It is generally agreed that striking a balance between resuming economic and social activities and keeping the effective reproductive number (R0) below 1 using non-pharmaceutical interventions is an important goal until and even after effective vaccines become available. Therefore, the need remains to understand how the virus is transmitted in order to identify high-risk environments and activities that disproportionately contribute to its spread so that effective preventative measures could be put in place. Contact tracing and household studies in particular provide robust evidence about the parameters of transmission. In this viewpoint, we discuss the available evidence from large-scale, well-conducted contact tracing studies from across the world and argue that SARS-CoV-2 transmission dynamics should inform policy decisions about mitigation strategies for targeted interventions according to the needs of the society by directing attention to the settings, activities and socioeconomic factors associated with the highest risks of transmission.

A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by SARS-CoV-2 may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in Covid-19 patients.

To determine whether NAC in high doses can avoid respiratory failure in patients with Covid-19.

It was a double-blind, randomized, placebo-controlled, unicentric trial, conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil. We enrolled 135 patients with severe Covid-19 (confirmed or suspected), with an oxyhemoglobin saturation of less than 94% or respiratory rate higher than 24 breaths/min. Patients were randomized to receive NAC 21g (approximately 300mg/kg) for 20 hours, or dextrose 5%. Primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to ICU, time in ICU, and mortality.

Baseline characteristics were very similar in the two groups, with no significant difference in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest CT scan findings. Sixteen patients (23.9%) in the Placebo group were submitted to endotracheal intubation and mechanical ventilation, compared to 14 patients (20.6%) in the NAC group (p=0.675). No difference was observed in secondary endpoints.

Administration of NAC in high doses did not affect the evolution of severe Covid-19.

Administration of NAC in high doses did not affect the evolution of severe Covid-19.

Acute lymphoblastic leukemia (ALL) is a frequent malignancy in childhood. The present study was aimed to investigate the effect of miR-223 in ALL and its underlying molecular mechanisms.

The mRNA expression of miR-223 and FOXO1 was detected by qRT-RCR in ALL children. The correlation between miR-223 and clinical indexes of ALL was determined. CCRF-CEM and NALM-6 cells were transfected with miR-223 mimic and miR-223 inhibitor, respectively. The proliferation, apoptosis, invasion and migration of CCRF-CEM and NALM-6 cells were measured by MTT, flow cytometry and transwell assay. The protein expression of FOXO1 was detected by Western blot. Additionally, dual-luciferase reporter and RNA pull-down assay were performed to investigate the target gene of miR-223 and validate their targeting relationship.

The mRNA expression of miR-223 was markedly down-regulated in ALL, but FOXO1 was up-regulated. The protein expression of FOXO1 was highly expressed in CCRF-CEM and NALM-6 cells. The expression of miR-223 was related to WBC, PLT, RBC and risk stratification. Overexpression of miR-223 not only inhibited cell proliferation, migration and invasion, but also induced cell apoptosis. Importantly, FOXO1 was a target gene of miR-223 in ALL cells. Silencing of FOXO1 reversed the effects of miR-223 inhibitor on cell proliferation, migration, invasion and apoptosis in ALL.

miR-223 could inhibit cell proliferation, migration and invasion, and promote apoptosis by targeting FOXO1 in ALL.

miR-223 could inhibit cell proliferation, migration and invasion, and promote apoptosis by targeting FOXO1 in ALL.

Overuse of unnecessary services, screening tests, and treatments is an ongoing problem for national health care systems. Overuse is at least partly driven by patient demand.

This study examined whether altering patients’ emotional state and appealing to patient altruism would reduce demand for three commonly overused UK health services.

In an online experiment, 1,267 UK volunteers were randomized to anxiety, compassion, or neutral conditions before viewing three overuse vignettes. In each vignette, use of the health service was recommended against by the doctor and participants were further randomized to one of three altruism frames, emphasizing the impact of overuse on the self, the self and others locally, or the self and others nationally. Participants rated the likelihood that they would pursue the health service and, assuming that they did not, how long they would be willing-to-wait for it.

Altruism frame had a small effect on intentions to use the health service. Those in the local or national (vs. self) frame were 4.7 and 6.1 percentage points, respectively, less likely to ask for the service. Emotion induction had no direct effect on outcomes. However, self-reporting higher levels of anxiety or compassion post-induction was associated with a small, greater likelihood in intentions to ask for the health service or willingness-to-wait, respectively. No interactions between frame and emotion were observed.

As a low-cost initiative, emphasizing the benefits to the self and local or national communities could be embedded in appeals designed to appropriately reduce health care overuse in the UK.

As a low-cost initiative, emphasizing the benefits to the self and local or national communities could be embedded in appeals designed to appropriately reduce health care overuse in the UK.

The study aims to evaluate protective effects of sophoricoside (Sop) on cardiac hypertrophy. Meanwhile, the potential and significance of Sop should be broadened and it should be considered as an attractive drug for the treatment of pathological cardiac hypertrophy and heart failure.

Using the phenylephrine (PE)-induced neonatal rat cardiomyocytes (NRCMs) enlargement model, the potent protection of Sop against cardiomyocytes enlargement was evaluated. The function of Sop was validated in mice received transverse aortic coarctation (TAC) or sham surgery. At 1 week after TAC surgery, mice were treated with Sop for the following 4 weeks, the hearts were harvested after echocardiography examination.

Our study revealed that Sop significantly mitigated TAC-induced heart dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, Sop treatment induced a remarkable activation of AMPK/mTORC1-autophagy cascade following sustained hypertrophic stimulation. Importantly, the protective effect of Sop was largely abolished by the AMPKα inhibitor Compound C, suggesting an AMPK activation-dependent manner of Sop function on suppressing pathological cardiac hypertrophy.

Sop ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy. Hence, Sop might be an attractive candidate for the treatment of pathological cardiac hypertrophy and heart failure.

Sop ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy. Hence, Sop might be an attractive candidate for the treatment of pathological cardiac hypertrophy and heart failure.

We systematically reviewed the literature to answer the following research questions 1) does IL-6 (receptor) antagonist therapy reduce mortality in COVID-19 patients compared to patients not treated with IL-6 (receptor) antagonists and 2) is there an increased risk of side effects in COVID-19 patients treated with IL-6 (receptor) antagonists compared to patients not treated with IL-6 (receptor) antagonists?.

We systematically searched PubMed, PMC PubMed Central, MEDLINE, WHO COVID-19 Database, Embase, Web-of-Science, COCHRANE LIBRARY, Emcare and Academic Search Premier (until June 30th2020). Random effects meta-analysis was used to pool the risk ratio and risk difference of individual studies. Risk of bias was appraised using the MINORS checklist.

The search strategy retrieved 743 unique titles of which 10 studies (all on tocilizumab) comprising 1358 patients were included. Nine out of ten studies were considered to be of high quality. Meta-analysis showed that the tocilizumab group had lower mortality than the control group. The risk ratio (RR) was 0.27 95%CI 0.12 to 0.59 and the risk difference (RD) was 12% 95%CI 4.6% to 20% in favour of the tocilizumab group. With only a few studies available there were no differences observed regarding side effects.

Our results showed that mortality was 12% lower for COVID-19 patients treated with tocilizumab compared to COVID-19 patients who were not treated with tocilizumab. The number needed to treat was 11, suggesting that for every 11 (severe) COVID-19 patients treated with tocilizumab 1 death is prevented. These results require confirmation by randomized controlled trials.

Our results showed that mortality was 12% lower for COVID-19 patients treated with tocilizumab compared to COVID-19 patients who were not treated with tocilizumab. The number needed to treat was 11, suggesting that for every 11 (severe) COVID-19 patients treated with tocilizumab 1 death is prevented. These results require confirmation by randomized controlled trials.Hemorrhage is the leading cause of preventable death of injured military and civilian patients, and subsequent infection risks endanger their lives or impede the healing of their wounds. Here, we report an injectable biodegradable hydrogel with hemostatic, antimicrobial, and healing-promoting properties. The hydrogel was prepared by dynamic cross-linking of a natural polysaccharide (dextran) with antimicrobial peptide ε-poly-l-lysine (EPL) and encapsulating base fibroblast growth factor (bFGF). The amino groups of EPL were allowed to react with the aldehyde of oxidized dextran (OD) through the Schiff-base reaction for the generation of hydrogels that have fast self-healing and injectable characteristics and adapt to the shapes of wounds. The prepared OD/EPL hydrogels promoted blood clotting in vitro and stopped bleeding in a rat liver injury model within 6 min through their platelet-aggregating ability and sealing effect. These hydrogels exhibited inherent antimicrobial effects without the use of antibiotics and effectively killed a broad spectrum of pathogenic microbes, including Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative Escherichia coli, and Pseudomonas aeruginosa and fungus Candida albicans in vitro. Moreover, these OD/EPL hydrogels were compatible with mammalian cells in vitro and in vivo and biodegradable in the mouse body. The loaded bFGF can be released sustainably, and it can promote angiogenesis, endothelial cell migration, and consequently accelerate the healing of wounds. The OD/EPL hydrogel inhibited MRSA infection in a rat full-thickness skin wound model and promoted healing. This kind of multifunctional hydrogel is a promising wound dressing for the emergency treatment of acute deep or penetrating injuries.