The Fascial Distortion Model in Military Aircrew with Chronic Neck Pain: A Case Study.

Musculoskeletal pain can be a significant safety risk to aircrew. Flight surgeons are the primary care providers for aircrew and are responsible for safely treating musculoskeletal pain. Certain medical interventions can be used to treat pain while maintaining the ability to fly safely. A previous F-18 Naval Flight Officer presented to the flight surgeon with chronic neck pain seeking noninvasive and nonpharmacological therapy. After one Osteopathic Manual Treatment session using the Fascial Distortion Model (FDM), the patient had improved pain and function. The aircrewman reported an 83% reduction in pain and a 200% improvement in cervical Range of Motion (ROM) immediately following treatment. Neck pain is a common complaint in aircrew. This pain can become an in-flight distraction, thus increasing the risk of aviation mishaps. FDM can decrease pain and increase ROM quickly, without equipment or a large amount of space and without the use of medications that may prohibit an aircrew member from flying. This case study shows the ability to treat a uniformed aircrewman with neck pain while onboard an aircraft. FDM is a technique that can be taught to all flight surgeons. Teaching future flight surgeons FDM techniques can improve the U.S. Navy's resources by decreasing time away from work along with decreasing medical costs. The use of osteopathic manipulation treatment significantly reduced an aircrewman's pain and increased ROM with one treatment while maintaining flight status per current aeromedical waiver guidelines.

Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

BACKGROUND: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups. RESULTS: Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was -7.1% points (95% CI: -13.1% to -2.4%), favoring echinocandins. The risk difference was -0.4% (95% CI: -7.5% to 6.7%) at 30 days. CONCLUSIONS: In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents. CLINICAL TRIALS REGISTRATION: NCT01869829.

Liver injury and fibrosis induced by dietary challenge in the Ossabaw miniature Swine.

BACKGROUND: Ossabaw miniature swine when fed a diet high in fructose, saturated fat and cholesterol (NASH diet) develop metabolic syndrome and nonalcoholic steatohepatitis (NASH) characterized by liver injury and fibrosis. This study was conducted to further characterize the development of NASH in this large animal model. METHODS: Ossabaw swine were fed standard chow (control group; n = 6) or NASH diet (n = 6) for 24 weeks. Blood and liver tissue were collected and liver histology were characterized at 0, 8, 16 and 24 weeks of dietary intervention. Hepatic apoptosis and lipid levels were assessed at week 24. RESULTS: The NASH diet group developed metabolic syndrome and progressive histologic features of NASH including: (a) hepatocyte ballooning at 8 weeks which progressed to extensive ballooning (>90% hepatocytes), (b) hepatic fibrosis at week 16, which progressed to moderate fibrosis, and (c) Kupffer cell accumulation with vacuolization at 8 weeks which progressed through week 24. The NASH diet group showed increased hepatocyte apoptosis that correlated with hepatic total and free cholesterol and free fatty acids, but not esterified cholesterol or triglycerides. CONCLUSIONS: This report further characterizes the progression of diet-induced NASH in the Ossabaw swine model. In Ossabaw swine fed the NASH diet: (a) hepatocyte injury and fibrosis can occur without macrovesicular steatosis or excess triglyceride accumulation; (b) hepatocyte ballooning generally precedes the development of fibrosis; (c) there is increased hepatocyte apoptosis, and it is correlated more significantly with hepatic free cholesterol than hepatic free fatty acids and had no correlation with hepatic triglycerides.

Metabolic Syndrome Abolishes Glucagon-Like Peptide 1 Receptor Agonist Stimulation of SERCA in Coronary Smooth Muscle.

Metabolic syndrome (MetS) doubles the risk of adverse cardiovascular events. Glucagon-like peptide 1 (GLP-1) receptor agonists induce weight loss, increase insulin secretion, and improve glucose tolerance. Studies in healthy animals suggest cardioprotective properties of GLP-1 receptor agonists, perhaps partially mediated by improved sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA) activity. We examined the acute effect of GLP-1 receptor agonists on coronary smooth muscle cells (CSM) enzymatically isolated from lean, healthy Ossabaw miniature swine. Intracellular Ca(2+) handling was interrogated with fura-2. The GLP-1 receptor agonist exenatide activated SERCA but did not alter other Ca(2+) transporters. Further, we tested the hypothesis that chronic, in vivo treatment with GLP-1 receptor agonist AC3174 would attenuate coronary artery disease (CAD) in swine with MetS. MetS was induced in 20 swine by 6 months' feeding of a hypercaloric, atherogenic diet. Swine were then randomized (n = 10/group) into placebo or AC3174 treatment groups and continued the diet for an additional 6 months. AC3174 treatment attenuated weight gain, increased insulin secretion, and improved glucose tolerance. Intravascular ultrasound and histology showed no effect of AC3174 on CAD. MetS abolished SERCA activation by GLP-1 receptor agonists. We conclude that MetS confers vascular resistance to GLP-1 receptor agonists, partially through impaired cellular signaling steps involving SERCA.

Relationship between adipose tissue insulin resistance and liver histology in nonalcoholic steatohepatitis: a pioglitazone versus vitamin E versus placebo for the treatment of nondiabetic patients with nonalcoholic steatohepatitis trial follow-up study.

UNLABELLED: The PIVENS (Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis [NASH]) trial demonstrated that pioglitazone and vitamin E improved liver histology to varying degrees, but the mechanisms are unknown. We conducted a study to examine the changes in adipose tissue insulin resistance (Adipo-IR) during the PIVENS trial and its relationship to histological endpoints. Adipo-IR (fasting nonesterified fatty acids [NEFAs] × fasting insulin) was calculated at baseline and after 16 and 96 weeks of therapy. Compared to placebo, the baseline Adipo-IR was not different in either the vitamin E group (P = 0.34) or the pioglitazone group (P = 0.29). Baseline Adipo-IR was significantly associated with fibrosis score (P = 0.02), but not with other histological features or nonalcoholic fatty liver disease (NAFLD) activity score (NAS). After 16 weeks, compared to placebo, the pioglitazone group had a significant reduction in Adipo-IR (-15.7 versus -1.91; P = 0.02), but this effect did not persist at 96 weeks (-3.25 versus -4.28; P = 0.31). Compared to placebo, Adipo-IR in the vitamin E group did not change significantly either after 16 weeks (P = 0.70) or after 96 weeks (P = 0.85). Change in Adipo-IR at week 16 was not associated with changes in any histological parameters at week 96, but improvement in Adipo-IR at week 96 was significantly associated with improvement in ballooning (P = 0.03), fibrosis (P = 0.004), and NAS (P = 0.01). CONCLUSION: Vitamin E improved liver histology independent of changes in Adipo-IR, and pioglitazone treatment acutely improved Adipo-IR, but this was not sustained. Changes in Adipo-IR were associated with changes in liver histology, including fibrosis.

Effect of different obesogenic diets on pancreatic histology in Ossabaw miniature swine.

OBJECTIVE: Obesity is a factor in the outcome and severity of pancreatic conditions. We examined the effect of hypercaloric diets on the pancreata of Ossabaw swine, a large animal model of metabolic syndrome and obesity. METHODS: Swine were fed with 1 of 4 diets: high-fructose (n = 9), atherogenic (n = 10), modified atherogenic (n = 6), or eucaloric standard diet (n = 12) for 24 weeks. Serum chemistries were measured, and pancreata were examined for histological abnormalities including steatosis, inflammation or fibrosis, insulin content, and oxidative stress. RESULTS: The fructose, atherogenic, and modified atherogenic diet groups exhibited obesity, metabolic syndrome, islet enlargement, and significantly increased pancreatic steatosis (22.9% ± 7.5%, 19.7% ± 7.7%, and 38.7% ± 15.3% fat in total tissue area, respectively) compared with controls (9.3% ± 1.9%; P < 0.05). The modified atherogenic diet group showed significantly increased oxidative stress levels as evidenced by elevated serum malondialdehyde (3.0 ± 3.3 vs 1.5 ± 0.3 µmol/L in controls; P = 0.006) and pancreatic malondialdehyde (0.1 ± 0.12 vs 0.04 ± 0.01 nmol/mg protein in controls; P = 0.01). None of the swine exhibited pancreatitis or cellular injury. CONCLUSIONS: Ossabaw swine fed with a modified atherogenic diet developed significant pancreatic steatosis and increased oxidative stress, but no other histological abnormalities were observed.