A novel role for myeloid endothelin-B receptors in hypertension

International audienceAIMS:Hypertension is common. Recent data suggest that macrophages (Mφ) contribute to, and protect from, hypertension. Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor with additional pro-inflammatory properties. We investigated the role of the ET system in experimental and clinical hypertension by modifying Mφ number and phenotype.METHODS AND RESULTS:In vitro, Mφ ET receptor function was explored using pharmacological, gene silencing, and knockout approaches. Using the CD11b-DTR mouse and novel mice with myeloid cell-specific endothelin-B (ETB) receptor deficiency (LysMETB-/-), we explored the effects of modifying Mφ number and phenotype on the hypertensive effects of ET-1, angiotensin II (ANG II), a model that is ET-1 dependent, and salt. In patients with small vessel vasculitis, the impacts of Mφ depleting and non-depleting therapies on blood pressure (BP) and endothelial function were examined. Mouse and human Mφ expressed both endothelin-A and ETB receptors and displayed chemokinesis to ET-1. However, stimulation of Mφ with exogenous ET-1 did not polarize Mφ phenotype. Interestingly, both mouse and human Mφ cleared ET-1 through ETB receptor mediated, and dynamin-dependent, endocytosis. Mφ depletion resulted in an augmented chronic hypertensive response to both ET-1 and salt. LysMETB-/- mice displayed an exaggerated hypertensive response to both ET-1 and ANG II. Finally, in patients who received Mφ depleting immunotherapy BP was higher and endothelial function worse than in those receiving non-depleting therapies.CONCLUSION:Mφ and ET-1 may play an important role in BP control and potentially have a critical role as a therapeutic target in hypertension

A novel role for myeloid endothelin-B receptors in hypertension

International audienceAIMS:Hypertension is common. Recent data suggest that macrophages (Mφ) contribute to, and protect from, hypertension. Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor with additional pro-inflammatory properties. We investigated the role of the ET system in experimental and clinical hypertension by modifying Mφ number and phenotype.METHODS AND RESULTS:In vitro, Mφ ET receptor function was explored using pharmacological, gene silencing, and knockout approaches. Using the CD11b-DTR mouse and novel mice with myeloid cell-specific endothelin-B (ETB) receptor deficiency (LysMETB-/-), we explored the effects of modifying Mφ number and phenotype on the hypertensive effects of ET-1, angiotensin II (ANG II), a model that is ET-1 dependent, and salt. In patients with small vessel vasculitis, the impacts of Mφ depleting and non-depleting therapies on blood pressure (BP) and endothelial function were examined. Mouse and human Mφ expressed both endothelin-A and ETB receptors and displayed chemokinesis to ET-1. However, stimulation of Mφ with exogenous ET-1 did not polarize Mφ phenotype. Interestingly, both mouse and human Mφ cleared ET-1 through ETB receptor mediated, and dynamin-dependent, endocytosis. Mφ depletion resulted in an augmented chronic hypertensive response to both ET-1 and salt. LysMETB-/- mice displayed an exaggerated hypertensive response to both ET-1 and ANG II. Finally, in patients who received Mφ depleting immunotherapy BP was higher and endothelial function worse than in those receiving non-depleting therapies.CONCLUSION:Mφ and ET-1 may play an important role in BP control and potentially have a critical role as a therapeutic target in hypertension

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

What the world could learn from the Haitian resilience while managing COVID-19

In the 1st trimester of 2020, there were mixed feelings among Haitians about the spread of the COVID-19 pandemic. In effect, many of the concerns emanating from the relatively weak health infrastructure in Haiti were analyzed from a resilience perspective. Many professionals living in Haiti with whom we have conversed believe that Haitians were better prepared to cope with the social distancing and mental health outcomes associated with the pandemic because of their 3-month exposure to the effects of Peyi Lòk ("country in lockdown") as well as previous major natural disasters. In that regard, previous traumatic exposures may serve as a buffer against the debilitating effects of the COVID-19 pandemic among Haitians. For the past 3 months, Haitians have naturally adopted a practical posture to cope with the pandemic where only school buildings are closed. Consequently, we remain convinced that from a psychological perspective, individuals from high-income countries that are severely affected by the COVID-19 pandemic could learn from the Haitian way of coping with large-scale disasters. (PsycInfo Database Record (c) 2020 APA, all rights reserved)

Rwanda's Resiliency During the Coronavirus Disease Pandemic

The coronavirus disease (COVID-19) pandemic has illustrated the wide range of preventative measures and responsive strategies of low- and middle-income countries (LMICs). LMICs have implemented lessons learned from previous periods of epidemics and uncertainties. Rwanda's pre-existing decentralized healthcare and mental health system which are in response to the mental health distress from the 1994 genocide, continues to be a formidable system that collaborate and combine efforts to address people's mental health needs. COVID-19 has heightened or exacerbated people's mental health within the country. Rwandans have been exposed to and endured adversities, yet their cultural forms of resilience serve as a mental health protective factor to also overcome COVID-19. Nonetheless, Rwanda has engaged in interventions targeting public safety, social and economic protection that specifically address vulnerable communitie's mental health needs. Lessons from preparedness for the Ebola virus disease (EVD) epidemic has contributed to Rwanda's organization and approach to combating COVID-19. Policies and best practices that were enacted during the EVD outbreak have guided Rwanda's response within the healthcare and mental health system. Coincidentally, this outbreak emerged during the 26th commemoration of the 1994 genocide against the Tutsi. Although for the first-time post genocide, Rwanda was not able to engage in public traditional forms of collective mourning and community healing, evidence of Rwandan's resilient spirit is demonstrated. Community resilience has been defined by Magis [401] as the "existence, development and engagement of community resources by community members to thrive in an environment characterized by change, uncertainty, unpredictability and surprise. ". Referring to this definition, community resilience has been an interwoven into the cultural framework that guided Rwandans in past challenges and continues to be evident now. Rwanda's resilience throughout this pandemic remains through ongoing psychoeducation, community awareness of mental health concerns, collective messages of highlighting mental health support, and solidarity. The global community can gain knowledge from Rwanda's learned lessons of their past which has positioned itself to stand on its resilient values in times of uncertainty such as COVID-19 and endeavor to overcome through national cohesion

Mental Health Among Children Older than 10 Years Exposed to the Haiti 2010 Earthquake: a Critical Review

Purpose of Review There is evidence that the exposure to a major natural disaster such as the 2010 earthquake in Haiti may have devastating short- and long-term effects on children's mental health and overall development. This review summarizes what has been reported in the past 3 years (2017-2020) regarding emotional, psychological, and behavioral effects of exposure to this particular earthquake on children 10 years and older. Recent Findings Twenty-six articles were screened, of which twenty-one were selected for final analysis. The main themes addressed in the literature over the 3 years concerned prevalence of post-traumatic stress disorder (PTSD), depression, determinants of resilience factors, prevalence of sexual violence as well as prenatal exposure, and subsequent autism behaviors/symptoms. The majority of the findings analyzed in this review on mental health in young Haitian survivors of the 2010 earthquake came from cross-sectional studies conducted in West region of Haiti, spefically Port-au-Prince. There was a paucity of longitudinal and translational data available. The results of this critical review can be used to inform disaster preparedness programs with the aim of protecting children's development and mental health, which are much needed on this disaster-prone island

The Herschel-SPIRE Legacy Survey (HSLS): the scientific goals of a shallow and wide submillimeter imaging survey with SPIRE

A large sub-mm survey with Herschel will enable many exciting science opportunities, especially in an era of wide-field optical and radio surveys and high resolution cosmic microwave background experiments. The Herschel-SPIRE Legacy Survey (HSLS), will lead to imaging data over 4000 sq. degrees at 250, 350, and 500 micron. Major Goals of HSLS are: (a) produce a catalog of 2.5 to 3 million galaxies down to 26, 27 and 33 mJy (50% completeness; 5 sigma confusion noise) at 250, 350 and 500 micron, respectively, in the southern hemisphere (3000 sq. degrees) and in an equatorial strip (1000 sq. degrees), areas which have extensive multi-wavelength coverage and are easily accessible from ALMA. Two thirds of the of the sources are expected to be at z > 1, one third at z > 2 and about a 1000 at z > 5. (b) Remove point source confusion in secondary anisotropy studies with Planck and ground-based CMB data. (c) Find at least 1200 strongly lensed bright sub-mm sources leading to a 2% test of general relativity. (d) Identify 200 proto-cluster regions at z of 2 and perform an unbiased study of the environmental dependence of star formation. (e) Perform an unbiased survey for star formation and dust at high Galactic latitude and make a census of debris disks and dust around AGB stars and white dwarfs

The Herschel-SPIRE Legacy Survey (HSLS): the scientific goals of a shallow and wide submillimeter imaging survey with SPIRE

White paper supplement to the proposal submitted by the HSLS science team to ESA for Herschel open-time programsA large sub-mm survey with Herschel will enable many exciting science opportunities, especially in an era of wide-field optical and radio surveys and high resolution cosmic microwave background experiments. The Herschel-SPIRE Legacy Survey (HSLS), will lead to imaging data over 4000 sq. degrees at 250, 350, and 500 micron. Major Goals of HSLS are: (a) produce a catalog of 2.5 to 3 million galaxies down to 26, 27 and 33 mJy (50% completeness; 5 sigma confusion noise) at 250, 350 and 500 micron, respectively, in the southern hemisphere (3000 sq. degrees) and in an equatorial strip (1000 sq. degrees), areas which have extensive multi-wavelength coverage and are easily accessible from ALMA. Two thirds of the of the sources are expected to be at z > 1, one third at z > 2 and about a 1000 at z > 5. (b) Remove point source confusion in secondary anisotropy studies with Planck and ground-based CMB data. (c) Find at least 1200 strongly lensed bright sub-mm sources leading to a 2% test of general relativity. (d) Identify 200 proto-cluster regions at z of 2 and perform an unbiased study of the environmental dependence of star formation. (e) Perform an unbiased survey for star formation and dust at high Galactic latitude and make a census of debris disks and dust around AGB stars and white dwarfs