Frontal Brain N-Acetylaspartate at Treatment Entry is Related to Future WHO Risk Drinking Levels in Individuals with Alcohol Use Disorder.

OBJECTIVE: To assess the viability of regional brain metabolite levels of individuals with alcohol use disorder (AUD) at treatment entry as a biomarker of post-treatment levels of alcohol use, categorized according to the World Health Organization risk drinking levels (WHO-RDL). METHOD: Eighty-five individuals initiating treatment for AUD (16 ± 13 days after last alcohol consumption), and 45 light/non-drinking controls (LN) completed a 1.5T proton multislice magnetic resonance spectroscopic imaging study. N-acetylaspartate (NAA), a marker of neuronal viability, and other metabolites were quantitated for cortical gray matter (GM), white matter (WM) and select subcortical regions. Individuals with AUD were classified according to their post-treatment alcohol consumption, as abstainers (AB, n=42), low risk (RL, n=20), or higher risk (RH, n=23), based on the WHO-RDL taxonomy. RESULTS: Within frontal GM, RH exhibited significantly lower NAA levels than LN and AB but did not differ from RL. RH had significantly lower NAA concentration in frontal WM than all groups who did not significantly differ from one another. RH showed significantly lower parietal WM NAA than LN and AB; RL and RH did not differ from one another. Across RH and RL, lower frontal GM and WM NAA was related to shorter period of abstinence before first post-treatment alcohol consumption and longer post-treatment duration of alcohol resumption. There were no significant group differences in myo-inositol or choline- or creatine-containing compound concentrations. CONCLUSIONS: Frontal and parietal lobar NAA concentrations, near treatment entry, are associated with WHO-RDL categorized post-treatment alcohol consumption levels and may serve as predictive biomarkers of clinical outcomes following treatment for AUD.

Pro-atherogenic medical conditions are associated with widespread regional brain metabolite abnormalities in those with alcohol use disorder.

AIMS: Widespread brain metabolite abnormalities in those with alcohol use disorder (AUD) were reported in numerous studies, but the effects of the pro-atherogenic conditions of hypertension, type 2 diabetes mellitus, hepatitis C seropositivity, and hyperlipidemia on metabolite levels were not considered. These conditions were associated with brain metabolite abnormalities in those without AUD. We predicted treatment-seeking individuals with AUD and pro-atherogenic conditions (Atherogenic+) demonstrate lower regional metabolite markers of neuronal viability [N-acetylaspartate (NAA)] and cell membrane turnover/synthesis [choline-containing compounds (Cho)], compared with those with AUD without pro-atherogenic conditions (Atherogenic-) and healthy controls (CON). METHODS: Atherogenic+ (n = 59) and Atherogenic- (n = 51) and CON (n = 49) completed a 1.5 T proton magnetic resonance spectroscopic imaging study. Groups were compared on NAA, Cho, total creatine, and myoinositol in cortical gray matter (GM), white matter (WM), and select subcortical regions. RESULTS: Atherogenic+ had lower frontal GM and temporal WM NAA than CON. Atherogenic+ showed lower parietal GM, frontal, parietal and occipital WM and lenticular nuclei NAA level than Atherogenic- and CON. Atherogenic- showed lower frontal GM and WM NAA than CON. Atherogenic+ had lower Cho level than CON in the frontal GM, parietal WM, and thalamus. Atherogenic+ showed lower frontal WM and cerebellar vermis Cho than Atherogenic- and CON. CONCLUSIONS: Findings suggest proatherogenic conditions in those with AUD were associated with increased compromise of neuronal integrity and cell membrane turnover/synthesis. The greater metabolite abnormalities observed in Atherogenic+ may relate to increased oxidative stress-related compromise of neuronal and glial cell structure and/or impaired arterial vasoreactivity/lumen viability.

Regional cortical brain volumes at treatment entry relates to post treatment WHO risk drinking levels in those with alcohol use disorder.

BACKGROUND: Abstinence following treatment for alcohol use disorder (AUD) is associated with significant improvements in psychiatric and physical health, however, recent studies suggest resumption of low risk levels of alcohol use can also be beneficial. The present study assessed whether post-treatment levels of alcohol use were associated with cortical brain volumedifferences at treatment entry. METHODS: Individuals seeking treatment for AUD (n=75) and light/non-drinking controls (LN, n=51) underwent 1.5T magnetic resonance imaging. The volumes of 34 bilateral cortical regions of interest (ROIs) were quantitated via FreeSurfer. Individuals with AUD were classified according to post-treatment alcohol consumption using the WHO risk drinking levels (abstainers: AB; low risk: RL; or higher risk: RH). Regional volumes for AB, RL and RH, at treatment entry, were compared to LN. RESULTS: Relative to LN, AB demonstrated smaller volumes in 18/68 (26%), RL in 24/68 (35%) and RH in 34/68 (50%) ROIs with the largest magnitude volume differences observed between RH and LN. RH and RL reported a higher frequency of depressive disorders than AB. Among RH and RL, level of depressive and anxiety symptomatology were associated with daily number of drinks consumed after treatment. CONCLUSIONS: Volumetric differences, at treatment entry, in brain regions implicated in executive function and salience networks corresponded with post-treatment alcohol consumption levels suggesting that pre-existing differences in neural integrity may contribute to treatment outcomes. Depressive and anxiety symptomatology was also associated with brain morphometrics and alcohol use patterns, highlighting the importance of effectively targeting these conditions during AUD treatment.

Regional cortical thickness recovery with extended abstinence after treatment in those with alcohol use disorder.

Several cross-sectional investigations reported widespread cortical thinning in those with alcohol use disorder (AUD). The few longitudinal studies investigating cortical thickness changes during abstinence are limited to the first month of sobriety. Consequently, cortical thickness changes during extended abstinence in those with AUD is unclear. In this study, AUD participants were studied at approximately 1 week (n = 68), 1 month (n = 88), and 7.3 months (n = 40) of abstinence. Forty-five never-smoking controls (CON) completed a baseline study, and 15 were reassessed after approximately 9.6 months. Participants completed magnetic resonance imaging studies at 1.5T, and cortical thickness for 34 bilateral regions of interest (ROI) was quantitated with FreeSurfer. AUD participants demonstrated significant linear thickness increases in 25/34 ROI over 7.3 months of abstinence. The rate of change from 1 week to 1 month was greater than 1 month to 7.3 months in 19/34 ROIs. Proatherogenic conditions were associated with lower thickness recovery in anterior frontal, inferior parietal, and lateral/mesial temporal regions. After 7.3 months of abstinence, AUD participants were statistically equivalent to CON on cortical thickness in 24/34 ROIs; the cortical thickness differences between AUD and CON in the banks superior temporal gyrus, post central, posterior cingulate, superior parietal, supramarginal, and superior frontal cortices were driven by thinner cortices in AUD with proatherogenic conditions relative to CON. In actively smoking AUD, increasing pack-years was associated with decreasing thickness recovery primarily in the anterior frontal ROIs. Widespread bilateral cortical thickness recovery over 7.3 months of abstinence was the central finding for this AUD cohort. The longitudinal and cross-sectional findings for AUD with proatherogenic suggests alterations in perfusion or vascular integrity may relate to structural recovery in those with AUD. These results support the adaptive and beneficial effects of sustained sobriety on brain structural recovery in people with AUD.

A mixed method approach to evaluating eating-related psychopathologies in collegiate student-athletes.

OBJECTIVE: To examine the presence of body image concerns, drive for muscularity, and disordered eating behaviors in collegiate student-athletes. PARTICIPANTS: One hundred and one NCAA Division I student-athletes participated in Phase I; 15 of these also participated in Phase II. METHODS: This study employed a mixed method, sequential explanatory design. Participants first completed survey measures assessing body image concern, drive for muscularity, and eating behaviors. These results influenced open-ended, semi-structured interviews, which were thematically analyzed. RESULTS: Body image and disordered eating behaviors were of greater concern than drive for muscularity. Student-athletes reported engaging in eating behaviors as opposed to not eating, yet these eating behaviors trended toward disordered behaviors such as obsessive "healthy eating" or orthorexia. CONCLUSIONS: This study took a novel methodological approach to examining student-athlete body image and eating behaviors. Results emphasize the need for further support and education for student-athletes around body image and eating behaviors.

Non-Solvent Induced Phase Separation (NIPS) for Fabricating High Filtration Efficiency (FE) Polymeric Membranes for Face Mask and Air Filtration Applications.

Protection against airborne viruses has become very relevant since the outbreak of SARS-CoV-2. Nonwoven face masks along with heating, ventilation, and air conditioning (HVAC) filters have been used extensively to reduce infection rates; however, some of these filter materials provide inadequate protection due to insufficient initial filtration efficiency (FE) and FE decrease with time. Flat sheet porous membranes, which have been used extensively to filter waterborne microbes and particulate matter due to their high FE have the potential to filter air pollutants without compromising its FE over time. Therefore, in this study, single layer polysulfone (PSf) membranes were fabricated via non-solvent induced phase separation (NIPS) and were tested for airflow rate, pressure drop and FE. Polyethylene glycol (PEG) and glycerol were employed as pore-forming agents, and the effect of the primary polymer and pore-forming additive molecular weights (MW) on airflow rate and pressure drop were studied at different concentrations. The thermodynamic stability of dope solutions with different MWs of PSf and PEG in N-methylpyrrolidone (NMP) at different concentrations was determined using cloud-point measurements to construct a ternary phase diagram. Surface composition of the fabricated membranes was characterized using contact angle and X-ray photoelectron spectroscopy (XPS), while membrane morphology was characterized by SEM, and tensile strength experiments were performed to analyze the membrane mechanical strength (MS). It was observed that an increase in PSf and PEG molecular weight and concentration increased airflow and decreased pressure drop. PSf60:PEG20:NMP (15:15:70)% w/w showed the highest air flow rate and lowest pressure drop, but at the expense of the mechanical strength, which was improved significantly by attaching the membrane to a 3D-printed polypropylene support. Lastly, the FE values of the membranes were similar to those of double-layer N95 filters and significantly higher than those of single layer of N95, surgical mask and HVAC (MERV 11) filters.

A randomized study of CrossFit Kids for fostering fitness and academic outcomes in middle school students.

Within the context of school-based physical education (PE), a strength and conditioning program called CrossFit Kids (CFK) has emerged as a potential intervention for positively impacting students. The purpose of this study was to evaluate through a randomized-controlled trial how academic and health-related fitness outcomes differed for middle school students (age = 12.73; 55.3 % male) who participated in a school-based CFK program (n=72) as compared to a group of students who participated in PE class (n=72). Questionnaire data were collected twice across the 9-month academic year and combined with FitnessGram and grade data. Students in both the intervention and comparison groups increased in health-related fitness outcomes (all p values < .017), and there was a significant treatment group by time interaction on school-reported grades [F(1, 124) = 7.270, p = .008, η_P^2 = .055]. Significant gender by time interaction effects were found for the relationship between CFK or PE participation and health-related fitness outcomes, but there were no significant interaction effects by gender on academic outcomes. Because developmental outcomes are conditional and result from the coaction of many factors, the findings suggest that some elements of CFK might be beneficial to build skills yet disadvantageous to academic outcomes.

Stereolithographic printing of ionically-crosslinked alginate hydrogels for degradable biomaterials and microfluidics.

3D printed biomaterials with spatial and temporal functionality could enable interfacial manipulation of fluid flows and motile cells. However, such dynamic biomaterials are challenging to implement since they must be responsive to multiple, biocompatible stimuli. Here, we show stereolithographic printing of hydrogels using noncovalent (ionic) crosslinking, which enables reversible patterning with controlled degradation. We demonstrate this approach using sodium alginate, photoacid generators and various combinations of divalent cation salts, which can be used to tune the hydrogel degradation kinetics, pattern fidelity, and mechanical properties. This approach is first utilized to template perfusable microfluidic channels within a second encapsulating hydrogel for T-junction and gradient devices. The presence and degradation of printed alginate microstructures were further verified to have minimal toxicity on epithelial cells. Degradable alginate barriers were used to direct collective cell migration from different initial geometries, revealing differences in front speed and leader cell formation. Overall, this demonstration of light-based 3D printing using non-covalent crosslinking may enable adaptive and stimuli-responsive biomaterials, which could be utilized for bio-inspired sensing, actuation, drug delivery, and tissue engineering.

Altered expression of signalling lymphocyte activation molecule receptors in T-cells from lupus nephritis patients-a potential biomarker of disease activity.

Objectives: The aim was to investigate whether the signalling lymphocyte activation molecule (SLAM) signalling pathways contribute to LN and whether SLAM receptors could be valuable biomarkers of disease activity. Methods: Peripheral blood mononuclear cells from 30National Research Ethics Service SLE patients with biopsy-proven LN were analysed by flow cytometry. Clinical measures of disease activity were assessed. The expression of the SLAM family receptors on T-cell subpopulations [CD4, CD8 and double negative (DN) T cells] was measured and compared between lupus patients with active renal disease and those in remission. Results: The frequency of CD8 T cells expressing SLAMF3, SLAMF5 and SLAMF7 was significantly lower in LN patients who were in remission. In contrast, these subsets were similar in patients with active renal disease and in healthy individuals. Patients with active nephritis had an increased percentage of circulating monocytes, consistent with a potential role played by these cells in glomerular inflammation. Changes in the frequency of DN T cells positive for SLAMF2, SLAMF4 and SLAMF7 were observed in lupus patients irrespective of the disease activity. We detected alterations in the cellular expression of the SLAM family receptors, but these changes were less obvious and did not reveal any specific pattern. The percentage of DN T cells expressing SLAMF6 could predict the clinical response to B-cell depletion in patients with LN. Conclusion: Our study demonstrates altered expression of the SLAM family receptors in SLE T lymphocytes. This is consistent with the importance of the SLAM-associated pathways in lupus pathogenesis.

Pediatric intestinal failure: Predictors of metabolic bone disease.

PURPOSE: The purpose of this study was to identify risk factors for the development of metabolic bone disease (MBD) in pediatric intestinal failure (IF). METHODS: A retrospective single-center study of 36 pediatric IF patients who were screened for MBD was performed. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). Simple regression analysis was initially performed to screen predictors, followed by multivariate step-wise linear regression analysis to identify risk factors of MBD. RESULTS: Mean lumbar spine BMD Z-score was -1.16 ± 1.32, and 50.0% of patients had a BMD Z-score less than -1.0. Deficiency of 25-hydroxyvitamin-D (25-OHD <30 ng/ml) was present in the 63.8% of patients, while 25.0% had hyperparathyroidism (intact parathyroid hormone (PTH)>55 pg/ml). Seven patients (19.4%) had bone pain, of which 4 (11.1%) suffered a pathologic fracture. Using multivariate analysis, parenteral nutrition (PN) duration predicted decreased BMD (B=-0.132, p=0.006). Serum 25-OHD nonsignificantly correlated with BMD Z-score (B=0.024, p=0.092). Interestingly, repeat DXA after increasing vitamin D supplementation showed no improvement in BMD Z-score (-1.18 ± 1.49 vs -1.36 ± 1.47, p=0.199). CONCLUSIONS: Pediatric IF is associated with a significant risk of MBD, which is predicted by the duration of PN-dependence. These findings underscore the importance of BMD monitoring. Better therapies for treating IF-associated MBD are needed.

Enteral autonomy in pediatric short bowel syndrome: predictive factors one year after diagnosis.

PURPOSE: This study examined predictors of achieving enteral autonomy among pediatric short bowel syndrome (SBS) patients remaining on parenteral nutrition (PN) beyond one year. METHODS: A retrospective single-institution study of 171 pediatric SBS patients (defined as ≥50% small bowel (SB) loss or ≥60 days of PN with onset before 6 weeks of age) was performed. Multivariate Cox proportional hazards analysis was conducted, with subgroup analysis of patients on PN for ≥1 year (n=59). Primary outcome was successful wean from PN. RESULTS: Over a follow-up of 4.1±4.8 years, 64.3% of children weaned from PN. Mortality was 15.2%. Presence of ≥10% expected SB length (hazard ratio [HR] 6.48, p=0.002) or an ileocecal valve (ICV; HR, 2.86, p<0.001) predicted PN weaning. Of those on PN ≥1 year, the wean rate was 50.8%, and ICV no longer predicted weaning (p=0.153). Predictors among those on PN ≥1 year were: ≥10% expected SB length (HR, 8.27, p=0.010), intestinal atresia (HR, 4.26, p=0.011), and necrotizing enterocolitis (NEC, HR, 2.84, p=0.025). CONCLUSIONS: SBS children on PN ≥1 year continue to wean from PN, and those with ≥10% of predicted SB length, NEC, or atresia are more likely to do so. These findings may help direct management and advice for these challenging patients.

Characterization of central venous catheter-associated deep venous thrombosis in infants.

PURPOSE: Deep venous thrombosis (DVT) is a frequent complication in infants with central venous catheters (CVCs). We performed this study to identify risk factors and risk-reduction strategies of CVC-associated DVT in infants. METHODS: Infants younger than 1 year who had a CVC placed at our center from 2005 to 2009 were reviewed. Patients with ultrasonically diagnosed DVT were compared to those without radiographic evidence. RESULTS: Of 333 patients, 47% (155/333) had femoral, 33% (111/333) had jugular, and 19% (64/333) had subclavian CVCs. Deep venous thromboses occurred in 18% (60/333) of patients. Sixty percent (36/60) of DVTs were in femoral veins. Femoral CVCs were associated with greater DVT rates (27%; 42/155) than jugular (11%; 12/111) or subclavian CVCs (9%; 6/64; P < .01). There was a 16% DVT rate in those with saphenofemoral Broviac CVCs vs 83% (20/24) in those with percutaneous femoral lines (P < .01). Multilumen CVCs had higher DVT rates than did single-lumen CVCs (54% vs 6%, P < .01), and mean catheter days before DVT diagnosis was shorter for percutaneous lines than Broviacs (13 ± 17 days vs 30 ± 37 days, P = .02). Patients with +DVT had longer length of stay (86 ± 88 days vs 48 ± 48 days, P < .01) and higher percentage of intensive care unit admission (82% vs 70%, P = .02). CONCLUSIONS: Deep venous thrombosis reduction strategies in infants with CVCs include avoiding percutaneous femoral and multilumen CVCs, screening percutaneous lines, and early catheter removal.

Discovering small molecules that promote cardiomyocyte generation by modulating Wnt signaling.

We have developed a robust in vivo small-molecule screen that modulates heart size and cardiomyocyte generation in zebrafish. Three structurally related compounds (Cardionogen-1 to Cardionogen-3) identified from our screen enlarge the size of the developing heart via myocardial hyperplasia. Increased cardiomyocyte number in Cardionogen-treated embryos is due to expansion of cardiac progenitor cells. In zebrafish embryos and murine embryonic stem (ES) cells, Cardionogen treatment promotes cardiogenesis during and after gastrulation, whereas it inhibits heart formation before gastrulation. Cardionogen-induced effects can be antagonized by increasing Wnt/ß-catenin signaling activity. We demonstrate that Cardionogen inhibits Wnt/ß-catenin-dependent transcription in murine ES cells and zebrafish embryos. Cardionogen can rescue Wnt8-induced cardiomyocyte deficiency and heart-specific phenotypes during development. These findings demonstrate that in vivo small-molecule screens targeting heart size can reveal compounds with cardiomyogenic effects and identify underlying target pathways.