Association between personality and tau-PET binding in cognitively normal older adults

Personality traits such as Neuroticism and Conscientiousness are associated with Alzheimer disease (AD) pathophysiology in cognitively normal (CN) and impaired individuals, and may represent potential risk or resilience factors, respectively. This study examined the cross-sectional relationship between personality traits and regional tau deposition using positron emission tomography (PET) in cognitively normal older adults. A cohort of CN (Clinical Dementia Rating (CDR) 0, n =?128) older adults completed the NEO Five-Factor Inventory to assess traits of Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness and underwent tau-PET and β-amyloid (Aβ)-PET imaging. We utilized linear regression models, adjusting for age, sex, geriatric depression score, and Aβ to evaluate the association between each of the personality traits and regional tau-PET accumulation. Elevated Neuroticism scores were associated with higher tau-PET accumulation in the amygdala (p =?.002), entorhinal cortex (p =?.012), and inferior temporal cortex (p =?.016), as well as with a composite tau-PET measure (p =?.002). In contrast, Extroversion, Openness, Agreeableness, and Conscientiousness were not associated with tau deposition in any of these regions (p’s?>?0.160). Our results indicate that increased Neuroticism is associated with higher tau pathophysiology in regions known to be vulnerable to AD pathophysiology in CN participants. High Neuroticism scores may therefore serve as a potential risk factor for tau accumulation. Alternatively, personality can change with the onset of AD, thus increased tau levels may affect Neuroticism scores. While future longitudinal studies are needed to determine directionality, our findings suggest early associations between Neuroticism and tau accumulation in CN adults.

     

Identifying strains that contribute to complex diseases through the study of microbial inheritance

It has been 35 y since Carl Woese reported in PNAS how sequencing ribosomal RNA genes could be used to distinguish the three domains of life on Earth. During the past decade, 16S rDNA sequencing has enabled the now frequent enumeration of bacterial communities that populate the bodies of humans representing different ages, cultural traditions, and health states. A challenge going forward is to quantify the contributions of community members to wellness, disease risk, and disease pathogenesis. Here, we explore a theoretical framework for studies of the inheritance of bacterial strains and discuss the advantages and disadvantages of various study designs for assessing the contribution of strains to complex diseases.     

Remote photobiomodulation: an emerging strategy for neuroprotection

<正>Photobiomodulation (PBM)-the irradiation of cells or tissues with low-intensity red to near-infrared light-is emerging as an effective means of enhancing cell and tissue resilience and repair. As reviewed elsewhere (Gordon et al., 2019), the intracellular effects of     

Intranasal hydromorphone for treatment of acute pain in children: A pilot study

ObjectivesWe aimed to describe the analgesic efficacy, duration of analgesia, and adverse event profile associated with intranasal hydromorphone in children with acute pain presenting to an emergency department.MethodsProspective dose titration pilot study of otherwise healthy children 4 to 17-years-old with moderate to severe pain who required a parenteral opioid. All patients received an initial intranasal hydromorophone dose of 0.03 mg/kg. The need for additional analgesia was assessed at 15 and 30 min; an additional 0.015 mg/kg was given at each assessment, if required. Need for rescue analgesic, pain intensity and adverse events were assessed until 6 h after hydromorphone administration or until patients were discharged, underwent a procedure to treat their painful condition, or received a rescue analgesic.ResultsWe enrolled 35 children. Fifteen, 11, and 9 children required a total dose of 0.03, 0.045, and 0.06 mg/kg, respectively. Patients in each dose group experienced an absolute decrease in pain score of ≥3/10 and percent reduction >40% within 5–15 min of completing dose-titration administration of hydromorphone. Duration of analgesia (i.e. time until rescue analgesic administered) >1 h was observed in 85.7% of patients. Patients not requiring rescue analgesics had mild or no pain until discharged or their painful conditions were treated. Three (8.6%) patients required a rescue analgesic <1 h after hydromorphone administration. There were no major adverse events.ConclusionsIntranasal hydromorphone led to rapid, clinically significant and frequently sustained decreases in pain intensity in children. No major adverse events were observed in this preliminary sample.Clinical Trials Registration Number: NCT02437669     

Role of Phenol-Soluble Modulins in Formation of Staphylococcus aureus Biofilms in Synovial Fluid

Staphylococcus aureus is a leading cause of prosthetic joint infections, which, as we recently showed, proceed with the involvement of biofilm-like clusters that cause recalcitrance to antibiotic treatment. Here we analyzed why these clusters grow extraordinarily large, reaching macroscopically visible extensions (>1 mm). We found that while specific S. aureus surface proteins are a prerequisite for agglomeration in synovial fluid, low activity of the Agr regulatory system and subsequent low production of the phenol-soluble modulin (PSM) surfactant peptides cause agglomerates to grow to exceptional dimensions. Our results indicate that PSMs function by disrupting interactions of biofilm matrix molecules, such as the polysaccharide intercellular adhesin (PIA), with the bacterial cell surface. Together, our findings support a two-step model of staphylococcal prosthetic joint infection: As we previously reported, interaction of S. aureus surface proteins with host matrix proteins such as fibrin initiates agglomeration; our present results show that, thereafter, the bacterial agglomerates grow to extremely large sizes owing to the lack of PSM expression under the specific conditions present in joints. Our findings provide a mechanistic explanation for the reported extreme resistance of joint infection to antibiotic treatment, lend support to the notions that Agr functionality and PSM production play a major role in defining different forms of S. aureus infection, and have important implications for antistaphylococcal therapeutic strategies.     

Brain activation changes following motor training in children with unilateral cerebral palsy: An fMRI study

BackgroundIntensive motor-learning-based interventions have demonstrated efficacy for improving motor function in children with unilateral spastic cerebral palsy (USCP). Although this improvement has been associated mainly with neuroplastic changes in the primary sensori-motor cortices, this plasticity may also involve a wider fronto-parietal network for motor learning.ObjectiveTo determine whether hand-arm bimanual intensive therapy including lower extremities (HABIT-ILE) induces brain activation changes in an extensive network for motor skill learning and whether these changes are related to functional changes observed after HABIT-ILE.MethodsIn total, 25 children with USCP were behaviourally assessed in manual dexterity and everyday activities before and after HABIT-ILE. Functional imagery monitored brain activity while participants manipulated objects using their less-affected, more-affected or both hands. Two random-effects-group analyses performed at the whole-brain level assessed the brain activity network before and after therapy. Three other random-effects-group analyses assessed brain activity changes after therapy. Spearman's correlations were used to evaluate the correlation between behavioural and brain activity changes.ResultsThe same fronto-parietal network was identified before and after therapy. After the intervention, the more-affected hand manipulation elicited a decrease in activity on the motor cortex of the non-lesional hemisphere and an increase in activity on motor areas of the lesional hemisphere. The less-affected hand manipulation generated a decrease in activity of sensorimotor areas in the non-lesional hemisphere. Both-hands manipulation elicited an increase in activity of both hemispheres. Furthermore, we observed an association between brain activity changes and changes in everyday activity assessments.ConclusionBrain activation changes were observed in a fronto-parietal network underlying motor skill learning with HABIT-ILE in children with USCP. Two different patterns were observed, probably related to different phases of motor skill learning, representing an increased practice-dependent brain recruitment or a brain activation refinement by more efficient means.ClinicalTrials.govNCT01700777 & NCT02667613.     

The effects of ginger supplementation on markers of inflammatory and oxidative stress: A systematic review and meta‐analysis of clinical trials

The present systematic review and meta‐analysis was conducted to investigate the effects of ginger supplementation on markers of inflammatory and oxidative stress. PubMed, Embase, Scopus, and Web of Science were systematically searched to identify relevant clinical trials evaluating the effects of ginger on serum CRP (C‐reactive protein), TNF‐α (tumor necrosis factor‐alpha), IL‐6 (interleukin‐6), PGE2 (prostaglandin E2), TAC (total antioxidant capacity), and MDA (malondialdehyde) from inception up to September 2019. Mean difference and 95% confidence intervals were pooled using a random‐effects model. Potential publication bias was assessed using visual inspection of funnel plot and Egger's weighted regression tests. After excluding irrelevant records, 20 full‐text articles that included 25 separate studies were included to the meta‐analysis. Pooled results of this study indicated a statistically significant effect of ginger on serum CRP, TNF‐α, IL‐6, TAC, and MDA levels following ginger supplementation in compared to the controls. Also, the effects of ginger on serum PGE2 was marginally significant. Moreover, the high heterogeneity was disappeared in subgroup analysis performed by age, duration, dosage, and quality. This current analysis indicates that ginger supplementation has a significant effects on serum inflammatory and oxidative stress markers.