123 patients (77 ± 8 years, 52% female), 34 showed a + ΔTSH. These patients had a lower TSH at admission (p < 0.001) and intra-hospital mortality (p = 0.003) than the others. In multiple logistic regression, TSH > 2.11 mU/L at baseline was associated with reduced odds to show + ΔTSH [odds ratio (95 CI) 0.29 (0.11-0.75); p = 0.011] in a model adjusted by age, sex and ACE-27. DISCUSSION: Inappropriately higher TSH levels at admission in hospitalized elderly patients were associated with a reduced ability to raise their TSH levels later on. The present results confront the idea that TSH levels at admission are irrelevant in this clinical context.

Litsea cubeba leaf essential oil from Vietnam: chemical diversity and its impacts on antibacterial activity.

The threat of bacterial resistance to antibiotics has created an urgent need to develop new antimicrobials. The aim of this study was to characterize the chemical diversity of Litsea cubeba leaf essential oil (EO) and its impacts on the antibacterial activity against pathogenic bacteria. Essential oils collected from seven provinces in North Vietnam (n = 25) were characterized by their high content in either 1,8-cineole or linalool. Linalool-type EOs were more effective against the eight bacterial strains tested than 1,8-cineole-type. Oil samples, LC19 (50% 1,8-cineole) and BV27 (94% linalool), were selected to investigate their antibacterial mechanisms against Escherichia coli. A strong bactericidal effect was observed after 4 and 2 h of exposure respectively. Microscopic analysis of treated E. coli cultures clearly showed that EOs caused changes in cell morphology, loss of integrity and permeability of the cell membrane, as well as DNA loss. However, the effects of both EOs were distinct. LC19 mostly affected cell membrane, led to a significant cell filamentation rate and altered cell width, whereas BV27 damaged cell membrane integrity leading to cell permeabilization and altered nucleoid morphology with the appearance of spot and visibly altered compaction. SIGNIFICANCE AND IMPACT OF THE STUDY: This study aimed to characterize the chemical diversity of Litsea cubeba leaf essential oil (EO) and its impacts on its antibacterial activity. Two major chemotypes (1,8-cineole or linalool rich) were identified in North Vietnam and both were bactericidal against several pathogenic bacteria. A distinct inhibitory effect of EO samples on Escherichia coli was observed. 1,8-cineole-rich sample (LC19) affected cell membrane, led to cell filamentation and perturbation of cell width, while the linalool-rich one (BV27) induced damages in the cell membrane and changes in the nucleoid morphology. The study demonstrates the importance of considering chemotype variations in terms of chemical composition as well as the mode of action.

Reducing complications and overall healthcare costs of hip fracture management: a retrospective study on the application of a Diagnostic Therapeutic Pathway in the Cosenza General Hospital.

BACKGROUND: Diagnostic Therapeutic Pathways (DTPs) are multidisciplinary plans designed by each healthcare organization for a specific category of patients to reduce the variability of professional behaviors and to ensure greater safety and better overall healthcare outcomes. Hip fractures are a frequent traumatic injury, particularly in the elderly, and DTPs recommend early surgical intervention, often not done due to organizational challenges and bureaucracy. Medical conditions suggesting a delay are not frequent, however long waiting times not only increase the risk of complications and mortality, but also increase the number of diagnostic test and physician consultations. This study tried to understand the benefits of performing surgical intervention within 48 hours in terms of cost savings, reduction of complications and better overall outcomes. We performed statistical analyses on data gathered from 130 patients submitted to DTPs, and we evaluated the benefits obtained by operating within 48 hours in terms of resource saving (number of physician consultations, hospitalization days, etc.), reduction in complications reported in the literature. METHODS: About 40% of clinical records of femoral fractures from 2015 at the Cosenza General Hospital were used in our statistical analysis taking into account independent variables such as age, sex,surgery waiting times and ASA (e.g. American Society of Anesthesiologists) score. Additionally, dependent variables such as: the type of complications during the hospital stay (e.g. infections, delirium, etc), days of hospitalization, and number of physician consultations were considered. RESULTS: The average waiting time for surgical intervention was 5.48 days (132 hr). Patients with ASA score of 4 had a greater chance of complications (p-value 0.03), whereas patients operated within 48 hours avoided complications, and spent fewer days in the hospital. The ASA score value correlated positively with the number of physician consultation, as the ASA score increased in number, so did the number of physician consultations. Moreover, each additional day of waiting increased the possibility of physician consultation by approximately 13. CONCLUSION: The lack of available hospital beds and staff shortages are the main reasons for the delay in performing surgery, this situation does not allow an efficient treatment and timely release of patients from the healthcare system. Therefore, there is an important need to implement standardized orthopedic and geriatric pathways (DTPs), inspired by the collaboration between healthcare system management, orthopedic and geriatric specialists, and physical therapists, to drive shorter days of hospitalization and better overall patient health outcome by performing surgery as soon as possible.

Attenuation of diet-induced obesity and induction of white fat browning with a chemical inhibitor of histone deacetylases.

BACKGROUND/OBJECTIVES: In the last decade, a strict link between epigenetics and metabolism has been demonstrated. Histone deacetylases (HDACs) have emerged as key epigenetic regulators involved in metabolic homeostasis in normal and pathologic conditions. Here we investigated the effect of the class I HDAC inhibitor MS-275 in a model of obesity induced by a high-fat diet (HFD). METHODS: C57BL6/J male mice were fed HFD for 17 weeks and then randomized in two groups, treated intraperitoneally with vehicle dimethylsulfoxide (DMSO) or with the class I selective HDAC inhibitor MS-275 every other day for 22 days. Glucose tolerance test and measurement of body temperature during cold exposure were performed. Adipose tissues and liver were phenotypically characterized through histological analysis. Gene and protein expression analysis of brown and white adipose tissues (WATs) were performed. RESULTS: MS-275 treated mice showed 10% reduction of body weight, lower adipocyte size and improved glucose tolerance. Inhibition of class I HDAC determined reduction of adipocyte size and of fat mass, paralleled by higher expression of adipose functionality markers and by increased rate of lipolysis and fatty acid ß-oxidation. MS-275 also promoted thermogenic capacity, related to 'browning' of visceral and subcutaneous WAT, showing increased expression of uncoupling protein 1. In brown adipose tissue, we observed limited effects on gene expression and only reduction of brown adipocyte size. CONCLUSIONS: This study provides evidence that class I HDAC inhibition stimulated functionality and oxidative potential of adipose tissue, improving glucose tolerance and ameliorating the metabolic profile in diet-induced obese mice.

Hypothyroidism in hospitalized elderly patients: a sign of worse prognosis.

PURPOSE: Overt hypothyroidism has adverse clinical consequences and might worsen prognosis in critically ill elderly patients. However, the difficult interpretation of thyroid function tests (TFT) due to non-thyroidal illness (NTI) has led to discouragement of screening for thyroid dysfunction. Our aim was to determine the prevalence of TFT compatible with hypothyroidism and to study its influence on mortality among hospitalized elderly patients. METHODS: In this prospective study we consecutively included all patients ≥60 years admitted by the Internal Medicine Department to the hospital ward (n = 451) of the Cesar Milstein Hospital in Buenos Aires, Argentina. TFT were done on day 1 and 8. Thyroid function categories were defined as overt and subclinical hypothyroidism, overt and subclinical hyperthyroidism, euthyroidism and NTI. Stage of chronic kidney disease (CKD), Adult Comorbidity Evaluation (ACE)-27, and intra-hospital mortality were recorded. The association between mortality and TFT categories was studied by Cox regression. RESULTS: Out of 451 patients (77.0 ± 7.9 years, 54% females) 76% were categorized as NTI, 4% as overt hypothyroid, 10% as subclinical hypothyroid, 1% as subclinical hyperthyroid and 9% as euthyroid. Overt hypothyroid patients showed significantly higher mortality than the rest of the groups (25%, p < 0.05) while ACE-27 was similar among all of them (p = 0.658). In addition, patients within the overt hypothyroid category showed a higher mortality rate than NTI in a model adjusted by Stage 5-CKD, ACE-27, sex and age [HR 3.1 (1.14-8.41), p < 0.026]. CONCLUSION: Overt hypothyroidism during hospitalization was associated with elevated mortality. Further studies would reveal if TFT alterations compatible with hypothyroidism should be diagnosed/treated in hospitalized elderly patients.

Antibacterial activity of Litsea cubeba (Lauraceae, May Chang) and its effects on the biological response of common carp Cyprinus carpio challenged with Aeromonas hydrophila.

AIMS: The aims of this study were to characterize the antibacterial activity and the chemotype of Litsea cubeba leaf essential oil (EO) harvested in North Vietnam and to investigate the biological effects induced by the leaf powder on growth, nonspecific immunity and survival of common carp (Cyprinus carpio) challenged with Aeromonas hydrophila. METHODS AND RESULTS: The EO showed the prevalence of linalool (95%, n = 5). It was bactericidal against the majority of tested strains, with minimum inhibitory concentrations ranging from 0·72 to 2·89 mg ml(-1) (Aer. hydrophila, Edwarsiella tarda, Vibrio furnissii, Vibrio parahaemolyticus, Streptococcus garvieae, Escherichia coli, Salmonella Typhimurium). The fish was fed with 0 (control), 2, 4 and 8% leaf powder supplementation diets for 21 days. Nonspecific immunity parameters (lysozyme, haemolytic and bactericidal activities of plasma) were assessed 21 days after feeding period and before the experimental infection. Weight gain, specific growth rate and feed conversion ratio were improved by supplementation of L. cubeba in a dose-related manner, and a significant difference appeared at the highest dose (8%) when compared to the control. The increase in plasma lysozyme was significant for all the treated groups. Haemolysis activity was higher for the groups fed with 4 and 8% plant powder. Antibacterial activity increased significantly for the 8% dose only. CONCLUSIONS: Litsea cubeba leaf powder increased nonspecific immunity of carps in dose-related manner. After infection with Aer. hydrophila, survivals of fish fed with 4 and 8% L. cubeba doses were significantly higher than those fed with 2% dose and the control. SIGNIFICANCE AND IMPACT OF THE STUDY: A range of 4-8% L. cubeba leaf powder supplementation diet (from specific linalool-rich chemotype) can be used in aquaculture to reduce antibiotic burden and impacts of diseases caused by Aer. hydrophila.

Liver X receptors, nervous system, and lipid metabolism.

Lipids in the nervous system are represented by cholesterol and phospholipids as constituents of cell membranes and, in particular, of myelin. Therefore, lipids are finely regulated to guarantee physiological functions. In the central nervous system, cholesterol is locally synthesized due to the presence of the blood brain barrier. In the peripheral nervous system cholesterol is either up-taken by lipoproteins and/or produced by de novo biosynthesis. Defects in lipid homeostasis in these tissues lead to structural and functional changes that often result in different pathological conditions depending on the affected pathways (i.e. cholesterol biosynthesis, cholesterol efflux, fatty acid biosynthesis etc.). Alterations in cholesterol metabolism in the central nervous system are linked to several disorders such as Alzheimer's disease, Huntington disease, Parkinson disease, Multiple sclerosis, Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and glioblastoma. In the peripheral nervous system changes in lipid metabolism are associated with the development of peripheral neuropathy that may be caused by metabolic disorders, injuries, therapeutics, and autoimmune diseases. Transcription factors, such as the Liver X receptors (LXR), regulate both cholesterol and fatty acid metabolism in several tissues including the nervous system. In the last few years several studies elucidated the biology of LXR in the nervous system due to the availability of knock-out mice and the development of synthetic ligands. Here, we review a survey of the literature focused on the central and peripheral nervous system and in physiological and pathological settings with particular attention to the roles played by LXR in both districts.

IgE, but not IgG4, antibodies to Ara h 2 distinguish peanut allergy from asymptomatic peanut sensitization.

BACKGROUND: There are no available clinical tests that can accurately predict peanut allergy (PA) and/or anaphylaxis. This study is aimed at evaluating whether the component-resolved diagnostic (CRD) IgE and IgG4 tests can (i) distinguish PA from asymptomatic peanut sensitization (PS) and (ii) differentiate anaphylactic from nonanaphylactic PA. METHODS: This study included 20 nonatopic controls, 58 asymptomatically peanut-sensitized children, 55 nonanaphylactic, and 53 anaphylactic PA cases from the Chicago Food Allergy Study. IgE and IgG4 to 103 allergens were measured using the ImmunoCAP ISAC technology and were compared among each group of children. The random forest test was applied to estimate each allergen's ability to predict PA and/or peanut anaphylaxis. RESULTS: Peanut allergy cases (with or without anaphylaxis) had significantly higher IgE reactivity to Ara h 1-3 (peanut allergens) and Gly m 5-6 (soy allergens) than asymptomatically sensitized children (P < 0.00001). Similar but more modest relationships were found for IgG4 to Ara h 2 (P < 0.01). IgE to Ara h 2 was the major contributor to accurate discrimination between PA and asymptomatic sensitization. With an optimal cutoff point of 0.65 ISU-E, it conferred 99.1% sensitivity, 98.3% specificity, and a 1.2% misclassification rate in the prediction of PA, which represented a higher discriminative accuracy than IgE to whole peanut extract (P = 0.008). However, none of the IgE and/or IgG4 tests could significantly differentiate peanut anaphylaxis from nonanaphylactic PA. CONCLUSIONS: IgE to Ara h 2 can efficiently differentiate clinical PA from asymptomatic PS, which may represent a major step forward in the diagnosis of PA.

Spatio-temporal analysis of cyprinid herpesvirus 3 genetic diversity at a local scale.

Cyprinid herpesvirus 3 (CyHV-3), the causative agent of koi herpesvirus disease, is a major threat for carp populations in many countries worldwide, including Indonesia. It has been shown that many genotypes circulate worldwide, all highly related to one of the two known lineages U/I and J. In this study, we evaluated the spatial and temporal distribution of CyHV-3 strains in a small enzootic area, the lake of Cirata (West Java, Indonesia). Of the 365 samples analysed, from clinical or asymptomatic fish, 244 were found positive for CyHV-3, suggesting a high occurrence of the virus. Genotyping of these viral specimens with a range of molecular markers revealed the presence of numerous haplotypes in the host population, all related to the J lineage. In single individuals, mixed-genotype infections occurred at high frequency. The present results demonstrate that polymorphic molecular markers are suitable to monitor the genetic evolution of a viral population in an enzootic area.

Achieving the learning curve in total thyroidectomy: a prospective evaluation on resident's training by CUSUM and KPSS analysis.

INTRODUCTION: Total thyroidectomy (TT) is one of the most common procedures among general and endocrine surgeons worldwide. The conventional approach by neck incision is still the most frequently used, despite the growth of mini-invasive approaches. Controversies exist about the optimal learning curve for resident surgeons approaching this procedure. The aim of this study was to compare TT performed by experienced surgeons and residents in two academic hospitals, to define the correct shape of the specific learning curve. METHODS: Between January 2016 and December 2018 patients undergoing TT in two academic departments were prospectively enrolled. In each department patients were divided into four groups: a reference group (A), consisting of 50 consecutive patients operated on by a senior surgeon, and three other groups (B, C, D) of 50 patients each where thyroidectomy was carried out by three different general surgery residents in their last 3 years of residency, respectively. Data were analysed by CUSUM and KPSS tests in order to compare operative time (OT) and its stabilisation during the learning curve. RESULTS: Data from CUSUM test reported that residents could perform TT with OT similar to the senior surgeon after approximately 25-30 procedures, while the KPSS test showed that residents became more stable after 30 procedures, with no increase in perioperative complications. CONCLUSIONS: This prospective study shows how a specific training in thyroid surgery can be reliable thanks to experienced tutors, and confirmed that the effect of dedicated and programmed training may result in positive outcomes for patients requiring thyroidectomy.

Assessment of efficacy and safety of micropulse diode laser treatment in glaucoma: One year follow-up. / Evaluación de la eficacia y seguridad del diodo láser micropulsado en el tratamiento de glaucoma: un año de seguimiento.

OBJECTIVE: To determine the effectiveness and safety of the micropulse transscleral technique in lowering intraocular pressure in patients with glaucoma. MATERIALS AND METHODS: A retrospective cohort study was conducted on 143 eyes with various glaucoma subtypes between October 2016 and December 2018. Patients were grouped for analysis based on glaucoma subtypes, preoperative demographics, previous surgical procedures, and postoperative results. The data collected was based on intra- and post-operative complications, intraocular pressure, visual acuity, the need of micropulse re-treatment, incisional glaucoma surgery, and increasing the dose/quantity of medications. A logistic and Cox regression model was performed to determine predictors of therapeutic failure, in addition to building Kaplan-Meier curves. RESULTS: The mean follow-up was 268 days, and 63% of the patients completed one year. The micropulse procedure achieved a mean intraocular pressure decline of 7.3mmHg (excluding neovascular glaucoma), independent of the glaucoma subtype. The percentage of patients who achieved intraocular pressure less than 20mmHg at 24h was 78%, with 80% at 3 months, 77% at 6 months, and 78% at 12 months. During the follow-up, 29.6% of the patients required additional treatment or a dose increase. Only 2patients presented with minimal postoperative complications. CONCLUSION: The treatment with transscleral micropulse is a safe and efficient technique for use in glaucoma, attaining a reduction in intraocular pressure and decrease in need of antihypertensive medications within the first year following the procedure.

Steroidogenic machinery in the adult rat colon.

Gastrointestinal function is known to be regulated by steroid molecules produced by the gonads, the adrenal glands and the gut microbiota. However, we have a limited knowledge on the functional significance of local steroid production by gastrointestinal tract tissue. On this basis, we have here evaluated, as a first methodological approach, the expression of steroidogenic molecules and the local levels of key steroids in the male rat colon. Our findings indicate that the colon tissue expresses molecules involved in the early steps of steroidogenesis and in the consecutive synthesis and metabolism of steroid hormones, such as progesterone, testosterone and 17ß-estradiol. In addition, the levels of the steroid hormone precursor pregnenolone and the levels of active metabolites of progesterone and testosterone, such as dihydroprogesterone, tetrahydroprogesterone, dihydrotestosterone and 17ß-estradiol, were higher in colon than in plasma. Higher levels of the androgen metabolite 3α-diol were detected in the colon in comparison with another non-classical steroidogenic tissue, such as the cerebral cortex. These findings suggest the existence of local steroid synthesis and metabolism in the colon, with the production of active steroid metabolites that may impact on the activity of the enteric nervous system and on the composition of the gut microbiota.

Sex dimorphism in an animal model of multiple sclerosis: Focus on pregnenolone synthesis.

Neuroactive steroids, molecules produced from cholesterol in steroidogenic cells (i.e., peripheral glands and nervous system) are physiological modulators and protective agents of nervous function. A possible role for neuroactive steroids in the sex-dimorphic clinical manifestation, onset and progression of Multiple Sclerosis (MS) has been recently suggested. To explore this possibility, we assessed the synthesis of the first steroidogenic product (pregnenolone; PREG) in the spinal cord of experimental autoimmune encephalomyelitis rats, a MS model. Data obtained indicate that the synthesis of PREG in the spinal cord is altered by the pathology in a sex-dimorphic way and depending on the pathological progression. Indeed, in male spinal cord the synthesis was already decreased at the acute phase of the disease (i.e., 14 days post induction - dpi) and maintained low during the chronic phase (i.e., 45 dpi), while in females this effect was observed only at the chronic phase. Substrate availability had also a role in the sex-dimorphic kinetics. Indeed, at the chronic phase, male animals showed a reduction in the levels of free cholesterol coupled to alteration of cholesterol metabolism into oxysterols; these effects were not observed in female animals. These findings suggest that the comprehension of the neurosteroidogenic processes could be relevant to better understand the sexual dimorphism of MS and to possibly design sex-oriented therapeutic strategies based on neuroactive steroids.

Food allergy is associated with an increased risk of asthma.

BACKGROUND: The atopic march is well documented, but the interrelationship of food allergy (FA) and asthma is not well understood. OBJECTIVE: The aim of this study was to examine the strength of the association and temporal relationships between FA and asthma. METHODS: This analysis included 271 children >or=6 years (older group) and 296 children <6 years (younger group) from a family-based FA cohort in Chicago, IL. Asthma was determined by parental report of physician diagnosis. FA status was determined based on the type and timing of clinical symptoms after ingestion of a specific food, and results of prick skin test (Multi-Test II) and allergen-specific IgE (Phadia ImmunoCAP). Analyses were carried out using logistic regression accounting for important covariates and auto-correlations among siblings. Kaplan-Meier curves were used to compare the time to onset of asthma with the FA status. RESULTS: Symptomatic FA was associated with asthma in both older [odds ratio (OR)=4.9, 95% confidence interval (CI): 2.5-9.5] and younger children (OR=5.3, 95% CI: 1.7-16.2). The association was stronger among children with multiple or severe food allergies, especially in older children. Children with FA developed asthma earlier and at higher prevalence than children without FA (Cox proportional hazard ratio=3.7, 95% CI: 2.2-6.3 for children >or=6 years, and hazard ratio=3.3, 95% CI: 1.1-10 for children <6 years of age). No associations were seen between asymptomatic food sensitization and asthma. CONCLUSIONS: Independent of markers of atopy such as aeroallergen sensitization and family history of asthma, there was a significant association between FA and asthma. This association was even stronger in subjects with multiple food allergies or severe FA.

Familial aggregation of food allergy and sensitization to food allergens: a family-based study.

BACKGROUND: The increasing prevalence of food allergy (FA) is a growing clinical and public health problem. The contribution of genetic factors to FA remains largely unknown. OBJECTIVE: This study examined the pattern of familial aggregation and the degree to which genetic factors contribute to FA and sensitization to food allergens. METHODS: This study included 581 nuclear families (2,004 subjects) as part of an ongoing FA study in Chicago, IL, USA. FA was defined by a set of criteria including timing, clinical symptoms obtained via standardized questionnaire interview and corroborative specific IgE cut-offs for > or =95% positive predictive value (PPV) for food allergens measured by Phadia ImmunoCAP. Familial aggregation of FA as well as sensitization to food allergens was examined using generalized estimating equation (GEE) models, with adjustment for important covariates including age, gender, ethnicity and birth order. Heritability was estimated for food-specific IgE measurements. RESULTS: FA in the index child was a significant and independent predictor of FA in other siblings (OR=2.6, 95% CI: 1.2-5.6, P=0.01). There were significant and positive associations among family members (father-offspring, mother-offspring, index-other siblings) for total IgE and specific IgE to all the nine major food allergens tested in this sample (sesame, peanut, wheat, milk, egg white, soy, walnut, shrimp and cod fish). The estimated heritability of food-specific IgE ranged from 0.15 to 0.35 and was statistically significant for all the nine tested food allergens. CONCLUSION: This family-based study demonstrates strong familial aggregation of FA and sensitization to food allergens, especially, among siblings. The heritability estimates indicate that food-specific IgE is likely influenced by both genetic and environmental factors. Together, this study provides strong evidence that both host genetic susceptibility and environmental factors determine the complex trait of IgE-mediated FA.

Computing a three-dimensional electronic energy manifold for the LiH + H <==> Li + H2 chemical reaction.

We present a new three-dimensional potential energy surface (PES) for the electronic ground state of the LiH + H <==> Li + H2 reaction and further analyze specific aspects of the lower four excited electronic states. Our reactive PESs are calculated using a CASSCF method followed by an MRCI treatment of the correlation energy. The ground-state three-dimensional surface is then fitted by using our own version of the Aguado-Paniagua interpolation form [Aguado, A.; Paniagua, M. J. Chem. Phys. 1992, 96, 1265]. A review of the previous computational work on this system, to which we compare our present findings, is given in the introduction of the paper: with respect to such earlier calculations of the ground-state PES [Dunne, L. J.; Murrell, J. N.; Jemmer, P. Chem. Phys. Lett. 2001, 336, 1], our data confirm the absence of a barrier along the path to the LiH depletion reaction and further reveal possible spurious features of the earlier computed surface which may in turn affect the resulting rates from low-energy dynamic studies of the title system.