Evaluating the effects of hypoxic storage on platelet function and health using a novel storage system.

BACKGROUND: Thousands of units of whole blood (WB) and blood components are transfused daily to treat trauma patients. Improved methods for blood storage are critical to support trauma-related care. The Hemanext ONE® system offers a unique method for hypoxic storage of WB, with successfully demonstrated storage of clinically viable RBCs. This work evaluated the system for the storage of WB, focusing on platelet health and function. STUDY DESIGN AND METHODS: WB was collected from healthy donors and processed through the Hemanext ONE® system. Hemoglobin oxygen saturation (HbSO2) levels of WB were depleted to 10%, 20%, or 30% of total HbSO2 and then stored in PVC bags sealed in oxygen-impermeable bags (except for normoxic control) with samples collected on days 1, 7, and 14 post-processing. Flow cytometry assessed the activation and apoptosis of platelets. Clot dynamics were assessed based on aggregometry and thromboelastography assays, as well as thrombin generation using a calibrated-automated thrombogram method. RESULTS: Hypoxic storage conditions were maintained throughout the storage period. Hypoxia triggered increased lactate production, but pH changes were negligible compared to normoxic control. Storage at 10% HbSO2 had a significant impact on platelet function, resulting in increased activation and reduced clot formation and aggregation. These effects were less significant at 20% and 30% HbSO2. DISCUSSION: This study indicates that platelets are sensitive to hypoxic storage and suffer significant metabolic and functional deterioration when stored at or below 10% HbSO2.

The effects of maternal calcium status during late gestation on lamb growth and survival in twin-bearing Merino ewes grazing pasture.

Our project aimed to investigate whether low maternal calcium status during late gestation decreased weight, growth and survival of lambs born to twin-bearing Merino ewes grazing pasture. On day 130 of gestation, approximately a 10 mL blood sample was collected from 108 twin-bearing Merino ewes. Blood pH and calcium ion concentration were measured in whole blood and serum was analysed for calcium, magnesium, phosphate, beta hydroxy butyrate, non-esterified fatty acids and cholesterol. Six to 18 h after birth and at 49 days of age, lamb live weight was recorded. Ewe serum calcium level at day 130 of gestation were divided into tertiles (1.58-2.13, 2.14-2.30, and 2.31-2.99 mmol/L) with ewes classified as either Low, Med or High (n = 36 per group). A general linear mixed model was used to analyse the data. Survival to 1, 2, 3 and 7 days of age was lower for lambs born to ewes in the Low calcium group compared with those born in the Med and High calcium groups (P < 0.05). At day 49 of age, lamb survival tended to be lower for lambs in the Low (73.6%) compared with Med (86.8%) and High (85.3%) calcium groups (P < 0.1). There were no differences in lamb body weight (P > 0.05). Calcium levels of ewes in the Low calcium group were, on average, indicative of subclinical hypocalcaemia, with this group of ewes also having the lowest lamb survival rate, suggesting that maternal subclinical hypocalcaemia reduces lamb survival. Further studies, particularly on improving maternal calcium levels, are warranted.

Assessing variants of uncertain significance implicated in hearing loss using a comprehensive deafness proteome.

Hearing loss is the leading sensory deficit, affecting ~ 5% of the population. It exhibits remarkable heterogeneity across 223 genes with 6328 pathogenic missense variants, making deafness-specific expertise a prerequisite for ascribing phenotypic consequences to genetic variants. Deafness-implicated variants are curated in the Deafness Variation Database (DVD) after classification by a genetic hearing loss expert panel and thorough informatics pipeline. However, seventy percent of the 128,167 missense variants in the DVD are "variants of uncertain significance" (VUS) due to insufficient evidence for classification. Here, we use the deep learning protein prediction algorithm, AlphaFold2, to curate structures for all DVD genes. We refine these structures with global optimization and the AMOEBA force field and use DDGun3D to predict folding free energy differences (∆∆GFold) for all DVD missense variants. We find that 5772 VUSs have a large, destabilizing ∆∆GFold that is consistent with pathogenic variants. When also filtered for CADD scores (> 25.7), we determine 3456 VUSs are likely pathogenic at a probability of 99.0%. Of the 224 genes in the DVD, 166 genes (74%) exhibit one or more missense variants predicted to cause a pathogenic change in protein folding stability. The VUSs prioritized here affect 119 patients (~ 3% of cases) sequenced by the OtoSCOPE targeted panel. Approximately half of these patients previously received an inconclusive report, and reclassification of these VUSs as pathogenic provides a new genetic diagnosis for six patients.

Faculty Development in Academic Hospital Medicine: a Scoping Review.

This scoping review sought to identify and describe the state of academic faculty development programs in hospital medicine and other specialties. We reviewed faculty development content, structure, metrics of success including facilitators, barriers, and sustainability to create a framework and inform hospital medicine leadership and faculty development initiatives. We completed a systematic search of peer-reviewed literature and searched Ovid MEDLINE ALL (1946 to June 17, 2021) and Embase (via Elsevier, 1947 to June 17, 2021). Twenty-two studies were included in the final review, with wide heterogeneity in program design, program description, outcomes, and study design. Program design included a combination of didactics, workshops, and community or networking events; half of the studies included mentorship or coaching for faculty. Thirteen studies included program description and institutional experience without reported outcomes while eight studies included quantitative analysis and mixed methods results. Barriers to program success included limited time and support for faculty attendance, conflicting clinical commitments, and lack of mentor availability. Facilitators included allotted funding and time for faculty participation, formal mentoring and coaching opportunities, and a structured curriculum with focused skill development supporting faculty priorities. We identified heterogeneous historical studies addressing faculty development across highly variable program design, intervention, faculty targeted, and outcomes assessed. Common themes emerged, including the need for program structure and support, aligning areas of skill development with faculty values, and longitudinal mentoring/coaching. Programs require dedicated program leadership, support for faculty time and participation, curricula focused on skills development, and mentoring and sponsorship.

Assessing Variants of Uncertain Significance Implicated in Hearing Loss Using a Comprehensive Deafness Proteome.

Hearing loss is the leading sensory deficit, affecting ~ 5% of the population. It exhibits remarkable heterogeneity across 223 genes with 6,328 pathogenic missense variants, making deafness-specific expertise a prerequisite for ascribing phenotypic consequences to genetic variants. Deafness-implicated variants are curated in the Deafness Variation Database (DVD) after classification by a genetic hearing loss expert panel and thorough informatics pipeline. However, seventy percent of the 128,167 missense variants in the DVD are "variants of uncertain significance" (VUS) due to insufficient evidence for classification. Here, we use the deep learning protein prediction algorithm, AlphaFold2, to curate structures for all DVD genes. We refine these structures with global optimization and the AMOEBA force field and use DDGun3D to predict folding free energy differences (∆∆G Fold ) for all DVD missense variants. We find that 5,772 VUSs have a large, destabilizing ∆∆G Fold that is consistent with pathogenic variants. When also filtered for CADD scores (> 25.7), we determine 3,456 VUSs are likely pathogenic at a probability of 99.0%. These VUSs affect 119 patients (~ 3% of cases) sequenced by the OtoSCOPE targeted panel. Approximately half of these patients previously received an inconclusive report, and reclassification of these VUSs as pathogenic provides a new genetic diagnosis for six patients.

Time outweighs the effect of host developmental stage on microbial community composition.

Thousands of microbial taxa in the soil form symbioses with host plants, and due to their contribution to plant performance, these microbes are often considered an extension of the host genome. Given microbial effects on host performance, it is important to understand factors that govern microbial community assembly. Host developmental stage could affect rhizosphere microbial diversity while, alternatively, microbial assemblages could change simply as a consequence of time and the opportunity for microbial succession. Previous studies suggest that rhizosphere microbial assemblages shift across plant developmental stages, but time since germination is confounded with developmental stage. We asked how elapsed time and potential microbial succession relative to host development affected microbial diversity in the rhizosphere using monogenic flowering-time mutants of Arabidopsis thaliana. Under our experimental design, different developmental stages were present among host genotypes after the same amount of time following germination, e.g. at 76 days following germination some host genotypes were flowering while others were fruiting or senescing. We found that elapsed time was a strong predictor of microbial diversity whereas there were few differences among developmental stages. Our results support the idea that time and, likely, microbial succession more strongly affect microbial community assembly than host developmental stage.

Supplementing pregnant Merino ewes with caffeine to improve neonatal lamb thermoregulation and viability.

Percentages of lamb mortalities prior to weaning are a significant and persistent problem for the Australian sheep industry. Maternal caffeine supplementation reduced stillbirths and improved viability in piglets; however, the efficacy of caffeine in enhancing viability and lamb survival is equivocal. The aim of this study was to determine the optimal concentration and duration of maternal caffeine supplementation to improve lamb viability; time to stand and suck with consumption of colostrum occurring, as well as survival to weaning. Multiparous Merino ewes were supplemented with either 0 (CTL), 10 (C10) or 20 mg/kg (C20) body weight (BW) caffeine in feed after day 120 of gestation (dG), or 20 mg/kg BW (LC20) caffeine from dG 142 until parturition. Ewes were housed indoors in individual lambing pens from dG 130 to 72 -h post-partum (pp). Values for pp ewe and lamb variables were analysed using a generalised linear mixed model in IBM SPSS version 25. While ewes within the CTL, C10 and LC20 groups consumed more caffeine compared to C20 ewes (P =  0.001), lambs of C20 ewes had greater rectal temperatures at 20 -h pp (P =  0.021), greater 4 -h serum IgG concentrations (P =  0.041), a longer latency to first sucking bout (P =  0.030), and a greater number of sucking attempts (P =  0.044) compared to lambs from CTL, C10 and LC20 ewes. These results indicate that caffeine supplementation during late-gestation stimulates neonatal lambs as a result of increased sucking (4 -h serum IgG) and increased temperatures within the first 24 -h.

Comparative performances of nomograms and conditional survival after resection of adrenocortical cancer.

BACKGROUND: Adrenocortical carcinomas (ACCs) carry a poor prognosis. This study assessed the comparative performance of existing nomograms in estimating the likelihood of survival, along with the value of conditional survival estimation for patients who had already survived for a given length of time after surgery. METHODS: This was an observational study based on a prospectively developed departmental database that recorded details of patients operated for ACC in a UK tertiary referral centre. RESULTS: Of 74 patients with ACC managed between 2001 and 2020, data were analysed for 62 patients (32 women and 30 men, mean(s.d.) age 51(17) years) who had primary surgical treatment in this unit. Laparoscopic (9) or open adrenalectomies (53) were performed alone or in association with a multivisceral resection (27). Most of the tumours were left-sided (40) and 18 were cortisol-secreting.Overall median survival was 33 months, with 1-, 3- and 5-year survival rates of 79, 49, and 41 per cent respectively. Age over 55 years, higher European Network for Study of Adrenal Tumours stage, and cortisol secretion were associated with poorer survival in univariable analyses. Four published nomograms suggested widely variable outcomes that did not correlate with observed overall survival at 1, 3 or 5 years after operation. The 3-year conditional survival at 2 years (probability of surviving to postoperative year 5) was 65 per cent, compared with a 5-year actuarial survival rate of 41 per cent calculated from the time of surgery. CONCLUSION: Survival of patients with ACC correlates with clinical parameters but not with published nomograms. Conditional survival might provide a more accurate estimate of survival for patients who have already survived for a certain amount of time after resection.

Patients triaged to neoadjuvant chemotherapy have higher rates of sarcopenia: An opportunity for prehabilitation.

OBJECTIVE: To compare baseline body composition measures (BCM), including sarcopenia, between patients with advanced epithelial ovarian cancer (EOC) undergoing primary cytoreductive surgery (PCS) versus neoadjuvant chemotherapy/interval cytoreductive surgery (NACT/ICS) and evaluate changes in BCM pre-NACT versus pre-ICS. METHODS: Patients with stage IIIC/IV EOC who underwent PCS or NACT with curative intent between 1/1/2012 and 7/31/2016 were included. Computed tomography scans were evaluated via a semi-automated program to determine BCM. Measures evaluated include skeletal muscle area (SMA), skeletal muscle density (SMD), skeletal muscle index (SMI), and skeletal muscle gauge (SMG). Sarcopenia was defined as SMI <39.0 cm2/m2. RESULTS: The study included 200 PCS patients and 85 NACT/ICS patients, of which 76 had both pre-NACT and pre-ICS scans. NACT patients were significantly more likely to be sarcopenic compared to PCS patients (40.0% vs 27.5%, p = 0.04). Mean SMA (107.3 vs 113.4 cm2, p = 0.004) and mean SMG (1344.6 vs. 1456.9 (cm2 x HU)/m2, p = 0.06) were lower in NACT patients. Among NACT/ICS patients, mean SMI significantly decreased -1.4 cm2/m2 (p = 0.005) at the time of surgery, resulting in a non-statistically significant increase in the percentage of sarcopenic patients from baseline (40.8% vs. 50.0%, p = 0.09). CONCLUSIONS: Sarcopenia is more common in patients with advanced EOC undergoing NACT compared to PCS when using an evidence-based triage system for triage decisions. Body composition changes significantly over the course of NACT. Sarcopenia may be an indicator of debility and another factor for consideration in treatment planning. Further research into body composition's effects on prognosis and altering sarcopenia is necessary.

Zanubrutinib: a new BTK inhibitor for treatment of relapsed/refractory mantle cell lymphoma.

Mantle cell lymphoma (MCL) has historically been an aggressive disease with poor long-term survival. In the last decade, Bruton tyrosine kinase (BTK) inhibition has emerged as a new treatment strategy for MCL, especially in the relapsed/refractory (r/r) setting. Zanubrutinib, a second-generation BTK inhibitor, was approved by the U.S. Food and Drug Administration (FDA) in late 2019 for r/r MCL on the basis of combined overall response rate of 84% in a total of 118 patients from two multicenter clinical trials, BGB-3111-AU-003 and BGB-3111-206. Duration of response was 14-18 months. Although 57% of patients developed grade 3 and 4 adverse side effects including anemia, pneumonia and neutropenia, only 8% discontinued treatment suggesting zanubrutinib monotherapy was fairly well tolerated. As compared to first-generation ibrutinib, zanubrutinib has higher BTK selectivity which may result in fewer off-target effects and improved potential for combination with other targeted therapies. In addition to a confirmatory phase III trial, there are multiple ongoing studies evaluating zanubrutinib as part of two- and three-drug regimens in MCL and other B-cell malignancies. These current results and areas of further interest indicate an exciting future for zanubrutinib in the treatment of MCL.

A comparative analysis of genetic hearing loss phenotypes in European/American and Japanese populations.

We present detailed comparative analyses to assess population-level differences in patterns of genetic deafness between European/American and Japanese cohorts with non-syndromic hearing loss. One thousand eighty-three audiometric test results (921 European/American and 162 Japanese) from members of 168 families (48 European/American and 120 Japanese) with non-syndromic hearing loss secondary to pathogenic variants in one of three genes (KCNQ4, TECTA, WFS1) were studied. Audioprofile characteristics, specific mutation types, and protein domains were considered in the comparative analyses. Our findings support differences in audioprofiles driven by both mutation type (non-truncating vs. truncating) and ethnic background. The former finding confirms data that ascribe a phenotypic consequence to different mutation types in KCNQ4; the latter finding suggests that there are ethnic-specific effects (genetic and/or environmental) that impact gene-specific audioprofiles for TECTA and WFS1. Identifying the drivers of ethnic differences will refine our understanding of phenotype-genotype relationships and the biology of hearing and deafness.

Neoadjuvant radiotherapy in rectal cancer - less is more?

AIM: There is significant international variation in the use of neoadjuvant radiation prior to total mesorectal excision. The MERCURY group advocate selective neoadjuvant chemoradiotherapy (CRT). We have performed a retrospective, single-centre study of patients treated with CRT, where only the circumferential resection margin is threatened, with the aim of identifying whether a more selective approach to CRT provides acceptable local relapse rates (LRRs). METHOD: All consecutive patients who underwent radical surgery for rectal adenocarcinoma over a 5-year period (2007-2012) in the Oxford University Trust were considered. Electronic hospital systems were reviewed to obtain patient and tumour demographics, treatment and follow-up information. All patients were classified into risk categories according to National Institute for Health and Care Excellence guidance. Data were analysed using Microsoft Excel and R. RESULTS: Two hundred and seventy-two patients were identified: 123, 89 and 60 in the high-, intermediate- and low-risk categories, respectively. Seventy-nine per cent of those in the high-risk group, 6% in the intermediate and 5% in the low-risk group underwent CRT. The overall 5-year LRR and distant recurrence rate (DRR) were 5.2% and 17.8%, respectively. The 5-year LRR for those who went straight to surgery was 2.0% and for those who had neoadjuvant CRT it was 7.4%. The DRR for these two groups was 8.5% and 18.9%, respectively. CONCLUSION: Our series demonstrates that the use of CRT only in margin-threatening tumours, results in an exceptionally low LRR for those without margin-threatening disease. In routine clinical care, this strategy can minimize the significant morbidity of multimodal treatment and allow earlier introduction of systemic therapy to minimize distant recurrence.

Intensity-Modulated Radiotherapy With a Simultaneous Integrated Boost in Rectal Cancer.

AIMS: Dose-response curves suggest that higher doses of radiotherapy improve the complete response rate in rectal cancer. The UK adopted the EXPERT trial dose and fractionation, 45 Gy in 25 fractions to the pelvis with a sequential 9 Gy in five fractions to the gross tumour, in patients where the aim was to maximise the complete response. In the Oxford University Hospital NHS Foundation Trust (Oxford, UK) we deliver a biological equivalent dose (BED5) in selected patients using intensity-modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) in 25 fractions. We carried out a retrospective analysis of our series to: (i) document the toxicity of this protocol; (ii) ascertain whether dose constraints from RTOG 0822 were appropriate; (iii) assess the response. MATERIALS AND METHODS: The demographics and treatment details for all consecutive patients treated with this protocol were collected using electronic systems. Patients received 45 Gy to the elective nodes and 52 Gy using a SIB to the gross tumour with capecitabine chemotherapy using IMRT or RapidArc plans. Acute toxicity was collected prospectively during weekly reviews. For the purpose of this study, a dedicated gastrointestinal radiologist reviewed all baseline and post-treatment magnetic resonance images and assigned a magnetic resonance tumour regression grade (mrTRG). RESULTS: Seventy-one patients were identified. Seventy completed radiotherapy with a median overall treatment time of 34 days (range 32-36 days); 67.6% received full-dose chemotherapy, with 21.2% receiving a reduced dose. There was a 4.2% incidence of grade 3+ non-haematological toxicity and 1.5% grade 3 + haematological toxicity. 4.2% were admitted during their radiotherapy, with one death due to a pelvic abscess. The RTOG 0822 constraints were achieved in ≥75% of cases, other than the high-dose bladder constraint. mrTRG 1-2 was seen in 47.8%, with mrTRG 1 seen in 23.9%. CONCLUSIONS: We suggest that our protocol shows acceptable acute toxicity, with promising mrTRG results, and could be adopted by centres as an IMRT equivalent dose for EXPERT dose and fractionation.

Prediction of short-term surgical complications in women undergoing pelvic exenteration for gynecological malignancies.

OBJECTIVE: Pelvic exenteration (PE) is an extensive surgery associated with high rates of postoperative morbidity and mortality. The absence of well-defined preoperative selection criteria to identify patients eligible for PE prompted the assessment of pre-operative predictors of 30-day major surgical complications. METHODS: Demographics and surgical characteristics of patients undergoing PE for gynecologic cancer in a single institution between 01/2004-12/2016 were reviewed. Postoperative complications within 30 days following surgery were graded using the Accordion grading system. Logistic regression was used to analyze potential risk factors for severe postoperative complications. RESULTS: A total of 138 patients were included in the cohort. Forty-five patients underwent total PE, 52 anterior PE, and 41 posterior PE. Among the 137 patients with follow-up, a severe postoperative complication was experienced by 37 patients (27.0%) and 3 patients (2.2%) experienced death within 90 days. The most frequent grade 3 complications were complications of urinary reconstruction (n = 15), wound dehiscence (n = 9), and abdominal abscess requiring intervention with drain or return to the operating room (n = 6). On multivariable analysis, independent predictors of severe postoperative complications were anterior or total PE (adjusted odds ratio (aOR): 11.66, 95% CI 2.56-53.18), pre-operative hemoglobin ≤10 mg/dl (aOR 2.70, 95% CI 1.02-7.14) and presence of 3+ comorbidities (aOR: 2.76, 95% CI 1.07-7.10). CONCLUSIONS: Major complications after exenteration are common. Surgical complexity and patient selection play a considerable role in predicting complications. These data can be used to better risk stratify patients undergoing PE.

Mortality of civilian patients with suspected traumatic haemorrhage receiving pre-hospital transfusion of packed red blood cells compared to pre-hospital crystalloid.

BACKGROUND: Major haemorrhage is a leading cause of mortality following major trauma. Increasingly, Helicopter Emergency Medical Services (HEMS) in the United Kingdom provide pre-hospital transfusion with blood products, although the evidence to support this is equivocal. This study compares mortality for patients with suspected traumatic haemorrhage transfused with pre-hospital packed red blood cells (PRBC) compared to crystalloid. METHODS: A single centre retrospective observational cohort study between 1 January 2010 and 1 February 2015. Patients triggering a pre-hospital Code Red activation were eligible. The primary outcome measure was all-cause mortality at 6 hours (h) and 28 days (d), including a sub-analysis of patients receiving a major and massive transfusion. Multivariable regression models predicted mortality. Multiple Imputation was employed, and logistic regression models were constructed for all imputed datasets. RESULTS: The crystalloid (n = 103) and PRBC (n = 92) group were comparable for demographics, Injury Severity Score (p = 0.67) and mechanism of injury (p = 0.73). Observed 6 h mortality was smaller in the PRBC group (n = 10, 10%) compared to crystalloid group (n = 19, 18%). Adjusted OR was not statistically significant (OR 0.48, CI 0.19-1.19, p = 0.11). Observed mortality at 28 days was smaller in the PRBC group (n = 21, 26%) compared to crystalloid group (n = 31, 40%), p = 0.09. Adjusted OR was not statistically significant (OR 0.66, CI 0.32-1.35, p = 0.26). A statistically significant greater proportion of the crystalloid group required a major transfusion (n = 62, 60%) compared to the PRBC group (n = 41, 40%), p = 0.02. For patients requiring a massive transfusion observed mortality was smaller in the PRBC group at 28 days (p = 0.07). CONCLUSION: In a single centre UK HEMS study, in patients with suspected traumatic haemorrhage who received a PRBC transfusion there was an observed, but non-significant, reduction in mortality at 6 h and 28 days, also reflected in a massive transfusion subgroup. Patients receiving pre-hospital PRBC were significantly less likely to require an in-hospital major transfusion. Further adequately powered multi-centre prospective research is required to establish the optimum strategy for pre-hospital volume replacement in patients with traumatic haemorrhage.

Clustering and variable selection in the presence of mixed variable types and missing data.

We consider the problem of model-based clustering in the presence of many correlated, mixed continuous, and discrete variables, some of which may have missing values. Discrete variables are treated with a latent continuous variable approach, and the Dirichlet process is used to construct a mixture model with an unknown number of components. Variable selection is also performed to identify the variables that are most influential for determining cluster membership. The work is motivated by the need to cluster patients thought to potentially have autism spectrum disorder on the basis of many cognitive and/or behavioral test scores. There are a modest number of patients (486) in the data set along with many (55) test score variables (many of which are discrete valued and/or missing). The goal of the work is to (1) cluster these patients into similar groups to help identify those with similar clinical presentation and (2) identify a sparse subset of tests that inform the clusters in order to eliminate unnecessary testing. The proposed approach compares very favorably with other methods via simulation of problems of this type. The results of the autism spectrum disorder analysis suggested 3 clusters to be most likely, while only 4 test scores had high (>0.5) posterior probability of being informative. This will result in much more efficient and informative testing. The need to cluster observations on the basis of many correlated, continuous/discrete variables with missing values is a common problem in the health sciences as well as in many other disciplines.

The Effectiveness of a Family-Centered Childhood Obesity Intervention at the YMCA: A Pilot Study.

OBJECTIVE: Community-based, family-centered obesity prevention/treatment initiatives have been shown to be effective in reducing body mass index (BMI) and improving healthy habits in children if implemented with high intensity and sufficient duration. Let's Go! 5-2-1-0 Program (5-2-1-0) was incorporated into family-centered, monthly physical activity classes and cooking classes over six months delivered by Young Men's Christian Association (YMCA) staff. We hypothesized that implementation of this intervention would improve 5-2-1-0 knowledge attainment, increase healthy behavior (based on 5- 2-1-0 curriculum), and improve BMI and waist circumference measurements in children. METHODS: Children attending YMCA summer camps in Rochester, MN, during 2016 were recruited via study packets mailed to their families. Height, weight, and waist circumference measurements as well as the results of the Modified Healthy Habits Survey and the 5-2-1-0 Knowledge Acquisition Survey were recorded for each participating child at baseline and 6-month follow-up. The intervention group received monthly healthy habit reminder emails, and was invited to monthly evening cooking and physical activity classes for 7 sessions over a 6-month period. RESULTS: Fifteen families in the intervention group attended classes. Of those, 13 families regularly participated in (attended at least 5 out of 7) both the monthly physical activity and cooking classes. The children in the intervention group had a significant improvement in the number of Knowledge Acquisition Survey questions answered correctly (p<0.001), while there was no improvement in the control group. As compared to children in the control group, there was no significant change in BMI or waist circumference or healthy habits in the intervention group. CONCLUSION: Our study findings indicate that our intervention resulted in improved knowledge about healthy habits, but did not significantly impact healthy habits or BMI. Potential reasons for this were the small sample size and the attenuated length and/or intensity of the intervention.

Development of Subject-Specific Proximal Femur Finite Element Models Of Older Adults with Obesity to Evaluate the Effects of Weight Loss on Bone Strength.

STUDY BACKGROUND: Recommendation of intentional weight loss in older adults remains controversial, due in part to the loss of bone mineral density (BMD) known to accompany weight loss. While finite element (FE) models have been used to assess bone strength, these methods have not been used to study the effects of weight loss. The purpose of this study is to develop subject-specific FE models of the proximal femur and study the effect of intentional weight loss on bone strength. METHODS: Computed tomography (CT) scans of the proximal femur of 25 overweight and obese (mean BMI=29.7 ± 4.0 kg/m2), older adults (mean age=65.6 ± 4.1 years) undergoing an 18-month intentional weight loss intervention were obtained at baseline and post-intervention. Measures of volumetric BMD (vBMD) and variable cortical thickness were derived from each subject CT scan and directly mapped to baseline and post-intervention models. Subject-specific FE models were developed using morphing techniques. Bone strength was estimated through simulation of a single-limb stance and sideways fall configuration. RESULTS: After weight loss intervention, there were significant decreases from baseline to 18 months in vBMD (total hip: -0.024 ± 0.013 g/cm3; femoral neck: -0.012 ± 0.014 g/cm3), cortical thickness (total hip: -0.044 ± 0.032 mm; femoral neck: -0.026 ± 0.039 mm), and estimated strength (stance: -0.15 ± 0.12 kN; fall: -0.04 ± 0.06 kN). Adjusting for baseline bone measures, body mass, and gender, correlations were found between weight change and change in total hip and femoral neck cortical thickness (all p<0.05). For every 1 kilogram of body mass lost cortical thickness in the total hip and femoral neck decreased by 0.003 mm and 0.004 mm, respectively. No significant correlations were present for the vBMD or strength data. CONCLUSION: The developed subject-specific FE models could be used to better understand the effects of intentional weight loss on bone health.