While vaccines have been tremendously successful in reducing the incidence of serious infectious diseases, newborns remain particularly vulnerable in the first few months of their life to ...life-threatening infections. A number of challenges exist to neonatal vaccination. However, recent advances in the understanding of neonatal immunology offer insights to overcome many of those challenges.
This review will present an overview of the features of neonatal immunity which make vaccination difficult, survey the mechanisms of action of available vaccine adjuvants with respect to the unique features of neonatal immunity, and propose a possible mechanism contributing to the inability of neonates to generate protective immune responses to vaccines.
We surveyed recent published findings on the challenges to neonatal vaccination and possible intervention strategies including the use of novel vaccine adjuvants to develop efficacious neonatal vaccines.
Challenges in the vaccination of neonates include interference from maternal antibody and excessive skewing towards Th2 immunity, which can be counteracted by the use of proper adjuvants.
Synergistic stimulation of multiple Toll-like receptors by incorporating well-defined agonist-adjuvant combinations to vaccines is a promising strategy to ensure a protective vaccine response in neonates.
Lateralized onlay reverse shoulder arthroplasty (RSA) are designed to ensure better clinical functional recovery and lower rate of complications compared to Grammont medialized inlay RSA. The purpose ...of the present study was to compare the clinical and radiographic outcomes between these two different designs.
Eighty-five consecutive patients undergoing RSA were retrospectively analyzed. Nine patients were lost at FU; thirty-four received a curved onlay 145° NSA (Ascend Flex group) and forty-two received a long straight inlay stem with a 155° NSA (Delta Xtend group). Patients were reviewed at an average follow-up of 46.8±13.2 months (Ascend Flex group) and 36±10.8 months (Delta Xtend group). Clinical outcome measures included Active range of motion (ROM), strength, visual analog scale (VAS), Constant-Murley score (CMS), and the American Shoulder and Elbow Surgeons score (ASES). Radiographic evaluation at final follow-up was performed to assess scapular notching, stress shielding, acromial or scapular fractures, heterotopic ossification, and radiolucent lines or implant loosening.
No differences emerged between the two groups in terms of VAS, ASES and CMS scores, pain, function, strength, mobility, active forward elevation, active internal rotation, active external rotation at 0° and 90° of abduction; abduction, forward elevation and external rotation strength (P = n.s). Statistically superior active abduction was observed in the Delta Xtend group (P = 0.0017). Scapular notching was observed in 12 shoulders (35.2%) in the Ascend Flex group (a grade 1) and in 10 shoulders (23.8%) in the Delta Xtend group (P= n.s.). No differences emerged between the two groups in terms of humeral or glenoid radiolucency (P= n.s.). Higher rate of humeral stress shielding rate was observed in the Ascend flex cohort (P= n.s.).
No statistically significant difference emerged between the 145° onlay curved stem versus the 155° inlay straight stem according to most of the evaluated parameters. Statistically superior active abduction was observed in the 155° group although it did not affect patients satisfaction.
African Americans are disproportionately exposed to adversity across the lifespan, which includes both stressful and traumatic events. Adversity, in turn, is associated with alterations in pain ...responsiveness. Racial differences in pain responsiveness among healthy adults are well established. However, the extent to which adversity type and timing are associated with alterations in pain responsiveness among healthy African-American adults is not well understood. The present study included 160 healthy African-American adults (98 women), ages 18 to 45. Outcome measures included pain tolerance and temporal summation of pain to evoked thermal pain. Composite scores were created for early-life adversity (childhood trauma, family adversity) and recent adversity (perceived stress, chronic stress burden). A measure of lifetime racial discrimination was also included. Higher levels of recent adversity were associated with higher temporal summation of pain, controlling for gender, age, and education. Neither early-life adversity nor lifetime racial discrimination were associated with temporal summation of pain. The present findings suggest that heightened temporal summation of pain among healthy African-American adults is associated with exposure to recent adversity events. Improved understanding of how recent adversity contributes to heightened temporal summation of pain in African Americans could help to mitigate racial disparities in pain experiences by identifying at-risk individuals who could benefit from early interventions.
In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. The ...etiology of these Anomalous Health Incidents (AHI) and subsequent symptoms remains unknown. This report investigates putative exposure-symptom pathology by assembling a network model of published bio-behavioral pathways and assessing how dysregulation of such pathways might explain loss of function in these subjects using data available in the published literature. Given similarities in presentation with mild traumatic brain injury (mTBI), we used the latter as a clinically relevant means of evaluating if the neuropsychological profiles observed in Havana Syndrome Havana Syndrome might be explained at least in part by a dysregulation of neurotransmission, neuro-inflammation, or both.
Automated text-mining of >9,000 publications produced a network consisting of 273 documented regulatory interactions linking 29 neuro-chemical markers with 9 neuropsychological constructs from the Brief Mood Survey, PTSD Checklist, and the Frontal Systems Behavior Scale. Analysis of information flow through this network produced a set of regulatory rules reconciling to within a 6% departure known mechanistic pathways with neuropsychological profiles in
= 6 subjects.
Predicted expression of neuro-chemical markers that jointly satisfy documented pathways and observed symptom profiles display characteristically elevated IL-1B, IL-10, NGF, and norepinephrine levels in the context of depressed BDNF, GDNF, IGF1, and glutamate expression (FDR < 5%). Elevations in CRH and IL-6 were also predicted unanimously across all subjects. Furthermore, simulations of neurological regulatory dynamics reveal subjects do not appear to be "locked in" persistent illness but rather appear to be engaged in a slow recovery trajectory.
This computational analysis of measured neuropsychological symptoms in Havana-based diplomats proposes that these AHI symptoms may be supported in part by disruption of known neuroimmune and neurotransmission regulatory mechanisms also associated with mTBI.
Determination and reporting of disease severity in emergency general surgery lacks standardization. Recently, the American Association for the Surgery of Trauma (AAST) proposed an anatomic severity ...grading system. We aimed to validate this system in patients with appendicitis and determine if cross-sectional imaging correlates with disease severity at operation.
Patients 18 years or older undergoing treatment for acute appendicitis between 2013 and 2015 were identified. Baseline demographics, procedure types were recorded, and AAST grades were assigned based on intraoperative and radiologic findings. Outcomes including length of stay, 30-day mortality, and complications based on Clavien-Dindo categories and National Surgical Quality Improvement Program variables. Summary statistical univariate, nominal logistic, and standard least squares analyses were performed comparing AAST grade with key outcomes. Bland-Altman analysis compared operative findings with preoperative cross-sectional imaging to compare assigning grades.
Three hundred thirty-four patients with mean (±SD) age of 39.3 years (±16.5) were included (53% men), and all patients had cross-sectional imaging. Two hundred ninety-nine underwent appendectomy, and 85% completed laparoscopic. Thirty-day mortality rate was 0.9%, complication rate was 21%. Increased (median interquartile range, IQR) AAST grade was recorded in patients with complications (2 1-4) compared with those without (1 1-1, p = 0.001). For operative management, (median IQR) AAST grades were significantly associated with procedure type: laparoscopic (1 1-1), open (4 2-5), conversion to open (3 1-4, p = 0.001). Increased (median IQR) AAST grades were significantly associated in nonoperative management: patients having a complication had a higher median AAST grade (4 3-5) compared with those without (3 2-3, p = 0.001). Bland-Altman analysis comparing AAST grade and cross-sectional imaging demonstrated no difference (-0.02 ± 0.02; p = 0.2; coefficient of repeatability 0.9).
The AAST grading system is valid in our population. Increased AAST grade is associated with open procedures, complications, and length of stay. The AAST emergency general surgery grade determined by preoperative imaging strongly correlated to operative findings.
Epidemiologic/prognostic study, level III.
Carbon fibers are unique reinforcing agents for lightweight composite materials due to their outstanding mechanical properties and low density. Current technologies are capable of producing carbon ...fibers with 90–95% of the modulus of perfect graphite (∼1025 GPa). However, these same carbon fibers possess less than 10% of the theoretical carbon fiber strength, estimated to be about 100 GPa. Traditionally, attempts to increase carbon fiber rigidity above a certain level results in lower breaking strength. Therefore, to develop advanced carbon fibers with both very high strength and modulus demands a new manufacturing methodology. Here, we report a method of manufacturing moderate strength, very high modulus carbon fibers from a very high molecular weight (VHMW) polyacrylonitrile (PAN) precursor without the use of nanomaterial additives such as nucleating or structure-templating agents, as have been used by others.
A substantial minority of women who experience interpersonal violence will develop posttraumatic stress disorder (PTSD). One critical challenge for preventing PTSD is predicting whose acute ...posttraumatic stress symptoms will worsen to a clinically significant degree. This 6-month longitudinal study adopted multilevel modeling and exploratory machine learning (ML) methods to predict PTSD onset in 58 young women, ages 18 to 30, who experienced an incident of physical and/or sexual assault in the three months prior to baseline assessment. Women completed baseline assessments of theory-driven cognitive and neurobiological predictors and interview-based measures of PTSD diagnostic status and symptom severity at 1-, 3-, and 6-month follow-ups. Higher levels of self-blame, generalized anxiety disorder severity, childhood trauma exposure, and impairment across multiple domains were associated with a pattern of high and stable posttraumatic stress symptom severity over time. Predictive performance for PTSD onset was similarly strong for a gradient boosting machine learning model including all predictors and a logistic regression model including only baseline posttraumatic stress symptom severity. The present findings provide directions for future work on PTSD prediction among interpersonal violence survivors that could enhance early risk detection and potentially inform targeted prevention programs.
This longitudinal study examined whether posttraumatic stress and depressive symptoms, posttraumatic cognitions, and ongoing cyberstalking exposures were independently associated with changes in pain ...outcomes among 82 young adult women with recent exposure to stalking. Multilevel models indicated that higher sensory pain intensity and pain-related interference were associated with more negative cognitions about the self. Higher affective pain intensity was associated with higher posttraumatic stress and depressive symptoms. Cyberstalking exposures were not associated with pain intensity or pain-related interference. Results reveal persistent pain complaints in recent stalking victims and highlight distinct psychological risk factors for pain intensity and pain-related interference.
•Stress response alterations may influence risk for posttraumatic stress disorder.•Stress response and habituation patterns were examined after interpersonal trauma.•Trauma survivors and healthy ...controls were assessed on 4 occasions over 6 months.•Survivors with PTSD had higher initial cortisol responses and stronger habituation.•Survivors without PTSD had blunted cortisol responses across all 4 stress tasks.
Alterations in major stress response systems are present during the immediate aftermath of trauma and may play a role in determining risk for developing posttraumatic stress disorder (PTSD). However, the dynamics and determinants of stress responses during this acute recovery phase, and their relevance for longitudinal clinical course and prognosis, have yet to be fully examined. The objectives of the present study were to characterize stress response and habituation patterns to repeated social stressors in women who recently experienced interpersonal trauma and to determine the extent to which these stress responses were associated with PTSD during prospective follow-up.
This longitudinal study examined salivary cortisol and alpha-amylase and heart rate (HR) responses to repeated stressors in 98 young women (ages 18–30). Participants included women who had experienced an incident of interpersonal trauma (i.e., physical and/or sexual assault) in the three months prior to their baseline assessment (n = 58) and a comparison group of healthy, non-traumatized women (n = 40). Women completed the Trier Social Stress Test (TSST), clinical interviews to evaluate posttraumatic stress symptom severity at the baseline assessment and again at 1-, 3-, and 6-month follow-ups.
Multilevel models revealed a pattern of robust initial cortisol TSST responses and habituation across successive TSSTs; alpha-amylase and HR responses showed no evidence of habituation across TSSTs. Among interpersonal trauma survivors, current PTSD status was associated with more pronounced cortisol responses to the first TSST. Survivors exhibited similarly blunted cortisol responses across follow-up TSSTs regardless of PTSD status, suggesting habituation of cortisol responses among survivors who developed PTSD. PTSD re-experiencing symptoms were uniquely associated with blunting of cortisol TSST responses.
Findings suggest that PTSD as a diagnostic entity is meaningfully associated with cortisol responses to repeated social stressors. Social-evaluative threat is a salient form of danger for interpersonal trauma survivors. Identifying the determinants of cortisol (non)habituation to repeated social-evaluative threat among interpersonal trauma survivors could inform the development of early interventions for PTSD.
Abstract Background Childhood maltreatment can trigger enduring changes in major stress response systems, particularly in the context of major depressive disorder (MDD). However, the relative impact ...of maltreatment versus MDD on hypothalamic-pituitary-adrenal axis and sympathetic-adrenal-medullary system stress reactivity is not well understood. Method This study examined salivary cortisol and alpha-amylase responses to the Trier Social Stress Test (TSST) in 26 maltreated (15 with current MDD) and 26 non-maltreated (17 with current MDD) women. Results Maltreated women showed greater anticipatory cortisol reactivity during the TSST protocol compared to non-maltreated women. Maltreated women also showed rapid deceleration in cortisol levels. Whereas non-maltreated women showed initial declines in alpha-amylase levels but rapidly increasing alpha-amylase levels during the TSST protocol, maltreated women did not exhibit changes in alpha-amylase levels during the TSST protocol. Contrary to expectation, MDD did not impact cortisol or alpha-amylase responses. Limitations The present study is limited by retrospective report of childhood maltreatment, cross-sectional design, and modest sample sizes. Conclusions These findings suggest that childhood maltreatment plays a greater role driving alterations in cortisol and alpha-amylase stress reactivity than MDD. Understanding the biological embedding of maltreatment is critical for elucidating mechanisms linking these experiences to risk for negative mental and physical health outcomes.
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