Cetylpyridinium Chloride Mouthwash to Reduce Shedding of Infectious SARS-CoV-2: A Double-Blind Randomized Clinical Trial.

The airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via respiratory fluids and droplets suggests that mouthwashes containing substances with virucidal activity can help reduce viral spread. We conducted a multicenter, double-blind, placebo-controlled, randomized trial to assess the virucidal activity of cetylpyridinium chloride (CPC) mouthwashes. Outpatients who tested positive for SARS-CoV-2 infection with or without symptoms were randomized to perform washes and gargles for 1 min with 15 mL of either colored distilled water or 0.07% CPC (Vitis CPC Protect) mouthwash. The study outcomes were the SARS-CoV-2 log10 viral RNA load and the nucleocapsid protein levels, both in saliva at 1 and 3 h after the intervention. In total, 118 patients were enrolled and randomized (mean [SD], age 46 [14] y). Thirteen of 118 participants (11%) did not complete follow-up or had insufficient sample volume for testing and were excluded from the analysis. The assessment of the viral load showed no significant differences between groups at any of the investigated points. However, the levels of SARS-CoV-2 nucleocapsid protein of lysed viruses were significantly higher in the CPC group compared with the control group at 1 h (adjusted difference 269.3 pg/mL; 95% confidence interval [CI], 97.1-441.5) and at 3 h postintervention (561.1 pg/mL; 95% CI, 380.0-742.2). In nonhospitalized patients with asymptomatic or mild symptomatic SARS-CoV-2 infection, a 0.07% CPC mouthwash, compared to placebo, was associated with a significant increase of nucleocapsid protein levels in saliva, indicating enhanced disruption of viral particles.

Skin lesions in neurofibromatosis type 2: diagnostic and prognostic significance of cutaneous (plexiform) schwannomas.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a genetic disease characterized by the appearance of multiple tumours in the nervous system. Cutaneous lesions are common and may provide useful diagnostic and prognostic information, but they have not been widely studied. OBJECTIVES: To characterize cutaneous lesions in a Spanish cohort of patients with NF2 and investigate associations with clinical and genetic severity. METHODS: We studied the clinical and histologic characteristics of cutaneous lesions in 49 patients with NF2 and analysed correlations with phenotype- and genotype-based severity scores. We collected information on the presence/absence of cutaneous lesions, location, age at onset, type of lesion, and histologic features. We also studied level of systemic involvement and genetic mutations involved. RESULTS: Forty-nine patients (31 women [63.3%] and 18 men [36.7%]) were analysed, and 33 (67.3%) had cutaneous lesions presumed to be schwannomas. According to their clinical form, they were distributed as follows: 24 patients (48%) had deep tumours, 21 (42%) had plaque-like lesions, and 3 (6%) had superficial tumours. Histologic examination from 27 lesions analysed out 23 patients showed classic schwannoma or hybrid schwannoma-neurofibroma features in the 8 deep tumours biopsied and plexiform schwannoma features in the 17 plaque-like lesions and the 2 superficial tumours analysed. Early onset (first 2 decades of life) was reported by all patients with plaques and superficial tumours. In our cohort, 100% of the patients with plaque-like lesions and superficial tumours with microscopic features of plexiform schwannoma were in the 2 groups with the most severe clinical phenotypes, and 82.6% of them were in the 3 most severe genotype-based classes. CONCLUSIONS AND RELEVANCE: Cutaneous lesions, specially plexiform schwannomas, are common in NF2, and they usually appear at an early age providing useful diagnostic and prognostic information. These tumours are part of the spectrum of cutaneous manifestations in this disease. Although its diagnostic and prognostic value has been pointed out, there are few studies focussed on their analysis.

Anal cytology screening in men who have sex with men with HIV at a university hospital in Bogotá, Colombia.

BACKGROUND: Risk of anal squamous cell carcinoma (anal cancer) is greater among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). We describe the frequency of and factors associated with abnormal anal cytology results in Colombian MSM living with HIV. METHODS: This retrospective observational cohort study included MSM ≥18 years old living with HIV screened with anal cytology at Hospital Universitario San Ignacio in Bogotá, Colombia between January 2019 and February 2020. A multivariable log-binomial regression model estimated associations with abnormal anal cytology. RESULTS: A total of 211 patients were included. Mean age was 35.6 years. Sixty-eight (32.3%) had an abnormal anal cytology result: ASC-US 33.8% (n = 23); LSIL 60.3% (n = 41); and HSIL 5.9% (n = 4). MSM with an STI diagnosis in the previous 12 months (RR 1.48, [95% CI 1.03-2.12], p = 0.032) or with a CD4+ T cell count <200 (RR 2.08 [95% CI 1.16-3.73], p = 0.014) were significantly more likely to have abnormal anal cytology. CONCLUSIONS: These data provide crucial information to guide scale up of anal cancer screening at select centers in Colombia. Our results also suggest STI prevention efforts and improved virological control among MSM living with HIV may have the secondary benefit of reducing the risk of anal cancer.

Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two forms of pulmonary hypertension (PH) characterized by obstructive vasculopathy. Endothelial dysfunction along with metabolic changes towards increased glycolysis are important in PAH pathophysiology. Less is known about such abnormalities in endothelial cells (ECs) from CTEPH patients. This study provides a systematic metabolic comparison of ECs derived from CTEPH and PAH patients. Metabolic gene expression was studied using qPCR in cultured CTEPH-EC and PAH-EC. Western blot analyses were done for HK2, LDHA, PDHA1, PDK and G6PD. Basal viability of CTEPH-EC and PAH-EC with the incubation with metabolic inhibitors was measured using colorimetric viability assays. Human pulmonary artery endothelial cells (HPAEC) were used as healthy controls. Whereas PAH-EC showed significant higher mRNA levels of GLUT1, HK2, LDHA, PDHA1 and GLUD1 metabolic enzymes compared to HPAEC, CTEPH-EC did not. Oxidative phosphorylation associated proteins had an increased expression in PAH-EC compared to CTEPH-EC and HPAEC. PAH-EC, CTEPH-EC and HPAEC presented similar HOXD macrovascular gene expression. Metabolic inhibitors showed a dose-dependent reduction in viability in all three groups, predominantly in PAH-EC. A different metabolic profile is present in CTEPH-EC compared to PAH-EC and suggests differences in molecular mechanisms important in the disease pathology and treatment.

The role of temporal distance of the events on the spatiotemporal dynamics of mental time travel to one's personal past and future.

Mental time travel to personal past and future events shows remarkable cognitive and neural similarities. Both temporalities seem to rely on the same core network involving episodic binding and monitoring processes. However, it is still unclear in what way the temporal distance of the simulated events modulates the recruitment of this network when mental time-travelling to the past and the future. The present study explored the electrophysiological correlates of remembering and imagining personal events at two temporal distances from the present moment (near and far). Temporal distance modulated the late parietal component (LPC) and the late frontal effect (LFE), respectively involved in episodic and monitoring processes. Interestingly, temporal distance modulations differed in the past and future event simulation, suggesting greater episodic processing for near as opposed to far future situations (with no differences on near and far past), and the implementation of greater post-simulation monitoring processes for near past as compared to far past events (with high demands on both near and far future). These findings show that both past and future event simulations are affected by the temporal distance of the events, although not exactly in a mirrored way. They are discussed according to the increasing role of semantic memory in episodic mental time travel to farther temporal distances from the present.

Protocol for assessing mortality reduction with the early use of noninvasive ventilation in prehospital emergency services: A multicentre, observational cohort study in Madrid, Spain.

BACKGROUND: Acute respiratory failure (ARF) has become one of the most prevalent serious pathologies encountered in the emergency medical service (EMS). In hospital settings, noninvasive ventilation (NIV) therapy prevents complications from more aggressive treatments for that condition. However, the scarce evidence on the benefits of NIV in prehospital EMS (i.e., during transport to the hospital) is inconclusive. OBJECTIVES: To determine whether the administration of NIV during prehospital EMS in cases of ARF reduces in-hospital mortality compared with starting NIV on arrival to in-patient EMS. METHODS: This is a multicentre, observational, prospective cohort study. We recruited a total of 317 patients from the Madrid region (Spain) who were prescribed NIV for their ARF using a nonprobabilistic consecutive sampling method. Analyses of the main outcome (in-hospital mortality) and secondary outcomes (length of hospital stay, readmissions, percentage of intensive care unit admissions, and cost-effectiveness) will include descriptive analyses of patients' characteristics, as well as bivariate and multivariate analyses and cost-effectiveness analysis. DISCUSSION: This study will provide data on NIV management in prehospital and in-patient EMS in patients with ARF. Results will contribute to the existing evidence on the benefits of NIV in the context of prehospital EMS while underlining the importance of a standardized formal training for physicians and nurses working in prehospital and in-patient EMSs. CONCLUSION: The VentilaMadrid study will provide valuable data on the clinical factors of patients receiving NIV in prehospital EMS. Further, were our hypothesis to be confirmed, our results would strongly suggest that the administration of NIV in prehospital EMS by medical and nursing profesionals formally trained in the technique reduces mortality and improves prognoses.

SARS-CoV-2 contact tracing among disadvantaged populations during epidemic intervals should be a priority strategy: results from a pilot experiment in Barcelona.

OBJECTIVES: The aim of this study was to trace contacts of coronavirus disease 2019 (COVID-19) hospitalised patients and determine the risk factors of infection in urban areas. STUDY DESIGN: Longitudinal analysis of contacts identified from index cases. METHODS: A contact tracing study was carried out in the Northern Metropolitan area of Barcelona, Spain, during the inter-epidemic lapse of May to July 2020, a period of low SARS-CoV-2 incidence. Index cases were notified from the referral hospital. Contacts were traced and followed up for 14 days. Reverse transcription polymerase chain reaction was performed on day 0 and day 14 for contacts. RESULTS: In total, 368 contacts were identified from 81 index cases (median of seven contacts per index case), from which 308 were traced successfully. The median age of contacts was 28 years, 62% (223 of 368) were men. During the follow-up period, 100 contacts tested positive for COVID-19 (32.5% [95% confidence interval {CI} = 27.3-38.0]), with a secondary infection rate of 48.3% (95% CI = 40.8-55.9) among housemates. Clusters of index and respective contacts tended to aggregate within disadvantaged neighbourhoods (P < 0.001), and non-national index cases (N = 28, 34.1%) resulted in higher secondary infection rates compared with nationals (51.0% [95% CI = 41.0-60.9] vs 22.3% [95% CI = 16.8-28.8]; P < 0.001). CONCLUSIONS: Disadvantaged communities experience a disproportionate burden of COVID-19 and may act as infection reservoirs. Contact tracing with a cross-cutting approach among these communities is required, especially during inter-epidemic periods.

Effectiveness of salivary stimulation using xylitol-malic acid tablets as coadjuvant treatment in patients with gastro-oesophageal reflux disease: early findings.

BACKGROUND: Besides dental erosion syndrome, other oral syndromes could benefit from the stimulation of salivary secretion, in patients with gastro-oesophageal reflux disease (GORD). Our aims is evaluate the improvement of oral extra-oesophageal manifestations in patients with GORD using xylitol-malic acid tablets to stimulate salivary secretion. MATERIAL AND METHODS: The effectiveness of salivary stimulation using xylitol-malic acid tablets (as a supplement to omeprazole 40 mg/day) was assessed in a clinical trial (n = 14) lasting six months with patients with prior positive pH-metry, through GORD extra-oesophageal clinical signs, GerdQ and RDQ questionnaires, odontological variables, basal salivary secretion, stimulated salivary secretion, pH and buffer capacity, mucosal erythema index and dental wear. STATISTICS: chi-square (Haberman post-hoc), ANOVA, and Mann-Whitney U; variables between visits were evaluated with McNemar's Student's t and Wilcoxon tests; p < 0.05. RESULTS: 100% of patients not taking xylitol-malic acid presented xerostomia, but only 14.3% of patients taking xylitol-malic acid (p < 0.01) did. The mean saliva-buffer capacity at the last visit for patients not taking xylitol-malic acid was 2.14 ± 0.38, versus 2.71 ± 0.49 for patients taking xylitol-malic acid (p < 0.05). Retro-sternal burning (p < 0.05), heartburn (p < 0.05) and regurgitation (p < 0.05) were also reduced. CONCLUSIONS: Xylitol-malic acid tablets improve quality of life among patients with GORD, by reducing dry mouth, increasing saliva buffering and reducing heartburn, retro-sternal burning and regurgitation.

Three-dimensional regional bi-ventricular shape remodeling is associated with exercise capacity in endurance athletes.

AIMS: Endurance athletes develop cardiac remodeling to cope with increased cardiac output during exercise. This remodeling is both anatomical and functional and shows large interindividual variability. In this study, we quantify local geometric ventricular remodeling related to long-standing endurance training and assess its relationship with cardiovascular performance during exercise. METHODS: We extracted 3D models of the biventricular shape from end-diastolic cine magnetic resonance images acquired from a cohort of 89 triathlon athletes and 77 healthy sedentary subjects. Additionally, the athletes underwent cardio-pulmonary exercise testing, together with an echocardiographic study at baseline and few minutes after maximal exercise. We used statistical shape analysis to identify regional bi-ventricular shape differences between athletes and non-athletes. RESULTS: The ventricular shape was significantly different between athletes and controls (p < 1e-6). The observed regional remodeling in the right heart was mainly a shift of the right ventricle (RV) volume distribution towards the right ventricular infundibulum, increasing the overall right ventricular volume. In the left heart, there was an increment of left ventricular mass and a dilation of the left ventricle. Within athletes, the amount of such remodeling was independently associated to higher peak oxygen pulse (p < 0.001) and weakly with greater post-exercise RV free wall longitudinal strain (p = 0.03). CONCLUSIONS: We were able to identify specific bi-ventricular regional remodeling induced by long-lasting endurance training. The amount of remodeling was associated with better cardiopulmonary performance during an exercise test.

Geographic distribution of chronic obstructive pulmonary disease prevalence in Africa, Asia and Australasia.

OBJECTIVE: To visualise spatial data on chronic obstructive pulmonary disease (COPD) prevalence in Africa, Asia and Australasia using a Geographic Information System (GIS) inverse distance weighted (IDW) interpolation technique.DESIGN: Prevalence rates from population surveys on individuals aged ≥40, with spirometry-confirmed COPD, were searched systematically. The prevalence observed in 59 selected surveys and the geographic coordinates of the places where they were conducted informed a GIS computer programme. The prevalence was represented by an ascending chromatic scale (blue-green-yellow-orange-brown-red) in the GIS maps.RESULTS: IDW-interpolation GIS maps were obtained of all the geographic areas investigated, and even from regions lacking data. Areas of high/very high prevalence were found in: Southern Africa and in most of the Central and Eastern Africa regions; in practically all of Central Asia; in the western regions of Southern Asia; in the southern regions of the East European Plain and the West Siberian Plain of Northern Asia; and in the Malay Archipelago. Intermediate prevalence predominated in Oceania and in most of the other regions of Africa and Asia.CONCLUSION: Despite some biases inherent to the interpolation method used in the present study, our approach provided an understandable visual perspective of the COPD prevalence distribution in these geographic regions.

Unusual Interface Dermatoses Distributed Along Blaschko's Lines in Adult Patients.

Linear dermatoses are unusual entities whose distribution reflects cutaneous mosaicism, even when they occur in adult life. Adult blaschkitis (AB) and lichen striatus (LS) always follow this peculiar distribution. Although usually referred to as distinct entities, the clinical and histopathological presentation of lichen striatus in adults may be similar to those of adult blaschkitis. Moreover, some cases with overlapping features between lichen striatus and linear lichen planus have been published, making precise diagnosis very difficult. Recently, the concept of a wide spectrum of blaschkolinear dermatoses with AB and LS located somewhere within it has been proposed but it has not gained general recognition. We report three cases of dermatoses following the lines of Blaschko in adults (two women and one male, ages 35, 50 and 56, respectively). They involved the upper extremity in two cases and the lower in the third. Clinically, they were interpreted as linear lichen planus or blaschkitis but, histopathologically, they showed features consistent with lichen striatus. Lesions subsided with topic steroids and/or tacrolimus ointment, they are an example of the significant overlapping between these three entities, demonstrating that they may exist on a spectrum both clinically and histopathologically and clinico-pathologic correlation is essential to achieve an accurate final diagnosis. A detailed review of previously published cases has also been made.

Global vision system in laparoscopy. / Sistema de visión global en laparoscopia.

OBJECTIVE: The main difficulty in laparoscopic or robot-assisted surgery is the narrow visual field, restricted by the endoscope's access port. This restriction is coupled with the difficulty of handling the instruments, which is due not only to the access port but also to the loss of depth of field and perspective due to the lack of natural lighting. In this article, we describe a global vision system and report on our initial experience in a porcine model. MATERIAL AND METHODS: The global vision system consists of a series of intraabdominal devices, which increase the visual field and help recover perspective through the simulation of natural shadows. These devices are a series of high-definition cameras and LED lights, which are inserted and fixed to the wall using magnets. The system's efficacy was assessed in a varicocelectomy and nephrectomy. RESULTS: The various intraabdominal cameras offer a greater number of intuitive points of view of the surgical field compared with the conventional telescope and appear to provide a similar view as that in open surgery. Areas previously inaccessible to the standard telescope can now be reached. The additional light sources create shadows that increase the perspective of the surgical field. CONCLUSION: This system appears to increase the possibilities for laparoscopic or robot-assisted surgery because it offers an instant view of almost the entire abdomen, enabling more complex procedures, which currently require an open pathway.

Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Barley Stripe Rust Resistance QTL: Development and Validation of SNP Markers for Resistance to Puccinia striiformis f. sp. hordei.

Quantitative trait loci (QTL) for barley stripe rust resistance were mapped in recombinant inbred lines (RIL) from a 'Lenetah' × 'Grannelose Zweizeilige' (GZ) cross. GZ is known for a major seedling resistance QTL on chromosome 4H but linked markers suitable for marker-assisted selection have not been developed. This study identified the 4H QTL (log of the likelihood [LOD] = 15.94 at 97.19 centimorgans [cM]), and additional QTL on chromosomes 4H and 6H (LOD = 5.39 at 72.7 cM and 4.24 at 34.46 cM, respectively). A QTL on chromosome 7H (LOD = 2.04 at 81.07 cM) was suggested. All resistance alleles were derived from GZ. Evaluations of adult plant response in Corvallis, OR in 2013 and 2015 provided evidence of QTL at the same positions. However, the minor QTL on 4H was not statistically significant in either location/year, while the 7H QTL was significant in both. The single-nucleotide polymorphism markers flanking the resistance QTL were validated in RIL from a '95SR316A' × GZ cross for their ability to predict seedling resistance. In 95SR316A × GZ, 91 to 92% of RIL with GZ alleles at the major 4H QTL and at least one other were resistant to moderate in reaction. In these populations, at least two QTL were required to transfer the barley stripe rust resistance from GZ.

Urinary high-mobility group box-1 associates specifically with lupus nephritis class V.

INTRODUCTION: High-mobility group box 1 protein (HMGB-1) has been implicated in the pathogenesis of lupus nephritis (LN). There is increased HMGB-1 expression in the kidneys and increased levels are observed in serum and urine of patients with LN. This study was performed to determine whether the increased urinary HMGB-1 was specific for active lupus or secondary to renal damage. METHODS: Urine from 61 lupus patients (32 had active LN and 29 had systemic lupus erythematosus (SLE) with no evidence of LN) and 14 control proteinuric patients (all with hypertension and eight also with diabetes) were included in this study. HMGB-1 was detected by Western blot. Urine protein was normalized to urine creatinine to account for volume of the specimen. RESULTS: Median normalized urine HMGB-1 levels were significantly elevated in LN patients compared to lupus patients without kidney disease (53.81 vs 9.46, p < 0.001). A difference in median levels was seen between LN classes, with a significant difference between proliferative and membranous disease (33.4 vs 138.8, p = 0.003). Urine protein to urine creatinine ratio (P/C) correlated with urinary HMGB-1 (r = 0.52, p < 0.001), but across the classes this was true only for membranous disease (r = 0.71, p = 0.022, proliferative, p = 0.63; mixed, p = 0.34). CONCLUSIONS: HMGB-1 is elevated in the urine of patients with active LN. Levels are associated with LN class, and higher levels of urinary HMGB-1 are seen in patients with class V when compared to both proliferative and mixed classes. Therefore, urinary HMGB-1 may be suggestive of membranous LN and warrants further evaluation in a large lupus cohort.