Defects in Mitochondrial Efficiency and H2O2 Emissions in Obese Women Are Restored to a Lean Phenotype With Aerobic Exercise Training

The notion that mitochondria contribute to obesity-induced insulin resistance is highly debated. Therefore, we determined whether obese (BMI 33 kg/m²), insulin-resistant women with polycystic ovary syndrome had aberrant skeletal muscle mitochondrial physiology compared with lean, insulin-sensitive women (BMI 23 kg/m²). Maximal whole-body and mitochondrial oxygen consumption were not different between obese and lean women. However, obese women exhibited lower mitochondrial coupling and phosphorylation efficiency and elevated mitochondrial H₂O₂ (mtH₂O₂) emissions compared with lean women. We further evaluated the impact of 12 weeks of aerobic exercise on obesity-related impairments in insulin sensitivity and mitochondrial energetics in the fasted state and after a high-fat mixed meal. Exercise training reversed obesity-related mitochondrial derangements as evidenced by enhanced mitochondrial bioenergetics efficiency and decreased mtH₂O₂ production. A concomitant increase in catalase antioxidant activity and decreased DNA oxidative damage indicate improved cellular redox status and a potential mechanism contributing to improved insulin sensitivity. mtH₂O₂ emissions were refractory to a high-fat meal at baseline, but after exercise, mtH₂O₂ emissions increased after the meal, which resembles previous findings in lean individuals. We demonstrate that obese women exhibit impaired mitochondrial bioenergetics in the form of decreased efficiency and impaired mtH₂O₂ emissions, while exercise effectively restores mitochondrial physiology toward that of lean, insulin-sensitive individuals.     

Orthopaedic Surgeons Receive the Most Industry Payments to Physicians but Large Disparities are Seen in Sunshine Act Data

Background

Industry payments made to physicians by drug and device manufacturers or group purchasing organizations are now reported to the Centers for Medicare and Medicaid Services (CMS) as a part of the Physician Payments Sunshine Act. Initial reports from the program show that orthopaedic surgeons lead all physician specialties in total and average industry payments. However, before further discussion of these payments and their implications can take place, it remains to be seen whether these figures are a true reflection of the field of orthopaedic surgery in general, rather than the result of a few outlier physicians in the field. In addition, the nature and sources of these funds should be determined to better inform the national dialogue surrounding these payments.

Questions/Purposes

We asked: (1) How do industry payments to orthopaedic surgeons compare with payments to physicians and surgeons in other fields, in terms of median payments and the Gini index of disparity? (2) How much do payments to the highest-receiving orthopaedic surgeons contribute to total payments? (3) What kind of industry payments are orthopaedic surgeons receiving? (4) How much do the highest-paying manufacturers contribute to total payments to orthopaedic surgeons?

Materials and Methods

We reviewed the most recent version of the CMS Sunshine Act Open Payments database released on December 19, 2014, containing data on payments made between August 1, 2013 and December 31, 2013. Data on total payments to individual physicians, physician specialty, the types of payments made, and the manufacturers making payments were reviewed. The Gini index of statistical dispersion was calculated for payments made to orthopaedic surgeons and compared with payments made to physicians and surgeons in all other medical specialties. A Gini index of 0 indicates complete equality of payments to everyone in the population, whereas an index of 1 indicates complete inequality, or all income going to one individual.

Results

A total of 15,376 orthopaedic surgeons receiving payments during the 5-month period were identified, accounting for USD 109,846,482. The median payment to orthopaedic surgeons receiving payments was USD 121 (interquartile range, USD 34–619). The top 10% of orthopaedic surgeons receiving payments (1538 surgeons) received at least USD 4160 and accounted for 95% of total payments. Royalties and patent licenses accounted for 69% of all industry payments to orthopaedic surgeons.

Conclusions

Even as a relatively small specialty, orthopaedic surgeons received substantial payments from industry (more than USD 110 million) during the 5-month study period. Whether there is a true return of value from these payments remains to be seen; however, future ethical and policy discussions regarding industry payments to orthopaedic surgeons should take into account the large disparities in payments that are present and also the nature of the payments being made. It is possible that patients and policymakers may view industry payments to orthopaedic surgeons more positively in light of these new findings.

Level of Evidence

Level III, Economic and Decision Analysis.     

The history of cryosurgery in Canada: A tale of two cities

Although not commonly available in Canada, cryosurgery (cryoablation) for prostate cancer has been practiced in many countries. The field of cryoablation has evolved significantly over the past 30 years. Two prostate cryoablation programs were started in Canada in the early 1990s, in London, ON and Calgary, AB, focusing, respectively, on salvage therapy following radiation failure and primary local treatment. This article chronicles the development of the two programs and outlines the scientific and clinical contributions by investigators at the two centers.     

CDC Kerala 15: Developmental Evaluation Clinic (2–10 y) – Developmental Diagnosis and Use of Home Intervention Package

Objective

To describe the last 5 years' experience of Child Development Centre (CDC), Kerala Developmental Evaluation Clinic II for children between 2 and 10 y, referred for suspicion of developmental lag in the preschool years and scholastic difficulty in the primary classes with specific focus on developmental profile and the experience of the home based intervention package taught to the mothers.

Methods

A team of evaluators including developmental therapist, preschool teacher with special training in clinical child development, speech therapist, special educator, clinical psychologist and developmental pediatrician assessed all the children referred to CDC Kerala. Denver Developmental Screening Test (DDST-II), Vineland Social Maturity Scale (VSMS) and Intelligent Quotient (IQ) tests were administered to all children below 6 y and those above 6 with apparent developmental delay.

Results

Speech/delay (35.9 %), behavior problem (15.4 %), global delay/ intellectual disability (15.4 %), learning problem (10.9 %), pervasive developmental disorders (7.7 %), seizure disorder (1.7 %), hearing impairment (0.7 %), and visual impairment (0.7 %) were the clinical diagnosis by a developmental pediatrician. Each child with developmental problem was offered a home based intervention package consisting of developmental therapy and special education items, appropriate to the clinical diagnosis of the individual child and the same was taught to the mother.

Conclusions

The experience of conducting the developmental evaluation clinic for children between 2 and 10 y has shown that a team consisting of developmental therapist, speech therapist, preschool teacher, special educator, clinical child psychologist and developmental pediatrician, using appropriate test results of the child could make a clinical diagnosis good enough for providing early intervention therapy using a home based intervention package.

     

CDC Kerala 16: Early Detection of Developmental Delay/Disability Among Children Below 6 y — A District Model

Objective

To develop a district model for establishing early detection of childhood disability below 6 y of age and to develop appropriate referral linkages for confirmation of the diagnosis and establish home based early intervention therapy to all needy children.

Methods

Trained Accredited Social Health Activist (ASHA) workers conducted the preliminary survey for identifying developmental delay/disability among children below 6 y of age using Trivandrum Developmental Screening Chart (TDSC) (0–6 y) and a team of experts assessed the screen positives in developmental evaluation camps conducted at primary health centres (PHCs).

Results

Community survey was carried out and 1,01,438 children below 6 y of age in Thiruvananthapuram district were screened by ASHA workers and 2,477 (2.45 %) positive cases (TDSC two or more item delay) were identified and these children were called for the developmental evaluation camps conducted at 80 PHCs in the district. Among the 1,329 children who reached the evaluation camps 43.1 % were normal. 24.98 % children had speech and language delay and 22.95 % children had multiple disabilities. Developmental delay was observed among 49.89 % children and cerebral palsy in 8.43 % and intellectual disability 16.85 % were confirmed. Visual impairment in 3.31 % and neuromuscular disorders in 1.35 were found among children evaluated in the camp.

Conclusions

The results of this district wide early detection of disability survey by trained ASHA workers among children below 6 y of age showed a community prevalence of 3.08 % observed, based on two or more item delay in TDSC and among these children, 43.1 % were normal, 49.89 % had developmental delay, 24.98 % had speech and language delay and 22.95 % had multiple disabilities.

     

Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.

To elucidate the mechanism of insulin's anticatabolic effect in humans, protein dynamics were evaluated in the whole-body, splanchnic, and leg tissues in six C-peptide-negative type I diabetic male patients in the insulin-deprived and insulin-treated states using two separate amino acid models (leucine and phenylalanine). L-(1-13C,15N)leucine, L-(ring-2H5)phenylalanine, and L-(ring-2H2) tyrosine were infused intravenously, and isotopic enrichments of [1-13C,15N]-leucine, (13C)leucine, (13C)ketoisocaproate, (2H5)phenylalanine, [2H4]tyrosine, (2H2)tyrosine, and 13CO2 were measured in arterial, hepatic vein, and femoral vein samples. Whole-body leucine flux, phenylalanine flux, and tyrosine flux were decreased (< 0.01) by insulin treatment, indicating an inhibition of protein breakdown. Moreover, insulin decreased (< 0.05) the rates of leucine oxidation and leucine transamination (P < 0.01), but the percent rate of ketoisocaproate oxidation was increased by insulin (P < 0.01). Insulin also reduced (< 0.01) whole-body protein synthesis estimated from both the leucine model (nonoxidative leucine disposal) and the phenylalanine model (disposal of phenylalanine not accounted by its conversion to tyrosine). Regional studies demonstrated that changes in whole body protein breakdown are accounted for by changes in both splanchnic and leg tissues. The changes in whole-body protein synthesis were not associated with changes in skeletal muscle (leg) protein synthesis but could be accounted for by the splanchnic region. We conclude that though insulin decreases whole-body protein breakdown in patients with type I diabetes by inhibition of protein breakdown in splanchnic and leg tissues, it selectively decreases protein synthesis in splanchnic tissues, which accounted for the observed decrease in whole-body protein synthesis. Insulin also augmented anabolism by decreasing leucine transamination.     

Fungal Orbital Cellulitis: Presenting Features,Management and Outcomes at a Referral Center

Purpose: To report a series of patients with fungal orbital cellulitis who underwent exenteration surgery and describe presenting features, management and outcomes at a referral center.

Methods: Retrospective case series.

Results: From November 2011 to March 2014, four patients underwent orbital exenteration for fungal orbital cellulitis at the University of Illinois. Three patients had mucormycosis and one had aspergillosis. All patients were treated with intravenous antifungals and underwent orbital exenteration. Two patients were successfully treated with supplemental intra-orbital catheter delivery of amphotericin B. Presenting visual acuity in the affected eye ranged from 20/25 to no light perception. Some level of ophthalmoplegia was present in three patients. Significantly elevated intraocular pressure was found in two patients. All patients with mucormycosis were found to have uncontrolled diabetes mellitus. One patient had a history of myelodysplastic syndrome, chronic hepatitis C infection, polysubstance abuse and Crohn’s disease. Another patient had a history of alcoholic liver cirrhosis, Crohn’s disease treated with systemic immunosuppression and renal cell carcinoma. The patient with aspergillosis had myelodysplastic syndrome and portal hypertension, and the initial presentation resembled giant cell arteritis. Two of four patients died during their hospitalization.

Conclusions: Fungal orbital cellulitis has a high mortality rate despite aggressive antifungal treatment and orbital exenteration performed soon after the diagnosis is confirmed. Patients often have a history of immunosuppression and the onset may be insidious. There must be a high rate of suspicion for fungal orbital cellulitis given the appropriate signs and medical history in order to avoid treatment delay.     

Bilateral periorbital and cervicofacial emphysema following retinal surgery and fluid gas exchange in a case of inadvertent globe perforation

Surgical emphysema is defined as gas or air trapped in the subcutaneous tissue plane. Here, we report a rare case of bilateral periorbital and cervicofacial subcutaneous emphysema following a vitreoretinal surgery for inadvertent globe perforation during the administration of peribulbar anesthesia. This condition, although self-resolving when restricted to the subcutaneous plane has the potential to spread into deeper tissue planes such as the retropharyngeal space. The presence of crepitus helps to distinguish it from angioneurotic edema. Ophthalmologists must be sensitive to the fact that surgical emphysema can be a very rare, but possible complication of an intraocular surgery following globe perforation.