Conscientious Objection to Animal Testing: A Preliminary Survey Among Italian Medical and Veterinary Students.

The use of animals for educational and research purposes is common in both veterinary and human medicine degree courses, and one that involves important ethical considerations. The aim of this study was to assess the extent of differences between the knowledge and attitudes of veterinary students and medical students on animal bioethics, on alternative strategies and on their right to conscientiously object to animal experimentation. To this end, a questionnaire was completed by 733 students (384 human medicine students (HMS) and 349 veterinary medicine students (VMS)). VMS were more aware than HMS (72.2% and 59.6%, respectively) of the existence of an Italian law on the right to conscientiously object to animal experimentation. However, very few of them had exercised this right. Many VMS (43.3%) felt that animal bioethics courses should be mandatory (only 17.4% of HMS felt the same way). More VMS than HMS (81.7% and 59.1%, respectively) expressed an interest in attending a course on alternatives to animal experimentation. The data suggest the need for appropriate educational interventions, in order to allow students to make choices based on ethical principles. Fostering close collaborations between departments of human medicine and veterinary medicine, for example, through shared study modules, could promote the development of ethical competence as a basic skill of students of both veterinary and human medicine courses.

Microgram amounts of abscisic acid in fruit extracts improve glucose tolerance and reduce insulinemia in rats and in humans.

2-Cis,4-trans-abscisic acid (ABA) is a plant hormone that is present also in animals. Several lines of evidence suggest that ABA contributes to the regulation of glycemia in mammals: nanomolar ABA stimulates insulin release from ß-pancreatic cells and glucose transporter-4-mediated glucose uptake by myoblasts and adipocytes in vitro; plasma ABA increases in normal human subjects, but not in diabetic patients, after a glucose load for an oral glucose tolerance test (OGTT). The presence of ABA in fruits prompted an exploration of the bioavailability of dietary ABA and the effect of ABA-rich fruit extracts on glucose tolerance. Rats underwent an OGTT, with or without 1 µg/kg ABA, either synthetic or present in a fruit extract. Human volunteers underwent an OGTT or a standard breakfast and lunch, with or without a fruit extract, yielding an ABA dose of 0.85 or 0.5 µg/kg, respectively. Plasma glucose, insulin, and ABA were measured at different time points. Oral ABA at 0.5-1 µg/kg significantly lowered glycemia and insulinemia in rats and in humans. Thus, the glycemia-lowering effect of low-dose ABA in vivo does not depend on an increased insulin release. Low-dose ABA intake may be proposed as an aid to improving glucose tolerance in patients with diabetes who are deficient in or resistant to insulin.

Inferior vena cava parameters predict re-admission in ischaemic heart failure.

BACKGROUND: The clinical history of heart failure (HF) is usually characterized by frequent hospitalizations for decompensation. Therefore, several markers of subclinical hemodynamic congestion are under investigation for predicting early rehospitalization. In this field, the potential of ultrasound inferior vena cava (IVC) assessment has been recently investigated in HF but not yet assessed in the different aetiological categories. MATERIAL AND METHODS: Forty-eight patients admitted for decompensated HF (n = 25 with ischaemic heart disease [IHD] and n = 23 non-IHD) underwent biochemical examination (including NT-proBNP), echocardiography and IVC assessment by hand-carried ultrasound (HCU). During 60-day follow-up after discharge, the re-hospitalization rate for HF was recorded to investigate the predictive power of NT-proBNP and IVC assessment among the two study groups. RESULTS: IHD and non-IHD patients with HF were similar except for gender distribution. During follow-up, 16·7% of patients were rehospitalized for decompensated HF, with higher prevalence in IHD group (28% vs. 4·3% P = 0·031). IVC assessment at discharge significantly predicted re-admission in the overall population and in IHD group, whereas NT-proBNP failed to predict rehospitalization in IHD group. In adjusted hazard ratio, only IVC min and the changes of IVC from admission significantly predicted re-admission. ROC analysis confirmed the change in IVC min as the best predictor of rehospitalization in patients with IHD. CONCLUSION: This pilot study showed a higher early re-admission rate in patients with HF due to IHD. In addition, the change in IVC min diameter from admission to discharge was the best predictor of re-admission in patients with IHD.

Interactions between vitamin D and IGF-I: from physiology to clinical practice.

The interplay between vitamin D and IGF-I is complex and occurs at both endocrine and paracrine/autocrine levels. Vitamin D has been shown to increase circulating IGF-I and IGFBP-3, with the consistent finding of a positive correlation between vitamin D and IGF-I serum values in population-based cohorts of healthy subjects. The modulation of IGF-I and IGFBP-3 concentrations by vitamin D may impact recombinant human (rh) GH dosing for the treatment of GHD. It might also underlie some of the extra-skeletal beneficial effects ascribed to vitamin D. On the other hand, IGF-I stimulates renal production of 1,25-dihydroxyvitamin D, which increases calcium and phosphate availability in the body and suppresses PTH secretion. This effect is responsible for an altered calcium-phosphate balance in uncontrolled acromegaly and might also account for the improvement in bone metabolism associated with rhGH treatment in patients with GHD. Data on the paracrine/autocrine vitamin D-IGF-I interactions are abundant, but mostly not linked to one another. As a result, it is not possible to draw a comprehensive picture of the physiological and/or pathological interrelations between vitamin D, IGF-I and IGF-binding proteins (IGFBP) in different tissues. A potential role of vitamin D action is related to its association with carcinogenesis, a paradigm being breast cancer. Current evidence indicates that, in breast tumours, vitamin D modulates the IGF-I/IGFBP ratio to decrease proliferation and increase apoptosis.

1,25-Dihydroxy vitamin D and coronary microvascular function.

PURPOSE: The active form of vitamin D (1,25(OH)(2)D) contributes to blood flow regulation in skeletal muscle. The aim of the present study was to determine whether this hormone also modulates coronary physiology, and thus whether abnormalities in its bioavailability contribute to excess cardiovascular risk in patients with disorders of mineral metabolism. METHODS: As a clinical model of the wide variability in 1,25(OH)(2)D bioavailability, we studied 23 patients (62 ± 8 years) with suspected primary hyperparathyroidism referred for myocardial perfusion imaging because of atypical chest pain and at least one cardiovascular risk factor. Dipyridamole and baseline myocardial blood flow indexes were assessed on G-SPECT imaging of (99m)Tc-tetrofosmin, with normalization of the myocardial count rate to the corresponding first-transit counts in the pulmonary artery. Coronary flow reserve (CFR) was defined as the ratio between dipyridamole and baseline myocardial blood flow indexes. In all patients, parathyroid hormone, 25-hydroxy vitamin D (25(OH)D) and 1,25(OH)(2)D serum levels were determined. RESULTS: Primary hyperparathyroidism was eventually diagnosed in 15 of the 23 patients. The mean 25(OH)D concentration was relatively low (21 ± 10 ng/mL) while the concentrations of 1,25(OH)(2)D varied widely but within the normal range (mean 95 ± 61 pmol/L). No patient showed reversible perfusion defects on G-SPECT. CFR was not correlated with either the serum concentration of 25(OH)D nor that of parathyroid hormone, but was strictly correlated with the serum level of 1,25(OH)(2)D (R = 0.8, p < 0.01). Moreover, patients with a 1,25(OH)(2)D concentration below the median value (86 pmol/L) had markedly lower CFR than the other patients (1.48 ± 0.40 vs. 2.51 ± 0.63, respectively; p < 0.001). CONCLUSION: Bioavailable 1,25(OH)(2)D modulates coronary microvascular function. This effect might contribute to the high cardiovascular risk of conditions characterized by chronic reduction in bioavailability of this hormone.

The plant hormone abscisic acid increases in human plasma after hyperglycemia and stimulates glucose consumption by adipocytes and myoblasts.

The plant hormone abscisic acid (ABA) is released from glucose-challenged human pancreatic ß cells and stimulates insulin secretion. We investigated whether plasma ABA increased during oral and intravenous glucose tolerance tests (OGTTs and IVGTTs) in healthy human subjects. In all subjects undergoing OGTTs (n=8), plasma ABA increased over basal values (in a range from 2- to 9-fold). A positive correlation was found between the ABA area under the curve (AUC) and the glucose AUC. In 4 out of 6 IVGTTs, little or no increase of ABA levels was observed. In the remaining subjects, the ABA increase was similar to that recorded during OGTTs. GLP-1 stimulated ABA release from an insulinoma cell line and from human islets, by ∼10- and 2-fold in low and high glucose, respectively. Human adipose tissue also released ABA in response to high glucose. Nanomolar ABA stimulated glucose uptake, similarly to insulin, in rat L6 myoblasts and in murine 3T3-L1 cells differentiated to adipocytes, by increasing GLUT-4 translocation to the plasma membrane. Demonstration that a glucose load in humans is followed by a physiological rise of plasma ABA, which can enhance glucose uptake by adipose tissues and muscle cells, identifies ABA as a new mammalian hormone involved in glucose metabolism.

Currarino syndrome with pelvic neuroendocrine tumor diagnosed by post-mortem genetic analysis of tissue specimens.

Currarino syndrome (CS) is an autosomal dominant disorder of embryonic development characterized by the triad of anorectal abnormalities, partial sacral agenesis, and presacral mass. Mutations of the HLXB9 gene have been identified in most CS cases, but a precise genotype-phenotype correlation has not been described so far. We report the clinical case of a 44-year-old Caucasian woman with malignant neuroendocrine transformation of a pre-sacrococcygeal mass combined with bicornuate uterus, dermoid cyst of the ovaries, and chronic constipation. After the patient died, a sacrococcygeal malformation and anterior meningocele were diagnosed in her 22-year-old son. CS diagnosis was then retrospectively confirmed by molecular analysis of normal and pathological tissue specimens of the mother, with identification of a HLXB9 mutation (c.727C>T; p.R243W). CS should be considered, and genetic counseling recommended, to all patients with presacral masses. Since malignant neuroendocrine transformation of presacral mass in CS is a possible complication, even thought rare, close follow up in these patients is advisable.

Relationship between fatty degeneration of thigh muscles and vitamin D status in the elderly: a preliminary MRI study.

OBJECTIVE: The purpose of this study was to study the relationship between fatty degeneration of thigh muscles and vitamin D status in elderly adults. SUBJECTS AND METHODS: For six months, 121 patients 65 years old or older were evaluated. Myopathy, muscular impairment, and conditions influencing vitamin D status other than diet and sunlight were exclusion criteria. Twenty patients (10 men and 10 women; mean age, 77.6 years) underwent MRI. Thigh muscles were scanned from the hip to the knee with T1- and T2-weighted spin-echo sequences. Skeletal muscles were evaluated for fatty degeneration and atrophy from grade 0 to 3 (grade 0 = normal appearance, grade 3 = severe changes). The relationship between muscular fatty degeneration, 25-hydroxyvitamin D (25-OHD) levels, and scores on Tinetti scales for balance and gait were examined. RESULTS: In the evaluation of the extensor muscles for fatty degeneration and atrophy, grade 0 was present in three patients (15%), grade 1 in 11 (55%), and grade 2 in six (30%). In the flexor muscles, grade 0 was found in one patient (5%), grade 1 in five (25%), and grade 2 in 14 (70%); grade 3 changes were not seen. Muscular fatty degeneration negatively correlated with 25-OHD levels (r = -0.50, p < 0.01) and the Tinetti scores (balance: r = -0.40, p < 0.05; gait: r = -0.50, p < 0.05). In 11 vitamin D-deficient patients (55%), there was selective complete atrophy of at least one thigh muscle. The gracilis and sartorius muscles were spared. CONCLUSION: In elderly adults, fatty degeneration of thigh muscles was associated with vitamin D deficiency and impaired balance and gait. Selective complete fatty degeneration of single muscles was observed.

Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes.

BACKGROUND: The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto's thyroiditis (HT), although fourteen EAATD patients with Graves' disease (GD) have been also reported. METHODS: We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term. RESULTS: Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management. CONCLUSIONS: GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.

Changes in sex steroid levels in women with epilepsy on treatment: relationship with antiepileptic therapies and seizure frequency.

PURPOSE: Reproductive dysfunction in epilepsy is attributed to the seizures themselves and also to antiepileptic drugs (AEDs), which affect steroid production, binding, and metabolism. In turn, neuroactive steroids may influence neuronal excitability. A previous study in this cohort of consecutive women with epilepsy showed that patients with more frequent seizures had higher cortisol and lower dehydroepiandrosterone sulfate levels than those with rare or absent seizures. The present study was aimed at evaluating, in these same women, the possible relationship between some clinical parameters, seizure frequency, AED therapies, and sex hormone levels. METHODS: Estradiol (E2), progesterone (Pg), sex hormone-binding globulin (SHBG), and free estrogen index (FEI) were measured during the luteal phase in 113 consecutive females, 16-47 years old, with different epilepsy syndromes on enzyme-inducing AED (EIAED) and/or non-enzyme-inducing AED (NEIAED) treatments, and in 30 age-matched healthy women. Hormonal data were correlated with clinical parameters (age, epilepsy syndrome, disease onset, and duration), seizure frequency assessed on the basis of a seizure frequency score (SFS), and AED therapies. RESULTS: E2, Pg, and FEI were lower, whereas SHBG levels were higher in the epilepsy patients than in the controls. However, sex steroid and SHBG levels were not different between groups of patients categorized according to SFS. Therapies with EIAEDs accounted for changes in E2 levels and FEI. CONCLUSIONS: Despite globally decreased sex steroid levels in serum, actual hormone titers were not significantly correlated with SFS in consecutive epilepsy women; rather, these hormonal changes were explained by AED treatments, mainly when EIAED polytherapies were given.

Seizure frequency and sex steroids in women with partial epilepsy on antiepileptic therapy.

PURPOSE: Neuroactive sex steroids influence neuron excitability, which is enhanced by estradiol (E2) and decreased by progesterone (Pg). In epilepsy, the production, metabolism, biologic availability, and activity of sex hormones may be affected by seizures themselves or by antiepileptic drugs (AEDs). This cross-sectional observational study was aimed at evaluating the relationships between sex steroids, seizure frequency, and other clinical parameters in women with partial epilepsy (PE) on AED treatments. METHODS: Serum E2, Pg, sex hormone binding globulin (SHBG) levels, free E2 (fE2), and E2/Pg ratios were determined during the follicular and luteal phases in 72 adult women with PE, and in 30 healthy controls. Hormonal data were correlated with seizure frequency, age, body weight, body mass index (BMI), disease onset and duration, and AED therapies. RESULTS: In patients, E2, fE2, and Pg levels were lower in both ovarian phases, whereas those of SHBG were higher than in controls. No significant changes in hormone levels and in prevalence of anovulatory cycles were observed between patients grouped according to their seizure frequency. However, when compared with those in healthy controls, luteal fE2 and Pg levels were chiefly impaired in women with more frequent seizures, mostly undergoing AED polytherapies, but not in those with absent or rarer seizures. CONCLUSIONS: The actual changes in sex steroid levels and E2/Pg ratios did not explain an increased seizure frequency in adult women with AED-treated PE, but patients with more severe disease showed more relevant changes in their sex hormone profile and impaired Pg levels during the luteal phase.

The primary role of radiological imaging in the diagnosis of rare musculoskeletal diseases. Emphasis on ultrasound.

Objective: In July 2017 a multidisciplinary clinical Center specialized in rare diseases was activated. A rare disease can involve the musculoskeletal system. A multimodality musculoskeletal imaging approach allows for a rapid diagnosis. The purpose of this study was to assess when musculoskeletal radiology, ultrasound in particular, plays a primary role in the diagnostic path of a rare disease. Methods and materials: The Center included a list of 621 main rare diseases. Pathologies in which radiology has a primary diagnostic role were extracted from the list. From September 2017 to January 2018 all conditions involving the musculoskeletal system, including the peripheral nervous system, were systematically evaluated by one radiologist. The second radiologist, an official consultant of the Center, verified the list for consistency. Descriptive analysis was performed. Results: A total of 101/621 (16%) rare diseases can be diagnosed for the first time in the diagnostic path of the patient with medical imaging. A total of 36/101 (36%) rare diseases involve the musculoskeletal system. A total of 14/36 (39%) are pediatric diseases, 10/36 (28%) are adult age diseases, while 12/36 (33%) diseases affect all ages. A total of 23/36 (64%) of the selected rare diseases could be diagnosed with MRI, 19/36 (53%) with CT, 23/36 (64%) with X-ray, 9/36 (25%) with an US, and 1/36 (3%) with PET. Conclusions: Musculoskeletal imaging could be important for a non-invasive diagnosis in up to 36/101 (36%) rare diseases, as well as for outcome prediction, especially in pediatrics. Musculoskeletal imaging plays a crucial role in the diagnosis of rare diseases and could strongly influence the clinical pathway. Ultrasound is crucial in up to 25% of patients with rare diseases affecting the musculoskeletal system.

Bioethics in Italian Medical and Healthcare Education. A Pilot Study.

BACKGROUND AND AIM OF THE WORK: Bioethics is relevant in healthcare and medical schools. However, unlike other foreign countries, its teaching in Italy has only been recently introduced, it is less extensively offered and no academic standards for bioethics education have been established. This research aims at understanding whether university bioethics courses attendees appreciate and consider teaching strategies to be effective with the objective of validating a coherent didactic approach to the discipline and stimulate further discussion on ways to improve it. METHODS: A standardized survey was administered to 1590 students attending undergraduate degree programs in medicine and healthcare at four Italian universities. RESULTS: The majority of interviewees (92.5%) had an interest in bioethics, considered it to be important for any life-sciences-related program (73.5%) and most healthcare (77.2%) and medical students (69.2%) suggested its teaching should be included in their curricula and made mandatory (66.3%) and continuous (57.7%), given its usefulness in clinical practice. Students consider bioethics as a care-integrated practice and appreciate teaching methods where it is integrated into clinical cases. Conceptual specificity and interdisciplinarity may affect the learning process and contribute to enhance students' analytical skills. CONCLUSIONS: Italian bioethics education should be revised to meet students' expectations and preferences. Its complex, multi-disciplinary and transversal nature suggests bioethical education to be flexible and integrated among different disciplines, thus stimulating a broader critical capacity through cases studies and other interactive teaching methods for helping students better deal with bioethics-inherent difficulties and improve the learning process.

Chronic Intake of Micrograms of Abscisic Acid Improves Glycemia and Lipidemia in a Human Study and in High-Glucose Fed Mice.

We tested the effect of chronic low-dose abscisic acid (ABA), a phytohormone-regulating human glucose tolerance, on the metabolic parameters that are dysregulated in prediabetes and metabolic syndrome (MS).Ten healthy subjects received 1 µg ABA/Kg body weight (BW)/day as an ABA-rich food supplement: (i) the glycemia profile after a carbohydrate-rich meal, with or without supplement, was compared; (ii) fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), and body mass index (BMI) after 75 days of daily supplementation of a habitual Mediterranean diet were compared with starting values.CD1 mice were fed a high-glucose diet with or without synthetic ABA (1 µg/Kg BW) for 4 months and the same parameters investigated in the human study were compared. The food supplement significantly reduced the area under the curve of glycemia after a carbohydrate-rich meal and FBG, HbA1c, TC, and BMI after chronic treatment. ABA-treated mice showed a significant reduction of HbA1c, TC, and body weight gain compared with untreated controls. The combined results from the human and murine studies allow us to conclude that the observed improvement of the metabolic parameters can be attributed to ABA and to advocate the use of ABA-containing food supplements in prediabetes and/or MS.

Cortical sources of awake scalp EEG in eating disorders.

OBJECTIVE: To investigate quantitative EEG (qEEG) in anorexia nervosa (AN) and bulimia nervosa (BN) in comparison with healthy controls. METHODS: Resting EEG was recorded in 30 healthy females (age: 27.1+/-5.5), 16-AN females (age: 26.4+/-9.5) and 12-BN females (age: 27.0+/-6.3). Cortical EEG sources (delta, theta, alpha 1, alpha 2, beta 1, beta 2) were modeled by LORETA solutions. The statistical analysis was performed considering the factors Group, power Band, and region of interest (central, frontal, parietal, occipital, temporal, limbic). RESULTS: Alpha 1 sources in central, parietal, occipital and limbic areas showed a greater amplitude in Controls versus AN and BN groups. Alpha 2 sources in parietal, occipital and limbic areas showed a greater amplitude in Controls than in both AN and BN groups. Alpha 1 sources in temporal area showed a greater amplitude in Controls compared to both the BN and AN groups as well as in the BN group compared to AN group. Central alpha 1 source correlated significantly with BMI in patients. CONCLUSIONS: These results support the hypothesis that eating disorders are related to altered mechanisms of cortical neural synchronization, especially in rolandic alpha rhythms. SIGNIFICANCE: To our knowledge this is the first study by LORETA able to detect modifications of cortical EEG activity in eating disorders.

Pemphigus vegetans Neumann type with anti-desmoglein and anti-periplakin autoantibodies.

Pemphigus vegetans is a rare variant of pemphigus vulgaris characterized by vegetating lesions in the folds and mouth and by the presence of autoantibodies against desmoglein 3. We describe two Caucasian patients with pemphigus vegetans, one of them presented antibodies to desmoglein 3 and 1 and the other one to desmoglein 3. Both patients also had circulating antibodies against a 190 kDa protein co-migrating with periplakin. Anti-periplakin reactivity is usually detected in paraneoplastic pemphigus, while it has never been reported in pemphigus vegetans. Our observation enlarges the spectrum of autoantibodies which may be associated with pemphigus vegetans. However, the pathophysiological significance of anti-periplakin reactivity in this pemphigus variant remains to be determined.