Molecular technology and the recombinant TSH have changed diagnostics of thyroid carcinoma with positive I-131 whole body scan but low serum thyroglobulin.

The early detection of recurrent differentiated thyroid carcinoma (DTC) cells in the post surgery DTC patients relies on the sensitivity of measuring both the level of thyroglobulin (Tg) and 131-Iodine distribution by Whole Body Scan (WBS). Undetectable level of Tg associated with negative WBS or elevated levels of Tg associated with positive WBS ("concordant") is ordinarily indicative of either absence or presence of disease. At times, elevated level of Tg with negative WBS or low levels of Tg with positive WBS ("discordant") could also occur. In the present study, we retrospectively reviewed series of 573 patients with DTC followed in the Diagnostic Imaging and Radiotherapy of the University "Federico II" of Naples between 1993 and 1997. We focused on 9 out of 573 patients (1.56%) who had a discordant pattern with low level of Tg/positive WBS in the post-surgical follow-up. Four patients were metastatic at presentation while 5 patients with metastasis during follow-up still remained in persistently low levels of Tg (<5 ng/mL). This result does point to some flaw in the evaluation of "discordant" cases. Reviewing data previously described series by resetting cut-off values of Tg <1 ng/ml as undetectable changed the apparent "discordant" subgroup of patients into "concordant". Recent introduction of recombinant human TSH (rhTSH) to enhance the expression level of Tg brought significant increase in the sensitivity of diagnostic evaluation of thyroid cancer patients. The role of burdensome WBS in the follow up evaluation of DTC patients is significantly reduced over time especially in low-risk patients while the relevance of Tg assay is steadily increased. Sensitive Tg assays, significantly improved our ability to assess disease status in follow-up of DTC. Given the possibility of late disease relapses, the need for long-term follow-up, and reduced delay in treatment of persistent disease, there is still need for greater sensitive diagnostic tools for DTC

Attentional control of gait and falls: Is cholinergic dysfunction a common substrate in the elderly and Parkinson's disease?

The aim of this study was to address whether deficits in the central cholinergic activity may contribute to the increased difficulty to allocate attention during gait in the elderly with heightened risk of falls. We recruited 50 participants with a history of two or more falls (33 patients with Parkinson's Disease and 17 older adults) and 14 non-fallers age-matched adults. Cholinergic activity was estimated by means of short latency afferent inhibition (SAI), a transcranial magnetic stimulation (TMS) technique that assesses an inhibitory circuit in the sensorimotor cortex and is regarded as a global marker of cholinergic function in the brain. Increased difficulty to allocate attention during gait was evaluated by measuring gait performance under single and dual-task conditions. Global cognition was also assessed. Results showed that SAI was reduced in patients with PD than in the older adults (fallers and non-fallers) and in older adults fallers with respect to non-fallers. Reduction in SAI indicates less inhibition i.e., less cholinergic activity. Gait speed was reduced in the dual task gait compared to normal gait only in our faller population and changes in gait speed under dual task significantly correlated with the mean value of SAI. This association remained significant after adjusting for cognitive status. These findings suggest that central cholinergic activity may be a predictor of change in gait characteristics under dual tasking in older adults and PD fallers independently of cognitive status

Do flexible inter-injection intervals improve the effects of botulinum toxin A treatment in reducing impairment and disability in patients with spasticity?

In patients treated with botulinum toxin-A (BoNT-A), toxin-directed antibody formation was related to the dosage and frequency of injections, leading to the empirical adoption of minimum time intervals between injections of 3&nbsp;months or longer. However, recent data suggest that low immunogenicity of current BoNT-A preparations could allow more frequent injections. Our hypothesis is that a short time interval between injections may be safe and effective in reducing upper limb spasticity and related disability. IncobotulinumtoxinA was injected under ultrasound guidance in spastic muscles of 11 subjects, who were evaluated just before BoNT-A injection (T0), and 1&nbsp;month (T1), 2&nbsp;months (T2) and 4&nbsp;months (T3) after injecting. At T1, in the case of persistent disability related to spasticity interfering with normal activities, patients received an additional toxin dose. Seven subjects received the additional dose at T1 because of persistent disability; 4 of them had a decrease of disability 1&nbsp;month later (T2). Rethinking the injection scheme for BoNT-A treatment may have a major impact in the management of spasticity and related disability. Future studies with larger sample sizes are warranted to confirm that injection schedules with short time intervals should no longer be discouraged in clinical practice

The "Gender factor" in wearing-off among patients with Parkinson’s disease: a post hoc analysis of DEEP study

Background. The early detection of wearing-off in Parkinson disease (DEEP) observational study demonstrated that women with Parkinson’s disease (PD) carry an increased risk (80.1%) for wearing-off (WO). This post hoc analysis of DEEP study evaluates gender differences onWO and associated phenomena. Methods. Patients on dopaminergic treatment for ≥1 year were included in this multicenter observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as the use of the 19-item wearing-off questionnaire (WOQ-19);WO was defined for scores ≥2. Post hoc analyses were conducted to investigate gender difference for demographic and clinical features with respect toWO. Results. Of 617 patients enrolled, 236 were women and 381 were men. Prevalence of WO was higher among women, according to both neurologists’ judgment (61.9% versus 53.8%, P = 0.045) and theWOQ-19 analysis (72.5% versus 64.0%, P = 0.034). In patients withWO (WOQ-19), women experienced ≥1 motor symptom in 72.5% versus 64.0% in men and ≥1 nonmotor symptom in 44.5% versus 36.7%, in men. Conclusions. Our results suggestWO as more common among women, for both motor and nonmotor symptoms. Prospective studies are warranted to investigate this potential gender-effect

Chemotherapy regimen GOLF induces apoptosis in colon cancer cells through multi-chaperone complex inactivation and increased Raf-1 ubiquitin-dependent degradation.

The multi-drug combination of oxaliplatin (OXA), 5-Fluorouracil (5-FU) and leucovorin (LF) is currently considered as the gold standard treatment for metastatic colorectal carcinoma. In previous studies, we have studied a chemotherapy regimen containing gemcitabine (GEM), OXA, LF, and 5-FU (named GOLF regimen) that has shown a good safety profile and highly significant anti-tumor activity. In the present study, we have investigated on the anti-tumour mechanisms of GOLF in human colon cancer HT-29 and WiDr cell lines. We have found that GOLF induced growth inhibition that was largely caused by apoptosis differently from other combinations. Moreover, the different drugs composing GOLF were highly synergistic in inducing growth inhibition. Apoptosis induced by GOLF combination was paralleled by PARP cleavage and caspase 9 and 3 activation that were not recorded in the other combinations. An about 85% decrease of the activity of Erk and Akt was found in GOLF-treated cells. These effects were likely due to decreased expression of the upstream activator Raf-1 and of Akt itself, respectively. The intracellular levels of these signalling components can be post-translationally regulated by ubiquitin-dependent degradation through proteasome. Therefore, we have evaluated the expression of some chaperone components and we have found that GOLF did not affect the expression of both heat shock protein (HSP) 90 and 27 but induced an about 90% increase of HSP70 levels suggesting the inactivation of the multi-chaperone complex. Moreover, an about 4-fold increase of the ubiquitination of Raf-1 was also found and the addition for 12 h of 10 microM proteasome inhibitor lactacystin caused an accumulation of the ubiquitinated isoforms of Raf-1. In conclusions, GOLF was a combination highly synergistic in inducing both growth inhibition and apoptosis of colon cancer cells. These effects likely occurred through the disruption of critical survival pathways and the inactivation of multi-chaperone complex

A randomised controlled cross-over double-blind pilot study protocol on THC:CBD oromucosal spray efficacy as an add-on therapy for post-stroke spasticity

Stroke is the most disabling neurological disorder and often causes spasticity. Transmucosal cannabinoids (tetrahydrocannabinol and cannabidiol (THC:CBD), Sativex) is currently available to treat spasticity-associated symptoms in patients with multiple sclerosis. Cannabinoids are being considered useful also in the treatment of pain, nausea and epilepsy, but may bear and increased risk for cardiovascular events. Spasticity is often assessed with subjective and clinical rating scales, which are unable to measure the increased excitability of the monosynaptic reflex, considered the hallmark of spasticity. The neurophysiological assessment of the stretch reflex provides a precise and objective method to measure spasticity. We propose a novel study to understand if Sativex could be useful in reducing spasticity in stroke survivors and investigating tolerability and safety by accurate cardiovascular monitoring

グリコシド結合形成反応を中心とした糖質化合物の化学変換

博士（理学）神戸大

Erratum to: Treatment of essential tremor: a systematic review of evidence and recommendations from the Italian Movement Disorders Association

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The impact of cognitive function deficits and their recovery on functional outcome in subjects affected by ischemic subacute stroke: results from the Italian multicenter longitudinal study CogniReMo

Background: The recovery of independence in activities of daily living is a fundamental goal of rehabilitation programs in subjects affected by subacute stroke. Rehabilitation is focused both on motor and cognitive aspects, and some evidence has reported cognitive deficits as prognostic factors of motor recovery. However, rehabilitation is a dynamic process during which executive functions and motor functions should be improved. Aim: The aim of the study is to evaluate the relationships between impairments in cognitive functions and recovery of functional independence in stroke patients during the subacute phase. Design: Multicenter observational study. Setting: Intensive rehabilitation units. Population: A sample of 319 stroke patients in subacute phase (70.6±11.6 years, 40.4% females), consecutively admitted from November 2019 to July 2021 at sixteen rehabilitation centers were enrolled in this observational, prospective and multicentric study with longitudinal assessments. Methods: Cognitive and functional assessments were performed at hospital admission and discharge, including Oxford Cognitive Screen, modified Barthel Index, Functional Independent Measure, Fugl-Meyer assessment scale and National Institutes of Health Stroke Scale. Results: A regression analysis identified five predictors (out of about 200 tested variables) of functional recovery related to four aspects assessed at admission: functional status (P&lt;0.001), lower limb functioning (P=0.002), attention (P=0.011), and executive functions (P=0.017). Furthermore, patients who recovered deficits in executive functions had the same recovery of those without deficits, whereas those who maintained deficits had a smaller recovery (P=0.019). Conclusions: The relationship between cognitive and motor deficits is increasingly highlighted and the recovery of executive functions deficits seems to contribute to motor recovery. Clinical rehabilitation impact: Our results suggest that the recovery of executive functions may promote the recovery of the functional outcome of the patient with subacute stroke. Future treatment protocols may benefit from paying more attention to the recovery of executive functions

Diabetes and Ramadan: need for a cultural action

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