Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of dopamine D1 receptors.

Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines' effects in social competition are not understood. Converging evidence points to the mesolimbic system as a potential site of action for at least some benzodiazepine-mediated effects. Furthermore, mitochondrial function in the nucleus accumbens (NAc) has been causally implicated in the link between anxiety and social competitiveness. Here, we show that diazepam facilitates social dominance, ameliorating both the competitive disadvantage and low NAc mitochondrial function displayed by high-anxious rats, and identify the ventral tegmental area (VTA) as a key site of action for direct diazepam effects. We also show that intra-VTA diazepam infusion increases accumbal dopamine and DOPAC, as well as activity of dopamine D1- but not D2-containing cells. In addition, intra-NAc infusion of a D1-, but not D2, receptor agonist facilitates social dominance and mitochondrial respiration. Conversely, intra-VTA diazepam actions on social dominance and NAc mitochondrial respiration are blocked by pharmacological NAc micro-infusion of a mitochondrial complex I inhibitor or an antagonist of D1 receptors. Our data support the view that diazepam disinhibits VTA dopaminergic neurons, leading to the release of dopamine into the NAc where activation of D1-signaling transiently facilitates mitochondrial function, that is, increased respiration and enhanced ATP levels, which ultimately enhances social competitive behavior. Therefore, our findings critically involve the mesolimbic system in the facilitating effects of diazepam on social competition and highlight mitochondrial function as a potential therapeutic target for anxiety-related social dysfunctions.

Study of the possible link of 25-hydroxyvitamin D with Epstein-Barr virus and human herpesvirus 6 in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Although the causes of multiple sclerosis (MS) remain partially unknown, environmental and genetic factors are thought to play a role in its aetiopathogenesis. Hypovitaminosis D, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) infections have been described as possible MS triggers. Our aim was to analyse the possible link between 25-hydroxyvitamin D [25(OH)D] and viruses in patients with MS. METHODS: We included 482 patients with MS in a 2-year study. Serum samples were collected to analyse 25(OH)D levels and, according to sample availability, antibody titres against EBV and HHV-6 by enzyme-linked immunosorbent assay. DNA was extracted from blood in order to analyse EBV and HHV-6 viral load by quantitative real-time polymerase chain reaction and to genotype MS-related single nucleotide polymorphisms (rs3135388, rs2248359 and rs12368653) when possible. RESULTS: The 25(OH)D levels were significantly higher in the first semester of the year than in the second. Carriers of the risk allele rs2248359-C showed lower 25(OH)D levels than non-carriers. For EBV, viral load was significantly higher when 25(OH)D levels were low, demonstrating an inverse correlation between 25(OH)D levels and EBV load. CONCLUSIONS: The 25(OH)D levels could be involved in the regulation of EBV replication/reactivation in patients with MS.

Eosinophilic Esophagitis: Demographic, Clinical, Endoscopic, Histologic, and Atopic Characteristics of Children and Teenagers in a Region in Central Spain.

BACKGROUND AND OBJECTIVE: Eosinophilic esophagitis (EoE) is an increasingly prevalent chronic inflammatory disease of the esophagus with an immunoallergic etiology. Few studies have been published on EoE in children and adolescents. The objective of this study was to analyze the demographic, clinical, serologic, endoscopic-histologic, and atopic characteristics of pediatric patients with EoE and to identify atopic and digestive comorbidities. METHODS: We conducted a prospective observational study in children and adolescents (<16 years) assessed in a specialized multidisciplinary EoE unit in a tertiary referral hospital in a central region of Spain between 2011 and 2015. RESULTS: Thirty-five patients were included in the study. Twenty-eight (80%) were male. The mean age was 9.6 years, 83% were atopic, and 28% reported a family history of atopy. The most common symptom was dysphagia (51%). Eosinophilia was detected in the blood of 60% of patients. Eosinophil cationic protein and total IgE were elevated in 88% and 77% of patients, respectively. The most frequent endoscopic finding was linear grooves (57%). Skin tests with aeroallergens were positive in 82% of patients (pollen 62% and food 60%). The main atopic comorbidities were asthma (48%) and rhinoconjunctivitis (37%). Digestive diseases were more often associated with gastritis and Helicobacter pylori infection (17%). CONCLUSIONS: Our results are similar to those previously reported. EoE is more common in boys and in individuals with a history of atopy and sensitization to airborne allergens and food. These results support the consideration of EoE as an atopic disease and underline the important role of allergists in early diagnosis and treatment.

Diagnosis and quantification of fibrosis, steatosis, and hepatic siderosis through multiparametric magnetic resonance imaging. / Diagnóstico y cuantificación de fibrosis, esteatosis y hepatosiderosis por medio de resonancia magnética multiparamétrica.

BACKGROUND: The presence of liver fibrosis is the common denominator in numerous chronic liver diseases that can progress to fibrosis and hepatocellular carcinoma. Most important, with respect to frequency, are viral hepatitis and non-alcoholic fatty liver disease, the prevalence of which is increasing in epidemic proportions. Liver biopsy, albeit imperfect, continues to be the criterion standard, but in many clinical situations tends to be replaced with noninvasive imaging methods. OBJECTIVES: The aim of the present article was to describe our imaging department experience with magnetic resonance elastography and to analyze and discuss recently published results in gastroenterology, hepatology, and radiology from other authors in the literature, complemented with a PubMed search covering the last 10 years. RESULTS AND CONCLUSIONS: Magnetic resonance elastography is an efficacious, noninvasive method with results that are concordant with liver biopsy. It is superior to ultrasound elastography because it evaluates a much greater volume of hepatic tissue and shows the often heterogeneous lesion distribution. The greatest advantage of the magnetic resonance protocol described is the fact that it quantifies fibrosis, fat content, and iron content in the same 25min examination specifically directed for that purpose, resulting in a favorable cost-benefit ratio for the patient and/or institution.

Proximalize osteotomy of tibial tuberosity (POTT) as a treatment for stiffness secondary to patella baja in total knee arthroplasty (TKA).

INTRODUCTION: Stiffness after a total knee arthroplasty (TKA) is one of the most common post-operative complications. The purpose of this study is the evaluation of the effectiveness of TT proximalization osteotomy of improving a lack of flexion and secondary pain in patella baja (infera) post-TKA. MATERIALS AND METHODS: Between April 2007 and July 2012, TT proximalization osteotomy was performed on 21 patients. The average preoperative flexion was 70° (in a range of 60-80). Clinical pre- and post-operative evaluations were performed with Knee Society Score, Western Ontario and McMaster Universities Arthritis Index scales and a satisfaction survey. Modified Blackburn-Peel index and Portner angle were used to evaluate patellar height. RESULTS: After an average follow-up of 35 months (range 18-48), an average flexion of 100° (range 90-100) and an overall satisfaction were obtained. Clinical scores improved significantly. The Blackburn-Peel index and Portner angle improved significantly from 0.3 (range 0.1-0.5) to 0.4 (0.3-0.5) and from 9 (3-15) to 12 (9-18), respectively. Three patients showed no signs of osteotomy consolidation. However, this was not linked to a lack of extension or an increase in local pain. CONCLUSION: TT proximalization osteotomy provides satisfactory results in improving a lack of flexion and pain in patella baja post-TKR.

Liver-specific gadoxetic acid-enhanced magnetic resonance for focal lesion evaluation.

Gadolinium-enhanced magnetic resonance for the evaluation of hepatic lesions is increasingly being used in clinical practice, especially in patients with suspicious focal lesions, whether benign or malignant. In regard to hepatocellular carcinoma, the diagnostic performance of magnetic resonance through the «conventional¼ protocols and multi-detector computerized tomography consisting of multiphase evaluation with intravenous contrast, largely depends on the size of the lesion. They are more reliable in lesions>2cm. However, in lesions measuring 1-2cm, establishing the definitive diagnosis is a real challenge, with sensitivity values of 45-65%, but generally with excellent specificity (>95%). Furthermore, if the lesion has a diameter<1cm, diagnosis is usually unreliable. In these last 2 settings, the complementary use of liver-specific contrast agents can be advantageous. The aim of our article was to review the current evidence on the usefulness of this new non-invasive diagnostic method in hepatic lesions.

Should all patients be optimized to the same preoperative hemoglobin level to avoid transfusion in primary knee arthroplasty?

BACKGROUND AND OBJECTIVE: Optimization of the preoperative hemoglobin (Hb) level is an effective way to reduce allogeneic transfusion in total knee arthroplasty (TKA) though the procedure is expensive, requires close monitoring and is often inconvenient for patients with reduced mobility. Our aim was to investigate the value of preoperative Hb levels to predict transfusion and thereby tailoring Hb optimization to patient characteristics. MATERIALS AND METHODS: All consecutive patients who undergone primary TKA in our center over 2 years, and received tranexamic acid intraoperatively, were reviewed. The adjusted association between preoperative Hb levels and transfusion was assessed by multivariate logistic regression, and the estimated probability of transfusion for individual patients was derived from the logistic model. RESULTS: Out of the 784 patients who meet the inclusion criteria, risk of transfusion was associated with poorer performance status, as measured by the America Association of Anestesiology (ASA) score III/IV (OR: 3·3, P < 0·001) and lower preoperative Hb level (OR 3·8 for each g/dl below 13 g/dl; P < 0·001). According to the Hb level, the estimated probability of transfusion was 0·03 (range: 0·03-0·64) for ASA I/II patients and 0·10 (range: 0·10-0·84) for ASA III/IV. CONCLUSION: Not all the patients undergoing TKA who receive tranexamic acid need the same preoperative Hb optimization target. Two easily available factors, such as the ASA score and the Hb level, can help individualize the Hb optimization target.

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.

The HUGE formula (hematocrit, urea and gender): association with cardiovascular risk.

OBJECTIVES: To evaluate the relationship between chronic renal failure (CFR) defined through HUGE (hematocrit, urea and gender) formula score and the patient's cardiovascular risk measured through cardiovascular disease antecedents such as ischemic cardiopathy, cerebrovascular disease and peripheral arterial disease. DESIGN AND METHODS: The sample consisted of 2,831 subjects. Mean age was 51.2±14.7 years and 53.5% were female. Serum creatinine, urea, hematocrit and 24h proteinuria were analyzed. HUGE score was calculated from gender, urea and hematocrit. GFR was estimated from uncalibrated serum creatinine using the abbreviated Modification of Diet in Renal Disease equation (MDRD-4). UAE was measured in first morning urine sample. RESULTS: Using HUGE formula 2.2% (n = 61) of subjects had CRF. Of them, 12 (19.7%) had cardiovascular disease history. Among patients without CRF (n = 2770), 194 subjects had history of previous cardiovascular diseases (0.07%; p < 0.001 Square Chi test). Using the MDRD-4 formula 4.0% of subjects (n = 113) had a GFR < 60 ml/min. Of them, 18 (15.9%) had cardiovascular disease history. Among patients without CRF (n = 2718), 188 subjects had history of previous cardiovascular diseases (0.07%; p < 0.001 Square Chi test). Odd's ratio for cardiovascular diseases using HUGE definition of CRF was 3.25 (p = 0.001, Mantel-Haenszel test). CFR was associated to higher pulse pressure (PP) and increased urinary albumin excretion. CONCLUSIONS: A significant cardiovascular risk was associated to the diagnosis of CRF through HUGE formula. This relation was closer than the obtained using MDRD estimated GFR in spite of a bigger sample. HUGE formula seems to be a useful tool for diagnosing CRF and evaluate the cardiovascular risk of these patients.

Spatial and temporal effects of port facilities expansion on the surface area of shallow coral reefs.

There is a close relationship between ports and reef areas, mainly because reefs provide protection to vessels against extreme weather events like storms and hurricanes. This historical relationship has generated severe impacts on reef ecosystems. In order to identify the main impacts from the construction of port facilities in shallow coral reef areas, we analyzed and described the effects of land reclamation and coastal structure construction associated to port growth throughout a century in the Sistema Arrecifal Veracruzano National Park, Mexico. We used aerial photographs and maps of the nineteenth and early twentieth century to assess the impacts caused by port expansion activities on shallow coral reefs. Three types of impacts were identified: (a) direct reef area loss caused by landfills and perpendicular coastal structures construction leading to the loss of nearly 50 % of the fringing reef near to the port; (b) fragmentation in short- and medium-term scale, which affects two fringing reefs, and (c) long-term modification of coastal dynamics leading to sedimentation and loss of a complete reef area. On the eve of a new expansion of Veracruz Port, we used the New Port Project Plan, long-shore net drift geomorphic indicators and the port impact typology from the 100-year period assessment to evaluate a possible future scenario. The scenario describes how the new expansion project will repeat the three types of impacts affecting a whole reef area, which is currently part of the National Park.