A dedicated surgical team for posterior spinal fusion in patients with adolescent idiopathic scoliosis improves OR efficiency.

PURPOSE: Standardized care pathways for adolescent idiopathic scoliosis (AIS) patients undergoing PSF improve clinical outcomes. We hypothesized that having dedicated spine personnel would decrease surgical time and improve clinical outcomes. METHODS: 367 patients with AIS had a PSF within a standardized perioperative care pathway. Cases with 1-3 dedicated spine team members (any combination of circulating nurse, surgical technologist, and anesthesiologist) were compared to teams with none. The impact of individual members was also analyzed. Parametric or non-parametric tests were used for each outcome based on the distribution of the data points. These included one-way ANOVA models, Kruskal-Wallis tests, and Fisher's exact tests. RESULTS: Surgical time and total OR time were significantly decreased with the participation of each additional dedicated team member resulting in 43.86 min less surgical time and 50.8 min less total OR time when three team members were present compared to no team members. If the nurse was a spine member, the surgical time was lower (p = 0.037). If the technologist was a team member, the surgical time and total OR time were lower (p = 0.002 and p = 0.001, respectively). Lastly, if the anesthesiologist was a member of the team, the anesthesia time was lower (p = 0.003). No significant clinical differences were observed. CONCLUSION: Having dedicated surgical team members decreases surgical and total OR time for AIS patients undergoing PSF, and this OR efficiency improves as the dedicated team is more robust. OR surgical teams did not influence clinical outcomes. Hospitals should strongly consider developing surgical teams to improve OR efficiency of PSF cases.

Scoliosis Screening.

The national recommendations for school screening programs for scoliosis in the United States have undergone a shift in perspective over the past two decades. In 2004, the United States Preventive Services Task Force recommended against screening programs but changed its recommendation to be inconclusive in 2018. Early diagnosis of scoliosis can allow for close monitoring of the deformity and early initiation of bracing treatment when appropriate, with the goal of preventing costly and invasive surgical intervention. Several different diagnostic tools are available, including Adam's forward bending test alone, Adam's forward bending test with scoliometry, the humpometer, and Moiré topography, each with varying degrees of sensitivity and specificity. Controversy prevails over the cost efficacy of screening programs and possible unnecessary exposure of adolescents to radiation for confirmatory radiographs after a positive screening test. However, the recent definitive evidence of bracing treatment efficacy in slowing the progression of scoliotic curves and preventing the need for surgery indicates that school screening programs may still have a role in allowing early diagnosis.

Comparison of shoulder internal rotation passive range of motion in various positions in nonathletic persons and the establishment of normative values for the sidelying position.

BACKGROUND: Loss of shoulder internal rotation (IR) range of motion (ROM) is prevalent in overhead athletes, but it can also be seen in nonathletic persons. A paucity of normative data exists, however, for shoulder IR ROM in positions other than supine, especially in nonathletic persons. The aim of this study was to determine shoulder IR ROM differences between the sidelying, semi-sidelying, and supine positions as well as to establish initial normative values for IR ROM for the sidelying and semi-sidelying positions in nonathletic persons. METHODS: IR ROM was measured on 204 nonathletic persons using the sidelying, semi-sidelying, and supine positions. Mean values of IR ROM for each position were calculated. Differences in IR ROM across the 3 positions and side-to-side differences were examined, including the influence of sex and age on IR ROM. RESULTS: Intra-rater and inter-rater reliability for the sidelying position was excellent. The sidelying position had significantly less IR ROM compared with the other positions, and there was a significant side-to-side IR ROM difference, greatest for the sidelying position (6.8°). Women had significantly more IR ROM than men did, with sidelying normative values of 49° and 55° for female dominant and nondominant shoulders, respectively, and 42° and 51° for male dominant and nondominant shoulders, respectively. CONCLUSION: This investigation establishes initial normative IR ROM values for the sidelying position for both shoulders and sexes. Health care providers can begin to examine IR ROM deficits using these normative values for the sidelying position.

TOTAL ARC OF MOTION IN THE SIDELYING POSITION: EVIDENCE FOR A NEW METHOD TO ASSESS GLENOHUMERAL INTERNAL ROTATION DEFICIT IN OVERHEAD ATHLETES.

BACKGROUND: Total arc of motion (TA) measured in a supine position has been utilized as a method to detect the presence of glenohumeral internal rotation deficit (GIRD) in overhead athletes. A component of supine TA is supine internal rotation (IR) range of motion (ROM), which has many variables including the amount and location of manual stabilization. A sidelying position for gathering IR ROM has recently been proposed and, when combined with supine external rotation (ER) ROM, constitutes a new method of quantifying TA. This new sidelying TA method, however, has no normative values for overhead athletes. PURPOSE: The purposes of this study were to develop normative values for sidelying TA in overhead athletes, determine any ROM difference between supine and sidelying TA, and examine side-to-side differences within the two TA methods. A secondary purpose of the study was to examine for any effect of gender or level of competition on the two TA methods. STUDY DESIGN: Cross-sectional study. METHODS: Passive supine IR ROM, supine ER ROM, and sidelying IR ROM were gathered on bilateral shoulders of 176 collegiate and recreational overhead athletes (122 male [21.4 ± 4.7 years, 71.7 ± 2.7 inches, 25.3 ± 2.7 BMI] and 54 female [21.4 ± 5.4 years, 67.6 ± 3.0 inches, 22.5 ± 2.37 BMI]). RESULTS: Sidelying TA mean for the dominant shoulder was 159.6 °±15.0 °; the non-dominant shoulder was 163.3 °±15.3 °. Sidelying TA for both shoulders (p < 0.0001) was 14 ° less than supine TA. Both TA methods exhibited a 4 ° dominant-shoulder deficit (p < 0.0001). For the dominant and non-dominant shoulder, respectively, there was no gender (p = 0.38, 0.54) or level of competition (p = 0.23, 0.39) effect on sidelying TA. CONCLUSION: In overhead athletes, sidelying TA is a viable alternative to supine TA when examining for the presence of GIRD. Gender and level of competition does not significantly affect sidelying TA, so the mean of 160 ° on the dominant shoulder and 163 ° on the non-dominant shoulder can be used by clinicians. LEVEL OF EVIDENCE: Level 3.

Prenatal diagnosis of musculoskeletal conditions.

Ultrasonography is a safe, cost-effective tool used to prenatally detect common musculoskeletal conditions, including clubfoot, skeletal dysplasias, limb-length discrepancies, spinal abnormalities, and hand and other upper extremity deformities. With increased detection of such abnormalities, prenatal parental counseling by orthopaedic surgeons is being requested more frequently. Counseling is important for family education on prognosis and treatment options. A thorough understanding of the common musculoskeletal conditions diagnosed on prenatal ultrasonography, classification of these conditions, and the correlations of these classifications to postnatal severity allows the orthopaedic surgeon to conduct well-informed counseling sessions with families. Accurate information and counseling aids parents in understanding their child's diagnosis, assists clinicians in planning treatment algorithms, and optimizes family preparedness.

Structures of Cryptococcus neoformans protein farnesyltransferase reveal strategies for developing inhibitors that target fungal pathogens.

Cryptococcus neoformans is a fungal pathogen that causes life-threatening infections in immunocompromised individuals, including AIDS patients and transplant recipients. Few antifungals can treat C. neoformans infections, and drug resistance is increasing. Protein farnesyltransferase (FTase) catalyzes post-translational lipidation of key signal transduction proteins and is essential in C. neoformans. We present a multidisciplinary study validating C. neoformans FTase (CnFTase) as a drug target, showing that several anticancer FTase inhibitors with disparate scaffolds can inhibit C. neoformans and suggesting structure-based strategies for further optimization of these leads. Structural studies are an essential element for species-specific inhibitor development strategies by revealing similarities and differences between pathogen and host orthologs that can be exploited. We, therefore, present eight crystal structures of CnFTase that define the enzymatic reaction cycle, basis of ligand selection, and structurally divergent regions of the active site. Crystal structures of clinically important anticancer FTase inhibitors in complex with CnFTase reveal opportunities for optimization of selectivity for the fungal enzyme by modifying functional groups that interact with structurally diverse regions. A substrate-induced conformational change in CnFTase is observed as part of the reaction cycle, a feature that is mechanistically distinct from human FTase. Our combined structural and functional studies provide a framework for developing FTase inhibitors to treat invasive fungal infections.

Characterizing the in vitro hepatic biotransformation of the flame retardant BDE 99 by common carp.

Polybrominated diphenyl ethers (PBDEs) are a class of flame retardant chemicals known to biomagnify in aquatic foodwebs. However, significant biotransformation of some congeners via reductive dehalogenation has been observed during in vivo and in vitro laboratory exposures, particularly in fish models. Little information is available on the enzyme systems responsible for catalyzing this metabolic pathway in fish. This study was undertaken to characterize the biotransformation of one primary BDE congener, 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), using in vitro techniques. Hepatic sub-cellular fractions were first prepared from individual adult common carp (Cyprinus carpio) to examine metabolism in both microsomal and cytosolic sub-cellular fractions. Debromination rates (i.e. BDE-99 biotransformation to BDE-47) were generally higher in the microsomal fraction than in the cytosolic fraction, and some intra-species variability was observed. Further experiments were conducted to determine the biotransformation kinetics and the influence of specific co-factors, inhibitors and competitive substrates on metabolism using pooled carp liver microsomes. The apparent K(m) and V(max) values were 19.4microM and 1120pmolesh(-1)mgprotein(-1), respectively. Iodoacetate (IaC) and the two thyroid hormones, reverse triodothyronine (rT3) and thyroxine (T4), significantly inhibited the debromination of BDE-99 in microsomal sub-cellular fractions with IC(50) values of 2.2microM, 0.83microM, and >1.0microM, respectively. These results support our hypothesis that deiodinase enzymes may be catalyzing the metabolism of PBDEs in fish liver tissues. Further studies are needed to evaluate metabolic activity in other species and tissues that contain these enzymes.

Latent mortality of juvenile snapping turtles from the Upper Hudson River, New York, exposed maternally and via the diet to polychlorinated biphenyls (PCBs).

We conducted a factorial experiment to compare sublethal and lethal responses of juvenile snapping turtles exposed maternally and/or through the diet to polychlorinated biphenyls (PCBs) over 14 months posthatching. Maternal exposure did not affect embryonic development or hatching success. Thyrosomatic indices were not influenced by treatments, although hepatosomatic indices were lower in animals having been exposed to PCBs maternally relative to those having been exposed both maternally and via the diet. Dietary PCB exposure reduced metabolic rates of juveniles in two of three assays conducted. Approximately eight months after hatching, high rates of mortality began to emerge in individuals having been exposed maternally to PCBs, and mortality rate correlated with [PCB](total) in eggs. Prior to death, individuals that died experienced lower growth rates than those that survived, suggesting chronic effects prior to death. By 14 months posthatching, only 40% of juveniles derived from females in the contaminated area had survived, compared to 90% from the reference area. Such latent effects of maternally derived contaminants suggest that assessments of environmental impacts based upon shorter-term studies may provide very conservative estimates of the severity of effects, as they cannot capture responses that may emerge later in the life cycle.

In vitro hepatic metabolism of 2,2',4,4',5-pentabromodiphenyl ether (BDE 99) in Chinook salmon (Onchorhynchus tshawytscha).

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants that persist in the environment and are present in geographically widespread fish species. PBDE concentrations can be particularly high in resident Chinook salmon (Onchorhynchus tshawytscha) in the Puget Sound, Washington. Although PBDE residues in salmon and other fish are often dominated by lower brominated congeners, these congeners are not produced commercially in the greatest quantity, suggesting bioaccumulation of the lower molecular weight PBDEs or debromination of more fully brominated congeners. We determined the capacity of Chinook liver fractions to debrominate 2,2',4,4',5-pentabromodiphenyl ether (BDE 99), a model PBDE congener readily debrominated by common carp (Cyprinus caprio). Liver subcellular fractions from two strains of Chinook were incubated with BDE 99 prior to liquid/liquid extraction followed by gas chromatography/mass spectrometry analysis (GC/MS analysis) to identify metabolites and debromination products. In contrast to common carp, debromination of BDE 99 to BDE 47 (2,2',4,4'-tetrabromodiphenyl ether) was not observed in microsomal fractions from either strain of Chinook salmon. However, Chinook salmon liver microsomes from both Chinook strains slowly debrominated BDE 99 to BDE 49 (2,2',4,5'-tetrabromodiphenyl ether), a unique debromination product whose formation has not been reported in other fish. Three-year-old males belonging to a Rapid River Spring Chinook salmon genetic strain showed a somewhat greater microsomal debromination capacity than older hatchery returning male Chinook, but were still inefficient in the debromination of BDE 99 relative to carp. Microsomal debromination of BDE 99 to BDE 49 was not NADPH-dependent, indicating a lack of cytochrome P450 involvement. By contrast, omission of the reductant dithiothreitol (DTT) from Chinook microsomal preparations resulted in a lack of BDE 99 debromination, suggesting the involvement of a microsomal reductase(s) or deiodinase (DI). Cytosolic fractions from Chinook salmon and Common carp debrominated BDE 99 to BDE 49 in vitro. However, carp cytosolic enzymes preferentially formed BDE 47. In summary, our data indicate significant differences among teleosts with respect to efficiency and metabolite profiles of BDE 99 debromination, and suggest that the high concentrations of BDE 47 in resident Chinook salmon from the Puget Sound are not a result of hepatic metabolism of BDE 99. The results of our study also suggest the involvement of an unidentified hepatic reductase or DI in PBDE debromination in fish.

Metabolism of polybrominated diphenyl ethers (PBDEs) by human hepatocytes in vitro.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are flame-retardant chemicals that accumulate in human tissues and are potential toxicants. Concentrations of PBDEs in human tissues have increased recently, and body burdens in the U.S. and Canadian populations are higher than in any other region. OBJECTIVES: Although metabolism in animal laboratory studies has been examined, no studies have explored the metabolism of these contaminants in human tissues. We undertook this study to determine whether PBDEs could be metabolized by human liver cells in vitro and to identify what types of metabolites are formed. METHODS: We exposed hepatocytes from three different donors (two cryopreserved batches and one fresh batch) to solutions containing 10 muM of either of two environmentally relevant and prominent PBDE congeners-BDE-99 or BDE-209-for periods of 24-72 hr. We also conducted gene expression analysis to provide information on potential induction of xenobiotic metabolizing enzymes. RESULTS: Exposing hepatocytes to BDE-99 resulted in the formation of 2,4,5-tribromo phenol, two monohydroxylated pentabrominated diphenyl ether metabolites, and a yet unidentified tetrabrominated metabolite. No hydroxylated or debrominated metabolites were observed in the cells exposed to BDE-209. This suggests that BDE-209 was not metabolized, that nonextractable, covalently protein-bound metabolites were formed, or that the exposure time was not long enough for BDE-209 to diffuse into the cell to be metabolized. However, we observed up-regulation of genes encoding for cytochrome P450 monooxygenase (CYP) 1A2, CYP3A4, deiodinase type 1, and glutathione S-transferase M1 in hepatocyes exposed to both BDE-99 and BDE-209. CONCLUSIONS: Our in vitro results suggest that the human liver will likely metabolize some BDE congeners (e.g., BDE-99) in vivo. These metabolites have been shown to elicit greater toxicity than the parent BDE congeners in laboratory bioassays; thus, more research on body burdens and human health effects from these metabolites are warranted.

Alternate and new brominated flame retardants detected in U.S. house dust.

Due to the voluntary withdrawals and/or bans on the use of two polybrominated diphenyl ether (PBDE) commercial mixtures, an increasing number of alternate flame retardant chemicals are being introduced in commercial applications. To determine if these alternate BFRs are present in indoor environments, we analyzed dust samples collected from 19 homes in the greater Boston, MA area during 2006. Using pure and commercial standards we quantified the following brominated flame retardant chemicals using GC/ECNI-MS methods: hexabromocyclododecane (sigma HBCD), bis(2,4,6,-tribromphenoxy)ethane (BTBPE), decabromodiphenyl ethane (DBDPE), and the brominated components found in Firemaster 550 (FM 550): 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB) and (2-ethylhexyl)tetrabromophthalate (TBPH), the latter compound being a brominated analogue of di(2-ethylhexyl)phthalate (DEHP). The concentrations of all compounds were log-normally distributed and the largest range in concentrations was observed for HBCD (sum of all isomers), with concentrations ranging from <4.5 ng/g to a maximum of 130,200 ng/g with a median value of 230 ng/g. BTBPE ranged from 1.6 to 789 ng/g with a median value of 30 ng/g and DBDPE ranged from <10.0 to 11,070 ng/g with a median value of 201 ng/g. Of the FM 550 components, TBB ranged from <6.6 to 15,030 ng/g with a median value of 133 ng/g; whereas TBPH ranged from 1.5 to 10,630 ng/g with a median value of 142 ng/g. Furthermore, the ratio of TBB/TBPH present in the dust samples ranged from 0.05 to 50 (average 4.4), varying considerably from the ratio observed in the FM 550 commercial mixture (4:1 by mass), suggesting different sources with different chemical compositions, and/or differential fate and transport within the home. Analysis of paired dust samples collected from different rooms in the same home suggests HBCD, TBB, and TBPH are higher in dust from the main living area compared to dust collected in bedrooms; however, BTBPE and DBDPE levels were comparable between rooms. This study highlights the fact that numerous types of brominated flame retardants are present in indoor environments, raising questions about exposure to mixtures of these contaminants.

Accumulation and maternal transfer of polychlorinated biphenyls in snapping turtles of the upper Hudson River, New York, USA.

We conducted field studies over three years to assess body burdens and maternal transfer of polychlorinated biphenyls (PCBs) as well as indices of sexual dimorphism in snapping turtles (Chelydra serpentina) of the upper Hudson River (NY, USA.) We collected adult turtles in areas known to be contaminated with PCBs and in nearby reference areas for measurement of body size, precloacal length, and penis size. We analyzed PCB concentrations in eggs collected over three years and in whole blood from adults in one year. Total PCB concentrations (mean +/- standard error) in eggs were 2,800 +/- 520 and 59 +/- 5 ng/g wet weight in the contaminated area and the reference area, respectively. Eggs from the contaminated area were significantly enriched in tri-, penta-, and hepta-PCBs relative to the reference area. Blood from adults in the contaminated area averaged 475 +/- 200 and 125 +/- 34 ng/g wet weight for males and females, respectively. In the reference area, blood PCB concentrations were 7 +/- 3 and 4 +/- 1 ng/g wet weight for males and females, respectively. Significant positive relationships were found between carapace length and blood PCB concentration for both sexes in the contaminated area; however, only a marginal relationship was found between female carapace length and concentration of PCBs in their eggs. Our results suggest that PCB contamination of the upper Hudson River presents risks of establishing high body burdens and of maternal transfer of PCBs to eggs, although our measures of gross morphology revealed no discernable expression of abnormal sexual development or reproduction.

Measurement of polybrominated diphenyl ethers on hand wipes: estimating exposure from hand-to-mouth contact.

Estimates of exposure to the flame-retardant polybrominated diphenyl ethers (PBDEs) in dust are very poor due to limited knowledge about dust ingestion. This study was undertaken to determine if PBDEs could be measured on hand wipes, and if so, to determine the distribution of levels present on the skin surface area to provide preliminary exposure estimates from hand-to-mouth contact. Hand wipes were collected from 33 individuals residing in the United States using sterile gauze pads soaked in isopropyl alcohol. The total PBDE residue collected on the wipes ranged from 2.60 to 1982 ng, with a median value of 130 ng, or normalized to hand surface area, a concentration of 135 pg/cm2. The fully brominated congener, BDE 209, was also detected and ranged from < DL to 270 ng with a median value of 26 ng. Congener patterns observed on the wipes were similar to patterns observed in house dust samples, consisting of congeners associated with the PentaBDE and DecaBDE mixtures, suggesting that the source of PBDEs to the hands may be dust particles. However, PBDE hand residues may also be a result of direct contact with PBDE-laden products, leading to adsorption to the skin surface oils. Repeated wipe sampling from three individuals suggests that sigmaPBDE levels on the hand may be relatively consistent for some individuals but not for others. Furthermore, levels of sigmaPBDEs were greater on the bottom of the hands relative to the top of the hands. Using these values we have calculated potential human exposure from hand-to-mouth contact. The median exposure estimates for children and adults are 1380 and 154 ng/day, respectively, whereas the 95th percentile exposure estimates were 6090 and 677 ng/day, respectively. These estimates are greater than dietary intake rates and suggest hand-to-mouth contact may be a key exposure route for PBDEs.