Systemic immune response to a CD40 agonist antibody in nonhuman primates.

The cell surface molecule CD40 is a member of the tumor necrosis factor receptor superfamily and is broadly expressed by immune cells including B cells, dendritic cells, and monocytes, as well as other normal cells and some malignant cells. CD40 is constitutively expressed on antigen-presenting cells, and ligation promotes functional maturation, leading to an increase in antigen presentation and cytokine production, and a subsequent increase in the activation of antigen-specific T cells. It is postulated that CD40 agonists can mediate both T cell-dependent and T cell-independent immune mechanisms of tumor regression in mice and patients.

A fiducial-based confidence interval for the linear combination of multinomial probabilities.

Across a broad set of applications, system outcomes may be summarized as probabilities in confusion or contingency tables. In settings with more than two outcomes (e.g.

Classification of EEG Signals Reveals a Focal Aftereffect of 10 Hz Motor Cortex Transcranial Alternating Current Stimulation.

Transcranial alternating current stimulation (tACS) modulates oscillations in a frequency- and location-specific manner and affects cognitive and motor functions. This effect appears during stimulation as well as "offline," following stimulation, presumably reflecting neuroplasticity. Whether tACS produces long-lasting aftereffects that are physiologically meaningful, is still of current debate.

Alpha oscillations modulate premotor-cerebellar connectivity in motor learning: Insights from transcranial alternating current stimulation.

Alpha oscillations (8-13 Hz) have been suggested to play an important role in dynamic neural processes underlying learning and memory. The goal of this study was to scrutinize the role of alpha oscillations in communication within a cortico-cerebellar network implicated in motor sequence learning. To this end, we conducted two EEG experiments using a serial reaction time task.

MMP9 mRNA is a potential diagnostic and treatment monitoring marker for PTSD: Evidence from mice and humans.

Although matrix metalloproteinase 9 (MMP9) has been found associated with various psychiatric disorders and with threat memories in humans, its role in post-traumatic stress disorder (PTSD) and related animal models is understudied. Thus, we analyzed MMP9 mRNA expression kinetics during two different stress experiments, i.e.

Oxytocin receptor is a potential biomarker of the hyporesponsive HPA axis subtype of PTSD and might be modulated by HPA axis reactivity traits in humans and mice.

This study aimed to identify yet unavailable blood biomarkers for the responsive and the hyporesponsive hypothalamic-pituitary-adrenal (HPA) axis subtypes of posttraumatic stress disorder (PTSD). As, I, we recently discovered the intranasal neuropeptide oxytocin to reduce experimentally provoked PTSD symptoms, II, expression of its receptor (OXTR) has hitherto not been assessed in PTSD patients, and III, oxytocin and OXTR have previously been related to the HPA axis, we considered both as suitable candidates. During a Trier Social Stress Test (TSST), we compared serum oxytocin and blood OXTR mRNA concentrations between female PTSD patients, their HPA axis reactivity subtypes and sex and age-matched healthy controls (HC).

The Relationship between Pet Ownership, Social Support, and Internalizing Symptoms in Students from the First to Fourth Year of College.

Internalizing symptoms are prevalent in students as they enter and complete college. Considering research suggesting mental health benefits of pet ownership, this study explores the relationship between pet ownership, social support (SS), and internalizing symptoms (IS) in a cohort of students across their 4-year college experience. With no differences at college entry, students growing up with pets had greater IS through the fourth year, and greater SS through the third year, than those without pets.

Posttraumatic growth during cognitive behavioural therapy for posttraumatic stress disorder: Relationship to symptom change and introduction of significant other assessment.

Posttraumatic growth (PTG) may play a role in the treatment of posttraumatic stress disorder (PTSD) as it is supposed to have either beneficial or dysfunctional effects on treatment-related PTS symptom (PTSS) changes. This study examined whether cognitive behavioral therapy (CBT) for PTSD patients can foster PTG assessed by self-reports and reports from significant others. Forty-eight PTSD patients participating in trauma-focused CBT were assessed twice: at the beginning of therapy (T1) and after 3 months of therapy (T2, N = 34).

Choosing between the BP and BN sequential strategies.

Cost and burden of diagnostic testing may be reduced if fewer tests can be applied. Sequential testing involves selecting a sequence of tests, but only administering subsequent tests dependent on results of previous tests. This research provides guidance to choosing between single tests or the believe the positive (BP) and believe the negative (BN) sequential testing strategies, using accuracy (as measured by the Youden Index) as the primary determinant.

OR Time and Sacral Pressure Injuries in Critically Ill Surgical Patients.

Critically ill patients are at risk for developing pressure injuries during operative and other invasive procedures. The purpose of this secondary analysis was to explore the relationship of OR time to sacral pressure injuries in critically ill patients using high frequency ultrasound as a method of assessment. The 41 participants examined in this study had both time in the OR and up to eight days of pressure injury data.

PTSD psychotherapy improves blood pressure but leaves HPA axis feedback sensitivity stable and unaffected: First evidence from a pre-post treatment study.

Although key to development of tailored drugs for augmentation treatment of psychotherapy for posttraumatic stress disorder (PTSD), the biological correlates of PTSD remission are still unknown, probably because pre-post treatment studies searching for them are rare. Not even the feedback sensitivity of the otherwise well-studied hypothalamic-pituitary-adrenal (HPA) axis nor arterial blood pressure (BP), which was previously reported to be elevated in PTSD patients, have so far been analyzed during PTSD treatment. To narrow this knowledge gap, we first performed an overnight dexamethasone suppression test (DST) in a mixed-sex cohort of 25 patients with severe PTSD vs.

Lack of Association of High Backrest With Sacral Tissue Changes in Adults Receiving Mechanical Ventilation.

Background: Although higher backrest elevation may be a theoretical risk for integrity of sacral tissues, few data support use of high backrest elevation.

Objective: To describe the effect of backrest elevation on the integrity of sacral tissue in critically ill adults receiving mechanical ventilation.

Methods: Patients from 3 critical care units (surgical trauma, medical respiratory, and neuroscience) who were expected to have mechanical ventilation for at least 24 hours were intubated and mechanical ventilation was started.

High-Frequency Ultrasound: Obtaining Optimal Images and the Effect of Image Artifacts on Image Quality.

High-frequency ultrasound (HFUS) images are being researched for use in the prevention, detection, and monitoring of pressure injuries in patients at risk. This seminal longitudinal study in mechanically ventilated adults describes image quality, the incidence of image artifacts, and their effect on image quality in critically ill subjects. Mechanically ventilated subjects from three adult intensive care units were enrolled, and multiple sacral images from each subject were obtained daily.

Reproductive and developmental toxicology studies with gantenerumab in PS2APP transgenic mice.

Gantenerumab is intended for the treatment of Alzheimer's disease. It is a fully human recombinant monoclonal IgG1 which binds aggregated forms of amyloid beta such as Aβ oligomers, fibrils and neuritic amyloid plaques. A full package of developmental and reproductive toxicity (DART) studies was performed in the PS2APP double-transgenic mouse model of Alzheimer's disease.

High-Frequency Ultrasound: Description of Sacral Tissue Characteristics in Healthy Adults.

Objectives: The purpose of this study was to describe selected sacral tissue characteristics in a convenience sample of healthy volunteer subjects.

Design: Descriptive.

Sample And Setting: Fifty healthy volunteers in a clinical learning center in a school of nursing.

Comparative assessment of immune complex-mediated hypersensitivity reactions with biotherapeutics in the non-human primate: Critical parameters, safety and lessons for future studies.

With the emergence of novel biotherapeutic formats and immunostimulatory biotherapeutics in cancer immunotherapy, an understanding of immune-complex (IC) mediated hypersensitivity reactions in toxicology studies - and their differentiation from pharmacology - remains key to the preclinical evaluation of these drugs. In this review we provide an in-depth evaluation and comparison of case examples where IC-mediated hypersensitivity reactions were observed in cynomolgus monkeys. We provide details of the parameters evaluated in each study to substantiate and guide the interpretation of these findings.

High frequency ultrasound sacral images in the critically ill: Tissue characteristics versus visual evaluation.

Purpose: High frequency ultrasound (HFUS) systems may identify tissue injury. We compared HFUS tissue characteristics (dermal thickness and dermal density) with visual image examination.

Methods: Longitudinal study in critically ill mechanically ventilated adults, from three ICUs (Surgical Trauma, Medical Respiratory, Neuroscience) enrolled within 24hours of airway intubation.

Tissue interface pressure and skin integrity in critically ill, mechanically ventilated patients.

Objective: To describe tissue interface pressure, time spent above critical pressure levels and the effect on skin integrity at seven anatomical locations.

Design, Setting, Patients: Descriptive, longitudinal study in critically ill mechanically ventilated adults, from Surgical Trauma ICU-STICU; Medical Respiratory ICU-MRICU; Neuroscience ICU-NSICU in a Mid-Atlantic urban university medical centre. Subjects were enroled in the study within 24hours of intubation.

Backrest Elevation and Tissue Interface Pressure by Anatomical Location During Mechanical Ventilation.

Background: Backrest elevations less than 30° are recommended to reduce pressure ulcers, but positions greater than 30° are recommended during mechanical ventilation to reduce risk for ventilator-associated pneumonia. Interface pressure may vary with level of backrest elevation and anatomical location (eg, sacrum, heels).

Objective: To describe backrest elevation and anatomical location and intensity of skin pressure across the body in patients receiving mechanical ventilation.

Posttraumatic Growth in Populations with Posttraumatic Stress Disorder-A Systematic Review on Growth-Related Psychological Constructs and Biological Variables.

Unlabelled: Posttraumatic growth (PTG) and Posttraumatic Stress Disorder (PTSD) are possible consequences of trauma. PTG is supposed to emerge from cognitive processes and can have functional and dysfunctional aspects. This systematic review aims to identify and evaluate publications assessing PTG in adults diagnosed with PTSD in order to analyse the relationship between both constructs, how PTG is related to specific psychological variables and if there are biological variables linked to PTG.

A nonparametric fiducial interval for the Youden index in multi-state diagnostic settings.

The Youden index is a commonly employed metric to characterize the performance of a diagnostic test at its optimal point. For tests with three or more outcome classes, the Youden index has been extended; however, there are limited methods to compute a confidence interval (CI) about its value. Often, outcome classes are assumed to be normally distributed, which facilitates computational formulas for the CI bounds; however, many scenarios exist for which these assumptions cannot be made.

Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients.

Analysis of the function of the hypothalamic-pituitary-adrenal (HPA)-axis in patients suffering from posttraumatic stress disorder (PTSD) has hitherto produced inconsistent findings, inter alia in the Trier Social Stress Test (TSST). To address these inconsistencies, we compared a sample of 23 female PTSD patients with either early life trauma (ELT) or adult trauma (AT) or combined ELT and AT to 18 age-matched non-traumatized female healthy controls in the TSST which was preceded by intensive baseline assessments. During the TSST, we determined a variety of clinical, psychological, endocrine and cardiovascular parameters as well as expression levels of four HPA-axis related genes.

Effects of position and operator on high-frequency ultrasound scan quality.

Objectives: High-frequency ultrasound may evaluate those at risk for pressure ulcers. Images may be obtained by clinicians with limited training. The prone position is recommended for obtaining sacral scans but may not be feasible in the critically ill.