Post-surgical Persistent Hyperparathyroidism Successfully Treated with Parathyroid Radiofrequency Ablation: A Case Report.

BACKGROUND: Currently, parathyroidectomy is the standard treatment for Primary Hyperparathyroidism (PHPT). Surgical treatment is often effective, although not free of complications and relapses. Minimally invasive techniques, such as Microwave Ablation (MWA) and Radiofrequency Ablation (RFA), are an alternative to surgery in selected patients. We have, herein, reported on the successful use of RFA in a patient with post-surgical persistent hyperparathyroidism. CASE PRESENTATION: A 54-year-old woman was referred to our Center for mild hypercalcemia with exams revealing Primary Hyperparathyroidism (PHPT). Neck ultrasound and Technetium- 99 Methoxy-isobutyl-isonitrile (99mTc-MIBI) scintigraphy scanning revealed a suspicious right parathyroid hyperplasia/adenoma. She underwent parathyroidectomy and histological examination showed a parathyroid nodular hyperplasia. During the follow-up, she suffered from persistent hyperparathyroidism due to the treatment of left parathyroid hypoplasia with RFA. Blood tests after the procedure showed the remission of the disease 7 months post-treatment. CONCLUSION: A minimally invasive technique for PHPT may represent a valid alternative to surgery, especially in patients with an elevated surgery-related risk. More studies are necessary to investigate the benefit of RFA as a first-line treatment in PHPT.

Fat oxidation rates and cardiorespiratory responses during exercise in different subject populations with post-acute sequelae of SARS-CoV-2 infection: a comparison with normative percentile values.

Introduction: Post-acute sequelae of SARS-CoV-2 infection (PASC) presents a spectrum of symptoms following acute COVID-19, with exercise intolerance being a prevalent manifestation likely linked to disrupted oxygen metabolism and mitochondrial function. This study aims to assess maximal fat oxidation (MFO) and exercise intensity at MFO (FATmax) in distinct PASC subject groups and compare these findings with normative data. Methods: Eight male subjects with PASC were involved in this study. The participants were divided into two groups: "endurance-trained" subjects (V˙O2max > 55 mL/min/kg) and "recreationally active" subjects (V˙O2max < 55 mL/min/kg). Each subject performed a graded exercise test until maximal oxygen consumption (V˙O2max) to measure fat oxidation. Subsequently, MFO was assessed, and FATmax was calculated as the ratio between V˙O2 at MFO and V˙O2 max. Results: The MFO and FATmax of "endurance-trained" subjects were 0.85, 0.89, 0.71, and 0.42 and 68%, 69%, 64%, and 53%, respectively. Three out of four subjects showed both MFO and FATmax values placed over the 80th percentile of normative data. The MFO and FATmax of "recreationally active" subjects were 0.34, 0.27, 0.35, and 0.38 and 47%, 39%, 43%, and 41%, respectively. All MFO and FATmax values of those subjects placed below the 20th percentile or between the 20th and 40th percentile. Discussion: Significant differences in MFO and FATmax values between 'endurance-trained' and "recreationally active" subjects suggest that specific endurance training, rather than simply an active lifestyle, may provide protective effects against alterations in mitochondrial function during exercise in subjects with PASC.

Italian version of the Brief Questionnaire of Olfactory Disorders (Brief-IT-QOD).

Objective: To evaluate the reliability and validity of the Italian version of the Brief Questionnaire of Olfactory Disorders (Brief-IT-QOD). Methods: The study consisted of six phases: item generation, reliability analysis (112 dysosmic patients for internal consistency analysis and 61 for test-retest reliability analysis), normative data generation (303 normosmic subjects), validity analysis (comparison of Brief-IT-QOD scores of healthy and dysosmic subjects and scores correlation with psychophysical olfactory testing TDI and SNOT-22 scores), responsiveness analysis (10 dysosmic chronic rhinosinusitis with nasal polyps patients before and after biologic therapy), and cut-off value determination (ROC curve analysis of Brief-IT-QOD sensitivity and specificity). Results: All subjects completed the Brief-IT-QOD. Internal consistency (α > 0.70) and test-retest reliability (ICC > 0.7) were acceptable and satisfactory for both questionnaire subscales. A significant difference between dysosmic and control subjects was found in both subscales (p < 0.05). Significant correlations between subscales scores and TDI and SNOT-22 scores were observed. Brief-IT-QOD scores before treatment were significantly higher than after biological therapy. Conclusions: Brief-IT-QOD is reliable, valid, responsive to changes in QoL, and recommended for clinical practice and outcome research.

Overexpression of UCP3 decreases mitochondrial efficiency in mouse skeletal muscle in vivo.

Uncoupling protein-3 (UCP3) is a mitochondrial transmembrane protein highly expressed in the muscle that has been implicated in regulating the efficiency of mitochondrial oxidative phosphorylation. Increasing UCP3 expression in skeletal muscle enhances proton leak across the inner mitochondrial membrane and increases oxygen consumption in isolated mitochondria, but its precise function in vivo has yet to be fully elucidated. To examine whether muscle-specific overexpression of UCP3 modulates muscle mitochondrial oxidation in vivo, rates of ATP synthesis were assessed by 31 P magnetic resonance spectroscopy (MRS), and rates of mitochondrial oxidative metabolism were measured by assessing the rate of [2-13 C]acetate incorporation into muscle [4-13 C]-, [3-13 C]-glutamate, and [4-13 C]-glutamine by high-resolution 13 C/1 H MRS. Using this approach, we found that the overexpression of UCP3 in skeletal muscle was accompanied by increased muscle mitochondrial inefficiency in vivo as reflected by a 42% reduction in the ratio of ATP synthesis to mitochondrial oxidation.

Digital innovations for retinal care in diabetic retinopathy.

AIM: The purpose of this review is to examine the applications of novel digital technology domains for the screening and management of patients with diabetic retinopathy (DR). METHODS: A PubMed engine search was performed, using the terms "Telemedicine", "Digital health", "Telehealth", "Telescreening", "Artificial intelligence", "Deep learning", "Smartphone", "Triage", "Screening", "Home-based", "Monitoring", "Ophthalmology", "Diabetes", "Diabetic Retinopathy", "Retinal imaging". Full-text English language studies from January 1, 2010, to February 1, 2022, and reference lists were considered for the conceptual framework of this review. RESULTS: Diabetes mellitus and its eye complications, including DR, are particularly well suited to digital technologies, providing an ideal model for telehealth initiatives and real-world applications. The current development in the adoption of telemedicine, artificial intelligence and remote monitoring as an alternative to or in addition to traditional forms of care will be discussed. CONCLUSIONS: Advances in digital health have created an ecosystem ripe for telemedicine in the field of DR to thrive. Stakeholders and policymakers should adopt a participatory approach to ensure sustained implementation of these technologies after the COVID-19 pandemic. This article belongs to the Topical Collection "Diabetic Eye Disease", managed by Giuseppe Querques.

Effects of Bilateral Dorsolateral Prefrontal Cortex High-Definition Transcranial Direct-Current Stimulation on Physiological and Performance Responses at Severe-Intensity Exercise Domain in Elite Road Cyclists.

PURPOSE: To investigate the effects of bilateral dorsolateral prefrontal cortex high-definition transcranial direct-current stimulation (HD-tDCS) on physiological and performance responses during exercise at the upper limit of the severe-intensity exercise domain in elite-level road cyclists. METHODS: Eleven elite-level road cyclists (VO2peak: 71.8 [3.1] mL·kg-1·min-1) underwent the HD-tDCS or SHAM condition in a double-blind, counterbalanced, and randomized order. After 20 minutes of receiving either HD-tDCS on dorsolateral prefrontal cortex (F3 and F4) or SHAM stimulation, participants completed a 10-minute constant-load trial (CLT1) at 90% of the first ventilatory threshold and a 2-minute CLT (CLT2) at peak power output. Thereafter, they performed a simulated 2-km time trial (TT). Maximal oxygen uptake, respiratory exchange ratio, heart rate, and rating of perceived exertion were recorded during CLT1 and CLT2, whereas performance parameters were recorded during the TT. RESULTS: In 6 out of 11 cyclists, the total time to complete the TT was 3.0% faster in HD-tDCS compared to SHAM. Physiological and perceptual variables measured during CLT1 and CLT2 did not change between HD-tDCS and SHAM. CONCLUSIONS: HD-tDCS over the dorsolateral prefrontal cortex seemed to improve cycling TT performance within the upper limit of the severe-intensity exercise domain, suggesting that an upregulation of the prefrontal cortex could be critical even in this exercise intensity domain. However, the limited dimension and the high interindividual variability require further studies to test these putative ergogenic effects.

Physical activity as a proxy to ameliorate inflammation in patients with type 2 diabetes and periodontal disease at high cardiovascular risk.

While the beneficial impact of physical activity has been ascertained in a variety of pathological scenarios, including diabetes and low-grade systemic inflammation, its potential remains still putative for periodontal health. Periodontal disease has been associated with inflammatory systemic alterations, which share a common denominator with type 2 diabetes mellitus and cardiovascular disease. Physical exercise, along with nutritional counseling, is a cornerstone in the treatment and prevention of type 2 diabetes, also able to reduce the prevalence of periodontal disease and cardiovascular risk. In addition, considering the higher incidence of periodontitis in patients with type 2 diabetes compared to healthy controls, the fascinating research question would be whether physical activity could relieve the inflammatory pressure exerted by the combination of these two diseases. This multi-disciplinary viewpoint discusses available literature in order to argument the hypothesis of a "three-way relationship" linking diabetes, periodontitis, and physical activity.

Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions.

It is now established that adipose tissue, skeletal muscle, and heart are endocrine organs and secrete in normal and in pathological conditions several molecules, called, respectively, adipokines, myokines, and cardiokines. These secretory proteins constitute a closed network that plays a crucial role in obesity and above all in cardiac diseases associated with obesity. In particular, the interaction between adipokines, myokines, and cardiokines is mainly involved in inflammatory and oxidative damage characterized obesity condition. Identifying new therapeutic agents or treatment having a positive action on the expression of these molecules could have a key positive effect on the management of obesity and its cardiac complications. Results from recent studies indicate that several nutritional interventions, including nutraceutical supplements, could represent new therapeutic agents on the adipo-myo-cardiokines network. This review focuses the biological action on the main adipokines, myokines and cardiokines involved in obesity and cardiovascular diseases and describe the principal nutraceutical approaches able to regulate leptin, adiponectin, apelin, irisin, natriuretic peptides, and follistatin-like 1 expression.

Minimally-invasive treatments for benign thyroid nodules: a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group.

Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS ≤3) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and ≥80% nodule volume ablation is expected (LoE = 3).

L-Carnitine Reduces Oxidative Stress and Promotes Cells Differentiation and Bone Matrix Proteins Expression in Human Osteoblast-Like Cells.

Bone fragility and associated fracture risk are major problems in aging. Oxidative stress and mitochondrial dysfunction play a key role in the development of bone fragility. Mitochondrial dysfunction is closely associated with excessive production of reactive oxygen species (ROS). L-Carnitine (L-C), a fundamental cofactor in lipid metabolism, has an important antioxidant property. Several studies have shown how L-C enhances osteoblastic proliferation and activity. In the current study, we investigated the potential effects of L-C on mitochondrial activity, ROS production, and gene expression involved in osteoblastic differentiation using osteoblast-like cells (hOBs) derived from elderly patients. The effect of 5mM L-C treatment on mitochondrial activity and L-C antioxidant activity was studied by ROS production evaluation and cell-based antioxidant activity assay. The possible effects of L-C on hOBs differentiation were assessed by analyzing gene and protein expression by Real Time PCR and western blotting, respectively. L-C enhanced mitochondrial activity and improved antioxidant defense of hOBs. Furthermore, L-C increased the phosphorylation of Ca2+/calmodulin-dependent protein kinase II. Additionally, L-C induced the phosphorylation of ERK1/2 and AKT and the main kinases involved in osteoblastic differentiation and upregulated the expression of osteogenic related genes, RUNX2, osterix (OSX), bone sialoprotein (BSP), and osteopontin (OPN) as well as OPN protein synthesis, suggesting that L-C exerts a positive modulation of key osteogenic factors. In conclusion, L-C supplementation could represent a possible adjuvant in the treatment of bone fragility, counteracting oxidative phenomena and promoting bone quality maintenance.

Metformin Counteracts HCC Progression and Metastasis Enhancing KLF6/p21 Expression and Downregulating the IGF Axis.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is the common tumor of the liver. Unfortunately, most HCC seem to be resistant to conventional chemotherapy and radiotherapy. The poor efficacy of antitumor agents is also due, at least in part, to the inefficient drug delivery and metabolism exerted by the steatotic/cirrhotic liver that hosts the tumor. Thus, novel approaches in chemotherapy may be needed to improve the survival rate in patients with HCC. Metformin (METF) has been found to lower HCC risk; however, the mechanisms by which METF performs its anticancer activity are not completely elucidated. Previous studies have showed METF action on growth inhibition in the liver in a dose/time-dependent manner and its antitumor role by targeting multiple pathways. We investigated molecular effects of METF in an in vitro human hepatoma model (HepG2), studying cell cycle regulators, tumorigenesis markers, and insulin-like growth factor (IGF) axis regulation. MATERIALS AND METHODS: HepG2 cells were treated with METF (400 µM) for 24, 48, and 72 hours. METF action on cell cycle progression and cellular pathways involved in metabolism regulation was evaluated by gene expression analysis, immunofluorescence, and Western blot assay. RESULTS: By assessing HepG2 cell viability, METF significantly decreased growth cell capacity raising KLF6/p21 protein content. Moreover, METF ameliorated the cancer microenvironment reducing cellular lipid drop accumulation and promoting AMPK activity. The overexpression of IGF-II molecule and the IGF-I receptor that plays a main role in HCC progression was counteracted by METF. Furthermore, the protein content of HCC principal tumor markers, CK19 and OPN, linked to the metastasis process was significantly reduced by METF stimulus. CONCLUSION: Our data show that METF could suppress HepG2 proliferation, through induction of cell cycle arrest at the G0/G1 phase. In addition, METF effect on the cancer microenvironment and on the IGF axis leads to the development of new METF therapeutic use in HCC treatment.

Pheochromocytoma in Congenital Cyanotic Heart Disease.

Studies on genome-wide transcription patterns have shown that many genetic alterations implicated in pheochromocytoma-paraganglioma (P-PGL) syndromes cluster in a common cellular pathway leading to aberrant activation of molecular response to hypoxia in normoxic conditions (the pseudohypoxia hypothesis). Several cases of P-PGL have been reported in patients with cyanotic congenital heart disease (CCHD). Patients affected with CCHD have an increased likelihood of P-PGL compared to those affected with noncyanotic congenital heart disease. One widely supported hypothesis is that chronic hypoxia represents the determining factor supporting this increased risk. We report the case of a 23-year-old woman affected with congenital tricuspid atresia surgically by the Fontan procedure. The patient was admitted to hospital with hypertensive crisis and dyspnea. Chest computed tomography revealed, incidentally, a 6-cm mass in the left adrenal lodge. Increased levels of noradrenaline (NA) and its metabolites were detected (plasma NA 5003.7 pg/ml, n.v.<480; urinary NA 1059.5 µg/24 h, n.v.<85.5; urinary metanephrine 489 µg/24 h, n.v.<320). The patient did not report any additional symptom related to catecholamine excess. The left adrenal tumor showed abnormal accumulation when 131I-metaiodobenzylguanidine scintigraphy was performed. A 18F-fluorodeoxyglucose positron emission tomography showed no significant metabolic activity in the left adrenal gland but intense uptake in the supra- and subdiaphragmatic brown adipose tissue, probably due to noradrenergic-stimulated glucose uptake. The patient underwent left open adrenalectomy after preconditioning with α- and ß-blockers and histopathological examination confirmed the diagnosis of pheochromocytoma (Ki-67<5%). Screening for germline mutations did not show any genes mutation (investigated mutations: RET, TMEM127, MAX, SDHD, SDHC, SDHB, SDHAF2, SDHA, and VHL). Clinicians should consider P-PGL when an unexplained clinical deterioration occurs in CCHD patients, even in the absence of typical paroxysmal symptoms.

Effect of Hazelnut Oil on Muscle Cell Signalling and Differentiation.

Nuts-enriched diets were shown to bear beneficial effects for human's health. Among nuts, hazelnut plays a major role in human nutrition and health because of its unique fatty acid composition (predominantly MUFA), fat soluble bioactives (tocopherols and phytosterols), vitamins (vitamin E), essential minerals (selenium), essential amino acids, antioxidant phenolics (caffeic acid), dietary fiber (soluble form), and bioactive phtytochemicals. The current study was designed to explore the cellular effects of two particular hazelnut strains (Ordu and Tonda).Four hazelnut oils were obtained from 2 common strains (Ordu hazelnut oil, Ordu cuticle oil, Tonda "gentile" hazelnut oil, Tonda "gentile" cuticle oil). The metabolic and nutritional effects of the four hazelnut oils were assessed using an in vitro model of mouse myoblasts, identifying the intracellular mechanisms involved in muscle differentiation and in the modulation of specific muscle genes.We demonstrated that hazelnut oils induced morphological changes in neo-formed myotubes increasing myotubes size. In particular, the diversified effects of the hazelnuts and cuticle oils on muscle fibres shape (on length and diameter respectively) determine a diversified pattern of action on elongation or hypertrophy of the muscle fibres. Furthermore, hazelnut oils regulate different pathways associated with myoblasts growth and development, stimulate signal transduction, and activate cell commitment and differentiation. The present results provide evidence that hazelnut oils may affect skeletal muscle growth and differentiation, constituting the proof of principle for the future development of novel foods and integrators.

Microbiota and metabolic diseases.

The microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi, living in different districts of the human body, such as the gastro-enteric tube, skin, mouth, respiratory system, and the vagina. Over 70% of the microbiota lives in the gastrointestinal tract in a mutually beneficial relationship with its host. The microbiota plays a major role in many metabolic functions, including modulation of glucose and lipid homeostasis, regulation of satiety, production of energy and vitamins. It exerts a role in the regulation of several biochemical and physiological mechanisms through the production of metabolites and substances. In addition, the microbiota has important anti-carcinogenetic and anti-inflammatory actions. There is growing evidence that any modification in the microbiota composition can lead to several diseases, including metabolic diseases, such as obesity and diabetes, and cardiovascular diseases. This is because alterations in the microbiota composition can cause insulin resistance, inflammation, vascular, and metabolic disorders. The causes of the microbiota alterations and the mechanisms by which microbiota modifications can act on the development of metabolic and cardiovascular diseases have been reported. Current and future preventive and therapeutic strategies to prevent these diseases by an adequate modulation of the microbiota have been also discussed.

Insulin-mimetic effects of short-term rapamycin in type 1 diabetic patients prior to islet transplantation.

BACKGROUND: The immunosuppressive drug rapamycin may influence insulin sensitivity in insulin-responsive tissues. AIMS: This study aimed at evaluating the effectiveness of rapamycin pre-treatment before pancreatic islet allotransplantation (ITx) in patients with type 1 diabetes mellitus (T1DM). METHODS: Forty-one T1DM patients were studied. Thirteen patients with poor glycemic control underwent a short-term rapamycin treatment before ITx (Group 1), and they were compared to 28 patients undergoing ITx without rapamycin pre-treatment (Group 2). Outcomes were daily insulin requirement (DIR), fasting blood glucose, HbA1c, C-peptide and the SUITO index of beta-cell function. A subgroup of patients pre-treated with rapamycin before ITx underwent euglycemic hyperinsulinemic clamp with [6,6-2H2] glucose before and after ITx to evaluate insulin sensitivity. RESULTS: We found a significant reduction in DIR after rapamycin pre-treatment (- 8 ± 6 U/day, mean ± SD, p < 0.001) and 1 year after ITx. DIR reduction 1 year after ITx was greater in Group 1 as compared to Group 2 (- 37 ± 15 vs. - 19 ± 13 U/day, p = 0.005) and remained significant after adjusting for gender, age, glucose and baseline HbA1c (beta = 18.2 ± 5.9, p = 0.006). Fasting glucose and HbA1c significantly decreased 1 year after ITx in Group 1 (HbA1c: - 2.1 ± 1.4%, p = 0.002), while fasting C-peptide (+0.5 ± 0.3 nmol/l, p = 0.002) and SUITO index increased (+57.4 ± 39.7, p = 0.016), without differences between the two groups. Hepatic glucose production decreased after rapamycin pre-treatment (- 1.1 ± 1.1 mg/kg/min, p = 0.04) and after ITx (- 1.6 ± 0.6 mg/kg/min, p = 0.015), while no changes in peripheral glucose disposal were observed. CONCLUSIONS: Rapamycin pre-treatment before ITx succeeds in reducing insulin requirement, enhancing hepatic insulin sensitivity. This treatment may improve short-term ITx outcomes, possibly in selected patients with T1DM complicated by insulin resistance. CLINICAL TRIAL: Clinicaltrials.gov NCT01060605; NCT00014911.

Bone marrow fat contributes to insulin sensitivity and adiponectin secretion in premenopausal women.

PURPOSE: Bone marrow fat is a functionally distinct adipose tissue that may contribute to systemic metabolism. This study aimed at evaluating a possible association between bone marrow fat and insulin sensitivity indices. METHODS: Fifty obese (n = 23) and non-obese (n = 27) premenopausal women underwent proton magnetic resonance spectroscopy to measure vertebral bone marrow fat content and unsaturation index at L4 level. Abdominal visceral, subcutaneous fat, and epicardial fat were also measured using magnetic resonance imaging. Bone mineral density was measured by dual-energy X-ray absorptiometry. Body composition was assessed by bioelectrical impedance analysis. Fasting serum glucose, insulin, lipids, adiponectin were measured; the insulin resistance index HOMA (HOMA-IR) was calculated. RESULTS: Bone marrow fat content and unsaturation index were similar in obese and non-obese women (38.5 ± 0.1 vs. 38.6 ± 0.1%, p = 0.994; 0.162 ± 0.065 vs. 0.175 ± 0.048, p = 0.473, respectively). Bone marrow fat content negatively correlated with insulin and HOMA-IR (r = -0.342, r = -0.352, respectively, p = 0.01) and positively with high density lipoprotein cholesterol (r = 0.270, p = 0.043). From a multivariate regression model including lnHOMA-IR as a dependent variable and visceral, subcutaneous, epicardial fat, and bone marrow fat as independent variables, lnHOMA-IR was significantly associated with bone marrow fat (ß = -0.008 ± 0.004, p = 0.04) and subcutaneous fat (ß = 0.003 ± 0.001, p = 0.04). Bone marrow fat, among the other adipose depots, was a significant predictor of circulating adiponectin (ß = 0.147 ± 0.060, p = 0.021). Bone marrow fat unsaturation index negatively correlated with visceral fat (r = -0.316, p = 0.026). CONCLUSIONS: There is a relationship between bone marrow fat content and insulin sensitivity in obese and non-obese premenopausal women, possibly mediated by adiponectin secretion. Visceral fat does not seem to regulate bone marrow fat content while it may affect bone marrow fat composition.

Adrenal Ganglioneuroblastoma in Adults: A Case Report and Review of the Literature.

Incidentally discovered adrenal masses are very common given the increased number of imaging studies performed in recent years. We here report a clinical case of a 20-year-old woman who presented with left flank pain. Ultrasound examination revealed a contralateral adrenal mass, which was confirmed at computed tomography (CT) scan. Hormonal hypersecretion was excluded. Given the size (11 × 10 × 7 cm) and the uncertain nature of the mass, it was surgically removed and sent for pathological analyses. Conclusive diagnosis was ganglioneuroblastoma. Ganglioneuroblastoma is an uncommon malignant tumor, extremely rare in adults, particularly in females. This neoplasm is frequently localized in adrenal gland.

Betaine promotes cell differentiation of human osteoblasts in primary culture.

BACKGROUND: Betaine (BET), a component of many foods, is an essential osmolyte and a source of methyl groups; it also shows an antioxidant activity. Moreover, BET stimulates muscle differentiation via insulin like growth factor I (IGF-I). The processes of myogenesis and osteogenesis involve common mechanisms with skeletal muscle cells and osteoblasts sharing the same precursor. Therefore, we have hypothesized that BET might be effective on osteoblast cell differentiation. METHODS: The effect of BET was tested in human osteoblasts (hObs) derived from trabecular bone samples obtained from waste material of orthopedic surgery. Cells were treated with 10 mM BET at 5, 15, 60 min and 3, 6 and 24 h. The possible effects of BET on hObs differentiation were evaluated by real time PCR, western blot and immunofluorescence analysis. Calcium imaging was used to monitor intracellular calcium changes. RESULTS: Real time PCR results showed that BET stimulated significantly the expression of RUNX2, osterix, bone sialoprotein and osteopontin. Western blot and immunofluorescence confirmed BET stimulation of osteopontin protein synthesis. BET stimulated ERK signaling, key pathway involved in osteoblastogenesis and calcium signaling. BET induced a rise of intracellular calcium by means of the calcium ions influx from the extracellular milieu through the L-type calcium channels and CaMKII signaling activation. A significant rise in IGF-I mRNA at 3 and 6 h and a significant increase of IGF-I protein at 6 and 24 h after BET stimulus was detected. Furthermore, BET was able to increase significantly both SOD2 gene expression and protein content. CONCLUSIONS: Our study showed that three signaling pathways, i.e. cytosolic calcium influx, ERK activation and IGF-I production, are enhanced by BET in human osteoblasts. These pathways could have synergistic effects on osteogenic gene expression and protein synthesis, thus potentially leading to enhanced bone formation. Taken together, these results suggest that BET could be a promising nutraceutical therapeutic agent in the strategy to counteract the concomitant and interacting impact of sarcopenia and osteoporosis, i.e. the major determinants of senile frailty and related mortality.

Moderate Intensity Training Impact on the Inflammatory Status and Glycemic Profiles in NOD Mice.

The nonobese diabetic (NOD) mouse represents a well-established experimental model analogous to human type 1 diabetes mellitus (T1D) as it is characterized by progressive autoimmune destruction of pancreatic ß-cells. Experiments were designed to investigate the impact of moderate-intensity training on T1D immunomodulation and inflammation. Under a chronic exercise regime, NOD mice were trained on a treadmill for 12 weeks (12 m/min for 30 min, 5 d/wk) while age-matched, control animals were left untrained. Prior to and upon completion of the training period, fed plasma glucose and immunological soluble factors were monitored. Both groups showed deteriorated glycemic profiles throughout the study although trained mice tended to be more compensated than controls after 10 weeks of training. An exercise-induced weight loss was detected in the trained mice with respect to the controls from week 6. After 12 weeks, IL-6 and MIP-1ß were decreased in the trained animals compared to their baseline values and versus controls, although not significantly. Morphometric analysis of pancreata revealed the presence of larger infiltrates along with decreased α-cells areas in the control mice compared to trained mice. Exercise may exert positive immunomodulation of systemic functions with respect to both T1D and inflammation, but only in a stringent therapeutic window.