Diffusion tensor imaging of incentive effects in prospective memory after pediatric traumatic brain injury

Few studies exist investigating the brain-behavior relations of event-based prospective memory (EB-PM) impairments following traumatic brain injury (TBI). To address this, children with moderate-to-severe TBI performed an EB-PM test with two motivational enhancement conditions and underwent concurrent diffusion tensor imaging (DTI) at 3 months post-injury. Children with orthopedic injuries (OI; n=37) or moderate-to-severe TBI (n=40) were contrasted. Significant group differences were found for fractional anisotropy (FA) and apparent diffusion coefficient for orbitofrontal white matter (WM), cingulum bundles, and uncinate fasciculi. The FA of these WM structures in children with TBI significantly correlated with EB-PM performance in the high, but not the low motivation condition. Regression analyses within the TBI group indicated that the FA of the left cingulum bundle (p=0.003), left orbitofrontal WM (p<0.02), and left (p<0.02) and right (p<0.008) uncinate fasciculi significantly predicted EB-PM performance in the high motivation condition. We infer that the cingulum bundles, orbitofrontal WM, and uncinate fasciculi are important WM structures mediating motivation-based EB-PM responses following moderate-to-severe TBI in children.     

Validation of the Intensive Care Delirium Screening Checklist in nonintubated intensive care unit patients in a resource-poor medical intensive care setting in South India

Objective

Delirium is a common, difficult-to-diagnose clinical condition in critical care units. The lack of recognition of delirium often results in increased morbidity and mortality. The study aimed to determine the validity and reliability of the Intensive Care Delirium Screening Checklist (ICDSC) in a resource-poor medical intensive care setting in South India.

Materials and methods

Fifty-three patients admitted into the medical intensive care unit of a teaching hospital who were neither mute nor intubated were recruited for the study. Trained residents administered the ICDSC to screen for delirium. A consultant psychiatrist used the International Classification of Diseases, 10th Revision diagnostic criteria for research to determine the presence of delirium.

Results

The optimal threshold for screening, as ICDSC total score of 3 or more, was obtained by using a receiver operating characteristic curve. Although a sensitivity and specificity of 75% and 74%, respectively, were obtained at the original cutoff of 4, a sensitivity of 90% and specificity of 61.54% were achieved with a cutoff of 3. In a subsample of 21 patients, interrater reliability was evaluated and found to be 0.947 (95% confidence interval, 0.870-0.979). The ICDSC had good internal consistency, with Cronbach α of .754 and Guttman split-half coefficient of 0.71. Factor analysis revealed a 2-factor structure, namely, altered sensorium/psychopathology and sleep-wake cycle problems.

Conclusions

Our findings indicate that in nonintubated intensive care unit patients, the ICDSC can be used to screen for delirium but should not be used as a diagnostic instrument in this patient population and that residents can be trained in the use of the instrument in resource-poor critical care settings. Using a different threshold for positivity of 3 rather than 4 appeared to offer improved screening characteristics in this resource-poor critical care setting.     

Experimental study on histological changes in the sinus membrane following sinus lift

The aim of this study is to assess the histological changes in the sinus mucosa adjacent to the alloplastic material used for subantral augmentation. Materials and Methods: The study included ten sheep and a dog. The first group of five sheep underwent a sinus lift procedure, using PerioGlas as an augmentation material; the second similar group of sheep was the control group. The dog underwent a sinus lift procedure, with PerioGlas augmentation, after the sinus membrane was intentionally perforated and two implants were placed in the same operative step. Results: Scanning electron microscopy (SEM) of the sinus mucosa in the control group revealed cells without cilia between goblet cells. The cilia were uniformly arranged in sections in the same direction. Changes occurred in the sinus mucosa after grafting, such as drastic reduction of ciliated cells, which seemed to be replaced by goblet cells. In all sheep undergoing grafting, generalized fibrosis was found in the mucosal area that came into contact with PerioGlas. In two of the sheep in which grafting was performed, mucoid cysts with pseudo stratified ciliated epithelium were present. Even when the sinus mucosa was perforated (in the dog), the inflammatory process developed in the mucosa did not prevent the integration of the graft and implants. In conclusion, following the sinus lift procedure, changes occur in the sinus membrane to adapt to the new situation, without the appearance of chronic or acute suppurative processes.     

Programmed death ligand 1 is over-expressed by neutrophils in the blood of patients with active tuberculosis

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the world's largest infectious disease problems. Despite decades of intensive study, the immune response to Mtb is incompletely characterised, reflecting the extremely complex interaction between pathogen and host. Pathways that may alter the balance between host protection and pathogenesis are therefore of great interest. One pathway shown to play a role in the pathogenesis of chronic infections, including TB, is the programmed death-1 (PD-1) pathway. We show here that the expression of the programmed death ligand 1 (PD-L1), which interacts with PD-1, is increased in whole blood from active TB patients compared with whole blood from healthy controls or Mtb-exposed individuals, and that expression by neutrophils is largely responsible for this increase.     

Postpubertal decrease in hippocampal dendritic spines of female rats

Hippocampal dendritic spine and synapse numbers in female rats vary across the estrous cycle and following experimental manipulation of hormone levels in adulthood. Based on behavioral studies demonstrating that learning patterns are altered following puberty, we hypothesized that dendritic spine number in rat hippocampal CA1 region would change postpubertally. Female Sprague-Dawley rats were divided into prepubertal (postnatal day (P) 22), peripubertal (P35) and postpubertal (P49) groups, with the progression of puberty evaluated by vaginal opening, and estrous cyclicity subsequently assessed by daily vaginal smears. Spinophilin immunoreactivity in dendritic spines was used as an index of spinogenesis in area CA1 stratum radiatum (CA1sr) of hippocampus. First, electron microscopy analyses confirmed the presence of spinophilin specifically in dendritic spines of CA1sr, supporting spinophilin as a reliable marker of hippocampal spines in young female rats. Second, stereologic analysis was performed to assess the total number of spinophilin-immunoreactive puncta (i.e. spines) and CA1sr volume in developing rats. Our results indicated that the number of spinophilin-immunoreactive spines in CA1sr was decreased 46% in the postpubertal group compared to the two younger groups, whereas the volume of the hippocampus underwent an overall increase during this same developmental time frame. Third, to determine a potential role of estradiol in this process, an additional group of rats was ovariectomized (OVX) prepubertally at P22, then treated with estradiol or vehicle at P35, and spinophilin quantified as above in rats perfused on P49. No difference in spinophilin puncta number was found in OVX rats between the two hormone groups, suggesting that this developmental decrease is independent of peripheral estradiol. These changes in spine density coincident with puberty may be related to altered hippocampal plasticity and synaptic consolidation at this phase of maturity.     

A Study of Physical Resilience and Aging (SPRING): Conceptual framework,rationale, and study design

Understanding the physiological basis of physical resilience to clinical stressors is crucial for the well-being of older adults. This article presents a novel framework to discover the biological underpinnings of physical resilience in older adults as part of the “Characterizing Resiliencies to Physical Stressors in Older Adults: A Dynamical Physiological Systems Approach” study, also known as The Study of Physical Resilience and Aging (SPRING). Physical resilience, defined as the capacity of a person to withstand clinical stressors and quickly recover or improve upon a baseline functional level, is examined in adults aged 55 years and older by studying the dynamics of stress response systems. The hypothesis is that well-regulated stress response systems promote physical resilience. The study employs dynamic stimulation tests to assess energy metabolism, the hypothalamic–pituitary–adrenal axis, the autonomic nervous system, and the innate immune system. Baseline characteristics influencing resilience outcomes are identified through deep phenotyping of physical and cognitive function, as well as of biological, environmental, and psychosocial characteristics. SPRING aims to study participants undergoing knee replacement surgery (n = 100), bone and marrow transplantation (n = 100), or anticipating dialysis initiation (n = 60). Phenotypic and functional measures are collected pre-stressor and at multiple times after stressor for up to 12 months to examine resilience trajectories. By improving our understanding of physical resilience in older adults, SPRING has the potential to enhance resilient outcomes to major clinical stressors. The article provides an overview of the study's background, rationale, design, pilot phase, implementation, and implications for improving the health and well-being of older adults.     

Screening and interventions to prevent nonalcoholic fatty liver disease/nonalcoholic steatohepatitis-associated hepatocellular carcinoma

Liver cancer is the sixth most commonly diagnosed cancer worldwide, with hepatocellular carcinoma (HCC) comprising most cases. Besides hepatitis B and C viral infections, heavy alcohol use, and nonalcoholic steatohepatitis (NASH)-associated advanced fibrosis/cirrhosis, several other risk factors for HCC have been identified (i.e. old age, obesity, insulin resistance, type 2 diabetes). These might in fact partially explain the occurrence of HCC in non-cirrhotic patients without viral infection. HCC surveillance through effective screening programs is still an unmet need for many nonalcoholic fatty liver disease (NAFLD) patients, and identification of pre-cirrhotic individuals who progress to HCC represents a substantial challenge in clinical practice at the moment. Patients with NASH-cirrhosis should undergo systematic HCC surveillance, while this might be considered in patients with advanced fibrosis based on individual risk assessment. In this context, interventions that potentially prevent NAFLD/ NASH-associated HCC are needed. This paper provided an overview of evidence related to lifestyle changes (i.e. weight loss, physical exercise, adherence to healthy dietary patterns, intake of certain dietary components, etc.) and pharmacological interventions that might play a protective role by targeting the underlying causative factors and pathogenetic mechanisms. However, well-designed prospective studies specifically dedicated to NAFLD/NASH patients are still needed to clarify the relationship with HCC risk.