A particular anatomic variation of the course of the left pulmonary artery

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Neuronal models of TDP-43 proteinopathy display reduced axonal translation, increased oxidative stress, and defective exocytosis

Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative disease mostly affecting people around 50–60 years of age. TDP-43, an RNA-binding protein involved in pre-mRNA splicing and controlling mRNA stability and translation, forms neuronal cytoplasmic inclusions in an overwhelming majority of ALS patients, a phenomenon referred to as TDP-43 proteinopathy. These cytoplasmic aggregates disrupt mRNA transport and localization. The axon, like dendrites, is a site of mRNA translation, permitting the local synthesis of selected proteins. This is especially relevant in upper and lower motor neurons, whose axon spans long distances, likely accentuating their susceptibility to ALS-related noxae. In this work we have generated and characterized two cellular models, consisting of virtually pure populations of primary mouse cortical neurons expressing a human TDP-43 fusion protein, wt or carrying an ALS mutation. Both forms facilitate cytoplasmic aggregate formation, unlike the corresponding native proteins, giving rise to bona fide primary culture models of TDP-43 proteinopathy. Neurons expressing TDP-43 fusion proteins exhibit a global impairment in axonal protein synthesis, an increase in oxidative stress, and defects in presynaptic function and electrical activity. These changes correlate with deregulation of axonal levels of polysome-engaged mRNAs playing relevant roles in the same processes. Our data support the emerging notion that deregulation of mRNA metabolism and of axonal mRNA transport may trigger the dying-back neuropathy that initiates motor neuron degeneration in ALS

Tamoxifen in treatment of hepatocellular carcinoma: a randomised controlled trial

Background Results from small randomised trials on tamoxifen in the treatment of hepatocellular carcinoma (HCC) are conflicting, We studied whether the addition of tamoxifen to best supportive care prolongs survival of patients with HCC. Methods Patients with any stage of HCC were eligible, irrespective of locoregional treatment. Randomisation was centralised, with a minimisation procedure accounting for centre, evidence of disease, and time from diagnosis. Patients were randomly allocated best supportive care alone or in addition to tamoxifen, Tamoxifen was given orally, 40 mg per day, from randomisation until death. Results 496 patients from 30 institutions were randomly allocated treatment from January, 1995, to January, 1997. Information was available for 477 patients. By Sept 15, 1997, 119 (50%) of 240 and 130 (55%) of 237 patients had died in the control and tamoxifen arms, respectively. Median survival was 16 months and 15 months (p=0.54), respectively, No differences were found within subgroups defined by prognostic variables. Relative hazard of death for patients receiving tamoxifen was 1.07 (95% CI 0.83-1.39). Interpretation Our findings show that tamoxifen is not effective in prolonging survival of patients with HCC

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection

Dalla Villa Strozzi alla Villa Mérode : una dimora per l'archeologia. Storia della prima sede dell’École française de Rome

Per un anno l’antica Villa Strozzi (fig. 1), adagiata sul crinale del Viminale, fu l’incantevole cornice delle lezioni di archeologia e epigrafia e della vita collegiale degli « membri » dell’appena costituita « Succursale de l’École française d’Athènes » a Roma (fig. 2). Albert Dumont, primo direttore e tenace promotore della nuova istituzione indirizzata allora agli studi dell’Antichità inaugurata nel 1873, aveva immediatamente compreso l’importanza di dotarla di un’effettiva autonomia : un..

Ipertensione Polmonare

Il volume, organizzato in 8 sezioni e 34 capitoli, tratta la clinica delle malattie respiratorie, i rapporti con le malattie concomitanti e i relativi aspetti organizzativi e normativi

PowerTap: All-digital Power Meter Modeling for Run-time Power Monitoring

The power consumption is a key metric to design computing platforms. In particular, the variety and complexity of current applications fueled an increasing number of run-time power-aware optimization solutions to dynamically trade the computational power for the power consumption. In this scenario, the online power monitoring methodologies are the core of any power-aware optimization, since the incorrect assessment of the run-time power consumption prevents any effective actuation. This work proposes PowerTap, an all-digital power modeling methodology for designing online power monitoring solutions. In contrast with state-of-the-art solutions, PowerTap adds domain-specific constraints to the data-driven power modeling problem. PowerTap identifies the power model iteratively to balance the accuracy error of the power estimates and the complexity of the final monitoring infrastructure. As a representative use-case, we employed a complex hardware multi-threaded SIMD processor, also considering different operating clock frequencies. The RTL implementation of the identified power model targeting an Xilinx Artix 7 XC7A200T FPGA highlights an accuracy error within 1.79% with an area overhead of 9.95% (LUT) and 3.87% (flip flops) and an average power overhead of 12.17 mW regardless of the operating conditions, i.e., number of software threads and operating frequency

Exhaled nitric oxide after inhalation of isotonic and hypotonic solutions in healthy subjects.

Airway nitric oxide (NO) homoeostasis is in¯uenced by chemical and mechanical stimuli in humans; airway epithelium, which is an important site of NO production, is sensitive to osmotic challenge. The effect of inhaled hypotonic solutions on exhaled NO (eNO) is not known. In this study we evaluated the effect of ultrasonically nebulized distilled water (UNDW), a hypotonic indirect stimulus, on eNO levels. A total of 10 non-smoking healthy subjects were enrolled in the study. eNO was detected by chemiluminescence, and speci®c airway conductance (sGaw) was measured by plethysmography. Bronchial challenges with UNDW and with an isotonic solution were performed according to a double-blind experimental design. Baseline levels of eNO were 28.1³14.7 p.p.b. UNDW did not cause any signi®cant change in sGaw (from 0.190³0.029 to 0.181³0.036 cmH2O[s−1). With respect to baseline values, the eNO concentration decreased signi®cantly after inhalation of 8 or 16 ml of UNDW (from 26.0³13.1 to 17.2³8.5 and 16.6³7.7 p.p.b. respectively; P!0.001, n¯10). After bronchial challenge with UNDW, eNO was signi®cantly reduced in comparison with after inhalation of the isotonic solution. In ®ve subjects, pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor NO synthesis, decreasedNOlevels from 21.7³8.5 to 10.0³3.3 p.p.b. Subsequent inhalation of 16 ml of UNDW did not cause any further decrease in NO levels (10.1³3.7 p.p.b. ; not signi®cant compared with L-NAME). We conclude that inhalation of aqueous solutions decreases eNO levels in healthy subjects, and that this effect is not associated with any signi®cant change in airway calibre. The UNDW-induced decrease in eNO is not enhanced by pretreatment with the NO synthase inhibitor L-NAME, suggesting that inhaled solutions may interfere with the airway NO pathway in humans