Long-Term, CD4+ Memory T Cell Response to SARS-CoV-2.

The first cases of coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were reported by Chinese authorities at the end of 2019. The disease spread quickly and was declared a global pandemic shortly thereafter. To respond effectively to infection and prevent viral spread, it is important to delineate the factors that affect protective immunity. Herein, a cohort of convalescent healthcare workers was recruited and their immune responses were studied over a period of 3 to 9 months following the onset of symptoms. A cross-reactive T cell response to SARS-CoV-2 and endemic coronaviruses, i.e., OC43 and NL63, was demonstrated in the infected, convalescent cohort, as well as a cohort composed of unexposed individuals. The convalescent cohort, however, displayed an increased number of SARS-CoV-2-specific CD4+ T cells relative to the unexposed group. Moreover, unlike humoral immunity and quickly decreasing antibody titers, T cell immunity in convalescent individuals was maintained and stable throughout the study period. This study also suggests that, based on the higher CD4 T cell memory response against nucleocapsid antigen, future vaccine designs may include nucleocapsid as an additional antigen along with the spike protein.

The influence of posttraumatic stress disorder numbing and hyperarousal symptom clusters in the prediction of physical health status in veterans with chronic tobacco dependence and posttraumatic stress disorder.

Smoking and PTSD are predictors of poor physical health status. This study examined the unique contribution of PTSD symptoms in the prediction of the SF-36 physical health status subscales accounting for cigarette smoking, chronic medical conditions, alcohol and drug use disorders, and depression. This study examined baseline interview and self-report data from a national tobacco cessation randomized, controlled trial (Veterans Affairs Cooperative Study 519) that enrolled tobacco-dependent veterans with chronic PTSD (N = 943). A series of blockwise multiple regression analyses indicated that PTSD numbing and hyperarousal symptom clusters explained a significant proportion of the variance across all physical health domains except for the Physical Functioning subscale, which measures impairments in specific physical activities. Our findings further explain the impact of PTSD on health status by exploring the way PTSD symptom clusters predict self-perceptions of health, role limitations, pain, and vitality.

PTSD, combat injury, and headache in Veterans Returning from Iraq/Afghanistan.

OBJECTIVE: To examine the relationship between posttraumatic stress disorder, combat injury, and headache in Operation Iraqi Freedom and Operation Enduring Freedom veterans at the VA San Diego Healthcare System. BACKGROUND: Previous investigations suggest that a relationship between posttraumatic stress disorder and primary headache disorders exists and could be complicated by the contribution of physical injury, especially one that results in loss of consciousness. These associations have not been systematically examined in Operation Iraqi Freedom and Operation Enduring Freedom veterans. METHODS: In this observational cross-sectional study, a battery of self-report, standardized questionnaires was completed by 308 newly registered veterans between March and October 2006. The Davidson Trauma Scale was used to determine the degree of posttraumatic stress disorder symptoms and combat-related physical injury was assessed by self-report. The presence of headache was based on a symptom checklist measure and self-reported doctor diagnoses. Logistic regression analysis was performed to predict presence of headache and determine odds ratios and 95% confidence intervals associated with demographic, military, in-theatre, and mental health characteristics. RESULTS: About 40% of the veterans met the criteria for posttraumatic stress disorder; 40% self-reported current headache, 10% reported a physician diagnosis of migraine, 12% a physician diagnosis of tension-type headache, and 6% reported both types of headache. Results from the logistic regression model indicated that combat-related physical injury (odds ratio: 2.25; 95% confidence interval: 1.17-4.33) and posttraumatic stress disorder (odds ratio: 4.13; 95% confidence interval: 2.44-6.99) were independent predictors of self-reported headache. Additional analyses found that veterans with both tension and migraine headache had higher rates of posttraumatic stress disorder (chi-square [d.f. = 3] = 15.89; P = .001) whereas veterans with migraine headache alone had higher rates of combat-related physical injury (chi-square [d.f. = 9] = 22.00; P = .009). CONCLUSION: Posttraumatic stress disorder and combat-related physical injury were related to higher rates of self-reported headache in newly returning veterans. Our finding that posttraumatic stress disorder and injury during combat are differentially related to migraine and tension-type headache, point to a complex relationship between physical and psychological trauma and headache. These findings have implications for a comprehensive approach to interventions for headache and the physical and psychological sequelae of trauma.

Trauma exposure, branch of service, and physical injury in relation to mental health among U.S. veterans returning from Iraq and Afghanistan.

Significant mental health symptoms are reported in troops deployed to Iraq and Afghanistan (OEF/OIF). Symptomatic troops are more likely to be discharged and become eligible for Department of Veterans Affairs (DVA) care. Prevalence and predictors of mental health symptoms were assessed in 339 OEF/OIF veterans and reservists registering at the San Diego DVA. Participants completed self-report questionnaires assessing combat exposure, posttraumatic stress disorder (PTSD) symptom frequency and severity, depression, and substance and alcohol abuse. A minority of participants (36%) did not screen positive for mental health symptoms; the remainder met threshold for caseness of PTSD, depression, or substance and alcohol abuse. Using a hierarchical logistic regression model, gender, age, race, and rank were not significantly related to PTSD caseness, whereas most recent branch of service and report of injury during combat were. Follow-up analyses revealed that trauma history and combat exposure varied by branch of service. Knowledge of base rates and vulnerability factors can aid in rapid detection of "at risk" individuals.

A Method for Determination and Simulation of Permeability and Diffusion in a 3D Tissue Model in a Membrane Insert System for Multi-well Plates.

In vitro cultivated skin models have become increasingly relevant for pharmaceutical and cosmetic applications, and are also used in drug development as well as substance testing. These models are mostly cultivated in membrane-insert systems, their permeability toward different substances being an essential factor. Typically, applied methods for determination of these parameters usually require large sample sizes (e.g., Franz diffusion cell) or laborious equipment (e.g., fluorescence recovery after photobleaching (FRAP)). This study presents a method for determining permeability coefficients directly in membrane-insert systems with diameter sizes of 4.26 mm and 12.2 mm (cultivation area). The method was validated with agarose and collagen gels as well as a collagen cell model representing skin models. The permeation processes of substances with different molecular sizes and permeation through different cell models (consisting of collagen gel, fibroblast, and HaCaT) were accurately described. Moreover, to support the above experimental method, a simulation was established. The simulation fits the experimental data well for substances with small molecular size, up to 14 x 10-10 m Stokes radius (4,000 MW), and is therefore a promising tool to describe the system. Furthermore, the simulation can considerably reduce experimental efforts and is robust enough to be extended or adapted to more complex setups.