MicroRNA-532-5p Regulates Pericyte Function by Targeting the Transcription Regulator BACH1 and Angiopoietin-1

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Longitudinal Analysis of Inflammatory Response to SARS-CoV-2 in the Upper Respiratory Tract Reveals an Association with Viral Load,Independent of Symptoms

Background

SARS-CoV-2 infection leads to high viral loads in the upper respiratory tract that may be determinant in virus dissemination. The extent of intranasal antiviral response in relation to symptoms is unknown. Understanding how local innate responses control virus is key in the development of therapeutic approaches.

Methods

SARS-CoV-2-infected patients were enrolled in an observational study conducted at the Geneva University Hospitals, Switzerland, investigating virological and immunological characteristics. Nasal wash and serum specimens from a subset of patients were collected to measure viral load, IgA specific for the S1 domain of the spike protein, and a cytokine panel at different time points after infection; cytokine levels were analyzed in relation to symptoms.

Results

Samples from 13 SARS-CoV-2-infected patients and six controls were analyzed. We found an increase in CXCL10 and IL-6, whose levels remained elevated for up to 3 weeks after symptom onset. SARS-CoV-2 infection also induced CCL2 and GM-CSF, suggesting local recruitment and activation of myeloid cells. Local cytokine levels correlated with viral load but not with serum cytokine levels, nor with specific symptoms, including anosmia. Some patients had S1-specific IgA in the nasal cavity while almost none had IgG.

Conclusion

The nasal epithelium is an active site of cytokine response against SARS-CoV-2 that can last more than 2 weeks; in this mild COVID-19 cohort, anosmia was not associated with increases in any locally produced cytokines.

     

Cortical synapse loss in progressive supranuclear palsy

Cortical synapse loss, the probable substrate of cognitive impairment in Alzheimer disease (AD), has not previously been evaluated in progressive supranuclear palsy (PSP). Hypothesizing that synapse loss would be greater in demented than non-demented PSP patients, we examined synaptophysin concentrations in 8 cases of PSP (5 demented and 3 nondemented cases). We found a decrease in mean synaptophysin concentration in these 8 cases in frontal, temporal, and parietal lobes, and in cerebellum, compared to the means in corresponding lobes of 16 controls. The decreases were similar to those in 28 cases of AD, but not as great. We determined synaptophysin concentration from motor cortex in only 4 of our PSP cases, 2 demented and 2 non-demented. The average concentrations in these 4 cases were lower than in AD motor cortex; both were lower than controls. When demented and non-demented PSP cases were compared, neocortical synaptophysin concentrations in non-demented PSP cases were lower than in demented cases. There appears to be a link between AD and PSP, in that synapse loss is found in both. However, the basis and significance of the prominent neocortical synapse loss in PSP, especially in non-demented subjects, remain to be explored.     

ACE I/D polymorphism and cardiac adaptations in adolescent athletes

PURPOSE: The aim of this cross-sectional study was to determine whether there is a correlation between left ventricular hypertrophy (LVH) and angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism in adolescent athletes. METHODS: Seventy-five competitive soccer players (aged 15 +/- 1.2 yr) and 52 untrained control subjects (aged 15 +/- 1.6 yr) were examined with echocardiography (echo) and bioelectrical impedance analysis. The ACE genotype of all subjects was determined by PCR and correlated with left ventricular mass (LVM) indices. RESULTS: Allele frequencies were comparable between athletes and controls. Body surface area (BSA), fat-free mass (FFM), and all mean echo measurements were significantly greater in athletes than in controls. LVM and LVM indices for both BSA and FFM were all significantly greater in athletes than in controls (LVM 195.3 +/- 32 g vs 165.3 +/- 37.6 g; LVM/BSA 115.5 +/- 18.9 g x mq(-1) vs 95 +/- 18.2 g x mq(-1); LVM/FFM 3.5 +/- 0.5 vs 3 +/- 0.54, P < 0.001 for the three variables). Left ventricular hypertrophy was found in 17 (23%) athletes. There was no correlation between ACE I/D polymorphism and athletes with LVH as the II and DD genotype frequencies were identical (41%). However, in athletes with LVH, the presence of the D allele was associated with a greater LVM index than compared to homozygous II genotype (LVM = 145 +/- 7.6 g x mq(-1) in DD+ID group vs 135 +/- 2.9 g x mq(-1) in II group, P = 0.008). CONCLUSIONS: The results of the study show that significant changes occur in cardiac morphology and function in adolescent athletes. Interestingly, the ACE I/D polymorphism was associated with the degree of cardiac hypertrophy but not with the occurrence of LVH itself.     

AIRPOLISHING EFFECT ON BOVINE ENAMEL AND THE POSTERIOR REMINERALIZING EFFECT OF SALIVA. AN IN VITRO STUDY

Purpose:

The aim of the present study was to evaluate the alterations of surface microhardness and wear caused by the sodium bicarbonate jet on bovine enamel and the further remineralizing effect of artificial saliva.

Methods:

Fifteen enamel samples (4,0mm × 4,0mm) were used, which constituted the groups: no treatment (MI); treatment with sodium bicarbonate jet (MII and DI); treatment with sodium bicarbonate jet and immersion in saliva for one hour (MIII and DII), 24 hours (MIV and DIII) and 7 days (MV and DIV). Microhardness tests were carried out using a microdurometer in groups M and wear tests by a rugosimeter in groups D. The data were assessed by the one criterion variance analysis and Tukey test.

Results:

The mean value of microhardness, in KHN, in groups MI, MII, MIII, MIV and MV were 359,80; 335,46; 369,20; 377,73 and 341,86, respectively, whereas the mean values in μm, of wear for group DI, DII, DIII and DIV were 0,564; 0,519; 0,441 and 0,428, respectively.

Conclusions:

The sodium bicarbonate jet caused a wear and a reduction in microhardness on the enamel surface; saliva promoted the recovery of initial condition surface microhardness and reduced the wear; the repairing effect of saliva on the surface microhardness alterations occurred within one hour of treatment, having no significant statistical difference from the effect obtained in 24 hours; the best saliva repairing effect on the wear occurred with treatment of 24 hours.     

The primary reflex effects of distension of the stomach on heart rate,arterial pressure and left ventricular contractility in the anaesthetized pig

The present study was planned to investigate whether distension of the stomach primarily affects the heart rate, arterial blood pressure and left ventricular inotropic state and to explore the reflex mechanisms involved. In 16 anaesthetized pigs, distension of gastric balloons with 0.8 1 of Ringer solution (gastric transmural pressure of about 13 mmHg) without controlling any haemodynamic variable caused an increase in arterial blood pressure. When this response was prevented, an increase in heart rate was obtained in each animal. In five pigs, the increase in heart rate was graded by step increments of distension. No significant changes in maximum rate of change of left ventricular pressure were observed in the sixteen pigs during gastric distensions performed whilst preventing changes in heart rate and arterial blood pressure. The responses of arterial blood pressure and heart rate were not influenced by the administration of atropine (four and six pigs respectively), while they were abolished by the administration of bretylium tosylate (ten pigs) and by bilateral vagotomy (six pigs; three cervical, three subdiaphragmatic). The present study showed that gastric distension which was likely to be innocuous in the anaesthetized pig reflexly increased arterial blood pressure and heart rate. The afferent limb of the reflex was in the vagal nerves and the efferent limb involved sympathetic pathways.     

Effect of professional cleaning and dental brushing with or without fluoridated dentifrice on enamel remineralization

An in situ evaluation of the potential rehardening effect of fluoridated and non-fluoridated toothpastes with or without air polishing was conducted. Ten volunteers, using acrylic palatal appliances containing two bovine enamel blocks with artificial carious lesions, took part in this study. Four times a day, after the main meals and at night, the volunteers, in a habitual way, brushed their natural teeth with the dentifrice indicated to the experimental design and after that the appliances were put again into the mouth. They were divided into 4 different groups: G1 - control - non-fluoridated dentifrice; G2 - fluoridated dentifrice; G3 - non-fluoridated dentifrice, but having a previous prophylaxis using air polishing; G4 - fluoridated dentifrice and previous air polishing. The effects of treatments on enamel rehardening were evaluated in the blocks that were assessed by surface microhardness, and the percentage of surface microhardness change (%reh) was calculated in relation to the baseline values. The results showed that %reh was higher in the groups with fluoridated dentifrice, and professional prophylaxis did not have an additional effect in the groups of fluoridated dentifrices (p<0.05). The data suggested that, in the absence of fluoride, removal of dental plaque helped to increase the process of enamel rehardening.     

The feasibility and usefulness of contrast exercise echocardiography for the assessment of left ventricular function in master athletes.

BACKGROUND: The number of competitive master athletes (MA, over 40 years) has been rising. Since the incidence of coronary artery disease (CAD) is increasing in this population, cardiovascular pre-participation screening, including a maximum exercise test, is recommended. In this context the addition of contrast to echo could be useful because wall thickening and motion are better markers of myocardial function when the whole endocardial border (EB) is visible. OBJECTIVE: To evaluate the feasibility and usefulness of rest and exercise contrast echo for the assessment of LV wall motion in competitive master athletes with suboptimal acoustic windows. METHODS: Forty consecutive MA underwent echo and contrast echo both at rest and during exercise. Contrast-enhanced images were achieved at rest and at peak exercise after administration of SonoVue (BR1), using apical 4 and 2-chamber views divided into 6 myocardial segments (MS). The EB resolution for each segment was graded as: 0=not visible, 1=barely visible, 2=well-delineated. RESULTS: In the baseline at-rest echo 17/40 (45%) patients were graded as score 0, 22/40 (55%) were graded as score 1 and only 1 athlete has reached score 2. In at-rest echo contrast 28/40 (70%) athletes have reached score 1 and 12/40 (30%) score 2. Nobody was graded as score 0. At the same time in the baseline peak-exercise echo 12/40 (30%) athletes were graded as score 0, 24/40 (60%) athletes reached score 1 and 4/40 (10%) score 2, while using contrast at peak-exercise echo 28/40 (70%) were grated as score 1 and 12/40 (30%) reached score 2. The differences about the grading of the score between the two groups with and without contrasts, at rest and at peak exercise, are statistically significant (p<0.001). Considering the whole of the MS analyzed in the majority of the athletic population studied, we can see that at-rest echo, 64/480 MS (13.3%) were graded as 0, 156/480 MS (32.5%) as 1 and 260/480 MS (54.2%) were graded 2, while in the peak-exercise 96/480 MS (20%) were graded as 0, 235/480 MS (48.9%) as 1 and 209/480 MS (43.5%) were graded 2. On the other hand, using contrast, in at-rest echo, 480/480 MS (100%) were graded as 2 while in the peak-exercise echo 460/480 MS (95.9%) were graded as 2 and 20/480 MS (4.1%) as 1. The percentage of the MS graded as 2 reach almost the whole number of the analyzed MS with a percentage increment in the at-rest and peak-exercise echo of 85% and 120%, respectively. CONCLUSIONS: Our results show that the use of contrast echo improves the visibility of the EB in a way that the two groups of competitive athletes show at rest and after exercise a significant increment of the score 2 compatible with a better visibility of the EB. These results suggest that contrast echo, both at rest and during exercise, is a better method for EB analysis to understand the behaviour of the wall motion in subjects with suboptimal acoustic windows, and could be suitable for cardiovascular screening in master athletes.