Detection and Management of Amyloid-Related Imaging Abnormalities in Patients with Alzheimer's Disease Treated with Anti-Amyloid Beta Therapy.

Amyloid-related imaging abnormalities (ARIA) are adverse events reported in Alzheimer's disease trials of anti-amyloid beta (Aß) therapies. This review summarizes the existing literature on ARIA, including bapineuzumab, gantenerumab, donanemab, lecanemab, and aducanumab studies, with regard to potential risk factors, detection, and management. The pathophysiology of ARIA is unclear, but it may be related to binding of antibodies to accumulated Aß in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues. Radiographically, ARIA-E is identified as vasogenic edema in the brain parenchyma or sulcal effusions in the leptomeninges/sulci, while ARIA-H is hemosiderin deposits presenting as microhemorrhages or superficial siderosis. ARIA tends to be transient and asymptomatic in most cases, typically occurring early in the course of treatment, with the risk decreasing later in treatment. Limited data are available on continued dosing following radiographic findings of ARIA; hence, in the event of ARIA, treatment should be continued with caution and regular monitoring. Clinical trials have implemented management approaches such as temporary suspension of treatment until symptoms or radiographic signs of ARIA have resolved or permanent discontinuation of treatment. ARIA largely resolves without concomitant treatment, and there are no systematic data on potential treatments for ARIA. Given the availability of an anti-Aß therapy, ARIA monitoring will now be implemented in routine clinical practice. The simple magnetic resonance imaging sequences used in clinical trials are likely sufficient for effective detection of cases. Increased awareness and education of ARIA among clinicians and radiologists is vital.

Combined molecular and mathematical analysis of long noncoding RNAs expression in fine needle aspiration biopsies as novel tool for early diagnosis of thyroid cancer.

PURPOSE: In presence of indeterminate lesions by fine needle aspiration (FNA), thyroid cancer cannot always be easily diagnosed by conventional cytology. As a consequence, unnecessary removal of thyroid gland is performed in patients without cancer based on the lack of optimized diagnostic criteria. Aim of this study is identifying a molecular profile based on long noncoding RNAs (lncRNAs) expression capable to discriminate between benign and malignant nodules. METHODS: Patients were subjected to surgery (n = 19) for cytologic suspicious thyroid nodules or to FNA biopsy (n = 135) for thyroid nodules suspicious at ultrasound. Three thyroid-specific genes (TG, TPO, and NIS), six cancer-associated lncRNAs (MALAT1, NEAT1, HOTAIR, H19, PVT1, MEG3), and two housekeeping genes (GAPDH and P0) were analyzed using Droplet Digital PCR (ddPCR). RESULTS: Based on higher co-expression in malignant (n = 11) but not in benign (n = 8) nodules after surgery, MALAT1, PVT1 and HOTAIR were selected as putative cancer biomarkers to analyze 135 FNA samples. Cytological and histopathological data from a subset of FNA patients (n = 34) were used to define a predictive algorithm based on a Naïve Bayes classifier using co-expression of MALAT1, PVT1, HOTAIR, and cytological class. This classifier exhibited a significant separation capability between malignant and benign nodules (P < 0.0001) as well as both rule in and rule out test potential with an accuracy of 94.12% and a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 91.67%. CONCLUSIONS: ddPCR analysis of selected lncRNAs in FNA biopsies appears a suitable molecular tool with the potential of improving diagnostic accuracy.

Manejo nutricional de ascitis quilosa: Serie de casos y revisión de la literatura

RESUMEN Las ascitis quilosa (AQ) es una entidad poco común producida por el acúmulo de linfa en la cavidad peritoneal. Su incidencia se describe en aumento progresivo, asociándose a una mortalidad de 40-70%. Se incluyeron 3 pacientes con diagnóstico de AQ evaluados en la visita de asistencia nutricional del Hospital Clínico de la Universidad Católica (UC) durante el año 2019. Caso 1: Paciente mujer de 47 años, consulta por dolor abdominal agudo realizándose apendicectomía. Estudio de líquido peritoneal con triglicéridos (TG) de 1.362 mg/dL. Inicia Nutrición Parenteral Total (NPTC) progresando luego a régimen oral. Estudio no revela lesiones de vasos linfáticos ni otras causas. Caso 2: Paciente varón de 68 años con cirrosis por alcohol, Child Pugh B. Ingresa por disnea y ascitis refractaria. Estudio de líquido ascítico y pleural, con TG de 439 mg/dL y 592 mg/dL respectivamente. Se manejó con toracocentesis y paracentesis evacuadoras, tratamiento con régimen hipograso y aporte de triglicéridos de cadena media (MCT) vía oral. Evolución tórpida requiriendo apoyo con NPTC, realizándose drenajes sucesivos, por lo que se instala TIPS. Caso 3: Paciente mujer de 63 años consulta por dolor hipogástrico con masa palpable subcostal derecha. Estudio confirma masa pancreática por lo que se realiza Whipple. Reingresa por náuseas y vómitos profusos, evidenciándose líquido ascítico con TG de 251 mg/dl. Se inicia NPTC, escasos débitos del drenaje iniciándose realimentación progresiva por vía oral. El análisis del líquido tras la paracentesis establece el diagnóstico de AQ pues la clínica es inespecífica. Las principales complicaciones están dadas por la pérdida de quilo: desnutrición, infecciones y sepsis. Las opciones de tratamiento incluyen: medidas dietéticas, fármacos e intervenciones percutáneas o quirúrgicas; siempre orientadas al alivio sintomático, con foco en tratar la causa. Si la tolerancia oral es óptima la primera medida es la supresión de la grasa y la suplementación con MCT para evitar déficit energético. Con el empleo de estas medidas se ha reportado el cierre espontáneo de fístulas y/o defectos de vasos linfáticos en un 75%-80%. Se concluye que no hay guías de recomendación y los estudios se basan en series de pocos casos clínicos. La ascitis quilosa es una entidad patológica rara, que representa una situación clínica crítica con consecuencias inmunológicas y nutricionales; y el tratamiento debe ser etiológico y el paso clave inicial es optimizar el estado nutricional del paciente.

ABSTRACT Chylous ascites (CA) is an uncommon entity caused by the accumulation of lymph in the peritoneal cavity, its incidence has been gradually increasing; being associated with a mortality of 40-70%. This work includes 3 patients with CA diagnosis evaluated by the Nutritional Assistance team in the Hospital Clínico of the Universidad Católica, Chile during 2019. Case 1: 47-year-old female, with acute abdominal pain that resulted in an appendectomy. Peritoneal fluid study showed triglycerides (TG) of 1362 mg/dL. Total Parenteral Nutrition (TPN) was initiated with successive changes to an oral regimen. The case was negative for lymphatic vessel injuries or other causes of AQ. Case 2: 68-year-old male with alcoholic cirrhosis, Child-Pugh B. The patient was admitted for dyspnea and refractory ascites. Ascites and pleural fluid study showed TG of 439 mg/dL and 592 mg/dL, respectively, whichwas managed with thoracentesis and evacuating paracentesis, treatment with a low-fat regimen, and oral medium chain triglycerides (MCT). Case 2 had a poor evolution requiring TPN and successive evacuations, with TIPS installed. Case 3: A 63-year-old female patient with hypogastric pain and palpable right subcostal mass. Study confirmed a pancreatic tumor and Whipple Surgery was performed. Case 3 was readmitted for nausea and vomiting, showing ascitic fluid with TG of 251 mg/dl. TPN was started, with decrease in drainage fluids and successful progressive oral refeeding. The analysis of the paracentesis fluid established the diagnosis of CA since the symptoms were nonspecific. The main complications were due to the loss of chyle: malnutrition, infections and sepsis. Treatment options included: dietary measures, drugs, and percutaneous or surgical interventions; always oriented to symptomatic relief, focused on etiologic treatment. If oral tolerance is optimal, the first measure should be fat suppression and supplementation with MCT to avoid energy deficit. With the use of these measures, spontaneous closure of fistulas and / or lymphatic vessel defects has been reported in 75% -80% of patients. There are no recommendation guidelines for CA and studies are based on series of a few clinical cases. CA is a rare disease, representing a critical clinical situation with immunological and nutritional consequences. Etiologic treatment must be prioritized with a focus on optimization of the nutritional status of the patient

Neural functional correlates of emotional processing in patients with first-episode psychoses: an activation likelihood estimation (ALE) meta-analysis.

BACKGROUND: Early emotional recognition impairment characterises rst-episode psychoses (FEP) and remains stable thereafter. Patients with FEP consistently show brain activation changes during emotional processing in functional neuroimaging studies. AIM AND METHODS: To identify and compare cerebral activation correlates of FEP patients and healthy controls (HCs) during emotional task performances, we performed an Activation Likelihood Estimation (ALE) meta-analysis of peer-reviewed functional magnetic resonance imaging (fMRI) studies. RESULTS: Five studies included 71 patients with FEP and 75 HCs. Within-group analyses showed that HCs activated during emotional task performance the bilateral inferior parietal lobule (BAs 39 and 40), left inferior frontal gyrus (BAs 9 and 47), right amygdala, left middle frontal gyrus (BA 9), right cingulate gyrus (BA 32), and right middle temporal gyrus (BA 21). FEP activations correlating with emotional tasks included the right cuneus (BA 17) and right angular gyrus (BA 39). CONCLUSIONS: During emotional task performance, FEP patients fail to activate an extensive brain network comprising emotional processing-related areas, including both cortical and subcortical areas.

Styrene enhances the noise induced oxidative stress in the cochlea and affects differently mechanosensory and supporting cells.

Experimental and human investigations have raised the level of concern about the potential ototoxicity of organic solvents and their interaction with noise. The main objective of this study was to characterize the effects of the combined noise and styrene exposure on hearing focusing on the mechanism of damage on the sensorineural cells and supporting cells of the organ of Corti and neurons of the ganglion of Corti. The impact of single and combined exposures on hearing was evaluated by auditory functional testing and histological analyses of cochlear specimens. The mechanism of damage was studied by analyzing superoxide anion and lipid peroxidation expression and by computational analyses of immunofluorescence data to evaluate and compare the oxidative stress pattern in outer hair cells versus the supporting epithelial cells of the organ of Corti. The oxidative stress hypothesis was further analyzed by evaluating the protective effect of a Coenzyme Q10 analogue, the water soluble Qter, molecule known to have protective antioxidant properties against noise induced hearing loss and by the analysis of the expression of the endogenous defense enzymes. This study provides evidence of a reciprocal noise-styrene synergism based on a redox imbalance mechanism affecting, although with a different intensity of damage, the outer hair cell (OHC) sensory epithelium. Moreover, these two damaging agents address preferentially different cochlear targets: noise mainly the sensory epithelium, styrene the supporting epithelial cells. Namely, the increase pattern of lipid peroxidation in the organ of Corti matched the cell damage distribution, involving predominantly OHC layer in noise exposed cochleae and both OHC and Deiters' cell layers in the styrene or combined exposed cochleae. The antioxidant treatment reduced the lipid peroxidation increase, potentiated the endogenous antioxidant defense system at OHC level in both exposures but it failed to ameliorate the oxidative imbalance and cell death of Deiters' cells in the styrene and combined exposures. Current antioxidant therapeutic approaches to preventing sensory loss focus on hair cells alone. It remains to be seen whether targeting supporting cells, in addition to hair cells, might be an effective approach to protecting exposed subjects.

Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory.

Non-fibrillar soluble oligomeric forms of amyloid-ß peptide (oAß) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAß initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aß, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAß levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAß to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aß on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aß and tau pathology.

[Regulatory disorders: a follow-up study]. / I disturbi della regolazione: uno studio di follow-up.

AIM: The self-regulation systems develop during early childhood resulting from the meeting of the constitutional characteristics of the child, his/her adaptability and environmental responses. The failure of the intersection of these dimensions leads to the onset of symptoms that can seriously affect the child's behavior and his/her relationship. Regulatory disorders of sensory processes (DR) were identified as independent nosographic category in the "Diagnostic Classification 0-3". The aim of this study was the description of the clinical features of a group of children for whom a diagnosis of regulatory disorders was made before the three years, and their development at school age. METHODS: The sample was composed of 28 children, 22 males and 6 females, selected from a group of 60 children, with a mean age at T0 of 34.8 months (range 14-56 months). The clinical reassessment was conducted after five years (T1), with a children's mean age of 103.5 months (range 71-150 months). RESULTS: Approximately 40% of school age participants shows no longer any disturbance, while the remaining % shows a very heterogeneous spectrum of disorders. CONCLUSION: The diagnosis of DR is sensitive enough to detect in infancy a wide range of developmental difficulties, but it is quite specific and relatively predictive about the child's subsequent development. Retrospectively the entire diagnostic profile provides more information than the primary diagnosis and the greatest impairment of the different dimensions explored predicts a more severe evolution.

Modulation of LTP at rat hippocampal CA3-CA1 synapses by direct current stimulation.

Transcranial direct current stimulation (tDCS) can produce a lasting polarity-specific modulation of cortical excitability in the brain, and it is increasingly used in experimental and clinical settings. Recent studies suggest that the after-effects of tDCS are related to molecular mechanisms of activity-dependent synaptic plasticity. Here we investigated the effect of DCS on the induction of one of the most studied N-methyl-d-aspartate receptor-dependent forms of long-term potentiation (LTP) of synaptic activity at CA3-CA1 synapses in the hippocampus. We show that DCS applied to rat brain slices determines a modulation of LTP that is increased by anodal and reduced by cathodal DCS. Immediate early genes, such as c-fos and zif268 (egr1/NGFI-A/krox24), are rapidly induced following neuronal activation, and a specific role of zif268 in the induction and maintenance of LTP has been demonstrated. We found that both anodal and cathodal DCS produce a marked subregion-specific increase in the expression of zif268 protein in the cornus ammonis (CA) region, whereas the same protocols of stimulation produce a less pronounced increase in c-fos protein expression in the CA and in dentate gyrus regions of the hippocampus. Brain-derived neurotrophic factor expression was also investigated, and it was found to be reduced in cathodal-stimulated slices. The present data demonstrate that it is possible to modulate LTP by using DCS and provide the rationale for the use of DCS in neurological diseases to promote the adaptive and suppress the maladaptive forms of brain plasticity.

Diagnóstico de la infección por Treponema pallidum en pacientes con sífilis temprana y neurosífilis mediante reacción de la polimerasa en cadena / Laboratory diagnosis of Treponema pallidum infection in patients with early syphilis and neurosyphilis through a PCR-based test

Syphilis is a sexually transmitted disease caused by Treponema pallidum. The diagnosis is based mainly in clinical presentation and non-specific assays. PCR-based diagnosis has been suggested as an attractive alternative method. The aim of this study was the validation of a PCR-based test for the diagnosis of early syphilis (ES) and neurosyphilis (NS). Clinical samples of mucocutaneous lesions and cerebrospinal fluid (CSF) specimens from patients previously diagnosed for ES and NS respectively using an enlarged gold standard, were tested by PCR. The reaction was done using primers targeting the tpN47gene. Twenty out of 21 mucocutaneous samples from patients diagnosed with ES were positive by PCR, with a clinical sensitivity of 95 percent. Four out of 8 CSF samples from patients previously diagnosed with NS were positive by PCR, with a clinical sensitivity of 50 percent. The clinical specificity for both ES and NS was 100 percent. The PCR sensitivity and specificity for mucocutaneous samples allowed us to implement this assay in our laboratory for routine diagnosis. Although the sensitivity of the PCR in CSF was low, it may be useful to support clinical diagnosis.

La sífilis es una enfermedad de transmisión sexual producida por Treponema pallidum, cuyo diagnóstico se realiza presuntivamente basándose en aspectos clínicos y análisis de especificidad limitada. La reacción de la polimerasa en cadena (RPC) ha sido planteada como una alternativa diagnóstica de mayor sensibilidad y especificidad. El objetivo de este trabajo fue validar una RPC para el diagnóstico de sífilis temprana (ST) y neurosífilis (NS). Se utilizaron muestras de lesiones muco-cutáneas y de LCR de pacientes con sospecha de cursar ST y NS respectivamente, previamente diagnosticados, utilizando un estándar de oro ampliado. La RPC fue realizada con partidores dirigidos al gen tpN47. De las 21 muestras de pacientes con ST, la RPC resultó positiva en 20, lo que resulta en una sensibilidad clínica de 95 por ciento. De las 8 muestras de pacientes con NS, la RPC resultó positiva en 4, obteniéndose una sensibilidad clínica de 50 por ciento. La especificidad clínica para ST y NS fue de 100 por ciento. La excelente sensibilidad y especificidad de la RPC para muestras muco-cutáneas permitió la exitosa implementación de este análisis en nuestro laboratorio para el diagnóstico de rutina. Si bien la sensibilidad de la RPC en LCR es baja, es muy útil para apoyar el diagnóstico clínico.

Dopamine D1-like receptor activation depolarizes medium spiny neurons of the mouse nucleus accumbens by inhibiting inwardly rectifying K+ currents through a cAMP-dependent protein kinase A-independent mechanism.

Dopamine/cAMP signaling has been reported to mediate behavioral responses related to drug addiction. It also modulates the plasticity and firing properties of medium spiny neurons (MSNs) in the nucleus accumbens (NAc), although the effects of cAMP signaling on the resting membrane potential (RMP) of MSNs has not been specifically defined. In this study, activation of dopamine D1-like receptors (D1Rs) by SKF-38393 elicited membrane depolarization and inward currents in MSNs from the NAc core of 14-17 day-old mice. Similar results were obtained following stimulation of adenylyl cyclase (AC) activity with forskolin or application of exogenous cAMP. Forskolin occluded SKF-38393's effects, thus indicating that D1R action is mediated by AC/cAMP signaling. Accordingly, AC blockade by SQ22536 significantly inhibited the responses to SKF-38393. Effects elicited by D1R stimulation or increased cAMP levels were unaffected by protein kinase A (PKA) or protein kinase C (PKC) blockade and were not mimicked by the Epac agonist, 8CPT-2Me-cAMP. Responses to forskolin were also not significantly modified by cyclic nucleotide-gated (CNG) channel blockade. Forskolin-induced membrane depolarization was associated with increased membrane input resistance. Voltage-clamp experiments revealed that forskolin and SKF-38393 effects were due to inhibition of resting K(+) currents exhibiting inward rectification at hyperpolarized potentials and a reversal potential (around -90 mV) that shifted with the extracellular K(+) concentration. Forskolin and D1R agonist effects were abolished by the inward rectifier K(+) (Kir)-channel blocker, BaCl(2). Collectively, these data suggest that stimulation of postsynaptic D1Rs in MSNs of the NAc core causes membrane depolarization by inhibiting Kir currents. This effect is mediated by AC/cAMP signaling but it is independent on PKA, PKC, Epac and CNG channel activation, suggesting that it may stem from cAMP's direct interaction with Kir channels. D1R/cAMP-mediated excitatory effects may influence the generation of output signals from MSNs by facilitating their transition from the quiescent down-state to the functionally active up-state.

Feasibility and validation of telespirometry in general practice: The Italian "Alliance" study.

INTRODUCTION: At variance from office spirometry, telespirometry has not been tested as a tool for improving the ability of general practitioners (GPs) to manage chronic airway diseases. METHODS: After adequate training, 937 Italian GPs agreed to perform telespirometry in subjects attending their clinics who had risk factors, persistent respiratory symptoms, or a previous diagnosis of asthma or COPD. Each subject performed at least three forced expiratory manoeuvres using a turbine spirometer. Traces were sent by telephone to a Telespirometry Central Office, where they were interpreted by a pulmonary specialist, according to defined criteria. The result was sent in real time to the GP to assist the management of the patient. RESULTS: During 2 years, 20,757 telespirometries were performed, with a mean of 22.2+/-25.2 examinations for each GP. 70% of the tests met the criteria for good or partial co-operation, allowing spirometric abnormalities to be detected in more than 40% of the tracings. The rate of telespirometries that could not be evaluated at all was reasonably low (9.2%). For a subset of the telespirometries, a comparison between acceptability criteria for telespirometry and those recommended for laboratory (ATS) or office spirometry showed that the majority of telespirometries with good co-operation satisfied completely, or with minor deviations, the ATS and Office criteria. CONCLUSIONS: Telespirometry was well accepted by Italian GPs, who obtained acceptable screening traces in a large percentage of subjects. Therefore it might be considered a useful alternative to office spirometry in improving the management of chronic airway diseases by GPs.

Alzheimer's amyloid beta-peptide (1-42) induces cell death in human neuroblastoma via bax/bcl-2 ratio increase: an intriguing role for methionine 35.

The beta amyloid (Abeta), the major protein component of brain senile plaques in Alzheimer's disease, is known to be directly responsible for the production of free radicals toxic to brain tissue and the redox state of Met-35 residue seems to play a particular and critical role in peptide's neurotoxic actions. In this study, we investigated, in human neuroblastoma cells (IMR-32), the relationship between the oxidative state of methionine, and both neurotoxic and pro-apoptotic actions induced by Abeta-peptide, comparing the effects of native peptide, in which the Met-35 is present in the reduced state, with those of a modified peptide with oxidized Met-35 (Abeta(1-42)(35Met-ox)), as well as an Abeta-derivative with Met-35 substituted with norleucine (Abeta(1-42)(35Nle)). The obtained results show that Abeta induces a time-dependent decrease in cell viability; Abeta(1-42)(35Met-ox) was significantly less potent, though inducing a remarkable decrease in cell viability compared to control. On the contrary, no toxic effects were observed after treatment with Abeta(1-42)(35Nle). Abeta-peptide as well as the amyloid modified peptide with oxidized Met-35 induced the pro-apoptotic gene bax over-expression after 24 h, whereas Abeta(1-42)(35Nle) had no effect. Conversely, bcl-2, an anti-apoptotic gene, became highly down-regulated by Abeta peptide treatment, in contrast to that evidenced by the Abeta(1-42)(35Met-ox) peptide. Finally, Abeta caused an increase in caspase-3 activity to be higher with respect to that shown by Abeta(1-42)(35Met-ox) while Abeta(1-42)(35Nle) had no effect. These results support the hypothesis that Abeta-induced neurotoxicity occurs via bax over-expression, bcl-2 down-regulation, and caspase-3 activation, first indicating that methionine 35 redox state may alter this cell death pathway.

Course of autism signs in the first year of life.

Autism spectrum disorders (ASD) are thought to be present right from birth, even if a minority of children displays a normal course during infancy followed by a regression during the second year of life. However, established criteria are not yet available to differentiate these different courses of ASD, and data coming from different sources have not yet been organized into a clear definition. The aim of this study was to elucidate the time of onset, as well as type, frequency and stability of symptoms during the first year of life in ASD. The behavioral summarized evaluation scale, applied to 40 home movies of children later diagnosed as having ASD, showed that most of the subjects (87.5%) display symptoms within the first year of life, when only a small group (12.5%) is completely symptom free. A group of more rated symptoms was found, constituting a typical pattern characterized by being withdrawn, and displaying poor social initiative, hypoactivity, and lack of emotional modulation. The importance of these findings is discussed in relation to early diagnosis and treatment.

Effects of defective herpes simplex vectors expressing neurotrophic factors on the proliferation and differentiation of nervous cells in vivo.

Neurotrophic factors (NTFs) are known to govern the processes involved in central nervous system cell proliferation and differentiation. Thus, they represent very attractive candidates for use in the study and therapy of neurological disorders. We constructed recombinant herpesvirus-based-vectors capable of expressing fibroblast growth factor-2 (FGF-2) and ciliary neurotrophic factor (CNTF) alone or in combinations. In vitro, vectors expressing FGF-2 and CNTF together, but not those expressing either NTF alone, caused proliferation of O-2A progenitors. Furthermore, based on double-labeling experiments performed using markers for neurons (MAP-2), oligodendrocytes (CNPase) and astrocytes (GFAP), most of the new cells were identified as astrocytes, but many expressed neuronal or oligodendrocytic markers. In vivo, vectors have been injected in the rat hippocampus. At 1 month after inoculation, a highly significant increase in BrdU-positive cells was observed in the dentate gyrus of animals injected with the vector expressing FGF-2 and CNTF together, but not in those injected with vectors expressing the single NTFs. Furthermore, double-labeling experiments confirmed in vitro data, that is, most of the new cells identified as astrocytes, some as neurons or oligodendrocytes. These data show the feasibility of the vector approach to induce proliferation and differentiation of neurons and/or oligodendrocytes in vivo.

Compound and rotational damping in warm deformed rare-earth nuclei.

The gamma decay in the quasicontinuum from selected configurations of the rotational nucleus 163Er has been measured with the EUROBALL array. A new analysis technique has allowed for the first time to directly measure the compound and rotational damping widths Gamma (micro) and Gamma (rot). Values of Gamma (micro) approximately 20 keV and Gamma (rot) approximately 200 keV are obtained in the spin region I approximately 30-40 variant Planck's over 2pi, in good agreement with microscopic cranked shell model calculations. A dependence of Gamma (micro) and Gamma (rot) on the K-quantum number of the nuclear states is also presented.

Recent clinical evidence of the efficacy and safety of thiamphenicol glycinate acetylcysteinate and thiamphenicol glycinate.

Thiamphenicol is a broad-spectrum antimicrobial agent active against penicillin-resistant Streptococcus pneumoniae, Staphylococcus aureus VISA strains, most methicillin-resistant isolates and atypical pathogens such as Mycoplasma pneumoniae and Chlamydia pneumoniae). Thiamphenicol is present as glycinate hydrochloride (TG) and glycinate acetylcysteinate (TGA) esters in the parenteral and aerosol dosage form. This multicenter, double-blind, randomized clinical trial aimed to evaluate the efficacy and tolerability of aerosol administration of TGA, compared to TG, in the treatment of acute and/or exacerbated infections of the respiratory tract. Results showed that both treatments ameliorated the symptoms (frequency and severity of cough, difficulty in expectoration) associated with the evaluated pathologies, i.e. tracheobronchitis, acute and exacerbated chronic bronchitis. The investigators rated both treatments Good or Very Good in 90% of patients at the end of treatment, with "Very Good" for patients treated with TGA (37%) compared to 28% of patients treated with TG. Both treatments were well tolerated with fewer than 5% of patients experiencing an adverse event.

Efficacy and safety of short course (5-day) moxifloxacin vs 7-day ceftriaxone in the treatment of acute exacerbations of chronic bronchitis (AECB).

The aim of this multicenter, open, randomized study was to compare the efficacy and tolerability of a 5-day treatment course with oral moxifloxacin (MXF) vs a 7-day course with i.m. ceftriaxone (CRO) in 476 patients with acute exacerbations of chronic bronchitis (AECB), and to conduct a cost minimization analysis of the two treatments from the perspectives of both the Italian National Health Service (INHS) and society. The study was conducted in Italy. Clinical success rates at test-of-cure in the 423 patients of the PP (Per Protocol) population (primary efficacy parameter) were 90.6% and 89.0% for MXF and CRO, respectively. Statistical non-inferiority of MXF vs CRO was confirmed. Similar results were found between study drugs on the secondary efficacy parameters, including success at end-of-treatment (95.3% for MXF vs 92.9% for CRO), success at test-of-cure in bacteriologically-positive patients (94.1% vs 90.7%) and eradication/presumed eradication rates (91.7% vs 93.3%). ITT (Intention-to-Treat) analysis confirmed these data. There was a low incidence of adverse events (10.8% vs 9.1%). During a 6-month follow-up period, relapse rates were lower for MXF vs CRO (23.3% vs 28.3%; p > .05). Compared with CRO, MXF was associated with cost savings per patient ranging from Euro226.57 (INHS perspective) to Euro448.23 (societal perspective), with lower hospitalization rate the major variable contributing to reduced costs. MXF appears to be an ideal candidate for AECB treatment.