Ingestion of a THC-Rich Cannabis Oil in People with Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To determine the benefit of a tetrahydrocannabinol (THC)-rich cannabis oil on symptoms and quality of life of fibromyalgia patients. METHODS: A double-blind, randomized, placebo-controlled clinical trial was conducted for eight weeks to determine the benefit of a THC-rich cannabis oil (24.44 mg/mL of THC and 0.51 mg/mL of cannabidiol [CBD]) on symptoms and quality of life of 17 women with fibromyalgia, residents of a neighborhood with a low socioeconomic profile and a high incidence of violence in the city of Florianopolis, Brazil. The initial dose was one drop (∼1.22 mg of THC and 0.02 mg of CBD) a day with subsequent increases according to symptoms. The Fibromyalgia Impact Questionnaire (FIQ) was applied at pre- and postintervention moments and in five visits over eight weeks. RESULTS: There were no significant differences on baseline FIQ score between groups. However, after the intervention, the cannabis group presented a significant decrease in FIQ score in comparison with the placebo group (P = 0.005) and in comparison with cannabis group baseline score. (P < 0.001). Analyzing isolated items on the FIQ, the cannabis group presented significant improvement on the "feel good," "pain," "do work," and "fatigue" scores. The placebo group presented significant improvement on the "depression" score after intervention. There were no intolerable adverse effects. CONCLUSIONS: Phytocannabinoids can be a low-cost and well-tolerated therapy to reduce symptoms and increase the quality of life of patients with fibromyalgia. Future studies are still needed to assess long-term benefits, and studies with different varieties of cannabinoids associated with a washout period must be done to enhance our knowledge of cannabis action in this health condition.

Cross-cultural validation of a taste test with paper strips.

Taste dysfunctions influence food choices, interpersonal communication and danger/health. A gustometry protocol is the mainstream for clinical taste disorders diagnosis and suggests possible therapeutics. No clinical gustometry protocol has been adapted and validated to the Portuguese population so far. We aim to validate a gustometry protocol based on strips made from filter paper impregnated with different taste solutions. Four concentrations each for sweet, sour, salty and bitter were administered to 75 subjects. Hypogeusia threshold is of 4.8 in this population. Repeated measures indicated a good reliability and validity for the taste strips (ρ 75 = 0.68, p < 0.001). Although Mediterranean food implies a heathy eating pattern, taste threshold scores may be lower because of its habituation to natural food flavoring. The taste strip gustometry protocol can be applied to the clinical practice in Portugal. It is quick, effective and cheap. The diagnostic utility of this method is indisputable, as well as the advantages we can obtain with its application, for early diagnosis and distinction between disorders of taste and smell.

[Detection of toxigenic genes nheA, nheB and nheC in Bacillus cereus strains isolated from powdered milk samples in Costa Rica]. / Presencia de los genes de toxigenicidad nheA, nheBy nheC en cepas de Bacillus cereus aisladas de leches deshidratadas en Costa Rica.

Powdered milk is a frequently consumed product that does not need to be kept under cold conditions. Nevertheless, different microorganisms may contaminate it. Powdered milk is a highly consumed product by Costa Rican population, and Bacillus cereus is a potentially pathogenic bacteria associated to it, with the ability to develop toxins depending on the presence of the respective codifying genes. The aim of this study was to determine the presence of the toxigenic genes nheA, nheB and nheC from B. cereus strains, found in powdered milk sold at the Costa Rican national market. Five different lots of ten brands of powdered milk, distributed in the metropolitan area of San José, Costa Rica were analyzed. B cereus load was quantified using the Most Probable Number technique and identified using the Vitek system. The presence of the toxigenic genes was determined using the PCR technique. The isolation frequency of this bacteria in the powdered milk samples analyzed reached 50%, with populations ranging from 3 to > 100 MPN/g. Five out from nineteen strains were found positive for the three toxigenic genes, indicating contamination with potentially toxigenic B. cereus in powdered milk distributed in the national market, and an important risk for public. health.

Surgical Management of Severe Mandibular Actinomycosis: Segmental Mandibulectomy and Fibula Free Flap for Optimal Outcomes.

Actinomycosis is a chronic, suppurative, granulomatous bacterial infection primarily associated with Actinomyces israelii. The condition can be categorized into three distinct clinical types based on the affected anatomical region: cervicofacial, pulmonary, or abdominopelvic actinomycosis. The standard treatment for actinomycosis involves antibiotic therapy, with an empiric penicillin regimen as the first-line approach. Surgical interventions comprise curettage of the affected bone, resection of necrotic tissues, excision of existing sinus tracts, and drainage of abscesses. These procedures are considered a last resort for cases of actinomycosis unresponsive to antibiotic therapy. In this context, we present a case of severely unresponsive actinomycosis that necessitated aggressive surgical resection of the infected mandibular bone, followed by immediate reconstruction using a fibula-free flap. The outcome yielded both favorable functional and aesthetic results.

[Analysis of the microbiological quality and potential presence of Listeria monocytogenes in custard apple (Annona muricata), mango (Mangifera indica) and passion fruit (Passiflora edulis) pulps from Costa Rica]. / Análisis de la calidad microbiológica y potencial presencia de Listeria monocytogenes en pulpas de guanábana (Annona muricata), mango (Mangifera indica) y maracuyá (Passiflora edulis) costarricenses.

The objective of this work was to determine some of the indicators associated to shelf life, hygiene, process and storage conditions for some of custard apple, mango and passion fruit pulps distributed by the main supermarket chains of the Metropolitan Area of San José, Costa Rica, as well as to examine the potential presence of Listeria monocytogenes in them. Sixty fruit pulp samples were analyzed. Tests included pH determination, total aerobic plate count, yeasts and mold count, lactic bacteria count, total and fecal most probable number and the presence/absence of Listeria monocytogenes in 25 g of the product. Fruit pulp's pH ranged between 3,1 and 3,9, and the microbiological counts obtained were relatively low except for one industry. None of the samples analyzed presented total or fecal coliforms. The presence of Listeria monocytogenes was confirmed in three samples, all of them coming from industry C. Low microbiological counts obtained may be due to the addition of preserving substances and to the pasteurization of some of the products; lack of these two elements may allow the presence of dangerous bacteria such as Listeria monocytogenes.

Epigenetic developmental programming and intergenerational effects of thyroid hormones.

Mounting evidence is showing that altered signaling through the nuclear hormone receptor superfamily can cause abnormal, long-term epigenetic changes which translate into pathological modifications and susceptibility to disease. These effects seem to be more prominent if the exposure occurs early in life, when transcriptomic profiles are rapidly changing. At this time, the coordination of the complex coordinated processes of cell proliferation and differentiation that characterize mammalian development. Such exposures may also alter the epigenetic information of the germ line, potentially leading to developmental changes and abnormal outcomes in subsequent generations. Thyroid hormone (TH) signaling is mediated by specific nuclear receptors, which have the ability to markedly change chromatin structure and gene transcription, and can also regulate other determinants of epigenetic marks. TH exhibits pleiotropic effects in mammals, and during development, its action is regulated in a highly dynamic manner to suit the rapidly evolving needs of multiple tissues. Their molecular mechanisms of action, timely developmental regulation and broad biological effects place THs in a central position to play a role in the developmental epigenetic programming of adult pathophysiology and, through effects on the germ line, in inter- and trans-generational epigenetic phenomena. These areas of epigenetic research are in their infancy, and studies regarding THs are limited. In the context of their characteristics as epigenetic modifiers and their finely tuned developmental action, here we review some of the observations underscoring the role that altered TH action may play in the developmental programming of adult traits and in the phenotypes of subsequent generations via germ line transmission of altered epigenetic information. Considering the relatively high prevalence of thyroid disease and the ability of some environmental chemicals to disrupt TH action, the epigenetic effects of abnormal levels of TH action may be important contributors to the non-genetic etiology of human disease.

Therapeutic Reduction Mammoplasty: Experience of a Single Institute.

INTRODUCTION: Breast cancer is the most common malignancy in women worldwide as reported by the World Health Organization. The concept of oncoplastic breast surgery appeared as an extension of breast-conserving surgery, applying breast reduction techniques with more acceptable aesthetic and functional outcomes. The purpose of the present study was to describe the breast cancer population of a single institute submitted to lumpectomy and bilateral immediate breast reduction or mastopexy and its complications. MATERIAL AND METHODS: This is a retrospective observational study including patients submitted to lumpectomy and immediate bilateral breast reduction or mastopexy. Patients and tumour characteristics, surgical technique, complications, follow-up period, and recurrence data were obtained and analyzed. RESULTS: A total of 49 patients were submitted to lumpectomy and bilateral breast therapeutic reduction/mastopexy, with a mean age of 56.47 ±8.58 years and a mean body mass index of 28.68kg/m2 ±3.94 kg/m² between January 2019 and December 2021. Invasive tumours of no specific type, associated or not, with carcinoma intraductal in situ were the most common histological type corresponding to almost 80% of the cases with T1 stage corresponding to more than half of the cases. Sixteen percent of the patients had early minor complications with wound dehiscence associated with wound delayed healing, corresponding to 75% of the cases. Body mass index had a statistical difference between groups (p=0,006, t-test). CONCLUSIONS: The low rates of minor and major complications show that immediate therapeutic breast reduction can be a suitable approach in selected cases.

Palatal brushing for the treatment of denture stomatitis: A multicentre randomized controlled trial.

PURPOSE: To determine the effectiveness of palatal brushing in the treatment of denture-related erythematous stomatitis (DES) in complete denture wearers. METHODS: This two-parallel-arm RCT was conducted in three university clinics in Brazil, Canada, and Chile. Participants (n=77) were randomly allocated to receive (i) instructions for palatal brushing and standard oral/denture hygiene ("intervention"); or (ii) standard oral/denture hygiene instructions only ("control"). Data collection was carried out at the baseline and at 3 and 6 months after intervention. Outcomes included the magnitude of oral Candida carriage and the degree of inflammation of denture-bearing tissues. Groups were compared using generalized estimating equations and chi-square test (α=0.05). RESULTS: Palatal inflammation levels were reduced significantly in the "intervention" compared to "control" group at 6 months (intervention: 70%, control: 40%; chi-square, p=0.04). There was no between-group significant difference in the Candida count from denture and palatal biofilms; however, a subgroup analysis restricted to baseline Candida carriers showed further reduction with the intervention at 6 months. No adversity was observed by trialist or reported by participants. CONCLUSIONS: Including palatal brushing in oral instructions for denture wearers has positive impact on DES-related mucosal inflammation. Thus, our findings endorse the inclusion of palatal brushing in standard oral hygiene instructions to treat DES.

Single crowns versus conventional fillings for the restoration of root filled teeth.

BACKGROUND: Endodontic treatment, involves removal of the dental pulp and its replacement by a root canal filling. Restoration of root filled teeth can be challenging due to structural differences between vital and non-vital root filled teeth. Direct restoration involves placement of a restorative material e.g. amalgam or composite directly into the tooth. Indirect restorations consist of cast metal or ceramic (porcelain) crowns. The choice of restoration depends on the amount of remaining tooth which may influence long term survival and cost. The comparative in service clinical performance of crowns or conventional fillings used to restore root filled teeth is unclear. OBJECTIVES: To assess the effects of restoration of endodontically treated teeth (with or without post and core) by crowns versus conventional filling materials. SEARCH METHODS: We searched the following databases: the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE via OVID, EMBASE via OVID, CINAHL via EBSCO, LILACS via BIREME and the reference lists of articles as well as ongoing trials registries.There were no restrictions regarding language or date of publication. Date of last search was 13 February 2012. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised controlled trials in participants with permanent teeth which have undergone endodontic treatment. Single full coverage crowns compared with any type of filling materials for direct restoration, as well as indirect partial restorations (e.g. inlays and onlays). Comparisons considered the type of post and core used (cast or prefabricated post), if any. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: One trial judged to be at high risk of bias due to missing outcome data, was included. 117 participants with a root filled premolar tooth restored with a carbon fibre post, were randomised to either a full coverage metal-ceramic crown or direct adhesive composite restoration. At 3 years there was no reported difference between the non-catastrophic failure rates in both groups. Decementation of the post and marginal gap formation occurred in a small number of teeth. AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the effectiveness of conventional fillings over crowns for the restoration of root filled teeth. Until more evidence becomes available clinicians should continue to base decisions on how to restore root filled teeth on their own clinical experience, whilst taking into consideration the individual circumstances and preferences of their patients.

Cytotoxicity of denture base and hard chairside reline materials: a systematic review.

STATEMENT OF PROBLEM: Adverse reactions to the materials used for the fabrication and reline of removable denture bases have been observed. PURPOSE: The purpose of this study was to systematically review the published literature on the cytotoxicity of denture base and hard reline materials. MATERIAL AND METHODS: MEDLINE via PubMed, Google Scholar, and Scopus databases for the period January 1979 to December 2009 were searched with the following key words: (biocompatibility OR cytotoxic* OR allergy OR "burning mouth" OR "cell culture techniques") AND ("acrylic resins" OR denture OR monomer OR relin* OR "denture liners"). The inclusion criteria included in vitro studies using either animal or human cells, in which the cytotoxicity of the denture base and hard chairside reline resins was tested. Studies of resilient lining materials and those that evaluated other parameters such as genotoxicity and mutagenicity were excluded. Articles published in the English language and in peer-reviewed journals focusing on the cytotoxicity of these materials were reviewed. RESULTS: A total of 1443 articles were identified through the search. From these, 20 studies were judged to meet the selection criteria and were included in the review. In the majority of the studies, continuous cell lines were exposed to eluates of specimens made from the materials, and mitochondrial activity was used to estimate cell viability. The tested acrylic resins were grouped according to 5 major categories: (1) heat-polymerized; (2) microwave-polymerized; (3) autopolymerizing; (4) light-polymerized; and (5) hard chairside reliners. CONCLUSIONS: This review provided some evidence that the heat-polymerized resins showed lower cytotoxic effects than autopolymerizing denture base acrylic resins and light or dual polymerized reline resins. However, because of the large number of variables in the reviewed literature, a definitive conclusion could not be drawn.

Effect of long-term water immersion on the fracture toughness of denture base and reline resins.

PURPOSE: This study evaluated the fracture toughness (FT) of one denture base (Lucitone 550 - L) and four hard reline resins [Ufi Gel Hard (UH), Tokuyama Rebase II (TR), New Truliner (NT) and Kooliner (K)], and the effect of long-term water storage on this property. MATERIALS AND METHODS: Forty specimens (40 × 8 × 4 mm) of each material were made, and FT was assessed after polymerisation (control of reliners), after 48 ± 2 h in water at 37°C (control of denture base resin) and after storage in water at 37°C for 7, 90 or 180 days (all materials). Data (MPa.m(1/2) ) were analysed by two-way anova and Games-Howell test (p = 0.05). RESULTS: Resin L exhibited the highest FT mean values. After 180 days of storage, FT mean values of L (3.37), UH (1.53) and K (1.20) were higher than those of the other periods. FT mean values of NT decreased from control (1.63) to 7 days (1.30) and then remained constant. FT mean values of TR (1.13) were similar in all periods of analysis. CONCLUSION: The denture base resin L showed higher FT mean values than the reline resins. Long-term water storage increased the FT of L, UH and K, reduced the FT of NT and did not influence the FT of TR.

[Bacteriological quality and toxigenic Bacillus cereus detection in cooked white rice sold at the metropolitan area of San José, Costa Rica]. / Calidad bacteriológica y detección de Bacillus cereus toxigénicos en arroz blanco cocido expendido en el área metropolitana de la provincia de San José, Costa Rica.

The wide use of rice is one of the factors that favors its implication in food borne diseases, and one of the most important pathogens associated to it is Bacillus cereus. The aim of this work was to evaluate the microbiological quality of 50 samples of white cooked rice sold in restaurants at the Metropolitan Area of San José, Costa Rica, including the determination of the total aerobic plate count, the Most Probable Number of total and fecal coliforms and Escherichia coli. MPN of Bacillus cereus and the detection of nheA, nheB and nHeC genes, associated to its toxicity, was also performed. Procedures described in the Compendium of Methods for the Microbiological Examination of Foods were followed for the bacteriological analysis, multiplex PCR was used for the detection of genes following the methodology described by Hansen et al, 2001. 46% of the samples analysed were positive for total coliforms, 34% for fecal coliforms, 16% for E. coli and 10% for B. cereus, being 8% toxigenic. These facts suggest that white cooked rice may represent a risk for Pubic Health and that improvements shall be performed in order to offer a safe and high quality product to consumers.

Early onset obesity due to a mutation in the human leptin receptor gene.

Summary: Leptin is secreted by adipocytes in response to fat storage and binds to its receptor (LEPR), which is ubiquitously expressed throughout the body. Leptin regulates energy expenditure and is anorexigenic. In this study, we describe the clinical and hormonal findings of three siblings with a personal history of rapid weight gain during the first months of life. They had delayed puberty, high levels of FSH (15.6 ± 3.7 mUI/mL; reference: 1.5-12.4) and LH (12.3 ± 2.2 mUI/mL; reference: 1.7-8.6), normal oestradiol and total testosterone and successful fertility. None of the patients had dyslipidemia, diabetes or thyroid disease. Next-generation sequencing identified a pathogenic homozygous variant c.2357T>C, p.(Leu786Pro) in LEPR. Their parents and children were heterozygous for this mutation. We compared clinical and biochemical findings of homozygous carriers with first-degree heterozygous family members and ten randomly selected patients with adult-onset morbid obesity. Homozygous carriers of the mutation had significantly higher BMI (32.2 ± 1.7 kg/m2 vs 44.5 ± 7.1 kg/m2, P = 0.023) and increased serum levels of leptin (26.3 ± 9.3 ng/mL vs 80 ± 36.4 ng/mL, P = 0.028) than their heterozygous relatives. Compared with the ten patients with adult-onset morbid obesity, serum levels of leptin were not significantly higher in homozygous carriers (53.8 ± 24.1 ng/mL vs 80 ± 36.4 ng/mL, P = 0.149), and thus serum levels of leptin were not a useful discriminative marker of LEPR mutations. We described a rare three-generation family with monogenic obesity due to a mutation in LEPR. Patients with early onset obesity should be considered for genetic screening, as the identification of mutations may allow personalized treatment options (e.g. MC4R-agonists) and targeted successful weight loss. Learning points: The early diagnosis of monogenic forms of obesity can be of great interest since new treatments for these conditions are becoming available. Since BMI and leptin levels in patients with leptin receptor mutations are not significantly different from those found in randomly selected morbid obese patients, a careful medical history is mandatory to suspect this condition. Loss of leptin receptor function has been associated with infertility. However, our patients were able to conceive, emphasizing the need for genetic counselling in affected patients with this condition.

Surgical pathology associated with Meckel´s diverticulum in a tertiary hospital: 12 year review.

OBJECTIVE: We want to present our experience about surgical pathology of Meckel´s diverticulum by means of a retrospective study. MATERIAL AND METHODS: We report a group of patients of our Department of General and Abdominal Surgery and Paediatric Surgery of our Hospital with Meckel´s diverticulum since January 1997 to January 2010. We report the clinical presentation, complementary test, interventions, and the postoperative follow up. RESULTS: 45 patients were operated in total, 33 of them in emergency surgery under the clinical form of acute abdominal pain; and the others 12 in programmed surgery, these cases came up more frequently like a clinical manifestations of latent abdominal pain, rectal bleeding and anemia. The complementary tests were so varied; abdominal ultrasounds were used in 63% of emergency cases and the 40% of programmed cases, in these patients,gammagraphy with Tc99 was the second test in frequency. Laparoscopy was used in 10 cases (22%). The main surgery technique used was diverticulectomy (82%). CONCLUSIONS: The presence of Meckel´s diverticulum has to be clinically suspected in all patients with abdominal pain of unknow naetiology. Access to the abdominal cavity using routine laparoscopy provides essential information on the diagnosis and for the treatment.

[Bacteriological quality of traditional, organic and hydroponic cultured lettuce in Costa Rica]. / Comparación de la calidad bacteriológica de la lechuga (Lactuca sativa) producida en Costa Rica mediante cultivo tradicional, orgánico o hidropónico.

The main objective of this work was to evaluate the microbiological quality of lettuces commercialized in the Metropolitan Area of San José, Costa Rica, and cultured in different ways, in order to detect differences between the culturing methods and the risk that these products may represent for Public Health. The study was done at the Food Microbiology Laboratory, Universidad de Costa Rica, from March to July, 2010. 30 lettuce samples were analyzed (10 obtained by traditional culture, 10 by organic culture and 10 by hydropony). All samples were obtained from markets where their origin was certified. Total aerobic plate count, total and fecal coliforms count and Escherichia coli were determined to all samples, as well as the presence/abscense of Salmonella spp. and Listeria monocytogenes in 25 g. Results obtained show that there is no statistically significant difference (p < 0.001) between the different types of cultures analyzed for any of the parameters evaluated. An important percentage of the samples presented coliforms, nevertheless, just one E. coli strain was isolated from a traditionally cultured lettuce sample. Four different Salmonella spp. strains were isolated from the samples as well as one Listeria monocytogenes strain. Data obtained show that the consumption of this product, raw or without an adequate hygiene and disinfection may represent a risk for health. Also, from the bacteriological point of view, there is no significant difference between the culturing methods evaluated, suggesting that the specific directions for each type of culture are not followed or that there is an inadequate handling of the products or post harvest contamination.

Successful long-term use of pioglitazone in Berardinelli-Seip lipodystrophy-associated diabetes.

SUMMARY: Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare autosomal recessive disease, characterized by the absence of subcutaneous adipose tissue, leptin deficiency and severe metabolic complications, such as insulin resistance, diabetes mellitus, and dyslipidemia. The most common mutation occurs in BCSL2 which encodes seipin, a protein involved in adipogenesis. We report a patient with BSCL who was diagnosed with diabetes at 11 years old. He was started on metformin 1000 mg twice daily, which lowered glycated hemoglobin (HbA1c) to less than 7%. Four months later, HbA1c raised above 7.5%, indicating secondary failure to metformin. Therefore, we added the peroxisome proliferator-activated receptor-gamma (PPARG) agonist, pioglitazone. Since then and for the last 5 years his HbA1c has been within the normal range. These findings indicate that pioglitazone should be considered as a valid alternative in the treatment of diabetes in BSCL patients. To the best of our knowledge, this is the first specific report of successful long-term treatment with pioglitazone in a patient with BSCL. LEARNING POINTS: Berardinelli-Seip congenital lipodystrophy (BSCL) is a recessive genetic disorder associated with severe insulin resistance and early onset diabetes, usually around puberty. Failure of oral antidiabetic medication occurs within the first years of treatment in BSCL patients. When failure to achieve metabolic control with metformin occurs, pioglitazone may be a safe option, lowering insulin resistance and improving both the metabolic control and lipodystrophic phenotype. Herein we show that pioglitazone can be a safe and efficient alternative in the long-term treatment of BSCL patients with diabetes.

Increased Hepatic Fat Content in Patients with Resistance to Thyroid Hormone Beta.

Background: Thyroid hormone (TH) has important functions in controlling hepatic lipid metabolism. Individuals with resistance to thyroid hormone beta (RTHß) who harbor mutations in the THRB gene experience loss-of-function of thyroid hormone receptor beta (TRß), which is the predominant TR isoform expressed in the liver. We hypothesized that individuals with RTHß may have increased hepatic steatosis. Methods: Controlled attenuation parameter (CAP) was assessed in individuals harboring the R243Q mutation of the THRB gene (n = 21) and in their wild-type (WT) first-degree relatives (n = 22) using the ultrasound-based transient elastography (TE) device (FibroScan). All participants belonged to the same family, lived on the same small island, and were therefore exposed to similar environmental conditions. CAP measurements and blood samples were obtained after an overnight fast. The observers were blinded to the status of the patients. Results: The hepatic fat content was increased in RTHß individuals compared with their WT relatives (CAP values of 263 ± 21 and 218.7 ± 43 dB/m, respectively, p = 0.007). The CAP values correlated with age and body mass index (BMI) (age: r = 0.55, p = 0.011; BMI: r = 0.51, p = 0.022) in the WT first-degree relatives but not in RTHß individuals, suggesting that the defect in TRß signaling was predominant over the effects of age and obesity. Circulating free fatty acid levels were significantly higher in RTHß individuals (0.29 ± 0.033 vs. 0.17 ± 0.025 mmol/L, p = 0.02). There was no evidence of insulin resistance evaluated by the homeostatic model assessment of insulin resistance in both groups studied. Conclusions: Our findings provide evidence that impairments in intrahepatic TRß signaling due to mutations of the THRB gene can lead to hepatic steatosis, which emphasizes the influence of TH in the liver metabolism of lipids and provides a rationale for the development TRß-selective thyromimetics. Consequently, new molecules with a very high TRß affinity and hepatic selectivity have been developed for the treatment of lipid-associated hepatic disorders, particularly nonalcoholic fatty liver disease.

A case report of multiple endocrine neoplasia type 1 and autoimmune disease: Coincidence or correlation?

RATIONALE: Multiple Endocrine Neoplasia type 1 (MEN1) is a familial syndrome that results from the disruption of a tumor suppressor protein called MENIN. Its management is challenging, as MEN1 affects different endocrine tissues and predisposes to both benign and malignant tumors. MENIN-deficient cells have recently been recognized to play a role in triggering autoimmunity. Herein, we present a case of MEN1 with multiple endocrine and autoimmune disorders. PATIENT CONCERNS: A 50 years old female with a 25 years history of complicated nephrolithiasis presented with primary hyperparathyroidism. DIAGNOSES: Over several decades, she was diagnosed with recurrent primary hyperparathyroidism, autoimmune thyroiditis, multinodular goiter, pernicious anemia, metastatic gastric type 1 neuroendocrine tumor, macroprolactinemia, gonadotropin deficiency, mucosa-associated lymphoid tissue lymphoma of the thyroid gland, positive anti-calcium sensor receptor antibodies, and BRCA 1/2-negative invasive breast cancer. The autoimmune regulator gene was sequenced, but no pathogenic variants were found. Next-generation sequencing revealed both a pathogenic MEN1 mutation and a benign CDC73 gene variant. Familial genetic screening revealed a large kindred with multiple carriers of one or both genetic variants (MEN1 = 19; CDC73 = 7). INTERVENTIONS: The patient underwent surgical excision of three parathyroid glands, total thyroidectomy and breast tumorectomy plus tamoxifen, and monthly injections of octreotide. The patient and family members with the MEN1 mutation are under a life-long surveillance program for MEN1 prototypic tumors. OUTCOMES: The patient was stable and alive during a 24-years follow-up period. LESSONS: With the present case, the authors highlight a new interplay between MENIN and the immune system, which may have implications for future targeted life-long surveillance and treatment of MEN1 patients.

[Evaluation of the polymerase chain reaction (PCR) for the detection and identification of Listeria monocytogens in fresh cheese coming from the metropolitan area of San José, Costa Rica]. / Evaluación de la prueba de reacción en cadena de la polimerasa (PCR) en la detección e identificación de Listeria monocytogenes en queso fresco proveniente del Area Metropolitana de San José, Costa Rica.

Food borne diseases are very important worldwide and their frequency is still high despite the different efforts focused in diminishing their morbidity and mortality. Listeria monocytogenes is one of the agents associated in this kind of diseases. In the lactic industry, this bacteria is important since raw milks as well as dairy products have been associated in outbreaks, being fresh cheese one of the most vulnerable products to the contamination with this bacteria. The traditional identification of the bacteria is done by a laborious, time consuming and low sensitive technique and the polymerase chain reaction may allow more precise and exact results in shorter time. For this reason the objective of the present study was to optimize the procedure to determine the sensitivity and specificity limits for the detection of L. monocytogenes from fresh cheese and the predictive value of the test. In order to achieve this objective, 76 pasteurized cheese samples were evaluated (45 samples were artificially inoculated at the lab and 31 were used as negative controls). The validation of the technique was done in 50 samples of non pasteurized fresh cheese. Traditional culture isolation was performed according to the methodology described in Compendium of Methods for the Microbiological Examination of Foods. PCR reaction for the detection of L. monocytogenes was based on the methodology described by Poutou,using primers characteristic of the genus and the listeriolisine O gene that is specie's specific. The optimal incubation period determined for the selective enrichment broth was of 48h, and a 100% sensitivity, specificity, predictive value (positive and negative) were obtained by PCR. The technique validation showed the specificity ofthe test in the detection of only the L. monocytogenes species, and not other genus or species that may appear in food matrixes or in food environments.

Physiologic Significance of Epigenetic Regulation of Thyroid Hormone Target Gene Expression.

BACKGROUND: In previous publications, we have reported our findings demonstrating that exposure to high maternal levels of thyroid hormones (TH) has life-long effects on the wild-type (WT, without THRB mutation) progeny of mothers with resistance to thyroid hormone beta (RTHß). The mechanism of this epigenetic effect remains unclear. OBJECTIVES: We reviewed the mechanisms involved in the epigenetic regulation of TH target genes and understand how they may explain the reduced sensitivity to TH in the WT progeny of RTHß mothers. METHODS: The availability of a large, formerly genotyped Azorean population with many individuals harboring the THRB mutation, R243Q, provided us a model to study the influence of fetal exposure to high maternal TH levels. RESULTS: The thyroid-stimulating hormone (TSH) response in WT adults was less suppressible following the administration of L-triiodothyronine (L-T3). This finding suggests reduced sensitivity to TH that is induced by an epigenetic mechanism resulting from exposure to high maternal levels of TH during pregnancy. The persistence of this effect across 3 generations of WT subjects favors transgenerational epigenetic inheritance. Based on preliminary studies in mice, we identified the naturally imprinted gene encoding deiodinase type 3, i.e., DIO3, as a possible mediator of this epigenetic effect through increased inactivation of TH. CONCLUSION: Increased D3 expression and consequently increased T3 degradation appear to be responsible for the reduced sensitivity of the anterior pituitary to administered L-T3. The imprinted DIO3 gene may be a candidate gene that mediates the epigenetic effect induced by exposure to high maternal levels of TH. However, we cannot exclude the role of other TH-responsive genes.