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Currently, there are no standardized requirements for pedagogical preparation for nurse educators at the state and national level. Various stakeholders have identified an issue in the preparation of nurse educators in academia. Current recommendations are that faculty have a master's or doctoral degree in nursing (American Association of Colleges of Nursing, 2017); however, requirements do not include educational preparation prior to or concurrent with starting a faculty position. This policy paper highlights a recommendation to require one of the following: the Certified Nurse Educator credential or certificate in teaching for educators without prior formal education in pedagogy. Outcomes of such a requirement would include nurse educators have a better understanding of the science of nursing education and preparation related to teaching. A second outcome is students receive an education that uses evidence-based teaching methods. • Currently, there is no standardized educational requirement to teach in nursing programs • Only 10,695 nurse educators are certified in the United States • Requiring pedagogical development impacts students, academic institutions, educators, and national regulatory bodies • Certified Nurse Educators have the potential to improve student outcomes [ABSTRACT FROM AUTHOR]

[Display omitted] Dedicator of cytokinesis 8 (DOCK8)-deficient patients have severe eczema, elevated IgE, and eosinophilia, features of atopic dermatitis (AD). We sought to understand the mechanisms of eczema in DOCK8 deficiency. Skin biopsy samples were characterized by histology, immunofluorescence microscopy, and gene expression. Skin barrier function was measured by transepidermal water loss. Allergic skin inflammation was elicited in mice by epicutaneous sensitization with ovalbumin (OVA) or cutaneous application of Staphylococcus aureus. Skin lesions of DOCK8-deficient patients exhibited type 2 inflammation, and the patients' skin was colonized by S aureus, as in AD. Unlike in AD, DOCK8-deficient patients had a reduced FOXP3:CD4 ratio in their skin lesions, and their skin barrier function was intrinsically intact. Dock8 −/− mice exhibited reduced numbers of cutaneous T regulatory (Treg) cells and a normal skin barrier. Dock8 −/− and mice with an inducible Dock8 deletion in Treg cells exhibited increased allergic skin inflammation after epicutaneous sensitization with OVA. DOCK8 was shown to be important for Treg cell stability at sites of allergic inflammation and for the generation, survival, and suppressive activity of inducible Treg cells. Adoptive transfer of wild-type, but not DOCK8-deficient, OVA-specific, inducible Treg cells suppressed allergic inflammation in OVA-sensitized skin of Dock8 −/− mice. These mice developed severe allergic skin inflammation and elevated serum IgE levels after topical exposure to S aureus. Both were attenuated after adoptive transfer of WT but not DOCK8-deficient Treg cells. Treg cell dysfunction increases susceptibility to allergic skin inflammation in DOCK8 deficiency and synergizes with cutaneous exposure to S aureus to drive eczema in DOCK8 deficiency. [ABSTRACT FROM AUTHOR]

• Measurement of functional dart thrower's motion is clinically feasible. • Lower functional dart thrower's motion was noted on affected wrists in postoperative and nonoperative patients. Cross-sectional and descriptive study Functional dart thrower's motion (F-DTM) is an obliquely oriented wrist motion that occurs in activities such as throwing and drinking from a cup. There is limited data on clinical measurement of F-DTM. The purpose of this study was to 1) describe and establish reference scores for F-DTM measurement for nonoperative and postoperative wrist patients 2) compare F-DTM between the affected and nonaffected sides and 3) determine F-DTM score agreement across three consecutive trials. Two certified hand therapists evaluated F-DTM in consecutive adult patients with a unilateral wrist condition undergoing nonoperative or postoperative therapy. Three trials of goniometer measurements for radial extension (RE) and ulnar flexion (UF) were assessed on the nonaffected and affected wrists. A total arc F-DTM was computed. Mean, 95% confidence intervals (CI), and Cohen's d effect size described side-to-side differences in RE, UF, and total arc F-DTM. Agreement in scores across trials was assessed with an intraclass correlation coefficient (ICC). Thirty-one nonoperative (mean ± SD age = 40.0 ± 13.9 years, 74% female, 94% right hand dominant) and 44 postoperative patients (mean ± SD age = 44.9 ± 14.9 years, 66% female, 84% right hand dominant) were enrolled. The average side-to-side difference, in degrees, in the nonoperative group was -6.4 (95% CI: -9.4 to -3.4, Cohen's d = 0.8) for RE, -10.4 (-16.7 to -4.0, d = 0.6) for UF, and -16.8 (-24.3 to -9.2, d = 0.8) for total arc F-DTM. The average side-to-side difference in the postoperative group was -33.6 (-38.8 to -28.3, d = 1.9) for RE, -34.7 (-40.6 to -28.7, d = 1.8) for UF, and -68.2 (-77.9 to -58.5, d = 2.1) for total arc F-DTM. The range of ICCs for F-DTM measurements was 0.82-0.96. Goniometer measurement of F-DTM is a clinically feasible method to quantify functional motion loss in an injured wrist population, particularly patients with postoperatively managed wrist conditions. [ABSTRACT FROM AUTHOR]

Given the enormous symptom relief benefit seen with cardiac myosin inhibitors, there is renewed focus to correctly identify hypertrophic cardiomyopathy (HCM) patients as obstructive versus non-obstructive. Overall, two thirds of HCM patients have clinically significant obstruction of blood flow out of the left ventricular outflow tract (LVOTO). A third of HCM patients, however, will only experience obstruction during challenging provocative maneuvers such as Valsalva, during volume depletion, or with exercise. Patients with "masked obstruction" are frequently mislabeled and subsequently mismanaged as non-obstructive. This study aims to identify features seen on cardiac magnetic resonance imaging (CMR) and on transthoracic echocardiography (TTE) that should heighten awareness that occult obstruction may be present, potentially prompting physicians to obtain exercise stress echocardiography. This study utilized retrospective data analysis from a large, single-center cohort over a six-month period. Subjects were included if both stress echocardiography and CMR were available. LVOTO was defined as peak LV outflow tract gradient ≥30 mmHg. Subjects were divided in to 1) Absent, 2) Masked and 3) Overt LVOTO. CMR was used to assess anatomical differences between groups. Continuous data was compared using ANOVA analysis, with secondary multiple comparison tests. Sixty one patients (30:31 M:F)(Age = 57.1 ± 14.4 yrs.) were included; Absent (n = 27), Masked (n = 21), Overt (n = 13). CMR data with ANOVA analysis is provided in Table 1. Multiple comparison testing of the Zone of Coaptation Length was significant between the Absent v. Masked groups (mean = 7.8 v. 10.1, 95% CI: -4.6 to -0.1, p = 0.04). (Figure 1) The height of the zone of coaptation is best understood as the length of contact between the anterior and posterior mitral leaflets in the basal to apical axis during systole. In this cohort, longer zone of coaptation lengths were more likely to associate with masked LVOTO than overt or absent LVOTO. During hyperdynamic contractility, this highly mobile region of the sub-valvular apparatus is likely pushed into the LVOT due to the Venturi Effect and/or from apical displacement of the papillary heads. Once in the LVOT, drag force is exerted on the apparatus resulting in obstruction. Anterior mitral length, a feature thought to predict obstruction from the echocardiography literature, did not predict masked or overt obstruction. Further investigation is warranted to better understand how cardiac MRI could prompt physicians to look for masked obstruction, as stress echocardiography is commonly underutilized. [ABSTRACT FROM AUTHOR]

Objective: Knee osteoarthritis (OA) is predominantly characterized by pain with weight-bearing activities. Pain at rest also occurs but the mechanisms for this are not clear. We evaluated the relations of nociceptive signal alterations to weight-bearing and non-weight-bearing pain in knee OA.Design: We used data from a NIH-funded longitudinal cohort of older adults with or at risk of knee OA. We evaluated quantitative sensory testing (QST) measures (pressure pain threshold (PPT) at patellae and the wrist; mechanical temporal summation (TS); conditioned pain modulation (CPM)). Each WOMAC pain question was dichotomized as having at least moderate pain, and we further categorized them as weight-bearing pain and non-weight-bearing pain. We evaluated the relation of QST measures to each pain outcome using logistic regression, adjusting for potential confounders.Results: 2,749 participants (5,479 knees) were included (mean age 64 ± 11, 57% female). Each SD unit decrease in patellar PPT was associated with greater odds of both weight-bearing pain (OR 1.51 (95% CI 1.27, 1.79)) and non-weight-bearing pain (OR 1.46 (1.20-1.77)), while wrist PPT was associated with greater odds of weight-bearing pain (OR 1.27 (1.15, 1.39)) but only with pain during sitting/lying (OR 1.20 (1.01, 1.43)). TS was significantly associated with greater odds of pain with walking and stairs (OR 1.11 (1.01, 1.23), 1.11 (1.03, 1.20), respectively). CPM was not associated with any pain outcomes.Conclusions: Our findings challenge the hypothesis that non-weight-bearing pain may reflect greater pain sensitization and/or inefficient CPM than weight-bearing pain in knee OA, suggesting other mechanisms are likely responsible. [ABSTRACT FROM AUTHOR]

Solar urticaria is a rare photodermatosis characterized by rapid-onset sunlight-induced urticaria, but its pathophysiology is not well understood. We sought to define cutaneous cellular and molecular events in the evolution of solar urticaria following its initiation by solar-simulated UV radiation (SSR) and compare with healthy controls (HC). Cutaneous biopsy specimens were taken from unexposed skin and skin exposed to a single low (physiologic) dose of SSR at 30 minutes, 3 hours, and 24 hours after exposure in 6 patients with solar urticaria and 6 HC. Biopsy specimens were assessed by immunohistochemistry and bulk RNA-sequencing analysis. In solar urticaria specimens, there was enrichment of several innate immune pathways, with striking early involvement of neutrophils, which was not observed in HC. Multiple proinflammatory cytokine and chemokine genes were upregulated (including IL20 , IL6 , and CXCL8) or identified as upstream regulators (including TNF, IL-1β, and IFN-γ). IgE and FcεRI were identified as upstream regulators, and phosphorylated signal transducer and activator of transcription 3 expression in mast cells was increased in solar urticaria at 30 minutes and 3 hours after SSR exposure, suggesting a mechanism of mast cell activation. Clinical resolution of solar urticaria by 24 hours mirrored resolution of inflammatory gene signature profiles. Comparison with available datasets of chronic spontaneous urticaria showed transcriptomic similarities relating to immune activation, but several transcripts were identified solely in solar urticaria, including CXCL8 and CSF2/3. Solar urticaria is characterized by rapid signal transducer and activator of transcription 3 activation in mast cells and involvement of multiple chemotactic and innate inflammatory pathways, with FcεRI engagement indicated as an early event. [ABSTRACT FROM AUTHOR]

In large metropolitan areas such as Toronto, planners are increasingly relying on urban densification to accommodate population growth sustainably. While infill developments support the city's long-term climate goals, on-going construction impacts air quality for local communities. Understanding how neighborhoods are impacted by these localized sources can be achieved by implementing a network of low-cost sensors. In this study, we placed twelve low-cost sensors on balconies in a Toronto neighborhood impacted by various construction projects. The study aims to capture the impact of construction and heavy-duty traffic and provide a better understanding of spatial variability in fine particulate matter (PM 2.5). The locations were compared using time series analysis, inverse distance weighing (IDW) for spatial heterogeneity, and spectral analysis to quantify the contribution of local sources. Sensors exhibited inter-sensor variability, which was corrected upon calibration. Sensors located near and far from construction sites showed similar temporal trends, however locations near construction sites measured greater PM 2.5 concentrations, where the hourly average concentration for sensors near construction sites ranged between 6.8 and 8.5 μg/m3 and sensors further away ranged between 5.4 and 6.2 μg/m3. Spatial variability was also captured by IDW where sensors near construction sites were more heterogenous and exhibited greater concentrations. Spectral analysis demonstrated that local sources contributed up to 23% of PM 2.5 levels near construction while distant locations had a maximum of 11% local contribution. By using a network of sensors, we explore how construction sites create localized hotspots within a neighborhood. [Display omitted] • Low-cost PM 2.5 sensors capture spatiotemporal variability within a construction hub. • Residents near construction sites experience higher spikes and averages for PM 2.5 • Spectral analysis of PM 2.5 time series isolates the contribution of local sources. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of 3 distinct comparison groups on associations between placental abnormalities and neonatal hypoxic-ischemic encephalopathy (HIE).Study Design: This single-center, prospective case-control study of singletons of gestational age ≥36 weeks with predefined criteria for HIE (n = 30) and 3 control groups was conducted from June 2015 to January 2018. The control groups were infants born by repeat cesarean delivery (n = 60), infants born small for gestational age (SGA; n = 80), and infants receiving positive-pressure ventilation (PPV) at birth (n = 70). One pathologist blinded to infant category reviewed placental sections using the Amsterdam Placental Workshop criteria. Logistic regression with group contrasts relative to HIE was used to analyze primary placental pathologies, and ORs with 95% CIs provided effect sizes.Results: The odds of maternal vascular malperfusion were increased among HIE group placentas compared with placentas of the repeat cesarean delivery (OR, 4.50; 95% CI, 1.45-14.00) and PPV (3.88; 1.35-11.16) groups, but not those of the SGA group. The odds of fetal vascular malperfusion were increased in the HIE group compared with the SGA group (OR, 9.75; 95% CI, 1.85-51.51). The odds of acute chorioamnionitis were higher in the HIE group compared only with the repeat cesarean delivery group, reflecting a similar incidence of chorioamnionitis in SGA group and PPV group placentas. The absence of placental findings was lowest in the HIE group (6.7%), followed by the SGA (18.8%), PPV (31.4%), and repeat cesarean delivery (75%) groups.Conclusions: Associations with placental abnormalities among infants with HIE varied based on the specific placental abnormality and the control group. Potentially important associations between placental pathology and HIE may be obscured if control groups are not well designed. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the fracture toughness and other properties of an experimental bulk-fill resin-based dental restorative material with five market-leading bulk-fill composites. An experimental bulk-fill composite/SDI Limited (SDI) and five commercial products (Filtek™ One Bulk Fill (A2)/3 M™ (FTO), Tetric® PowerFill (IVA)/Ivoclar Vivadent (TPF), SDR® Flow+/Dentsply Sirona (SDR), EverX Posterior™/GC Dental (EXP), and EverX Flow™ (Bulk)/GC Dental (EXF)) were evaluated and compared. All composites were dispensed according to each manufacturer's instructions and light-cured with an LED curing light (Radii Xpert, SDI). Strength and opacity specimens were stored in a humidor (37°C/60 min) before demolding and immersed in deionized water (37°C/23 h) before testing. Fracture toughness samples (3 ×5 x 25 mm) were prepared with a 2.5 mm central notch and fractured on a universal testing machine (Instron® model 5942). Fracture toughness was calculated using single edge notch bend test ASTM D5045. Flexural strength and modulus were evaluated according to ISO-4049:2019. Volumetric shrinkage was evaluated via density balance (Mettler Toledo MS204S) according to ISO-17304:2013. Depth of cure was evaluated according to ISO-4049:2019(E), using a stainless steel mold of diameter 4 mm and depth 12 mm. All composites were light-cured for 20 s using an LED curing light (Radii Xpert, SDI) calibrated to 1500 mW/cm2. Opacity was measured with a spectrophotometer (X-Rite SP-64) using discs prepared according to ISO-4049:2019(E). Data were analyzed using an unpaired t-test. Results are reported in Table 1. Fracture toughness of the experimental bulk-fill composite was found to be between 36% and 170% higher than market-leading bulk-fill composites tested. Additionally, crack propagation for the experimental material, along with fiber-reinforced composite products EXP and EXF, was observed to be of a slow, controlled nature, while FTO, TPF, and SDR samples experienced a rapid and catastrophic break. The experimental bulk-fill composite restorative showed a significantly higher fracture toughness when compared with the market-leading bulk-fill composites tested in this study. In other properties tested, the experimental composite was comparable to or better than market-leading composite products. This provides support for the use of the experimental bulk-fill composite restorative in clinical situations, particularly those in which additional fracture-resistance is required, such as in patients with bruxism. [Display omitted] [ABSTRACT FROM AUTHOR]

Aim: To describe the respiratory and nutritional supportive care and hospitalisations required in the real-world scenario in children with SMA type 1 treated with nusinersen.Methods: Single-centre observational cohort study of children with SMA1 commencing nusinersen from November 2016 to September 2018. Motor, respiratory and nutritional clinical characteristics and management are described from initiation of nusinersen for a minimum of two years.Results: Nine children (5 females, 4 males), median age 10.7 months (range 2.7-181.2) commenced treatment with nusinersen and outcomes were assessed over a total of 270.5 patient months and 209 hospital admissions. Supportive care in newly-diagnosed patients (n = 7) included gastrostomy insertion (n = 4) and commencement of noninvasive ventilation (n = 4) at an average of 8.3 and 4.5 months after diagnosis, respectively. The annualised hospitalisation rate was 9.3/patient/year, average length of stay (LOS) of 3.3 days (SD = 5.6). Children with two SMN2 copies required more gastrostomies (p < 0.05) and had more frequent admissions (p < 0.05). Number of total admissions halved from the first to the second year of treatment in all patients (p < 0.005).Interpretation: Children with treated SMA1 experienced considerable respiratory and bulbar comorbidities, necessitating substantial respiratory and nutritional supportive care. Proactive respiratory and nutritional surveillance and management is essential in SMA1 patients treated with nusinersen. [ABSTRACT FROM AUTHOR]

Little is currently known about the nutrition and growth outcomes in children with neuromuscular disorders (NMDs), and these are likely disease dependent. The aim of this study was to describe the range of nutritional issues in pediatric NMDs and identify similarities and differences in growth outcomes and nutritional needs in children with a variety of NMDs at different ages, with the goal of informing future services. In this cross-sectional study we collected data on growth, dietetic interventions and nutrition-related issues in 160 children who attended a multidisciplinary clinic in a tertiary children's hospital, from February to December 2019. Children with significant weakness affecting mobility before the age of 3 years were clinically grouped into 'early-onset NMDs'. Across our clinic, 42.5% children had a history of chronic gastrointestinal issues, and 34.4% received dietetic care on the day of clinical visit. Children with early-onset NMDs had significantly higher prevalence of swallowing issues, gastroesophageal reflux, and vomiting, as well as higher frequency of dietetic consultations, high energy diet, swallowing assessment and tube-feeding, compared to later-onset NMDs (p < 0.05). In total, 49.2% children with NMDs had an abnormal weight, in which the prevalence of underweight (n = 24, 19.2%) was significantly higher compared to normal Australian children (8.2%) (p < 0.05). In Duchenne muscular dystrophy, over 50% children were overweight/obese. Among children with NMDs, there were many disease-specific nutrition-related symptoms, growth issues, and dietetic practices that were tailored to individual needs. Future studies should focus on measuring the impact of specific dietetic practices on growth and nutritional outcomes, as well as developing a precision medicine approach tailored to the individual nutritional needs of children with NMDs. • Abnormal body mass index is common in children with neuromuscular disorders (NMDs), as seen in almost half our cohort. • Chronic gastrointestinal problems are common in children with NMDs, as seen in 42.5% of our cohort. • Children with early-onset rather than later-onset NMDs have more issues with swallowing and being underweight. • Children with Duchenne muscular dystrophy are more likely to be overweight. • A precision medicine approach is needed to optimise growth and nutritional outcomes of each patient. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy is treated with onasemnogene abeparvovec, which replaces the missing survival motor neuron 1 gene via an adeno-associated virus vector. As of July 1, 2020, we had identified 3 infants who developed thrombotic microangiopathy following onasemnogene abeparvovec. Early recognition and treatment of drug-induced thrombotic microangiopathy may lessen mortality and morbidity. [ABSTRACT FROM AUTHOR]

Restored teeth undergo more damage than intact teeth. Therefore, the scientific investigation of their mechanical and physical behaviour under varying oral conditions is vital. The current study is to numerically investigate the stresses on a class-II mesio-occluso-distal (MOD) restored molar due to thermal and thermomechanical stimuli with varying input properties such as coefficient of thermal expansion and elastic properties. This is performed to optimise the dental restoration material, thereby reducing the stresses and failure of the restoration. An upper molar was scanned using μ-CT for segmenting and modelling the enamel and dentine. A class-II MOD cavity was then prepared on the model, after which non-manifold meshing was generated. The coefficient of thermal expansion (CTE) and elastic modulus (E) properties of the restoration were varied from 20 × 10−6 °C-1 to 55 × 10−6 °C-1 and 5 GPa–20 GPa, respectively. After the material properties and boundary conditions were set for the finite element (FE) analysis, the thermal and thermomechanical loading analyses were performed to demonstrate the influence of input parameters on the stress. The maximum values of principal stresses on the restoration-enamel junction and the restoration were evaluated. The results were statistically processed using analysis of variance, response surface methodology (RSM) and optimisation analysis to estimate the most optimum inputs for minimising principal stresses. The study reveals that the location of principal stress occurs at the restoration-enamel junction (REJ) and the restoration changes based on the composite material value of E and CTE due to thermal and thermomechanical stimuli. The REJ showed higher principal stress than restoration during the application of both thermal and thermomechanical stimuli, making it more vulnerable to fracture and failure. Moreover, the study showed non-linear variations in the values and locations of principal stresses due to thermal and thermomechanical stimuli with the change in the property of the restoration composite used. Finally, this study derived an optimised restorative value for CTE and E due to the application of thermal and simultaneous thermal and mechanical stimuli. This study highlights the importance of choosing the suitable material properties of the restoration composite by dental clinicians to repair a large class MOD cavity. The findings from this study also suggest that the difference in the values of E and CTE in a dental restoration composite when compared with the enamel causes a lack of uniformity in mechanical and thermal properties, thereby forming stress concentrations at the interfaces. The study establishes two optimised CTE and E values for the MOD restoration composite as 25 × 10−6 °C-1 and 20 GPa and 37 × 10−6 °C-1 and 5 GPa, respectively. • The 3D model of a tooth was generated from μ-CT data, and a class II mesial-occlusal-distal cavity was designed. • Non-manifold meshing techniques were performed to attain uniform meshing through interfaces. • Responses to thermal and simultaneous thermomechanical stimuli were investigated due to varying input thermal and mechanical properties. • Locations of principal stresses for restored molar due to input thermal expansion coefficient and elastic modulus were determined. • The optimised thermal and mechanical properties for thermal and thermomechanical stimuli were analysed from critical observations. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is challenging to reliably diagnose. Comprehensive evaluation requires advanced imaging, genetic testing, and detailed clinical history. We hypothesized that clinical and imaging parameters from referring centers can predict the likelihood of confirming a diagnosis of HCM at a tertiary care center. A chart review of patients presenting to establish care at the University of Virginia HCM Center of Excellence between September 2020 and October 2022 was conducted. Referral diagnosis was either confirmed or rejected following comprehensive evaluation of outside and new imaging studies with the clinician and cardiac imager. Clinical and imaging characteristics from pre-referral studies were then used to construct a model for predictors of ruling out or confirming the diagnosis of HCM using machine learning methods (least absolute shrinkage and selection operator [LASSO] logistic regression). Alternative diagnoses were found in 38 (18.1%) of the 210 patients (median age 60 years; 50% female). Increased LVEDVi, greater septal thickness measurements, greater left atrial size, asymmetric hypertrophy on echocardiography, and the presence of an ICD were associated with higher odds ratios for confirming a diagnosis of HCM, whereas increasing age and the presence of diabetes were more predictive of rejecting the diagnosis (AUC = 0.902, p < 0.0001) (Figure 1 and Figure 2). Clinical and imaging parameters may predict diagnostic accuracy in patients presenting to a tertiary care center for presumed HCM. Further validation of this model in larger cohorts may enhance its clinical utility in referring centers. [ABSTRACT FROM AUTHOR]

Scoping review. Dart thrower's motion (DTM) of the wrist primarily arises from the midcarpal joint, and minimizes stress to the scapholunate interosseous ligament (SLIL). After SLIL injury or surgery, early controlled DTM may reduce the effects of prolonged immobilization, while protecting SLIL integrity. To summarize the literature on the effects of DTM on the injured and surgically repaired SLIL and the extent to which various DTM orthotic designs promote SLIL recovery. A systematic literature search was conducted within 6 databases for articles published between 2003 and March 2018. Eligible studies examined DTM in the context of SLIL injury or repair. Relevant data were extracted by 2 independent reviewers. Of 425 identified articles, 15 were eligible for inclusion. Five biomechanical studies examined the influence of DTM on the injured SLIL, whereas 5 articles described DTM orthotic designs. Also included were five articles that reported outcomes when DTM was used in the rehabilitation protocol. The included studies suggest limiting end ranges of DTM in the injured/repaired SLIL, while blocking orthogonal plane movements. Custom orthotic designs may accomplish this goal. DTM has been used in comprehensive therapy programs in small case studies reporting short-term and intermediate clinical outcomes. Caution should be exercised with using DTM on the torn SLIL as gap increases, particularly at the end-range motion. Orthosis designs have potential to limit this motion to midrange, while allowing early movement. Further high-level research is needed to understand the influence of DTM on injured and postsurgical populations. • Dart thrower's motion (DTM) minimizes stress to the intact scapholunate ligament (scapholunate interosseous ligament [SLIL]). • Torn SLIL may show a gap with DTM, particularly at end range. • DTM orthotics may limit orthogonal plane motion but allow controlled DTM. • DTM may be incorporated into a comprehensive rehabilitation program for SLIL tears. • Preliminary data from descriptive studies show potential effects of these programs. [ABSTRACT FROM AUTHOR]

Aim: Preoperatively elevated pulmonary vascular resistance (PVR) is a contraindication to heart transplantation (HT). Transpulmonary pressure gradient (TPG) is one of the main variables used in PVR determination (ie, PVR = TPG/cardiac output). Unlike PVR, which is subject to the shortcoming of cardiac output estimation, TPG is directly measured. We aimed to evaluate the relationship of TPG obtained before left ventricular assist device (LVAD) implantation on post-HT survival.Methods and Results: A total of 490 patients were implanted with Heartmate II LVADs in the multicenter Heartmate II Bridge-to-Transplantation clinical trial, and 416/490 had pre-LVAD TPG data available. Outcomes during LVAD support and after HT stratified by both PVR and TPG were studied. The median pre-LVAD TPG was 10 mm Hg. Baseline demographic and clinical characteristics were similar for patients with and without TPG >10 mm Hg. Outcomes during LVAD support (ie, recovery to LVAD explantation, HT, or ongoing device support) for patients below and above the median TPG were similar. However, post-HT 1-year survival rate was significantly higher for patients with TPG ≤10 mm Hg compared with those with TPG >10 mm Hg (91% vs 80%; P = .016). Analysis based on the median PVR of 2.68 Wood units did not stratify post-HTx 1-year survival rates between the groups (89% vs 83%; P = .25).Conclusions: Elevated TPG, rather than high PVR, before LVAD implantation was associated with increased mortality following HT. Pre-LVAD TPG may be useful to identify a cohort that requires close follow-up with serial hemodynamic monitoring before HT. [ABSTRACT FROM AUTHOR]

Interleukin 6 (IL6) and tumor necrosis factor contribute to the development of colitis-associated cancer (CAC). We investigated these signaling pathways and the involvement of G protein subunit alpha i1 (GNAI1), GNAI2, and GNAI3 in the development of CAC in mice and humans. B6;129 wild-type (control) or mice with disruption of Gnai1 , Gnai2 , and/or Gnai3 or conditional disruption of Gnai2 in CD11c+ or epithelial cells were given dextran sulfate sodium (DSS) to induce colitis followed by azoxymethane (AOM) to induce carcinogenesis; some mice were given an antibody against IL6. Feces were collected from mice, and the compositions of microbiomes were analyzed by polymerase chain reactions. Dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) isolated from spleen and colon tissues were analyzed by flow cytometry. We performed immunoprecipitation and immunoblot analyses of colon tumor tissues, MDSCs, and mouse embryonic fibroblasts to study the expression levels of GNAI1, GNAI2, and GNAI3 and the interactions of GNAI1 and GNAI3 with proteins in the IL6 signaling pathway. We analyzed the expression of Gnai2 messenger RNA by CD11c+ cells in the colonic lamina propria by PrimeFlow, expression of IL6 in DCs by flow cytometry, and secretion of cytokines in sera and colon tissues by enzyme-linked immunosorbent assay. We obtained colon tumor and matched nontumor tissues from 83 patients with colorectal cancer having surgery in China and 35 patients with CAC in the United States. Mouse and human colon tissues were analyzed by histology, immunoblot, immunohistochemistry, and/or RNA-sequencing analyses. GNAI1 and GNAI3 (GNAI1;3) double-knockout (DKO) mice developed more severe colitis after administration of DSS and significantly more colonic tumors than control mice after administration of AOM plus DSS. Development of increased tumors in DKO mice was not associated with changes in fecal microbiomes but was associated with activation of nuclear factor (NF) κB and signal transducer and activator of transcription (STAT) 3; increased levels of GNAI2, nitric oxide synthase 2, and IL6; increased numbers of CD4+ DCs and MDSCs; and decreased numbers of CD8+ DCs. IL6 was mainly produced by CD4+/CD11b+, but not CD8+, DCs in DKO mice. Injection of DKO mice with a blocking antibody against IL6 reduced the expansion of MDSCs and the number of tumors that developed after CAC induction. Incubation of MDSCs or mouse embryonic fibroblasts with IL6 induced activation of either NF-κB by a JAK2-TRAF6-TAK1-CHUK/IKKB signaling pathway or STAT3 by JAK2. This activation resulted in expression of GNAI2, IL6 signal transducer (IL6ST, also called GP130) and nitric oxide synthase 2, and expansion of MDSCs; the expression levels of these proteins and expansion of MDSCs were further increased by the absence of GNAI1;3 in cells and mice. Conditional disruption of Gnai2 in CD11c+ cells of DKO mice prevented activation of NF-κB and STAT3 and changes in numbers of DCs and MDSCs. Colon tumor tissues from patients with CAC had reduced levels of GNAI1 and GNAI3 and increased levels of GNAI2 compared with normal tissues. Further analysis of a public human colorectal tumor DNA microarray database (GSE39582) showed that low Gani1 and Gnai3 messenger RNA expression and high Gnai2 messenger RNA expression were significantly associated with decreased relapse-free survival. GNAI1;3 suppresses DSS-plus-AOM–induced colon tumor development in mice, whereas expression of GNAI2 in CD11c+ cells and IL6 in CD4+/CD11b+ DCs appears to promote these effects. Strategies to induce GNAI1;3, or block GNAI2 and IL6, might be developed for the prevention or therapy of CAC in patients. [ABSTRACT FROM AUTHOR]

Purpose To compare clinical outcomes of patients who required a prolonged length of stay in the postanesthesia care unit (PACU) with a control group. Design A single-center purposive-sampled retrospective medical record and database audit. Methods Patients with prolonged PACU stays were compared to a group of patients whose stay was less than median for outcome measures: rapid response team (RRT) activation, cardiac arrest, unanticipated intensive care unit admissions, and survival to discharge. Findings A total of 1,867 patients were included in the analysis (n = 931 prolonged stay and n = 933 control group). Prolonged stay in PACU was higher among patients who were older, had higher American Society of Anesthesiologist score, and were discharged to wards during the afternoon or late nursing shift. RRT activation after discharge from PACU occurred in more patients in the study group compared with the control group (7% vs 1%, respectively). There were no cardiac arrests recorded in either group within the 24 hours after PACU discharge period. Conclusions Prolonged stay in the PACU for 2 or more hours because of clinical reasons appears to be associated with a higher incidence of clinical deterioration in the ward setting requiring RRT intervention within 24 hours after discharge from PACU. [ABSTRACT FROM AUTHOR]

Identifying methods to improve assay sensitivity in randomized clinical trials (RCTs) may facilitate the discovery of efficacious pain treatments. RCTs evaluating pain treatments typically use average pain intensity (API) or worst pain intensity (WPI) as the primary efficacy outcome. However, little evidence is available comparing the assay sensitivity of these 2 measures. In this systematic review and meta-analysis, we comprehensively reviewed all low back pain, osteoarthritis pain, fibromyalgia, diabetic peripheral neuropathy pain, and postherpetic neuralgia RCTs that used a parallel group design. Eligibility required: 1) primary RCT report published between 1980 and 2016, 2) comparing 1 or more active, efficacious pharmacologic pain treatment(s) with placebo, and 3) providing data on the standardized effect size (SES) for API as well as WPI for all treatment arms. Twenty-seven active versus placebo comparisons were identified in 23 eligible articles. Using a random-effects meta-analysis, API SES and WPI SES did not differ significantly (difference = -.021, 95% confidence interval = -.047 to .004, P = .12). The findings indicate that, depending on the objectives of the study, either API or WPI could be used as a primary outcome measure in clinical trials for the chronic pain conditions included in this analysis.Perspective: Understanding the comparative assay sensitivity of API and WPI may advance pain treatment research. A meta-analysis of trials of efficacious pharmacologic treatments in 5 pain conditions did not show a statistically significant difference between the assay sensitivity of API and WPI. [ABSTRACT FROM AUTHOR]

Great progress has been made in the clinical translation of several therapeutic strategies for spinal muscular atrophy (SMA), including measures to selectively address Survival Motor Neuron (SMN) protein deficiency with SMN1 gene replacement or modulation of SMN2 encoded protein levels, as well as neuroprotective approaches and supporting muscle strength and function. This review highlights these novel therapies. This is particularly vital with the advent of the first disease modifying therapy, which has brought to the fore an array of questions surrounding who, how and when to treat, and stimulated challenges in resource limited healthcare systems to streamline access for those eligible for drug therapy. The overhaul of the landscape for all those involved in SMA extends to the design of further drug trials and the necessity of multidisciplinary supportive care to potentiate the effects of disease modifying medications. The impact of respiratory complications in SMA is central to management in the current era of emerging novel therapies. These fundamental changes in our knowledge and management approach to those with SMA are explored further in this review. [ABSTRACT FROM AUTHOR]

Valid and reliable biomarkers can play an important role in clinical trials as indicators of biological or pathogenic processes or as a signal of treatment response. Currently, there are no biomarkers for pain qualified by the U.S. Food and Drug Administration or the European Medicines Agency for use in clinical trials. This article summarizes an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials meeting in which 3 potential biomarkers were discussed for use in the development of analgesic treatments: 1) sensory testing, 2) skin punch biopsy, and 3) brain imaging. The empirical evidence supporting the use of these tests is described within the context of the 4 categories of biomarkers: 1) diagnostic, 2) prognostic, 3) predictive, and 4) pharmacodynamic. Although sensory testing, skin punch biopsy, and brain imaging are promising tools for pain in clinical trials, additional evidence is needed to further support and standardize these tests for use as biomarkers in pain clinical trials.Perspective: The applicability of sensory testing, skin biopsy, and brain imaging as diagnostic, prognostic, predictive, and pharmacodynamic biomarkers for use in analgesic treatment trials is considered. Evidence in support of their use and outlining problems is presented, as well as a call for further standardization and demonstrations of validity and reliability. [ABSTRACT FROM AUTHOR]

Chemotherapy for bone tumors is a major challenge because of the inability of therapeutics to penetrate dense bone mineral. We hypothesize that a nanostructured formulation with high affinity for bone could deliver drug to the tumor while minimizing off-target toxicity. Here, we evaluated the efficacy and toxicity of a novel bone-targeted, pH-sensitive liposomal formulation containing doxorubicin in an animal model of bone metastasis. Biodistribution studies with the liposome showed good uptake in tumor, but low accumulation of doxorubicin in the heart. Mice treated with the bone-targeted liposome formulation showed a 70% reduction in tumor volume, compared to 35% reduction for free doxorubicin at the same dose. Both cardiac toxicity and overall mortality were significantly lower for animals treated with the bone-targeted liposomes compared to free drug. Bone-targeted, pH-sensitive, doxorubicin containing liposomes represent a promising approach to selectively delivering doxorubicin to bone tumors while minimizing cardiac toxicity. [ABSTRACT FROM AUTHOR]

Background Current recommendations of antithrombotic therapy for HeartMate II (HMII) patients include the use of both an anticoagulant and an antiplatelet agent. Because bleeding is still the most frequent adverse event, the TRACE (STudy of Reduced Anti-Coagulation/Anti-platelet Therapy in Patients with the HeartMatE II) study was initiated to evaluate the incidence of adverse events in HMII patients on reduced antithrombotic (RT) therapy. Methods HMII patients (n = 101) from nine centers were enrolled in the European arm of TRACE and were managed on a single anticoagulant (vitamin K antagonist) with no antiplatelet agents. An analysis of bleeding and thrombotic adverse events from all 101 patients with 2-year follow-up after initiation of RT therapy is reported here. Results Median age was 56 years (range, 18 to 72 years), 93% were men, 70% had an Interagency Registry for Mechanically Assisted Circulatory Support profile 1 to 3, and 82% received the HMII as a bridge to transplantation. Ninety-two percent were placed on RT therapy as a center standard of care or due to physician preference and 6% as a response to bleeding. Median HMII support duration on RT therapy was 25 months (range, 1 to 93 months). Median international normalized ratio was 2.31 [quartile 1 to quartile 3: 2.07 to 2.60]. At 2 years, freedom from bleeding, ischemic stroke, hemorrhagic stroke, and pump thrombosis after initiation of RT therapy was 81% ± 6%, 96% ± 2%, 94% ± 3%, and 94% ± 3%, respectively. Conclusions The 2-year analysis of the observational European TRACE study suggests that managing HMII patients with a vitamin K antagonist with a target international normalized ratio of 2.3 without antiplatelet therapy may help to reduce the incidence of major bleeding without increasing the risk of thromboembolic events, including ischemic stroke and pump thrombosis. [ABSTRACT FROM AUTHOR]

Chronic cancer pain is a serious complication of malignancy or its treatment. Currently, no comprehensive, universally accepted cancer pain classification system exists. Clarity in classification of common cancer pain syndromes would improve clinical assessment and management. Moreover, an evidence-based taxonomy would enhance cancer pain research efforts by providing consistent diagnostic criteria, ensuring comparability across clinical trials. As part of a collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) and the American Pain Society (APS), the ACTTION-APS Pain Taxonomy initiative worked to develop the characteristics of an optimal diagnostic system. After the establishment of these characteristics, a working group consisting of clinicians and clinical and basic scientists with expertise in cancer and cancer-related pain was convened to generate core diagnostic criteria for an illustrative sample of 3 chronic pain syndromes associated with cancer (ie, bone pain and pancreatic cancer pain as models of pain related to a tumor) or its treatment (ie, chemotherapy-induced peripheral neuropathy). A systematic review and synthesis was conducted to provide evidence for the dimensions that comprise this cancer pain taxonomy. Future efforts will subject these diagnostic categories and criteria to systematic empirical evaluation of their feasibility, reliability, and validity and extension to other cancer-related pain syndromes.Perspective: The ACTTION-APS chronic cancer pain taxonomy provides an evidence-based classification for 3 prevalent syndromes, namely malignant bone pain, pancreatic cancer pain, and chemotherapy-induced peripheral neuropathy. This taxonomy provides consistent diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms for these potentially serious cancer pain conditions that can be extended and applied with other cancer-related pain syndromes. [ABSTRACT FROM AUTHOR]

Microplastic (MP) pollution is an ongoing problem in coastal systems, where wastewater treatment plants (WWTPs) deposit particles daily. This study examined MP characteristics at WWTP outflow and control sites in St. Andrew Bay in Northwestern Florida, USA. WWTP sites contained mostly polypropylene fragments (180.1 μm avg. size), while reference sites contained polypropylene fragments, and polyethylene and polyester fibers (315.3 μm avg. size). MP sizes were strongly linked to distance from the nearest WWTP, while shape and polymer compositions were more closely related to dissolved oxygen concentrations and distance to the nearest water input source. The prevalence of polypropylene fragments at WWTP sites suggests that extreme weather events during the study flushed land-based debris into the system, where it was buried in the sediments. Increased abundances of polyester and polyethylene terephthalate in the winter at WWTP sites are indicative of the role that laundering synthetic textiles plays in coastal MP pollution. [Display omitted] • Microplastic (MP) characteristics were assessed in coastal northwestern Florida. • Fragment was the most abundant MP shape at wastewater treatment plant (WWTP) sites. • Polypropylene was the most abundant MP polymer at WWTPs, especially in the winter. • MP sizes were significantly smaller at WWTP outflow sites than at reference sites. • Textile laundering and extreme weather events can cause seasonality in MP pollution. [ABSTRACT FROM AUTHOR]

Background: The dramatic increase in the number of childhood cancer survivors over the last 60years has made monitoring and minimising long term side effects of cancer treatment increasingly important. Chemotherapy induced peripheral neuropathy (CIPN) has been described with many commonly used chemotherapy agents. This article provides a critical overview of pediatric CIPN, its incidence, clinical manifestations, late effects, and recent advances in understanding of risk factors and pharmacogenomics as well as evaluating current assessment strategies and treatment approaches.Methods: Neurotoxicity data was systematically collated from Medline, Embase and Pubmed and analysed for quality, relevance and originality in three stages prior to inclusion. Quality scoring was done using the QUALSYST assessment tool.Results: A total of 61 studies met inclusion criteria. Peripheral neuropathy is common and may be long lasting with characteristics specific to each chemotherapy agent. There is significant variability in reported incidence and natural history, related to challenges in clinical assessment and diagnosis. Emerging risk factors for CIPN include treatment factors such as dose, duration and concurrent medication and patient factors such as age and inherited susceptibilities. Recent identification of individual genetic variations has advanced understanding of pathomechanisms and may direct future treatment approaches.Conclusion: While these studies guide suggestions for current clinical practice, further systematic research with development of strategies for amelioration and prevention of CIPN is necessary. Standardised assessment protocols and objective outcomes measures of CIPN applicable to patients of different ages are critical to enabling the development of novel treatments and facilitation of future clinical trials and treatment individualisation. [ABSTRACT FROM AUTHOR]

Background: Left ventricular assist devices (LVADs) improve survival, quality of life (QOL), and functional capacity (FC) among patients with end-stage heart failure. Few data are available regarding characteristics associated with QOL and FC response.Methods and Results: Patients enrolled in the Heartmate II clinical trials that were alive with ongoing LVAD support at 6 months were included. QOL response criteria included scoring above the lowest quartile on either the Minnesota Living With Heart Failure Questionnaire or the Kansas City Cardiomyopathy Questionnaire. FC responder criteria included improvement in 6-minute walk distance (6MWD) >70 meters from baseline, a 6MWD >220 meters at 6 months, or New York Heart Association functional class I or II. Independent variables associated with QOL nonresponse included history of diabetes (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.20-2.78), lower mean pulmonary arterial pressure (OR 0.97, 95% CI 0.95-0.99), or a Heartmate II right ventricular risk score >2 (OR 1.77, 95% CI 1.00-3.12). Variables associated with FC nonresponse included history of COPD (OR 1.92, 95% CI 1.22-3.03) or diabetes (OR 1.52, 95% CI 1.01-2.27). Compared with responders, QOL and FC nonresponders had reduced long-term survival.Conclusions: Preoperative comorbidities, including diabetes, COPD, and right heart failure, may limit the QOL and FC response to LVAD therapy and should be considered during the shared decision-making process. [ABSTRACT FROM AUTHOR]

Thermogenic fat differentiation and function can be promoted through multiple pathways, resulting in a common cell phenotype characterized by the expression of Uncoupling Protein-1 and the ability to dissipate energy, but local and systemic stimuli are necessary to promote adequate thermogenic fat vascularization, which is a precondition for the transport of substrate and the dissipation of heat. Angiopoietin-2 is an important driver of vascularization, and its transcription is in part promoted by estrogen signaling. In this study we demonstrate that adipose tissue-specific knock out of Angiopoietin-2 causes a female-specific reduced thermogenic fat differentiation and function, resulting in obesity and impaired glucose tolerance with end-organ features consistent with metabolic syndrome. In humans, angiopoietin-2 levels are higher in females than in males, and are inversely correlated with adiposity and age more strongly in pre-menopause when compared to post-menopause. Collectively, these data indicate a novel and important role for estrogen-mediated Angiopoietin-2 adipose tissue production in the protection against calorie overload in females, and potentially in the development of postmenopausal weight gain. • Angiogenesis plays a permissive role in inducible thermogenic fat function. • Estrogen-driven adipose tissue angiogenesis controls metabolism in mice and humans. • Adipose tissue Angiopoietin-2 deletion is a novel model of female-specific obesity. • In humans, the interaction between ANG2 levels, age, and adiposity is sex-specific. [ABSTRACT FROM AUTHOR]

Background Obesity is a risk factor for cholelithiasis leading to acute cholecystitis which is treated with cholecystectomy. The purpose of this study was to analyze the associations between body mass index class and the intended operative approach (laparoscopic versus open) for and outcomes of cholecystectomy for acute cholecystitis. Methods We conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program data from 2008–2013. The effects of body mass index class on intended procedure type (laparoscopic versus open), conversion from laparoscopic to open operation, and outcomes after cholecystectomy were examined using multivariable logistic regression. Results Data on 20,979 patients who underwent cholecystectomy for acute cholecystitis showed that 18,228 (87%) had a laparoscopic operation; 639 (4%) of these patients required conversion to an open approach; and 2,751 (13%) underwent intended open cholecystectomy. There was an independent association between super obesity (body mass index 50+) and an intended open operation (odds ratio 1.53, 95% confidence interval 1.14–2.05, P = .01). An intended open procedure (odds ratio 3.10, 95% confidence interval 2.40–4.02, P < .0001) and conversion (odds ratio 3.45, 95% confidence interval 2.16–5.50, P < .0001) were associated with increased risk of death/serious morbidity in a model, even when controlling for all other important factors. In the same model, body mass index class was not associated with increased death/serious morbidity. Outcomes after conversion were not substantially worse than outcomes after intended open cholecystectomy. Conclusion This study supports the possibility that an intended open approach to acute cholecystitis, not body mass index class, is associated with worse outcomes after cholecystectomy. An initial attempt at laparoscopy may benefit patients, even those at the highest end of the body mass index spectrum. [ABSTRACT FROM AUTHOR]

Crude oil released from the Deepwater Horizon disaster into the Gulf of Mexico posed potential impacts to infaunal invertebrates inhabiting near shore habitats. The effects of sediment-associated weathered slick oil on the amphipod Leptocheirus plumulosus was assessed using 28-d exposures to total PAH sediment concentrations ranging from 0.3 to 24 mg/kg (sum of 50 PAHs or tPAH50). Survival and growth rate were significantly decreased in the 2.6, 11.4 and 24.2 mg/kg treatments, but only growth in 5.5 mg/kg. Offspring production was dramatically decreased but was variable and significantly different only for 24.2 mg/kg. The concentrations associated with 20% decreases relative to reference were 1.05 (95% CI = 0–2.89) mg/kg tPAH50 for growth rate and 0.632 (95% CI = 0.11–2.15) mg/kg tPAH50 for offspring production. The concentrations of PAHs affecting amphipods are within the range of concentrations measured in marsh areas reportedly impacted by DWH oil after its release. [ABSTRACT FROM AUTHOR]

Objective: Although at increased risk for developing dementia compared with white patients, older African Americans are diagnosed later in the course of dementia. Using the common sense model (CSM) of illness perception, we sought to clarify processes promoting timely diagnosis of mild cognitive impairment (MCI) for African American patients.Design, Setting, Participants: In-person, cross-sectional survey data were obtained from 187 African American (mean age: 60.44 years). Data were collected at social and health-focused community events in three southern Wisconsin cities.Measurements: The survey represented a compilation of published surveys querying CSM constructs focused on early detection of memory disorders, and willingness to discuss concerns about memory loss with healthcare providers. Derived CSM variables measuring perceived causes, consequences, and controllability of MCI were included in a structural equation model predicting the primary outcome: Willingness to discuss symptoms of MCI with a provider.Results: Two CSM factors influenced willingness to discuss symptoms of MCI with providers: Anticipation of beneficial consequences and perception of low harm associated with an MCI diagnosis predicted participants' willingness to discuss concerns about cognitive changes. No association was found between perceived controllability and causes of MCI, and willingness to discuss symptoms with providers.Conclusions: These data suggest that allaying concerns about the deleterious effects of a diagnosis, and raising awareness of potential benefits, couldinfluence an African American patient's willingness to discuss symptoms of MCI with a provider. The findings offer guidance to designers of culturally congruent MCI education materials, and healthcare providers caring for older African Americans. . [ABSTRACT FROM AUTHOR]

To assess the hypotheses that a restored tooth structure for a class II occlusal-distal (OD) cavity can be reinforced by optimizing the cavity geometry and choosing composites with adequate mechanical properties. A human maxillary molar tooth was scanned, and segmented. The 2D profiles of dentin and enamel were drawn and imported to ABAQUS software. Eighteen restored tooth models with different cavity occlusal depths (OcDs) and internal cavity angles were developed. A semi-circular stone part was used to apply contact loads to the restored tooth model. After setting up the required interactions and boundary conditions, a written Python code was used to automatically assign a wide range of elastic moduli, from 2 GPa to 26 GPa, to the composite restorations, and assign constant material properties to the enamel and dentine. For simplicity, the behaviour of the mechanical material was postulated homogeneous and elastic, while the FE analyses were linearly carried out in this study. Also, the code enabled the FEA software to conduct the stress analyses, determine maximum principal stresses, and record the obtained results. The internal cavity angle formed between the mesial wall and the pulpal floor of the cavity significantly changed the peak maximum principal stress both in the enamel and restoration. The peak stress concentrations were observed mostly at the enamel-restoration interface, with an almost perpendicular orientation to this interface. Regarding the effect of occlusal cavity depth (OcD), the model with the shallowest cavity (OcD = 1.5 mm) represented greater resistance to applied loads than the model with deeper cavities (OcD = 2.0 mm and OcD 2.5 mm). The composite modulus (CM) in the range of 10–18 GPa reduced the maximum principal stress concentrations in the enamel. The lowest result for maximum principal stress was observed in the model with OcD = 1.5 mm, CM = 10 GPa and internal cavity angles = 100°, which was the strongest model against contact loads. Class II OD cavities with optimal geometry have reduced induced stress levels, thus being able to be more mechanically robust against contact load transmitted by a stone. Cavity geometry designs with obtuse (more than 90°) internal cavity angles were significantly efficient in minimizing peak stress concentrations. The results indicated that for the model with obtuse internal cavity angles, choosing a composite with optimised properties can diminish stress, particularly at the tooth-restoration interface. Furthermore, the shallowest the cavity, the sturdier the restoration was, especially when the interface tooth-restoration laid on enamel and not on dentine. [Display omitted] [ABSTRACT FROM AUTHOR]

Parametric statistical methods are common in human pain research. They require normally distributed data, but this assumption is rarely tested. The current study analyzes the appropriateness of parametric testing for outcomes from the cold pressor test (CPT), a common human experimental pain test. We systematically reviewed published CPT studies to quantify how often researchers test for normality and how often they use parametric versus nonparametric tests. We then measured the normality of CPT data from 7 independent small to medium cohorts and 1 study of >10,000 subjects. We then examined the ability of 2 common mathematical transformations to normalize our skewed data sets. Lastly, we performed Monte Carlo simulations on a representative data set to compare the statistical power of the parametric t-test versus the nonparametric Wilcoxon Mann-Whitney test. We found that only 39% of published CPT studies (47/122) mentioned checking data distribution, yet 72% (88/122) used parametric statistics. Furthermore, among our 8 data sets, CPT outcomes were virtually always nonnormally distributed, and mathematical transformations were largely ineffective in normalizing them. The simulations demonstrated that the nonparametric Wilcoxon Mann-Whitney test had greater statistical power than the parametric t-test for all scenarios tested: For small effect sizes, the Wilcoxon Mann-Whitney test had up to 300% more power. Perspective These results demonstrate that parametric analyses of CPT data are routine but incorrect and that they likely increase the chances of failing to detect significant between-group differences. They suggest that nonparametric analyses become standard for CPT studies and that assumptions of normality be routinely tested for other types of pain outcomes as well. [ABSTRACT FROM AUTHOR]

Summary Objectives Hemagglutination inhibiting (HI) antibodies correlate with influenza vaccine protection but their association with protection induced by natural infection has received less attention and was studied here. Methods 940 people from 270 unvaccinated households participated in active ILI surveillance spanning 3 influenza seasons. At least 494 provided paired blood samples spanning each season. Influenza infection was confirmed by RT-PCR on nose/throat swabs or serum HI assay conversion. Results Pre-season homologous HI titer was associated with a significantly reduced risk of infection for H3N2 (OR 0.61, 95%CI 0.44–0.84) and B (0.65, 95%CI 0.54–0.80) strains, but not H1N1 strains, whether re-circulated (OR 0.90, 95%CI 0.71–1.15), new seasonal (OR 0.86, 95%CI 0.54–1.36) or pandemic H1N1-2009 (OR 0.77, 95%CI 0.40–1.49). The risk of seasonal and pandemic H1N1 decreased with increasing age (both p < 0.0001), and the risk of pandemic H1N1 decreased with prior seasonal H1N1 (OR 0.23, 95%CI 0.08–0.62) without inducing measurable A/California/04/2009-like titers. Conclusions While H1N1 immunity was apparent with increasing age and prior infection, the effect of pre-season HI titer was at best small, and weak for H1N1 compared to H3N2 and B. Antibodies targeting non-HI epitopes may have been more important mediators of infection-neutralizing immunity for H1N1 compared to other subtypes in this setting. [ABSTRACT FROM AUTHOR]

The Ultima TPS MoM THR was designed and developed as a 2nd generation MoM THR specifically aimed at younger more active patients due to the anticipated low wear rates and increased longevity of MoM THRs. In 2010, published clinical data highlighted the early failure of the Ultima TPS MoM due to fretting-crevice corrosion at the stem–cement interface. Since 2010 similar observations have been reported by other clinical centres implicating competitor products as well as the Ultima TPS MoM THR. In an attempt to replicate the electrochemical reaction and interactions established across MoM THR systems, fretting-crevice corrosion tests subjected to galvanic coupling were conducted. Galvanic coupling was seen to significantly increase the rates of corrosion under static and dynamic conditions. This was due to the large potential differences developed across the system between active and passive areas, increasing the rates of corrosion and metallic ion release from the stem–cement interface. [ABSTRACT FROM AUTHOR]

Travellers' perception of their risk for acquiring travel-related conditions is an important contributor to decisions and behaviors during travel. In this study, we aimed to assess the differences between traveller-perceived and expert-assessed risk of travel-related conditions in children and adults travelling internationally and describe factors that influence travellers' perception of risk. Children and adults were recruited at the Hospital for Sick Children's Family Travel Clinic between October 2014 and July 2015. A questionnaire was administered to participants to assess their perceived risk of acquiring 32 travel-related conditions using a 7-point Likert scale. Conditions were categorized as vector-borne diseases, vaccine-preventable diseases, food and water borne diseases, sexually transmitted infections and other conditions. Two certified travel medicine experts reviewed each patient's chart and assigned a risk score based on the same 7-point Likert scale. Traveller and expert risk scores were compared using paired t-tests. In total, 207 participants were enrolled to participate in this study, 97 children (self-reported, n = 8; parent-reported, n = 89), and 110 adults. Travel-related risk for adults and parents answering for their children were significantly underestimated when compared to expert-assessed risk for 26 of the 32 assessed conditions. The underestimated conditions were the same for both adults and parents answering for children. Travel-related risk was not over-estimated for any condition. Adults underestimated their children's and their own risk for most travel-related conditions. Strategies to improve the accuracy of risk perception of travel-related conditions by travellers are needed to optimize healthy travel for children and their families. • Understanding travellers' perception of risk is key for pre-departure counselling. • Adults underestimate their child and their own risk of travel-acquired conditions. • A large proportion of travel-acquired conditions are unknown to travellers. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the present study was to investigate the outcomes of first metatarsophalangeal replacement for hallux rigidus using the Smith & Nephew ToeFit-Plus™ implant. We assessed the outcomes of 69 first metatarsophalangeal joint replacements using the American Orthopaedic Foot and Ankle Society score preoperatively and annually postoperatively, with retrospective radiologic review. All operations were performed by the same surgeon within 2 centers. A total of 69 arthroplasties were performed within the study period (57 patients). The median American Orthopaedic Foot and Ankle Society score at 1 year was 100 (interquartile range 100 to 100), at 2 years was 100 (interquartile range 95 to 100), at 3 years was 100 (interquartile range 87.5 to 100), and at 4 years, it was 100 (interquartile range 91.25 to 100). Radiolucencies around the phalangeal component were seen in 23 cases; however, this was symptomatic in only 2 patients, who required revision surgery. Our early results have shown that first metatarsophalangeal joint replacement surgery with the ToeFit-Plus™ prosthesis results in significant improvements in the American Orthopaedic Foot and Ankle Society scores for most patients; however, longer term follow-up is required to monitor the clinical effect of radiolucency around the phalangeal component. [ABSTRACT FROM AUTHOR]

Abstract: Methadone is used for the treatment of opioid addiction and for treatment of chronic pain. The safety of methadone has been called into question by data indicating a large increase in the number of methadone-associated overdose deaths in recent years that has occurred in parallel with a dramatic rise in the use of methadone for chronic pain. The American Pain Society and the College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society, commissioned an interdisciplinary expert panel to develop a clinical practice guideline on safer prescribing of methadone for treatment of opioid addiction and chronic pain. As part of the guideline development process, the American Pain Society commissioned a systematic review of various aspects related to safety of methadone. After a review of the available evidence, the expert panel concluded that measures can be taken to promote safer use of methadone. Specific recommendations include the need to educate and counsel patients on methadone safety, use of electrocardiography to identify persons at greater risk for methadone-associated arrhythmia, use of alternative opioids in patients at high risk of complications related to corrected electrocardiographic QTc interval prolongation, careful dose initiation and titration of methadone, and diligent monitoring and follow-up. Although these guidelines are based on a systematic review, the panel identified numerous research gaps, most recommendations were based on low-quality evidence, and no recommendations were based on high-quality evidence. Perspective: This guideline, based on a systematic review of the evidence on methadone safety, provides recommendations developed by a multidisciplinary expert panel. Safe use of methadone requires clinical skills and knowledge in use of methadone to mitigate potential risks, including serious risks related to risk of overdose and cardiac arrhythmias. [Copyright &y& Elsevier]