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Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a discrete nosological entity characterized by punctate and curvilinear gadolinium enhancement "peppering" the pons and a strong response to steroids. MRI images typically show pontine and cerebellar punctate-enhancing lesions, which occasionally spread up to the juxtacortical areas and down to the spinal cord. Interestingly, the more distant the lesion is from the pons, the less intense they become. Herein, we describe an extremely rare case of CLIPPERS presenting with predominant spinal cord involvement; then, we searched in the literature the available cases with a similar presentation. Our case focuses attention on a rare MRI CLIPPERS presentation. Since CLIPPERS has a dramatic response to corticosteroid treatment, it is fundamental to promptly recognize its MRI pattern to start treatment as soon as possible. [ABSTRACT FROM AUTHOR]

Purpose: Left ventricular thrombus (LVT) after ST-elevation myocardial infarction still presents diagnostic and therapeutic challenges. The LEVITATION survey was designed to take a picture of LVT management in current clinical practice. Methods: The survey covered diagnostic, therapeutic, and prophylactic issues and was completed by 104 European cardiac centers. Most of them (59%) were university or tertiary centers. Results: The survey showed anterior apical a-/dyskinesia, large MI, spontaneous echo-contrast, late presentation with delayed PCI, and TIMI flow 0–1 as the most important perceived risk factors for LVT formation. Serial ultrasound imaging is the most used tool to diagnose LVT (88% of the centers), with contrast-enhanced ultrasound and cardiac MR performed in case of poor apex visualization or spontaneous echo-contrast. One third (34%) of the centers uses prophylactic anticoagulation to prevent LVT formation. In the presence of LVT, low molecular weight heparin is the most used in-hospital therapy. At discharge, vitamin K antagonist and direct oral anticoagulants are used in 67 and 32% of the cases, respectively. Triple antithrombotic therapy with aspirin plus clopidogrel and VKA is the most used strategy at discharge (55%), whereas a single antiplatelet therapy is preferred only in the case of moderate-to-high risk of bleeding. To assess LVT total regression, half of the centers use contrast-enhanced ultrasound and/or cardiac-MR. The duration of anticoagulation is usually 3–6 months (55%), with long-term prolongation in case of LVT persistence or recurrence. Conclusion: The survey has depicted for the first time the current real-world management of this neglected topic and has highlighted several grey zones that are still present and not supported by evidence. [ABSTRACT FROM AUTHOR]

Object: Quantitative electroencephalography (qEEG) has shown promising results as a predictor of clinical impairment in stroke. We systematically reviewed published papers that focus on qEEG metrics in the resting EEG of patients with mono-hemispheric stroke, to summarize current knowledge and pave the way for future research. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched the literature for papers that fitted our inclusion criteria. Rayyan QCRR was used to allow deduplication and collaborative blinded paper review. Due to multiple outcomes and non-homogeneous literature, a scoping review approach was used to address the topic. Results: Or initial search (PubMed, Embase, Google scholar) yielded 3200 papers. After proper screening, we selected 71 papers that fitted our inclusion criteria and we developed a scoping review thar describes the current state of the art of qEEG in stroke. Notably, among selected papers 53 (74.3%) focused on spectral power; 11 (15.7%) focused on symmetry indexes, 17 (24.3%) on connectivity metrics, while 5 (7.1%) were about other metrics (e.g. detrended fluctuation analysis). Moreover, 42 (58.6%) studies were performed with standard 19 electrodes EEG caps and only a minority used high-definition EEG. Conclusions: We systematically assessed major findings on qEEG and stroke, evidencing strengths and potential pitfalls of this promising branch of research. [ABSTRACT FROM AUTHOR]

During the SARS-CoV2 pandemic, several cases of Posterior Reversible Encephalopathy Syndrome (PRES) and of Reversible Cerebral Vasoconstriction Syndrome (RCVS) in COVID-19 patients have been reported, but the link between these syndromes and COVID-19 is unclear. We performed a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to evaluate whether SARS-CoV2 infection or the drugs used to treat it could be deemed potential risk factors for PRES or RCVS. We performed a literature search. We found 70 articles (60 on PRES and 10 on RCVS) concerning n = 105 patients (n = 85 with PRES, n = 20 with RCVS). We analyzed the clinical characteristics of the two populations separately, then performed an inferential analysis to search for other independent risk factors. We found fewer than usual PRES-related (43.9%) and RCVS-related (45%) risk factors in patients with COVID-19. Such a low incidence of risk factors for PRES and RCVS might suggest the involvement of COVID-19 as an additional risk factor for both diseases due to its capability to cause endothelial dysfunction. We discuss the putative mechanisms of endothelial damage by SARS-CoV2 and antiviral drugs which may underlie the development of PRES and RCVS. [ABSTRACT FROM AUTHOR]

Isolated cognitive relapses (ICRs) have been a matter of debate for the past few years. Currently, there is no clear consensus on such an entity, as cognitive decline usually accompanies typical multiple sclerosis (MS) relapses. Herein, we present the neuropsychological and neurophysiological manifestations of a patient who suddenly complained of confusion and memory loss, showing insight into her deficit, in absence of sensorimotor disturbances. Neuroimaging revealed a large tumefactive gadolinium-enhancing lesion localized in the left medial temporal lobe. The patient's symptoms persisted for months afterwards, despite corticosteroid treatment. We believe our patient experienced a true ICR. ICRs are rare entities in MS, but we should be alert to their existence in order to treat them promptly. Deepening their pathophysiology is equally important and neuropsychology combined with neurophysiology may be useful in this regard. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 infection has been associated with various neurological manifestations. Since patients affected by SARS-CoV-2 infection present coagulation and immune system dysregulation, ischemic or haemorragic stroke is not uncommon, irrespective of respiratory distress. However, the occurrence of focal neurological deficits together with other symptoms like headache, cortical blindness, seizure and altered mental status should prompt the diagnosis of Posterior Reversible Encephalopathy Syndrome (PRES). Antithrombotic treatment, the alteration of endothelial function, and coagulopathy due to COVID-19 and PRES leading to the breakdown of blood–brain barrier may then contribute to the occurrence of a brain haemorrhage. Methods: We describe the case of a COVID-19 patient who developed bilateral occipital lobe haemorrhages suggestive of haemorrhagic PRES. We then reviewed the available literature about haemorrhagic evolution of PRES in COVID-19. Results: We describe the clinical and radiological features of five COVID-19 patients who developed haemorrhagic PRES. Conclusions: Coagulopathy and endothelial dysfunction resulting from the massive release of cytokines during the host immune response may be key factors in the pathogenesis of COVID-19-related PRES. Antithrombotic therapy and the leakage of the blood–brain barrier can subsequently increase the risk of haemorrhagic transformation of the lesioned brain tissue. A prompt diagnosis of PRES is mandatory, since the timely interruption/reversal of antithrombotic therapy may be a key determinant for a good prognosis. [ABSTRACT FROM AUTHOR]

Background: Falls could be serious events in Parkinson's disease (PD). Patient remote monitoring strategies are on the raise and may be an additional aid in identifying patients who are at risk of falling. The aim of the study was to evaluate if balance and timed-up-and-go data obtained by a smartphone application during COVID-19 lockdown were able to predict falls in PD patients. Methods: A cohort of PD patients were monitored for 4 weeks during the COVID-19 lockdown with an application measuring static balance and timed-up-and-go test. The main outcome was the occurrence of falls (UPDRS-II item 13) during the observation period. Results: Thirty-three patients completed the study, and 4 (12%) reported falls in the observation period. The rate of falls was reduced with respect to patient previous falls history (24%). The stand-up time and the mediolateral sway, acquired through the application, differed between "fallers" and "non-fallers" and related to the occurrence of new falls (OR 1.7 and 1.6 respectively, p < 0.05), together with previous falling (OR 7.5, p < 0.01). In a multivariate model, the stand-up time and the history of falling independently related to the outcome (p < 0.01). Conclusions: Our study provides new data on falls in Parkinson's disease during the lockdown. The reduction of falling events and the relationship with the stand-up time might suggest that a different quality of falls occurs when patient is forced to stay home — hence, clinicians should point their attention also on monitoring patients' sit-to-stand body transition other than more acknowledged features based on step quality. [ABSTRACT FROM AUTHOR]

The exact prediction of outcome of patients with Merkel cell carcinoma (MCC) of the skin is difficult to determine, although several attempts have been made to identify clinico-pathologic prognostic factors. The Ki67 proliferative index is a well-known marker routinely used to define the prognosis of patients with neuroendocrine neoplasms. However, its prognostic value has been poorly investigated in MCC, and available published results are often contradictory mainly because restricted to small series in the absence of standardized methods for Ki67 evaluation. For this reason, we explored the potential prognostic role of Ki67 proliferative index in a large series of MCCs using the WHO standardized method of counting positive cells in at least 500 tumor cells in hot spot areas on camera-captured printed images. In addition, since MCC may be considered as the cutaneous counterpart of digestive neuroendocrine carcinomas (NECs), we decided to stratify MCCs using the available and efficient Ki67 threshold of 55%, which was found prognostic in digestive NECs. This choice was also supported by the Youden index analysis. In addition, we analyzed the prognostic value of other clinico-pathologic parameters using both univariate and multivariate analysis. Ki67 index appeared significantly associated with prognosis at univariate analysis together with stage IV, lack of MCPyV, and p63 expression, but not at the multivariate analysis, where survival resulted independently influenced by p63 expression and tumor stage, only. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Brain magnetic resonance imaging (MRI) showed multiple high-signal lesions on diffusion-weighted imaging (DWI) with decreased apparent diffusion coefficient values scattered in the left frontal lobe cortex, insula, and parietal and temporal lobe, indicating the presence of multiple acute infarcts (Fig. Traditionally, the mechanism underlying the development of post-stroke chorea or dystonia includes a lesion in basal ganglia or subthalamic nucleus (STN) [[1]]. 1 Magnetic resonance imaging (MRI) on admission and illustrative scheme of the neural network involved in our patient's stroke-related movement disorder. [Extracted from the article]

To describe the efficacy of intravitreal chemotherapy (IViC) preceded by intra-arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma. This non-comparative interventional case series retrospectively reviewed the medical records of six patients who presented within months of each other with unilateral retinoblastoma, Reese-Ellsworth stage Vb/D of ABC classification in the affected eye. After clinical and ophthalmoscopic evaluation, they underwent MRI to exclude local and CNS dissemination. The IAC was given to treat retinal masses and intravitreal injections to treat vitreous seeding. Patients had received two cycles (six infusions) of IAC, and from six up to ten melphalan injections into the vitreous, with an interval of 7-10 days between them. From one to four intravitreal injections were performed for partial remission or consolidation. No permanent complications of procedures have been reported. All patients underwent to bimonthly MRI examination, during treatment and every 3 months for 1 year after last injection, to exclude orbital dissemination. Successful control (100 %) of tumor masses and vitreous seeds was achieved in all cases at 12 months follow-up. Complications were posterior lens opacity, acute ischemic papillitis, partial CVR thrombosis, hypotonia (case 1), partial vitreous hemorrhage (case 4). No complications appeared in cases 2, 3, 5, and 6. No intraocular or orbital tumor recurrence or retinoblastoma metastases (follow-up range, 12-33 months) were observed. Sequential IAC and intravitreal melphalan for advanced retinoblastoma allowed to provide retinal and vitreous seed control. [ABSTRACT FROM AUTHOR]

Why do risk premia vary over time? We examine this problem theoretically and empirically by studying the effect of market belief on risk premia. Individual belief is taken as a fundamental primitive state variable. Market belief is observable; it is central to the empirical evaluation and we show how to measure it. Our asset pricing model is familiar from the noisy REE literature but we adapt it to an economy with diverse beliefs. We derive equilibrium asset prices and implied risk premium. Our approach permits a closed form solution of prices; hence we trace the exact effect of market belief on the time variability of asset prices and risk premia. We test empirically the theoretical conclusions. Our main result is that, above the effect of business cycles on risk premia, fluctuations in market belief have significant independent effect on the time variability of risk premia. We study the premia on long positions in Federal Funds Futures, 3- and 6-month Treasury Bills (T-Bills). The annual mean risk premium on holding such assets for 1-12 months is about 40-60 basis points and we find that, on average, the component of market belief in the risk premium exceeds 50% of the mean. Since time variability of market belief is large, this component frequently exceeds 50% of the mean premium. This component is larger the shorter is the holding period of an asset and it dominates the premium for very short holding returns of less than 2 months. As to the structure of the premium we show that when the market holds abnormally favorable belief about the future payoff of an asset the market views the long position as less risky hence the risk premium on that asset declines. More generally, periods of market optimism (i.e. 'bull' markets) are shown to be periods when the market risk premium is low while in periods of pessimism (i.e. 'bear' markets) the market's risk premium is high. Fluctuations in risk premia are thus inversely related to the degree of market optimism about future prospects of asset payoffs. This effect is strong and economically very significant. [ABSTRACT FROM AUTHOR]

We show the dynamics of diverse beliefs is the primary propagation mechanism of volatility in asset markets. Hence, we treat the characteristics of the market beliefs as a primary, primitive, explanation of market volatility. We study an economy with stock and riskless bond markets and formulate a financial equilibrium model with diverse and time varying beliefs. Agents’ states of belief play a key role in the market, requiring an endogenous expansion of the state space. To forecast prices agents must forecast market states of belief which are beliefs of ‘‘others’’ hence our equilibrium embodies the Keynes ‘‘Beauty Contest.’’ A ‘‘market state of belief’’ is a vector which uniquely identifies the distribution of conditional probabilities of agents. Restricting beliefs to satisfy the rationality principle of Rational Belief (see Kurz, 1994, 1997) our economy replicates well the empirical record of the (i) moments of the price/dividend ratio, risky stock return, riskless interest rate and the equity premium; (ii) Sharpe ratio and the correlation between risky returns and consumption growth; (iii) predictability of stock returns and price/dividend ratio as expressed by: (I) Variance Ratio statistic for long lags, (II) autocorrelation of these variables, and (III) mean reversion of the risky returns and the predictive power of the price/dividend ratio. Also, our model explains the presence of stochastic volatility in asset prices and returns. Two properties of beliefs drive market volatility: (i) rationalizable over confidence implying belief densities with fat tails, and (ii) rationalizable asymmetry in frequencies of bull or bear states. [ABSTRACT FROM AUTHOR]

We study some implications of the Theory of Rational Beliefs to monetary policy. We show that monetary policy in a Rational Beliefs environment can have an important effect on the characteristics of economic fluctuations. In Rational Beliefs Equilibria money is generically non-neutral unlike Rational Expectations Equilibria in which money is neutral and monetary policy is ineffective. Under Rational Beliefs Equilibria nominal prices and real output change not only in response to changes in the exogenous growth rate of money but also in response to changes in the state of beliefs. In Rational Beliefs Equilibria monetary shocks have real effects even when they are observed but are not fully anticipated. Furthermore, the non-neutrality of money results in a short run Phillips curve. When money "flutters, real output sputters" [8]. We show that Endogenous Uncertainty and the distribution of market beliefs are the major explanatory variables of such fluctuations. Under Rational Expectations monetary policy is ineffective because agents neutralize it by predicting correctly the effect of the policy. Under Rational Beliefs it is shown instead that inflation and recessions can be substantially aggravated by the distribution of market beliefs. [ABSTRACT FROM AUTHOR]

Summary. We advance the theory that the distribution of beliefs in the market is the most important propagation mechanism of economic volatility. Our model is based on the theory of Rational Beliefs (RB) and Rational Belief Equilibrium (RBE) developed by Kurz (1994, 1997). We argue that the diverse market puzzles which are examined, such as the equity premium puzzle, are all driven by the structure of market expectations. In support of our view, we present an RBE model with which we study financial markets. The model is able to simulate the correct order of magnitude of: (i) the long term mean and standard deviation of the price\dividend ratio; (ii) the long term mean and standard deviation of the risky rate of return on equities; (iii) the long term mean and standard deviation of the riskless rate; (iv) the long term mean equity premium. In addition, the model predicts (v) the GARCH property of risky asset returns; (vi) the observed pattern of the predictability of long returns on assets, and (vii) the Forward Discount Bias in foreign exchange markets. The common economic explanation for these phenomena is the existence of heterogenous agents with diverse but correlated beliefs such that some agents are optimistic and some pessimistic about future capital gains. The model has a unique parameterization under which the model makes all the above predictions simultaneously. The parameterization requires the optimists to be in the majority but the rationality of belief conditions of the RBE require the pessimists to have a higher intensity level. In simple terms, the large equity premium and the low equilibrium riskless rate are the result of the fact that at any moment of time [ABSTRACT FROM AUTHOR]

The effect of nicotine absorbed transdermally from a patch (TNS) and. from cigarette smoking on insulin secretion and action in Type 2 diabetes has been compared. Twelve Type 2 diabetic smoking patients, aged 51 y, with diabetes for 9 y, treated either with diet and/or oral hypoglycaemic agents, were studied on three occasions according to a double-blind, placebo-controlled cross-over design. The subjects were investigated 12 h after their last cigarette or application of one patch of TNS 30 cm or TNS placebo, or whilst smoking their usual cigarette. Insulin secretion was assessed by a glucagon (1 mg IV) stimulation test. On a second occasion, insulin action was assessed by a hyperglycaemic-hyperinsulinaemic clamp, the spontaneous hyperglycaemia of the fasting state (8.61 mmol·l) being maintained during a 4 h insulin infusion (at 0.1 mU · kg · min for the initial 2 h, and 1 mU · kg . min during the last 2 h). TNS and the cigarette did not affect endogenous insulin secretion as compared to placebo. During the initial 2 h of the clamp study, plasma insulin increased from 88 to 155 pmol · l, hepatic glucose production (3-H-glucose) was less suppressed after TNS (4.31 μmol · kg · min) than after placebo (2.5 μmol · kg min), but was more suppressed than after cigarette smoking (5.61 μmol · kg · min). In the last 2 h of the clamp (plasma insulin 646 pmol · l), glucose utilization was less stimulated after TNS (36.1 μmol · kg · min) vs placebo (39.8 μmol · kg · min), but more than after cigarette smoking (33.6 μmol · kg · min), primarily because of a decrease in glucose storage. Free fatty acid and lipid oxidation were significantly less suppressed by hyperinsulinaemia after TNS and cigarette smoking vs placebo. Nicotine impairs insulin action on the liver, adipose tissue and muscle and may contribute to hyperglycaemia in Type 2 diabetes. TNS diminishes the action of insulin to a lesser extent than cigarette smoking. Thus, TNS may represent a 'metabolically' safe measure to help patients with Type 2 diabetes to quit smoking. [ABSTRACT FROM AUTHOR]

It has been established that angiotensin II stimulation may limit the antihypertensive potential of diuretic therapy in some patients. It is less clear, however, whether renin-angiotensin II stimulation is the cause of the flat blood pressure dose-response relationship to diuretics. To investigate this, 75 out-patients with essential hypertension were treated with chlorthalidone 12.5, 25 or 50 mg o.d. for 3 weeks, in a double-blind, placebo controlled cross-over study. Chlorthalidone significantly reduced blood pressure in all the groups, a plateau being reached at 25 mg o.d. Similarly, plasma renin activity was increased by each dose level of chlorthalidone, but it showed a different trend, being increased to a comparable extent at 12.5 mg and 25 mg o.d., and still higher at 50 mg o.d. Thus, greater stimulation of renin was coincident with the levelling of the blood pressure response to chlorthalidone. However no significant correlation was found between interindividual plasma renin activity and change in blood pressure, either in the entire series, or in each treatment subset. The data suggest overall that renin stimulation may influence the characteristic dose-hypotensive response relationship to diuretic agents in antihypertensive therapy, but it is unlikely that measurement of individual plasma renin activity will provide an useful guide to the optimal dose of a diuretic agents. [ABSTRACT FROM AUTHOR]

In a multicentre, double-blind (DB), within-patient study, the antihypertensive effectiveness and tolerability of two oral administration schedules of metoprolol (M) 100 mg b.i.d. versus 200 mg once daily (o.d.), were investigated in 103 outpatients with mild to moderate essential hypertension. The study lasted 14 weeks and was divided into 3 periods: a) 2 weeks of single-blind (SB) placebo wash-out; b) 4 weeks of SB administration of M 100 mg b.i.d.; at the end of the second week of this period, chlorthalidone (C) 25 mg was added in patients with a recumbent diastolic blood pressure (BP) still >95 mmHg and was continued throughout the following period; and c) DB cross-over administration of M 200 mg/d for 4 weeks on a b.i.d. schedule and 4 weeks on a once daily schedule. In comparison with pretreatment values, heart rate and systolic and diastolic BP were reduced (p<0.001) by both M administration schedules; there was no differences between the once and twice daily treatment regimens. During M once daily, betablockade was still maintained over 24 hours or longer, as the heart rate remained significantly lower than the basal value. In 57 patients, C was added at the end of the second week of SB M administration, and a further decrease in BP was observed; again, there was no significant change during once and twice daily M administration. Unwanted effects during M treatment were of minor severity, and the majority occurred when C, too, was added. [ABSTRACT FROM AUTHOR]

A double-blind, cross-over study in 16 patients with essential hypertension was carried out, to evaluate any possible interference by indomethacin, a known prostaglandin-synthetase inhibitor, with the antihypertensive effect of oxprenolol, a non-selective beta-adrenoceptor blocking agent. Both indomethacin and oxprenolol, as well as the two drugs combined, inhibited plasma renin activity; no change was found in urinary sodium excretion or body weight. Oxprenolol alone caused a highly significant decrease in the systolic (−10.4 mmHg, p<0.001), diastolic (−7.4 mmHg, p<0.001) and mean (−7.7 mmHg, p<0.01) blood pressures, whereas indomethacin did not influence blood pressure. When the two drugs were given in combination, blood pressure decreased (systolic: −5.9 mmHg; diastolic: −4.0 mmHg; mean: −4.6 mmHg), but the changes induced in blood pressure were reduced by about 50% when compared with those in the oxprenolol alone period. The data show that indomethacin seems to interfere with the antihypertensive effect of oxprenolol, by an action which may be due to the inhibition of prostaglandin synthesis. [ABSTRACT FROM AUTHOR]

In a multicentre, double-blind, between-patient study the hypotensive effect of oxprenolol was investigated in 329 patients with mild to moderate hypertension. A factorial experimental design with three factors was chosen: oxprenolol - none or daily doses of 20, 40, 60 and 80 mg; dihydralazine and hydrochlorothiazide, respectively, none or 30 mg daily. Each treatment was given for 4 weeks after an adequate period of withdrawal from any other possible hypotensive therapy and one week of placebo wash-out. Irrespective of the association with dihydralazine and/or hydrochlorothiazide, oxprenolol had a hypotensive effect linearly related to dose for standing systolic (P<0.05) and diastolic (P<0.01) pressure, and for lying diastolic (P<0.05) pressure. The addition of dihydralazine enhanced the time-course of the hypotensive effect of oxprenolol, particularly the 80 mg dose level. In general, the combination of oxprenolol with dihydralazine and hydrochlorothiazide caused larger reductions in blood pressure, particularly with oxprenolol 80 mg. In the latter group, the eventual falls in blood pressure were 30.5 and 14.4 mmHg for lying systolic and diastolic, respectively; and 32.1 and 20.0 mmHg for the standing systolic and diastolic pressures. The drug was well tolerated; major side effects (heart failure and bronchospasm) occurred in three patients. [ABSTRACT FROM AUTHOR]

The efficacy and tolerability of cephacetrile and ampicillin in the treatment of urinary tract infections have been compared in a between patient, single blind, multicentre controlled trial. 68 in-patients were treated with cephacetrile or ampicillin in doses of 1 to 4 g/day, according to their creatinine clearances, for an average of 10 days. The two drugs had similar therapeutic effects, i.e. they produced significant decreases in leucocyturia ( p<0.001) and urinary culture colony counts ( p<0.001). No side effects were observed. The direct Coombs' test remained negative in all patients, even in those with advanced renal failure. To determined whether renal function was affected by treatment, creatinine clearance, and cylindruria, erythrocyturia and proteinuria were assessed in 24 h urine samples, before and after drug administration. None of these parameters were altered, except for a decrease in cylindruria ( p<0.05) after cephacetrile. It was concluded that cephacetrile was as active as ampicillin in the treatment of urinary tract infections and that there was no evidence of nephrotoxicity in the doses employed. [ABSTRACT FROM AUTHOR]

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In cerebellar Purkinje cells (PCs) type-1 metabotropic glutamate (mGlu1) receptors play a key role in motor learning and drive the refinement of synaptic innervation during postnatal development. The cognate mGlu5 receptor is absent in mature PCs and shows low expression levels in the adult cerebellar cortex. Here we found that mGlu5 receptors were heavily expressed by PCs in the early postnatal life, when mGlu1α receptors were barely detectable. The developmental decline of mGlu5 receptors coincided with the appearance of mGlu1α receptors in PCs, and both processes were associated with specular changes in CpG methylation in the corresponding gene promoters. It was the mGlu1 receptor that drove the elimination of mGlu5 receptors from PCs, as shown by data obtained with conditional mGlu1α receptor knockout mice and with targeted pharmacological treatments during critical developmental time windows. The suppressing activity of mGlu1 receptors on mGlu5 receptor was maintained in mature PCs, suggesting that expression of mGlu1α and mGlu5 receptors is mutually exclusive in PCs. These findings add complexity to the the finely tuned mechanisms that regulate PC biology during development and in the adult life and lay the groundwork for an in-depth analysis of the role played by mGlu5 receptors in PC maturation. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "A Novel Mutation Producing Premature Termination Codon at the OPA1 Gene Causes Autosomal Dominant Optic Atrophy," that was published in the previous issues of the "Journal of Neurology."

Summary. In Rational Beliefs Equilibria money is generically non-neutral. Given the expectational perspective proposed by the Theory of Rational Belief Equilibrium, we show that one of the most important factors in the emergence of money non-neutrality is played by Endogenous Uncertainty. This, in contrast to the Rational Expectations results of money neutrality and policy ineffectiveness, leads to a scenario in which monetary policy has an impact on the real economy and price volatility. The heterogeneity of beliefs together with the distribution and intensity of agents' states of optimism/pessimism can amplify the real effect of monetary policy and/or generate endogenous fluctuations in the economy which are not explained by any exogenous shock. We claim that money non-neutrality is mostly an expectations driven phenomenon. Indeed, additional assumptions of asymmetry of information and/or unanticipated monetary policy are not needed to explain the real effect of monetary policy as it is customary in the New Classical Theory. [ABSTRACT FROM AUTHOR]