Cell-cell communication, which enables cells to coordinate their activity and is essential for growth, development and function, is usually ascribed a chemical or electrical origin. However, cells can exert forces and respond to environment elasticity and to mechanical deformations created by their neighbours 1-13 . The extent to which this mechanosensing ability facilitates intercellular communication remains unclear. Here we demonstrate mechanical communication between cells directly for the first time, providing evidence for a long-range interaction that induces long-lasting alterations in interacting cells. We show that an isolated cardiac cell can be trained to beat at a given frequency by mechanically stimulating the underlying substrate. Deformations are induced using an oscillatory mechanical probe that mimics the deformations generated by a beating neighbouring cardiac cell. Unlike electrical field stimulation, the probe-induced beating rate is maintained by the cell for an hour after the stimulation stops, implying that long-term modifications occur within the cell. These long-term alterations provide a mechanism for cells that communicate mechanically to be less variable in their electromechanical delay. Mechanical coupling between cells therefore ensures that the final outcome of action potential pacing is synchronized beating. We further show that the contractile machinery is essential for mechanical communication.Here we sought to separate the mechanical component of intercellular communication from indirect effects, such as a change in the amount or type of secreted chemo-attractants. We did so by introducing a 'mechanical cell' . The 'mechanical cell' consists of a probe that mimics the mechanical aspect of a cell by generating substrate deformations identical to the ones induced by a neighbouring beating cell. Previous studies have shown that mechanical stimulation of a quiescent cell or an engineered cardiac construct can induce beating 12,14 . However, in those studies, the magnitude and direction of forces applied were not controlled as to mimic the magnitude and direction of forces applied by cells. In addition, the duration of stimulation was extremely brief and the cells did not synchronize with the probe. These studies therefore did not provide a demonstration or characterization of cellular mechanical communication.Here, we use a 'mechanical cell' to apply deformations identical to those generated by an aligned beating cardiac cell both in magnitude and in directionality. We show that such deformations can synchronize cell beating. This provides clear evidence for mechanical cellular communication. Training of both quiescent and spontaneously beating cells takes up to 10-15 min and the induced beating frequency persists for over an hour after stimulation had stopped. These results demonstrate that mechanical communication is a unique type of interaction that is both long ranged and induces long-lasting alterations in interacting cells. We further demonstrate that mechanical communication...
SARS-CoV-2 is an RNA virus, a member of the coronavirus family of respiratory viruses that includes SARS-CoV-1 and MERS. COVID-19, the clinical syndrome caused by SARS-CoV-2, has evolved into a global pandemic with more than 2,900,000 people infected. It has had an acute and dramatic impact on health care systems, economies, and societies of affected countries within these few months. Widespread testing and tracing efforts are employed in many countries in order to contain and mitigate this pandemic. Recent data has indicated that fecal shedding of SARS-CoV-2 is common, and that the virus can be detected in wastewater. This indicates that wastewater monitoring is a potentially efficient tool for epidemiological surveillance of SARS-CoV-2 infection in large populations at relevant scales. Collecting raw sewage data, representing specific districts, and crosslinking this data with the number of infected people from each location, will enable us to derive and provide quantitative surveillance tools. In particular, this will provide important means to (i) estimate the extent of outbreaks and their spatial distributions, based primarily on in-sewer measurements (ii) manage the early-warning system quantitatively and efficiently (and similarly, verify disease elimination). Here we report the development of a virus concentration method using PEG or alum, providing an important a tool for detection of SARS-CoV-2 RNA in sewage and relating it to the local populations and geographic information. This will provide a proof of concept for the use of sewage associated virus data as a reliable epidemiological tool.
On February 26, 2021, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr). The availability of COVID-19 vaccines represents an opportunity to mitigate the effects of the global pandemic. Achieving high vaccination coverage through intensive vaccination campaigns has the potential to substantially reduce COVID-19-associated morbidity and mortality. Clinical trials have demonstrated the efficacy of COVID-19 vaccines in preventing mild and severe COVID-19 in a controlled setting. However, clinical trials are not designed to assess the population impact of vaccination in a real-world setting (1,2). Israel initiated a national vaccination campaign using the Pfizer-BioNTech BNT162b2 (Pfizer-BioNTech) vaccine in December 2020, prioritizing persons aged >60 years, health care workers, and persons with underlying medical conditions. By February 2021, 2-dose vaccination coverage among persons aged ≥70 years was 84%. To assess the effect of COVID-19 vaccination on the occurrence of severe disease, an ecological study was conducted. Requiring mechanical ventilation was used as a proxy for severe COVID-19. The number of COVID-19 patients aged ≥70 years (who had the highest 2-dose vaccination coverage, 84.3%) requiring mechanical ventilation was compared with that of patients aged <50 years, who had the lowest 2-dose vaccination coverage (9.9%). Since implementation of the second dose of the vaccination campaign, the ratio of COVID-19 patients requiring mechanical ventilation aged ≥70 years to those aged <50 years has declined 67%, from 5.8:1 during October-December 2020 to 1.9:1 in February 2021. These findings provide preliminary evidence of the effectiveness of vaccines in preventing severe cases of COVID-19 at the national level in Israel. Receipt of COVID-19 vaccines by eligible persons can help limit spread of disease and potentially reduce the occurrence of severe disease. The first case of COVID-19 in Israel, a country with a population of approximately 9 million, was reported in February 2020. As of February 9, 2021, approximately 700,000 cases and 5,200 deaths had been reported (3). Nonpharmaceutical interventions have included three national stay-at-home orders, † multiple rounds of school closures, restrictions on commercial activity and travel, and a mask mandate, among others. The most recent
Objective To analyze the correlation between COVID-19 vaccination percentage and socioeconomic status (SES). Methods A nationwide ecologic study based on open-sourced, anonymized, aggregated data provided by the Israel Ministry of Health. The correlations between municipal SES, vaccination percentage, and active COVID-19 cases during the vaccination campaign were analyzed by using weighted Pearson correlations. To assess the adequacy of first dose vaccination rollout relative to the municipality COVID-19 disease burden, a metric termed the vaccination need ratio was devised by dividing the total number of active cases (per 10,000 people) by the vaccination percentage of the population over 60 in each municipality, and its correlation with the SES was examined. Results 23 days after initiation of the vaccination campaign, 760,916 (56.8%) individuals over the age of 60 were vaccinated in Israel with the first dose of the BNT162b2 COVID-19 vaccine. A negative correlation was found between the COVID-19 active case burden and the vaccination percentage of the study population in each municipality (r=-0.47, 95% confidence interval [-0.59 to -0.30]). The vaccination percentage significantly correlated with the municipal SES (r=0.83, 95% confidence interval [0.79 to 0.87]). This finding persisted but was attenuated over a five-week period. A negative correlation between the vaccination need ratio and municipal SES (r=-0.80, 95% confidence interval [-0.88 to -0.66]) was found. Conclusion Lower COVID-19 vaccination percentage was associated with lower SES and high active disease burden. Vaccination efforts should focus on areas with lower SES and high disease burden to assure equality of vaccine allocation and potentially provide a more diligent disease mitigation.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus, a member of the coronavirus family of respiratory viruses that includes severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East respiratory syndrome (MERS). It has had an acute and dramatic impact on health care systems, economies, and societies of affected countries during the past 8 months. Widespread testing and tracing efforts are being employed in many countries in attempts to contain and mitigate this pandemic. Recent data has indicated that fecal shedding of SARS-CoV-2 is common and that the virus RNA can be detected in wastewater. This indicates that wastewater monitoring may provide a potentially efficient tool for the epidemiological surveillance of SARS-CoV-2 infection in large populations at relevant scales. In particular, this provides important means of (i) estimating the extent of outbreaks and their spatial distributions, based primarily on in-sewer measurements, (ii) managing the early-warning system quantitatively and efficiently, and (iii) verifying disease elimination. Here we report different virus concentration methods using polyethylene glycol (PEG), alum, or filtration techniques as well as different RNA extraction methodologies, providing important insights regarding the detection of SARS-CoV-2 RNA in sewage. Virus RNA particles were detected in wastewater in several geographic locations in Israel. In addition, a correlation of virus RNA concentration to morbidity was detected in Bnei-Barak city during April 2020. This study presents a proof of concept for the use of direct raw sewage-associated virus data, during the pandemic in the country as a potential epidemiological tool.
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