Minority Stress, Psychological Distress, Sexual Compulsivity, and Avoidance-Based Motivations Associated with Methamphetamine Use Among Sexual Minority Men Living with HIV: Examining Direct and Indirect Associations Using Cross-Sectional Structural Equation Modeling.

OBJECTIVE: Sexual minority men (SMM) living with HIV report significantly greater methamphetamine use compared with heterosexual and HIV-negative peers. Greater use may be related to stressors (e.g., HIV-related stigma) faced by SMM living with HIV and subsequent psychological and behavioral sequelae. We tested an integrated theoretical model comprised of pathways between stigma, discrimination, childhood sexual abuse, psychological distress, sexual compulsivity, and cognitive escape in predicting methamphetamine use among SMM living with HIV. METHODS: Among 423 SMM living with HIV, we tested a structural equation model examining factors hypothesized to be directly and indirectly associated with methamphetamine use. Analyses were adjusted for demographic covariates and sampling bias. RESULTS: The model showed good fit (CFI = 0.96, RMSEA = 0.01). Heterosexist discrimination was associated with psychological distress (ß = 0.39, p < 0.001) and psychological distress was associated with sexual compulsivity (ß = 0.33, p < 0.001). Sexual compulsivity was associated with cognitive escape (ß = 0.31, p < 0.001), which was associated with methamphetamine use (ß = 0.51, p < 0.001). Psychological distress was associated with methamphetamine use via serial indirect effects of sexual compulsivity and cognitive escape (ß = 0.05, p < 0.05). CONCLUSIONS: Heterosexist discrimination contributed to psychological distress among SMM living with HIV. Psychological distress is linked to methamphetamine use via sexual compulsivity and cognitive avoidance. Interventions seeking to reduce the likelihood that SMM living with HIV use methamphetamine should include coping strategies specific to heterosexism and related psychological distress.

Network signatures define consciousness state during focal seizures.

OBJECTIVE: Epilepsy is a common neurological disorder affecting 1% of the global population. Loss of consciousness in focal impaired awareness seizures (FIASs) and focal-to-bilateral tonic-clonic seizures (FBTCSs) can be devastating, but the mechanisms are not well understood. Although ictal activity and interictal connectivity changes have been noted, the network states of focal aware seizures (FASs), FIASs, and FBTCSs have not been thoroughly evaluated with network measures ictally. METHODS: We obtained electrographic data from 74 patients with stereoelectroencephalography (SEEG). Sliding window band power, functional connectivity, and segregation were computed on preictal, ictal, and postictal data. Five-minute epochs of wake, rapid eye movement sleep, and deep sleep were also extracted. Connectivity of subcortical arousal structures was analyzed in a cohort of patients with both SEEG and functional magnetic resonance imaging (fMRI). Given that custom neuromodulation of seizures is predicated on detection of seizure type, a convolutional neural network was used to classify seizure types. RESULTS: We found that in the frontoparietal association cortex, an area associated with consciousness, both consciousness-impairing seizures (FIASs and FBTCSs) and deep sleep had increases in slow wave delta (1-4 Hz) band power. However, when network measures were employed, we found that only FIASs and deep sleep exhibited an increase in delta segregation and a decrease in gamma segregation. Furthermore, we found that only patients with FIASs had reduced subcortical-to-neocortical functional connectivity with fMRI versus controls. Finally, our deep learning network demonstrated an area under the curve of .75 for detecting consciousness-impairing seizures. SIGNIFICANCE: This study provides novel insights into ictal network measures in FASs, FIASs, and FBTCSs. Importantly, although both FIASs and FBTCSs result in loss of consciousness, our results suggest that ictal network changes in FIASs uniquely resemble those that occur during deep sleep. Our results may inform novel neuromodulation strategies for preservation of consciousness in epilepsy.

The interictal suppression hypothesis is the dominant differentiator of seizure onset zones in focal epilepsy.

Successful surgical treatment of drug-resistant epilepsy traditionally relies on the identification of seizure onset zones (SOZs). Connectome-based analyses of electrographic data from stereo electroencephalography (SEEG) may empower improved detection of SOZs. Specifically, connectome-based analyses based on the Interictal Suppression Hypothesis (ISH) posit that when the patient is not having a seizure, SOZs are inhibited by non-SOZs through high inward connectivity and low outward connectivity. However, it is not clear whether there are other motifs that can better identify potential SOZs. Thus, we sought to use unsupervised machine learning to identify network motifs that elucidate SOZs and investigate if there is another motif that outperforms the ISH. Resting-state SEEG data from 81 patients with drug-resistant epilepsy undergoing a pre-surgical evaluation at Vanderbilt University Medical Center were collected. Directed connectivity matrices were computed using the alpha band (8-12Hz). Principal component analysis (PCA) was performed on each patient's connectivity matrix. Each patient's components were analyzed qualitatively to identify common patterns across patients. A quantitative definition was then used to identify the component that most closely matched the observed pattern in each patient. A motif characteristic of the Interictal Suppression Hypothesis (high-inward and low-outward connectivity) was present in all individuals and found to be the most robust motif for identification of SOZs in 64/81 (79%) patients. This principal component demonstrated significant differences in SOZs compared to non-SOZs. While other motifs for identifying SOZs were present in other patients, they differed for each patient, suggesting that seizure networks are patient specific, but the ISH is present in nearly all networks. We discovered that a potentially suppressive motif based on the Interictal Suppression Hypothesis was present in all patients, and it was the most robust motif for SOZs in 79% of patients. Each patient had additional motifs that further characterized SOZs, but these motifs were not common across all patients. This work has the potential to augment clinical identification of SOZs to improve epilepsy treatment.

Frequent Dietary Multi-Mycotoxin Exposure in UK Children and Its Association with Dietary Intake.

Mycotoxins are potent fungal toxins that frequently contaminate agricultural crops and foods. Mycotoxin exposure is frequently reported in humans, and children are known to be particularly at risk of exceeding safe levels of exposure. Urinary biomonitoring is used to assess overall dietary exposure to multiple mycotoxins. This study aims to quantify multi-mycotoxin exposure in UK children and to identify major food groups contributing to exposure. Four repeat urine samples were collected from 29 children (13 boys and 16 girls, aged 2.4-6.8 years), and food diaries were recorded to assess their exposure to eleven mycotoxins. Urine samples (n = 114) were hydrolysed with ß-glucuronidase, enriched through immunoaffinity columns and analysed by LC-MS/MS for deoxynivalenol (DON), nivalenol (NIV), T-2/HT-2 toxins, zearalenone (ZEN), ochratoxin A (OTA) and aflatoxins. Food diaries were analysed using WinDiet software, and the daily intake of high-risk foods for mycotoxin contamination summarised. The most prevalent mycotoxins found in urine samples were DON (95.6% of all samples), OTA (88.6%), HT-2 toxin (53.5%), ZEN (48.2%) and NIV (26.3%). Intake of total cereal-based foods was strongly positively associated with urinary levels of DON and T-2/HT-2 and oat intake with urinary T-2/HT-2. Average daily mycotoxin excretion ranged from 12.10 µg/d (DON) to 0.03 µg/d (OTA), and co-exposure to three or more mycotoxins was found in 66% of samples. Comparing mycotoxin intake estimates to tolerable daily intakes (TDI) demonstrates frequent TDI exceedances (DON 34.2% of all samples, T-2/HT-2 14.9%, NIV 4.4% and ZEN 5.2%). OTA was frequently detected at low levels. When mean daily OTA intake was compared to the reference value for non-neoplastic lesions, the resulting Margin of Exposure (MoE) of 65 was narrow, indicating a health concern. In conclusion, this study demonstrates frequent exposure of UK children to multiple mycotoxins at levels high enough to pose a health concern if exposure is continuous.

Fulfilling the Promise of Breathomics: Considerations for the Discovery and Validation of Exhaled Volatile Biomarkers.

The exhaled breath represents an ideal matrix for non-invasive biomarker discovery, and exhaled metabolomics have the potential to be clinically useful in the era of precision medicine. In this concise translational review we will specifically address volatile organic compounds in the breath, with a view towards fulfilling the promise of these as actionable biomarkers, in particular for lung diseases. We review the literature paying attention to seminal work linked to key milestones in breath research; discuss potential applications for breath biomarkers across disease areas and healthcare systems, including the perspectives of industry; and outline critical aspects of study design that will need to be considered for any pivotal research going forward, if breath analysis is to provide robust validated biomarkers that meet the requirements for future clinical implementation.

Effects of ballistic transport on the thermal resistance and temperature profile in nanowires.

Abstract: Effects of ballistic transport on the temperature profiles and thermal resistance in nanowires are studied. Computer simulations of nanowires between a heat source and a heat sink have shown that in the middle of such wires the temperature gradient is reduced compared to Fourier's law with steep gradients close to the heat source and sink. In this work, results from molecular dynamics and phonon Monte Carlo simulations of the heat transport in nanowires are compared to a radiator model which predicts a reduced gradient with discrete jumps at the wire ends. The comparison shows that for wires longer than the typical mean free path of phonons the radiator model is able to account for ballistic transport effects. The steep gradients at the wire ends are then continuous manifestations of the discrete jumps in the model.

Improving the Barrier and Mechanical Properties of Paper Used for Packing Applications with Renewable Hydrophobic Coatings Derived from Camelina Oil.

This study looked at using modified camelina oil to develop sustainable coatings that could replace those derived from petroleum-based materials for use in packaging and other industrial sectors. Solvent-free synthesis of maleic anhydride grafted camelina oil (MCO) was carried out at two different temperatures (200 and 230 °C) to obtain sustainable hydrophobic coating materials for paper substrates. Maleic anhydride grafting of camelina oil was confirmed with attenuated total reflectance-Fourier transform infrared and NMR spectroscopic techniques, and up to 16% grafting of maleic anhydride was achieved, as determined by the titration method. MCO, obtained at different reaction temperatures, was coated onto cellulosic paper and evaluated for its hydrophobicity, mechanical, oxygen, and water vapor barrier properties. Scanning electron microscopy indicated the homogeneous dispersion of coating material onto the paper substrate. MCO-coated papers (MCO-200C paper and MCO-230C paper) provided a water contact angle of above 90° which indicates that the modified oil was working as a hydrophobic coating. Water vapor permeability (WVP) testing of coated papers revealed a reduction in WVP of up to 94% in comparison to the uncoated paper. Moreover, an improved oxygen barrier property was also observed for paper coated with both types of MCO. Analysis of the mechanical properties showed a greater than 70% retention of tensile strength and up to a five-fold increase in elongation at break of coated versus uncoated papers. Overall, the results show that camelina oil, a renewable resource, can be modified to produce environmentally friendly hydrophobic coating materials with improved mechanical and water vapor barrier properties that can serve as a potential coating material in the packaging industry. The results of this research could find applications in the huge paper packaging industries, specially in food packaging.

PROTAX-GPU: a scalable probabilistic taxonomic classification system for DNA barcodes.

DNA-based identification is vital for classifying biological specimens, yet methods to quantify the uncertainty of sequence-based taxonomic assignments are scarce. Challenges arise from noisy reference databases, including mislabelled entries and missing taxa. PROTAX addresses these issues with a probabilistic approach to taxonomic classification, advancing on methods that rely solely on sequence similarity. It provides calibrated probabilistic assignments to a partially populated taxonomic hierarchy, accounting for taxa that lack references and incorrect taxonomic annotation. While effective on smaller scales, global application of PROTAX necessitates substantially larger reference libraries, a goal previously hindered by computational barriers. We introduce PROTAX-GPU, a scalable algorithm capable of leveraging the global Barcode of Life Data System (>14 million specimens) as a reference database. Using graphics processing units (GPU) to accelerate similarity and nearest-neighbour operations and the JAX library for Python integration, we achieve over a 1000 × speedup compared with the central processing unit (CPU)-based implementation without compromising PROTAX's key benefits. PROTAX-GPU marks a significant stride towards real-time DNA barcoding, enabling quicker and more efficient species identification in environmental assessments. This capability opens up new avenues for real-time monitoring and analysis of biodiversity, advancing our ability to understand and respond to ecological dynamics. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

Overcoming Delays in the Progress against Cancer: Identifying Tobacco Use among Cancer Patients Enrolled in Clinical Trials.

Though smoking causes adverse cancer treatment outcomes and smoking cessation can improve survival, prior literature demonstrates deficits in collecting tobacco use information in clinical trials. Results by Streck and colleagues represent a thorough structured assessment of tobacco use and alternative tobacco product use in patients enrolled in cooperative group trials. Among patients with predominantly non-tobacco related cancers, observations demonstrate that approximately 27% of patients reported using one or more forms of tobacco use after diagnosis. Alternative tobacco use was reported by many patients, including patterns of dual use. Results demonstrate the feasibility of collecting comprehensive structured tobacco use information, and further support the need to address tobacco and cessation even among patients with non-tobacco related cancers. See related article by Streck and colleagues, Cancer Epidemiol Biomarkers Prev 2023;32:1552-57.

Motive and Opportunity: MYC rearrangements in high-grade B-cell lymphoma with MYC and BCL2 rearrangements-an LLMPP study.

Rearrangements that place the oncogenes MYC, BCL2, or BCL6 adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both MYC and BCL2 rearrangements are classified as high-grade B-cell lymphoma with MYC and BCL2 rearrangements ("double hit": HGBCL-DH-BCL2) and are associated with aggressive disease and poor outcomes. Although it is established that MYC rearrangements involving immunoglobulin (IG) loci are associated with inferior outcomes relative to those involving other non-IG superenhancers, the frequency of, and mechanisms driving, IG vs non-IG MYC rearrangements have not been elucidated. Here we used custom targeted capture and/or whole genome sequencing to characterize oncogene rearrangements across 883 mature B-cell lymphomas including Burkitt lymphoma, follicular lymphoma, DLBCL, and HGBCL-DH-BCL2 tumors. We demonstrate that, while BCL2 rearrangement topology is consistent across entities, HGBCL-DH-BCL2 have distinct MYC rearrangement architecture relative to tumors with single MYC rearrangements or with both MYC and BCL6 rearrangements (HGBCL-DH-BCL6), including both a higher frequency of non-IG rearrangements and different architecture of MYC::IGH rearrangements. The distinct MYC rearrangement patterns in HGBCL-DH-BCL2 occur on the background of high levels of somatic hypermutation across MYC partner loci in HGBCL-DH-BCL2, creating more opportunity to form these rearrangements. Furthermore, because one IGH allele is already disrupted by the existing BCL2 rearrangement, the MYC rearrangement architecture in HGBCL-DH-BCL2 likely reflects selective pressure to preserve both BCL2 and B cell receptor expression. These data provide new mechanistic explanations for the distinct patterns of MYC rearrangements observed across different lymphoma entities.

Detection of mpox virus in wastewater provides forewarning of clinical cases in Canadian cities.

Wastewater-based surveillance (WBS) has shown to be an effective tool in monitoring the spread of SARS-CoV-2 and has helped guide public health actions. Consequently, WBS has expanded to now include the monitoring of mpox virus (MPXV) to contribute to its mitigation efforts. In this study, we demonstrate a unique sample processing and a molecular diagnostic strategy for MPXV detection that can inform on the epidemiological situation of mpox outbreaks through WBS. We conducted WBS for MPXV in 22 Canadian wastewater treatment plants (WWTPs) for 14 weeks. Three MPXV qPCR assays were assessed in this study for the detection of MPXV which include the G2R assays (G2R_WA and G2R_G) developed by the Centers for Disease Control and Prevention (CDC) in 2010, and an in-house-developed assay that we have termed G2R_NML. The G2R_NML assay was designed using reference genomes from the 2022 MPXV outbreak and provides a larger qPCR amplicon size to facilitate Sanger sequencing. Results show that all three assays have similar limits of detection and are able to detect the presence of MPXV in wastewater. The G2R_NML assay produced a significantly greater number of Sanger sequence-confirmed MPXV results compared to the CDC G2R assays. Detection of MPXV was possible where provincial surveillance indicated overall low caseloads, and in some sites forewarning of up to several weeks was observed. Overall, this study proposes that WBS of MPXV provides additional information to help fill knowledge gaps in clinical case-surveillance and is potentially an essential component to the management of mpox.

Estrogen stimulates fetal vascular endothelial growth factor expression and microvascularization.

We recently showed that the ratio of capillaries to myofibers in skeletal muscle, which accounts for 80% of insulin-directed glucose uptake and metabolism, was reduced in baboon fetuses in which estrogen was suppressed by maternal letrozole administration. Since vascular endothelial growth factor (VEGF) promotes angiogenesis, the present study determined the impact of estrogen deprivation on fetal skeletal muscle VEGF expression, capillary development, and long-term vascular and metabolic function in 4- to 8-year-old adult offspring. Maternal baboons were untreated or treated with letrozole or letrozole plus estradiol on days 100-164 of gestation (term = 184 days). Skeletal muscle VEGF protein expression was suppressed by 45% (P < 0.05) and correlated (P = 0.01) with a 47% reduction (P < 0.05) in the number of capillaries per myofiber area in fetuses of baboons in which serum estradiol levels were suppressed 95% (P < 0.01) by letrozole administration. The reduction in fetal skeletal muscle microvascularization was associated with a 52% decline (P = 0.02) in acetylcholine-induced brachial artery dilation and a 23% increase (P = 0.01) in mean arterial blood pressure in adult progeny of letrozole-treated baboons, which was restored to normal by letrozole plus estradiol. The present study indicates that estrogen upregulates skeletal muscle VEGF expression and systemic microvessel development within the fetus as an essential programming event critical for ontogenesis of systemic vascular function and insulin sensitivity/glucose homeostasis after birth in primate offspring.

TRAF3 loss-of-function reveals the noncanonical NF-κB pathway as a therapeutic target in diffuse large B cell lymphoma.

Here, we report recurrent focal deletions of the chr14q32.31-32 locus, including TRAF3, a negative regulator of NF-κB signaling, in de novo diffuse large B cell lymphoma (DLBCL) (24/324 cases). Integrative analysis revealed an association between TRAF3 copy number loss with accumulation of NIK, the central noncanonical (NC) NF-κB kinase, and increased NC NF-κB pathway activity. Accordingly, TRAF3 genetic ablation in isogenic DLBCL model systems caused upregulation of NIK and enhanced NC NF-κB downstream signaling. Knockdown or pharmacological inhibition of NIK in TRAF3-deficient cells differentially impaired their proliferation and survival, suggesting an acquired onco-addiction to NC NF-κB. TRAF3 ablation also led to exacerbated secretion of the immunosuppressive cytokine IL-10. Coculturing of TRAF3-deficient DLBCL cells with CD8+ T cells impaired the induction of Granzyme B and interferon (IFN) γ, which were restored following neutralization of IL-10. Our findings corroborate a direct relationship between TRAF3 genetic alterations and NC NF-κB activation, and highlight NIK as a potential therapeutic target in a defined subset of DLBCL.

Who Can Be Discharged Home after Adult Spinal Deformity Surgery?

Introduction: After adult spinal deformity (ASD) surgery, patients often require postoperative rehabilitation at an inpatient rehabilitation (IPR) center or a skilled nursing facility (SNF). However, home discharge is often preferred by patients and hsas been shown to decrease costs. In a cohort of patients undergoing ASD surgery, we sought to (1) report the incidence of discharge to home, (2) determine the factors significantly associated with discharge to home in the form of a simple scoring system, and (3) evaluate the impact of discharge disposition on patient-reported outcome measures (PROMs). Methods: A single-institution, retrospective cohort study was undertaken for patients undergoing ASD surgery from 2009 to 2021. Inclusion criteria were ≥ 5-level fusion, sagittal/coronal deformity, and at least 2-year follow-up. Exposure variables included preoperative, perioperative, and radiographic data. The primary outcome was discharge status (dichotomized as home vs. IPR/SNF). Secondary outcomes included PROMs, such as the numeric rating scales (NRSs) for back and leg pain, the Oswestry Disability Index (ODI), and EQ-5D. A subanalysis comparing IPR to SNF discharge was conducted. Univariate analysis was performed. Results: Of 221 patients undergoing ASD surgery with a mean age of 63.6 ± 17.6, 112 (50.6%) were discharged home, 71 (32.2%) were discharged to an IPR center, and 38 (17.2%) were discharged to an SNF. Patients discharged home were significantly younger (55.7 ± 20.1 vs. 71.8 ± 9.1, p < 0.001), had lower rate of 2+ comorbidities (38.4% vs. 45.0%, p = 0.001), and had less hypertension (57.1% vs. 75.2%, p = 0.005). Perioperatively, patients who were discharged home had significantly fewer levels instrumented (10.0 ± 3.0 vs. 11.0 ± 3.4 levels, p = 0.030), shorter operative times (381.4 ± 139.9 vs. 461.6 ± 149.8 mins, p < 0.001), less blood loss (1101.0 ± 977.8 vs. 1739.7 ± 1332.9 mL, p < 0.001), and shorter length of stay (5.4 ± 2.8 vs. 9.3 ± 13.9 days, p < 0.001). Radiographically, preoperative SVA (9.1 ± 6.5 vs. 5.2 ± 6.8 cm, p < 0.001), PT (27.5 ± 11.1° vs. 23.4 ± 10.8°, p = 0.031), and T1PA (28.9 ± 12.7° vs. 21.6 ± 13.6°, p < 0.001) were significantly higher in patients who were discharged to an IPR center/SNF. Additionally, the operating surgeon also significantly influenced the disposition status (p < 0.001). A scoring system of the listed factors was proposed and was validated using univariate logistic regression (OR = 1.55, 95%CI = 1.34-1.78, p < 0.001) and ROC analysis, which revealed a cutoff value of > 6 points as a predictor of non-home discharge (AUC = 0.75, 95%CI = 0.68-0.80, p < 0.001, sensitivity = 63.3%, specificity = 74.1%). The factors in the scoring system were age > 56, comorbidities ≥ 2, hypertension, TIL ≥ 10, operative time > 357 mins, EBL > 1200 mL, preop SVA > 6.6 cm, preop PT > 33.6°, and preop T1PA > 15°. When comparing IPR (n = 71) vs. SNF (n = 38), patients discharged to an SNF were significantly older (74.4 ± 8.6 vs. 70.4 ± 9.1, p = 0.029) and were more likely to be female (89.5% vs. 70.4%, p = 0.024). Conclusions: Approximately 50% of patients were discharged home after ASD surgery. A simple scoring system based on age > 56, comorbidities ≥ 2, hypertension, total instrumented levels ≥ 10, operative time > 357 mins, EBL > 1200 mL, preop SVA > 6.6 cm, preop PT > 33.6°, and preop T1PA > 15° was proposed to predict non-home discharge. These findings may help guide postoperative expectations and resource allocation after ASD surgery.

Universal Tobacco Screening and Opt-Out Treatment Referral Strategy Among Patients Diagnosed With Cancer by Race and Ethnicity.

This quality improvement study examines whether a universal screening and opt-out referral model could promote racial and ethnic equity in access and use of tobacco treatment among patients with cancer.

Reward Circuit Local Field Potential Modulations Precede Risk Taking.

Risk taking behavior is a symptom of multiple neuropsychiatric disorders and often lacks effective treatments. Reward circuitry regions including the amygdala, orbitofrontal cortex, insula, and anterior cingulate have been implicated in risk-taking by neuroimaging studies. Electrophysiological activity associated with risk taking in these regions is not well understood in humans. Further characterizing the neural signalling that underlies risk-taking may provide therapeutic insight into disorders associated with risk-taking. Eleven patients with pharmacoresistant epilepsy who underwent stereotactic electroencephalography with electrodes in the amygdala, orbitofrontal cortex, insula, and/or anterior cingulate participated. Patients participated in a gambling task where they wagered on a visible playing card being higher than a hidden card, betting $5 or $20 on this outcome, while local field potentials were recorded from implanted electrodes. We used cluster-based permutation testing to identify reward prediction error signals by comparing oscillatory power following unexpected and expected rewards. We also used cluster-based permutation testing to compare power preceding high and low bets in high-risk (<50% chance of winning) trials and two-way ANOVA with bet and risk level to identify signals associated with risky, risk averse, and optimized decisions. We used linear mixed effects models to evaluate the relationship between reward prediction error and risky decision signals across trials, and a linear regression model for associations between risky decision signal power and Barratt Impulsiveness Scale scores for each patient. Reward prediction error signals were identified in the amygdala (p=0.0066), anterior cingulate (p=0.0092), and orbitofrontal cortex (p=6.0E-4, p=4.0E-4). Risky decisions were predicted by increased oscillatory power in high-gamma frequency range during card presentation in the orbitofrontal cortex (p=0.0022), and by increased power following bet cue presentation across the theta-to-beta range in the orbitofrontal cortex ( p =0.0022), high-gamma in the anterior cingulate ( p =0.0004), and high-gamma in the insula ( p =0.0014). Risk averse decisions were predicted by decreased orbitofrontal cortex gamma power ( p =2.0E-4). Optimized decisions that maximized earnings were preceded by decreases within the theta to beta range in orbitofrontal cortex ( p =2.0E-4), broad frequencies in amygdala ( p =2.0E-4), and theta to low-gamma in insula ( p =4.0E-4). Insula risky decision power was associated with orbitofrontal cortex high-gamma reward prediction error signal ( p =0.0048) and with patient impulsivity ( p =0.00478). Our findings identify and help characterize reward circuitry activity predictive of risk-taking in humans. These findings may serve as potential biomarkers to inform the development of novel treatment strategies such as closed loop neuromodulation for disorders of risk taking.

Brain-wide human oscillatory local field potential activity during visual working memory.

Oscillatory activity in the local field potential (LFP) is thought to be a marker of cognitive processes. To understand how it differentiates tasks and brain areas in humans, we recorded LFPs in 15 adults with intracranial depth electrodes, as they performed visual-spatial and shape working memory tasks. Stimulus appearance produced widespread, broad-band activation, including in occipital, parietal, temporal, insular, and prefrontal cortex, and the amygdala and hippocampus. Occipital cortex was characterized by most elevated power in the high-gamma (100-150 Hz) range during the visual stimulus presentation. The most consistent feature of the delay period was a systematic pattern of modulation in the beta frequency (16-40 Hz), which included a decrease in power of variable timing across areas, and rebound during the delay period. These results reveal the widespread nature of oscillatory activity across a broad brain network and region-specific signatures of oscillatory processes associated with visual working memory.

Epigenetic studies in children at risk of stunting and their parents in India, Indonesia and Senegal: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: In 2020, an estimated 150 million children under the age of 5 years were stunted. Stunting results from early-life adversity and it is associated with significant physical and cognitive deficit, lifelong socioeconomic disadvantage and reduced life expectancy. There is a need to understand the causes of stunting and its effects in order to develop strategies to avoid it and to mitigate the consequences once stunting has occurred. Epigenetics is an important mechanism through which early-life factors are thought to influence biological function, with long-term consequences. We describe a series of epigenetic studies designed to understand how early-life adversity results in stunting and to inform the development of practical tools such as predictive markers and therapeutic targets. This work is part of the UKRI GCRF Action Against Stunting Hub. METHODS AND ANALYSIS: The project-in India, Indonesia and Senegal-comprises an observational study of mothers, fathers, and offspring (n=500) spanning the first 1000 days of life, and an intervention study in each country. Epigenetic status (DNA methylation) is determined in saliva from babies collected within 1 month of birth and again at 18 months of age, and from mothers and fathers around the time of birth. Epigenome-wide analysis is carried out using the Illumina EPIC array, augmented by high-definition sequencing approaches. Statistical analysis is carried out at the level of candidate genes/regions, higher dimensional epigenetic states and epigenome-wide association. Data analysis focuses on the determinants of stunting, the effectiveness of interventions, population comparisons and the link between epigenetics and other thematic areas, which include anthropometry, microbiome, gut health, parasitology, cognition, nutrition, food hygiene and water sanitation, food systems and the home environment. ETHICS AND DISSEMINATION: This study has been approved by the relevant Ethics Committees in Indonesia, India and Senegal, and the UK. Research data will be published and posted in public repositories.

Problematic alcohol use among gay, bisexual, and other men who have sex with men in Canada: the role of proximal stressors and anxiety.

BACKGROUND: Gay, bisexual, and other men who have sex with men (GBM) report high rates of problematic alcohol use, anxiety, and depression. This may, in part, be due to stressors related to their sexual identity (i.e., minority stressors). However, few studies have examined both distal and proximal stressors, as well as the specific psychological mechanisms by which these stressors may be related to alcohol use outcomes, in a representative sample of GBM. We explored the relationship between distal and proximal stressors and alcohol use outcomes, as well as the role of anxiety and depression as potential mediators of these relationships. METHODS: We analyzed the baseline data of 2,449 GBM from Engage, a cohort study of sexually active GBM recruited using respondent-driven sampling (RDS) in Montreal, Toronto, and Vancouver from February 2017 to August 2019. Using structural equation modeling, we examined the associations between distal minority stressors (i.e., experiences of heterosexist harassment, rejection, and discrimination), proximal minority stressors (i.e., internalized homonegativity, concerns about acceptance, concealment, and lack of affirmation), anxiety and depression, and alcohol consumption and alcohol use problems. RDS-adjusted analyses controlled for age, income, sexual orientation, ethnicity, recruitment city, and HIV serostatus. RESULTS: There were positive direct associations between distal stress and proximal stress, anxiety, and depression, but not alcohol use outcomes. Proximal stress had a positive direct association with anxiety, depression, and alcohol use problems, but not alcohol consumption. Anxiety was positively associated with alcohol consumption and alcohol use problems. Depression was negatively associated with alcohol consumption but not alcohol use problems. Regarding indirect effects, distal stress was associated with alcohol use outcomes via proximal stress and anxiety, but not via depression. CONCLUSIONS: We found support for a minority stress model as it relates to alcohol use outcomes among GBM. Findings suggest that proximal minority stress and anxiety differentially impact the problematic alcohol use among GBM who experience heterosexist discrimination. Clinical providers should consider incorporating the treatment of proximal minority stressors and anxiety into existing alcohol interventions for GBM.

Combined Anterior-Posterior vs. Posterior-Only Approach in Adult Spinal Deformity Surgery: Which Strategy Is Superior?

Introduction: Whether a combined anterior-posterior (AP) approach offers additional benefits over the posterior-only (P) approach in adult spinal deformity (ASD) surgery remains unknown. In a cohort of patients undergoing ASD surgery, we compared the combined AP vs. the P-only approach in: (1) preoperative/perioperative variables, (2) radiographic measurements, and (3) postoperative outcomes. Methods: A single-institution, retrospective cohort study was performed for patients undergoing ASD surgery from 2009 to 2021. Inclusion criteria were ≥5-level fusion, sagittal/coronal deformity, and 2-year follow-up. The primary exposure was the operative approach: a combined AP approach or P alone. Postoperative outcomes included mechanical complications, reoperation, and minimal clinically important difference (MCID), defined as 30% of patient-reported outcome measures (PROMs). Multivariable linear regression was controlled for age, BMI, and previous fusion. Results: Among 238 patients undergoing ASD surgery, 34 (14.3%) patients underwent the AP approach and 204 (85.7%) underwent the P-only approach. The AP group consisted mostly of anterior lumbar interbody fusion (ALIF) at L5/S1 (73.5%) and/or L4/L5 (38.0%). Preoperatively, the AP group had more previous fusions (64.7% vs. 28.9%, p < 0.001), higher pelvic tilt (PT) (29.6 ± 11.6° vs. 24.6 ± 11.4°, p = 0.037), higher T1 pelvic angle (T1PA) (31.8 ± 12.7° vs. 24.0 ± 13.9°, p = 0.003), less L1-S1 lordosis (-14.7 ± 28.4° vs. -24.3 ± 33.4°, p < 0.039), less L4-S1 lordosis (-25.4 ± 14.7° vs. 31.6 ± 15.5°, p = 0.042), and higher sagittal vertical axis (SVA) (102.6 ± 51.9 vs. 66.4 ± 71.2 mm, p = 0.005). Perioperatively, the AP approach had longer operative time (553.9 ± 177.4 vs. 397.4 ± 129.0 min, p < 0.001), more interbodies placed (100% vs. 17.6%, p < 0.001), and longer length of stay (8.4 ± 10.7 vs. 7.0 ± 9.6 days, p = 0.026). Radiographically, the AP group had more improvement in T1PA (13.4 ± 8.7° vs. 9.5 ± 8.6°, p = 0.005), L1-S1 lordosis (-14.3 ± 25.6° vs. -3.2 ± 20.2°, p < 0.001), L4-S1 lordosis (-4.7 ± 16.4° vs. 3.2 ± 13.7°, p = 0.008), and SVA (65.3 ± 44.8 vs. 44.8 ± 47.7 mm, p = 0.007). These outcomes remained statistically significant in the multivariable analysis controlling for age, BMI, and previous fusion. Postoperatively, no significant differences were found in mechanical complications, reoperations, or MCID of PROMs. Conclusions: Preoperatively, patients undergoing the combined anterior-posterior approach had higher PT, T1PA, and SVA and lower L1-S1 and L4-S1 lordosis than the posterior-only approach. Despite increased operative time and length of stay, the anterior-posterior approach provided greater sagittal correction without any difference in mechanical complications or PROMs.