PTSD moderates the association between subjective cognitive decline and Alzheimer's disease biomarkers in older veterans.

OBJECTIVES: Post-traumatic stress disorder (PTSD) and subjective cognitive decline (SCD) are independent risk factors for Alzheimer's disease (AD) and dementia, but the association of their interaction on AD biomarkers have yet to be characterized. This study aimed to examine the impact of PTSD on the association between SCD and tau and amyloid positron emission tomography (PET) as well as global cognition in older Veterans. METHOD: This study included 87 Vietnam-Era Veterans without dementia (42 with PTSD; 45 without PTSD) from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative. All participants had both tau and amyloid PET imaging as well as cognitive testing. SCD was measured using the Everyday Cognition questionnaire. RESULTS: While SCD was associated with tau PET, amyloid PET, and global cognition, PTSD moderated these associations for tau and amyloid PET levels. Specifically, Veterans without PTSD had a stronger positive relationship between SCD and AD biomarkers when compared to those with PTSD. CONCLUSION: Higher SCD was associated with greater tau and amyloid burden and worse cognitive performance across the sample, though the tau and amyloid associations were stronger for Veterans without PTSD. Results highlight the potential benefit of comprehensive clinical assessments including consideration of mental health among older Veterans with SCD to understand the underlying cause of the cognitive concerns. Additionally, more work is needed to understand alternative mechanisms driving SCD in older Veterans with PTSD.

Elucidating the Impact of Rare Earth or Transition Metal Identity on the Physical and Electronic Structural Properties of a Series of Redox-Active Tris(amido) Complexes.

The use of redox-active ligands with the f-block elements has been employed to promote unique chemical transformations and explore their unique emergent electronic properties for a myriad of applications. In this study, we report eight new tris(amido) metal complexes: 1-Ln (Ln = Tb3+, Dy3+, Ho3+, Er3+, Tm3+, and Yb3+), 1-La, and 1-Ti (an early transition metal analogue). The one-electron oxidation of the tris(amido) ligand was conducted to generate semi-iminato complexes 2-Ln, 2-La, and 2-Ti, and these complexes were studied using EPR. Tris(amido) complexes 1-Ln, 1-La, and 1-Ti were fully characterized using a range of spectroscopic (NMR and UV-vis/NIR) and physical techniques (X-ray diffraction and cyclic voltammetry, with the exception of 1-La). Computational methods were employed to further elucidate the electronic structures of these complexes. Lastly, complexes 1-Ln, 1-La, and 1-Ti were probed as catalysts for alkyl-alkyl cross-coupling, and the initial rate of the reaction was measured to explore the influence of the metal ion.

Diagnostic utility of electrocardiogram for screening of cardiac injury on cardiac magnetic resonance in post-hospitalised COVID-19 patients: A prospective multicenter study.

BACKGROUND: The role of ECG in ruling out myocardial complications on cardiac magnetic resonance (CMR) is unclear. We examined the clinical utility of ECG in screening for cardiac abnormalities on CMR among post-hospitalised COVID-19 patients. METHODS: Post-hospitalised patients (n = 212) and age, sex and comorbidity-matched controls (n = 38) underwent CMR and 12­lead ECG in a prospective multicenter follow-up study. Participants were screened for routinely reported ECG abnormalities, including arrhythmia, conduction and R wave abnormalities and ST-T changes (excluding repolarisation intervals). Quantitative repolarisation analyses included corrected QT (QTc), corrected QT dispersion (QTc disp), corrected JT (JTc) and corrected T peak-end (cTPe) intervals. RESULTS: At a median of 5.6 months, patients had a higher burden of ECG abnormalities (72.2% vs controls 42.1%, p = 0.001) and lower LVEF but a comparable cumulative burden of CMR abnormalities than controls. Patients with CMR abnormalities had more ECG abnormalities and longer repolarisation intervals than those with normal CMR and controls (82% vs 69% vs 42%, p < 0.001). Routinely reported ECG abnormalities had poor discriminative ability (area-under-the-receiver-operating curve: AUROC) for abnormal CMR, AUROC 0.56 (95% CI 0.47-0.65), p = 0.185; worse among female than male patients. Adding JTc and QTc disp improved the AUROC to 0.64 (95% CI 0.55-0.74), p = 0.002, the sensitivity of the ECG increased from 81.6% to 98.0%, negative predictive value from 84.7% to 96.3%, negative likelihood ratio from 0.60 to 0.13, and reduced sex-dependence variabilities of ECG diagnostic parameters. CONCLUSION: Post-hospitalised COVID-19 patients have more ECG abnormalities than controls. Normal ECGs, including normal repolarisation intervals, reliably exclude CMR abnormalities in male and female patients.

Cognitive and psychiatric symptom trajectories 2-3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK.

BACKGROUND: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2-3 years, and whether symptoms at 2-3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2-3 years were associated with occupation change. People with lived experience were involved in the study. FINDINGS: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2-3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16-1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2-3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2-3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0-48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0-17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2-3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6-31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04-2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21-1·98] for every point increase in CCI-20). INTERPRETATION: Psychiatric and cognitive symptoms appear to increase over the first 2-3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19. FUNDING: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research.

Cognitive Motor Dissociation in Disorders of Consciousness.

BACKGROUND: Patients with brain injury who are unresponsive to commands may perform cognitive tasks that are detected on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness. METHODS: In this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness. We assessed the response to commands on task-based fMRI or EEG in participants without an observable response to verbal commands (i.e., those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state-minus) and in participants with an observable response to verbal commands. The presence or absence of an observable response to commands was assessed with the use of the Coma Recovery Scale-Revised (CRS-R). RESULTS: Data from fMRI only or EEG only were available for 65% of the participants, and data from both fMRI and EEG were available for 35%. The median age of the participants was 37.9 years, the median time between brain injury and assessment with the CRS-R was 7.9 months (25% of the participants were assessed with the CRS-R within 28 days after injury), and brain trauma was an etiologic factor in 50%. We detected cognitive motor dissociation in 60 of the 241 participants (25%) without an observable response to commands, of whom 11 had been assessed with the use of fMRI only, 13 with the use of EEG only, and 36 with the use of both techniques. Cognitive motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In contrast, responses on task-based fMRI or EEG occurred in 43 of 112 participants (38%) with an observable response to verbal commands. CONCLUSIONS: Approximately one in four participants without an observable response to commands performed a cognitive task on fMRI or EEG as compared with one in three participants with an observable response to commands. (Funded by the James S. McDonnell Foundation and others.).

Enolase inhibitors as therapeutic leads for Naegleria fowleri infection.

Infections with the pathogenic free-living amoebae Naegleria fowleri can lead to life-threatening illnesses including catastrophic primary amoebic meningoencephalitis (PAM). Efficacious treatment options for these infections are lacking and the mortality rate remains >95% in the US. Glycolysis is very important for the infectious trophozoite lifecycle stage and inhibitors of glucose metabolism have been found to be toxic to the pathogen. Recently, human enolase 2 (ENO2) phosphonate inhibitors have been developed as lead agents to treat glioblastoma multiforme (GBM). These compounds, which cure GBM in a rodent model, are well-tolerated in mammals because enolase 1 (ENO1) is the predominant isoform used systemically. Here, we describe findings that demonstrate these agents are potent inhibitors of N. fowleri ENO (NfENO) and are lethal to amoebae. In particular, (1-hydroxy-2-oxopiperidin-3-yl) phosphonic acid (HEX) was a potent enzyme inhibitor (IC50 = 0.14 ± 0.04 µM) that was toxic to trophozoites (EC50 = 0.21 ± 0.02 µM) while the reported CC50 was >300 µM. Molecular docking simulation revealed that HEX binds strongly to the active site of NfENO with a binding affinity of -8.6 kcal/mol. Metabolomic studies of parasites treated with HEX revealed a 4.5 to 78-fold accumulation of glycolytic intermediates upstream of NfENO. Last, nasal instillation of HEX increased longevity of amoebae-infected rodents. Two days after infection, animals were treated for 10 days with 3 mg/kg HEX, followed by one week of observation. At the end of the one-week observation, eight of 12 HEX-treated animals remained alive (resulting in an indeterminable median survival time) while one of 12 vehicle-treated rodents remained, yielding a median survival time of 10.9 days. However, intranasal HEX delivery was not curative as brains of six of the eight survivors were positive for amoebae. These findings suggest that HEX requires further evaluation to develop as a lead for treatment of PAM.

CTEPH is an uncommon complication of COVID-19: UK national surveillance and observational screening cohort studies.

INTRODUCTION: Pulmonary embolism (PE) is a well-recognised complication of COVID-19 infection, and chronic thromboembolic pulmonary disease with and without pulmonary hypertension (CTEPD/CTEPH) are potential life-limiting consequences. At present the burden of CTEPD/CTEPH is unclear and optimal and cost-effective screening strategies yet to be established. METHODS: We evaluated the CTEPD/CTEPH referral rate to the UK national multidisciplinary team (MDT) during the 2017-2022 period to establish the national incidence of CTEPD/CTEPH potentially attributable to COVID-19-associated PE with historical comparator years. All individual cases of suspected CTEPH were reviewed by the MDT for evidence of associated COVID-19. In a separate multicentre cohort, the risk of developing CTEPH following hospitalisation with COVID-19 was calculated using simple clinical parameters at a median of 5 months post hospital discharge according to existing risk scores using symptoms, ECG and NT pro-BNP. RESULTS: By the second year of the pandemic, CTEPH diagnoses had returned to the pre-pandemic baseline (23.1 versus 27.8 cases per month, p=0.252). Of 334 confirmed CTEPD/CTEPH cases, 4 (1.2%) patients were identified to have CTEPH potentially associated with COVID-19 PE, and a further 3 (0.9%) CTEPD without PH. Of 1094 patients (mean age 58 years, 60.4% male) hospitalised with COVID-19 screened across the UK, 11 (1.0%) were at high risk of CTEPH at follow-up, none of whom had a diagnosis of CTEPH made at the national MDT. CONCLUSION: A-priori risk of developing CTEPH following COVID-19-related hospitalisation is low. Simple risk scoring is a potentially effective way of screening patients for further investigation.

Development of the Technical Assistance Engagement Scale: a modified Delphi study.

BACKGROUND: Technical assistance (TA) is a tailored approach to capacity building that is commonly used to support implementation of evidence-based interventions. Despite its widespread applications, measurement tools for assessing critical components of TA are scant. In particular, the field lacks an expert-informed measure for examining relationship quality between TA providers and recipients. TA relationships are central to TA and significantly associated with program implementation outcomes. The current study seeks to address the gap in TA measurement tools by providing a scale for assessing TA relationships. METHODS: We utilized a modified Delphi approach involving two rounds of Delphi surveys and a panel discussion with TA experts to garner feedback and consensus on the domains and items that compose the TA Engagement Scale. RESULTS: TA experts represented various U.S. organizations and TA roles (e.g., provider, recipient, researcher) with 25 respondents in the first survey and 26 respondents in the second survey. The modified Delphi process resulted in a scale composed of six domains and 22 items relevant and important to TA relationships between providers and recipients. CONCLUSION: The TA Engagement Scale is a formative evaluation tool intended to offer TA providers the ability to identify strengths and areas for growth in the provider-recipient relationship and to communicate about ongoing needs. As a standard measurement tool, it lends a step toward more systematic collection of TA data, the ability to generate a more coherent body of TA evidence, and enables comparisons of TA relationships across settings.

APOE×BDNF Interaction and Poorer Cognitive Outcomes Among Veterans With Mild Traumatic Brain Injury: An Exploratory Study.

OBJECTIVE: The authors examined the interaction between apolipoprotein E (APOE) ε4 and brain-derived neurotrophic factor (BDNF) Val66Met alleles on neuropsychological functioning among veterans with histories of mild traumatic brain injury (mTBI). METHODS: Participants were 78 veterans with mTBI (85% males; mean±SD age=32.95±7.00 years; mean time since injury=67.97±34.98 months) who completed a structured clinical interview and underwent a comprehensive neuropsychological assessment. Participants also provided a buccal swab for determination of their APOE and BDNF genotypes. Three cognitive composite scores were calculated from the neuropsychological assessment, reflecting visuospatial speed (seven variables), executive functioning (10 variables), and memory (eight variables). Two-way analyses of covariance (ANCOVAs) adjusted for age, sex, and race-ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning. RESULTS: ANCOVAs revealed no significant main effects of APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE-by-BDNF genotype interaction for all three cognitive composite measures (visuospatial speed: ηp2=0.055; executive functioning: ηp2=0.064; and memory: ηp2=0.068). Specifically, the ε4+/Met+ (N=8) subgroup demonstrated the poorest cognitive functioning relative to all other allele subgroups (ε4+/Met-: N=12, ε4-/Met+: N=23, and ε4-/Met-: N=35). CONCLUSIONS: This exploratory study is the first to show that, compared with other allele subgroups assessed, veterans with both ε4 and Met alleles demonstrated the poorest cognitive functioning across several cognitive domains known to be negatively affected in the context of mTBI. Further research with larger sample sizes is needed to replicate these findings.

Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

One of the justifiable criticisms of human genetic studies is the underrepresentation of participants from diverse populations. Lack of inclusion must be addressed at-scale to identify causal disease factors and understand the genetic causes of health disparities. We present genome-wide associations for 2068 traits from 635,969 participants in the Department of Veterans Affairs Million Veteran Program, a longitudinal study of diverse United States Veterans. Systematic analysis revealed 13,672 genomic risk loci; 1608 were only significant after including non-European populations. Fine-mapping identified causal variants at 6318 signals across 613 traits. One-third (n = 2069) were identified in participants from non-European populations. This reveals a broadly similar genetic architecture across populations, highlights genetic insights gained from underrepresented groups, and presents an extensive atlas of genetic associations.

Sex differences in postconcussive symptom reporting in those with history of concussion: Findings from the federal interagency traumatic brain injury research (FITBIR) database.

Objective: This study investigated influence of biological sex on postconcussive symptoms (PCS) following concussion using the Federal Interagency Traumatic Brain Injury Research (FITBIR) database. Method: All studies with publicly released data as of 4/7/21 that included both males and females, enough information to determine severity of injury consistent with concussion, a measure of PCS, and objective measures of neurocognitive functioning were used. This resulted in 6 studies with a total of 9890 participants (3206 females, 6684 males); 815 participants completed the Neurobehavioral Symptom Inventory (NSI), 471 completed the Rivermead Post-Concussion Symptoms Questionnaire (RPSQ), and 8604 completed the Sport Concussion Assessment Tool-3rd Edition (SCAT 3). Questionnaires were harmonized and the following symptom composite scores were computed: total score, somatic, cognitive, and affective. Data were analyzed using linear mixed-effects models. Results: Females endorsed higher total symptoms relative to males and that military personnel endorsed higher symptoms relative to civilians. Additionally, there was a small but significant interaction effect, such that female military personnel endorsed even higher symptoms than would be predicted by the main effects. Similar patterns were observed for somatic, cognitive, and affective symptom domains. Conclusions: Further understanding sex differences in PCS reporting is key to informing the most appropriate treatment options. Future work will need to examine whether sex differences in symptom reporting is due to sex differences in endorsement styles or genuine differences in symptom presentation, as well as the relationship between study population (e.g., military, civilian, sport) and sex on objective cognitive functioning and other functional outcomes.

Diagnostic MRI Score to Differentiate Susac Syndrome from Primary Angiitis of the Central Nervous System and Multiple Sclerosis.

OBJECTIVE: Susac syndrome (SuS), multiple sclerosis (MS), and primary angiitis of the central nervous system (PACNS) present diagnostic challenges due to overlapping clinical features. We aimed to enhance diagnostic precision by developing the SPAMS (SuS, PACNS, MS) score, a practical radiological tool. METHODS: This multicenter study included 99 patients (43 SuS, 37 MS, 19 PACNS) from South American countries. Relevant MRI features were identified through an elastic-net model determined key variables. RESULTS: The SPAMS score assigned 2 points for snowball lesions, 1 point for spokes-like lesions, or if there are more than 4 lesions in the corpus callosum, corpus callosum involvement, or cerebellar involvement. It subtracted 1 point if gadolinium-enhancing lesions or 4 points if Dawson's fingers are present. Bootstrapping validated the optimal cutoff at 2 points, exhibiting a diagnostic performance of area under the curve = 0.931, sensitivity = 88%, specificity = 89%, positive predictive value = 88%, negative predictive value = 89%, and accuracy = 88%. INTERPRETATION: When specific MRI findings coexisted, the SPAMS score differentiated SuS from MS and PACNS. Access to MRI and standard protocol sequences makes it a valuable tool for timely diagnosis and treatment, potentially preventing disability progression and severe clinical outcomes. ANN NEUROL 2024.

Long-term impact of COVID-19 hospitalisation among individuals with pre-existing airway diseases in the UK: a multicentre, longitudinal cohort study - PHOSP-COVID.

Background: The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods: Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results: A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p<0.001), had higher burden of anxiety (29.1% versus 22.0%, p=0.002), depression (31.2% versus 24.7%, p=0.006), higher percentage of impaired mobility using short physical performance battery ≤10 (57.4% versus 45.2%, p<0.001) and 27% had a new disability (assessed by the Washington Group Short Set on Functioning) versus 16.6%, p=0.014. HRQoL assessed using EQ-5D-5L Utility Index was lower in the airways group (mean±SD 0.64±0.27 versus 0.73±0.25, p<0.001). Burden of breathlessness, fatigue and cough measured using a study-specific tool was higher in the airways group. Conclusion: Individuals with pre-existing airway diseases hospitalised due to COVID-19 were less likely to feel fully recovered, had lower physiological performance measurements, more burden of symptoms and reduced HRQoL up to 1 year post-hospital discharge.

The relationship between intraosseous catheter tip placement, flow rates, and infusion pressures in a high bone density cadaveric swine (Sus scrofa) model.

Background: Intraosseous (IO) infusion is a life-preserving technique when intravenous access is unobtainable. Successful IO infusion requires sufficiently high flow rates to preserve life but at low enough pressures to avoid complications. However, IO catheter tips are often misplaced, and the relative flow rates and pressures between IO catheter tips placed in medullary, trabecular, and cortical bone are not well described, which has important implications for clinical practice. Objectives: We developed the Zone Theory of IO Catheter Tip Placement based on bone density and proximity to the venous central sinus and then tested the influence of catheter tip placement locations on flow rates and pressures in a cadaveric swine model. Methods: Three cross-trained participants infused 500 mL of crystalloid fluid into cadaveric swine humerus and sternum (N = 210 trials total) using a push‒pull method with a 60 cm3 syringe. Computed tomography scans were scored by radiologists and categorized as zone 1 (medullary space), zone 2 (trabecular bone), or zone 3 (cortical bone) catheter tip placements. Differences between zones in flow rates, mean pressures, and peak pressures were assessed using analysis of variance and analysis of covariance to account for participant and site differences at the p < 0.05 threshold. Results: Zone 1 and zone 2 placements were essentially identical in flow rates, mean pressures, and peak pressures (each p > 0.05). Zone 1 and zone 2 placements were significantly higher in flow rates and lower in pressures than zone 3 placements (each p < 0.05 or less). Conclusion: Within the limitations of an unpressurized cadaveric swine model, the present findings suggest that IO catheter tip placements need not be perfect to acquire high flow rates at low pressures, only accurate enough to avoid the dense cortical bone of zone 3. Future research using in vivo animal and human models is needed to better define the clinical impact of IO catheter placement on infusion flow rates and pressures.

Development and validation of an electronic health record-based algorithm for identifying TBI in the VA: A VA Million Veteran Program study.

The purpose of this study was to develop and validate an algorithm for identifying Veterans with a history of traumatic brain injury (TBI) in the Veterans Affairs (VA) electronic health record using VA Million Veteran Program (MVP) data. Manual chart review (n = 200) was first used to establish 'gold standard' diagnosis labels for TBI ('Yes TBI' vs. 'No TBI'). To develop our algorithm, we used PheCAP, a semi-supervised pipeline that relied on the chart review diagnosis labels to train and create a prediction model for TBI. Cross-validation was used to train and evaluate the proposed algorithm, 'TBI-PheCAP.' TBI-PheCAP performance was compared to existing TBI algorithms and phenotyping methods, and the final algorithm was run on all MVP participants (n = 702,740) to assign a predicted probability for TBI and a binary classification status choosing specificity = 90%. The TBI-PheCAP algorithm had an area under the receiver operating characteristic curve of 0.92, sensitivity of 84%, and positive predictive value (PPV) of 98% at specificity = 90%. TBI-PheCAP generally performed better than other classification methods, with equivalent or higher sensitivity and PPV than existing rules-based TBI algorithms and MVP TBI-related survey data. Given its strong classification metrics, the TBI-PheCAP algorithm is recommended for use in future population-based TBI research.

Effect of co-administration of gallic acid and quercetin or gallic acid and rutin on impaired spermatogenesis and oxidative damage in a busulfan-treated rat model.

Gallic acid (GAL), rutin (RUT), and quercetin (QUE) are common antioxidant agents in fruits and vegetables with intriguing pharmacological effects. In the present study, we compared the therapeutic outcomes of GAL + QUE in comparison with GAL + RUT co-treatment in a busulfan (BUS) model of testicular injury in Wistar rats. BUS (4 mg kg-1 body weight (b.w) was injected intraperitoneally daily for 4 days. GAL + RUT or GAL + QUE (20 mg kg-1 b. w) was delivered by oral gavage for 52 days. Examination of the testes of BUS-treated rats both biochemically and under light microscopy revealed an increased level of lipid peroxidation, DNA fragmentation, glutathione-S-transferase, lactate dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase and acid phosphatase with a concomitant decrease in the level of antioxidants: glutathione, ascorbic acid, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, suggesting testicular injury. Tissue sections confirmed the testicular injury-induced by BUS, including diminished spermatogenesis score index, tubular diameter, gonado-somatic index, testis weight, epithelia thickness and higher percentage of aberrant tubules. GAL + QUE co-administration had better recovery effects than GAL + RUT on the biochemical markers and protected against BUS-induced testicular damage. GAL + QUE treatment regimen has better capacity to maintain the antioxidant capacity of the testes and is more potent at reducing BUS-induced oxidative damage compared to GAL + RUT.

The Epidemiology of Ocular Chlamydia trachomatis Infection within Districts Persistently Endemic for Trachoma in Amhara, Ethiopia.

Persistent trachoma is a growing concern to trachoma control programs globally and programs serving Ethiopia specifically. Persistent trachoma is defined as a district with two or more trachoma impact surveys (TISs) at which the prevalence of trachomatous inflammation-follicular (TF) among children ages 1-9 years is ≥5%, the elimination threshold. Because the global target for trachoma elimination as a public health problem is 2030, research is needed to better characterize persistent trachoma. This study described the epidemiology of ocular Chlamydia trachomatis infection, the causative bacteria of trachoma, in seven contiguous districts experiencing persistent trachoma. In 2019, multistage cluster random sampling TISs were conducted in the seven districts after 10 years of interventions. All individuals ages ≥1 year were examined for trachoma clinical signs by certified graders, and conjunctival swabs were collected from children ages 1-5 years to test for C. trachomatis infection. The district TF prevalence ranged from 11.8% (95% CI:7.6-16.0%) to 36.1% (95% CI:27.4-44.3%). The range of district-level C. trachomatis infection prevalence was between 2.7% and 34.4%. Statistically significant spatial clustering of high-infection communities was observed in the study districts, and children with infection were more likely than those without to be found in households with clinical signs of trachoma and those without latrines. These seven districts appear to constitute a persistent hotspot in Amhara, where an additional 3-5 years or more of interventions will be required. The global program will need to strengthen and enhance intervention strategies within persistent districts if elimination by 2030 is to be achieved.

Prediction of Vacuum Ultraviolet/Ultraviolet Gas-Phase Absorption Spectra Using Molecular Feature Representations and Machine Learning.

Ultraviolet (UV) absorption spectroscopy is a widely used tool for quantitative and qualitative analyses of chemical compounds. In the gas phase, vacuum UV (VUV) and UV absorption spectra are specific and diagnostic for many small molecules. An accurate prediction of VUV/UV absorption spectra can aid the characterization of new or unknown molecules in areas such as fuels, forensics, and pharmaceutical research. An alternative to quantum chemical spectral prediction is the use of artificial intelligence. Here, different molecular feature representation techniques were used and developed to encode chemical structures for testing three machine learning models to predict gas-phase VUV/UV absorption spectra. Structure data files (.sdf) and VUV/UV absorption spectra for 1397 volatile and semivolatile chemical compounds were used to train and test the models. New molecular features (termed ABOCH) were introduced to better capture pi-bonding, aromaticity, and halogenation. The incorporation of these new features benefited spectral prediction and demonstrated superior performance compared to computationally intensive molecular-based deep learning methods. Of the machine learning methods, the use of a Random Forest regressor returned the best accuracy score with the shortest training time. The developed machine learning prediction model also outperformed spectral predictions based on the time-dependent density functional theory.