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Medullary thyroid carcinoma (MTC) accounts for only 3% of all thyroid carcinomas: 75% as sporadic MTC (sMTC) and 25% as hereditary MTC (hMTC) in the context of multiple endocrine neoplasia type 2 (MEN2). Early diagnosis is possible by determining the tumour marker calcitonin (Ctn) when clarifying nodular goitre and by detecting the mutation in the proto-oncogene RET in the MEN2 families. If the Ctn level is only slightly elevated, up to 30 pg/ml in women and up to 60 pg/ml in men, follow-up checks are advisable. At higher levels, surgery should be considered; at a level of > 100 pg/ml, surgery is always advisable. The treatment of choice is total thyroidectomy, possibly with central lymphadenectomy. In the early stage, cure is possible with adequate surgery; in the late stage, treatment with tyrosine kinase inhibitors is an option. RET A mutation analysis should be performed on all patients with MTC. During follow-up, a biochemical distinction is made between: healed (Ctn not measurably low), biochemically incomplete (Ctn increased without tumour detection) and structural tumour detection (metastases on imaging). After MTC surgery, the following results should be available for classification in follow-up care: (i) histology, Ctn immunohistology if necessary, (ii) classification according to the pTNM scheme, (iii) the result of the RET analysis for categorisation into the hereditary or sporadic variant and (iiii) the postoperative Ctn value. Tumour progression is determined by assessing the Ctn doubling time and the RECIST criteria on imaging. In most cases, “active surveillance” is possible. In the case of progression and symptoms, the following applies: local (palliative surgery, radiotherapy) before systemic (tyrosine kinase inhibitors).

Introduction: Colovesical fistula (CVF) is a condition with various aetiologies and presentations. Surgical treatment is necessary in most cases. Due to its complexity, open approach is preferred. However, laparoscopic approach is reported in the management of CVF due to diverticular disease. The aim of this study was to analyse the management and outcome of patients with CVF of different aetiologies treated with laparoscopic approach. Patients and Methods: This was a retrospective study. We retrospectively reviewed all patients undergoing elective laparoscopic management of CVF from March 2015 to December 2019. Statistical Analysis Used: None. Results: Nine patients underwent laparoscopic management of CVF. There were no intraoperative complications or conversions to open surgery. A sigmoidectomy was performed in eight cases. In one patient, a fistulectomy with sigmoid and bladder defect closure was performed. In two cases of locally advanced colorectal cancer with bladder invasion, a multi-stage procedure with temporary colostomy was chosen. In three cases, with no intraoperative leakage, we did not perform bladder suture. Four Clavien I–II complications were recorded. Two fragile patients died in the post-operative period. No patients required re-operation. At a median follow-up of 21 months (interquartile range: 6–47), none of the patients had recurrence of fistula. Conclusions: CVF can be managed with laparoscopic approach by skilled laparoscopic surgeons in different clinical scenarios. Bladder suture is not necessary if leakage is absent. Informed counselling to the patient must be guaranteed concerning the risk of major complications and mortality in case of CVF due to malignant disease.

With its combination of online and face-to-face interaction, blended learning is increasingly being employed in postgraduate education. To date, most empirical research on the topic has focused on the design and relative effectiveness of online versus in-person learning. Meanwhile, any exploration of the costs of its delivery has often been neglected. In this study, we propose a framework to assess the costs and cost-effectiveness of alternative designs of blended postgraduate programs, and then empirically apply it to an innovative blended Master of Business Administration (MBA) course as compared with similar MBAs taught at the same institution, with the differences lying in their proportions of online content and the intensity of their use. We applied the Community of Inquiry framework to show that the program with the most intensive use of online learning is also the most effective in terms of student cognitive gain. However, it is not the most cost-effective when compared to other, less online-intensive alternatives. We also found that this result depends on the scalability constraints imposed by the design of the programs. The implications of the scalability versus the quality versus the costs of blended education are then discussed.

Abstract Introduction Current research points to the importance personality pathology and Major Depression e as relevant psycopathological risk factors for understanding suicidal risk in adolescence. Literature has mainly focused on the role of BPD, however current orientations in personality pathological functioning suggest that BPD may be the representative of a general personality disturbance, a factor of vulnerability underlying diverse psychopathological variants and aspects of maladaptive functioning. However, recent studies seem to have neglected the contributions that other specific personality disorders and personality pathology as a general factor of vulnerability for suicidality; and only marginally investigated the interaction of personality disorder (PD) as an overall diagnosis and individual PDs and major depression (MDD). In this paper, the independent and cumulative effects of MDD and DSM-IV PDs on suicidal risk are investigated in a sample of adolescents observed in a longitudinal window of observation ranging from three months preceding the assessment to a six-month follow up period of clinical monitoring. Methods A sample of 118 adolescents (mean age = 15.48 ± 1.14) referred for assessment and treatment on account of suicidal ideation or behavior were administered the CSSRS, SCID II, Kiddie-SADS at admission at inpatient and outpatient Units. All subjects included in the study had reported suicidal ideation or suicide attempts at the C-SSRS; The CSSRS was applied again to all patients who reported further suicidal episodes during the six-months follow-up period of clinical monitoring. Dimensional diagnoses of PDs was obtained by summing the number of criteria met by each subject at SCID-%-PD 5, In order, to test the significance of the associations between the variables chosen as predictors (categorical and dimensional PDs and MD diagnosis), and the suicidal outcomes variables suicide attempts, number of suicide attempts and potential lethality of suicide attempt, non-parametric bivariate correlations, logistic regression models and mixed-effects Poisson regression were performed PD. Results The categorical and dimensional diagnosis of PD showed to be a significant risk factors for suicide attempt and their recurrence, independently of BPD, that anyway was confirmed to be a specific significant risk factor for suicidal behaviors. Furthermore, PD assessed at a categorical and dimensional level and Major Depression exert an influence on suicidal behaviors and their lethality both as independent and cumulative risk factors. Limitations Besides incorporating dimensional thinking into our approach to assessing psychopathology, our study still relied on traditionally defined assessment of PD. Future studies should include AMPD-defined personality pathology in adolescence to truly represent dimensional thinking. Conclusion These results point to the importance of early identification of the level of severity of personality pathology at large and its co-occurrence with Major Depression for the management of suicidal risk in adolescence.

Abstract Background Tolosa-Hunt syndrome (THS) and recurrent painful ophthalmoplegic neuropathy (RPON) are rare diseases reported within the “Painful lesions of the cranial nerves” section of the International Classification of Headache Disorders-3rd edition (ICHD-3). In case of a first painful attack, differential diagnosis could be challenging and many pitfalls are due to the rarity of the disorders and the lack of information about correct medical management in youngsters. Case presentation Our main purpose was to report a new case of THS and a new case of RPON describing management and diagnostic investigation at the time of the first episode. In both cases of THS (13 years old) and RPON (14 years old) a unilateral periorbital headache associated with acute onset of ipsilateral third cranial nerve paresis, scarcely responding to non-steroidal anti-inflammatory drugs (NSAID), was present at the beginning of the first attack. Brain MRI with "time-of-flight" (TOF) angiography and the need to administer steroids (after 72 h from onset) in order to stop pain were the most important handles allowing us to adopt the correct management both in THS or RPON since onset and to face recurrences in RPON by avoiding useless therapy during follow-up. Conclusion Unilateral periorbital headache associated with third-fourth or sixth cranial nerve paresis should ideally be investigated with a full work-up, comprehensive of brain MRI with TOF angiography since the first attack. In cases with negative brain MRI spontaneous resolution should be considered and watchful waiting might be advisable before starting steroid therapy.

PURPOSE: Contrast Enhancement Magnetic Resonance (CEMR) and Contrast-Enhanced Mammography (CEM) are important diagnostic tools to evaluate breast cancer patients, and both are objects of interest in the literature. The purpose of this systematic review was to select publications from the last ten years in order to evaluate the literature contributions related to the frequency of contrast agents used, administration techniques and the presence of adverse reactions. METHODS: We have selected, according to the PRISMA statement, publications reviewed on Pub Med in the period from 1 January 2012 to 31 December 2022. The search engine was activated using the following keywords: “CESM”, “CEM”, “CEDM”, “Contrast mammography” for CEM, “DCE-MRI”, “Contrast Enhancement MRI” for CEMR, excluding reviews, book chapters and meta-analyses. From the total number of publications, we made a preliminary selection based on titles and abstracts and excluded all articles published in languages other than English and all experimental studies performed on surgical specimen or animal population, as well as all articles for which the extended version was not available. Two readers evaluated all the articles and compiled a pre-compiled form accordingly. RESULTS: After a preliminary collection of 571 CEM publications, 118 articles were selected, relating to an overall population of 21,178 patients. From a total of 3063 CEMR publications, 356 articles relating to an overall population of 45,649 patients were selected. The most used contrast agents are Iohexol for CEM (39.83%) and Gadopentetic acid (Gd-DTPA) for CEMR (32.5%). Regarding the CEM contrast administration protocol, in 84.7% of cases a dose of 1.5 mL/kg was used with an infusion rate of 2–3 mL/s. Regarding the CEMR infusion protocol, in 71% of cases a dose of 1 mmol/kg was used at an infusion rate of 2–4 mL/s. Twelve out of 118 CEM articles reported allergic reactions, involving 29 patients (0.13%). In DCE-MRI, only one out of 356 articles reported allergic reactions, involving two patients (0.004%). No severe reactions were observed in either cohort of exams. CONCLUSIONS: CEM and CEMR are essential contrast methods to evaluate breast diseases. However, from the literature analysis, although there are preferences on the uses of the contrast agent (Iohexol for CESM, G-DTPA for CEMR), a wide range of molecules are still used in contrast methods, with different administration protocols. Based on the collected data, it is possible to state that both methods are safe, and no severe reactions were observed in our evaluation.

By applying a microwave drive to a specially designed Josephson circuit, we have realized a double-well model system: a Kerr oscillator submitted to a squeezing force. We have observed, for the first time, the spectroscopic fingerprint of a quantum double-well Hamiltonian when its barrier height is increased: a pairwise level kissing (coalescence) corresponding to the exponential reduction of tunnel splitting in the excited states as they sink under the barrier. The discrete levels in the wells also manifest themselves in the activation time across the barrier which, instead of increasing smoothly as a function of the barrier height, presents steps each time a pair of excited states is captured by the wells. This experiment illustrates the quantum regime of Arrhenius’s law, whose observation is made possible here by the unprecedented combination of low dissipation, time-resolved state control, 98.5% quantum nondemolition single shot measurement fidelity, and complete microwave control over all Hamiltonian parameters in the quantum regime. Direct applications to quantum computation and simulation are discussed.

Canine degenerative myelopathy is a fatal neurodegenerative disorder that affects the spinal cord. It is a late-onset disease, with symptoms becoming evident later in life at approximately 8 years of age. The principal aim of this study was to retrospectively evaluate allelic and genotypic frequencies of the c.118G > A and c.52A > T mutations located on the SOD1 gene in an Italian canine population to provide detailed information on the prevalence of the mutations in the country. The genetic data of different breeds were collected through DNA tests over a nine-year period in the Italian canine population. For each dog, the breed, sex, age, and DNA test results were recorded. Allelic and genotypic frequencies were calculated. A total of 1667 DNA tests for the c.118G > A and c.52A > T mutations were carried out on 84 breeds. For the analysis of prevalence, only breeds counting more than 20 subjects have been considered, for a total of 1410 DNA tests obtained from 13 different breeds. In the population tested for the c.118G > A mutation, 65.47% (n. 893) of the subjects were clear, 25.59% (n. 349) were heterozygous carriers, and 8.94% (n. 122) were homozygous for the mutated allele. The mutation showed the highest frequency in Pembroke Welsh Corgis (55.49%) and the lowest frequencies in Poodles (6.32%) and Australian Shepherds (7.14%). The allelic frequency of the c.52A > T mutation was 7.61% in the Bernese Mountain dog. Neither variant differed between females and males in genotypic frequencies. The present study provides insights into the allelic and genotypic frequencies of canine degenerative myelopathy in different dog breeds in Italy.

Background and Objectives: Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid paresis in children. The aim of this study was to describe the clinical and electrophysiological findings and outcomes of children with GBS diagnosed in our unit. Moreover, the literature on pediatric GBS cases from the past 5 years was reviewed. In this retrospective study, we reported data on 12 patients (9 male and 3 female patients; mean age: 5 y, 4 mo; range: 9 mo–11 y) clinically diagnosed at the Child Neurology Unit of the AUSL-IRCCS of Reggio Emilia, Italy, between 2000 and 2017 and a brief analysis/comparison with data from the literature. Materials and Methods: Data were collected from medical charts. Results: In our cohort, male patients were more frequent than female ones (9 vs. 3), and upper respiratory tract infection (n = 8, 66.7%) was the most frequent triggering factor. The main clinical symptoms on admission were distal lower limbs’ weakness with gait difficulties (83.3%), pain (50%), upper limbs’ weakness (50%), and dysphagia for liquids (25%). Peripheral neurophysiological studies revealed acute inflammatory demyelinating polyradiculoneuropathy (AIDP) in 66.6% of the children, acute motor and sensory axonal neuropathy (AMSAN) in 25%, and acute motor axonal neuropathy (AMAN) in 8.3%. Ten individuals (83.3%) received timely treatment with intravenous immunoglobulins (IVIG), and, out of these ten patients, 58% received concomitant treatment with IV methylprednisolone because of a progressive disease course. Complete remission was observed in the majority of individuals (91.6%) within 6 months of symptom onset. Conclusions: Different subtypes of GBS can affect children; however, the outcome is usually positive. Early treatment appears to be important for a favorable outcome.

Abstract DNA methylation is important for gene expression and alterations in DNA methylation are involved in the development and progression of cancer and other major diseases. Analysis of DNA methylation patterns has until now been dependent on either a chemical or an enzymatic pre-treatment, which are both time consuming procedures and potentially biased due to incomplete treatment. We present a qPCR technology, EpiDirect®, that allows for direct PCR quantification of DNA methylations using untreated DNA. EpiDirect® is based on the ability of Intercalating Nucleic Acids (INA®) to differentiate between methylated and unmethylated cytosines in a special primer design. With this technology, we develop an assay to analyze the methylation status of a region of the MGMT promoter used in treatment selection and prognosis of glioblastoma patients. We compare the assay to two bisulfite-relying, methyl-specific PCR assays in a study involving 42 brain tumor FFPE samples, revealing high sensitivity, specificity, and the clinical utility of the method.