Gil Weintraub

Energetic consequences of thermal and nonthermal food processing

Processing food extensively by thermal and nonthermal techniques is a unique and universal human practice. Food processing increases palatability and edibility and has been argued to increase energy gain. Although energy gain is a well-known effect from cooking starch-rich foods, the idea that cooking meat increases energy gain has never been tested. Moreover, the relative energetic advantages of cooking and nonthermal processing have not been assessed, whether for meat or starch-rich foods. Here, we describe a system for characterizing the energetic effects of cooking and nonthermal food processing. Using mice as a model, we show that cooking substantially increases the energy gained from meat, leading to elevations in body mass that are not attributable to differences in food intake or activity levels. The positive energetic effects of cooking were found to be superior to the effects of pounding in both meat and starch-rich tubers, a conclusion further supported by food preferences in fasted animals. Our results indicate significant contributions from cooking to both modern and ancestral human energy budgets. They also illuminate a weakness in current food labeling practices, which systematically overestimate the caloric potential of poorly processed foods.

A Novel Osteogenic Oxysterol Compound for Therapeutic Development to Promote Bone Growth: Activation of Hedgehog Signaling and Osteogenesis through Smoothened Binding

Osteogenic factors are often used in orthopedics to promote bone growth, improve fracture healing, and induce spine fusion. Osteogenic oxysterols are naturally occurring molecules that were shown to induce osteogenic differentiation in vitro and promote spine fusion in vivo. The purpose of this study was to identify an osteogenic oxysterol more suitable for clinical development than those previously reported, and evaluate its ability to promote osteogenesis in vitro and spine fusion in rats in vivo. Among more than 100 oxysterol analogues synthesized, Oxy133 induced significant expression of osteogenic markers Runx2, osterix (OSX), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN) in C3H10T1/2 mouse embryonic fibroblasts and in M2‐10B4 mouse marrow stromal cells. Oxy133‐induced activation of an 8X‐Gli luciferase reporter, its direct binding to Smoothened, and the inhibition of Oxy133‐induced osteogenic effects by the Hedgehog (Hh) pathway inhibitor, cyclopamine, demonstrated the role of Hh pathway in mediating osteogenic responses to Oxy133. Oxy133 did not stimulate osteogenesis via BMP or Wnt signaling. Oxy133 induced the expression of OSX, BSP, and OCN, and stimulated robust mineralization in primary human mesenchymal stem cells. In vivo, bilateral spine fusion occurred through endochondral ossification and was observed in animals treated with Oxy133 at the fusion site on X‐ray after 4 weeks and confirmed with manual assessment, micro‐CT (µCT), and histology after 8 weeks, with equal efficiency to recombinant human bone morphogenetic protein‐2 (rhBMP‐2). Unlike rhBMP‐2, Oxy133 did not induce adipogenesis in the fusion mass and resulted in denser bone evidenced by greater bone volume/tissue volume (BV/TV) ratio and smaller trabecular separation. Findings here suggest that Oxy133 has significant potential as an osteogenic molecule with greater ease of synthesis and improved time to fusion compared to previously studied oxysterols. Small molecule osteogenic oxysterols may serve as the next generation of bone anabolic agents for therapeutic development.

Contributions of a specialty clinic for children and adolescents with Down syndrome

We investigated what added value, if any, a Down syndrome specialty clinic brings to the healthcare needs of children and adolescents with Down syndrome. For this quality improvement study, we performed a retrospective chart review of 105 new patients with Down syndrome, ages 3 and older, seen during the inaugural year of our specialty clinic. We asked how many of our patients were already up‐to‐date on the healthcare screenings recommended for people with Down syndrome. We further analyzed what tests we ordered, which referrals we suggested, and, ultimately, what new diagnoses of co‐occurring medical conditions were made. Only 9.8% of our patients were current on all of the recommended Down syndrome healthcare screenings. Parents came to clinic with a variety of concerns, and after laboratory tests, radiologic studies, and subspecialty referrals, we made many new diagnoses of gastrointestinal conditions (e.g., constipation and celiac disease), seasonal allergies, dermatologic conditions (e.g., xerosis), behavioral diagnoses (e.g., autism spectrum disorder and disruptive behavior not otherwise specified), and clarifications of neurologic conditions. A Down syndrome specialty clinic can identify and address many healthcare needs of children and adolescents with Down syndrome beyond that which is provided in primary care settings.

Effect of cervical kyphotic deformity type on the motion characteristics and dynamic spinal cord compression.

Study Design. Retrospective analysis of kinematic magnetic resonance images. Objective. To provide baseline data on the segmental angular and translational motion of the degenerated cervical spine by subtype of kyphotic cervical deformity and to elucidate the relationship between motion and degree of spinal cord compression. Summary of Background Data. Kyphotic deformities of the cervical spine are relatively common and are classified as either global or focal. Nevertheless, the effects of kyphotic subtype on cervical segmental motion and degree of spinal cord compression are unknown. Methods. A total of 1171 symptomatic patients (618 females, 553 males) underwent cervical kinematic magnetic resonance imaging in the neutral, flexion, and extension positions. Cervical spines demonstrating kyphosis were included and classified into 3 groups: (1) “global kyphotic deformity” (C-type) (n = 54); (2) “sigmoid deformity” (S-type) with kyphotic upper and lordotic lower cervical segments (n = 29); and (3) “reverse sigmoid deformity” (R-type) with lordotic upper and kyphotic lower cervical segments (n = 39). Translational motion, angular motion, and degree of spinal cord compression were evaluated for each cervical level along with the changes associated with flexion and extension. Results. In the C- and R-types, angular motion with extension was increased in the upper cervical spine, where there was kyphosis; when compared with the S-type, in which there was lordosis in the upper segments. The results were opposite for flexion angular motion. R-type displayed more translational motion at C3–C4 and C5–C6. Degree of static spinal cord compression of R-type was higher than the others at C3–C4. The dynamic spinal cord compression increased in extension more than flexion in all subtypes. Conclusion. Cervical spine studies that aim to investigate kyphotic deformities should make efforts to discern the different subtypes of kyphotic deformities to more accurately characterize and study the effects that the sagittal alignment has on the kinematics of the spine and the degree of spinal cord compression. Level of Evidence: 3

Growth-Factor Nanocapsules That Enable Tunable Controlled Release for Bone Regeneration.

Growth factors are of great potential in regenerative medicine. However, their clinical applications are largely limited by the short in vivo half-lives and the narrow therapeutic window. Thus, a robust controlled release system remains an unmet medical need for growth-factor-based therapies. In this research, a nanoscale controlled release system (degradable protein nanocapsule) is established via in situ polymerization on growth factor. The release rate can be finely tuned by engineering the surface polymer composition. Improved therapeutic outcomes can be achieved with growth factor nanocapsules, as illustrated in spinal cord fusion mediated by bone morphogenetic protein-2 nanocapsules.

A predictive model for obstructive sleep apnea and Down syndrome

Obstructive sleep apnea (OSA) occurs frequently in people with Down syndrome (DS) with reported prevalences ranging between 55% and 97%, compared to 1–4% in the neurotypical pediatric population. Sleep studies are often uncomfortable, costly, and poorly tolerated by individuals with DS. The objective of this study was to construct a tool to identify individuals with DS unlikely to have moderate or severe sleep OSA and in whom sleep studies might offer little benefit. An observational, prospective cohort study was performed in an outpatient clinic and overnight sleep study center with 130 DS patients, ages 3–24 years. Exclusion criteria included previous adenoid and/or tonsil removal, a sleep study within the past 6 months, or being treated for apnea with continuous positive airway pressure. This study involved a physical examination/medical history, lateral cephalogram, 3D photograph, validated sleep questionnaires, an overnight polysomnogram, and urine samples. The main outcome measure was the apnea‐hypopnea index. Using a Logic Learning Machine, the best model had a cross‐validated negative predictive value of 73% for mild obstructive sleep apnea and 90% for moderate or severe obstructive sleep apnea; positive predictive values were 55% and 25%, respectively. The model included variables from survey questions, medication history, anthropometric measurements, vital signs, patients age, and physical examination findings. With simple procedures that can be collected at minimal cost, the proposed model could predict which patients with DS were unlikely to have moderate to severe obstructive sleep apnea and thus may not need a diagnostic sleep study.

Descriptive Epidemiology of Injuries Sustained in National Collegiate Athletic Association Men’s and Women’s Volleyball, 2013-2014 to 2014-2015:

Background: There were 18,844 volleyball players in the National Collegiate Athletic Association (NCAA) in the 2014-2015 academic year. Little research has examined sex-based differences among these athletes. Purpose: To examine injury epidemiology in NCAA men’s and women’s volleyball athletes. Study Design: Descriptive epidemiology study. Level of Evidence: Level 3. Methods: Injury surveillance data from the 2013-2014 through 2014-2015 academic years were obtained from the NCAA Injury Surveillance Program for 6 men’s and 33 women’s collegiate volleyball teams. Injury rates per 1000 athlete-exposures (AEs) and injury rate ratios (IRRs) with 95% CIs were calculated. Time-loss (TL) injuries resulted in participation restriction for at least 24 hours, and non-time-loss (NTL) injuries resulted in participation restriction of less than 24 hours. Results: Overall, 83 and 510 injuries were reported in men and women, respectively, leading to injury rates of 4.69 and 7.07 per 1000 AEs. The injury rate was greater in women than men (IRR, 1.51; 95% CI, 1.19-1.90). TL injury rates were 1.75 and 2.62 per 1000 AEs for men and women, respectively. The ankle was the most commonly injured body part among TL injuries (men, 25.8%; women, 24.3%); the knee was the most commonly injured body part among NTL injuries (men, 25.5%; women, 16.3%). Among TL injuries, common diagnoses included sprains (men, 25.8%; women, 31.2%) and concussions (men, 19.4%; women, 14.8%). Most TL concussions were due to ball contact (men, 83.3%; women, 53.6%). Compared with men, women had a greater NTL overuse injury rate (IRR, 3.47; 95% CI, 1.61-7.46). Compared with women, men had a greater TL injury rate associated with ball contact (IRR, 2.24; 95% CI, 1.07-4.68). Conclusion: There are differences in injury patterns and rates between male and female intercollegiate volleyball players. Although a limited-contact sport, a notable number of concussions were sustained, mostly from ball contact. Clinical Relevance: Understanding injury patterns may aid clinicians in injury diagnosis, management, and prevention.

Symmetrical Drug-related Intertriginous and Flexural Exanthema Induced by Doxycycline

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction characterized by erythema over the buttocks, thighs, groin, and flexural regions most commonly associated with the use of beta-lactam antibiotics. Although the exact pathophysiology of this disease remains unknown, it is theorized to be the result of a delayed hypersensitivity response presenting as a cutaneous eruption days to weeks after exposure to the drug. The treatment involves discontinuation of the suspected medication, symptomatic control of pruritus, and topical steroid therapy. A 51-year-old woman with homocystinuria and fibromyalgia was admitted with fevers, pancytopenia (later diagnosed to be acute myelogenous leukemia), and a targetoid cutaneous eruption in the setting of a recent tick bite. She was subsequently noted to have symmetric, pruritic, erythematous papules over the lateral neck, retroauricular regions, lateral aspects of the inframammary regions, medial upper arms, axillae, and the lower abdomen two weeks after starting doxycycline. Considering the morphology, distribution, and intense pruritis associated with the eruption, a diagnosis of SDRIFE was made. Doxycycline discontinuation along with topical steroid therapy resulted in the resolution of the eruption and pruritus. Given the widespread use of doxycycline, clinicians should be aware of this possible side effect.

The facial morphology in Down syndrome: A 3D comparison of patients with and without obstructive sleep apnea

Obstructive sleep apnea (OSA) occurs at a high prevalence in patients with Down syndrome (DS). A polysomnogram, which is often cumbersome and challenging, remains the gold standard method of diagnosing OSA. OSA in patients with DS is often attributed to skeletal and soft‐tissue structural alterations that are characteristic of the DS phenotype; as such, we hypothesized that assessing anthropometric facial measurements may be predictive of OSA in patients with DS. We used the 3dMDface sterophotography system to capture and create 3D facial images, and we subsequently identified facial landmarks using a single, experienced investigator and utilizing proprietary software to calculate inter‐landmark distances and angles. We compared our findings with similar data for neurotypically developing participants. We further compared the findings in participants with DS with and without OSA. Participants with DS had maxillomandibular hypoplasia with smaller ear, nose, and eye measurements compared to neurotypically developing peers. We found no statistically significant differences in 3D photogrammetric measurements between participants with DS with or without OSA.

Reply to Wollstonecroft et al.: Cooking increases the bioavailability of starch from diverse plant sources

We thank Wollstonecroft et al. for supporting the evidence that not all calories are equal (1). We found that the bioavailability of calories from lean beef (Bos taurus) and sweet potato (Ipomoea batatas) increased with food processing (2). For both foods, cooking had a larger impact on bioavailability than pounding, and when these processing methods were applied in combination, cooking improved a pounded diet whereas pounding did not improve a cooked diet. Our findings emphasize that the biochemical assays used in the production of modern nutrition labels do not fully account for the energetic significance of food processing. Such assays ignore important costs of the digestive process that are typically lowered by processing, including diet-induced thermogenesis and nutrients metabolized by gut bacteria instead of the human host.