Differential cellular and humoral immune responses in immunocompromised individuals following multiple SARS-CoV-2 vaccinations

Introduction: The heterogeneity of the immunocompromised population means some individuals may exhibit variable, weak or reduced vaccine-induced immune responses, leaving them poorly protected from COVID-19 disease despite receiving multiple SARS-CoV-2 vaccinations. There is conflicting data on the immunogenicity elicited by multiple vaccinations in immunocompromised groups. The aim of this study was to measure both humoral and cellular vaccine-induced immunity in several immunocompromised cohorts and to compare them to immunocompetent controls. Methods: Cytokine release in peptide-stimulated whole blood, and neutralising antibody and baseline SARS-CoV-2 spike-specific IgG levels in plasma were measured in rheumatology patients (n=29), renal transplant recipients (n=46), people living with HIV (PLWH) (n=27) and immunocompetent participants (n=64) post third or fourth vaccination from just one blood sample. Cytokines were measured by ELISA and multiplex array. Neutralising antibody levels in plasma were determined by a 50% neutralising antibody titre assay and SARS-CoV-2 spike specific IgG levels were quantified by ELISA. Results: In infection negative donors, IFN-γ, IL-2 and neutralising antibody levels were significantly reduced in rheumatology patients (p=0.0014, p=0.0415, p=0.0319, respectively) and renal transplant recipients (p<0.0001, p=0.0005, p<0.0001, respectively) compared to immunocompetent controls, with IgG antibody responses similarly affected. Conversely, cellular and humoral immune responses were not impaired in PLWH, or between individuals from all groups with previous SARS-CoV-2 infections. Discussion: These results suggest that specific subgroups within immunocompromised cohorts could benefit from distinct, personalised immunisation or treatment strategies. Identification of vaccine non-responders could be critical to protect those most at risk

Salve Regina University Act on Climate: Strategic Plan for the University to Reach State Carbon Neutrality Goals

In order to become more sustainable and meet the mandate set by the 2021 Rhode Island Act on Climate law (RI General Law §42-6.2), Salve Regina University must work to reach net-zero greenhouse gas emissions by the year 2050. Action to meet these standards begins now and must be continually built upon to ensure that Salve Regina University, as leader in Rhode Island, is always working for a more sustainable future. Throughout the Spring 2022 semester, students of the BIO-140: Humans and Their Environment course instructed by Dr. Jameson Chace have researched ways in which Salve Regina can begin on the path to zero greenhouse gas emissions today. By focusing on change in the areas of energy, transportation, food, financial investments, and sequestration, Salve Regina can reduce the greenhouse gas emissions of today for a more sustainable tomorrow. Recommendations are broken into three time periods. Action for today to achieve by 2030 include improving energy efficiency, installing the first electric vehicle (EV) parking/charging stations, increasing carbon sequestration, reducing beef in the campus diet, and assessing the carbon impact of university financial holdings. Actions to be initiated soon and to be achieved by 2040 include shifting away from natural gas heating when system renewals take place, increasing EV parking to meet rising demand, during turnover replace current university vehicles with electric or hybrid, continuing with sequestration efforts on campus, begin phasing out high carbon diet items, and by 2040 the university investment portfolio should be carbon neutral. If carbon neutrality can be reached by 2050 the most challenging aspects of campus life that need to change will require planning now and thoughtful implementation. The class in 2022 envisions a campus in 2050 where solar lights illuminate campus and buildings through the night, all university vehicles and most faculty and staff vehicles are electric and are found charging during the day at solar powered charging stations, dining services in Miley supports community agriculture and includes incentives for meatless and low carbon meal plans, the university has become a leader in low carbon/green market investing demonstrating how careful planning can reap high returns, and carbon sequestration on campus grounds has maximized such that off campus carbon offsets are established with local land trusts to complete the carbon neutrality goals. In doing so no only will the university be recognized as a state-wide leader in climate action, but will also be a global leader in working towards a world that is more harmonious, just, and merciful.https://digitalcommons.salve.edu/bio140_arboretum/1033/thumbnail.jp

Aberrant cortical development is driven by impaired cell cycle and translational control in a DDX3X syndrome model.

Mutations in the RNA helicase, DDX3X, are a leading cause of Intellectual Disability and present as DDX3X syndrome, a neurodevelopmental disorder associated with cortical malformations and autism. Yet, the cellular and molecular mechanisms by which DDX3X controls cortical development are largely unknown. Here, using a mouse model of Ddx3x loss-of-function we demonstrate that DDX3X directs translational and cell cycle control of neural progenitors, which underlies precise corticogenesis. First, we show brain development is sensitive to Ddx3x dosage; complete Ddx3x loss from neural progenitors causes microcephaly in females, whereas hemizygous males and heterozygous females show reduced neurogenesis without marked microcephaly. In addition, Ddx3x loss is sexually dimorphic, as its paralog, Ddx3y, compensates for Ddx3x in the developing male neocortex. Using live imaging of progenitors, we show that DDX3X promotes neuronal generation by regulating both cell cycle duration and neurogenic divisions. Finally, we use ribosome profiling in vivo to discover the repertoire of translated transcripts in neural progenitors, including those which are DDX3X-dependent and essential for neurogenesis. Our study reveals invaluable new insights into the etiology of DDX3X syndrome, implicating dysregulated progenitor cell cycle dynamics and translation as pathogenic mechanisms

Salve Regina University Act on Climate: Strategic Plan for the University to Reach State Carbon Neutrality Goals

In order to become more sustainable and meet the mandate set by the 2021 Rhode Island Act on Climate law (RI General Law §42-6.2), Salve Regina University must work to reach net-zero greenhouse gas emissions by the year 2050. Action to meet these standards begins now and must be continually built upon to ensure that Salve Regina University, as leader in Rhode Island, is always working for a more sustainable future. Throughout the Spring 2022 semester, students of the BIO-140: Humans and Their Environment course instructed by Dr. Jameson Chace have researched ways in which Salve Regina can begin on the path to zero greenhouse gas emissions today. By focusing on change in the areas of energy, transportation, food, financial investments, and sequestration, Salve Regina can reduce the greenhouse gas emissions of today for a more sustainable tomorrow. Recommendations are broken into three time periods. Action for today to achieve by 2030 include improving energy efficiency, installing the first electric vehicle (EV) parking/charging stations, increasing carbon sequestration, reducing beef in the campus diet, and assessing the carbon impact of university financial holdings. Actions to be initiated soon and to be achieved by 2040 include shifting away from natural gas heating when system renewals take place, increasing EV parking to meet rising demand, during turnover replace current university vehicles with electric or hybrid, continuing with sequestration efforts on campus, begin phasing out high carbon diet items, and by 2040 the university investment portfolio should be carbon neutral. If carbon neutrality can be reached by 2050 the most challenging aspects of campus life that need to change will require planning now and thoughtful implementation. The class in 2022 envisions a campus in 2050 where solar lights illuminate campus and buildings through the night, all university vehicles and most faculty and staff vehicles are electric and are found charging during the day at solar powered charging stations, dinning services in Miley supports community agriculture and includes incentives for meatless and low carbon meal plans, the university has become a leader in low carbon/green market investing demonstrating how careful planning can reap high returns, and carbon sequestration on campus grounds has maximized such that off campus carbon offsets are established with local land trusts to complete the carbon neutrality goals. In doing so no only will the university be recognized as a state-wide leader in climate action, but will also be a global leader in working towards a world that is more harmonious, just, and merciful

Salve Regina University Act on Climate: Strategic Plan for the University to Reach State Carbon Neutrality Goals

In order to become more sustainable and meet the mandate set by the 2021 Rhode Island Act on Climate law (RI General Law §42-6.2), Salve Regina University must work to reach net-zero greenhouse gas emissions by the year 2050. Action to meet these standards begins now and must be continually built upon to ensure that Salve Regina University, as leader in Rhode Island, is always working for a more sustainable future. Throughout the Spring 2022 semester, students of the BIO-140: Humans and Their Environment course instructed by Dr. Jameson Chace have researched ways in which Salve Regina can begin on the path to zero greenhouse gas emissions today. By focusing on change in the areas of energy, transportation, food, financial investments, and sequestration, Salve Regina can reduce the greenhouse gas emissions of today for a more sustainable tomorrow. Recommendations are broken into three time periods. Action for today to achieve by 2030 include improving energy efficiency, installing the first electric vehicle (EV) parking/charging stations, increasing carbon sequestration, reducing beef in the campus diet, and assessing the carbon impact of university financial holdings. Actions to be initiated soon and to be achieved by 2040 include shifting away from natural gas heating when system renewals take place, increasing EV parking to meet rising demand, during turnover replace current university vehicles with electric or hybrid, continuing with sequestration efforts on campus, begin phasing out high carbon diet items, and by 2040 the university investment portfolio should be carbon neutral. If carbon neutrality can be reached by 2050 the most challenging aspects of campus life that need to change will require planning now and thoughtful implementation. The class in 2022 envisions a campus in 2050 where solar lights illuminate campus and buildings through the night, all university vehicles and most faculty and staff vehicles are electric and are found charging during the day at solar powered charging stations, dinning services in Miley supports community agriculture and includes incentives for meatless and low carbon meal plans, the university has become a leader in low carbon/green market investing demonstrating how careful planning can reap high returns, and carbon sequestration on campus grounds has maximized such that off campus carbon offsets are established with local land trusts to complete the carbon neutrality goals. In doing so no only will the university be recognized as a state-wide leader in climate action, but will also be a global leader in working towards a world that is more harmonious, just, and merciful

Management of coronary disease in patients with advanced kidney disease

BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction

Health status after invasive or conservative care in coronary and advanced kidney disease

BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of &lt;30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, 120.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, 122.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, 121.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, 122.2 to 3.4). CONCLUSIONS Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used