Dose reduction for fluoroscopically guided injections: phantom simulation and patient procedures.

OBJECTIVE: To demonstrate fluoroscopy dose reduction through both simulated injections on a phantom and patient injections. MATERIALS AND METHODS: Our study was IRB-approved and HIPAA-compliant. Simulation on a phantom was used to estimate effective dose, entrance dose, and organ doses for hip joint injections without and with dose minimization technique (DMT). Additionally, 1,094 joint, bursae, and tendon sheath injections performed by three operators in the same fluoroscopy suite were evaluated both before and after application of DMT. Fluoroscopy time (FT), dose, and dose area product (DAP) of injections were compared using unpaired t-tests with P > 0.05 considered statistically significant. RESULTS: For the phantom simulation comparing injections without DMT and with DMT, the total DAP was 191.7 vs 18.7 µGy·m2, and the entrance dose was 10.2 vs 3.6 mGy, respectively. For both men and women, DMT reduces effective dose and organ doses. For all injections, the FT (0.7 to 0.2 min), dose (5.6 to 1.9 mGy), and DAP (56.9 to 19.1 µGy·m2) for all three operators decreased with DMT and remained statistically significant when stratified by the two most common injections, glenohumeral and hip joint injections (P < 0.05). CONCLUSIONS: FT, effective dose, entrance dose, and DAP can be reduced with the use of simple easy-to-learn techniques, which will benefit both the patient and the radiologist.

Benzyltriboronates: Building Blocks for Diastereoselective Carbon-Carbon Bond Formation.

A highly diastereoselective carbon-carbon bond-forming reaction involving the tandem coupling of benzyltriboronates, enoates, and alkyl halides is described. This method was enabled by the discovery of α-diimine nickel catalysts that promote the chemoselective triborylation of benzylic C(sp3)-H bonds using B2Pin2 (Pin = pinacolate). The C-H functionalization method is effective with methylarenes and for the diborylation of secondary benzylic C-H bonds, providing direct access to polyboron building blocks from readily available hydrocarbons. Combination of the benzylic perborylation with a new deborylative conjugate addition-alkylation method enables a one-pot procedure in which multiple simple precursors are combined to generate diastereopure products containing quaternary stereocenters.

Cobalt-Catalyzed Benzylic Borylation: Enabling Polyborylation and Functionalization of Remote, Unactivated C(sp(3))-H Bonds.

Cobalt dialkyl and bis(carboxylate) complexes bearing α-diimine ligands have been synthesized and demonstrated as active for the C(sp(3))-H borylation of a range of substituted alkyl arenes using B2Pin2 (Pin = pinacolate) as the boron source. At longer reaction times, rare examples of polyborylation were observed, and in the case of toluene, all three benzylic C-H positions were functionalized. Coupling benzylic C-H activation with alkyl isomerization enabled a base-metal-catalyzed method for the borylation of remote, unactivated C(sp(3))-H bonds.

Injuries in elite Jamaican netballers.

OBJECTIVES: The purpose of this study is to identify the nature, spectrum and frequency of injuries among national netballers in Jamaica. METHODS: A retrospective study utilizing a questionnaire was used to gather the necessary information among netball players over a five-year period spanning two world cups. A 31-item questionnaire on player's profile, protective equipment, site of injury and associated factors of injury was completed by a study population recruited from players who had represented Jamaica at the senior level, under 21 or under 16 age groups between 2003 and 2007. Statistical analysis was done using the SPSS version 12. RESULTS: Most of the injuries were confined to the ankle and knee, with the playing surface and poor landing technique the main reasons for the injuries. CONCLUSIONS: There are wide variations in training, players' fitness, levels of coaching and the standards of playing courts, all of which might have contributed to players' injuries.

Deep sequencing reveals extensive variation in the gut microbiota of wild mosquitoes from Kenya.

The mosquito midgut is a hostile environment that vector-borne parasites must survive to be transmitted. Commensal bacteria in the midgut can reduce the ability of mosquitoes to transmit disease, either by having direct anti-parasite effects or by stimulating basal immune responses of the insect host. As different bacteria have different effects on parasite development, the composition of the bacterial community in the mosquito gut is likely to affect the probability of disease transmission. We investigated the diversity of mosquito gut bacteria in the field using 454 pyrosequencing of 16S rRNA to build up a comprehensive picture of the diversity of gut bacteria in eight mosquito species in this population. We found that mosquito gut typically has a very simple gut microbiota that is dominated by a single bacterial taxon. Although different mosquito species share remarkably similar gut bacteria, individuals in a population are extremely variable and can have little overlap in the bacterial taxa present in their guts. This may be an important factor in causing differences in disease transmission rates within mosquito populations.

Positron emission tomography evaluation of oxime countermeasures in live rats using the tracer O-(2-[18 F]fluoroethyl)-O-(p-nitrophenyl)methylphosphonate [18 F]-VXS.

Oxime antidotes regenerate organophosphate-inhibited acetylcholinesterase (AChE). Although they share a common mechanism of AChE reactivation, the rate and amount of oxime that enters the brain are critical to the efficacy, a process linked to the oxime structure and charge. Using a platform based on the organophosphate [18 F]-VXS as a positron emission tomography tracer for active AChE, the in vivo distribution of [18 F]-VXS was evaluated after an LD50 dose (250 µg/kg) of the organophosphate paraoxon (POX) and following oximes as antidotes. Rats given [18 F]-VXS tracer alone had significantly higher radioactivity (two- to threefold) in the heart and lung than rats given LD50 POX at 20 or 60 min prior to [18 F]-VXS. When rats were given LD50 POX followed by 2-PAM (cationic), RS194b (ionizable), or monoisonitrosoacetone (MINA) (neutral), central nervous system (CNS) radioactivity returned to levels at or above untreated naive rats (no POX), whereas CNS radioactivity did not increase in rats given the dication oximes HI-6 or MMB-4. MINA showed a significant, pairwise increase in CNS brain radioactivity compared with POX-treated rats. This new in vivo dynamic platform using [18 F]-VXS tracer measures and quantifies peripheral and CNS relative changes in AChE availability after POX exposure and is suitable for comparing oxime delivery and AChE reactivation in rats.

Golimumab, a human antibody to tumour necrosis factor {alpha} given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study.

OBJECTIVE: The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. METHODS: Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24. RESULTS: The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively. CONCLUSION: The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.

Donor site morbidity following iliac crest bone graft.

OBJECTIVES: To evaluate the complications of harvesting autogenous bone from the iliac crest. METHODS: A retrospective review of patients undergoing iliac crest bone grafting at the University Hospital of the West Indies, during the period 2000-2004, was performed. One hundred and three patients were identified. Thirty-two patients were successfully contacted and 30 completed the questionnaire. There were 18 males (60%) and 12 females (40%). Their ages ranged from 13 years to 80 years (average 45.6 years). RESULTS: Of the 30 patients, 22 (73.3%) had complications. Fourteen (46.6%) patients had temporary pain; five (16.6%) had chronic pain. Two (6.6%) changed position of clothing due to discomfort at the graft site; five (16.6%) experienced difficulty walking, one reported itching of the scar one had altered sensation and one was unhappy with the scar. Fourteen patients (46.6%) had minor complications and eight patients (26.6%) had major complications. CONCLUSION: Autogenous iliac crest bone grafting is associated with significant complications.

Hypertrophic Cardiomyopathy in Liver Transplantation Patients.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder that presents with a hypertrophied nondilated left ventricle. In the absence of other known causes of cardiomyopathy, it is often associated with left ventricular outflow tract obstruction during systole, systolic anterior motion of the mitral valve, mitral regurgitation, and increased risk of sudden cardiac death. When HCM coexists with end-stage liver disease, it can be further complicated by cirrhosis-associated cardiovascular abnormalities, including hyperdynamic circulation, systolic and diastolic dysfunction, and electrophysiologic abnormalities. METHODS: We retrospectively examined patient characteristics, comorbidities, preoperative echocardiogram results, sudden cardiac death risk prediction model score, and 1-year postoperative mortality of patients with HCM who underwent liver transplantation at our institution from January 1, 2000, through January 1, 2015. RESULTS: Of the 2,812 liver transplantations performed during the study period, we identified 15 patients with a preoperative diagnosis of HCM. When comparing the patients who did vs did not survive the first year after orthotopic liver transplantation, we identified significant differences in maximal left ventricular wall thickness (P = .004) and resting left ventricular outflow tract gradient (P = .004). Preoperative left atrium size (measured by echocardiography; P = .66) and the sudden cardiac death risk prediction model score (P = .32) were not significantly associated with 1-year survival. CONCLUSIONS: Preoperative left ventricular outflow tract gradient exceeding 60 mm Hg was strongly associated with death during the first year after transplant. These results suggest that the severity of HCM influences patient outcomes.

Antithymocyte Globulin Use for Corticosteroid Nonresponsive Rejection After Liver Transplantation.

BACKGROUND AND AIMS: Acute cellular rejection after liver transplantation usually responds to intravenous corticosteroids, yet some episodes are corticosteroid-nonresponsive. We report our experience using antithymocyte globulin therapy for corticosteroid-nonresponsive acute cellular rejection in liver transplant recipients. METHODS: From January 1, 2002 to January 1, 2010, 1436 patients underwent 1548 liver or liver with other organ transplantations at our institution. We identified all patients treated with antithymocyte globulin during this timeframe for corticosteroid-nonresponsive rejection. RESULTS: Twenty patients required antithymocyte globulin for 21 episodes of corticosteroid-nonresponsive rejection. Antithymocyte globulin was started a median (range) of 27 (7-2434) days post-transplantation, and median total antithymocyte globulin dose and duration was 10.5 (7.5-26.25) mg/kg and 7 (5-13) days, respectively. Resolution or marked histological improvement of rejection on Day 7 liver allograft biopsies occurred in 90% of rejection episodes treated with antithymocyte globulin. Three-year graft and patient survival rates were 60% and 65%, respectively, compared with 79% and 84% in patients not requiring antithymocyte globulin. CONCLUSIONS: Antithymocyte globulin was an effective therapy for corticosteroid-nonresponsive rejection, with excellent short-term outcomes. Some liver transplant recipients failed to respond, and long-term survival was reduced, even in those who responded to antithymocyte globulin.

The Illizarov method in infected non-union of long bones.

OBJECTIVE: To review the results of the management of infected non-union of long bones using the Illizarov fixator. METHODS: Eight patients with non-union of long bones associated with current or prior infection were treated between 1998 and 2006. Seven patients were treated between 2004 and 2006. There were seven males and one female with an average age of 32 years (range 17-53 years). Four non-unions were located in the tibia, two were present in the humerus, one was present in the femur and one was intraarticular. Five non-unions were treated with acute compression, two were treated with bone transport and the frame was used in a static mode in one. RESULTS: There was one excellent, three good, one fair and three poor results. CONCLUSION: The Illizarov technique is an important treatment method for surgeons performing posttraumatic reconstructive surgery. Non-union, infection, shortening and deformity are all addressed simultaneously.

Cobalt-Catalyzed Stereoretentive Hydrogen Isotope Exchange of C(sp3)-H Bonds.

Cobalt dialkyl complexes bearing α-diimine ligands proved to be active precatalysts for the nondirected, C(sp3)-H selective hydrogen isotope exchange (HIE) of alkylarenes using D2 gas as the deuterium source. Alkylarenes with a variety of substitution patterns and heteroatom substituents on the arene ring were successfully labeled, enabling high levels of incorporation into primary, secondary, and tertiary benzylic C(sp3)-H bonds. In some cases, the HIE proceeded with high diastereoselectivity and application of the cobalt-catalyzed method to enantioenriched substrates with benzylic stereocenters provided enantioretentive hydrogen isotope exchange at tertiary carbons.

Thromboelastography as a Predictor of Outcomes Following Liver Transplantation.

BACKGROUND: Thromboelastography (TEG) has been used perioperatively during liver transplantation (LT) to provide a real-time global hemostasis assessment for targeted blood product replacement. We aimed to analyze the relationship between post-LT TEG results and outcomes. METHODS: We retrospectively analyzed patients undergoing LT from November 2008 to December 2014 at Mayo Clinic Florida. All 441 single-organ 1st-time LT patients aged ≥18 years requiring post-LT intensive care unit management were included. TEG parameters including r time, k time, α angle, and maximum amplitude were measured regularly during the first 24 hours after LT. Outcomes included return to the operating room secondary to bleeding, length of hospitalization, survival, and early allograft dysfunction. RESULTS: A prolonged and/or lengthening r time, k time, and r+k time were all independently associated with increased length of hospitalization after LT. Increased maximum amplitude on the first post-LT TEG was associated with early allograft dysfunction. No notable associations of TEG parameters with survival or return to operating room were observed. CONCLUSIONS: The association of absolute and temporal TEG value changes with increased length of hospitalization and early allograft dysfunction suggests that TEG may have a role in identifying patients at high risk for these outcomes.

Metabolism of 7,12-dimethylbmethylbenz(a)anthracene by macrophages and uptake of macrophage-derived metabolites by respiratory tissues in vitro.

Cultured mouse macrophages and tracheal and lung tissue each produced the same ethyl acetate-soluble derivatives of 7,12-dimethylbenz(a)anthracene (DMBA). The derivatives produced in the different cultures were indistinguishable by thin-layer chromatography and by high-pressure liquid chromatography but differed in their relative proportions. The greatest difference was seen between lungs and macrophages. The predominant metabolite produced by lungs was 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene, while macrophages produced equal quantities of both 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene and a second uncharacterized derivative, Metabolite B, at low DMBA doses (less than 0.05 microgram/ml medium) and primarily Metabolite B at higher DMBA doses (greater than 0.05 microgram/ml medium). Macrophages released the majority of the ethyl acetate-soluble metabolites that they produced into the surrounding medium. With the exception of 8,9-dihydro-8,9-dihydroxy-7,12dimethylbenz(a)anthracene, these derivatives were accumulated within tracheal and lung tissue when these organs were cocultivated with macrophages in the presence of DMBA.

Exercise-induced increases in myocardial adenosine 3',5'-cyclic monophosphate and phosphodiesterase activity.

Numerous cellular biochemical events caused by hormones are mediated through cyclic AMP. Although many changes occur in the cell during exercise that could be attributed to this nucleotide, little evidence is available implicating it as an important regulator of exercise metabolism. In this investigation it was found that a 60 min bout of treadmill exercise caused a 2.4-fold increase in myocardial cyclic AMP immediately following the work. Rather than the immediate nucleotide hydrolysis that was expected, it was found that the elevated cyclic AMP level remained for approx. 24 h before returning to control levels. Cardiac glycogen fell to 30% of control after work but supercompensated 60% above control within 1 h following exercise. Therefore, cardiac cyclic AMP was elevated at a time when glycogen was being synthesized. Study of the temporal relationship between the exercise-induced increase in cyclic AMP and cyclic nucleotide phosphodiesterase indicated that the work caused an increase in the hearts' capacity to hydrolyze cyclic AMP. Measurement of heart phosphodiesterase at substrate concentrations of 1.0 and 100 microM produced significant increases in enzyme activity immediately following exercise which remained elevated for 48 h and was back to control activity 96 h following work. These data present a potentially fascinating model for the study of the dissociation between cyclic AMP, glycogenesis and elevations in phosphodiesterase activity in the heart.

Assessing multimodal school travel safety in North Carolina.

School transportation has been the subject of numerous federal and state policies since the early twentieth century-the Safe Routes to School program is the most recent example. However, few recent studies have thoroughly analyzed the risks and costs associated with different modes of transportation to school. Our descriptive study assessed the injury and fatality rates and related safety costs of different modes of school transportation using crash and exposure data from North Carolina, USA from 2005 to 2012. We found that riding with a teen driver is the most dangerous mode on a per trip basis with injury rates 20 times higher and fatality rates 90 times higher than school buses, which had the lowest injury rates. Non-motorized modes had per trip injury rates equivalent to school buses but per trip fatality rates were 15 times higher than for school buses. The economic costs of school travel-related injuries and fatalities for walking, biking, and teen drivers were substantially higher than other modes. This research has important policy implications because it quantified the risks of different school travel modes which allows policymakers to consider how safety investments can reduce risks. Decades of effort by schools, communities, and the government have made school buses a very safe mode and endeavored to reduce risks to teen drivers. This study highlighted the need for these same actors to reduce the risks of injury for walking and bicycling. As more improvements are made to infrastructure around schools, repeated studies of this type will allow practitioners to examine whether the improvements help mitigate the risks.

Estrogen induction of very low density apolipoprotein II synthesis, a major avian liver yolk protein, involves the recruitment of hepatocytes.

The mechanism of steroid hormone action was studied in the cockerel liver. Very low density apolipoprotein II (apo-VLDL-II), a yolk protein, is a low molecular weight apolipoprotein that is inducible by estrogen. The intracellular apo-VLDL-II messenger RNA (mRNA) concentration under various hormonal conditions was examined by a dot-blot assay. The concentration was very low in untreated cockerels (approximately 0.5 molecule per cell). It increased to 8,000 molecules per cell within 24 h of estrogen treatment and reached a maximum level of approximately 70,000 molecules per cell after 14 daily doses of estrogen. The distribution of hepatocytes harboring apo-VLDL-II and its mRNA was studied by immunohistochemistry and by in situ nucleic acid hybridization to cloned [3H]apo-VLDL-II complementary DNA (cDNA). The number of cells containing the immunoreactive protein and the hybridizable mRNA increased from extremely low (0.3% and 0.27%, respectively) to substantial (11% and 10%, respectively) at 24 h after estrogen treatment and to extremely high (94% and 92%, respectively) in maximally treated animals. Our studies indicate that, in addition to enhanced transcription and stabilization of mRNA, the recruitment of liver cells previously not engaged in the synthesis of apo-VLDL-II is an important mechanism by which the hormone induces the hepatic production of this protein. The phenomenon of recruitment and the heterogeneity of the functional capacity of individual hepatocytes to respond to estrogen may be important to our understanding of estrogen action in the liver.

Somatostatin production by a human medullary thyroid carcinoma cell line.

Somatostatin (SRIF, SRIF-14) is a known product of the normal and malignant parafollicular cell of the thyroid. In this report we characterize SRIF production by the TT cells, a line of transformed calcitonin-producing cells derived from a human medullary thyroid carcinoma. The cells were found to contain (5-12 ng/10(6) cells) and secrete (3-10 ng/10(6) cells X 48 h) immunoreactive SRIF. Molecular sieve chromatography of cell extracts under denaturing conditions showed a major peak with a mol wt slightly larger than 12,700, probably representing pro-SRIF and a second peak which coeluted with SRIF; in one gel chromatogram a very small peak was also noted which coeluted with SRIF-28, but represented less than 0.4% of the total immunoreactive SRIF. Short term secretion of calcitonin and SRIF was stimulated by calcium in vitro (0.5-4 mM) in a dose-related manner. mRNA isolated from the TT cells hybridized to a specific bovine fetal pancreatic SRIF DNA (BFPS-2); there was no hybridization to identical amounts of mRNA from the atT-20/D16, 3T3, or RINC5F cell lines. In vitro translation of the TT cell mRNA followed by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the product revealed a single protein band of approximately 13,000 daltons. It was completely abolished when the immunoprecipitation was performed in the presence of excess unlabeled SRIF. Northern transfer of TT cell cytoplasmic RNA and hybridization with FBPS-2 cDNA showed a single hybridizing band with an apparent size of approximately 750 nucleotides. Our observations demonstrate the production of SRIF by a continuous line of human medullary thyroid carcinoma cells and provide a model for studying the biosynthesis and secretion of SRIF in the parafollicular cell.