Creation and preclinical evaluation of a novel mussel-inspired, biomimetic, bioactive bone graft scaffold: direct comparison with Infuse bone graft using a rat model of spinal fusion.

OBJECTIVE: Infuse bone graft is a widely used osteoinductive adjuvant; however, the simple collagen sponge scaffold used in the implant has minimal inherent osteoinductive properties and poorly controls the delivery of the adsorbed recombinant human bone morphogenetic protein-2 (rhBMP-2). In this study, the authors sought to create a novel bone graft substitute material that overcomes the limitations of Infuse and compare the ability of this material with that of Infuse to facilitate union following spine surgery in a clinically translatable rat model of spinal fusion. METHODS: The authors created a polydopamine (PDA)-infused, porous, homogeneously dispersed solid mixture of extracellular matrix and calcium phosphates (BioMim-PDA) and then compared the efficacy of this material directly with Infuse in the setting of different concentrations of rhBMP-2 using a rat model of spinal fusion. Sixty male Sprague Dawley rats were randomly assigned to each of six equal groups: 1) collagen + 0.2 µg rhBMP-2/side, 2) BioMim-PDA + 0.2 µg rhBMP-2/side, 3) collagen + 2.0 µg rhBMP-2/side, 4) BioMim-PDA + 2.0 µg rhBMP-2/side, 5) collagen + 20 µg rhBMP-2/side, and 6) BioMim-PDA + 20 µg rhBMP-2/side. All animals underwent posterolateral intertransverse process fusion at L4-5 using the assigned bone graft. Animals were euthanized 8 weeks postoperatively, and their lumbar spines were analyzed via microcomputed tomography (µCT) and histology. Spinal fusion was defined as continuous bridging bone bilaterally across the fusion site evaluated via µCT. RESULTS: The fusion rate was 100% in all groups except group 1 (70%) and group 4 (90%). Use of BioMim-PDA with 0.2 µg rhBMP-2 led to significantly greater results for bone volume (BV), percentage BV, and trabecular number, as well as significantly smaller trabecular separation, compared with the use of the collagen sponge with 2.0 µg rhBMP-2. The same results were observed when the use of BioMim-PDA with 2.0 µg rhBMP-2 was compared with the use of the collagen sponge with 20 µg rhBMP-2. CONCLUSIONS: Implantation of rhBMP-2-adsorbed BioMim-PDA scaffolds resulted in BV and bone quality superior to that afforded by treatment with rhBMP-2 concentrations 10-fold higher implanted on a conventional collagen sponge. Using BioMim-PDA (vs a collagen sponge) for rhBMP-2 delivery could significantly lower the amount of rhBMP-2 required for successful bone grafting clinically, improving device safety and decreasing costs.

Associations between nutritional intake, stress and hunger biomarkers, and anxiety and depression during the treatment of anorexia nervosa in adolescents and young adults.

Adolescents and young adults (AYA) with anorexia nervosa (AN) frequently have co-occurring anxiety and depression, which can negatively impact prognosis. To inform treatment of co-occurring anxiety and depression, we assessed the association of nutritional intake and hunger/stress hormones on anxiety and depression using a six-month longitudinal study of 50 AYA females receiving care for AN. At baseline and six months, we measured anxiety (Spielberger State/Trait Anxiety Inventory [STAI]), depression (Beck Depression Inventory [BDI]), body mass index (BMI), 3-day dietary intake (total calories and proportion of fat, carbohydrate, protein), and serum cortisol, leptin, and adiponectin. We performed mixed effects linear regression analyses, adjusting for age, duration of AN, and percentage of median BMI (%mBMI). At baseline, median age was 16.3 (interquartile range [IQR]=2.5) years, duration of AN was 6 (IQR=8.8) months and %mBMI was 87.2 (IQR=10.5)%. Fifty-six percent had clinically significant anxiety; 30% had depression. Over 6 months, participants had significant improvements in %mBMI (+2.2[IQR=9.2]%, p<.01), STAI (-9.0[IQR=25.0], p<.01), and BDI (-5.0[IQR=13.8], p<.01) scores. Participants with larger improvements in caloric intake had greater improvements in STAI (p=.03) and BDI scores (p=.04). Larger improvement in BDI was significantly associated with increased fat intake (p<.01), but not carbohydrate or protein intake. Change in STAI was not associated with changes in fat, carbohydrate, or protein intake. Changes in STAI or BDI scores were not associated with changes in cortisol, leptin, or adiponectin. Increased caloric intake may augment treatment of co-occurring anxiety and depression, and increased fat intake may improve depression for AYA with AN.

Pap Smear and Mammogram Screening Rates in a Refugee and General OB/GYN Clinic: A Retrospective Review.

Although multiple studies have shown that resettled refugee women are less likely to receive preventative cancer screenings like pap smears and mammograms, a small number have demonstrated the opposite. This retrospective chart review, conducted between January 2017 and October 2018, compares pap smear and mammogram rates of patients seen in a refugee-specific OB/GYN clinic with patients from the general OB/GYN clinic at the same institution. Data from 298 patients (149 refugee and 149 general clinic patients matched by age and date-of-visit) were analyzed. Pap smear screening rates were 90.60% in the refugee group and 73.83% in the general group [p < 0.009, aOR 3.46 (1.36-8.81)], while mammogram screening rates were 36.84% and 38.60%, respectively (p = 0.46). The provision of holistic services meeting refugee women's unique needs can effectively increase pap smear screening rates.

Trait mindfulness and cannabis use-related factors in adolescents and young adults with frequent use.

Background: Mindfulness-based interventions (MBIs) are effective in adult substance-use treatment and may be helpful for adolescents and young adults (AYAs). One target of MBIs is to improve trait mindfulness, which has been associated with better lifestyle and health outcomes. To inform MBIs for reducing cannabis use in AYAs, we sought to identify how trait mindfulness was associated with cannabis-related problems and quit attempts, as well as with motivation to change use in youth who report frequent use. Methods: Participants aged 15-24 years using cannabis ≥ 3x/week were recruited from AYA clinics in a northeastern US city to participate in a cannabis-use intervention pilot, randomized trial. At baseline, we assessed cannabis-use history, problems associated with use, attempts to quit, and trait mindfulness. All participants were offered two sessions of motivational enhancement therapy, during which they rated motivation to quit cannabis. Regression analyses were conducted to assess associations between trait mindfulness and cannabis use-related problems, attempts to quit, and motivation to change. Results: Seventy participants, mean age 20.7 ± 1.9 years, enrolled. Sixty percent identified as female, 47% as Black non-Hispanic, and 31% as Hispanic. Participants started using cannabis at mean age 15.0 ± 2.8 years and were using ≥ 3x/week by 17.0 ± 2.3 years. Higher mindfulness scores were associated with fewer cannabis-related problems (p = 0.004) and fewer quit attempts (p = 0.035). The number of cannabis-related problems did not significantly mediate the relationship between mindfulness and quit attempts. Trait mindfulness did not predict motivation to change cannabis use. Conclusions: Among AYAs using cannabis frequently, higher trait mindfulness was associated with both fewer cannabis use--related problems and fewer quit attempts. Future research should assess whether trait mindfulness is an appropriate target for decreasing cannabis use and the utility of MBIs for reducing cannabis-use behaviors.

Unmet Health and Social Welfare Needs of Women Who Inject Drugs in San Francisco.

We characterize social welfare and health care needs of women who inject drugs in a community-based survey in San Francisco. A total of 139 women were enrolled; 74.8% were homeless, and 67.6% earned below poverty level. Indicators of health care and prevention program access included: 95.7% with health insurance, 90.6% used a needle exchange program, and 58.2% tested for HIV two or more times. However, only 8.6% received HPV vaccination and there was unmet contraception need for 79.0% of women. Only 28.7% of those testing positive for HCV infection had received treatment. Physical and sexual violence in the last year were common (41.0% and 18.0%, respectively). Women who inject drugs would benefit from integrated health and social services including addressing interpersonal violence, sexual and reproductive health, and HIV and HCV prevention needs. Women-only needle exchange programs and safe injection sites may be effective delivery points for these services.

Mindfulness-based interventions for adolescent health.

PURPOSE OF REVIEW: Mindfulness, the practice of paying attention to the present moment, purposefully and nonjudgmentally, has been gaining popularity as adjunct treatment for adolescents with a range of physical and mental health problems. Research conducted in adults and emerging research conducted in adolescents has shown that mindfulness-based interventions can improve outcomes in several areas. The purpose of this review is to discuss recent research on the effects of mindfulness and suggest exercises that primary care clinicians can offer to their adolescent patients. RECENT FINDINGS: Research has shown positive effects of mindfulness across several health conditions commonly encountered during adolescence. Mindfulness-based Interventions can reduce symptoms of anxiety and depression. The application of mindfulness can help with the prevention and treatment of binge eating, over-eating, and restrictive eating disorders. In the treatment of substance use disorders, mindfulness can improve emotion regulation and reduce symptoms of withdrawal and craving. Mindfulness can also lead to improvement in overall quality of life for patients suffering from chronic pain. Lastly, mindfulness can be useful for adolescents with ADHD, sleep problems, chronic illness, and stress related to performance sports. SUMMARY: Although research in adolescents remains limited, mindfulness holds promise in the treatment of a range of health conditions in adolescents.

Local glutamate release in the rat ventral lateral thalamus evoked by high-frequency stimulation.

Thalamic deep brain stimulation (DBS) is proven therapy for essential tremor, Parkinson's disease and Tourette's syndrome. We tested the hypothesis that high-frequency electrical stimulation results in local thalamic glutamate release. Enzyme-linked glutamate amperometric biosensors were implanted in anesthetized rat thalamus adjacent to the stimulating electrode. Electrical stimulation was delivered to investigate the effect of frequency, pulse width, voltage-controlled or current-controlled stimulation, and charge balancing. Monophasic electrical stimulation-induced glutamate release was linearly dependent on stimulation frequency, intensity and pulse width. Prolonged stimulation evoked glutamate release to a plateau that subsequently decayed back to baseline after stimulation. Glutamate release was less pronounced with voltage-controlled stimulation and not present with charge balanced current-controlled stimulation. Using fixed potential amperometry in combination with a glutamate bioprobe and adjacent microstimulating electrode, the present study has shown that monophasic current-controlled stimulation of the thalamus in the anesthetized rat evoked linear increases in local extracellular glutamate concentrations that were dependent on stimulation duration, frequency, intensity and pulse width. However, the efficacy of monophasic voltage-controlled stimulation, in terms of evoking glutamate release in the thalamus, was substantially lower compared to monophasic current-controlled stimulation and entirely absent with biphasic (charge balanced) current-controlled stimulation. It remains to be determined whether similar glutamate release occurs with human DBS electrodes and similar charge balanced stimulation. As such, the present results indicate the importance of evaluating local neurotransmitter dynamics in studying the mechanism of action of DBS.

What makes tight glycemic control tight? The impact of variability and nutrition in two clinical studies.

INTRODUCTION: Tight glycemic control (TGC) remains controversial while successful, consistent, and effective protocols remain elusive. This research analyzes data from two TGC trials for root causes of the differences achieved in control and thus potentially in glycemic and other outcomes. The goal is to uncover aspects of successful TGC and delineate the impact of differences in cohorts. METHODS: A retrospective analysis was conducted using records from a 211-patient subset of the GluControl trial taken in Liege, Belgium, and 393 patients from Specialized Relative Insulin Nutrition Titration (SPRINT) in New Zealand. Specialized Relative Insulin Nutrition Titration targeted 4.0-6.0 mmol/liter, similar to the GluControl A (N = 142) target of 4.4-6.1 mmol/liter. The GluControl B (N = 69) target was 7.8-10.0 mmol/liter. Cohorts were matched by Acute Physiology and Chronic Health Evaluation II score and percentage males (p > .35); however, the GluControl cohort was slightly older (p = .011). Overall cohort and per-patient comparisons (median, interquartile range) are shown for (a) glycemic levels achieved, (b) nutrition from carbohydrate (all sources), and (c) insulin dosing for this analysis. Intra- and interpatient variability were examined using clinically validated model-based insulin sensitivity metric and its hour-to-hour variation. RESULTS: Cohort blood glucose were as follows: SPRINT, 5.7 (5.0-6.6) mmol/liter; GluControl A, 6.3 (5.3-7.6) mmol/liter; and GluControl B, 8.2 (6.9-9.4) mmol/liter. Insulin dosing was 3.0 (1.0-3.0), 1.5 (0.5-3), and 0.7 (0.0-1.7) U/h, respectively. Nutrition from carbohydrate (all sources) was 435.5 (259.2-539.1), 311.0 (0.0-933.1), and 622.1 (103.7-1036.8) kcal/day, respectively. Median per-patient results for blood glucose were 5.8 (5.3-6.4), 6.4 (5.9-6.9), and 8.3 (7.6-8.8) mmol/liter. Insulin doses were 3.0 (2.0-3.0), 1.5 (0.8-2.0), and 0.5 (0.0-1.0) U/h. Carbohydrate administration was 383.6 (207.4-497.7), 103.7 (0.0-829.4), and 207.4 (0.0-725.8) kcal/day. Overall, SPRINT gave approximately 2x more insulin with a 3-4x narrower, but generally non-zero, range of nutritional input to achieve equally TGC with less hypoglycemia. Specialized Relative Insulin Nutrition Titration had much less hypoglycemia (<2.2 mmol/liter), with 2% of patients, compared to GluControl A (7.7%) and GluControl B (2.9%), indicating much lower variability, with similar results for glucose levels <3.0 mmol/liter. Specialized Relative Insulin Nutrition Titration also had less hyperglycemia (>8.0 mmol/liter) than groups A and B. GluControl patients (A+B) had a approximately 2x wider range of insulin sensitivity than SPRINT. Hour-to-hour variation was similar. Hence GluControl had greater interpatient variability but similar intrapatient variability. CONCLUSION: Protocols that dose insulin blind to carbohydrate administration can suffer greater outcome glycemic variability, even if average cohort glycemic targets are met. While the cohorts varied significantly in model-assessed insulin resistance, their variability was similar. Such significant intra- and interpatient variability is a further significant cause and marker of glycemic variability in TGC. The results strongly recommended that TGC protocols be explicitly designed to account for significant intra- and interpatient variability in insulin resistance, as well as specifying or having knowledge of carbohydrate administration to minimize variability in glycemic outcomes across diverse cohorts and/or centers.

Model-based insulin and nutrition administration for tight glycaemic control in critical care.

OBJECTIVE: Present a new model-based tight glycaemic control approach using variable insulin and nutrition administration. BACKGROUND: Hyperglycaemia is prevalent in critical care. Current published protocols use insulin alone to reduce blood glucose levels, require significant added clinical effort, and provide highly variable results. None directly address both the practical clinical difficulties and significant patient variation seen in general critical care, while also providing tight control. METHODS: The approach presented manages both nutritional inputs and exogenous insulin infusions using tables simplified from a model-based, computerised protocol. Unique delivery aspects include bolus insulin delivery for safety and variable enteral nutrition rates. Unique development aspects include the use of simulated virtual patient trials created from retrospective data. The model, protocol development, and first 50 clinical case results are presented. RESULTS: High qualitative correlation to within +/-10% between simulated virtual trials and published clinical results validates the overall approach. Pilot tests covering 7358 patient hours produced an average glucose of 5.9 +/- 1.1 mmol/L. Time in the 4-6.1 mmol/L band was 59%, with 84% in 4.0-7.0 mmol/L, and 92% in 4.0-7.75 mmol/L. The average feed rate was 63% of patient specific goal feed and the average insulin dose was 2.6U/hour. There was one hypoglycaemic measurement of 2.1 mmol/L. No departures from protocol or clinical interventions were required at any time. SUMMARY: Modulating both low dose insulin boluses and nutrition input rates challenges the current practice of using only insulin in larger doses to reduce hyperglycaemic levels. Clinical results show very tight control in safe glycaemic bands. The approach could be readily adopted in any typical ICU.