T Cells' Immunological Synapses Induce Polarization of Brain Astrocytes In Vivo and In Vitro: A Novel Astrocyte Response Mechanism to Cellular Injury

Astrocytes usually respond to trauma, stroke, or neurodegeneration by undergoing cellular hypertrophy, yet, their response to a specific immune attack by T cells is poorly understood. Effector T cells establish specific contacts with target cells, known as immunological synapses, during clearance of virally infected cells from the brain. Immunological synapses mediate intercellular communication between T cells and target cells, both in vitro and in vivo. How target virally infected astrocytes respond to the formation of immunological synapses established by effector T cells is unknown.Herein we demonstrate that, as a consequence of T cell attack, infected astrocytes undergo dramatic morphological changes. From normally multipolar cells, they become unipolar, extending a major protrusion towards the immunological synapse formed by the effector T cells, and withdrawing most of their finer processes. Thus, target astrocytes become polarized towards the contacting T cells. The MTOC, the organizer of cell polarity, is localized to the base of the protrusion, and Golgi stacks are distributed throughout the protrusion, reaching distally towards the immunological synapse. Thus, rather than causing astrocyte hypertrophy, antiviral T cells cause a major structural reorganization of target virally infected astrocytes.Astrocyte polarization, as opposed to hypertrophy, in response to T cell attack may be due to T cells providing a very focused attack, and thus, astrocytes responding in a polarized manner. A similar polarization of Golgi stacks towards contacting T cells was also detected using an in vitro allogeneic model. Thus, different T cells are able to induce polarization of target astrocytes. Polarization of target astrocytes in response to immunological synapses may play an important role in regulating the outcome of the response of astrocytes to attacking effector T cells, whether during antiviral (e.g. infected during HIV, HTLV-1, HSV-1 or LCMV infection), anti-transplant, autoimmune, or anti-tumor immune responses in vivo and in vitro

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Relative hypotension and adverse kidney-related outcomes among critically ill patients with shock a multicenter, prospective cohort study

Rationale: There are no prospective observational studies exploring the relationship between relative hypotension and adverse kidneyrelated outcomes among critically ill patients with shock. Objectives: To investigate the magnitude of relative hypotension during vasopressor support among critically ill patients with shock and to determine whether such relative hypotension is associated with new significant acute kidney injury (AKI) or major adverse kidney events (MAKE) within 14 days of vasopressor initiation. Methods: At seven multidisciplinary ICUs, 302 patients, aged >40 years and requiring >4 hours of vasopressor support for nonhemorrhagic shock, were prospectively enrolled.Weassessed the time-weighted average of the mean perfusion pressure (MPP) deficit (i.e., the percentage difference between patients' preillness basal MPP and achievedMPP)during vasopressor support and the percentage of time points with an MPP deficit.20% as key exposure variables. New significant AKI was defined as an AKI-stage increase of two or more (Kidney Disease: Improving Global Outcome creatinine-based criteria). Measurements and Main Results: The median MPP deficit was 19% (interquartile range, 13-25), and 54% (interquartile range, 19-82) of time points were spent with an MPP deficit.20%. Seventy-three (24%) patients developed new significant AKI; 86 (29%) patients developed MAKE. For every percentage increase in the time-weighted average MPP deficit, multivariable-adjusted odds of developing new significant AKI and MAKE increased by 5.6% (95% confidence interval, 2.2-9.1; P = 0.001) and 5.9% (95% confidence interval, 2.2-9.8; P = 0.002), respectively. Likewise, for every one-unit increase in the percentage of time points with an MPP deficit.20%, multivariable-adjusted odds of developing new significant AKI andMAKEincreased by 1.2% (0.3-2.2; P = 0.008) and 1.4% (0.4-2.4; P = 0.004), respectively. Conclusions: Vasopressor-treated patients with shock are often exposed to a significant degree and duration of relative hypotension, which is associated with new-onset, adverse kidney-related outcomes

An 85-ka record of climate change in lowland Central America

Drill cores obtained from Lake Petén Itzá, Petén, Guatemala, contain a ∼85-kyr record of terrestrial climate from lowland Central America that was used to reconstruct hydrologic changes in the northern Neotropics during the last glaciation. Sediments are composed of alternating clay and gypsum reflecting relatively wet and dry climate conditions, respectively. From ∼85 to 48 ka, sediments were dominated by carbonate clay indicating moist conditions during Marine Isotope Stages (MIS) 5a, 4, and early 3. The first gypsum layer was deposited at ∼48 ka, signifying a shift toward drier hydrologic conditions and the onset of wet–dry oscillations. During the latter part of MIS 3, Petén climate varied between wetter conditions during interstadials and drier states during stadials. The pattern of clay–gypsum (wet–dry) oscillations during the latter part of MIS 3 (∼48–23 ka) closely resembles the temperature records from Greenland ice cores and North Atlantic marine sediment cores and precipitation proxies from the Cariaco Basin. The most arid periods coincided with Heinrich Events when cold sea surface temperatures prevailed in the North Atlantic, meridional overturning circulation was reduced, and the Intertropical Convergence Zone (ITCZ) was displaced southward. A thick clay unit was deposited from 23 to 18 ka suggesting deposition in a deep lake, and pollen accumulated during the same period indicates vegetation consisted of a temperate pine-oak forest. This finding contradicts previous inferences that climate was arid during the Last Glacial Maximum (LGM) chronozone (21±2 ka). At ∼18 ka, Petén climate switched from moist to arid conditions and remained dry from 18 to 14.7 ka during the early deglaciation. Moister conditions prevailed during the warmer Bolling–Allerod (14.7–12.8 ka) with the exception of a brief return to dry conditions at ∼13.8 ka that coincides with the Older Dryas and meltwater pulse 1A. The onset of the Younger Dryas at 12.8 ka marked the return of gypsum and hence dry conditions. The lake continued to precipitate gypsum until ∼10.3 ka when rainfall increased markedly in the early Holocene

Re-evaluation of Climate Change in Lowland Central America During the Last Glacial Maximum Using New Sediment Cores from Lake Petén Itzá, Guatemala

Glaciological data derived from moraines, and multiproxy data from lake sediment cores (e.g. fossil pollen, diatoms, and isotope data) indicate cooling in the Central American tropics during the last ice age. Contrary to prior inferences, however, new lake core data from Lake Petén Itzá, lowland Guatemala, indicate that climate was not particularly dry on the Yucatan Peninsula during the last glacial maximum (LGM) chronozone, around 23,000–19,000 cal. yr BP. We present pollen and lithologic data from Lake Petén Itzá and an improved chronology for climate changes in lowland Central America over the last 25,000 years. The driest period of the last glaciation was not the LGM, but rather the deglacial period (∼18,000–11,000 cal. yr BP). Causes of climate shifts during the last glaciation are ascribed to precessional changes in insolation, the position of the Inter-Tropical Convergence Zone, and southward penetration of polar air masses