Predictors of psychosocial adaptation in children with CHD.

Survival of CHD has significantly improved, but children with CHD remain susceptible to neurodevelopmental and psychosocial impairments. Our goal was to investigate the association between socio-demographic factors and psychosocial adaptation for future intervention. A retrospective cross-sectional study of an independent children's hospital's records was conducted. Psychosocial adaptation was measured by the Pediatric Cardiac Quality of Life Inventory Psychosocial Impact score (range 0-50, higher score indicates greater psychosocial adaptation). Bivariate and regression analyses were performed to estimate relationships between Psychosocial Impact score and socio-demographic variables including Child Opportunity Index, family support, financial support, academic support, and extracurricular activities. A total of 159 patients were included. Compared to patients in high opportunity neighbourhoods, patients in low opportunity neighbourhoods had a 9.27 (95% confidence interval [-17.15, -1.40], p = 0.021) point lower Psychosocial Impact score, whereas patients in moderate opportunity neighbourhoods had a 15.30 (95% confidence interval [-25.38, -5.22], p = 0.003) point lower Psychosocial Impact score. Compared to patients with adequate family support, those with limited support had a 6.23 point (95% confidence interval [-11.82, -0.643], p = 0.029) lower Psychosocial Impact score. Patients in moderate opportunity neighbourhoods had a higher Psychosocial Impact score by 11.80 (95% confidence interval [1.68, 21.91], p = 0.022) when they also had adequate family support compared to those with limited family support. Our findings indicate that among children with CHD, psychosocial adaptation is significantly impacted by neighbourhood resources and family support structures. These findings identify possible modifiable and protective factors to improve psychosocial adaptation in this vulnerable population.

Phenomenological Constraints on the Transport Properties of QCD Matter with Data-Driven Model Averaging.

Using combined data from the Relativistic Heavy Ion and Large Hadron Colliders, we constrain the shear and bulk viscosities of quark-gluon plasma (QGP) at temperatures of ∼150-350 MeV. We use Bayesian inference to translate experimental and theoretical uncertainties into probabilistic constraints for the viscosities. With Bayesian model averaging we propagate an estimate of the model uncertainty generated by the transition from hydrodynamics to hadron transport in the plasma's final evolution stage, providing the most reliable phenomenological constraints to date on the QGP viscosities.

Current status of scoliosis school screening: targeted screening of underserved populations may be the solution.

OBJECTIVES: The growing body of evidence documenting the effectiveness of brace treatment for scoliosis has renewed interest in potential benefits of early detection through school screening. We aimed to assess the prevalence and identify barriers of screening. We hypothesized that school screening is more frequent in schools that have a nurse on staff compared to schools without nurse on staff. STUDY DESIGN: A questionnaire survey. METHODS: All schools located in four counties in Louisiana, United States of America comprising the New Orleans metropolitan area between September 2015 and January 2016 were contacted by phone to assess rates of scoliosis screening, report the availability of a school nurse, and specify barriers if screening was not performed. RESULTS: Two hundred and ninety-one schools responded to the survey including 152 public, 30 charter, and 109 private schools (101 had religious affiliation). A staff nurse was available in 180 schools (61.8%). Only 21 schools (7.2%) performed scoliosis screening. The majority were charter schools (11 schools), while six were private and four were public (P < 0.0001). Of these 21 schools, 16 (76.2%) had a nurse on staff while five schools did not (P = 0.16). Lack of a referral pathway in the event of a positive screen was the most common barrier to performing scoliosis screening. CONCLUSION: Scoliosis screening is infrequent in the examined school districts. Efforts to support school screening can facilitate clear referral pathways for schools in the event of a positive screen. These findings suggest a potential need for different pathway of scoliosis screening. Pediatricians and family physicians can assist with scoliosis screening during the annual visit. While universal screening is overburdensome and likely unnecessary, targeted screening of underserved populations may prove to be beneficial. Further investigation should include assessment of the economic viability of targeted screening programs. LEVEL OF EVIDENCE: IV.

Dimensions of the paediatric femur: anatomical limitations of flexible intramedullary nailing.

PURPOSE: Although spica casting remains the benchmark for treating diaphyseal femur fractures in preschool children, some authors advocate using flexible intramedullary nails in certain situations. The aim of the current study was to evaluate the anatomic feasibility of flexible nailing in young children. METHODS: Consecutive patients between the ages of zero and ten years with normal femurs who received femur radiographs at a tertiary paediatric hospital over a two-year period were included. Anteroposterior femur radiographs were evaluated for length and isthmus width measurements. Each femur was templated for flexible nail size. The proportions of each age group capable of accommodating two flexible nails up to 4.0 mm in size were determined and compared. RESULTS: A total of 381 full-length femur radiographs were reviewed. There was a strong, direct linear relationship between age and femoral length (R2 = 0.896) and a moderate correlation between age and femoral isthmus width (R2 = 0.417). Although the percentage of femurs able to accommodate flexible nails continued to increase with age, this increase did not represent a significant difference when comparing preschool-aged children with older age groups. CONCLUSIONS: Age and femoral length demonstrated a strong, positive correlation while age and isthmus width had weaker correlation. The ability of femurs to accommodate flexible nails increased with age with most children age two years and older able to accommodate two flexible nails of at least 2.5 mm in size. LEVEL OF EVIDENCE: III.

Fluoroscopic imaging overestimates the screw tip to subchondral bone distance in a cadaveric model of slipped capital femoral epiphysis.

PURPOSE: Intra-operative imaging plays a key role in screw placement for slipped capital femoral epiphysis (SCFE). Complications have been associated with inadequate screw position. The purpose of this study was to evaluate computed tomography (CT) (3D fluoroscopy) and standard fluoroscopy (C-arm) images as compared with direct anatomic measurement to determine final screw position in a cadaveric SCFE model. METHODS: Osteotomy with pinning was performed at the physeal scar in ten cadaveric hips. A standardised approach-withdrawal technique was performed with C-arm images taken at 15° increments. We also obtained a CT (3D fluoroscopy) scan of each hip. The screw tip-subchondral bone (STSB) distance was measured on digital imaging software and also with a digital calliper directly when the femoral head was cut in plane to expose the STSB distance anatomically. Statistical analysis included t-tests and Fisher's exact test. RESULTS: Moderate SCFE osteotomies were achieved with a mean Southwick angle (39.5° ± 7°). The 60° fluoroscopic image was found to be the most representative image (41% of the time) compared with both anteroposterior (AP) and lateral images (8% and 21%). Both fluoroscopy (2.7 ± 0.8 mm, p < 0.001) and CT (1.6 ± 0.7 mm, p = 0.03) overestimated the STSB distance compared with direct measurement (0.94 ±  0.51 mm). Two-thirds (67%) of CT measurements were within 1 mm of the cadaveric measurement, while only 20% of C-arm measurements fulfilled this criterion (p = 0.04). CONCLUSIONS: Both standard fluoroscopy and CT overestimated the STSB distance when compared with direct measurement in a cadaveric model of SCFE. Surgeons should be aware of the limitations of intra-operative imaging to determine the STSB distance. We suggest that using the known pitch of a screw (2.9 mm in a 7.3-mm cannulated screw) as an intra-operative tool to help guide screw placement.

Improvement of scalp and nail lesions with ixekizumab in a phase 2 trial in patients with chronic plaque psoriasis.

BACKGROUND: Scalp and nail psoriasis have a major impact on quality of life and are traditionally resistant to therapy. Ixekizumab is a monoclonal antibody that targets IL-17A, a key cytokine in psoriasis pathogenesis. OBJECTIVE: Changes in nail and scalp psoriasis associated with ixekizumab treatment were evaluated in a post hoc analysis of a phase 2 study comprising a 20-week randomized, placebo-controlled (RCT) period and 48 weeks of an open-label extension (OLE) period. METHODS: There were 142 patients with moderate-to-severe plaque psoriasis at baseline of the RCT. Patients were randomized to receive placebo, 10, 25, 75 or 150 mg of ixekizumab injected subcutaneously at weeks 0, 2, 4, 8, 12 and 16. In the OLE, all patients received 120 mg ixekizumab every 4 weeks. Nail Psoriasis Severity Index (NAPSI) and Psoriasis Scalp Severity Index (PSSI) were used to evaluate nail and scalp psoriasis respectively. Fifty-eight (41.0%) patients had nail psoriasis (NAPSI > 0) and 105 (74.0%) had scalp psoriasis (PSSI > 0) at baseline; these cases were evaluated for the present analyses. RESULTS: At RCT week 20, patients with scalp psoriasis in the 25-, 75- and 150-mg groups had significant mean change and percent improvement from baseline PSSI of -16.3 (75.3%; P = 0.001), -11.6 (83.7%; P = 0.001) and -18.2 (82.2%; P < 0.001) respectively compared to -6.0 (18.8%) in placebo. Patients with nail psoriasis in the 75- and 150-mg groups had significant improvements from baseline NAPSI of -26.3 (63.8%; P = 0.003) and -23.1 (52.6%; P = 0.009) respectively compared to 0.4 (-1.7%) in placebo. By OLE week 48, 78.0% of patients with scalp psoriasis and 51.0% of patients with nail psoriasis experienced complete resolution of lesions (PSSI = 0 or NAPSI = 0). CONCLUSIONS: Ixekizumab monotherapy improved scalp psoriasis quickly with maintenance of clinical response and complete resolution of plaques in the majority of patients. Additionally, over 50.0% of patients with nail psoriasis experienced complete resolution of nail lesions by OLE week 48.

Efficacy and safety of open-label ixekizumab treatment in Japanese patients with moderate-to-severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis.

BACKGROUND: Ixekizumab, an anti-IL-17A monoclonal antibody, demonstrated a high level of efficacy in moderate-to-severe plaque psoriasis (PP) patients. OBJECTIVE: To evaluate the efficacy and safety of open-label ixekizumab in Japanese patients with moderate-to-severe PP, erythrodermic psoriasis (EP) and generalized pustular psoriasis (GPP). METHODS: Patients received 160-mg subcutaneous ixekizumab injection at Week 0, 80-mg every 2 weeks through Week 12 and 80-mg every 4 weeks through Week 24. Efficacy and safety are reported through 24 weeks; additional safety data are available for some patients. RESULTS: A total of 78 patients with PP, 8 with EP and 5 with GPP enrolled. In PP patients, PASI75 and PASI90 response rates were 98.7% (77/78) and 83.3% (65/78) at Week 12 respectively. In EP patients, PASI75 and PASI90 were 100.0% (8/8) and 62.5% (5/8) and in GPP patients were 80.0% (4/5) and 60.0% (3/5). Overall, 84.0% (76/91) had a treatment-emergent AE through ≥24 weeks. There were no serious AEs, deaths, cases of tuberculosis or invasive fungal infections. LIMITATIONS: No control group and small sample sizes, especially for EP and GPP. CONCLUSION: By Week 12, nearly all patients with PP, EP and GPP achieved PASI75. The safety profile was consistent with reported results and no unexpected safety signals were observed.

Prevalence of dental trauma and use of mouthguards in rugby union players.

BACKGROUND: There is a high prevalence of orofacial trauma in rugby union players. Mouthguards reduce complications following dental injuries, should dental injuries occur. The aim of this study was to investigate the prevalence of oral trauma and the significance of mouthguard use in adult amateur rugby union players in New South Wales, Australia. METHODS: Questionnaires were distributed to players in rugby union clubs. It questioned players about their mouthguard use and orofacial trauma experience; the type of injury, complications, if a mouthguard was worn, where treatment was sought and outcome. RESULTS: The prevalence of orofacial trauma in rugby union players is 64.9%. The most common injury was laceration to intraoral and extraoral soft tissues at 44.5%. Of all orofacial injuries reported, 41.9% were to the dentition. Following dental injury, loss of the tooth was the most common complication (34.7%). 76.9% of players wore mouthguards. By wearing a mouthguard, the risk reduction for ongoing complications following dental injuries was 18.5% (p-value = 0.009). Of these, 10.4% (p-value = 0.45) represented loss of the tooth. CONCLUSIONS: Rates of orofacial trauma and complications in amateur rugby union players are high in Australia. Use of mouthguards results in significant risk reduction for complications following dental injuries, including loss of tooth.

A pilot study of the safety and efficacy of picolinic acid gel in the treatment of acne vulgaris.

BACKGROUND: Cost limitations, adverse effects or lack of efficacy limit the use of current topical therapies in mild to moderate acne vulgaris. OBJECTIVES: To determine the safety and efficacy of picolinic acid, a novel zinc finger therapy, in the treatment of mild to moderate acne vulgaris. METHODS: Twenty subjects with mild to moderate acne vulgaris were treated at our centre during an open-label study with 10% picolinic acid gel (PCL-016) twice daily to the face over 12 weeks. RESULTS: Fifteen patients completed the 12-week open-label study. A reduction of 58.2% (P < 0.001) in mean total lesion count, 55.5% (P < 0.001) in mean inflammatory lesion count and 59.7% (P < 0.005) in noninflammatory lesion count was seen in this population. No serious adverse events or clinically significant changes in laboratory values were noted. CONCLUSIONS: Results from this study suggest that 10% picolinic acid gel applied twice daily may be safe and effective in the treatment of mild to moderate acne vulgaris.

Scleromyxoedema: treatment of cutaneous and systemic manifestations with high-dose intravenous immunoglobulin.

Scleromyxoedema is a rare disease characterized by cutaneous sclerosis, mucin deposition and paraproteinaemia. Internal disease is common, particularly musculoskeletal, gastrointestinal and central nervous system involvement. We report a series of three consecutive patients with scleromyxoedema treated with high-dose intravenous immunoglobulin (hdIVIg). Each of the three patients had relatively low levels of a highly basic IgG-lambda paraprotein, and each has demonstrated a sustained response of both their cutaneous and extracutaneous disease to hdIVIg. As all patients had perioral skin involvement and microstomia, one measure of cutaneous improvement was the increase in intraincisor distance. Extracutaneous manifestations of scleromyxoedema that improved included ureteral stricture, vocal strength and dysphagia.

Incidence of cryptorchidism in dogs and cats.

Over a period of 54 months, 3518 dogs and 3806 cats were castrated; 240 of the dogs and 50 of the cats were cryptorchid. Pedigree dogs, in particular the German shepherd dog, boxer and chihuahua were over-represented. Among the dogs, right-sided inguinal cryptorchidism was the most common form, followed by right-sided abdominal cryptorchidism. The location of the affected testicle(s) was most variable in the boxer. Among the cats, left- or right-sided inguinal cryptorchidism were the most common forms of the condition.

The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice.

Both human GH (hGH) and a lipolytic fragment (AOD9604) synthesized from its C-terminus are capable of inducing weight loss and increasing lipolytic sensitivity following long-term treatment in mice. One mechanism by which this may occur is through an interaction with the beta-adrenergic pathway, particularly with the beta(3)-adrenergic receptors (beta(3)-AR). Here we describe how hGH and AOD9604 can reduce body weight and body fat in obese mice following 14 d of chronic ip administration. These results correlate with increases in the level of expression of beta(3)-AR RNA, the major lipolytic receptor found in fat cells. Importantly, both hGH and AOD9604 are capable of increasing the repressed levels of beta(3)-AR RNA in obese mice to levels comparable with those in lean mice. The importance of beta(3)-AR was verified when long-term treatment with hGH and AOD9604 in beta(3)-AR knock-out mice failed to produce the change in body weight and increase in lipolysis that was observed in wild-type control mice. However, in an acute experiment, AOD9604 was capable of increasing energy expenditure and fat oxidation in the beta(3)-AR knock-out mice. In conclusion, this study demonstrates that the lipolytic actions of both hGH and AOD9604 are not mediated directly through the beta(3)-AR although both compounds increase beta(3)-AR expression, which may subsequently contribute to enhanced lipolytic sensitivity.

Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment.

OBJECTIVE: To observe the chronic effects of human growth hormone (hGH) and AOD9604 (a C-terminal fragment of hGH) on body weight, energy balance, and substrate oxidation rates in obese (ob/ob) and lean C57BL/6Jmice. In vitro assays were used to confirm whether the effects of AOD9604 are mediated through the hGH receptor, and if this peptide is capable of cell proliferation via the hGH receptor. METHOD: Obese and lean mice were treated with hGH, AOD or saline for 14 days using mini-osmotic pumps. Body weight, caloric intake, resting energy expenditure, fat oxidation, glucose oxidation, and plasma glucose, insulin and glycerol were measured before and after treatment. BaF-BO3 cells transfected with the hGH receptor were used to measure in vitro 125I-hGH receptor binding and cell proliferation. RESULTS: Both hGH and AOD significantly reduced body weight gain in obese mice. This was associated with increased in vivo fat oxidation and increased plasma glycerol levels (an index of lipolysis). Unlike hGH, however, AOD9604 did not induce hyperglycaemia or reduce insulin secretion. AOD9604 does not compete for the hGH receptor and nor does it induce cell proliferation, unlike hGH. CONCLUSIONS: Both hGH and its C-terminal fragment reduce body weight gain, increase fat oxidation, and stimulate lipolysis in obese mice, yet AOD9604 does not interact with the hGH receptor. Thus, the concept of hGH behaving as a pro-hormone is further confirmed. This data shows that fragments of hGH can act in a manner novel to traditional hGH-stimulated pathways.

Antinuclear antibodies in dermatology.

Antinuclear antibodies are used in the diagnosis and evaluation of patients with connective tissue diseases. The study of antinuclear antibodies has also fundamentally expanded our understanding of nuclear anatomy and function. This article reviews the clinically relevant antinuclear antibodies and their disease associations. Developing an understanding of the utilities and limitations of antinuclear antibodies is essential to providing the expert diagnoses prognoses, and care expected of a dermatologist.

Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism.

A small synthetic peptide sequence of human growth hormone (hGH), AOD-9401, has lipolytic and antilipogenic activity similar to that of the intact hormone. Here we report its effect on lipid metabolism in rodent models of obesity and in human adipose tissue to assess its potential as a pharmacological agent for the treatment of human obesity. C57BL/6J (ob/ob) mice were orally treated with either saline (n = 8) or AOD-9401 (n = 10) for 30 days. From day 16 onward, body weight gain in AOD-9401-treated animals was significantly lower than that of saline-treated controls. Food consumption did not differ between the two groups. Analyses of adipose tissue ex vivo revealed that AOD-9401 significantly reduced lipogenic activity and increased lipolytic activity in this tissue. Increased catabolism was also reflected in an acute increase in energy expenditure and glucose and fat oxidation in ob/ob mice treated with AOD-9401. In addition, AOD-9401 increased in vitro lipolytic activity and decreased lipogenic activity in isolated adipose tissue from obese rodents and humans. Together, these findings indicate that oral administration of AOD-9401 alters lipid metabolism in adipose tissue, resulting in a reduction of weight gain in obese animals. The marked lipolytic and antilipogenic actions of AOD-9401 in human adipose tissues suggest that this small synthetic hGH peptide has potential in the treatment of human obesity.

Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials.

BACKGROUND: Pamidronate therapy previously has been shown to reduce skeletal complications effectively for up to 12 months in breast carcinoma patients with bone metastases. The current study data provide further follow-up results regarding the effects of long term (up to 24 months) pamidronate treatment in women with breast carcinoma and osteolytic metastases. METHODS: Follow-up results from two prospective, multicenter, randomized, double-blind, placebo-controlled intervention trials conducted at academic and community oncology centers were combined to provide a large data set with which to evaluate the long term efficacy and safety of pamidronate therapy. Seven hundred fifty-four women with Stage IV breast carcinoma and osteolytic metastases were randomized to the 2 treatment arms of the trial. Three patients were excluded from the intent-to-treat population for the analysis. A total of 751 evaluable patients were randomized to receive either a 90-mg intravenous pamidronate infusion (367 patients) or a placebo infusion (384 patients) every 3-4 weeks. The primary outcome measures were skeletal morbidity rate (events/year), proportion of patients developing a skeletal complication, and time to first skeletal complication. RESULTS: Of the 367 women receiving pamidronate, 115 (31.3%) completed the trial and 81 (22.1%) discontinued the study due to adverse events. Of the 384 women who received placebo, 100 (26.0%) completed the study and 76 (19.8%) discontinued the study due to adverse events. The skeletal morbidity rate was 2.4 in the pamidronate group and 3.7 in the placebo group (P < 0.001). In the pamidronate group, 186 of the 367 patients (51%) had skeletal complications compared with 246 of the 384 patients in the placebo group (64%) (P < 0.001). The median time to first skeletal complication was 12.7 months in the pamidronate group and 7 months in the placebo group (P < 0.001). Six patients treated with pamidronate discontinued treatment due to drug-related adverse events. Pain and analgesic scores were significantly worse in the placebo group compared with those patients in the pamidronate group. CONCLUSIONS: In the current study, monthly infusions of 90 mg of pamidronate as a supplement to antineoplastic therapy were found to be well tolerated and superior to antineoplastic therapy alone in preventing skeletal complications and palliating symptoms for at least 24 months in breast carcinoma patients with osteolytic bone metastases.

The conformational and biological analysis of a cyclic anti-obesity peptide from the C-terminal domain of human growth hormone.

The three-dimensional solution structure of antiobesity drug (AOD), a 15-residue, disulfide-bonded, cyclic peptide, cyclo(6,13)-H2N-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe-OH, derived from the C-terminal domain of the human growth hormone (hGH) (residues 177-191) was determined using two-dimensional 1H NMR spectroscopy. AOD stimulates lipolysis and inhibits lipogenesis, in vitro, in rodent, porcine and human adipose tissues. These biological effects suggest that AOD is a potential therapeutic candidate for the treatment of obesity. Conformational studies of AOD were conducted in aqueous solution and in water/dimethylsulfoxide mixtures. In general, spectral quality was superior in the water/ dimethylsulfoxide mixtures. The cyclic region of AOD in water/dimethylsulfoxide adopts type I beta-turns at residues Ser8-Val9-Glu10-Gly11 and Ser12-Cys13-Gly14-Phe15, each preceded by loop-like structures. Comparison of the conformation of this peptide with residues 177-191 in the native hGH protein X-ray crystal structure indicates that the synthetic peptide retains some structural similarity to the intact protein. This study provides evidence that the C-terminal region of hGH is a specific functional domain of the multifunctional hGH protein.