Towards predicting PTSD symptom severity using portable EEG-derived biomarkers.

Posttraumatic Stress Disorder (PTSD) is a heterogeneous mental health disorder that occurs following traumatic experience. Understanding its neurobiological basis is crucial to advance early diagnosis and treatment. Electroencephalography (EEG) can be used to explore the neurobiological basis of PTSD. However, only limited research has explored mobile EEG, which is important for scalability. This proof-of-concept study delves into mobile EEG-derived biomarkers for PTSD and their potential implications. Over four weeks, we measured PTSD symptoms using the PTSD checklist for DSM-5 (PCL-5) at multiple timepoints, and we recorded multiple EEG sessions from 21 individuals using a mobile EEG device. In total, we captured 38 EEG sessions, each comprising two recordings that lasted approximately 180 seconds, to evaluate reproducibility. Next, we extracted Shannon entropy, as a measure of the randomness or unpredictability of the signal and spectral power for the fronto-temporal regions of interest, including electrodes at AF3, AF4, T7, and T8 for each EEG recording session. We calculated the partial correlation between the EEG variables and PCL-5 measured closest to the EEG session, using age, sex, and the grouping variable 'batch' as covariates. We observed a significant negative correlation between Shannon entropy in fronto-temporal regions and PCL-5 scores. Specifically, this association was evident in the AF3 (r = -0.456, FDR-corrected p = 0.01), AF4 (r = -0.362, FDR-corrected p = 0.04), and T7 (r = -0.472, FDR-corrected p = 0.01) regions. Additionally, we found a significant negative association between the alpha power estimated from AF4 and PCL-5 (r=-0.429, FDR-corrected p=0.04). Our findings suggest that EEG data acquired using a mobile EEG device is associated with PTSD symptom severity, offering valuable insights into the neurobiological mechanisms underlying PTSD.

Validation of Pelvis and Trunk Range of Motion as Assessed Using Inertial Measurement Units.

Trunk and pelvis range of motion (ROM) is essential to perform activities of daily living. The ROM may become limited with aging or with neuromusculoskeletal disorders. Inertial measurement units (IMU) with out-of-the box software solutions are increasingly being used to assess motion. We hypothesize that the accuracy (validity) and reliability (consistency) of the trunk and pelvis ROM during steady-state gait in normal individuals as measured using the Opal APDM 6 sensor IMU system and calculated using Mobility Lab version 4 software will be comparable to a gold-standard optoelectric motion capture system. Thirteen healthy young adults participated in the study. Trunk ROM, measured using the IMU was within 5-7 degrees of the motion capture system for all three planes and within 10 degrees for pelvis ROM. We also used a triad of markers mounted on the sternum and sacrum IMU for a head-to-head comparison of trunk and pelvis ROM. The IMU measurements were within 5-10 degrees of the triad. A greater variability of ROM measurements was seen for the pelvis in the transverse plane. IMUs and their custom software provide a valid and reliable measurement for trunk and pelvis ROM in normal individuals, and important considerations for future applications are discussed.

Microglia are dispensable for experience-dependent refinement of mouse visual circuitry.

To test the hypothesized crucial role of microglia in the developmental refinement of neural circuitry, we depleted microglia from mice of both sexes with PLX5622 and examined the experience-dependent maturation of visual circuitry and function. We assessed retinal function, receptive field tuning of visual cortex neurons, acuity and experience-dependent plasticity. None of these measurements detectibly differed in the absence of microglia, challenging the role of microglia in sculpting neural circuits.

A Feasibility Study on Re-establishing the Bioavailability/Bioequivalence Unit of the Department of Pharmacology and Toxicology, College of Medicine-University of the Philippines Manila.

Objectives: The Bioavailability/Bioequivalence Unit (BA/BE Unit) of the Department of Pharmacology and Toxicology, College of Medicine, University of the Philippines Manila which has not been operational since 2012, is due for renewal of its accreditation. To date, there are only three Philippine Food and Drug Administration-accredited laboratories that perform bioequivalence studies in the Philippines. One of the prerequisites of registering specific generic medicines is the conduct of Bioequivalence (BE) studies which are performed to ensure that the generic drug is at par with the innovator drug. Thus, this study aimed to determine the feasibility of re-establishing the BA/BE Unit as a bioequivalence testing center. Methods: The feasibility study done is a qualitative descriptive analysis based on expansive literature review and performance of SWOT analysis within the BA/BE unit. Literatures were selected based on its assessed relevance to the study. The databases checked were PubMed and Google Scholar. The terms used were from the Medical Subject Heading (MeSH) including feasibility studies, therapeutic equivalency, and generic drugs. Literature review was performed on the factors affecting the four types of feasibility studies (market, technical, financial, and organizational). A SWOT analysis of the BA/BE Unit was done through the review of records and documents of previous BE studies and focus group discussion among the BA/BE Unit team members. Results: The BA/BE Unit conducted 24 bioequivalence studies from 2006-2009 and still receives inquiries from drug companies. It implements its QMS throughout the pre-analytical, analytical, and post-analytical stages of the workflow. Its organizational structure consists of qualified professionals with updated GCP and GLP certificates. Because of the adequately equipped facility, lower honoraria for government-employed personnel, and lower expenses for laboratories and in-patient admissions, the cost of conducting a bioequivalence study in the BA/BE Unit will be lower than in other BE centers. Conclusion: Based on the SWOT analysis and market, technical, financial, and organizational considerations, re-establishing the BA/BE Unit as a bioequivalence testing center is feasible.

Critical thresholds of long-pressure reactivity index and impact of intracranial pressure monitoring methods in traumatic brain injury.

BACKGROUND: Moderate-to-severe traumatic brain injury (TBI) has a global mortality rate of about 30%, resulting in acquired life-long disabilities in many survivors. To potentially improve outcomes in this TBI population, the management of secondary injuries, particularly the failure of cerebrovascular reactivity (assessed via the pressure reactivity index; PRx, a correlation between intracranial pressure (ICP) and mean arterial blood pressure (MAP)), has gained interest in the field. However, derivation of PRx requires high-resolution data and expensive technological solutions, as calculations use a short time-window, which has resulted in it being used in only a handful of centers worldwide. As a solution to this, low resolution (longer time-windows) PRx has been suggested, known as Long-PRx or LPRx. Though LPRx has been proposed little is known about the best methodology to derive this measure, with different thresholds and time-windows proposed. Furthermore, the impact of ICP monitoring on cerebrovascular reactivity measures is poorly understood. Hence, this observational study establishes critical thresholds of LPRx associated with long-term functional outcome, comparing different time-windows for calculating LPRx as well as evaluating LPRx determined through external ventricular drains (EVD) vs intraparenchymal pressure device (IPD) ICP monitoring. METHODS: The study included a total of n = 435 TBI patients from the Karolinska University Hospital. Patients were dichotomized into alive vs. dead and favorable vs. unfavorable outcomes based on 1-year Glasgow Outcome Scale (GOS). Pearson's chi-square values were computed for incrementally increasing LPRx or ICP thresholds against outcome. The thresholds that generated the greatest chi-squared value for each LPRx or ICP parameter had the highest outcome discriminatory capacity. This methodology was also completed for the segmentation of the population based on EVD, IPD, and time of data recorded in hospital stay. RESULTS: LPRx calculated with 10-120-min windows behaved similarly, with maximal chi-square values ranging at around a LPRx of 0.25-0.35, for both survival and favorable outcome. When investigating the temporal relations of LPRx derived thresholds, the first 4 days appeared to be the most associated with outcomes. The segmentation of the data based on intracranial monitoring found limited differences between EVD and IPD, with similar LPRx values around 0.3. CONCLUSION: Our work suggests that the underlying prognostic factors causing impairment in cerebrovascular reactivity can, to some degree, be detected using lower resolution PRx metrics (similar found thresholding values) with LPRx found clinically using as low as 10 min-by-minute samples of MAP and ICP. Furthermore, EVD derived LPRx with intermittent cerebrospinal fluid draining, seems to present similar outcome capacity as IPD. This low-resolution low sample LPRx method appears to be an adequate substitute for the clinical prognostic value of PRx and may be implemented independent of ICP monitoring method when PRx is not feasible, though further research is warranted.

Functional Domains of Substance Use and their Implications to Trauma: A Systematic Review of Neuroimaging Studies.

Substance use disorder (SUD) is a significant health problem, and trauma exposure is a known risk factor for the escalation of substance use. However, the shared neural mechanisms through which trauma is associated with substance use are still unknown. Therefore, we systematically review neuroimaging studies focusing on three domains that may contribute to the overlapping mechanisms of SUD and trauma-reward salience, negative emotionality, and inhibition. Using PRISMA guidelines, we identified 45 studies utilizing tasks measuring these domains in alcohol, tobacco, and cannabis use groups. Greater reward, lesser regulation of inhibitory processes, and mixed findings of negative emotionality processes in individuals who use substances versus controls were found. Specifically, greater orbitofrontal cortex, ventral tegmental area, striatum, amygdala, and hippocampal activation was found in response to reward-related tasks, and reduced activation was found in the inferior frontal gyrus and hippocampus in response to inhibition-related tasks. Importantly, no studies in trauma-exposed individuals met our review criteria. Future studies examining the role of trauma-related factors are needed, and more studies should explore inhibition- and negative-emotionality domains in individuals who use substances to uncover clinically significant alterations in these domains that place an individual at greater risk for developing a SUD.

Magnesium enhances aurintricarboxylic acid's inhibitory action on the plasma membrane Ca2+-ATPase.

Our research aimed to elucidate the mechanism by which aurintricarboxylic acid (ATA) inhibits plasma membrane Ca2+-ATPase (PMCA), a crucial enzyme responsible for calcium transport. Given the pivotal role of PMCA in cellular calcium homeostasis, understanding how it is inhibited by ATA holds significant implications for potentially regulating physiopathological cellular processes in which this pump is involved. Our experimental findings revealed that ATA employs multiple modes of action to inhibit PMCA activity, which are influenced by ATP but also by the presence of calcium and magnesium ions. Specifically, magnesium appears to enhance this inhibitory effect. Our experimental and in-silico results suggest that, unlike those reported in other proteins, ATA complexed with magnesium (ATA·Mg) is the molecule that inhibits PMCA. In summary, our study presents a novel perspective and establishes a solid foundation for future research efforts aimed at the development of new pharmacological molecules both for PMCA and other proteins.

Severity influences categorical likelihood communications: A case study with Southeast Asian weather forecasters.

Risk assessments are common in multiple domains, from finance to medicine. They require evaluating an event's potential severity and likelihood. We investigate the possible dependence of likelihood and severity within the domain of impact-based weather forecasting (IBF), following predictions derived from considering asymmetric loss functions. In a collaboration between UK psychologists and partners from four meteorological organisations in Southeast Asia, we conducted two studies (N = 363) eliciting weather warnings from forecasters. Forecasters provided warnings denoting higher likelihoods for high severity impacts than low severity impacts, despite these impacts being described as having the same explicit numerical likelihood of occurrence. This 'Severity effect' is pervasive, and we find it can have a continued influence even for an updated forecast. It is additionally observed when translating warnings made on a risk matrix to numerical probabilities.

The Relations Among Childhood Maltreatment and Later Intimate Partner Violence Victimization With and Without a Weapon in a Sample of Pregnant Black Individuals.

Black pregnant and postpartum individuals are at risk for intimate partner violence (IPV), and those with a history of childhood maltreatment and IPV are even more likely to be re-victimized during pregnancy. However, it is unknown if specific types of child maltreatment predict later IPV with and without a weapon better than others. The current study sought to (i) document the prevalence of childhood maltreatment and IPV and (ii) examine the relations among types of childhood maltreatment and later IPV with and without a weapon within a sample of Black individuals seeking prenatal care at a large public hospital in the southeastern United States. Participants (n = 186; mean age = 27.2 years, SD = 5.3) completed measures assessing childhood maltreatment and IPV with and without a weapon. Approximately 68.5% of participants (n = 124) endorsed experiencing childhood maltreatment, while 42.6% (n = 78) endorsed experiencing IPV. The bivariate relations among five childhood maltreatment types (i.e., sexual, physical, and emotional abuse, physical and emotional neglect) and IPV with and without a weapon were assessed. All childhood maltreatment subtype scores-except childhood physical neglect-were significantly higher among participants who reported a history of IPV with or without a weapon compared to participants who denied a history of IPV with or without a weapon. Logistic regression models revealed childhood sexual abuse emerged as the only significant predictor of experiencing IPV with a weapon (B = 0.10, p = .003) and IPV without a weapon (B = 0.11, p = .001). For every point increase in childhood sexual abuse subtype score, the odds of experiencing IPV with and without a weapon increased by 10% (OR = 1.10, 95%CI [1.04, 1.18]) and 12% (OR = 1.12, [1.05, 1.20]), respectively. Findings suggest that screening for childhood sexual abuse may provide a critical opportunity for maternity care providers to identify individuals at increased risk for IPV victimization with and without a weapon.

Short Peptide and Amino Acid-Based Supramolecular Ionogels and Eutectogels.

The capability of peptide and amino acid-based molecules to act as ionogelators and eutectogelators entrapping ionic liquids (ILs) and deep eutectic solvents (DESs) forming ionogels and eutectogels has gathered attention in recent decades. The self-assembly process, primarily driven by non-covalent interactions as hydrogen bonding, remains serendipitous in nature. This review provides a comprehensive and detailed report on self-assembly of unmodified and modified amino acids and peptides in the non-conventional solvents, ILs and DESs. Understanding these processes holds great promise for the development of innovative soft-materials, and to the progress of supramolecular systems in non-conventional solvent environments.

Contrasting carbon cycle along tropical forest aridity gradients in West Africa and Amazonia.

Tropical forests cover large areas of equatorial Africa and play a substantial role in the global carbon cycle. However, there has been a lack of biometric measurements to understand the forests' gross and net primary productivity (GPP, NPP) and their allocation. Here we present a detailed field assessment of the carbon budget of multiple forest sites in Africa, by monitoring 14 one-hectare plots along an aridity gradient in Ghana, West Africa. When compared with an equivalent aridity gradient in Amazonia, the studied West African forests generally had higher productivity and lower carbon use efficiency (CUE). The West African aridity gradient consistently shows the highest NPP, CUE, GPP, and autotrophic respiration at a medium-aridity site, Bobiri. Notably, NPP and GPP of the site are the highest yet reported anywhere for intact forests. Widely used data products substantially underestimate productivity when compared to biometric measurements in Amazonia and Africa. Our analysis suggests that the high productivity of the African forests is linked to their large GPP allocation to canopy and semi-deciduous characteristics.

Neuroimaging of posttraumatic stress disorder in adults and youth: progress over the last decade on three leading questions of the field.

Almost three decades have passed since the first posttraumatic stress disorder (PTSD) neuroimaging study was published. Since then, the field of clinical neuroscience has made advancements in understanding the neural correlates of PTSD to create more efficacious treatment strategies. While gold-standard psychotherapy options are available, many patients do not respond to them, prematurely drop out, or never initiate treatment. Therefore, elucidating the neurobiological mechanisms that define the disorder can help guide clinician decision-making and develop individualized mechanisms-based treatment options. To this end, this narrative review highlights progress made in the last decade in adult and youth samples on three outstanding questions in PTSD research: (1) Which neural alterations serve as predisposing (pre-exposure) risk factors for PTSD development, and which are acquired (post-exposure) alterations? (2) Which neural alterations can predict treatment outcomes and define clinical improvement? and (3) Can neuroimaging measures be used to define brain-based biotypes of PTSD? While the studies highlighted in this review have made progress in answering the three questions, the field still has much to do before implementing these findings into clinical practice. Overall, to better answer these questions, we suggest that future neuroimaging studies of PTSD should (A) utilize prospective longitudinal designs, collecting brain measures before experiencing trauma and at multiple follow-up time points post-trauma, taking advantage of multi-site collaborations/consortiums; (B) collect two scans to explore changes in brain alterations from pre-to-post treatment and compare changes in neural activation between treatment groups, including longitudinal follow up assessments; and (C) replicate brain-based biotypes of PTSD. By synthesizing recent findings, this narrative review will pave the way for personalized treatment approaches grounded in neurobiological evidence.

Advances in understanding bat infection dynamics across biological scales.

Over the past two decades, research on bat-associated microbes such as viruses, bacteria and fungi has dramatically increased. Here, we synthesize themes from a conference symposium focused on advances in the research of bats and their microbes, including physiological, immunological, ecological and epidemiological research that has improved our understanding of bat infection dynamics at multiple biological scales. We first present metrics for measuring individual bat responses to infection and challenges associated with using these metrics. We next discuss infection dynamics within bat populations of the same species, before introducing complexities that arise in multi-species communities of bats, humans and/or livestock. Finally, we outline critical gaps and opportunities for future interdisciplinary work on topics involving bats and their microbes.

Large invertebrate decomposers contribute to faster leaf litter decomposition in Fraxinus excelsior-dominated habitats: Implications of ash dieback.

Leaf litter decomposition is a major component of nutrient cycling which depends on the quality and quantity of the leaf material. Ash trees (Fraxinus excelsior, decay time âˆ¼ 0.4 years) are declining throughout Europe due to a fungal pathogen (Hymenoscyphus fraxineus), which is likely to alter biochemical cycling across the continent. The ecological impact of losing species with fast decomposing leaves is not well quantified. In this study we examine how decomposition of three leaf species with varying decomposition rates including ash, sycamore (Acer pseudoplatanus, decay time âˆ¼ 1.4 years), and beech (Fagus sylvatica, decay time âˆ¼ 6.8 years) differ in habitats with and without ash as the dominant overstorey species. Ten plots (40 m × 40 m) were set up in five locations representing ash dominated and non-ash dominated habitats. In each plot mesh bags (30 cm × 30 cm, 0.5 mm aperture) with a single leaf species (5 g) were used to include (large holes added) and exclude macrofauna invertebrates (with a focus on decomposer organisms such as earthworms, millipedes, and woodlice). The mesh bags were installed in October 2020 and retrieved without replacement at exponential intervals after 6, 12, 24 and 48 weeks. Total leaf mass loss was highest in the ash dominated habitat (ash dominated: 88.5%, non-ash dominated: 66.5%) where macrofauna were the main contributor (macrofauna: 96%, microorganisms/mesofauna: 4%). The difference between macrofauna vs microorganisms and mesofauna was less pronounced in the non-ash dominated habitat (macrofauna: 68%, microorganisms/mesofauna: 31%). Our results suggest that if ash dominated habitats are replaced by species such as sycamore, beech, and oak, the role of macrofauna decomposers will be reduced and leaf litter decomposition rates will decrease by 25%. These results provide important insights for future ash dieback management decisions.

The adjuvant effect of oil-based gastric lavage on the outcome of acute Aluminum phosphide poisoning: a systematic review and meta-analysis.

Introduction: Aluminum Phosphide (AlP) poisoning constituted the most common cause of poisoning death in some low- and middle-income countries (LMICs). This study aimed to evaluate the safety and efficacy of oil-based gastric lavage (GL) compared with standard therapy for the treatment of AlP poisoning. Materials and methods. This systematic review complied with "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) Protocols. A comprehensive search was carried out, identifying randomized controlled trials (RCTs), including anyone presenting within 6 h of exposure to AlP, and the administration of GL with oils, including liquid paraffin or coconut oil. Results: We identified 7 RCTs. The evidence from 4 RCTs indicates that GL with paraffin oil is an effective treatment for acute AlP poisoning, decreasing the mortality rate (RR = 0.62; 95% CI = 0.48 to 0.81; participants = 226; I 2 = 10%; low-quality evidence). We estimate the Number Needed to Treat of 4. Likewise, this intervention reduces the need for intubation and mechanical ventilation (RR = 0.62; 95% CI = 0.40 to 0.79; I2 = 0%; low-quality evidence). Regarding GL with coconut oil, the evidence from 4 RCTs, indicates a slight reduction in mortality (RR = 0.82; 95% CI = 0.69 to 0.98; participants = 112; I2 = 0%; very low-quality evidence). Conclusions: Limited evidence suggests that GL with paraffin oil is effective in reducing the mortality rate. Likewise, limited evidence showed in favor of paraffin oil concerning the need for intubation and mechanical ventilation. Very limited evidence suggests that GL with coconut oil could reduce mortality. Both interventions would have a benign safety profile.

The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2, hospitalized and received supplemental O2, admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

Inhibitory medial zona incerta pathway drives exploratory behavior by inhibiting glutamatergic cuneiform neurons.

The cuneiform nucleus (CnF) regulates locomotor activity, which is canonically viewed as being primarily involved in initiating locomotion and regulating speed. Recent research shows greater context dependency in the locomotor functions of this nucleus. Glutamatergic neurons, which contain vesicular glutamate transporter 2 (vGLUT2), regulate context-dependent locomotor speed in the CnF and play a role in defensive behavior. Here, we identify projections from the medial zona incerta (mZI) to CnF vGLUT2 neurons that promote exploratory behavior. Using fiber photometry recordings in male mice, we find that mZI gamma-aminobutyric acid (GABA) neurons increase activity during periods of exploration. Activation of mZI GABAergic neurons is associated with reduced spiking of CnF neurons. Additionally, activating both retrogradely labeled mZI-CnF GABAergic projection neurons and their terminals in the CnF increase exploratory behavior. Inhibiting CnF vGLUT2 neuronal activity also increases exploratory behavior. These findings provide evidence for the context-dependent dynamic regulation of CnF vGLUT2 neurons, with the mZI-CnF circuit shaping exploratory behavior.

Integrating "Super Skills for Exams" Programme in the School Curriculum to Support Adolescents Preparing for Their National Examinations in Turkey.

Examination stress is the most common stressor reported by adolescents across the globe. Exam stress involves mental distress related to anticipated academic challenges or fear of failure in the examinations, test anxiety, or fear of being unable to meet certain expectations of themselves or others. The aim of this study was to determine the effectiveness of a transdiagnostic resilience program (Super Skills for Exams; SSE), when integrated in the school curriculum and delivered by the school counsellors, in reducing exam stress among adolescents who are preparing for their national examinations. SSE is based on the principles of Cognitive Behaviour Therapy (CBT), behavioural activation, and social skills training, and includes sessions in promoting healthy lifestyles. Participants were 7129 (3661 female and 3468 male) adolescents in grades 7 and 8, from all the 245 secondary schools from Ugur College in seven regions and 31 cities across Turkey. All the participants completed a set of questionnaires to measure self-efficacy for learning and test anxiety, academic stress, emotion regulation, and lifestyles. Results revealed significant reduction in academic stress (i.e., test anxiety, work pressure, self-expectation, and despondency) and maladaptive emotion regulation strategies, and significant increase in self-efficacy and adaptive regulation strategies following the intervention. Adolescents who participated in SSE reported an increase in the consumption of healthy food. This study provides preliminary empirical support for the integration of SSE within the school curriculum for helping adolescents cope with exam stress as they prepare for their national exams.