Post-traumatic stress in older, community-dwelling adults with hypertension during the COVID-19 pandemic: An investigation of pre-pandemic sociodemographic, health, and vascular and inflammatory biomarker predictors.

COVID-19 pandemic-related traumatic stress (PRTS) symptoms are reported in various populations, but risk factors in older adults with chronic medical conditions, remain understudied. We therefore examined correlates and pre-pandemic predictors of PRTS in older adults with hypertension during COVID-19. Participants in California, aged 61-92 years (n = 95), participated in a pre-pandemic healthy aging trial and later completed a COVID-19 assessment (May to September 2020). Those experiencing ⩾1 PRTS symptom (n = 40), and those without PRTS symptoms (n = 55), were compared. The PRTS+ group had poorer mental and general health and greater impairment in instrumental activities of daily living. Pre-pandemic biomarkers of vascular inflammation did not predict increased odds of PRTS; however, greater pre-pandemic anxiety and female gender did predict PRTS during COVID-19. Our findings highlight PRTS as a threat to healthy aging in older adults with hypertension; targeted approaches are needed to mitigate this burden, particularly for females and those with pre-existing anxiety.

G protein-coupled receptors: A target for microbial metabolites and a mechanistic link to microbiome-immune-brain interactions.

Human-microorganism interactions play a key role in human health. However, the underlying molecular mechanisms remain poorly understood. Small-molecules that offer a functional readout of microbe-microbe-human relationship are of great interest for deeper understanding of the inter-kingdom crosstalk at the molecular level. Recent studies have demonstrated that small-molecules from gut microbiota act as ligands for specific human G protein-coupled receptors (GPCRs) and modulate a range of human physiological functions, offering a mechanistic insight into the microbe-human interaction. To this end, we focused on analysis of bacterial metabolites that are currently recognized to bind to GPCRs and are found to activate the known downstream signaling pathways. We further mapped the distribution of these molecules across the public mass spectrometry-based metabolomics data, to identify the presence of these molecules across body sites and their association with health status. By combining this with RNA-Seq expression and spatial localization of GPCRs from a public human protein atlas database, we inferred the most predominant GPCR-mediated microbial metabolite-human cell interactions regulating gut-immune-brain axis. Furthermore, by evaluating the intestinal absorption properties and blood-brain barrier permeability of the small-molecules we elucidated their molecular interactions with specific human cell receptors, particularly expressed on human intestinal epithelial cells, immune cells and the nervous system that are shown to hold much promise for clinical translational potential. Furthermore, we provide an overview of an open-source resource for simultaneous interrogation of bioactive molecules across the druggable human GPCRome, a useful framework for integration of microbiome and metabolite cataloging with mechanistic studies for an improved understanding of gut microbiota-immune-brain molecular interactions and their potential therapeutic use.

Tai Chi versus health education as a frailty intervention for community-dwelling older adults with hypertension.

BACKGROUND: Frailty is associated with poor outcomes among older adults with hypertension and complicates its pharmacological management. Here, we assessed whether 12-weeks of instructor-guided, group Tai Chi (TC) practice improved frailty relative to Healthy Aging Practice-centered Education (HAP-E) classes in older adults with hypertension. METHODS: Secondary analysis of a randomized controlled trial in San Diego County, USA, of 167 community-dwelling individuals aged ≥ 60 yrs (70% female; 72.1 ± 7.5 yrs), defined as non-frail (66%) or frail (34%) based on 53-item deficit accumulation frailty index (FI). Linear mixed-effects models were used to assess pre-to-post intervention differences in FI and logistic regression to explore differential odds of clinically meaningful FI change. RESULTS: One hundred thirty-one participants completed post-intervention assessments. Frailty decreased pre-to-post intervention in the TC (ΔFI = - 0.016, d = - 0.39, - 0.75 to - 0.03), but not the HAP-E arm (ΔFI = - 0.009, d = - 0.13, - 0.52-0.27), despite no significant group differences between the TC and HAP-E arms (d = - 0.11, - 0.46-0.23). Furthermore, greater odds of improved FI were observed for frail participants in the TC (OR = 3.84, 1.14-14.9), but not the HAP-E (OR = 1.34, 0.39-4.56) arm. Subgroup analysis indicated treatment effects in TC were attributed to frail participants (frail: ΔFI = - 0.035, d = - 0.68, -1.26 to - 0.08; non-frail: ΔFI = - 0.005, d = - 0.19, - 0.59-0.22), which was not the case in the HAP-E arm (frail: ΔFI = - 0.017, d = - 0.23, - 0.81-0.35; non-frail: ΔFI = - 0.003, d = - 0.07, - 0.47-0.33). Frail participants were no more likely to drop-out of the study than non-frail (71% vs. 69% retained). CONCLUSIONS: Twelve weeks of twice-weekly guided TC practice was well-tolerated, associated with decreases in frailty, and increased odds of clinically meaningful FI improvement at post-intervention.

Assessing Pediatric Mild Traumatic Brain Injury and Its Recovery Using Resting-State Magnetoencephalography Source Magnitude Imaging and Machine Learning.

The objectives of this machine-learning (ML) resting-state magnetoencephalography (rs-MEG) study involving children with mild traumatic brain injury (mTBI) and orthopedic injury (OI) controls were to define a neural injury signature of mTBI and to delineate the pattern(s) of neural injury that determine behavioral recovery. Children ages 8-15 years with mTBI (n = 59) and OI (n = 39) from consecutive admissions to an emergency department were studied prospectively for parent-rated post-concussion symptoms (PCS) at: 1) baseline (average of 3 weeks post-injury) to measure pre-injury symptoms and also concurrent symptoms; and 2) at 3-months post-injury. rs-MEG was conducted at the baseline assessment. The ML algorithm predicted cases of mTBI versus OI with sensitivity of 95.5 ± 1.6% and specificity of 90.2 ± 2.7% at 3-weeks post-injury for the combined delta-gamma frequencies. The sensitivity and specificity were significantly better (p < 0.0001) for the combined delta-gamma frequencies compared with the delta-only and gamma-only frequencies. There were also spatial differences in rs-MEG activity between mTBI and OI groups in both delta and gamma bands in frontal and temporal lobe, as well as more widespread differences in the brain. The ML algorithm accounted for 84.5% of the variance in predicting recovery measured by PCS changes between 3 weeks and 3 months post-injury in the mTBI group, and this was significantly lower (p < 10-4) in the OI group (65.6%). Frontal lobe pole (higher) gamma activity was significantly (p < 0.001) associated with (worse) PCS recovery exclusively in the mTBI group. These findings demonstrate a neural injury signature of pediatric mTBI and patterns of mTBI-induced neural injury related to behavioral recovery.

Tai chi or health education for older adults with hypertension: effects on mental health and psychological resilience to COVID-19.

OBJECTIVE: To compare the effectiveness of 12 weeks of community-based, in-person, group Tai Chi (TC) and Health Education (HAP-E) in improving health and wellbeing in older adults with hypertension and in promoting psychological resilience during COVID-19. METHODS: A 12-week randomized controlled trial (RCT) in San Diego County, USA. Self-reported depressive symptoms, anxiety, sleep disturbances, gratitude, resilience, mental and physical health were assessed in-person pre- and post-intervention, and by long-term follow-up surveys during COVID-19. Linear mixed-effects models were used to assess study arm differences over time and logistic regression to identify predictors of positive intervention response. RESULTS: Of 182 randomized participants (72.6 ± 7.9 yrs; 72% female), 131 completed the intervention. Modest improvements in health and wellbeing occurred post-intervention in both arms (Cohen's d: TC = 0.38, 95% CI: 0.25-0.51; HAP-E = 0.24, 0.11-0.37), though positive intervention responses were more than twice as likely in TC (OR = 2.29, 1.07-4.57). Younger age, higher anxiety, and poorer mental health at baseline predicted greater odds of response. Small declines in health and wellbeing were reported at the first COVID-19 follow-up, with smaller declines in the TC arm (Cohen's d: TC = -0.15, -0.31-0.00; HAP-E = -0.34, -0.49 to -0.19). Health and wellbeing stabilized at the second COVID-19 follow-up. Most participants (>70%) reported that the interventions benefitted their health and wellbeing during COVID-19. CONCLUSION: TC and HAP-E improved health and wellbeing, though TC conferred greater odds of an improved mental health response. Declines in health and wellbeing were observed at pandemic follow-up, with smaller declines in the TC arm, suggesting increased resilience.

The impact of paleoclimatic changes on body size evolution in marine fishes.

Body size is an important species trait, correlating with life span, fecundity, and other ecological factors. Over Earth's geological history, climate shifts have occurred, potentially shaping body size evolution in many clades. General rules attempting to summarize body size evolution include Bergmann's rule, which states that species reach larger sizes in cooler environments and smaller sizes in warmer environments, and Cope's rule, which poses that lineages tend to increase in size over evolutionary time. Tetraodontiform fishes (including pufferfishes, boxfishes, and ocean sunfishes) provide an extraordinary clade to test these rules in ectotherms owing to their exemplary fossil record and the great disparity in body size observed among extant and fossil species. We examined Bergmann's and Cope's rules in this group by combining phylogenomic data (1,103 exon loci from 185 extant species) with 210 anatomical characters coded from both fossil and extant species. We aggregated data layers on paleoclimate and body size from the species examined, and inferred a set of time-calibrated phylogenies using tip-dating approaches for downstream comparative analyses of body size evolution by implementing models that incorporate paleoclimatic information. We found strong support for a temperature-driven model in which increasing body size over time is correlated with decreasing oceanic temperatures. On average, extant tetraodontiforms are two to three times larger than their fossil counterparts, which otherwise evolved during periods of warmer ocean temperatures. These results provide strong support for both Bergmann's and Cope's rules, trends that are less studied in marine fishes compared to terrestrial vertebrates and marine invertebrates.

Salivary bacterial signatures in depression-obesity comorbidity are associated with neurotransmitters and neuroactive dipeptides.

BACKGROUND: Depression and obesity are highly prevalent, often co-occurring conditions marked by inflammation. Microbiome perturbations are implicated in obesity-inflammation-depression interrelationships, but how the microbiome mechanistically contributes to pathology remains unclear. Metabolomic investigations into microbial neuroactive metabolites may offer mechanistic insights into host-microbe interactions. Using 16S sequencing and untargeted mass spectrometry of saliva, and blood monocyte inflammation regulation assays, we identified key microbes, metabolites and host inflammation in association with depressive symptomatology, obesity, and depressive symptomatology-obesity comorbidity. RESULTS: Gram-negative bacteria with inflammation potential were enriched relative to Gram-positive bacteria in comorbid obesity-depression, supporting the inflammation-oral microbiome link in obesity-depression interrelationships. Oral microbiome was more highly predictive of depressive symptomatology-obesity co-occurrences than of obesity or depressive symptomatology independently, suggesting specific microbial signatures associated with obesity-depression co-occurrences. Mass spectrometry analysis revealed significant changes in levels of signaling molecules of microbiota, microbial or dietary derived signaling peptides and aromatic amino acids among depressive symptomatology, obesity and comorbid obesity-depression. Furthermore, integration of the microbiome and metabolomics data revealed that key oral microbes, many previously shown to have neuroactive potential, co-occurred with potential neuropeptides and biosynthetic precursors of the neurotransmitters dopamine, epinephrine and serotonin. CONCLUSIONS: Together, our findings offer novel insights into oral microbial-brain connection and potential neuroactive metabolites involved.

Traumatic Brain Injury in Children and Adolescents: Psychiatric Disorders 24 Years Later.

OBJECTIVE: The investigators aimed to extend findings regarding predictive factors of psychiatric outcomes among children and adolescents with traumatic brain injury (TBI) from 2 to 24 years postinjury. METHODS: Youths aged 6-14 years who were hospitalized following TBI from 1992 to 1994 were assessed at baseline for TBI severity and for preinjury psychiatric, adaptive, and behavioral functioning; family functioning; family psychiatric history; socioeconomic status; and intelligence within weeks of injury. Predictors of psychiatric outcomes following pediatric TBI at 3, 6, 12, and 24 months postinjury have previously been reported. In this study, repeat psychiatric assessments were completed at 24 years postinjury with the same cohort, now adults aged 29-39 years, with the outcome measure being presence of a psychiatric disorder not present before the TBI ("novel psychiatric disorder"). RESULTS: Fifty participants with pediatric TBI were initially enrolled, and the long-term outcome analyses focused on data from 45 individuals. Novel psychiatric disorder was present in 24 out of 45 (53%) participants. Presence of a current novel psychiatric disorder was independently predicted by the presence of a preinjury lifetime psychiatric disorder and by severity of TBI. CONCLUSIONS: Long-term psychiatric outcome (mean=23.92 years [SD=2.17]) in children and adolescents hospitalized for TBI can be predicted at the point of the initial hospitalization encounter by the presence of a preinjury psychiatric disorder and by greater injury severity.

Long-Term Psychiatric Outcomes in Adults with History of Pediatric Traumatic Brain Injury.

The objective of the study was to compare psychiatric outcomes in adults with and without history of pediatric traumatic brain injury (TBI). Youth ages 6 to 14 years hospitalized for TBI from 1992 to 1994 were assessed at baseline and at 3, 6, 12, and 24 months post-injury. In the current study, psychiatric assessments were repeated at 24 years post-injury with the same cohort, now adults ages 29 to 39 years. A control group of healthy adults also was recruited for one-time cross-sectional assessments. Outcome measures included: 1) presence of a psychiatric disorder since the 24-month assessment not present before the TBI ("novel psychiatric disorder," NPD), or in the control group, the presence of a psychiatric disorder that developed after the mean age of injury of the TBI group plus 2 years; and 2) Time-to-Event for onset of an NPD during the same time periods. In the TBI group, NPDs were significantly more common, and presence of a current NPD was significantly predicted by presence of a pre-injury lifetime psychiatric disorder and by abnormal day-of-injury computed tomography (CT) scan. Compared with controls, the TBI group also had significantly shorter Time-to-Event for onset of any NPD. These findings demonstrate that long-term psychiatric outcomes in adults previously hospitalized for pediatric TBI are significantly worse when compared with adult controls without history of pediatric TBI, both in terms of prevalence and earlier onset of NPD. Further, in the TBI group, long-term NPD outcome is predicted independently by presence of pre-injury psychiatric disorder and abnormal day-of-injury CT scan.

Searching for host immune-microbiome mechanisms in obsessive-compulsive disorder: A narrative literature review and future directions.

Obsessive-compulsive disorder (OCD) is disabling and often treatment-refractory. Host immunity and gut microbiota have bidirectional communication with each other and with the brain. Perturbations to this axis have been implicated in neuropsychiatric disorders, but immune-microbiome signaling in OCD is relatively underexplored. We review support for further pursuing such investigations in OCD, including: 1) gut microbiota has been associated with OCD, but causal pathogenic mechanisms remain unclear; 2) early environmental risk factors for OCD overlap with critical periods of immune-microbiome development; 3) OCD is associated with increased risk of immune-mediated disorders and changes in immune parameters, which are separately associated with the microbiome; and 4) gut microbiome manipulations in animal models are associated with changes in immunity and some obsessive-compulsive symptoms. Theoretical pathogenic mechanisms could include microbiota programming of cytokine production, promotion of expansion and trafficking of peripheral immune cells to the CNS, and regulation of microglial function. Immune-microbiome signaling in OCD requires further exploration, and may offer novel insights into pathogenic mechanisms and potential treatment targets for this disabling disorder.

Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms.

The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals' lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.

Self-reported sleep disturbances are associated with poorer cognitive performance in older adults with hypertension: a multi-parameter risk factor investigation.

OBJECTIVES: Given the evidence of multi-parameter risk factors in shaping cognitive outcomes in aging, including sleep, inflammation, cardiometabolism, and mood disorders, multidimensional investigations of their impact on cognition are warranted. We sought to determine the extent to which self-reported sleep disturbances, metabolic syndrome (MetS) factors, cellular inflammation, depressive symptomatology, and diminished physical mobility were associated with cognitive impairment and poorer cognitive performance. DESIGN: This is a cross-sectional study. SETTING: Participants with elevated, well-controlled blood pressure were recruited from the local community for a Tai Chi and healthy-aging intervention study. PARTICIPANTS: One hundred forty-five older adults (72.7 ± 7.9 years old; 66% female), 54 (37%) with evidence of cognitive impairment (CI) based on Montreal Cognitive Assessment (MoCA) score ≤24, underwent medical, psychological, and mood assessments. MEASUREMENTS: CI and cognitive domain performance were assessed using the MoCA. Univariate correlations were computed to determine relationships between risk factors and cognitive outcomes. Bootstrapped logistic regression was used to determine significant predictors of CI risk and linear regression to explore cognitive domains affected by risk factors. RESULTS: The CI group were slower on the mobility task, satisfied more MetS criteria, and reported poorer sleep than normocognitive individuals (all p < 0.05). Multivariate logistic regression indicated that sleep disturbances, but no other risk factors, predicted increased risk of evidence of CI (OR = 2.00, 95% CI: 1.26-4.87, 99% CI: 1.08-7.48). Further examination of MoCA cognitive subdomains revealed that sleep disturbances predicted poorer executive function (ß = -0.26, 95% CI: -0.51 to -0.06, 99% CI: -0.61 to -0.02), with lesser effects on visuospatial performance (ß = -0.20, 95% CI: -0.35 to -0.02, 99% CI: -0.39 to 0.03), and memory (ß = -0.29, 95% CI: -0.66 to -0.01, 99% CI: -0.76 to 0.08). CONCLUSIONS: Our results indicate that the deleterious impact of self-reported sleep disturbances on cognitive performance was prominent over other risk factors and illustrate the importance of clinician evaluation of sleep in patients with or at risk of diminished cognitive performance. Future, longitudinal studies implementing a comprehensive neuropsychological battery and objective sleep measurement are warranted to further explore these associations.

Cerogobius petrophilus (Perciformes: Gobiidae), a new gobiid genus and species from the Red Sea.

A new genus and species of cryptobenthic goby, Cerogobius petrophilus is described from the Red Sea based on nine specimens not exceeding 2.5 cm in total length, collected from a stone-rubble habitat at Thuwal, Saudi Arabia, at depths of 8-15 m. It was also observed underwater at the southern tip of Ras Mohammed and Marsa Alam in Egypt. Cerogobius petrophilus sp. nov. is unique among other gobies in its habitat, and in this regard it superficially resembles some species of blennies, occupying tight holes in stones covered with short algae. Molecular phylogenetic data suggest a close relationship between Cerogobius petrophilus sp. nov. and Hetereleotris, but the former differs from the latter morphologically in head shape with specific proportions of orbit and snout, forward-set position of eyes, a moderately large mouth, a long horn-like tentacle at the nostrils in the middle of snout, caudal peduncle deep and short, and in details of cephalic sensory system. A full description of the new genus and species is provided and is accompanied with osteological data that potentially can be informative in further comparisons with Hetereleotris.

Comparison of cryptobenthic reef fish communities among microhabitats in the Red Sea.

Knowledge of community structure within an ecosystem is essential when trying to understand the function and importance of the system and when making related management decisions. Within the larger ecosystem, microhabitats play an important role by providing inhabitants with a subset of available resources. On coral reefs, cryptobenthic fishes encompass many groups and make up an important proportion of the biodiversity. However, these fishes are relatively small, exhibit extreme visual or behavioral camouflage, and, therefore, are often overlooked. We examined the differences in fish community structure between three common reef microhabitats (live hard coral, dead coral rubble, and sand) using ichthyocide stations in the central Red Sea. Using a combination of morphological and genetic (cytochrome oxidase I (COI) barcoding) techniques, we identified 326 individuals representing 73 species spread across 17 families, from fifteen 1 m2 quadrats. Fish assemblages in the three microhabitats were significantly different from each other. Rubble microhabitats yielded the highest levels of fish abundance, richness, and diversity, followed by hard coral, and then sand. The results show that benthic composition, even at a small scale, influences cryptobenthic communities. This study also provides new COI sequence data to public databases, in order to further the research of cryptobenthic fishes in the Red Sea region.