Gibbon all’italiana. The Italian Restoration Edition of the History of the Decline and Fall of the Roman Empire

Ricostruzione delle vicende editoriali e delle strategie di manipolazione della traduzione italiana di una delle controverse opere della storiografia britannica del XVIII secol

Target-Based Identification of Whole-Cell Active Inhibitors of Biotin Biosynthesis in Mycobacterium tuberculosis

SummaryBiotin biosynthesis is essential for survival and persistence of Mycobacterium tuberculosis (Mtb) in vivo. The aminotransferase BioA, which catalyzes the antepenultimate step in the biotin pathway, has been established as a promising target due to its vulnerability to chemical inhibition. We performed high-throughput screening (HTS) employing a fluorescence displacement assay and identified a diverse set of potent inhibitors including many diversity-oriented synthesis (DOS) scaffolds. To efficiently select only hits targeting biotin biosynthesis, we then deployed a whole-cell counterscreen in biotin-free and biotin-containing medium against wild-type Mtb and in parallel with isogenic bioA Mtb strains that possess differential levels of BioA expression. This counterscreen proved crucial to filter out compounds whose whole-cell activity was off target as well as identify hits with weak, but measurable whole-cell activity in BioA-depleted strains. Several of the most promising hits were cocrystallized with BioA to provide a framework for future structure-based drug design efforts

Target-Based Identification of Whole-Cell Active Inhibitors of Biotin Biosynthesis in Mycobacterium tuberculosis

SummaryBiotin biosynthesis is essential for survival and persistence of Mycobacterium tuberculosis (Mtb) in vivo. The aminotransferase BioA, which catalyzes the antepenultimate step in the biotin pathway, has been established as a promising target due to its vulnerability to chemical inhibition. We performed high-throughput screening (HTS) employing a fluorescence displacement assay and identified a diverse set of potent inhibitors including many diversity-oriented synthesis (DOS) scaffolds. To efficiently select only hits targeting biotin biosynthesis, we then deployed a whole-cell counterscreen in biotin-free and biotin-containing medium against wild-type Mtb and in parallel with isogenic bioA Mtb strains that possess differential levels of BioA expression. This counterscreen proved crucial to filter out compounds whose whole-cell activity was off target as well as identify hits with weak, but measurable whole-cell activity in BioA-depleted strains. Several of the most promising hits were cocrystallized with BioA to provide a framework for future structure-based drug design efforts

Validation of the italian version of the Cluster Headache Impact Questionnaire (CHIQ)

Background: The Cluster Headache Impact Questionnaire (CHIQ) is a specific and easy-to-use questionnaire to assess the current impact of cluster headache (CH). The aim of this study was to validate the Italian version of the CHIQ. Methods: We included patients diagnosed with episodic CH (eCH) or chronic CH (cCH) according to the ICHD-3 criteria and included in the “Italian Headache Registry” (RICe). The questionnaire was administered to patients through an electronic form in two sessions: at first visit for validation, and after 7 days for test-retest reliability. For internal consistency, Cronbach’s alpha was calculated. Convergent validity of the CHIQ with CH features and the results of questionnaires assessing anxiety, depression, stress, and quality of life was evaluated using Spearman’s correlation coefficient. Results: We included 181 patients subdivided in 96 patients with active eCH, 14 with cCH, and 71 with eCH in remission. The 110 patients with either active eCH or cCH were included in the validation cohort; only 24 patients with CH were characterized by a stable attack frequency after 7 days, and were included in the test-retest cohort. Internal consistency of the CHIQ was good with a Cronbach alpha value of 0.891. The CHIQ score showed a significant positive correlation with anxiety, depression, and stress scores, while showing a significant negative correlation with quality-of-life scale scores. Conclusion: Our data show the validity of the Italian version of the CHIQ, which represents a suitable tool for evaluating the social and psychological impact of CH in clinical practice and research

Complications of mechanical thrombectomy for acute ischemic stroke: Incidence, risk factors, and clinical relevance in the Italian Registry of Endovascular Treatment in acute stroke

BACKGROUND: There are limited data concerning procedure-related complications of endovascular thrombectomy for large vessel occlusion strokes. AIMS: We evaluated the cumulative incidence, the clinical relevance in terms of increased disability and mortality, and risk factors for complications. METHODS: From January 2011 to December 2017, 4799 patients were enrolled by 36 centers in the Italian Registry of Endovascular Stroke Treatment. Data on demographic and procedural characteristics, complications, and clinical outcome at three months were prospectively collected. RESULTS: The complications cumulative incidence was 201 per 1000 patients undergoing endovascular thrombectomy. Ongoing antiplatelet therapy (p < 0.01; OR 1.82, 95% CI: 1.21-2.73) and large vessel occlusion site (carotid-T, p < 0.03; OR 3.05, 95% CI: 1.13-8.19; M2-segment-MCA, p < 0.01; OR 4.54, 95% CI: 1.66-12.44) were associated with a higher risk of subarachnoid hemorrhage/arterial perforation. Thrombectomy alone (p < 0.01; OR 0.50, 95% CI: 0.31-0.83) and younger age (p < 0.04; OR 0.98, 95% CI: 0.97-0.99) revealed a lower risk of developing dissection. M2-segment-MCA occlusion (p < 0.01; OR 0.35, 95% CI: 0.19-0.64) and hypertension (p < 0.04; OR 0.77, 95% CI: 0.6-0.98) were less related to clot embolization. Higher NIHSS at onset (p < 0.01; OR 1.04, 95% CI: 1.02-1.06), longer groin-to-reperfusion time (p < 0.01; OR 1.05, 95% CI: 1.02-1.07), diabetes (p < 0.01; OR 1.67, 95% CI: 1.25-2.23), and LVO site (carotid-T, p < 0.01; OR 1.96, 95% CI: 1.26-3.05; M2-segment-MCA, p < 0.02; OR 1.62, 95% CI: 1.08-2.42) were associated with a higher risk of developing symptomatic intracerebral hemorrhage compared to no/asymptomatic intracerebral hemorrhage. The subgroup of patients treated with thrombectomy alone presented a lower risk of symptomatic intracerebral hemorrhage (p < 0.01; OR 0.70; 95% CI: 0.55-0.90). Subarachnoid hemorrhage/arterial perforation and symptomatic intracerebral hemorrhage after endovascular thrombectomy worsen both functional independence and mortality at three-month follow-up (p < 0.01). Distal embolization is associated with neurological deterioration (p < 0.01), while arterial dissection did not affect clinical outcome at follow-up. CONCLUSIONS: Complications globally considered are not uncommon and may result in poor clinical outcome. Early recognition of risk factors might help to prevent complications and manage them appropriately in order to maximize endovascular thrombectomy benefits

Efficacy of essential oil mouthwash with and without alcohol: a 3-Day plaque accumulation model

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate the antiplaque effect of a new alcohol free essential oil mouthwash with respect to a control of an essential oil with alcohol mouthwash, using an <it>in vivo </it>plaque regrowth model of 3-days.</p> <p>Methods</p> <p>The study was designed as a double-masked, randomized, crossover clinical trial, involving 30 volunteers to compare two different essential oil containing mouthwashes, during a 3-day plaque accumulation model. After receiving a thorough professional prophylaxis at the baseline, over the next 3-days each volunteer refrained from all oral hygiene measures and had two daily rinses with 20 ml of the test mouthwash (alcohol free essential oil) or the control mouthwash (essential oil with alcohol). At the end of the each experimental period, plaque was assessed and the panelists filled out a questionnaire. Each subject underwent a 14 days washout period and there was a second allocation.</p> <p>Results</p> <p>The essential oil mouthwash with ethanol shows a better inhibitory effect of plaque regrowth in 3-days than the mouthwash test with only essential oil in the whole mouth (plaque index = 2.18 against 2.46, respectively, p < 0.05); for the lower jaw (plaque index = 2.28 against 2.57, respectively, p < 0.05); for the upper jaw (plaque index = 2.08 against 2.35, respectively, p < 0.05); for the incisors (plaque index = 1.93 against 2.27, respectively, p < 0.05); and the canines (plaque index = 1.99 against 2.47, respectively, p < 0.05).</p> <p>Conclusion</p> <p>The essential oil containing mouthwash without alcohol seems to have a less inhibiting effect on the plaque regrowth than the traditional alcoholic solution.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01411618">NCT01411618</a></p

Behavioral and psychological effects of coronavirus disease-19 quarantine in patients with dementia

Background: In March 2020, the World Health Organization declared a global pandemic due to the novel coronavirus SARS-CoV-2 and several governments planned a national quarantine in order to control the virus spread. Acute psychological effects of quarantine in frail elderly subjects with special needs, such as patients with dementia, have been poorly investigated. The aim of this study was to assess modifications of neuropsychiatric symptoms during quarantine in patients with dementia and their caregivers. Methods: This is a sub-study of a multicenter nation-wide survey. A structured telephone interview was delivered to family caregivers of patients with diagnosis of Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VD), followed regularly at 87 Italian memory clinics. Variations in behavioral and psychological symptoms (BPSD) were collected after 1 month since quarantine declaration and associations with disease type, severity, gender, and caregiver\u2019s stress burden were analyzed. Results: A total of 4,913 caregivers participated in the survey. Increased BPSD was reported in 59.6% of patients as worsening of preexisting symptoms (51.9%) or as new onset (26%), and requested drug modifications in 27.6% of these cases. Irritability, apathy, agitation, and anxiety were the most frequently reported worsening symptoms and sleep disorder and irritability the most frequent new symptoms. Profile of BPSD varied according to dementia type, disease severity, and patients\u2019 gender. Anxiety and depression were associated with a diagnosis of AD (OR 1.35, CI: 1.12\u20131.62), mild to moderate disease severity and female gender. DLB was significantly associated with a higher risk of worsening hallucinations (OR 5.29, CI 3.66\u20137.64) and sleep disorder (OR 1.69, CI 1.25\u20132.29), FTD with wandering (OR 1.62, CI 1.12\u20132.35), and change of appetite (OR 1.52, CI 1.03\u20132.25). Stress-related symptoms were experienced by two-thirds of caregivers and were associated with increased patients\u2019 neuropsychiatric burden (p&lt;0.0001). Conclusion: Quarantine induces a rapid increase of BPSD in approximately 60% of patients and stress-related symptoms in two-thirds of caregivers. Health services need to plan a post-pandemic strategy in order to address these emerging needs

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p&lt;0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p&lt;0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding