Detection of hydroquinone by Raman spectroscopy in patients with melasma before and after treatment.

BACKGROUND: Melasma is an acquired, facial hyperpigmentation without a specific origin. It is regularly associated with multiple etiologic factors such as pregnancy, genetic, racial, and from estrogen administration. Among the methods to treat skin hyperpigmentation a series of skin bleaching agents have been used. At present, the most commonly used agent is known as hydroquinone. Nowadays, it is known that hydroquinone can cause cancer in animals with unknown relevance to humans. MATERIAL AND METHODS: In this work, Raman spectroscopy was used to observe the presence of hydroquinone in the skin of 18 patients who have been under treatment for melasma. RESULTS: A significant increase in the Raman signal was observed in the six bands associated with hydroquinone after melasma treatment. CONCLUSION: The authors believe that monitoring the presence of hydroquinone may be useful for an optimal personalized treatment of melasma and to provide the specialist a support tool to control the administration of this type of bleaching agents.

Machine learning to refine decision making within a syndromic surveillance service.

BACKGROUND: Worldwide, syndromic surveillance is increasingly used for improved and timely situational awareness and early identification of public health threats. Syndromic data streams are fed into detection algorithms, which produce statistical alarms highlighting potential activity of public health importance. All alarms must be assessed to confirm whether they are of public health importance. In England, approximately 100 alarms are generated daily and, although their analysis is formalised through a risk assessment process, the process requires notable time, training, and maintenance of an expertise base to determine which alarms are of public health importance. The process is made more complicated by the observation that only 0.1% of statistical alarms are deemed to be of public health importance. Therefore, the aims of this study were to evaluate machine learning as a tool for computer-assisted human decision-making when assessing statistical alarms. METHODS: A record of the risk assessment process was obtained from Public Health England for all 67,505 statistical alarms between August 2013 and October 2015. This record contained information on the characteristics of the alarm (e.g. size, location). We used three Bayesian classifiers- naïve Bayes, tree-augmented naïve Bayes and Multinets - to examine the risk assessment record in England with respect to the final 'Decision' outcome made by an epidemiologist of 'Alert', 'Monitor' or 'No-action'. Two further classifications based upon tree-augmented naïve Bayes and Multinets were implemented to account for the predominance of 'No-action' outcomes. RESULTS: The attributes of each individual risk assessment were linked to the final decision made by an epidemiologist, providing confidence in the current process. The naïve Bayesian classifier performed best, correctly classifying 51.5% of 'Alert' outcomes. If the 'Alert' and 'Monitor' actions are combined then performance increases to 82.6% correctly classified. We demonstrate how a decision support system based upon a naïve Bayes classifier could be operationalised within an operational syndromic surveillance system. CONCLUSIONS: Within syndromic surveillance systems, machine learning techniques have the potential to make risk assessment following statistical alarms more automated, robust, and rigorous. However, our results also highlight the importance of specialist human input to the process.

Exploring Campylobacter seasonality across Europe using The European Surveillance System (TESSy), 2008 to 2016.

BackgroundCampylobacteriosis is the most commonly reported food-borne infection in the European Union, with an annual number of cases estimated at around 9 million. In many countries, campylobacteriosis has a striking seasonal peak during early/mid-summer. In the early 2000s, several publications reported on campylobacteriosis seasonality across Europe and associations with temperature and precipitation. Subsequently, many European countries have introduced new measures against this food-borne disease.AimTo examine how the seasonality of campylobacteriosis varied across Europe from 2008-16, to explore associations with temperature and precipitation, and to compare these results with previous studies. We also sought to assess the utility of the European Surveillance System TESSy for cross-European seasonal analysis of campylobacteriosis.MethodsWard's Minimum Variance Clustering was used to group countries with similar seasonal patterns of campylobacteriosis. A two-stage multivariate meta-analysis methodology was used to explore associations with temperature and precipitation.ResultsNordic countries had a pronounced seasonal campylobacteriosis peak in mid- to late summer (weeks 29-32), while most other European countries had a less pronounced peak earlier in the year. The United Kingdom, Ireland, Hungary and Slovakia had a slightly earlier peak (week 24). Campylobacteriosis cases were positively associated with temperature and, to a lesser degree, precipitation.ConclusionAcross Europe, the strength and timing of campylobacteriosis peaks have remained similar to those observed previously. In addition, TESSy is a useful resource for cross-European seasonal analysis of infectious diseases such as campylobacteriosis, but its utility depends upon each country's reporting infrastructure.

Retrospective study of perampanel efficacy and tolerability in myoclonic seizures.

OBJECTIVES: Perampanel is an antiepileptic drug (AED) approved for add-on treatment of focal seizures (with or without generalization) and primary generalized tonic-clonic (GTC) seizures. Our objective was to explore the effectiveness and tolerability of adjunctive perampanel in patients with drug-resistant myoclonic seizures, after failure of other AEDs. MATERIALS AND METHODS: Retrospective, multicenter, observational study. Data were collected from individual patient clinical files and analysed using appropriate descriptive statistics and inferential analyses. RESULTS: Data are reported for 31 patients with mean age 36.4 years, who had an average epilepsy duration of 18 years, previously taken an average of 5.03 AEDs, and were taking an average of 2.4 AEDs on perampanel initiation. Patients exhibited myoclonic, GTC, absence, tonic and focal seizures, and most had associated cognitive decline and/or ataxia. Median time on perampanel was 6 months, most common dose was 6 mg, and overall retention rate was 84%. The responder rate for myoclonic seizures was defined via reduction of days with myoclonic seizures per month. At 6 months, 15 (48.4%) of the 31 patients were classed as myoclonic seizure responders, 10 (32.3%) were myoclonic seizure free, and 39% saw improvements in functional ability. Of 17 patients with GTC seizures at baseline, 9 (53%) were responders at 6 months, and 8 (47.1%) were seizure free. The most frequent side effects were psychiatric disorders, instability, dizziness and irritability, and mostly resolved with dose reduction. Five patients discontinued perampanel due to side effects. CONCLUSIONS: Perampanel caused clinically meaningful improvements in patients with drug-resistant myoclonic seizures. It was generally well tolerated, but psychiatric and neurological side effects sometimes required follow-up and dose reduction.

VNS and pregnancy: A multicentric experience of four cases.

BACKGROUND: Vagus nerve stimulation system (VNS) has been employed worldwide as adjunctive therapy in drug-resistant epileptic patients. Only nine previous pregnancies with six-positive outcomes have been reported in women with epilepsy treated with VNS since 1998. AIMS OF THE STUDY: To communicate the experience of pregnancies in women treated with VNS in our country. METHODS: Clinical data of four female patients treated with VNS during pregnancy and delivery in five gestations is described. RESULTS: Four pregnancy outcomes were positive and one ended in spontaneous abortion, probably more related to the use antiepileptic drugs than VNS itself. Two births were vaginal and the other two with cesarean section. None of the complications during delivery were attributed to VNS. No teratogenicity was documented. CONCLUSIONS: Based on our experience VNS constitutes a safe therapy for the treatment of drug-resistant epilepsy in women of childbearing potential and during pregnancy and delivery. Larger series will be useful to confirm this finding.

EARLY-ESLI study: Long-term experience with eslicarbazepine acetate after first monotherapy failure.

PURPOSE: Evaluate real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with focal epilepsy. METHOD: Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. RESULTS: Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events (AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. CONCLUSION: Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up.

Key Issues in Hymenoptera Venom Allergy: An Update.

In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis.

Raman spectroscopy analysis of the skin of patients with melasma before standard treatment with topical corticosteroids, retinoic acid, and hydroquinone mixture.

BACKGROUND: Melasma is an abnormal acquired hyperpigmentation of the face of unknown origin, it is considered a single disease and very little has been found regarding its pathogenesis. It is usually assumed that melasma is due to excessive melanin production, but previous work using Raman spectroscopy showed degraded molecules of melanin in some melasma subjects, which may help to explain the success or failure of the standard therapy. METHODS: We perform Raman spectroscopy measurements on in vivo skin from melasma patients before treatment to identify the molecular structure of melanin within every melasma lesion. The Raman spectra were grouped according to the treatment response from patient, and the Raman spectra were analyzed. RESULTS: Raman spectroscopy measurements showed a different molecular structure of the patients who did not respond to treatment, those patients shows atypical Raman skin spectrum with peaks associated with melanin not well defined, which is consistent with molecular degradation and protein breakdown. CONCLUSION: Our results are consistent with our previous work in the sense that melasma patients who do not respond to treatment have an abnormal melanin. We believe it will eventually help to decide the treatment of melasma in clinical dermatology.

Osteoprotegerin and zoledronate bone effects during orthodontic tooth movement.

OBJECTIVES: To assess the effects of local delivery of recombinant fusion protein osteoprotegerin (OPG-Fc) and bisphosphonate zoledronate on bone and periodontal ligament in a rat tooth movement model. MATERIALS AND METHODS: Maxillary first molars of 36 male Sprague-Dawley rats were displaced mesially using a calibrated spring connected to an anterior mini-screw. Two different drugs were used: a single dose of Zoledronate (16 µg) and a twice-weekly dose of OPG-Fc (5.0 mg/kg) were injected. Tooth movement was measured on scanned plaster casts. Structural and immunohistochemical analysis of the orthodontic-induced changes in bone included receptor activator of nuclear factor ĸ (RANK), Runx, type 1 collagen, matrix metalloproteinases (MMPs) 2 and 9, tissue inhibitors of metalloproteinases (TIMPs) 1 and 2, and vimentin. RESULTS: Both groups showed a reduction in mesial molar displacement. Animals receiving OPG-Fc demonstrated only 52%, 31%, and 21% of the total mesial molar displacement compared to control rats at 7, 14, and 21 days, respectively (*p < 0.001). For rats receiving zoledronate tooth displacement decreased significantly with 52%, 46% and 30%, respectively (*p < 0.001). At 14 and 21 days, OPG-Fc group showed significantly less molar displacement than the zoledronate group (*p < 0.001). RANK, Runx, vimentin, MMP-9 and tissues-inhibitor metalloproteinase 1 immunoreactivity were reduced in zoledronate treated animals and even more in OPG treated animals. CONCLUSION: Local delivery of OPG-Fc or zoledronate inhibits bone resorption and therefore tooth movement. OPG-Fc was more effective than zoledronate in blocking the action of osteoclasts.

The Spanish Neurological Society official clinical practice guidelines in epilepsy.

Previous Official Clinical Practice Guidelines (CPGs) in Epilepsy were based on expert opinions and developed by the Epilepsy Study Group of the Spanish Neurological Society (GE-SEN). The current CPG in epilepsy is based on the scientific method, which extracts recommendations from published scientific evidence. A reduction in the variability in clinical practice through standardization of medical practice has become its main function. SCOPE AND OBJECTIVES: This CPG is focused on comprehensive care for individuals affected by epilepsy as a primary and predominant symptom, regardless of the age of onset and medical policy. METHODOLOGY: 1. Creation of GE-SEN neurologists working group, in collaboration with Neuropediatricians, Neurophysiologists and Neuroradiologists. 2. Identification of clinical areas to be covered: diagnosis, prognosis and treatment. 3. Search and selection of the relevant scientific evidence. 4. Formulation of recommendations based on the classification of the available scientific evidence. RESULTS: It contains 161 recommendations of which 57% are consensus between authors and publishers, due to an important lack of awareness in many fields of this pathology. CONCLUSIONS: This Epilepsy CPG formulates recommendations based on explicit scientific evidence as a result of a formal and rigorous methodology, according to the current knowledge in the pre-selected areas. This paper includes the CPG chapter dedicated to emergency situations in seizures and epilepsy, which may present as a first seizure, an unfavorable outcome in a patient with known epilepsy, or status epilepticus as the most severe manifestation.

Associated Inosine to interferon: results of a clinical trial in multiple sclerosis.

BACKGROUND: Uric acid (UA) could act as a natural peroxynitrite scavenger with antioxidant properties. It has been proposed that hyperuricemia might protect against multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS starting treatment with interferon beta-1a 44 µg sc 3/week were randomly assigned to receive either inosine 3 g/day or placebo in a double-blind manner. Follow-up was 12 months. Outcome measures were adverse events and UA laboratory results. Secondary end point was clinical and radiological activity of MS. Relapse rates, percentage of patients without relapses, and progression to secondary MS (SPMS) were assessed. RESULTS: Thirty six patients were included. Two patients in the inosine group showed UA serum level above 10 mg/ml, and symptoms derived from renal colic not leading to hospital admission. Ten additional patients had asymptomatic hyperuricemia (>7 mg). Efficacy parameters (clinical and radiological) were similar between groups. No patient progressed to SPMS CONCLUSIONS: Inosine administration was associated with hyperuricemia and renal colic with no additional effect on MS. We cannot conclude inosine is a safe and well-tolerated drug. Doses of around 2 g/day may be more appropriate for future trials.

Prognosis in epilepsy: initiating long-term drug therapy.

INTRODUCTION: Prognosis in epilepsy refers to the probability of either achieving seizure remission (SR), whether spontaneously or using antiepileptic drugs (AED), or failing to achieve control of epileptic seizures (ES) despite appropriate treatment. Use of AED is recommended after a second unprovoked ES. For a first episode, the decision of whether or not to start drug treatment depends on the risk of recurrence and the advantages or disadvantages of the antiepileptic drug. The main goal of treatment is achieving absence of ES without adverse effects (AE). AED is selected according to epilepsy type and the demographic and clinical characteristics of the patient. DEVELOPMENT: A PubMed search located articles and recommendations by the most relevant scientific societies and clinical practice guidelines concerning epilepsy prognosis and treatment. Evidence and recommendations are classified according to the prognostic criteria of the Oxford Centre for Evidence-Based Medicine (2001) and the European Federation of Neurological Societies (2004) for therapeutic actions. CONCLUSIONS: Most newly diagnosed epileptic patients achieve good control over their ES. The majority of the AEDs available at present provide effective control over all types of ES, and choice therefore depends on the patient's individual characteristics. Treatment should be initiated as monotherapy at the lowest effective dose, which in half of all patients provides ES control and is well tolerated. In cases in which the first AED is not effective, alternative therapy should be started, and monotherapy should be employed before combination therapy where possible. The probability of achieving good control over ES decreases with each successive treatment failure.

Drug-resistant epilepsy: definition and treatment alternatives.

INTRODUCTION: Drug-resistant epilepsy affects 25% of all epileptic patients, and quality of life decreases in these patients due to their seizures. Early detection is crucial in order to establish potential treatment alternatives and determine if the patient is a surgical candidate. DEVELOPMENT: PubMed search for articles, recommendations published by major medical societies, and clinical practice guidelines for drug-resistant epilepsy and its medical and surgical treatment options. Evidence and recommendations are classified according to the criteria of the Oxford Centre for Evidence-Based Medicine (2001) and the European Federation of Neurological Societies (2004) for therapeutic actions. CONCLUSIONS: Identifying patients with drug-resistant epilepsy is important for optimising drug therapy. Experts recommend rational polytherapy with antiepileptic drugs to find more effective combinations with fewer adverse effects. When adequate seizure control is not achieved, a presurgical evaluation in an epilepsy referral centre is recommended. These evaluations explore how to resect the epileptogenic zone without causing functional deficits in cases in which this is feasible. If resective surgery is not achievable, palliative surgery or neurostimulation systems (including vagus nerve, trigeminal nerve, or deep brain stimulation) may be an option. Other treatment alternatives such as ketogenic diet may also be considered in selected patients.

Importance of ventricular function in the election of electro heart mode.

The integration of the ventricular function is essential when making decisions over a patient subjected to cardiac electrostimulation in order to understand the structure followed in the new cardiac stimulation and resynchronising therapy guides. To support the importance of ventricular function in cardiac electrostimulation it is important to know: (i)the deleterious effect of stimulation on the right ventricle apex; (ii)the effect over the left ventricular function produced by complete blockage of the left branch, and (iii)left ventricular disfunction as arrythmogenic substrate. When it comes to decide what type of cardiac electrostimualtion to apply we will know: the percentage of ventricular stimulation needed and its ventricular function. A normal ventricular function will enable electrostimulation from the right ventricle apex or alternative site. On the contrary, if this value is lower than 50% the most recommended electrostimulation is cardiac resynchronisation (CRT-P), which will be accompanied by defibrillation (CRT-D) if FEVI is lower than 35%.

Greenhouse gas emissions from stabilization ponds in subtropical climate.

Waste stabilization ponds (WSPs) are a cost-efficient method to treat municipal and non-toxic industrial effluents. Numerous studies have shown that WSPs are a source of greenhouse gas (GHG). However, most reports concerned anaerobic ponds (AP) and few have addressed GHG emissions from facultative (FP) and aerobic/maturation ponds (MPs). In this paper, GHG emissions from three WSP in series are presented. These WSPs were designed as anaerobic, facultative and aerobic/maturation and were treating agricultural wastewater. CH4 fluxes from 0.6 +/- 0.4 g CH4 m(-2) d(-1) in the MP, to 7.0 +/- 1.0 g CH4 m(-2) d(-1) in the (AP), were measured. A linear correlation was found between the loading rates of the ponds and CH4 emissions. Relatively low CO2 fluxes (0.2 +/- 0.1 to 1.0 +/- 0.8 g CO2 m(-2) d(-1)) were found, which suggest that carbonate/bicarbonate formation is caused by alkaline pH. A mass balance performed showed that 30% of the total chemical oxygen demand removed was converted to CH4. It has been concluded that the WSP system studied emits at least three times more GHG than aerobic activated sludge systems and that the surface loading rate is the most important design parameter for CH4 emissions.

Cognitive rehabilitation program in patients with multiple sclerosis: A pilot study.

INTRODUCTION: In recent years, there has been an increase of studies dedicated to cognitive rehabilitation in patients with multiple sclerosis (MS); however, few of these analyze the impact on such variables as cognitive reserve. The study aims to explore the effects of a cognitive rehabilitation program comprising a combination of cognitive and physical exercises, as well as group sessions to improve cognitive performance, emotional state, and cognitive reserve index. METHOD: Fifty patients with MS were subdivided into 2 groups: the control group, which performed aerobic exercise (n=25), and the experimental group (n=25), which participated in the integrated cognitive rehabilitation program (ICRP). All participants were evaluated 3 times (baseline, post-treatment, and long-term) with the Brief Repeatable Battery of Neuropsychological Tests, Cognitive Reserve Scale, Beck Depression Inventory, and a scale evaluating trait and state anxiety. RESULTS: Compared with the control group, patients in the experimental group showed improvements in cognitive function, with significant changes in measures of information processing speed, attention, memory, cognitive reserve index, and long-term mood. CONCLUSIONS: The ICRP was effective in improving cognitive and emotional function in MS, and increased the cognitive reserve index.

Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial.

AIMS/HYPOTHESIS: The aim of this work was to evaluate the efficacy and safety of canagliflozin vs placebo and sitagliptin in patients with type 2 diabetes who were being treated with background metformin. METHODS: This randomised, double-blind, four-arm, parallel-group, Phase 3 study was conducted at 169 centres in 22 countries between April 2010 and August 2012. Participants (N = 1,284) with type 2 diabetes aged ≥ 18 and ≤ 80 years who had inadequate glycaemic control (HbA1c ≥ 7.0% [53 mmol/mol] and ≤10.5% [91 mmol/mol]) on metformin therapy received canagliflozin 100 mg or 300 mg, sitagliptin 100 mg, or placebo (n = 368, 367, 366, 183, respectively) for a 26 week, placebo- and active-controlled period followed by a 26 week, active-controlled period (placebo group switched to sitagliptin [placebo/sitagliptin]) and were included in the modified intent-to-treat analysis set. Randomisation was performed using a computer-generated schedule; participants, study centres and the sponsor were blinded to group assignment. The primary endpoint was change from baseline in HbA1c at week 26; secondary endpoints included changes in HbA1c (week 52) and fasting plasma glucose (FPG), body weight, and systolic blood pressure (BP; weeks 26 and 52). Adverse events (AEs) were recorded throughout the study. RESULTS: At week 26, canagliflozin 100 mg and 300 mg reduced HbA1c vs placebo (-0.79%, -0.94%, -0.17%, respectively; p < 0.001). At week 52, canagliflozin 100 mg and 300 mg demonstrated non-inferiority, and canagliflozin 300 mg demonstrated statistical superiority, to sitagliptin in lowering HbA1c (-0.73%, -0.88%,-0.73%, respectively); differences (95% CI) vs sitagliptin were 0% (-0.12, 0.12) and -0.15% (-0.27, -0.03), respectively. Canagliflozin 100 mg and 300 mg reduced body weight vs placebo (week 26: -3.7%, -4.2%, -1.2%, respectively; p < 0.001) and sitagliptin (week 52: -3.8%, -4.2%, -1.3%, respectively; p < 0.001). Both canagliflozin doses reduced FPG and systolic BP vs placebo (week 26) and sitagliptin (week 52) (p < 0.001). Overall AE and AE-related discontinuation rates were generally similar across groups, but higher with canagliflozin 100 mg. Genital mycotic infection and osmotic diuresis-related AE rates were higher with canagliflozin; few led to discontinuations. Hypoglycaemia incidence was higher with canagliflozin. CONCLUSIONS/INTERPRETATION: Canagliflozin improved glycaemia and reduced body weight vs placebo (week 26) and sitagliptin (week 52) and was generally well tolerated in patients with type 2 diabetes on metformin. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov NCT01106677 FUNDING: This study was supported by Janssen Research & Development, LLC.

Limbic encephalitis: a clinical-radiological comparison between herpetic and autoimmune etiologies.

BACKGROUND: Herpetic (HE) and autoimmune (AE) encephalitis share clinical and radiological features. We compared both types of encephalitis with the aim of making a differential clinical-radiological pattern. MATERIALS AND METHODS: All cases with a clinical diagnosis of encephalitis who attended our hospital between 1999 and 2012 were reviewed. We selected those cases with positive polymerase chain reaction for herpes simplex virus 1 (HSV-1) in the cerebrospinal fluid (CSF), and those with antineuronal antibodies or paraneoplastic etiology. We compared epidemiological, clinical, CSF, electroencephalographic and radiological findings. RESULTS: Twelve patients with positive polymerase chain reaction for HSV-1, and 10 patients with antineuronal antibody or paraneoplastic etiology were found. The only features found exclusively in one group were the presence of psychiatric symptoms and tumors in AE. Acute onset of symptoms, fever and aphasia were more frequent in HE, which showed higher level of proteins and erythrocyte count in CSF. Neuroimaging was abnormal in all cases of HE, but only in 60% of AE. Insular and diffuse temporal lobe involvement and absence of basal ganglia involvement were more frequent in HE, and mesial temporal involvement in AE. The highest diagnostic values for differentiating HE from AE were the association of acute onset of symptoms and fever (sensitivity 0.92, specificity 1), and the absence of basal ganglia involvement (sensitivity 0.82, specificity 1). CONCLUSIONS: There are few differences between HE and AE. Psychiatric symptoms and association with tumors were unique for AE. Acute onset with fever and absence of basal ganglia involvement in magnetic resonance imaging support a diagnosis of HE.

Serum IL-12 is increased in Mexican obese subjects and associated with low-grade inflammation and obesity-related parameters.

Interleukin-(IL-) 12 has been recently suggested to participate during development of insulin resistance in obese mice. Nevertheless, serum IL-12 levels have not been accurately determined in overweight and obese humans. We thus studied serum concentrations of IL-12 in Mexican adult individuals, examining their relationship with low-grade inflammation and obesity-related parameters. A total of 147 healthy individuals, 43 normal weight, 61 overweight, and 43 obese subjects participated in the study. Circulating levels of IL-12, tumor necrosis factor-alpha (TNF- α ), leptin, insulin, glucose, total cholesterol, and triglyceride were measured after overnight fasting in all of the study subjects. Waist circumference and body fat percentage were recorded for all the participants. Serum IL-12 was significantly higher in overweight and obese individuals than in normal weight controls. Besides being strongly related with body mass index (r = 0.5154), serum IL-12 exhibited a significant relationship with abdominal obesity (r = 0.4481), body fat percentage (r = 0.5625), serum glucose (r = 0.3158), triglyceride (r = 0.3714), and TNF- α (r = 0.4717). Thus, serum levels of IL-12 are increased in overweight and obese individuals and show a strong relationship with markers of low-grade inflammation and obesity in the Mexican adult population. Further research is needed to understand the role of IL-12 in developing obesity-associated alterations in humans.

Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism.

Maturity-onset diabetes of the young type 3 (MODY3) is caused by haploinsufficiency of hepatocyte nuclear factor-1alpha (encoded by TCF1). Tcf1-/- mice have type 2 diabetes, dwarfism, renal Fanconi syndrome, hepatic dysfunction and hypercholestrolemia. Here we explore the molecular basis for the hypercholesterolemia using oligonucleotide microchip expression analysis. We demonstrate that Tcf1-/- mice have a defect in bile acid transport, increased bile acid and liver cholesterol synthesis, and impaired HDL metabolism. Tcf1-/- liver has decreased expression of the basolateral membrane bile acid transporters Slc10a1, Slc21a3 and Slc21a5, leading to impaired portal bile acid uptake and elevated plasma bile acid concentrations. In intestine and kidneys, Tcf1-/- mice lack expression of the ileal bile acid transporter (Slc10a2), resulting in increased fecal and urinary bile acid excretion. The Tcf1 protein (also known as HNF-1alpha) also regulates transcription of the gene (Nr1h4) encoding the farnesoid X receptor-1 (Fxr-1), thereby leading to reduced expression of small heterodimer partner-1 (Shp-1) and repression of Cyp7a1, the rate-limiting enzyme in the classic bile acid biosynthesis pathway. In addition, hepatocyte bile acid storage protein is absent from Tcf1-/- mice. Increased plasma cholesterol of Tcf1-/- mice resides predominantly in large, buoyant, high-density lipoprotein (HDL) particles. This is most likely due to reduced activity of the HDL-catabolic enzyme hepatic lipase (Lipc) and increased expression of HDL-cholesterol esterifying enzyme lecithin:cholesterol acyl transferase (Lcat). Our studies demonstrate that Tcf1, in addition to being an important regulator of insulin secretion, is an essential transcriptional regulator of bile acid and HDL-cholesterol metabolism.