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Abstract Chemotherapy frequently causes debilitating gastrointestinal symptoms, which are inadequately managed by current treatments. Recent research indicates the gut microbiome plays a role in the pathogenesis of these symptoms. The current study aimed to identify pre-chemotherapy microbiome markers that predict gastrointestinal symptom severity after breast cancer chemotherapy. Fecal samples, blood, and gastrointestinal symptom scores were collected from 59 breast cancer patients before, during, and after chemotherapy. Lower pre-chemotherapy microbiome alpha diversity and abundance of specific microbes (e.g., Faecalibacterium) predicted greater chemotherapy-induced gastrointestinal symptoms. Notably, tumor and diet characteristics were associated with lower pre-chemotherapy alpha diversity. Lower baseline alpha diversity also predicted higher chemotherapy-induced microbiome disruption, which was positively associated with diarrhea symptoms. The results indicate certain cancer patients have lower microbiome diversity before chemotherapy, which is predictive of greater chemotherapy-induced gastrointestinal symptoms and a less resilient microbiome. These patients may be strong candidates for pre-chemotherapy microbiome-directed preventative interventions (e.g., diet change).

Abstract Background Autism and schizophrenia spectrum disorders (SSDs) both feature atypical social cognition. Despite evidence for comparable group-level performance in lower-level emotion processing and higher-level mentalizing, limited research has examined the neural basis of social cognition across these conditions. Our goal was to compare the neural correlates of social cognition in autism, SSDs, and typically developing controls (TDCs). Methods Data came from two harmonized studies in individuals diagnosed with autism or SSDs and TDCs (aged 16–35 years), including behavioral social cognitive metrics and two functional magnetic resonance imaging (fMRI) tasks: a social mirroring Imitate/Observe (ImObs) task and the Empathic Accuracy (EA) task. Group-level comparisons, and transdiagnostic analyses incorporating social cognitive performance, were run using FSL’s PALM for each task, covarying for age and sex (1000 permutations, thresholded at p

Abstract Depressive symptoms in Schizophrenia Spectrum Disorders (SSDs) negatively impact suicidality, prognosis, and quality of life. Despite this, efficacious treatments are limited, largely because the neural mechanisms underlying depressive symptoms in SSDs remain poorly understood. We conducted a systematic review to provide an overview of studies that investigated the neural correlates of depressive symptoms in SSDs using neuroimaging techniques. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases from inception through June 19, 2023. Specifically, we focused on structural and functional magnetic resonance imaging (MRI), encompassing: (1) T1-weighted imaging measuring brain morphology; (2) diffusion-weighted imaging assessing white matter integrity; or (3) T2*-weighted imaging measures of brain function. Our search yielded 33 articles; 14 structural MRI studies, 18 functional (f)MRI studies, and 1 multimodal fMRI/MRI study. Reviewed studies indicate potential commonalities in the neurobiology of depressive symptoms between SSDs and major depressive disorders, particularly in subcortical and frontal brain regions, though confidence in this interpretation is limited. The review underscores a notable knowledge gap in our understanding of the neurobiology of depression in SSDs, marked by inconsistent approaches and few studies examining imaging metrics of depressive symptoms. Inconsistencies across studies’ findings emphasize the necessity for more direct and comprehensive research focusing on the neurobiology of depression in SSDs. Future studies should go beyond “total score” depression metrics and adopt more nuanced assessment approaches considering distinct subdomains. This could reveal unique neurobiological profiles and inform investigations of targeted treatments for depression in SSDs.

Summary: Background: Contemporary surgical practices for traumatic brain injury (TBI) remain unclear. We describe the clinical profile of an 18-centre US TBI cohort with cranial surgery. Methods: The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (2014–2018; ClinicalTrials.gov #NCT02119182) enrolled subjects who presented to trauma centre and received head computed tomography within 24-h (h) post-TBI. We performed a secondary data analysis in subjects aged ≥17-years with hospitalisation. Clinical characteristics, surgery type/timing, hospital and six-month outcomes were reported. Findings: Of 2032 subjects (age: mean = 41.4-years, range = 17–89-years; male = 71% female = 29%), 260 underwent cranial surgery, comprising 65% decompressive craniectomy, 23% craniotomy, 12% other surgery. Subjects with surgery (vs. without surgery) presented with worse neurological injury (median Glasgow Coma Scale = 6 vs. 15; midline shift ≥5 mm: 48% vs. 2%; cisternal effacement: 61% vs. 4%; p

Abstract Functional impairments contribute to poor quality of life in schizophrenia spectrum disorders (SSD). We sought to (Objective I) define the main functional phenotypes in SSD, then (Objective II) identify key biopsychosocial correlates, emphasizing interpretable data-driven methods. Objective I was tested on independent samples: Dataset I (N = 282) and Dataset II (N = 317), with SSD participants who underwent assessment of multiple functioning areas. Participants were clustered based on functioning. Objective II was evaluated in Dataset I by identifying key features for classifying functional phenotype clusters from among 65 sociodemographic, psychological, clinical, cognitive, and brain volume measures. Findings were replicated across latent discriminant analyses (LDA) and one-vs.-rest binomial regularized regressions to identify key predictors. We identified three clusters of participants in each dataset, demonstrating replicable functional phenotypes: Cluster 1—poor functioning across domains; Cluster 2—impaired Role Functioning, but partially preserved Independent and Social Functioning; Cluster 3—good functioning across domains. Key correlates were Avolition, anhedonia, left hippocampal volume, and measures of emotional intelligence and subjective social experience. Avolition appeared more closely tied to role functioning, and anhedonia to independent and social functioning. Thus, we found three replicable functional phenotypes with evidence that recovery may not be uniform across domains. Avolition and anhedonia were both critical but played different roles for different functional domains. It may be important to identify critical functional areas for individual patients and target interventions accordingly.

Objectives An estimated 14–23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort.Methods Data from hospitalized subjects with Glasgow Coma Scale score of 3–12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014–2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1–3 (vs. 4–8)) at 3, 6, and 12 months after injury.Results Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01–4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months.Conclusions After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed.Level of evidence IV.Trial registration number NCT02119182.

Summary: During COVID-19 in the US, social determinants of health (SDH) have driven health disparities. However, the use of SDH in COVID-19 vaccine modeling is unclear. This review aimed to summarize the current landscape of incorporating SDH into COVID-19 vaccine transmission modeling in the US. Medline and Embase were searched up to October 2022. We included studies that used transmission modeling to assess the effects of COVID-19 vaccine strategies in the US. Studies’ characteristics, factors incorporated into models, and approaches to incorporate these factors were extracted. Ninety-two studies were included. Of these, 11 studies incorporated SDH factors (alone or combined with demographic factors). Various sets of SDH factors were integrated, with occupation being the most common (8 studies), followed by geographical location (5 studies). The results show that few studies incorporate SDHs into their models, highlighting the need for research on SDH impact and approaches to incorporating SDH into modeling. Funding: This research was funded by the Centers for Disease Control and Prevention (CDC).

Abstract Trained detection dogs have a unique ability to find the sources of target odors in complex fluid environments. How dogs derive information about the source of an odor from an odor plume comprised of odorants with different physical properties, such as diffusivity, is currently unknown. Two volatile chemicals associated with explosive detection, ammonia (NH3, derived from ammonium nitrate-based explosives) and 2-ethyl-1-hexanol (2E1H, associated with composition C4 plastic explosives) were used to ascertain the effects of the physical properties of odorants on the search behavior and motion of trained dogs. NH3 has a diffusivity 3.6 times that of 2E1H. Fourteen civilian detection dogs were recruited to train on each target odorant using controlled odor mimic permeation systems as training aids over 6 weeks and then tested in a controlled-environment search trial where behavior, motion, and search success were analyzed. Our results indicate the target-odorant influences search motion and time spent in the stages of searching, with dogs spending more time in larger areas while localizing NH3. This aligns with the greater diffusivity of NH3 driving diffusion-dominated odor transport when dogs are close to the odor source in contrast to the advection-driven transport of 2E1H at the same distances.

Abstract Youths with high levels of callous-unemotional (CU) traits and aggression are at an increased risk for developing antisocial behaviours into adulthood. In this population, neurostructural grey matter abnormalities have been observed in the prefrontal cortex. However, the directionality of these associations is inconsistent, prompting some to suggest they may vary across development. Although similar neurodevelopmental patterns have been observed for other disorders featuring emotional and behavioural dysregulation, few studies have tested this hypothesis for CU traits, and particularly not for aggression subtypes. The current study sought to examine grey matter correlates of CU traits and aggression (including its subtypes), and then determine whether these associations varied by age. Fifty-four youths (10–19 years old) who were characterized for CU traits and aggression underwent MRI. Grey matter volume and surface area within the anterior cingulate cortex was positively associated with CU traits. The correlation between CU traits and medial orbitofrontal cortex (mOFC) volume varied significantly as a function of age, as did the correlation between reactive aggression and mOFC surface area. These associations became more positive with age. There were no significant findings for proactive/total aggression. Results are interpreted considering the potential for delayed cortical maturation in youths with high CU traits/aggression.

Abstract Traumatic brain injury (TBI) affects how the brain functions in the short and long term. Resulting patient outcomes across physical, cognitive, and psychological domains are complex and often difficult to predict. Major challenges to developing personalized treatment for TBI include distilling large quantities of complex data and increasing the precision with which patient outcome prediction (prognoses) can be rendered. We developed and applied interpretable machine learning methods to TBI patient data. We show that complex data describing TBI patients' intake characteristics and outcome phenotypes can be distilled to smaller sets of clinically interpretable latent factors. We demonstrate that 19 clusters of TBI outcomes can be predicted from intake data, a ~ 6× improvement in precision over clinical standards. Finally, we show that 36% of the outcome variance across patients can be predicted. These results demonstrate the importance of interpretable machine learning applied to deeply characterized patients for data-driven distillation and precision prognosis.

Abstract Background Injuries, the leading cause of death in children 1–17 years old, are often preventable. Injury patterns are impacted by changes in the child’s environment, shifts in supervision, and caregiver stressors. The objective of this study was to evaluate the incidence and proportion of injuries, mechanisms, and severity seen in Pediatric Emergency Departments (PEDs) during the COVID-19 pandemic. Methods This multicenter, cross-sectional study from January 2019 through December 2020 examined visits to 40 PEDs for children

Background: Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion. Therefore, more accurate diagnostic markers are needed for sport-related concussion. Methods: This was a multicenter, prospective, case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association–Department of Defense Concussion Assessment, Research, and Education Consortium conducted between 2015 and 2019. The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints. Athletes with concussion were divided into 6 h post-injury (0–6 h post-injury) and after 6 h post-injury (7–48 h post-injury) groups. We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305 proteins in plasma samples from athletes with and without sport-related concussion. Results: A total of 140 athletes with concussion (79.3% males; aged 18.71 ± 1.10 years, mean ± SD) and 21 non-concussed athletes (76.2% males; 19.14 ± 1.10 years) were included in this study. We identified 338 plasma proteins that significantly differed in abundance (319 upregulated and 19 downregulated) in concussed athletes compared to non-concussed athletes. The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve (AUC) of 0.954 (95% confidence interval: 0.922‒0.986). Specifically, after 6 h of injury, the individual AUC of plasma erythrocyte membrane protein band 4.1 (EPB41) and alpha-synuclein (SNCA) were 0.956 and 0.875, respectively. The combination of EPB41 and SNCA provided the best AUC (1.000), which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury. Conclusion: Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.

With the shift to online learning, many instructors have been forced into course delivery that involves educational lecture videos. There are a number of different elements that impact the quality of educational videos and overall student experience (e.g. instructor eye gaze, audio levels, screen sizing). More specifically, research has demonstrated that segmented videos have educational benefits over the traditional didactic ones. The present experiment aimed to examine whether interspersed interactive content could increase post-secondary students’ retention and engagement above simple segmentation. As such, young adults experienced one of four lesson types: didactic video, segmented videos, segmented videos with interactive content, and a condensed version of the interactive segmented videos. Then, they were asked to complete an engagement scale, an online learning experience questionnaire, and a surprise test. The results demonstrated a performance benefit to segmented videos for post-secondary students who prefer to learn in person as opposed to online.

IntroductionMild traumatic brain injury (mTBI) is a heterogenous injury which can be difficult to characterize and manage. Using cross-sectional network analysis (NA) to conceptualize mTBI symptoms offers an innovative solution to identify how mTBI symptoms relate to each other. The centrality hypothesis of network theory posits that certain symptoms in a network are more relevant (central) or have above average influence over the rest of the network. However, no studies have used NA to characterize the interrelationships between symptoms in a cohort of patients who presented with mTBI to a U.S. Level 1 trauma center emergency department and how subacute central symptoms relate to long-term outcomes.MethodsPatients with mTBI (Glasgow Coma Scale = 13–15) evaluated across 18 U.S. Level 1 trauma centers from 2013 to 2019 completed the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) at 2 weeks (W2) post-injury (n = 1,593) and at 3 months (M3), 6 months (M6), and 12 months (M12) post-injury. Network maps were developed from RPQ subscale scores at each timepoint. RPQ scores at W2 were associated with M6 and M12 functional and quality of life outcomes.ResultsNetwork structure did not differ across timepoints, indicating no difference in symptoms/factors influence on the overall symptom network across time. The cognitive factor had the highest expected influence at W2 (1.761), M3 (1.245), and M6 (1.349). Fatigue had the highest expected influence at M12 (1.275). The emotional factor was the only other node with expected influence >1 at any timepoint, indicating disproportionate influence of emotional symptoms on overall symptom burden (M3 = 1.011; M6 = 1.076).DiscussionSeveral symptom factors at 2-weeks post-injury were more strongly associated with incomplete recovery and/or poorer injury-related quality of life at 6 and 12 months post-injury than previously validated demographic and clinical covariates. The network analysis suggests that emotional, cognitive, and fatigue symptoms may be useful treatment targets in this population due to high centrality and activating potential of the overall symptom network.

The relationship between systemic inflammation and secondary injury in traumatic brain injury (TBI) is complex. We investigated associations between inflammatory markers and clinical confirmation of TBI diagnosis and prognosis. The prospective TRACK-TBI Pilot (Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot) study enrolled TBI patients triaged to head computed tomography (CT) and received blood draw within 24?h of injury. Healthy controls (HCs) and orthopedic controls (OCs) were included. Thirty-one inflammatory markers were analyzed from plasma. Area under the receiver operating characteristic curve (AUC) was used to evaluate discriminatory ability. AUC >0.7 was considered acceptable. Criteria included: TBI diagnosis (vs. OC/HC); moderate/severe vs. mild TBI (Glasgow Coma Scale; GCS); radiographic TBI (CT positive vs. CT negative); 3- and 6-month Glasgow Outcome Scale-Extended (GOSE) dichotomized to death/greater relative disability versus less relative disability (GOSE 1?4/5?8); and incomplete versus full recovery (GOSE

Abstract Many patients with mild traumatic brain injury (mTBI) are at risk for mental health problems such as posttraumatic stress disorder (PTSD). The objective of this study was to determine whether the polygenic risk for PTSD (or for related mental health disorders or traits including major depressive disorder [MDD] and neuroticism [NEU]) was associated with an increased likelihood of PTSD in the aftermath of mTBI. We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma center patients. One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5 score ≥33) at 6 months post-injury. We used summary statistics from recent GWAS studies of PTSD, MDD, and NEU to generate polygenic risk scores (PRS) for individuals in our sample. A multivariable model that included age, sex, pre-injury history of mental disorder, and cause of injury explained 7% of the variance in the PTSD outcome; the addition of the PTSD-PRS (and five ancestral principal components) significantly increased the variance explained to 11%. The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly four times higher (aOR = 3.71, 95% CI 1.80–7.65) than in the lowest PTSD-PRS quintile. There was no evidence of a statistically significant interaction between PTSD-PRS and prior history of mental disorder, indicating that PTSD-PRS had similar predictive utility among those with and without pre-injury psychiatric illness. When added to the model, neither MDD-PRS nor NEU-PRS were significantly associated with the PTSD outcome. These findings show that the risk for PTSD in the context of mTBI is, in part, genetically influenced. They also raise the possibility that an individual’s PRS could be clinically actionable if used—possibly with other non-genetic predictors—to signal the need for enhanced follow-up and early intervention; this precision medicine approach needs to be prospectively studied.

Objective Robotic guidance provides indirect visualization of key anatomic landmarks to facilitate minimally invasive surgery (MIS) and is emerging as a reliable and accurate technique for posterior spine instrumentation. We sought to describe eight years of experience with robotic guidance at a high-volume, multi-surgeon center. We hypothesize that robotic guidance will lead to (1) low rates of complication, readmissions, and revision surgery, (2) reduced fluoroscopic radiation exposure, (3) and accurate thoracolumbar instrumentation. Methods A retrospective review of complications, revision surgery, and readmission rates in patients undergoing thoracolumbar fusion surgery utilizing three robotic generations. Secondary analysis was conducted comparing the three robotic generations for complications, revision surgery, accuracy, and readmission rates along with intraoperative fluoroscopic duration. Results A total of 628 patients (3,874 robotic-guided screws) ages 12–81 years-old (43.9% male) were included in the study. At one year, the cumulative complication incidence was 15.5% with a 10.3% incidence of surgical complications (3.7% wound, 1.2% robot-related, and 5.4% non-robot-related complications). At one year, the revision surgery incidence was 9.4%. There was no statistical difference between complications, readmission, or revision surgery after initial admission among the three robotic generations. The average intraoperative fluoroscopic duration was 53.8 seconds (11.9 seconds per screw and 17.6 seconds per instrumented level). Conclusion Robotic guidance in thoracolumbar instrumented fusions was associated with low complication, revision surgery, and readmission rates. Our results suggest robotic guidance can provide accurate guidance with minimal adverse events in thoracolumbar instrumentation.

ObjectiveThe aim of this study was to investigate phosphorylated tau (p-tau181) protein in plasma in a cohort of mild traumatic brain injury (mTBI) patients and a cohort of concussed athletes.MethodsThis pilot study comprised two independent cohorts. The first cohort—part of a Traumatic Head Injury Neuroimaging Classification (THINC) study—with a mean age of 46 years was composed of uninjured controls (UIC, n = 30) and mTBI patients (n = 288) recruited from the emergency department with clinical computed tomography (CT) and research magnetic resonance imaging (MRI) findings. The second cohort—with a mean age of 19 years—comprised 133 collegiate athletes with (n = 112) and without (n = 21) concussions. The participants enrolled in the second cohort were a part of a multicenter, prospective, case-control study conducted by the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium at six CARE Advanced Research Core (ARC) sites between 2015 and 2019. Blood was collected within 48 h of injury for both cohorts. Plasma concentration (pg/ml) of p-tau181 was measured using the Single Molecule Array ultrasensitive assay.ResultsConcentrations of plasma p-tau181 in both cohorts were significantly elevated compared to controls within 48 h of injury, with the highest concentrations of p-tau181 within 18 h of injury, with an area under the curve (AUC) of 0.690–0.748, respectively, in distinguishing mTBI patients and concussed athletes from controls. Among the mTBI patients, the levels of plasma p-tau181 were significantly higher in patients with positive neuroimaging (either CT+/MRI+, n = 74 or CT−/MRI+, n = 89) compared to mTBI patients with negative neuroimaging (CT−/MRI−, n = 111) findings and UIC (P-values < 0.05).ConclusionThese findings indicate that plasma p-tau181 concentrations likely relate to brain injury, with the highest levels in patients with neuroimaging evidence of injury. Future research is needed to replicate and validate this protein assay's performance as a possible early diagnostic biomarker for mTBI/concussions.

Minimally invasive spine surgery reduces tissue dissection and retraction, decreasing the morbidity associated with traditional open spine surgery by decreasing blood loss, blood transfusion, complications, and pain. One of the key challenges with a minimally invasive approach is achieving consistent posterior fusion. Although advantageous in all fusion surgeries, solid posterior fusion is particularly important in spinal deformity, revisions, and fusions without anterior column support. A minimally invasive surgical approach accomplished without sacrificing the quality of the posterior fusion has the potential to decrease both short- and long-term complications compared to the traditional open techniques. Innovations in navigated and robotic-assisted spine surgery continue to address this need. In this article, we will outline the feasibility of achieving posterior facet fusion using the Mazor X Stealth Edition Robotic Guidance System.

Abstract Background Metabolic syndrome (MetS) is a clustering of metabolic risk factors, including large waist circumference (WC). Other anthropometric parameters and visceral fat mass (VFM) predicted from these may improve MetS detection. Our aim was to assess the ability of such parameters to predict this clustering in a cross-sectional, diagnostic study. Method Participants were 82 males and 86 females, aged 20–74 years, of Asian Indian ethnicity. VFM was estimated by dual-energy X-ray absorptiometry (DXA) through identification of abdominal subcutaneous fat layer boundaries. Non-anthropometric metabolic risk factors (triglycerides, HDL cholesterol, blood pressure and glucose) were defined using MetS criteria. We estimated the ability of anthropometry and VFM to detect ≥ 2 of these factors by receiver operating characteristic (ROC) and precision-recall curves. Results Two or more non-anthropometric metabolic risk factors were present in 45 (55%) males and 29 (34%) females. The area under the ROC curve (AUC) to predict ≥ 2 of these factors using WC was 0.67 (95% confidence interval: 0.55–0.79) in males and 0.65 (0.53–0.77) in females. Optimal WC cut-points were 92 cm for males (63% accuracy) and 79 cm for females (53% accuracy). VFM, DXA-measured sagittal diameter and suprailiac skinfold thickness yielded higher AUC point estimates (by up to 0.06), especially in females where these measures improved accuracy to 69%, 69% and 65%, respectively. Pairwise combinations that included WC further improved accuracy. Conclusion Our findings indicate that cut-points for readily obtained measures other than WC, or in combination with WC, may provide improved detection of MetS risk factor clusters.

PurposeChildren who experience maltreatment are at high risk for posttraumatic stress disorder (PTSD). Children’s Advocacy Centers (CACs) can facilitate access to treatment following maltreatment allegations. We describe PTSD symptoms and intervention decision-making for children served by CACs.MethodsChildren served by CACs in a single state were screened for PTSD symptoms using a structured mental health screening/referral protocol. CAC staff used an electronic form that provided guidance for decision-making. We examined descriptive statistics for PTSD symptoms and risk and tested associations between child characteristics and symptoms. We described CAC staff’s delivery of brief interventions and referral decisions and tested associations with child characteristics and symptoms.ResultsTwo thousand and three hundred fifty children completed screening between 2018 and 2020. Almost half (45.5%) exhibited traumatic stress symptoms suggesting high probability of PTSD at the time of their CAC visit. Children who identified as female or transgender male and older children were more likely to be at high risk for PTSD. Brief interventions were delivered to 66% of children, and most were referred to evidence-based trauma treatment (53.1%) or community mental health services (39.0%). Categorization as moderate or high PTSD risk was associated with a higher likelihood of brief intervention delivery and referral to trauma treatment.ConclusionMany children served by CACs are likely to meet criteria for PTSD at their initial visit. CAC staff demonstrated the ability to deliver brief interventions and make referrals to mental health treatment. Use of structured screening/referral protocols may improve early identification and treatment access for children experiencing PTSD symptoms.

IntroductionThis study reports on an assessment of mental health needs among Scotland's prison population which aimed to describe the scale and nature of need as well as identify opportunities to improve upon the services available. The project was commissioned by the Scottish Government to ensure that future changes to the services available to support the mental health and wellbeing of people in prison would be evidence-based and person-centered.MethodsA standardized approach to health needs assessments was employed. The study was comprised of four phases. In phase I a rapid literature review was undertaken to gather evidence on the prevalence of mental health needs experienced by people in prison in the UK. In Phase II a multi-method and multi-informant national mapping exercise involving providers to all Scottish prisons was undertaken to describe the mental health services available, and any gaps in these services, for people in and leaving prison. In Phase III prevalence estimates of several mental health needs were derived for Scotland's current prison population, modeled from a national survey dataset of Scotland's community population using logistic regression. Finally in Phase IV, professional stakeholders and individuals with lived experience were interviewed to understand their experiences and insights on challenges to supporting the mental health and wellbeing of people in prison, and ideas on how these challenges could be overcome.ResultsEvidence across the four phases of this needs assessment converged indicating that existing provision to support the mental health of people in prison in Scotland was considered inadequate to meet these needs. Barriers to effective partnership working for justice, health, social work and third sector providers appear to have led to inadequate and fragmented care, leaving prisoners without the support they need during and immediately following imprisonment.ConclusionsJoint and coordinated action from justice, health and social care, and third sector providers is needed to overcome enduring and structural challenges to supporting the mental health of people in prison. Eighteen evidence-based recommendations were proposed to the Scottish Government relating to the high-level and operational-level changes required to adequately meet the prison population's mental health needs.

Abstract Social cognitive impairments are core features of schizophrenia spectrum disorders (SSD) and are associated with greater functional impairment and decreased quality of life. Metabolic disturbances have been related to greater impairment in general neurocognition, but their relationship to social cognition has not been previously reported. In this study, metabolic measures and social cognition were assessed in 245 participants with SSD and 165 healthy comparison subjects (HC), excluding those with hemoglobin A1c (HbA1c) > 6.5%. Tasks assessed emotion processing, theory of mind, and social perception. Functional connectivity within and between social cognitive networks was measured during a naturalistic social task. Among SSD, a significant inverse relationship was found between social cognition and cumulative metabolic burden (β = −0.38, p

This study was designed to determine how raw scores correspond between two alternative measures of functional recovery from traumatic brain injury (TBI), the Functional Status Examination (FSE) and the Glasgow Outcome Scale-Extended (GOSE). Using data from 357 persons with moderate-severe TBI who participated in a large clinical trial, we performed item response theory analysis to characterize the relationship between functional ability measured by the FSE and GOSE at 6 months post-injury. Results revealed that raw scores for the FSE and GOSE can be linked, and a table is provided to translate scores from one instrument to the other. For example, a FSE score of 7 (on its 0?21 scale, where higher scores reflect more impairment) is equivalent to a GOSE score of 6 (where GOSE is scaled on an 8-point scale, with higher scores reflecting less impairment). These results allow clinicians or researchers who have a score for a person on one instrument to cross-reference it to a score on the other instrument. Importantly, this enables researchers to combine data sets where some persons only completed the GOSE and some only the FSE. In addition, an investigator could save participant time by eliminating one instrument from a battery of tests, yet still retain a score on that instrument for each participant. More broadly, the findings help anchor scores from these two instruments to the broader continuum of injury-related functional limitations.

Aim: T-helper cells could play an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), a common B-cell neoplasm. Although CLL cells can present soluble antigens targeted from the B-cell receptor to T-helper cells via major histocompatibility complex (MHC) class II, antigens recognized by some CLL cells may be encountered in a particulate form. Here the ability of CLL cells to internalize and present anti-immunoglobulin M (IgM) beads as a model for the interaction of CLL cells with particulate antigens was investigated. Methods: The effect of anti-IgM beads on antigen presentation pathways was analyzed using RNA-seq and internalization of anti-IgM beads by primary CLL cells was investigated using confocal microscopy and flow cytometry. Antigen presentation was investigated by analyzing activation of a T-cell line expressing a T-cell receptor specific for a peptide derived from mouse κ light chains after incubating CLL cells with a mouse κ light chain-containing anti-IgM monoclonal antibody. Kinase inhibitors were used to characterize the pathways mediating internalization and antigen presentation. Results: Stimulation of surface IgM of CLL cells increased expression of the antigen presentation machinery and CLL cells were able to phagocytose anti-IgM beads. Internalization of anti-IgM beads was associated with MHC class II-restricted activation of cognate T-helper cells. Antigen presentation by CLL cells was dependent on activity of spleen tyrosine kinase (SYK) and phosphatidylinositol 3-kinase delta (PI3Kδ) but was unaffected by inhibitors of Bruton’s tyrosine kinase (BTK). Conclusions: CLL cells can internalize and present antigen from anti-IgM beads. This capacity of CLL cells may be particularly important for recruitment of T-cell help in vivo in response to particulate antigens.

Coronavirus disease 2019 (COVID-19) is associated with adverse impacts in the cardiovascular system, but the mechanisms driving this response remain unclear. In this study, we conducted “pseudoviral infection” of SARS-CoV-2 subunits to evaluate their toxic effects in cardiomyocytes (CMs), that were derived from human induced pluripotent stem cells (hiPSCs). We found that the ectopic expression of S and ORF-9B subunits significantly impaired the contractile function and altered the metabolic profiles in human cardiomyocytes. Further mechanistic study has shown that the mitochondrial oxidative phosphorylation (OXPHOS), membrane potential, and ATP production were significantly decreased two days after the overexpression of S and ORF-9B subunits, while S subunits induced higher level of reactive oxygen species (ROS). Two weeks after overexpression, glycolysis was elevated in the ORF-9B group. Based on the transcriptomic analysis, both S and ORF-9B subunits dysregulated signaling pathways associated with metabolism and cardiomyopathy, including upregulated genes involved in HIF-signaling and downregulated genes involved in cholesterol biosynthetic processes. The ORF-9B subunit also enhanced glycolysis in the CMs. Our results collectively provide an insight into the molecular mechanisms underlying SARS-CoV-2 subunits-induced metabolic alterations and cardiac dysfunctions in the hearts of COVID-19 patients.

Background: The opioid epidemic in the US has led prescribers to reevaluate postoperative pain control particularly in the field of spine surgery, where postoperative analgesia requirements and consumption have historically been high. There is a need to mitigate the quantity of unused pills after surgery by adjusting prescribing practices. Achieving the balance of pain control after surgery without overprescribing opioids may be accomplished by developing a modified approach to prescribing practices; however, there is a need to first understand the opioid requirements of the modern spine surgery patient with respect to their elective spine surgery. Therefore, the primary aim of this study was to determine the percentage of opioids not utilized at 90-days after elective spine surgery. Secondary aims were to identify differences in the percentage of unused opioids between surgical subgroups and preoperative opioid status, to determine factors associated with opioid utilization, and to estimate the distribution of opioids consumed to control pain up to the 90th percentile in each surgical subgroup. Methods: In this prospective, observational cohort study, adults undergoing elective spine surgery at a multi-surgeon, single center were prospectively enrolled and divided into subgroups: anterior cervical, lumbar decompression, and short-segment lumbar fusion. Prescribed MMEs were identified from prescriptions, consumed MMEs were obtained from pill counts, and the percent leftover was calculated. Distributions of MMEs consumed were analyzed to compare utilization between preoperative opioid users or non-users within each surgical subgroup. Results: Of 117 patients, 41.9% were preoperative opioid users. The percentage of unused opioids by surgical subgroup was: 45.4% cervical, 57.3% lumbar decompression, and 37.4% lumbar fusion (p=0.066). The percentage of unused opioids by preoperative opioid exposure was greater in the opioid non-users (58.0%) than users (28.4%, p

The Rosalind Franklin Society (RFS), in partnership with Mary Ann Liebert, Inc., publishers, enthusiastically congratulate our distinguished recipient of the 2022 annual RFS Award in Science for this journal, which recognizes the outstanding research and published work of women and underrepresented minority scientists, physicians, and engineers. Lindsay D. Nelson, Brooke E. Magnus, Nancy R. Temkin, Sureyya Dikmen, Geoffrey T. Manley, and Steve Balsis, ?How Do Scores on the Functional Status Examination (FSE) Correspond to Scores on the Glasgow Outcome Scale-Extended (GOSE)?? Neurotrauma Reports 3, no. 1 (January 2022): 122?128, http://doi.org/10.1089/neur.2021.0057. Abstract We used item response theory (IRT) to determine how raw scores correspond between two widely used measures of functional recovery from traumatic brain injury (TBI), the Functional Status Examination (FSE) and the Glasgow Outcome Scale-Extended (GOSE). Using data from 357 persons with moderate-severe TBI, we modeled the relationship between domain-level scores on the instruments and the latent dimension of disability level at 6 months postinjury. Results revealed that raw scores for the FSE and GOSE can be linked, and a table was provided to translate scores from one instrument to the other. These results allow clinicians or researchers who have a score for a person on one instrument to cross-reference it to a score on the other instrument. Importantly, this enables researchers to combine data sets where some persons only completed the GOSE and some only the FSE. In addition, an investigator could save participant time by eliminating one instrument from a battery of tests, yet still retain a score on that instrument for each participant. More broadly, the findings help anchor scores from these two instruments to the broader continuum of injury-related functional limitations. Biosketch Dr. Nelson is an associate professor and board-certified clinical neuropsychologist at the Medical College of Wisconsin's Center for Neurotrauma Research, where she conducts clinical and translational studies of traumatic brain injury (TBI). She has served as principal investigator on several federally and institutionally funded studies, with a focus on identifying distinct clinical phenotypes of TBI, improving measurement of clinical outcomes, and better understanding individual differences in patient outcomes. Dr. Nelson serves on the executive committee of the International Initiative for TBI Research (InTBIR) and is a co-investigator on the largest American studies of sport-related concussion (Concussion Assessment Research and Education [CARE] Consortium) and civilian TBI (Transforming Research and Clinical Knowledge in TBI [TRACK-TBI]) conducted to date. Nelson is funded by the National Institutes of Health, Department of Defense, Centers for Disease Control and Prevention, and other sources.

Peripheral injuries are common in patients who experience mild traumatic brain injury (mTBI). However, the additive or interactive effects of polytrauma on psychosocial adjustment, functional limitations, and clinical outcomes after head injury remain relatively unexamined. Using a recently developed structured injury symptom interview, we assessed the perception and relative importance of peripheral injuries at 3 months post-injury in patients with mTBI as defined by the American Congress of Rehabilitation Medicine. Our sample of Level 1 trauma patients (n?=?74) included individuals who were treated and released from the emergency department (n?=?43) and those admitted to an inpatient unit (n?=?31). Across the sample, 91% of patients with mTBI experienced additional non-head injuries known to commonly impact recovery following mTBI, a majority of whom ranked pain as their worst peripheral injury symptom. Forty-nine percent of the mTBI sample (54% of the subsample with concurrent mTBI and peripheral injuries) reported being more bothered by peripheral injury symptoms than mTBI. Differences between patients with mTBI with worse mTBI symptoms versus those with worse peripheral injury symptoms are described. Conventional measures of injury severity do not capture patients' perceptions of the totality of their injuries, which limits the development of patient-centered treatments. Future research should enroll patients with mTBI diverse in peripheral injury severity and develop standardized assessments to characterize peripheral symptoms, enabling better characterization of the relevance of concurrent injuries in recovery and outcomes of patients with mTBI.

Abstract Androgen deprivation therapy (ADT) for men with prostate cancer (PCa) results in accelerated bone loss and increased risk of bone fracture. The aim of the present study was to evaluate serum bone markers—sclerostin, Dickkopf-1 (DKK-1) and osteoprotegerin (OPG), in a cohort of 88 PCa patients without known bone metastases, managed with and without ADT, and to analyse their relationship with bone mineral density (BMD) and sex steroids. The cross-sectional analysis between acute-, chronic- and former-ADT groups and PCa controls showed that sclerostin and OPG levels significantly differed between them (p = 0.029 and p = 0.032). Groups contributing to these significant changes were recorded. There were no significant differences in serum DKK-1 levels across the four groups (p = 0.683). In the longitudinal analysis, significant % decreases within groups were seen for DKK-1 [chronic-ADT (− 10.06%, p = 0.0057), former-ADT (− 12.77%, p = 0.0239), and in PCa controls group (− 16.73, p = 0.0022); and OPG levels in chronic ADT (− 8.28%, p = 0.003) and PCa controls group (− 12.82%, p = 0.017)]. However, % changes in sclerostin, DKK-1, and OPG did not differ significantly over 6-months across the evaluated groups. Sclerostin levels showed significant positive correlations with BMD at baseline in the ADT group, while in PCa controls this correlation existed at both baseline and 6-month time points. Sclerostin correlated negatively with testosterone in former ADT users and in PCa controls. Possible prognostic features denoted by parallel increases in sclerostin and BMD are discussed.

ObjectiveTo investigate the plasma proteomic profiling in identifying biomarkers related to return to sport (RTS) following a sport-related concussion (SRC).MethodsThis multicenter, prospective, case-control study was part of a larger cohort study conducted by the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium, athletes (n = 140) with blood collected within 48 h of injury and reported day to asymptomatic were included in this study, divided into two groups: (1) recovery

Sleep-wake disturbance (SWD) results from sport-related concussion (SRC) and may increase risk of protracted post-injury symptoms. However, methodological limitations in the extant literature limit our understanding of the role of SWD in SRC. This study examined the association between acute/subacute SRC and two sleep behaviors?sleep duration and efficiency?as measured by self-report and commercially available actigraphy (CA) in a sample of football players enrolled in a larger prospective longitudinal study of concussion. Fifty-seven high school and Division 3 male football players with SRC (mean [M] age?=?18.00 years, standard deviation [SD]?=?1.44) and 26 male teammate controls (M age?=?18.54 years, SD?=?2.21) were enrolled in this prospective pilot study. Sleep duration and sleep efficiency were recorded nightly for 2 weeks (starting 24?48?h post-injury in the SRC group) via CA and survey delivered via mobile application. There was no significant relationship between SRC and objectively recorded sleep measures, a null finding. However, the SRC group reported a brief (3-day) reduction in sleep efficiency after injury (M SRC?=?82.18, SD?=?12.24; M control?=?89.2, SD?=?4.25; p?=?0.013; Cohen's d?=?0.77), with no change in sleep duration. Self-reported and actigraph-assessed hours of sleep were weakly and insignificantly correlated in the SRC group (r?=??0.21, p?=?0.145), whereas they were robustly correlated in the non-injured control group (r?=?0.65, p?=?0.004). SWD post-SRC was not observed in objectively measured sleep duration or sleep efficiency and was modest and time-limited based on self-reported sleep efficiency. The weak correlation between self-reported and objective sleep behavior measures implies that subjective experience of SWD post-SRC may be due to factors other than actual changes in these observable sleep behaviors. Clinically, SWD in the early-subacute stages of recovery from SRC may not be adequately measurable via current CA. Subjective SWD may require alternative methods of evaluation (e.g., clinical actigraph or sleep study).

The endoplasmic reticulum network consists of tubules with high membrane curvature in cross-section, generated by the reticulons and REEPs, but how they introduce curvature is poorly understood. Here authors show that REEPs form homodimers and use their amphipathic helix and trans-membrane segments to introduce high membrane curvature that can even lead to the formation of lipoprotein particles.

Objective: The minor allele (A) of the rs373863828 variant (p.Arg457Gln) in CREBRF is restricted to indigenous peoples of the Pacific islands (including New Zealand Māori and peoples of Polynesia), with a frequency of up to 25% in these populations. This allele associates with a large increase in body mass index (BMI) but with significantly lower risk of type-2 diabetes (T2D). It remains unclear whether the increased BMI is driven by increased adiposity or by increased lean mass. Methods: We undertook body composition analysis using DXA in 189 young men of Māori and Pacific descent living in Aotearoa New Zealand. Further investigation was carried out in two orthologous Arg458Gln knockin mouse models on FVB/NJ and C57BL/6j backgrounds. Results: The rs373863828 A allele was associated with lower fat mass when adjusted for BMI (p < 0.05) and was associated with significantly lower circulating levels of the muscle inhibitory hormone myostatin (p < 0.05). Supporting the human data, significant reductions in adipose tissue mass were observed in the knockin mice. This was more significant in older mice in both backgrounds and appeared to be the result of reduced age-associated increases in fat mass. The older male knockin mice on C57BL/6j background also had increased grip strength (p < 0.01) and lower levels of myostatin (p < 0.05). Conclusion: Overall, these results prove that the rs373863828 A-allele is associated with a reduction of myostatin levels which likely contribute to an age-dependent lowering of fat mass, at least in males.

Catherine Hays,1 Melanie Sparrow,2 Selina Taylor,1 Daniel Lindsay,3 Beverley Glass2 1Centre for Rural and Remote Health, James Cook University, Mount Isa, Queensland, Australia; 2Pharmacy, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; 3College of Public Health, Medical and Veterinary Science, James Cook University, Townsville, Queensland, AustraliaCorrespondence: Catherine HaysCentre for Rural and Remote Health, James Cook University, PO Box 2572, Mount Isa, Queensland 4825, AustraliaTel +61 7 4745 4500Fax +61 7 4749 5130Email catherine.hays@jcu.edu.auPurpose: Poor health outcomes for patients living in rural and remote areas of Australia are often attributed to the lack of a range of accessible health professionals delivering health services. Community pharmacists are already an integral part of these communities and as such are often the most frequently consulted health professionals. The aim of this study was to explore rural pharmacist knowledge and experiences of expanded pharmacy and to identify the barriers and enablers to remote pharmacists providing expanded pharmacy services (EPS), which can be described as services outside of usual medication management tasks.Methods: Rural and remote pharmacists (Modified Monash Model (MMM) categories 2– 7) participated in an online survey. Descriptive statistics and chi-squared tests were performed and data from open-ended questions were analyzed, categorized into themes and quantitized.Results: Two-thirds (n=13, 68%) of rural pharmacists surveyed (n=19) had knowledge of EPS in rural pharmacies and the majority (n=17, 89%) agreed that these services would benefit rural communities. Mental health service referral was considered very/extremely important by the majority (n=16, 84%) of respondents; however, no pharmacists were currently providing mental health screening services while (n=15, 79%) were willing to provide these services. While staff shortages, costs, time and training were indicated to be the main barriers to the provision of EPS, enablers included accessibility of rural pharmacies and a perceived need.Conclusion: This study indicated that pharmacists are already providing some EPS and see value in their implementation; however, what constitutes an expanded service was unclear to some participants. Mental health services were highlighted as most important demonstrating a recognized burden of mental illness in rural and remote locations. Findings from this pilot study will provide further understanding for future development of the pharmacist’s scope of practice and implementation of EPS.Keywords: pharmacy, workforce, rural and remote, health outcomes, expanded scope

Abstract Background Asian Chinese are more susceptible to deposition of visceral adipose tissue (VAT) and type 2 diabetes (T2D) development than European Caucasians when matched for gender, age and body mass index (BMI). Our aims were: (i) characterise the ethnicity-specific metabolomic signature of visceral adiposity measured by dual energy X-ray absorptiometry (DXA) and fasting plasma glucose (FPG), and (ii) identify individuals susceptible to worse metabolic health outcomes. Methods Fasting plasma samples from normoglycaemic (n = 274) and prediabetic (n = 83) participants were analysed with liquid chromatography–mass spectrometry using untargeted metabolomics. Multiple linear regression adjusting for age, gender and BMI was performed to identify metabolites associated with FPG and VAT calculated as percentage of total body fat (%VATTBF) in each ethnic group. Metabolic risk groups in each ethnicity were stratified based on the joint metabolomic signature for FPG and %VATTBF and clinically characterised using partial least squares-discriminant analysis (PLS-DA) and t-tests. Results FPG was correlated with 40 and 110 metabolites in Caucasians and Chinese respectively, with diglyceride DG(38:5) (adjusted β = 0.29, p = 3.00E−05) in Caucasians and triglyceride TG(54:4) (adjusted β = 0.28, p = 2.02E−07) in Chinese being the most significantly correlated metabolite based on the p-value. %VATTBF was correlated with 85 and 119 metabolites in Caucasians and Chinese respectively, with TG(56:2) (adjusted β = 0.3, p = 8.25E−09) in Caucasians and TG(58:3) (adjusted β = 0.25, p = 2.34E−08) in Chinese being the most significantly correlated. 24 metabolites associated with FPG were common to both ethnicities including glycerolipid species. 67 metabolites associated with %VATTBF were common to both ethnicities including positive correlations with dihydroceramide, sphingomyelin, glycerolipid, phosphatidylcholine, phosphatidylethnolamine, and inverse correlations with ether-linked phosphatidylcholine. Participant re-stratification found greater total and central adiposity, worse clinical lipid profiles, higher serum glucoregulatory peptides and liver enzymes in normal fasting glucose (NFG) individuals with a prediabetic metabolomic profile than NFG individuals with a normoglycaemic metabolomic profile in both ethnicities. Conclusions Untargeted metabolomics identified common and disparate metabolites associated with FPG and %VATTBF, with an ethnic-dimorphic signature for these metabolic traits. These signatures could improve risk stratification and identify NFG individuals with an adverse cardiometabolic and T2D risk profile.

Background and Aim Data on the trends in the prevalence of chronic liver disease (CLD) in Korea are scarce. This study aimed to evaluate whether the CLD prevalence changed between 1998–2001 and 2016–2017. Methods Data were extracted from the Korea National Health and Nutrition Examination Survey (1998–2001 to 2016–2017; n=25,893). Non-alcoholic fatty liver disease (NAFLD) was defined as a hepatic steatosis index >36 in the absence of any other evidence of CLD. The definition of alcohol-related liver disease (ALD) was excessive alcohol consumption (≥210 g/week for men and ≥140 g/week for women) and an ALD/NAFLD index >0. Results The prevalence of NAFLD increased from 18.6% (95% confidence interval [CI], 17.8–19.5%) in 1998–2001 to 21.5% (95% CI, 20.6–22.6%) in 2016–2017. During the same time period, increases were observed in the prevalence of obesity (27.0 vs. 35.1%), central obesity (29.4 vs. 36.0%), diabetes (7.5 vs. 10.6%), and excessive drinking (7.3 vs. 10.5%). ALD prevalence also increased from 3.8% (95% CI, 3.4–4.2%) to 7.0% (95% CI, 6.4–7.6%). In contrast, chronic hepatitis B decreased from 5.1% (95% CI, 4.6–5.5%) to 3.4% (95% CI, 3.0–3.8%). The prevalence of chronic hepatitis C was approximately 0.3% in 2016–2017. Conclusions The prevalence of NAFLD and ALD increase among Korean adults. Our results suggest potential targets for interventions to reduce the future burden of CLD.

ObjectivePrevalence of type 2 diabetes (T2D) is disproportionately higher in younger outwardly lean Asian Chinese compared to matched Caucasians. Susceptibility to T2D is hypothesised due to dysfunctional adipose tissue expansion resulting in adverse abdominal visceral and organ fat accumulation. Impact on early risk, particularly in individuals characterised by the thin-on-the-outside-fat-on-the-inside (TOFI) phenotype, is undetermined.MethodsSixty-eight women [34 Chinese, 34 Caucasian; 18–70 years; body mass index (BMI), 20–45 kg/m2] from the TOFI_Asia study underwent magnetic resonance imaging and spectroscopy to quantify visceral, pancreas, and liver fat. Total body fat was (TBF) assessed by dual-energy x-ray absorptiometry, and fasting blood biomarkers were measured. Ethnic comparisons, conducted using two-sample tests and multivariate regressions adjusted for age, % TBF and ethnicity, identified relationships between abdominal ectopic fat depots with fasting plasma glucose (FPG), insulin resistance (HOMA2-IR), and related metabolic clinical risk markers in all, and within ethnic groups.ResultsDespite being younger and of lower bodyweight, Chinese women in the cohort had similar BMI and % TBF compared to their Caucasian counterparts. Protective high-density lipoprotein cholesterol, total- and high-molecular weight adiponectin were significantly lower, while glucoregulatory glucagon-like peptide-1 and glucagon significantly higher, in Chinese. There were no ethnic differences between % pancreas fat and % liver fat. However, at low BMI, % pancreas and % liver fat were ∼1 and ∼2% higher in Chinese compared to Caucasian women. In all women, % pancreas and visceral adipose tissue had the strongest correlation with FPG, independent of age and % TBF. Percentage (%) pancreas fat and age positively contributed to variance in FPG, whereas % TBF, amylin and C-peptide contributed to IR which was 0.3 units higher in Chinese.ConclusionPancreas fat accumulation may be an early adverse event, in TOFI individuals, with peptides highlighting pancreatic dysfunction as drivers of T2D susceptibility. Follow-up is warranted to explore causality.

Maternal size, weight gain in pregnancy, fetal gender, environment and gestational age are known determinants of birth weight. It is not clear which component of maternal weight or gained weight during pregnancy influences birth weight. We evaluated the association of maternal total body water measured by the deuterium dilution technique (TBW-D2O) at 17 and 34 weeks of gestation with birth weight. A secondary aim was to examine the utility of bioimpedance spectroscopy (BIS) to determine total body water (TBW-BIS) in pregnancy. At 17 and 34 weeks of pregnancy, ninety-nine women (fifty-one rural and forty-eight urban) from Pune, India had measurements of body weight, TBW-D2O, TBW-BIS and offspring birth weight. At 17 weeks of gestation, average weights for rural and urban women were 45⋅5 ± 4⋅8 (sd) and 50⋅7 ± 7⋅8 kg (P < 0⋅0001), respectively. Maternal weight gains over the subsequent 17 weeks for rural and urban women were 6⋅0 ± 2⋅2 and 7⋅5 ± 2⋅8 kg (P = 0⋅003) and water gains were 4⋅0 ± 2⋅4 and 4⋅8 ± 2⋅8 kg (P = 0⋅092), respectively. In both rural and urban women, birth weight was positively, and independently, associated with gestation and parity. Only for rural women, between 17 and 34 weeks, was an increase in dry mass (weight minus TBW-D2O) or a decrease in TBW-D2O as a percentage of total weight associated with a higher birth weight. At both 17 and 34 weeks, TBW-BIS increasingly underestimated TBW-D2O as the water space increased. Differences in body composition during pregnancy between rural and urban environments and possible impacts of nutrition transition on maternal body composition and fetal growth were demonstrated.

ObjectiveWhile there is an emerging role of pancreatic fat in the aetiology of type 2 diabetes mellitus (T2DM), its impact on the associated decrease in insulin secretion remains controversial. We aimed to determine whether pancreatic fat negatively affects β-cell function and insulin secretion in women with overweight or obesity but without T2DM.Methods20 women, with normo- or dysglycaemia based on fasting plasma glucose levels, and low (< 4.5%) vs high (≥ 4.5%) magnetic resonance (MR) quantified pancreatic fat, completed a 1-hr intravenous glucose tolerance test (ivGTT) which included two consecutive 30-min square-wave steps of hyperglycaemia generated by using 25% dextrose. Plasma glucose, insulin and C-peptide were measured, and insulin secretion rate (ISR) calculated using regularisation deconvolution method from C-peptide kinetics. Repeated measures linear mixed models, adjusted for ethnicity and baseline analyte concentrations, were used to compare changes during the ivGTT between high and low percentage pancreatic fat (PPF) groups.ResultsNo ethnic differences in anthropomorphic variables, body composition, visceral adipose tissue (MR-VAT) or PPF were measured and hence data were combined. Nine women (47%) were identified as having high PPF values. PPF was significantly associated with baseline C-peptide (p = 0.04) and ISR (p = 0.04) in all. During the 1-hr ivGTT, plasma glucose (p 0.05). Notably, the incremental areas under the curves for both first and second phase ISR were 0.04 units lower in the high than low PPF groups, but this was not significant (p > 0.05).ConclusionIn women with overweight or obesity but without T2DM, PPF did not modify β-cell function as determined by ivGTT-assessed ISR. However, the salient feature in biphasic insulin secretion in those with ≥4.5% PPF may be of clinical importance, particularly in early stages of dysglycaemia may warrant further investigation.

Introduction. Degenerative disc disease is a common cause of chronic low back pain. Surgical intervention is an invasive treatment associated with high costs. There is growing interest in regenerative medicine as a less invasive but direct disc treatment for chronic discogenic low back pain. Objective. To evaluate clinical improvement of primary discogenic low back pain with intradiscal injection of autologous bone marrow aspirate concentrate (BMAC). Study Design. Prospective cohort study. Setting. Single, multiphysician center. Patients. 32 adult patients undergoing intradiscal injection of autologous BMAC for the treatment of primary discogenic low back pain. Interventions. Intradiscal injection of autologous BMAC. Main Outcome Measures. Primary outcome measure is visual analog back pain scale (VAS back pain). Secondary outcome measures include ODI, VAS leg pain, and EQ-5D-5L scores. Outcomes were compared from baseline to 1 year. Results. Thirty-two patients (56.3% male) with a mean age of 45.9 years were enrolled, giving 92 treated levels. Mean VAS back and leg pain scores improved from 5.4 to 3.0 (p

The Pacific Islands Families (PIF) study is a birth cohort study designed to increase knowledge about the growth and development of Pacific children living in Auckland, New Zealand. Adolescence is a critical time of growth and development, yet the roles of physical function and body composition in metabolic health at this life stage are not clear. We aimed to investigate associations between measures of physical function (the 6-minute-walk-test (6MWT)), heart rate changes before and after the 6MWT, handgrip strength, body composition including appendicular skeletal muscle mass (ASMM) measured by dual-energy X-ray absorptiometry and biomarkers of metabolic health from a fasting blood sample.A total of 200 youth (98 girls, 102 boys) aged 14–15 years, from the birth-cohort of children in the Pacific Islands families study were measured. In girls, the proportion of ASMM was lower and fat higher than in boys. Controlling for age, a 1% increase in ASMM predicted a longer walk distance (+6.3, 95%CI 2.2, 10.4 m in girls; +7.1, 95%CI 4.4, 9.1 m in boys) and lower heart rate following the 6MWT. ASMM and fat mass were independently predictive of maximal handgrip strength which was increased by 1.4 (1.0,1.8) kg in girls and 1.7 (1.3, 2.0) kg in boys for each kg increase in ASMM and reduced by 0.23 (0.08, 0.38) kg in girls and 0.26 (0.14, 0.37) kg in boys for each kg increase in fat mass. Lower total cholesterol and LDL were associated with an increase in distance walked in boys only. For each year of age, distance walked was reduced by 34 (15, 53) m in girls and 59 (36,84) m in boys. These findings should be explored further in the context of other influences such as food security, opportunities for physical activity and cultural expectations.

Prior studies indicate a pathogenic role of neuroinflammation in psychiatric disorders; however, there are no accepted methods that can reliably measure low-level neuroinflammation non-invasively in these individuals. Magnetic resonance spectroscopic imaging (MRSI) is a versatile, non-invasive neuroimaging technique that demonstrates sensitivity to brain inflammation. MRSI in conjunction with echo-planar spectroscopic imaging (EPSI) measures brain metabolites to derive whole-brain and regional brain temperatures, which may increase in neuroinflammation. The validity of MRSI/EPSI for measurement of low level neuroinflammation was tested using a safe experimental model of human brain inflammation – intramuscular administration of typhoid vaccine. Twenty healthy volunteers participated in a double-blind, placebo-controlled crossover study including MRSI/EPSI scans before and 3 h after vaccine/placebo administration. Body temperature and mood, assessed using the Profile of Mood States, were measured every hour up to four hours post-treatment administration. A mixed model analysis of variance was used to test for treatment effects. A significant proportion of brain regions (44/47) increased in temperature post-vaccine compared to post-placebo (p

Seed lots of tomato and capsicum (Solanum lycopersicon and Capsicum annuum, respectively) are required to be free of quarantine pests before their entry to Australia is permitted. Testing of samples from 118 larger seed lots in the period 2019–2021 revealed that 31 (26.3%) carried one or more of four Tobamovirus species, including tomato mottle mosaic virus (ToMMV), which is a quarantine pest for Australia. Testing of samples from a further 659 smaller seed lots showed that 123 (18.7%) carried a total of five Tobamovirus species, including ToMMV and tomato brown rugose fruit virus (ToBRFV), which is also a quarantine pest for Australia. Estimated prevalence of contamination by tobamoviruses ranged from 0.388% to 0.004% in contaminated larger seed lots. Analyses of these data allow us to estimate probabilities of detection of contamination under different regulatory settings.

Encapsulin nanocompartments are an emerging class of prokaryotic protein-based organelle consisting of an encapsulin protein shell that encloses a protein cargo. Genes encoding nanocompartments are widespread in bacteria and archaea, and recent works have characterized the biochemical function of several cargo enzymes. However, the importance of these organelles to host physiology is poorly understood. Here, we report that the human pathogen Mycobacterium tuberculosis (Mtb) produces a nanocompartment that contains the dye-decolorizing peroxidase DyP. We show that this nanocompartment is important for the ability of Mtb to resist oxidative stress in low pH environments, including during infection of host cells and upon treatment with a clinically relevant antibiotic. Our findings are the first to implicate a nanocompartment in bacterial pathogenesis and reveal a new mechanism that Mtb uses to combat oxidative stress.

The relative ability of the small laccase (sLac) and dye-decoloring peroxidase (DyP2) from Amycolatopsis sp. 75iv2 to transform a variety of lignins was investigated using time-of-flight secondary ion mass spectrometry (ToF-SIMS). The enzymes modified organosolv hardwood lignin to different extents even in the absence of an added mediator. More particularly, sLac decreased the lignin modification metric S (S-lignin)/Ar (total aromatics) by 58% over 16h, while DyP2 lowered this ratio by 31% in the absence of exogenous H2O2. When used on their own, both sLac and DyP2 also modified native lignin present in aspen wood powder, albeit to lesser extents than in the organosolv lignin. The addition of ABTS for sLac and Mn2+ as well as H2O2 for DyP2 led to increased lignin modification in aspen wood powder as reflected by a decrease in the G/Ar metric by up to a further 13%. This highlights the importance of exogenous mediators for transforming lignin within its native matrix. Furthermore, the addition of ABTS reduced the selectivity of sLac for S-lignin over G-lignin, indicating that the mediator also altered the product profiles. Finally, when sLac was included in reactions containing DyP2, in part to generate H2O2in situ, the relative abundance of lignin products differed from individual enzymatic treatments. Overall, these results identify possible routes to tuning lignin modification or delignification through choice of enzyme and mediator. Moreover, the current study expands the application of ToF-SIMS to evaluating enzyme action on technical lignins, which can accelerate the discovery and engineering of industrially relevant enzymes for lignin valorization.

The valorization of lignin, a major component of plant-derived biomass, is essential to sustainable biorefining. We identified the major monoaromatic compounds present in black liquor, a lignin-rich stream generated in the kraft pulping process, and investigated their bacterial transformation. Among tested solvents, acetone extracted the greatest amount of monoaromatic compounds from softwood black liquor, with guaiacol, vanillin, and acetovanillone, in an approximately 4:3:2 ratio, constituting ~90% of the total extracted monoaromatic content. 4-Ethanol guaiacol, vanillate, and 4-propanol guaiacol were also present. Bacterial strains that grew on minimal media supplemented with the BL extracts at 1mM total aromatic compounds included Pseudomonas putida KT2442, Sphingobium sp. SYK-6, and Rhodococcus rhodochrous EP4. By contrast, the extracts inhibited the growth of Rhodococcus jostii RHA1 and Rhodococcus opacus PD630, strains extensively studied for lignin valorization. Of the strains that grew on the extracts, only R. rhodochrous GD01 and GD02, isolated for their ability to grow on acetovanillone, depleted the major extracted monoaromatics. Genomic analyses revealed that EP4, GD01, and GD02 share an average nucleotide identity (ANI) of 98% and that GD01 and GD02 harbor a predicted three-component carboxylase not present in EP4. A representative carboxylase gene was upregulated ~100-fold during growth of GD02 on a mixture of the BL monoaromatics, consistent with the involvement of the enzyme in acetovanillone catabolism. More generally, quantitative RT-PCR indicated that GD02 catabolizes the BL compounds in a convergent manner via the β-ketoadipate pathway. Overall, these studies help define the catabolic capabilities of potential biocatalytic strains, describe new isolates able to catabolize the major monoaromatic components of BL, including acetovanillone, and facilitate the design of biocatalysts to valorize under-utilized components of industrial lignin streams.

PREMISE The successful application of universal targeted sequencing markers, such as those developed for the Angiosperms353 probe set, within populations could reduce or eliminate the need for specific marker development, while retaining the benefits of full‐gene sequences in population‐level analyses. However, whether the Angiosperms353 markers provide sufficient variation within species to calculate demographic parameters is untested. METHODS Using herbarium specimens from a 50‐year‐old floristic survey in Texas, we sequenced 95 samples from 24 species using the Angiosperms353 probe set. Our data workflow calls variants within species and prepares data for population genetic analysis using standard metrics. In our case study, gene recovery was affected by genomic library concentration only at low concentrations and displayed limited phylogenetic bias. RESULTS We identified over 1000 segregating variants with zero missing data for 92% of species and demonstrate that Angiosperms353 markers contain sufficient variation to estimate pairwise nucleotide diversity (π)—typically between 0.002 and 0.010, with most variation found in flanking non‐coding regions. In a subset of variants that were filtered to reduce linkage, we uncovered high heterozygosity in many species, suggesting that denser sampling within species should permit estimation of gene flow and population dynamics. DISCUSSION Angiosperms353 should benefit conservation genetic studies by providing universal repeatable markers, low missing data, and haplotype information, while permitting inclusion of decades‐old herbarium specimens.

Purpose: MPPC syndrome has been described as a syndrome that presents with chorioretinal coloboma, posterior megalolenticonus, persistent fetal vasculature, and chorioretinal coloboma. The purpose of our study is to report three patients who present with a variation of MPPC syndrome who each underwent pars plana vitrectomy, pars plana lensectomy, and amblyopic management. Clinical characteristics, ancillary test findings, and post-surgical functional results are compared to what is reported in the literature. Methods: Retrospective review of medical records of patients who presented with microcornea, persistent fetal vasculature, chorioretinal coloboma, and microphthalmia who underwent surgical correction at Bascom Palmer Eye Institute. Results: 3 patients (6 eyes) were included, two males and one female. All patients were born full term, vaginally, and had no family history of genetic abnormalities affecting the eye. All patients had color fundus images, fluorescein angiography (FA) and echography. Four eyes underwent surgery. Following surgical intervention, patients demonstrated improved visual acuity, and improved functional status. Conclusion and Importance: Patients with microcornea, PFV, chorioretinal coloboma, and microphthalmos, can benefit from surgical intervention when functional decline or media opacities are noted. Though difficult to assess accurate visual acuity and visual improvement pre-operatively and post-operatively, it is evident that our patients demonstrated improvement in functionality and vision following surgical intervention.

It remains unclear how urban emissions influence the formation of secondary organic aerosols (SOA), including in the Amazon forest. Here, the authors simulate the formation of SOAs in the Amazon using a high-resolution regional chemical transport model. They find that urban emissions of NOx from Manaus enhance the production of biogenic SOA by 60–200%.