Latarjet procedure restores range of motion at six months postoperatively: a prospective cohort study utilizing motion capture analysis.

BACKGROUND: There is a common concern that range of motion (ROM) is negatively affected by the Latarjet procedure. We hypothesize that the Latarjet procedure results in full recuperation of ROM postoperatively and significantly improved patient reported outcome measures. METHODS: Patient data were prospectively collected from a randomized controlled trial to analyze outcomes after open Latarjet procedure. Inclusion criteria involved a minimum follow-up of six months and unilateral shoulder instability. Study outcome was assessed by postoperative ROM at six months postoperatively and compared to the preoperative ROM of the ipsilateral shoulder as well as the ROM of the unaffected contralateral shoulder. All ROM measurements were performed utilizing a motion capture system to ensure consistent and reliable measurements. RESULTS: The study included a total of 84 patients. ROM was measured in external rotation with the shoulder adducted (ER1), external rotation with the shoulder abducted 90 degrees (ER2), internal rotation with the arm abducted 90 degrees (IR2), and active forward elevation (AE). The average difference in ROM between the operated arm vs. the contralateral healthy arm at six months postoperatively was 3.4 degrees in ER1 (p=0.19), 4.2 degrees in ER2 (p=0.086), 2.2 degrees in IR2 (p=0.36), and 2.4 degrees in AE (p=0.045). Sub-analysis of patients with and without sling use revealed no significant difference in ROM between the operated shoulder and contralateral shoulder at six months in either group, with the exception of ER2 in the sling group. In this latter group, ROM was 71 degrees in the operated arm and 79 degrees in the contralateral arm (p=0.0094). Average preoperative pain score was 25.7 (21.4-30.1, 95%CI) vs. 13.0 postoperatively at six months (9.50-16.5, 95%CI) (p <0.00001). Average preoperative SANE instability was 42.9 (38.4-47.3, 95%CI) vs. 86.2 postoperatively at six months (83.6-88.7, 95%CI) (p <0.00001). Average preoperative Rowe score was 38.5 (34.3-42.7, 95%CI) vs. 84.3 at six postoperative months (81.1-87.4, 95%CI) (p<0.00001). CONCLUSIONS: Latarjet procedure performed for anterior instability utilizing a capsular repair result in complete ROM recovery in ER1, ER2, and IR2 at six months postoperatively, with only a slight discrepancy in active elevation. Sling use after the Latarjet procedure results in no benefit over postoperative recovery without the use of a sling. Sling use negatively affects the ROM in ER2, taking as reference the contralateral arm of the same patient, when compared to patients that did not use a sling postoperatively.

Evaluation of Transmission Near the Christiansen Wavelength for Dynamic Sand Samples.

Many optical applications, including free-space optical communications, lidar, and astronomical measurements, are impacted by the presence of light-scattering particles also known as obscurants. Scattering from particles consisting of sand, dust, dirt, and other substances can significantly degrade optical signals. For many obscurants, the index of refraction is dependent on the wavelength of light, and there exists a Christiansen wavelength (λc) at which scattering is at a minimum. At λc the index of refraction of the scattering particles (ns) matches that of the surrounding medium, in this case air (with refractive index na). This condition makes the scattering particulates almost invisible to the propagating light, minimizing scattering and increasing transmission at λc. Previously, the authors showed a technique for measuring the index of refraction n(λ) and the extinction coefficient k(λ) using spectroscopic ellipsometry for various sand samples. Spectroscopic measurements on static sand samples demonstrated good agreement with the predicted spectral properties and highlighted the presence of a Christiansen feature near 8 µm. However, in outdoor environments, the scattering particles are never stationary but in a constant state of motion. In this work, spectroscopic measurements on dynamic sand samples (sand that is falling through the optical beam path) show two Christiansen features seen previously in predicted and observed static sand measurements. Additionally, we characterize, for the first time, transmission around a Christiansen feature using a tunable laser and show results consistent with other spectroscopic measurements.

Biocomposite thermoplastic polyurethanes containing evolved bacterial spores as living fillers to facilitate polymer disintegration.

The field of hybrid engineered living materials seeks to pair living organisms with synthetic materials to generate biocomposite materials with augmented function since living systems can provide highly-programmable and complex behavior. Engineered living materials have typically been fabricated using techniques in benign aqueous environments, limiting their application. In this work, biocomposite fabrication is demonstrated in which spores from polymer-degrading bacteria are incorporated into a thermoplastic polyurethane using high-temperature melt extrusion. Bacteria are engineered using adaptive laboratory evolution to improve their heat tolerance to ensure nearly complete cell survivability during manufacturing at 135 °C. Furthermore, the overall tensile properties of spore-filled thermoplastic polyurethanes are substantially improved, resulting in a significant improvement in toughness. The biocomposites facilitate disintegration in compost in the absence of a microbe-rich environment. Finally, embedded spores demonstrate a rationally programmed function, expressing green fluorescent protein. This research provides a scalable method to fabricate advanced biocomposite materials in industrially-compatible processes.

Effect of Ergocalciferol on ß-Cell Function in New-Onset Type 1 Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial evaluates the effectiveness of ergocalciferol vs placebo in youths with newly diagnosed type 1 diabetes.

A feasibility cadaver study for placing screws in various pelvic osseous fracture pathways using a robotic arm.

INTRODUCTION: The use of a robotic system for the placement of pedicle screws in spine surgeries is well documented in the literature. However, there is only a single report in the United States describing the use of a robotic system to place two screws in osseous fixation pathways (OFPs) commonly used in the treatment of pelvic and acetabular fractures in a simulated bone model. The purpose of this study was to demonstrate the use of a robotic system to place screws in multiple, clinically relevant OFPs in a cadaveric model and to quantitatively measure accuracy of screw placement relative to the preoperative plan. METHODS: A single cadaveric specimen was obtained for the purpose of this study. All surrounding soft tissues were left intact. Screws were placed in OFPs, namely iliosacral (IS), trans-sacral (TS), Lateral Compression-II (LC-II), antegrade anterior column (AC) and antegrade posterior column (PC) of the right hemipelvis using standard, fluoroscopically assisted percutaneous or mini-open technique. Following the placement of screws into the right hemipelvis using standard techniques, screws were planned and placed in the same OFPs of the contralateral hemipelvis using the commercially available ExcelsiusGPS® robotic system (Globus Medical Inc., Audubon, PA). After robotic-assisted screw placement, a post-procedure CT scan was obtained to evaluate actual screw placement against the pre-procedure plan. A custom-made image analysis program was devised to measure screw tip/tail offset and angular offset on axial and sagittal planes. RESULTS: For different OFPs, the mean tip offset, tail offset and angular offsets were 1.6 ± 0.9 mm (Range 0.0-3.6 mm), 1.4 ± 0.4 mm (Range 0.3-2.5 mm) and 1.1 ± 0.4° (Range 0.5-2.1), respectively. CONCLUSION: In this feasibility study, surgeons were able to place screws into the clinically relevant fracture pathways of the pelvis using ExcelsiusGPS® for robotic-assisted surgery. The measured accuracy was encouraging; however, further investigation is needed to demonstrate that robotic-assisted surgery can be used to successfully place the screws in the bony corridors of the pelvis to treat traumatic pelvic injuries.

Reducing Hemoglobin A1C Levels in Type II Diabetes: A Retrospective Analysis of the Renew Procedure.

INTRODUCTION: Periodontal disease and type 2 diabetes are interrelated, with inflammation playing a significant role in the progression of both conditions. Previous research has demonstrated the potential of various treatments, such as diet, exercise, and periodontal therapies, to improve glycemic control in diabetic patients. METHOD: This study proposed a novel surgical approach, the Renew Procedure, as a potential solution to enhance glycemic control in type 2 diabetic patients with periodontal issues. The procedure involves the removal of all teeth, the elimination of oral and maxillofacial infections, the placement of dental implants, and the provision of implant-supported and implant-retained removable dentures. RESULTS: Preliminary findings indicated a significant reduction in HbA1c levels post-surgery, suggesting that this approach may improve overall oral health, reduce inflammation, and consequently lower HbA1c levels. CONCLUSION: Further research is necessary to confirm the efficacy of the proposed solution, but these initial results highlight the importance of addressing oral health through comprehensive strategies for diabetic and periodontitis patients.

A Stepwise Approach to Analyzing Musculoskeletal Imaging Data With Artificial Intelligence.

The digitization of medical records and expanding electronic health records has created an era of "Big Data" with an abundance of available information ranging from clinical notes to imaging studies. In the field of rheumatology, medical imaging is used to guide both diagnosis and treatment of a wide variety of rheumatic conditions. Although there is an abundance of data to analyze, traditional methods of image analysis are human resource intensive. Fortunately, the growth of artificial intelligence (AI) may be a solution to handle large datasets. In particular, computer vision is a field within AI that analyzes images and extracts information. Computer vision has impressive capabilities and can be applied to rheumatologic conditions, necessitating a need to understand how computer vision works. In this article, we provide an overview of AI in rheumatology and conclude with a five step process to plan and conduct research in the field of computer vision. The five steps include (1) project definition, (2) data handling, (3) model development, (4) performance evaluation, and (5) deployment into clinical care.

Glenoid-based reference system to differentiate shoulder pathologies on plain radiographs.

BACKGROUND: Shoulder radiographs are used for evaluation and the planning of treatment of various pathologies. Making a diagnosis of these pathologies on plain radiographs occurs by recognizing the relationship of the humeral head on the registry of the glenoid. Quantification of these changes in registry does not currently exist. We hypothesize that a geometric relationship of the humeral head and the glenoid exists that is defined on an anteroposterior Grashey view radiograph by the relationship of the best-fit circle of the humeral head relative to the best-fit circle of the glenoid such that relative measurements will define the normal shoulder and the pathologic shoulder. METHODS: One hundred fifty-six shoulders were included: 53 normal shoulders, 51 with primary glenohumeral osteoarthritis (GHOA), and 52 with cuff tear arthropathy (CTA). Humeral head best-fit circle was used to define the circle of the humeral head (cHH). A glenoid best-fit circle (cG) was defined by the following rules: (1) best fit of the glenoid articular surface and (2) was limited by the acromion such that either (a) it reaches maximal interaction with the inferior surface of the acromion or (b) the perimeter of the circle is at the lateralmost point of the acromion. The relationship between cHH and cG is defined by measurement of cHH in horizontal and vertical planes relative to the glenoid circle reference. The horizontal displacement angle (HDA) measures the horizontal position of cHH relative to cG, representing the degree of medialization toward the glenoid. The vertical displacement angle (VDA) measures the vertical position of cHH relative to cG, representing the degree of superiorization toward the acromion. Angles were compared by diagnosis and sex. RESULTS: The mean HDA was 61.0° (95% confidence interval [CI] 60.3°-61.7°) in normal shoulders, 79.9° (95% CI 76.9°-82.9°) in GHOA, and 63.4° (95% CI 61.7°-65.1°) in CTA (P < .001). The mean VDA was 43.1° (95% CI 42.2°-44.0°) in normal shoulders, 40.9° (95% CI 39.9°-42.0°) in GHOA, and 59.7° (95% CI 57.6°-61.7°) in CTA (P < .001). Interobserver reliability was 0.991 (95% CI 0.94-1.0) and intraobserver reliability was 0.998 (95% CI 0.99-1.0). The geometric relationship of cHH to the glenoid circle reference was plotted for each group. CONCLUSION: A geometric relationship exists of the humeral head in reference to the glenoid circle. Together, the HDA and the VDA distinguish between a normal shoulder and those with GHOA or CTA. This suggests that this novel methodology may provide a preoperative planning tool that is easily accessible.

Robotic-assisted percutaneous pelvis fixation: A case report.

Key Clinical Message: It may be possible to extend the use of the robotic arm to pelvic and acetabular surgery leading to safe, repeatable screw placement, and less radiation exposure for patients, surgeons and OR staff. Abstract: In this case, a novel, robotic-assisted technique was used to place a sacroiliac screw in a patient with unstable injuries of the pelvic ring. Intraoperative and postoperative fluoroscopic, radiographic, and CT imaging demonstrated a safely positioned 6.5 mm cannulated screw without unplanned cortical violation or impingement on neurovascular structures. To our knowledge, this is the first such reported case using a robot widely available in the Americas or Europe.

Feasibility and acceptability of an mHealth, home-based exercise intervention in colorectal cancer survivors: A pilot randomized controlled trial.

OBJECTIVE: To determine the feasibility and acceptability of an mHealth, home-based exercise intervention among stage II-III colorectal cancer (CRC) survivors within 5-years post-resection and adjuvant therapy. METHODS: This pilot randomized controlled trial of a 12-week mHealth, home-based exercise intervention, randomly assigned CRC survivors to a high-intensity interval training (HIIT) or moderate-intensity continuous exercise (MICE) prescription. The following assessments were carried out at baseline and end-of-study (EOS): handgrip strength, short physical performance battery (SPPB), PROMIS physical function, neuropathy total symptom score-6 (NTSS-6), Utah early neuropathy scale (UENS), cardiopulmonary exercise testing, anthropometrics, and body composition via BOD POD, modified Godin leisure-time activity questionnaire. Feasibility, as defined by number of completed prescribed workouts and rate of adherence to individualized heart rate (HR) training zones, was evaluated at EOS. Acceptability was assessed by open-ended surveys at EOS. Descriptive statistics were generated for participant characteristics and assessment data. RESULTS: Seven participants were included in this pilot study (MICE: n = 5, HIIT: n = 2). Median age was 39 years (1st quartile: 36, 3rd quartile: 50). BMI was 27.4 kg/m2 (1st quartile: 24.5, 3rd quartile: 29.7). Most participants had stage III CRC (71%, n = 5). We observed an 88.6% workout completion rate, 100% retention rate, no adverse events, and qualitative data indicating improved quality of life and positive feedback related to ease of use, accountability, motivation, and autonomy. Mean adherence to HR training zones was 95.7% in MICE, and 28.9% for the high-intensity intervals and 51.0% for the active recovery intervals in HIIT; qualitative results revealed that participants wanted to do more/work-out harder. CONCLUSION: An mHealth, home-based delivered exercise intervention, including a HIIT prescription, among stage II-III CRC survivors' post-resection and adjuvant therapy was tolerable and showed trends towards acceptability.

Does Preoperative Opioid Consumption Influence Patient Satisfaction following Total Knee Arthroplasty?

Chronic opioid use prior to total knee arthroplasty (TKA) has been implicated in adverse outcomes. The purpose of this study was to evaluate clinical outcome measures and patient satisfaction in patients with a history of preoperative chronic opioid use undergoing primary TKA. A retrospective cohort study was performed on 296 consecutive patients undergoing primary TKA. Seventy-four (25%) patients were identified with chronic preoperative opioid use (study group; 22 males, 52 females). A 3:1 matched cohort ratio of control versus study group was utilized resulting in a control group consisting of 222 patients (97 males, 125 females) without chronic opioid use prior to surgery. There was no statistically significant difference in age, BMI, or follow-up. Average follow-up was 23.4 months in the control group and 23.6 months in the study group (p = 0.87). Clinical data including patient satisfaction (Likert score), Knee Society (KS) Knee scores, KS Function scores, Forgotten Joint Score (FJS), length of stay (LOS), and complications were evaluated. Patient satisfaction at the most recent visit was 92.8% in the control group versus 83.8% in the chronic opioid group (p = 0.0016). Differences in patient-reported outcomes measures comparing the control and study cohorts included KS Function Score of 83.23 versus 75.31 (p = 0.0034). The FJS of 63.7 versus 58 (p = 0.1883) and the KS Knee Score of 89.5 versus 88.1 (p = 0.4075) were not significant. Postoperative opioid usage for the control versus the study group was 62/222 (27.9%) versus 56/74 (75.7%) at 4 to 8 weeks (p <0.0001), and 4/222 (1.80%) versus 27/74 (36.5%) at 12 months (p <0.0001). Overall complication occurrence was 18.9% in the study group versus 11.3% in the control group (p = 0.11). Patients with history of chronic preoperative opioid use had significantly lower patient satisfaction and KS Function scores and increased postoperative opioid usage at 12 months compared with patients without a history of opioid use prior to TKA.

A Biologically Degradable and BioseniaticTM Feedstock for the High-Quality 3D Printing of Anatomical Models.

A Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) -based filament was evaluated as an alternative feedstock for Fused Deposition Modeling (FDM) of instructional and clinical medical specimens. PHBHHx-based prints of domestic cat vertebrae, skull bone, and an aortic arch cast were found comparable to conventional materials. PHBHHx-based filament and extrudate samples were evaluated for biological degradability, to meet the BioseniaticTM standard, defined by the University of Georgia New Materials Institute. Both samples achieved more than 90% mineralization within 32 days in industrial composting conditions.

Prediabetes: Adherence to Nutrition Visits Decreases HbA1c in Children and Adolescents.

Background: Prediabetes, the precursor of type 2 diabetes (T2D), is on the rise in the US, but the determinants of its progression are poorly characterized in youth. Objective: To determine the impact of nutrition visits, as a surrogate marker of lifestyle modification, on the trajectory of prediabetes over a 4-year period. Hypothesis: Adherence to nutrition visits could reduce BMI and lower HbA1c. Methods: A 4-year retrospective study of 108 youth with prediabetes who were recommended to receive medical nutrition therapy every 3 months following their diagnosis. Subjects were divided into 2 groups: the non-adherent group who had ≤1 nutrition visit/year, and the adherent group with ≥2 nutrition visits/year. Results: There were 46 male subjects, mean age 12.4 ± 3.6y; and 62 female subjects, mean age, 13.3 ± 3.0y, p=0.2. The adherent group (n=44, 41.5%) had higher BMI z-scores, but similar values for HbA1c, metformin use, and racial/ethnic composition compared to the non-adherent group. Overall, 18(17.0%) subjects progressed to T2D in 4y and consisted of 14(22.6%) of the 62 non-adherent subjects and 4(9.1%) of the 44 adherent subjects. The non-adherent subjects progressed to T2D at a mean duration of 25.8 ± 12.6 months while the adherent subjects progressed at a mean duration of 34.9 ± 11.8 months. The hazard ratio of progression from prediabetes to T2D for the non-adherent versus adherent group was 3.88 (95%CI 1.26-11.98, p=0.02). The results remained significant after adjusting for age, sex, race/ethnicity, BMI, and metformin use. Conclusion: Adherence to nutrition visits was associated with a 4-fold reduction in the likelihood to progress from prediabetes to T2D in US youth.

Problematic Behaviors and Predicting Online Risk Behaviors in High School Students.

Adolescent behavior now occurs offline and online. Frequently studied and treated independently, the relationship between offline problem behaviors and online risk taking is not well understood. This study asked whether there are any problematic behaviors predictive of online risk taking by high school students. Using a 2009 dataset of 2,077 high school students grades 9-12, five areas of offline problematic behaviors were examined: Academic problems, anxiety, behavioral wrongdoing, bullying, and social-emotional. Nine binary results were classified as online risk: Sexting, online harassment (perpetrating and experiencing), visiting sex sites, talking about sex, receiving sexual pictures, meeting offline, anything sexual happened, feeling nervous or uncomfortable. Behavioral wrongdoing (fighting, school suspension, trouble with police, theft), emerged as a significant predictor appearing in all nine models, followed by bullying experience (bully or victim) in six models. Identifying common problem behaviors that predict online risk taking are key components in developing strategies to promote adolescent health and well-being.

Primary THA Using Thin Polyethylene Liners and Large Femoral Heads: A Minimum 5-Year Follow-Up.

BACKGROUND: Large femoral head sizes are commonly used in total hip arthroplasty (THA) to minimize the risk of instability. With small acetabular cup-size, large femoral head diameter often results in the use of thin polyethylene liners. The purpose of this study was to evaluate clinical and radiographic results of large femoral heads against thin polyethylene liners with minimum 5-year follow-up. METHODS: This was a retrospective review identifying 58 primary THAs utilizing thin polyethylene inserts from one manufacturer (X3 polyethylene, Stryker, Mahwah, NJ) and large femoral heads (36 mm or greater) with minimum 5-year follow-up. A total of 3 patients were deceased and 11 lost to follow-up, leaving 44 patients for review. All patients were female with mean age 65.7 (range 26-85) and mean body mass index (BMI) 29.9 (range 19.6-45.4). Average length of follow-up was 8.5 years (range 5.1-11.3). Outcome measures included survivorship, complications, PROMs and radiographic analysis. RESULTS: There were four revisions: two aseptic loosening, one prosthetic joint infection, and one recurrent dislocation. Average HOOS-Jr, FJS-12, and patient satisfaction using Likert score was 94.3/100, 92.9/100, and 4.69/5.00, respectively, with 94% of patients reporting being satisfied or very satisfied. Radiographic analysis at average of 8.5 years demonstrated well-fixed implants without evidence of progressive radiolucent lines, osteolysis, or failure of the polyethylene liner. Survivorship using failure of the thin polyethylene liner as the endpoint was 100% at an average of 8.5 years. CONCLUSION: Thin polyethylene liners used with large femoral head sizes in small acetabular cups demonstrated excellent results at average 8.5-year follow-up with no cases of liner fracture or osteolysis.

Impact of a targeted volume-increase nutrition guideline on growth and body mass index in premature infants: A retrospective review.

BACKGROUND: The negative impact of disproportionate growth in premature infants is well documented, but optimal nutrition practices needed to prevent an unhealthy body mass index (BMI) remain unclear. METHODS: An evidence-based, volume-increase guideline that advanced feeding volumes from 150-160 to 170-180 ml/kg/day between the postmenstrual age (PMA) of 31 0/7 and 34 0/7 weeks was implemented in October 2017 for infants born at ≤32 0/7 weeks' gestational age. Data were collected on 262 infants' weight and length at birth and at discharge for 20 months before and 21 months after guideline implementation, and retrospective analysis was conducted to determine disproportionate growth by comparing BMIs (in g/cm2 ) at birth and at discharge. Changes in infants' body habitus were determined through bivariate analysis of weight and length z-scores from the Fenton growth curve. RESULTS: Implementation of a targeted volume nutrition guideline resulted in fewer infants with growth failure, defined as weight <10th percentile (19.5% vs 11.2%; P = .06) at discharge. Infants who received treatment according to the targeted nutrition guideline had a statistically significant reduction in disproportionately low BMI (8.6% vs 2.5%; P = .0380) and an increase in disproportionately high BMIs (4.3% vs 12.3%; P = .025). There was minor change in the percentage of disproportionately large infants who received the guidelines from birth to discharge (11.5% vs 12.3%). CONCLUSIONS: A targeted volume-increase nutrition guideline may prevent growth failure, with some effects on disproportionate growth in preterm infants born at ≤32 0/7 weeks' gestational age.

Ergocalciferol in New-onset Type 1 Diabetes: A Randomized Controlled Trial.

CONTEXT: The effect of the anti-inflammatory and immunomodulatory actions of vitamin D on the duration of partial clinical remission (PR) in youth with type 1 diabetes (T1D) is unclear. OBJECTIVE: This work aimed to determine the effect of adjunctive ergocalciferol on residual ß-cell function (RBCF) and PR in youth with newly diagnosed T1D who were maintained on a standardized insulin treatment protocol. The hypothesis was that ergocalciferol supplementation increases RBCF and prolongs PR. METHODS: A 12-month, randomized, double-blind, placebo-controlled trial was conducted of 50 000 IU of ergocalciferol per week for 2 months, and then once every 2 weeks for 10 months, vs placebo in 36 individuals aged 10 to 21 years, with T1D of less than 3 months and a stimulated C-peptide (SCP) level greater than or equal to 0.2 nmol/L (≥ 0.6 ng/mL). The ergocalciferol group had 18 randomly assigned participants (10 male/8 female), mean age 13.3 ±â€…2.8 years, while the control group had 18 participants (14 male/4 female), aged 14.3 ±â€…2.9 years. RESULTS: The ergocalciferol treatment group had statistically significantly higher serum 25-hydroxyvitamin D at 6 months (P = .01) and 9 months (P = .02) than the placebo group. At 12 months, the ergocalciferol group had a statistically significantly lower serum tumor necrosis factor α (TNF-α) concentration (P = .03). There were no statistically significant differences between the groups at each time point from baseline to 12 months for SCP concentration (P = .08), glycated hemoglobin A1c (HbA1c) (P = .09), insulin dose-adjusted A1c (IDAA1c), or total daily dose of insulin. Temporal trends for rising HbA1c (P = .04) and IDAA1c (P = .02) were statistically significantly blunted in the ergocalciferol group. CONCLUSION: Ergocalciferol statistically significantly reduced serum TNF-α concentration and the rates of increase both in A1c and IDAA1c, suggesting a protection of RBCF and PR in youth with newly diagnosed T1D.

Partial Clinical Remission Reduces Lipid-Based Cardiovascular Risk in Adult Patients With Type 1 Diabetes.

Importance: Risk factors for atherosclerotic cardiovascular disease (ASCVD) are well established in type 2 diabetes (T2D), but not in type 1 diabetes (T1D). The impact of partial clinical remission (PR) on short-term ASCVD risk in T1D is unclear. Aim: To investigate the impact of PR on the earliest ASCVD risk phenotype in adult T1D using factor analysis to compare the lipid phenotypes of T1D, T2D and controls after stratifying the T1D cohort into remitters and non-remitters. Subjects and Methods: A study of 203 adults subjects consisting of 86 T2D subjects, and 77 T1D subjects stratified into remitters (n=49), and non-remitters (n=28). PR was defined as insulin-dose adjusted HbA1c of ≤9, and obesity as a BMI ≥30 kg/m2. Factor analysis was used to stratify the groups by ASCVD risk by factorizing seven lipid parameters (TC, LDL, HDL, non-HDL, TC/HDL, TG, TG/HDL) into 2 orthogonal factors (factor 1: TC*LDL; factor 2: HDL*TG) that explained 90% of the variance in the original seven parameters. Results: The analysis of individual lipid parameters showed that TC/HDL was similar between the controls and remitters (p=NS) but was significantly higher in the non-remitters compared to the remitters (p=0.026). TG/HDL was equally similar between the controls and remitters (p=NS) but was lower in the remitters compared to the non-remitters (p=0.007). TG was significantly lower in the remitters compared to T2D subjects (p<0.0001) but was similar between T2D subjects and non-remitters (p=NS). Non-HDL was significantly lower in the controls versus non-remitters (p=0.0003) but was similar between the controls and remitters (p=NS). Factor analysis showed that the means of factor 1 and factor 2 composite scores for dyslipidemia increased linearly from the controls, remitters, non-remitters to T2D, p value 0.0042 for factor 1, and <0.0001 for factor 2, with remitters having similar lipid phenotype as controls, while non-remitters were similar to T2D. Conclusions: Partial clinical remission of T1D is associated with a favorable early lipid phenotype which could translate to reduced long-term CVD risk in adults.

Differential DNA methylation and transcriptional signatures characterize impairment of muscle stem cells in pediatric human muscle contractures after brain injury.

Limb contractures are a debilitating and progressive consequence of a wide range of upper motor neuron injuries that affect skeletal muscle function. One type of perinatal brain injury causes cerebral palsy (CP), which affects a child's ability to move and is often painful. While several rehabilitation therapies are used to treat contractures, their long-term effectiveness is marginal since such therapies do not change muscle biological properties. Therefore, new therapies based on a biological understanding of contracture development are needed. Here, we show that myoblast progenitors from contractured muscle in children with CP are hyperproliferative. This phenotype is associated with DNA hypermethylation and specific gene expression patterns that favor cell proliferation over quiescence. Treatment of CP myoblasts with 5-azacytidine, a DNA hypomethylating agent, reduced this epigenetic imprint to TD levels, promoting exit from mitosis and molecular mechanisms of cellular quiescence. Together with previous studies demonstrating reduction in myoblast differentiation, this suggests a mechanism of contracture formation that is due to epigenetic modifications that alter the myogenic program of muscle-generating stem cells. We suggest that normalization of DNA methylation levels could rescue myogenesis and promote regulated muscle growth in muscle contracture and thus may represent a new nonsurgical approach to treating this devastating neuromuscular condition.