BACKGROUND: Obesity is becoming increasingly common in obstetric and gynecologic populations, which may affect the safety of surgical termination of pregnancy. STUDY DESIGN: We performed a retrospective review of all patients undergoing second-trimester surgical termination of pregnancy by under ultrasound guidance termination between 13 0/7 and 24 0/7 weeks of gestational age (GA) to compare perioperative risks in obese and nonobese women. Complication rates, operative times and anesthesia times were compared between obese [body mass index (BMI) ≥30 kg/m(2)] and nonobese women (BMI <30). RESULTS: Of 1044 women, 29.0% were obese. The mean complication rate was 6.1% and similar between groups (5.5% nonobese, 7.6% obese, p=.20). Operative times were 4.4 min longer and mean anesthesia times were 5 min longer in obese patients (p<.001 for each). There was a nonsignificant trend toward more complications with gestational ages above 18 weeks (5.5% vs. 7.7%, p=.20). A history of one or more cesarean sections had an independent association with major complications after adjustment for confounders (adjusted odds ratio 4.2, p=.001). CONCLUSIONS: Both anesthesia and operative times were modestly increased in obese women versus nonobese women undergoing second-trimester surgical termination, without significant differences in complication rates. For patients at advanced GA with prior cesarean delivery, clinicians should be aware of the potential increase in complications as well as increased operative time in obese women, and counsel appropriately.

Propiconazole is a mouse hepatotumorigenic fungicide designed to inhibit CYP51, a key enzyme in the biosynthesis of ergosterol in fungi and is widely used in agriculture to prevent fungal growth. Metabolomic studies in mice revealed that propiconazole increased levels of hepatic cholesterol metabolites and bile acids, and transcriptomic studies revealed that genes within the cholesterol biosynthesis, cholesterol metabolism and bile acid biosyntheses pathways were up-regulated. Hepatic cell proliferation was also increased by propiconazole. AML12 immortalized hepatocytes were used to study propiconazole's effects on cell proliferation focusing on the dysregulation of cholesterol biosynthesis and resulting effects on Ras farnesylation and Erk1/2 activation as a primary pathway. Mevalonate, a key intermediate in the cholesterol biosynthesis pathway, increases cell proliferation in several cancer cell lines and tumors in vivo and serves as the precursor for isoprenoids (e.g. farnesyl pyrophosphate) which are crucial in the farnesylation of the Ras protein by farnesyl transferase. Farnesylation targets Ras to the cell membrane where it is involved in signal transduction, including the mitogen-activated protein kinase (MAPK) pathway. In our studies, mevalonic acid lactone (MVAL), a source of mevalonic acid, increased cell proliferation in AML12 cells which was reduced by farnesyl transferase inhibitors (L-744,832 or manumycin) or simvastatin, an HMG-CoA reductase inhibitor, indicating that this cell system responded to alterations in the cholesterol biosynthesis pathway. Cell proliferation in AML12 cells was increased by propiconazole which was reversed by co-incubation with L-744,832 or simvastatin. Increasing concentrations of exogenous cholesterol muted the proliferative effects of propiconazole and the inhibitory effects of L-733,832, results ascribed to reduced stimulation of the endogenous cholesterol biosynthesis pathway. Western blot analysis of subcellular fractions from control, MVAL or propiconazole-treated cells revealed increased Ras protein in the cytoplasmic fraction of L-744,832-treated cells, while propiconazole or MVAL reversed these effects. Western blot analysis indicated that phosphorylation of Erk1/2, a protein downstream of Ras, was increased by propiconazole. These data indicate that propiconazole increases cell proliferation by increasing the levels of cholesterol biosynthesis intermediates presumably through a negative feedback mechanism within the pathway, a result of CYP51 inhibition. This feedback mechanism increases Erk1/2 signaling through mevalonate-mediated Ras activation. These results provide an explanation for the observed effects of propiconazole on hepatic cholesterol pathways and on the increased hepatic cell proliferation induced by propiconazole in mice.

BACKGROUND: Diversity among health professionals is believed to be an important step toward improving patient communication and addressing health disparities. Orthopaedic surgery traditionally has been overly represented by Caucasian males, and it remains one of the least racially and gender-diversified surgical subspecialties. As the US population becomes increasingly diverse, a concomitant increase in ethnic diversity and gender diversity is needed to ensure that all Americans receive high-quality, culturally competent health care. QUESTIONS/PURPOSES: We asked whether (1) representation of female orthopaedic residents and clinical faculty and (2) representation of ethnic minority orthopaedic residents, clinical faculty, and basic science faculty increased during the past 15 years since our original study. METHODS: A questionnaire, created on SurveyMonkey(®), was distributed by email to the coordinators of all 152 orthopaedic residency training programs in the United States. RESULTS: Eighty (53%) responses were received. The percentage of female orthopaedic surgery residents and female clinical faculty has nearly doubled since 1995. The percentages of African American, Asian/Pacific Islander, and Hispanic orthopaedic residents, and of clinical faculty have increased. Orthopaedic basic science research faculty is 83% male and is comprised primarily of Caucasians (62%) and Asian/Pacific Islanders (24%). CONCLUSIONS: Despite the increase in diversity in the orthopaedic workforce during the past 15 years, ethnic and gender disparities persist among orthopaedic residency programs regarding residents, clinical faculty, and basic research faculty. To increase diversity in orthopaedic residency programs, an emphasis on recruiting ethnic and gender minority candidates needs to become a priority in the orthopaedic academic community.

CASE DESCRIPTION A 2-year-old spayed female Border Collie was treated with IV lipid emulsion (ILE) after ingesting 6 mg/kg (2.73 mg/lb) of an equine ivermectin anthelmintic paste 8 hours prior to examination. CLINICAL FINDINGS On initial examination, the dog had stable cardiovascular signs but had diffuse muscle tremors and was hyperthermic. Neurologic evaluation revealed that the dog was ataxic and had mydriasis with bilaterally absent menace responses and pupillary light reflexes. The remaining physical examination findings were unremarkable. Results of CBC, serum biochemical analysis, venous blood gas analysis, and measurement of plasma lactate concentration were also within reference limits. TREATMENT AND OUTCOME The dog was treated with ILE in addition to supportive care with IV fluid therapy and cardiovascular, respiratory, and neurologic monitoring. The use of ILE treatment was initiated in this patient on the basis of previous clinical and experimental evidence supporting its use for toxicosis resulting from lipid-soluble agents. An initial bolus of 1.5 mL/kg (0.68 mL/lb) of a 20% sterile lipid solution was administered IV over 10 minutes, followed by a constant rate infusion of 0.25 mL/kg/min (0.11 mL/lb/min) over 60 minutes that was administered twice to treat clinical signs of ivermectin toxicosis. The dog was discharged from the hospital 48 hours after admission and was clinically normal within 4 days after ivermectin ingestion. Further diagnostic evaluation subsequently revealed that this dog was unaffected by the multidrug resistance gene (MDR-1) deletion, known as the ATP-binding cassette polymorphism. CLINICAL RELEVANCE Ivermectin toxicosis in veterinary patients can result in death without aggressive treatment, and severe toxicosis often requires mechanical ventilation and intensive supportive care. This is particularly true in dogs affected by the ATP-binding cassette polymorphism. Novel ILE treatment has been shown to be effective in human patients with lipid-soluble drug toxicoses, although the exact mechanism is unknown. In the patient in the present report, ILE was used successfully to treat ivermectin toxicosis, and results of serial measurement of serum ivermectin concentration supported the proposed lipid sink mechanism of action.

  Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus results in leukocyte destruction and tissue necrosis (Pediatric Dermatology 2007;24:401). It can be associated with a spectrum of clinical manifestations that range from localized staphylococcal skin infections to sometimes severe necrotizing pneumonia (Clin Infect Dis 1999;29:1128). We report a case of four siblings, three brothers whose atopic dermatitis was complicated by cutaneous lesions and furunculosis, while their 21-month-old sister had a fatal PVL positive staphylococcal pneumonia.

FKBP65 is an endoplasmic reticulum (ER)-localized chaperone and rotamase, with cargo proteins that include tropoelastin and collagen. In humans, mutations in FKBP65 have recently been shown to cause a form of osteogenesis imperfecta (OI), a brittle bone disease resulting from deficient secretion of mature type I collagen. In this work, we describe the rapid proteolysis of FKBP65 in response to ER stress signals that activate the release of ER Ca(2+) stores. A large-scale screen for stress-induced cellular changes revealed FKBP65 proteins to decrease within 6-12 h of stress activation. Inhibiting IP(3)R-mediated ER Ca(2+) release blocked this response. No other ER-localized chaperone and folding mediators assessed in the study displayed this phenomenon, indicating that this rapid proteolysis of folding mediator is distinctive. Imaging and cellular fractionation confirmed the localization of FKBP65 (72 kDa glycoprotein) to the ER of untreated cells, a rapid decrease in protein levels following ER stress, and the corresponding appearance of a 30-kDa fragment in the cytosol. Inhibition of the proteasome during ER stress revealed an accumulation of FKBP65 in the cytosol, consistent with retrotranslocation and a proteasome-based proteolysis. To assess the role of Ca(2+)-binding EF-hand domains in FKBP65 stability, a recombinant FKBP65-GFP construct was engineered to ablate Ca(2+) binding at each of two EF-hand domains. Cells transfected with the wild-type construct displayed ER localization of the FKBP65-GFP protein and a proteasome-dependent proteolysis in response to ER stress. Recombinant FKBP65-GFP carrying a defect in the EF1 Ca(2+)-binding domain displayed diminished protein in the ER when compared to wild-type FKBP65-GFP. Proteasome inhibition restored mutant protein to levels similar to that of the wild-type FKBP65-GFP. A similar mutation in EF2 did not confer FKBP65 proteolysis. This work supports a model in which stress-induced changes in ER Ca(2+) stores induce the rapid proteolysis of FKBP65, a chaperone and folding mediator of collagen and tropoelastin. The destruction of this protein may identify a cellular strategy for replacement of protein folding machinery following ER stress. The implications for stress-induced changes in the handling of aggregate-prone proteins in the ER-Golgi secretory pathway are discussed. This work was supported by grants from the National Institutes of Health (R15GM065139) and the National Science Foundation (DBI-0452587).

Lead exposure in New Jersey raptors was assessed by analyzing liver samples from carcasses obtained from wildlife rehabilitators. Samples were collected from 221 individuals representing 13 species. Concentrations were within the range of normal background exposure in 12 species. One red-tailed hawk had a liver lead concentration consistent with clinical poisoning (7.4 μg/g wet weight), which represents an incidence of 1%(1/104) in that species and 0.5%(1/221) in the overall sample. A second red-tailed hawk had a liver lead concentration consistent with subclinical exposure (2.1 μg/g wet weight). The combined incidence of elevated exposure (subclinical exposure + clinical poisoning) was 2%(2/104) in red-tailed hawks and 1%(2/221) in the overall sample.

Serum chemistry panels and complete mineral and heavy metal screens were performed on blood samples from eight adult northern goshawks (Accipiter gentilis) breeding in Pennsylvania. Serum chemistry panels were performed to determine the health status of each bird. Biochemical values measured included serum glucose, sodium, potassium, chloride, magnesium, uric acid, creatine kinase, and aspartate transaminase. Glucose, creatine kinase, and aspartate transaminase values were elevated when compared with published values for northern goshawks and other species of raptors. Complete mineral screens were performed to better document the blood mineral content of northern goshawks. Plasma calcium, copper, iron, magnesium, total phosphorus, potassium, sodium, and zinc levels were determined. Whole blood heavy metal screens were done to evaluate the northern goshawk's exposure to environmental arsenic, cadmium, lead, thallium, and selenium. Arsenic, cadmium, lead, and thallium whole blood levels of less than 0.05 ppm in all birds indicated that the northern goshawks were not being exposed to significant levels of heavy metals in their environment. Whole blood selenium levels of the northern goshawks were above the minimum dietary requirement for avian species (0.130-0.200 ppm) and below published toxic selenium concentrations.

There is a lack of information on mineral requirements of free-ranging white-tailed deer (Odocoileus virginianus). In addition, mineral deficiencies or excesses may play a role in the development of parasitism/malnutrition syndrome. We measured hepatic mineral values in apparently healthy white-tailed deer from two sites in Virginia, USA, as well as in deer with presumptive parasitism/malnutrition syndrome during 2005-2007. Deer with presumptive parasitism/malnutrition syndrome that were displaying signs of emaciation and chronic diarrhea had significantly higher mean hepatic levels of magnesium (Mg) and zinc (Zn) compared with healthy deer. Healthy deer in our study from northern Virginia, USA (i.e., Fairfax, Fauquier, Loudoun, and Prince William counties) had significantly lower mean hepatic selenium (Se) levels compared with deer from Nottoway County, Virginia, USA, which is 200 km distant. Healthy deer from northern Virginia, USA, also had significantly lower mean hepatic cobalt (Co), copper (Cu), and molybdenum (Mo) levels. Adult deer had significantly higher mean levels of hepatic iron (Fe) compared with fawns. In addition, male deer had significantly higher mean hepatic Co levels compared with female deer. The significantly higher mean (+/-SD) level of Zn in sick deer from northern Virginia, USA (78.7+/-54.9 mug/g versus 35.8+/-7.4 mug/g in healthy deer) is potentially clinically significant, although no signs consistent with Zn poisoning were observed. All deer in our study from northern Virginia, USA, had marginal or deficient levels of Cu (mean+/-SD=27.4+/-18.3 mug/g) and Se (mean=0.08+/-0.03 mug/g), which may be predisposing this population to the development of parasitism/malnutrition syndrome.