Durability of symptomatic responses obtained with adjunctive vagus nerve stimulation in treatment-resistant depression

Objective: To compare the durations of response achieved with adjunctive vagus nerve stimulation (VNS + TAU) vs treatment as usual (TAU) alone in treatment-resistant depression (TRD) over a 5-year period in the TRD registry. Materials and methods: Data from 271 participants on TAU and 328 participants on VNS + TAU were analyzed. Response was defined as \u3e /=50% decrease in baseline Montgomery-Asberg Depression Rating Scale (MADRS) score at postbaseline visit and was considered retained until the decrease was \u3c 40%. MADRS was obtained quarterly in year 1 and biannually thereafter. Time-to-events were estimated using Kaplan-Meier method and compared using log-rank test. HR was estimated using Cox proportion hazard model. Results: In the VNS + TAU arm, 62.5% (205/328) of participants had a first response over 5 years compared with 39.9% (108/271) in TAU. The time to first response was significantly shorter for VNS + TAU than for TAU (P \u3c 0.01). For responders in the first year, median time to relapse from first response was 10.1 months (Q1=4.2, Q3=31.5) for VNS + TAU vs 7.3 months (Q1=3.1, Q3=17.6) for TAU (P \u3c 0.01). HR=0.6 (95% CI: 0.4, 0.9) revealed a significantly lower chance for relapse in VNS + TAU. Probability of retaining first response for a year was 0.39 (0.27, 0.51) for TAU and 0.47 (0.38, 0.56) for VNS + TAU. Timing of the onset of the response did not impact the durability of the response. Conclusion: VNS therapy added to TAU in severe TRD leads to rapid onset and higher likelihood of response, and a greater durability of the response as compared to TAU alone

Concentration of conjugated linoleic acid (CLA) and other fatty acids in Parmigiano-reggiano cheese

Coniugated linoleic acid (CLA) is a nutrient that can exert several beneficial effects on the health of consumers and is mainly found in meat and dairy products from ruminants. In order to characterize the lipid fraction of Parmigiano-Reggiano cheese, 255 samples of cheese were analyzed. Samples differed for geographical origin (different provinces constituting the Parmigiano-Reggiano cheese area of production), altitude of the cheese factory location (plain, hills or mountains; P, H or M), and seasoning time (< 22 months, between 22 and 30 months, or > 30 months). All samples were analyzed for their lipid content and fatty acids composition. Total lipid content of cheese was not influenced by any of the variables considered and averaged 24.4 %. Content of all fatty acids was not significantly affected by seasoning time. In particular, content of CLA averaged 0.32 mg/100 mg of fat. The altitude of the cheese factory location had a significant influence on the concentration of several fatty acids. Cheese samples coming from factories located on mountains showed significantly (P < 0.05) higher concentrations of C18:0 (stearic acid; 6.1 vs 5.5 and 5.3 mg/100 mg of fat for M, H and P, respectively), C18:1 cis (oleic acid; 13.0 vs 11.5 and 11.5 mg/100 mg of fat for M, H and P, respectively), C18:1 trans (vaccenic acid; 1.04 vs 0.89 and 0.76 mg/100 mg of fat for M, H and P, respectively), and CLA (0.37 vs 0.32 and 0.28 mg/100 mg of fat for M, H and P, respectively). Similarly, the concentration of some fatty acids was influenced by the province of origin, but this effect seemed to be mainly related to the different presence of cheese factories located on mountains in each province. The present results show that the area of production of Parmigiano-Reggiano cheese significantly influences its lipid fraction. In particular, cheese from factories located on mountains show a higher content of CLA and vaccenic acid, probably due to a higher utilization of green forages which are very rich in linoleic and α-linolenic acid, both precursors of CLA

Extruded soybean and flaxseed enhance fat composition of milk for Parmigiano-Reggiano cheese

Twenty Friesian dairy cows were used in an experimental trial to study the effects of extruded full-fat soybean and flaxseed dietary supplementation, at the level authorized by Consorzio of Parmigiano-Reggiano cheese(CPRC) feeding guidelines (1.0 and 0.4 kg/cow/day), on milk production and fatty acid composition. Diet was typically based on alfalfa and mixed hays and cereals. Compared with the concentrations before trial start, CLA and DHA were significantly increased by dietary treatment. These results confirm that the inclusion of extruded full-fat soybean and flaxseed, in the amount authorized by CPRC rules, in the diet of dairy cows is a possible strategy to enhance milk fat composition

Effect of feeding whole soybean and linseed on milk and Parmigiano Reggiano cheese lipid fraction

Aim of this study was to assess the effects of feeding whole soybean flakes and whole extruded linseed to dairy cows on milk lipid fraction and Parmigiano Reggiano cheese produced from it; specifically, PUFA and CLA contents were evaluated. For 14 weeks, a herd of 145 cows received a diet with a daily supplementation of 1 kg of whole soybean flakes and 0.3 kg of whole extruded linseed. In the pre-trial period, cows received an isoproteic ration devoid of both seeds. From 20 cows selected from the herd, individual milk, bulk morning milk and vat milk samples of the entire herd were taken every 14 days. After 24 months of aging, cheese samples were taken from twelve cheese wheels, obtained from milk produced at 0, 4, 8, 10, 12 and 14 weeks on the same days as bulk milk and vat milk samples were made. Fatty acid composition of the lipid fraction was determined in all milk and cheese samples. Feeding whole extruded linseed and soybean flakes has determined a decrease in short-chain fatty acids content and an increase in total CLA concentration of the milk. Bulk milk, vat milk and aged cheese analysis samples confirmed a decrease of short-chain fatty acids content in milk and revealed a decrease in n-6/n-3 fatty acid and in saturated/unsaturated fatty acid ratios. In conclusion, feeding a ration including whole soybean flakes and extruded linseed can improve the nutritional characteristics of milk and of Parmigiano Reggiano cheese, particularly with respect to their lipid fractions

The effect of ketamine on cognition, anxiety, and social functioning in adults with psychiatric disorders: A systematic review and meta-analysis

Background: It has been shown that ketamine can improve suicidality and depression. Evidence for other dimensions of psychopathology is lacking. We undertook a systematic review to investigate the effect of ketamine on cognition, anxiety, quality of life, and social functioning in adults with psychiatric disorders. Methods: PubMed (Medline), Scopus, PsycINFO, and EMBASE were searched up to April 2022. Randomized controlled trials (RCTs) on ketamine [or its S (+) enantiomer] reporting data on cognition, anxiety, quality of life, social functioning in adults with psychiatric disorders were included. Standardized mean difference (SMD) was used for summarizing continuous outcomes. Results: Twenty-two reports were included in the final selection, of which 20, corresponding to 1,298 participants, were included in the quantitative synthesis. Affective disorders were the predominant diagnostic category. Median follow-up time was 21 days. The evidence was rated moderate to very low. In most trials, ketamine was administered intravenously or as adjuvant to electro-convulsant therapy (ECT). Only 2 trials of intranasal esketamine were identified. The effect of ketamine on depression was confirmed (SMD: −0.61 [95% CI: −1.06; −0.16]). Furthermore, by pooling results of 6 RCTs, ketamine may be effective in reducing anxiety symptoms (SMD: −0.42 [95% CI: −0.84; 0.003]), particularly when administered not within ECT (5 trials; SMD: −0.58 [95% CI: −1.07; −0.09]). However, there was moderate heterogeneity of results. Patients treated with ketamine also had an improvement in social functioning (SMD: −0.31 [95% CI: −0.52; −0.10]), although the estimate was based only on 2 studies. No difference to comparators was found with respect to cognition and quality of life. Conclusion: Alongside the antidepressant effect, ketamine may also improve anxiety and social functioning in adults with affective disorders

Quantification of corticospinal tracts in brainstem surgery: Initial experiences with diffusion tensor imaging at 3-T-MRI

Background EMD 525797 (DI17E6) is a deimmunized, humanized monoclonal immunoglobulin G2 antibody against the αv subunit of human integrins. Blocking αv integrins may be an effective strategy for inhibiting prostate cancer (PCa) metastasis. Objective Evaluate EMD 525797 safety/tolerability and pharmacokinetics (PK) in castration-resistant PCa patients. Secondary objectives included antitumor activity assessments. Design, setting, and participants A phase 1 open-label study in 26 patients (four European centers). Eligible patients (≥18 yr) had histologically proven PCa with bone metastases after prior chemotherapy and evidence of progressive disease (PD) based on prostate-specific antigen (PSA) values. Intervention Patients received three intravenous EMD 525797 infusions (250, 500, 1000, or 1500 mg every 2 wk). Outcome measurements and statistical analysis Treatment-emergent adverse events (TEAEs) and dose-limiting toxicities (DLTs) were assessed. PK parameters were calculated according to noncompartmental standard methods. Antitumor activity measures were response after 6 wk, changes in PSA levels, and pain interference total score. Descriptive statistics were used. Results and limitations Patients were treated for a mean of 16.8 ± 16.7 wk. No DLTs were reported in any of the cohorts. All patients experienced TEAEs, which were considered drug-related in 11 patients. Four deaths occurred during the trial and were considered not related to EMD 525797. EMD 525797 showed dose-dependent, nonlinear PK. Eighteen of 26 patients did not show PD for ≥18 wk. Two patients (500-mg cohort), treated for 42.4 and 76.3 wk, had clinically significant PSA reductions and pain relief, including one patient with confirmed partial response. This trial was not specifically designed to assess clinical activity, and further investigations are needed in randomized controlled trials. Conclusions No DLTs were reported in any of the evaluated cohorts. There was evidence of clinical activity. For the currently ongoing phase 2 trial, EMD 525797 doses of 750 and 1500 mg every 3 wk were chosen. Trial registration NCT00958477 (EMR 62242-002). © 2013 European Association of Urology.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Tolerability and dose-related effects of nebivolol in elderly patients with heart failure: data from the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (SENIORS) trial

Background The SENIORS trial showed that nebivolol reduced the risk of death or cardiovascular (CV) hospitalization in elderly patients with heart failure (HF). We aimed to assess tolerability and dose-related effects of the beta-blocker nebivolol in elderly patients from the SENIORS trial. Methods Patients assigned to nebivolol (n = 103 1) were classified into 4 groups, according to the dose achieved at the end of titration phase (maintenance dose): 0 mg (n = 74), low dose (1.25 or 2.5 mg, n = 142), medium dose (5 mg, n = 127), and target dose (10 mg, n = 688) and compared with those allocated to placebo (n = 1030). Age, sex and ejection fraction were similar between the groups, but prior myocardial infarction, coronary revascularization, and serum creatinine levels were lower in patients who achieved higher maintenance doses of nebivolol. Results After adjustment, all-cause mortality or CV hospitalization was significantly reduced in the 10 mg dose group compared with placebo (hazard ratio [HR] 0.75, 95% Cl 0.63-0.90) which was similar to the medium dose group (HR 0.73, 95% Cl 0.52-1.02). The low dose group had an apparently lower benefit (HR 0.88, 95% Cl 0.64-1.20), whereas patients unable to tolerate any dose of nebivolol had an increased risk of death or CV hospitalization (HR 1.95, 95% Cl 1.38-2.75). Conclusions The benefits of nebivolol in elderly patients with HF appear to be related to the maintenance dose achieved. Patients unable to tolerate any dose have the worst prognosis

Inchiesta su Gramsci

Antonio Gramsci è oggetto non soltanto di studi e ricerche, ma anche di polemiche che negli ultimi anni hanno conosciuto una notevole recrudescenza, segnale in fondo di una inesausta vitalità del pensiero di uno degli autori italiani più studiati e tradotti a livello internazionale. Ma le polemiche testimoniano altresì che esistono momenti e vicende della biografia gramsciana, su cui ancora necessitano scavi documentari, ipotesi di lavoro, o semplici riletture di testi e documenti già noti. Il libro nasce, da una parte, dalla registrazione delle polemiche tuttora in corso, ma dall’altro, dalla consapevolezza che anche le contese apparentemente stolte e superflue, possono aiutare a sciogliere nodi, o quanto meno a porre nuove domande: purché si sia animati da autentica volontà di sapere, come la rivista «Historia Magistra», dal cui seno il libro è in qualche modo scaturito. Fondato su un Questionario, il volume ha raccolto le risposte di 26 studiosi e studiose, coordinati da Angelo d’Orsi, autore anche della robusta Introduzione. In appendice un testo del nipote di Gramsci, Antonio junior