Alpha-synuclein/synapsin III pathological interplay boosts the motor response to methylphenidate

: Loss of dopaminergic nigrostriatal neurons and fibrillary α-synuclein (α-syn) aggregation in Lewy bodies (LB) characterize Parkinson's disease (PD). We recently found that Synapsin III (Syn III), a phosphoprotein regulating dopamine (DA) release with α-syn, is another key component of LB fibrils in the brain of PD patients and acts as a crucial mediator of α-syn aggregation and toxicity. Methylphenidate (MPH), a monoamine reuptake inhibitor (MRI) efficiently counteracting freezing of gait in advanced PD patients, can bind α-syn and controls α-syn-mediated DA overflow and presynaptic compartmentalization. Interestingly, MPH results also efficient for the treatment of attention deficits and hyperactivity disorder (ADHD), a neurodevelopmental psychiatric syndrome associated with Syn III and α-syn polymorphisms and constituting a risk factor for the development of LB disorders. Here, we studied α-syn/Syn III co-deposition and longitudinal changes of α-syn, Syn III and DA transporter (DAT) striatal levels in nigrostriatal neurons of a PD model, the human C-terminally truncated (1-120) α-syn transgenic (SYN120 tg) mouse, in comparison with C57BL/6J wild type (wt) and C57BL/6JOlaHsd α-syn null littermates. Then, we analyzed the locomotor response of these animals to an acute administration of MPH (d-threo) and other MRIs: cocaine, that we previously found to stimulate Syn III-reliant DA release in the absence of α-syn, or the selective DAT blocker GBR-12935, along aging. Finally, we assessed whether these drugs modulate α-syn/Syn III interaction by fluorescence resonance energy transfer (FRET) and performed in silico studies engendering a heuristic model of the α-syn conformations stabilized upon MPH binding. We found that only MPH was able to over-stimulate a Syn III-dependent/DAT-independent locomotor activity in the aged SYN120 tg mice showing α-syn/Syn III co-aggregates. MPH enhanced full length (fl) α-syn/Syn III and even more (1-120) α-syn/Syn III interaction in cells exhibiting α-syn/Syn III inclusions. Moreover, in silico studies confirmed that MPH may reduce α-syn fibrillation by stabilizing a protein conformation with increased lipid binding predisposition. Our observations indicate that the motor-stimulating effect of MPH can be positively fostered in the presence of α-syn/Syn III co-aggregation. This evidence holds significant implications for PD and ADHD therapeutic management

The size criteria in minimally invasive video-assisted thyroidectomy

BACKGROUND: Thyroid size is a very important criteria of MIVAT exclusion because the working space provided by the technique is limited. The aim of this work has been to verify the suitability of MIVAT and its applicability in clinical practice, not only in patients with a thyroid volume up to 25 ml but also in patients with a thyroid volume included from 25 to 50 ml. METHODS: From January 2003 to February 2006, 33 patients have been selected for MIVAT. A completely gasless procedure was carried out through a central 20 to 35 mm skin incision performed "high" between the cricoid and jugular notch. RESULTS: The patients were separated in 2 groups. The first group (less than 25 ml) included 23 patients, the second group (from 25 to 50 ml) included 10 patients. The skin incision performed was from 20 to 25 mm (mean 23.61 mm ± 1.83) long in the first group and from 25 to 35 mm (mean 27.8 mm ± 2.20) long in the second one; this difference is significant (t test p < 0.001). CONCLUSION: Our study suggest that the MIVAT using for thyroids bigger than 25 ml and up to 50 ml in volume is feasible and safe. This way allows more patients, excluded before, to take the advantages of minimally invasive approach

The minimally invasive open video-assisted approach in surgical thyroid diseases

BACKGROUND: The targets of minimally invasive surgery (MIVA) could be summarised by: achievement of the same results as those obtained with traditional surgery, less trauma, better post-operative course, early discharge from hospital and improved cosmetic results. The minimally invasive techniques in thyroid surgery can be described as either endoscopic "pure" approach (completely closed approach with or without CO(2 )insufflation), or "open approach" with central neck mini-incision or "open video-assisted approach". Traditionally, open thyroidectomy requires a 6 to 8 cm, or bigger, transverse wound on the lower neck. The minimally invasive approach wound is much shorter (1.5 cm for small nodules, up to 2–3 cm for the largest ones, in respect of the exclusion criteria) upon the suprasternal notch. Patients also experience much less pain after MIVA surgery than after conventional thyroidectomy. This is due to less dissection and destruction of tissues. Pathologies treated are mainly nodular goiter; the only kind of thyroid cancer which may be approached with endoscopic surgery is a small differentiated carcinoma without lymph node involvement. The patients were considered eligible for MIVA hemithyroidectomy and thyroidectomy on the basis of some criteria, such as gland volume and the kind of disease. In our experience we have chosen the minimally invasive open video-assisted approach of Miccoli et al. (2002). The aim of this work was to verify the suitability of the technique and the applicability in clinical practice. METHODS: A completely gasless procedure was carried out through a 15–30 mm central incision about 20 mm above the sternal notch. Dissection was mainly performed under endoscopic vision using conventional endoscopic instruments. The video aided group included 11 patients. All patients were women with a average age of 54. RESULTS: We performed thyroidectomy in 8 cases and hemithyroidectomy in 3 cases. The operative average time has been 170 minutes. CONCLUSION: Nowadays this minimally invasive surgery, in selected patients, clearly demonstrates excellent results regarding patient cure rate and comfort, with shorter hospital stay, reduced postoperative pain and most attractive cosmetic results

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10–500 s in a frequency band of 40–1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10−5 and 9.4×10−4  Mpc−3 yr−1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves

Surgical treatment of retrosternal goiter

Background. The definition of substernal goiter is not uniform and varies among authors. We can define substernal - or retrosternal - goiter a thyroid formation with cervical departure that goes beyond the superior thoracic strait for at least 3 cm and that preserves, generally, the connections between the cervical and thoracic portion, maintaining a direct vascularization supplied by the thyroid arteries. The "forgotten" goiter is an extremely rare disease: a mediastinic thyroid mass found after total thyroidectomy. Materials and Method. 595 patients with thyroid pathology have been treated surgically in our Department. Fifty (8.4%) of these were suffered from a cervico-mediastinic goiter. The diagnosis has been confirmed by the thyroid ecotomography, by the radiologic examination of the chest, by the neck-chest CT examination, by the MR of the mediastinum and by the thyroid scintigraphy. Discussion: The surgical treatment, in retrosternal goiters, is related to the experiences of surgeons. For the majority of the surgeons almost all antero-superior mediastinal goiters can be removed across a cervicotomy, only in few cases in association with a sternal split. In our experience the cervical approach is the only surgical access used for all the patients. The complication rate following substernal goiter resection is higher than the average rate for cervical thyroidectomy. However, in our series we did not observed permanent recurrential lesions, only in one case a light hypophonia has been observed. After the intervention, in all patients the symptomatology caused by the mediastinal compression has disappeared

Anaplastic thyroid carcinoma: a case of a young woman that reports a survival exceeding 6 years

Anaplastic thyroid carcinoma (ATC) is an uncommun and highly aggressive malignancy. Differentiated follicular and papillary thyroid carcinomas account for most (80-90%) thyroid malignancies with ATC accounting for less than 5%. A diagnosis of ATC is usually fatal with a mean survival of 3-9 months and only 10-15% alive at 2 years. Histologic examination reveals that many of them contain a papillary structure or follicular components in focal areas and genetic alteration is the driving for genesis of cancer and progression. These studies showing that ATC represents a terminal "de-differentiation" of pre-existing differentiated carcinoma. Most of patients are incurable, nevertheless a multimodality approach, incorporating surgery with the aim to obtain complete macroscopic resection and achieve clear resections margins followed by adjuvant treatment RT (radiotherapy) and/or chemotherapy, improve local control and extend the survival. The aim of the present study has been to review a case of a young women with ATC that reports a survival exceeding 6 years

The size criteria in minimally invasive video-assisted thyroidectomy

Abstract Background Thyroid size is a very important criteria of MIVAT exclusion because the working space provided by the technique is limited. The aim of this work has been to verify the suitability of MIVAT and its applicability in clinical practice, not only in patients with a thyroid volume up to 25 ml but also in patients with a thyroid volume included from 25 to 50 ml. Methods From January 2003 to February 2006, 33 patients have been selected for MIVAT. A completely gasless procedure was carried out through a central 20 to 35 mm skin incision performed "high" between the cricoid and jugular notch. Results The patients were separated in 2 groups. The first group (less than 25 ml) included 23 patients, the second group (from 25 to 50 ml) included 10 patients. The skin incision performed was from 20 to 25 mm (mean 23.61 mm ± 1.83) long in the first group and from 25 to 35 mm (mean 27.8 mm ± 2.20) long in the second one; this difference is significant (t test p Conclusion Our study suggest that the MIVAT using for thyroids bigger than 25 ml and up to 50 ml in volume is feasible and safe. This way allows more patients, excluded before, to take the advantages of minimally invasive approach.</p