Sialoendoscopia: una nueva alternativa en el tratamiento de la patología salival. Nuestra experiencia

Objectives: Sialoendoscopy is a procedure used to visualize the salivary ducts and their pathology. It can be used either as a diagnostic method to rule out inflammatory processes in the parotid and submandibular glands (diagnostic sialoendoscopy) or to treat pathological areas (stenosis, extract foreign bodies or sialolithiasis) through the use of appropriate instruments (interventionist sialoendoscopy). We attempt to prove a declining rate of salivary gland excision. Patients and method: Sialoendoscopy was performed in 8 patients. Results: Of these, 50 % of patients were diagnosed as having sialolithiasis and the other 50 % had chronic sialoadenitis. In patients with sialolithiasis, sialoendoscopy allowed the extraction of the calculus in two patients (50 %). In the remainder, sialoendoscopy provided confirmation of the diagnosis in all cases. Conclusions: Sialoendoscopy is a new technique for use in the diagnosis, treatment and post-operative management of sialolithiasis, sialoadenitis and other salivary gland pathologies

The Problem of Large Leptonic Mixing

Unlike in the quark sector where simple $S_3$ permutation symmetries can generate the general features of quark masses and mixings, we find it impossible (under conditions of hierarchy for the charged leptons and without considering the see-saw mechanism or a more elaborate extension of the SM) to guarantee large leptonic mixing angles with any general symmetry or transformation of only known particles. If such symmetries exist, they must be realized in more extended scenarios.Comment: RevTeX, 4 pages, no figure

Nasal delivery devices: A comparative study on cadaver model

Nasal nebulization is a more effective method of delivering topical medication than nasal spray. The purpose of this study was to assess the deposition patterns of nebulization in delivering topical agents to the nasal cavities in the human cadaveric model using a color-based method. We have compared these following nasal devices: single-dose vial irrigation, syringe-irrigation, common nasal spray, Spray-sol, MAD nasal, and Rinowash nasal douche. Endoscopic images were recorded at six anatomical regions prior to and following each nasal device application and four reviewers evaluated the amount of surface area staining. At the nasal vestibule, the blue dye distribution achieved with Spray-sol was more extensive than nasal sprays. At inferior turbinate and nasal cavity floor, single dose vial, syringe, MAD nasal, Spray-sol, and Rinowash demonstrated a greater extent of dye distribution than nasal spray. At the middle turbinate, the average score of both Spray-sol and MAD nasal was significantly higher than other nasal investigated devices. At the nasopharynx, Spray-sol nebulization covers a surface significantly greater than other devices. Compared to traditional sprays, Spray-sol and MAD nasal provided a more effective method of delivering topical agents to the deeper and higher portions of the nasal cavities

Genetic overlap between diagnostic subtypes of ischemic stroke

Background and Purpose: Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Methods: Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. Results: High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10-4) and profile scores (rg=0.72; 95% confid

Serum magnesium and calcium levels in relation to ischemic stroke : Mendelian randomization study

ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 7 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 7 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema : Subgroup analysis of the MEAD study

Background: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods: Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34.68 Early Treatment Diabetic Retinopathy Study letters (20/200.20/50 Snellen equivalent), and central retinal thickness (CRT) 65300 \u3bcm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was 6515-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Results: Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n=261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had 6515-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 \u3bcm with DEX 0.7 versus -39.0 \u3bcm with sham(P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. Conclusions: DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population

Broadband multi-wavelength properties of M87 during the 2017 Event Horizon Telescope campaign

High Energy AstrophysicsInstrumentatio

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Linee Guida per la Prevenzione della Solidificazione dell'Aceto

Gestione della batteria, resa ed età dell’aceto balsamico tradizionale. La produzione di Aceto Balsamico Tradizionale (ABT) di Modena e Reggio Emilia prevede un periodo di invecchiamento di almeno 12 anni in una batteria di barili. Dal procedimento del “rincalzo” si ottiene però una miscela di aceti per cui l’età dell’ABT non è di immediata determinazione: l’utilizzo di un modello di calcolo ne permette però la stima in base ai volumi in ingresso ed in uscita, legati alla resa della batteria ed al tasso di evaporazione. Il controllo di tali fattori mediante una gestione oculata dell’acetaia risulta quindi determinante per valorizzare l’ABT prodotto, sia in termini di grado di maturazione che di ritenzione di sostanze importanti sotto il profilo sensoriale.Aceti balsamici tradizionali (ABT) provenienti da diversi produttori sono stati analizzati con tecniche strumentali complementari e indipendenti per valutare la struttura a diversi livelli di scala, il comportamento reologico, la concentrazione di glucosio e fruttosio e la distribuzione delle dimensioni molecolari. I dati sperimentali dimostrano che, dal punto di vista fisico, l’ABT è una dispersione colloidale complessa con una forte eterogeneità nelle dimensioni molecolari e nella microstruttura. La struttura di questa dispersione cambia lentamente durante l’invecchiamento in batteria (stato di non equilibrio) e, in condizioni permissive, può subire fenomeni di separazione di fase (intorbidimento e precipitazione), cristallizzazione di soluti e/o gelificazione (solidificazione in massa) anche a temperatura ambiente, sia in batteria sia dopo l’imbottigliamento. Una stima indiretta e approssimata del grado di solidificazione raggiunto nell’ABT e del rischio d’instabilità residuo può essere fatta analizzando quattro variabili fisico-compositive facilmente misurabili: indice rifrazione espresso in gradi Brix, concentrazione del D-glucosio e del D-fruttosio, viscosità dinamica misurata a 500s-1. L’opportuna combinazione di queste misurazioni sono anche un valido indicatore dell’invecchiamento dell’aceto e della corretta gestione delle batterie per la sua produzione: in particolare, bassa concentrazione zuccherina e alto grado Brix indicano aceti con età relativamente elevate e che hanno subito un lento processo d’invecchiamento. Infine, questo studio ci ha permesso di individuare e proporre alcune linee guida per ridurre il rischio di solidificazione negli AB