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Although general recommendations exist regarding the correct placement of the skin incision and the direction of deep dissection for closed antegrade intramedullary nailing of the femur, in surgical practice simultaneously establishing the correct entry point and exact direction for insertion of the entry instrument in the lateral (sagittal) plane may be difficult. This is due to sub-optimal radiographic images in the lateral plane as a result of the overlying shadows of the pelvis, variations in the degree of rotation of the femur during patient positioning and fracture reduction manoeuvres, variations in the degree of anterior bowing of the femoral shaft and the anatomy of the greater trochanter, and deviations of the plane of deep dissection caused by the glutei muscle fibres. This may lead to the need for several attempts with increased damage to the glutei muscles, high exposure to radiation and the risk of an iatrogenic fracture. The present technical note describes a simple method for swift, easy and accurate access to the medullary canal during closed antegrade femoral nailing. [ABSTRACT FROM AUTHOR]

The article presents several case studies related to alcohol detoxification. A 29-year-old unemployed and homeless man was admitted to a hospital for alcohol and diazepam detoxification. A 29-year-old unemployed man, married with one child was admitted to hospital for alcohol detoxification. A 35-year-old single, unemployed man who lived in a hostel for the homeless was admitted to hospital for alcohol and methadone detoxification and had declared injection of illicit drugs.

The article comments on the development of benzodiapines as a drug used to treat people suffering from anxiety in Great Britain. The drug is recommended to treat insomnia when it is severe, disabling or subjecting the individual to extreme distress. The Committee on the Safety of Medicines released emphatic guidelines about the use of benzodiazepine drugs.

An untitled poem authored by Andrew Shattuck McBride is presented. First Line: a butterfly's; Last Line: my day unpinned.

A letter to the editor is presented in response to the article "Naltrexone Implants After In-Patient Treatment for Opioid Dependence: Randomised Controlled Trial," by N. Kunøe and colleagues which appeared in a 2009 issue.

Comments on the myth of needle fixation. Unwillingness of patients to give up injectable drugs; Uses of the injectable drugs; Insufficiency of optimal prescribing treatment and syringe exchanges.

The structural and physicochemical properties of the adamantane nucleus account for its use as a chemical scaffold in multiple drugs. In the last years, we have developed new polycyclic scaffolds as surrogates of the adamantane group with encouraging results in multiple targets. As adamantane is a common structural feature in several 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors, we have explored the ability of the 6,7,8,9,10,11-hexahydro-5 H -5,9:7,11-dimethanobenzo[9]annulen-7-yl scaffold to act as a surrogate of the adamantane nucleus in a novel series of 11β-HSD1 inhibitors. Of note, within this family of compounds one derivative is endowed with submicromolar 11β-HSD1 inhibitory activity. Molecular modeling studies support the binding of the compounds to the active site of the enzyme. However, a fine tuning of the hydrophobicity of the size-expanded nucleus may be beneficial for the inhibitory potency. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "A comparison of home detoxification and minimal intervention strategies for problem drinkers," by C. Bennie in the 1998 issue.

A letter to the editor is presented that presents cases of auditory hallucinations in schizophrenic patients.

Context.--Lymph node status and the number of lymph node (LN) positive for cancer cells are the most important prognostic factors in breast cancer. Extranodal tumor extension (ENTE) has been used as a histopathologic feature to classify patients into high risk versus low risk for local recurrence. However, in the current era of early detection and systemic therapy, the prognostic significance of ENTE is not as well defined in patients with 1 to 3 LNs positive for cancer. Objective.--To determine whether the amount of tumor burden in an axillary dissection or the presence of ENTE provides any additional information regarding patient outcome in patents with 1 to 3 positive LN results. Design.--Clinical and pathologic factors were identified for 456 patients with breast cancer at the University of Texas MD Anderson Cancer Center, Houston, who had pT1 tumors and 1 to 3 LNs positive for cancer and were treated by mastectomy, with or without postmastectomy radiotherapy, between 1978 and 2007. Results.--Of the 456 patients, 257 (56.4%), 141 (31.6%), and 58 (12.7%) patients had 1, 2, or 3 positive LN results, respectively. Extranodal tumor extension was present in 99 patients (21.7%) and was absent in the remaining 357 cases (78.3%). Seventy-six patients (16.7%) received radiation therapy. Patients had both worse overall survival time and disease-free survival when ENTE was present, regardless of the amount, as long as the treatment era was not included in the multivariate analysis (pre-2000 versus post-2000). However, ENTE was no longer significant on multivariate analysis when the year of treatment was taken into account. Conclusions.--The number of positive LNs remains an important predictor of survival in patients with 1 to 3 positive LN results, but the prognostic significance of ENTE in this cohort of patients has diminished over time. [ABSTRACT FROM AUTHOR]

High-energy X-ray diffraction is used to investigate the evolution of elastic lattice strains in rolled Ti-6Al-4V specimens during cyclic loading in-situ with and without the inclusion of a 120 s dwell period. A 1 mm segment of the gauge section is monitored throughout the first 100 cycles for specimens extracted along the rolling direction (RD), the transverse direction (TD) and 45° between the two, to explore the effects of texture on the evolution of the micromechanical response. Five families of lattice planes from the hexagonal α phase are analysed with emphasis on lattice strain measured at the peak of each cycle, while macroscopic strain accumulation is simultaneously monitored via Digital Image Correlation. In cyclic loading conditions including a dwell period at load, a prominent increase in elastic strains is observed in prismatic and basal lattice planes with the specimen loaded 45° from the rolling direction. In the absence of dwell, both RD and TD specimen orientations exhibited subtle cyclic hardening in all families of lattice planes probed despite negligible evolution in accumulated macroscopic plastic strain. Estimations of lattice orientation-dependent stresses are also presented using directional moduli to examine redistribution of load across sets of grains with the increasing cycle count. [ABSTRACT FROM AUTHOR]

Abstract: The initial boundary value problem corresponding to a model of strain gradient plasticity due to [Gurtin, M., Anand, L., 2005. A theory of strain gradient plasticity for isotropic, plastically irrotational materials. Part I: Small deformations. J. Mech. Phys. Solids 53, 1624–1649] is formulated as a variational inequality, and analysed. The formulation is a primal one, in that the unknown variables are the displacement, plastic strain, and the hardening parameter. The focus of the analysis is on those properties of the problem that would ensure existence of a unique solution. It is shown that this is the case when hardening takes place. A similar property does not hold for the case of softening. The model is therefore extended by adding to it terms involving the divergence of plastic strain. For this extended model the desired property of coercivity holds, albeit only on the boundary of the set of admissible functions. [Copyright &y& Elsevier]

Motivated by the inability of classical computational plasticity to fully exploit modern scientific computing, a multifield formulation for finite strain plasticity is presented. This avoids a local integration of the elastoplastic model. In the multifield approach, the balance of linear momentum, the flow relation and the Karush–Kuhn–Tucker constraints are collectively cast in a variational format. In addition to the deformation, both the plastic strain and the consistency parameter are global degrees of freedom in the resulting spatially discrete problem. The ensuing proliferation of global degrees of freedom in the multifield approach is addressed by exploiting the block sparse structure of the algebraic system together with a tailored block matrix solver which can utilise emerging hardware architectures. A series of numerical problems demonstrate the validity, capability and efficiency of the proposed approach. [ABSTRACT FROM AUTHOR]

Recent findings suggest that treatment with 11β-HSD1 inhibitors provides a novel approach to deal with age-related cognitive dysfunctions, including Alzheimer's disease. In this work we report potent 11β-HSD1 inhibitors featuring unexplored pyrrolidine-based polycyclic substituents. A selected candidate administered to 12-month-old SAMP8 mice for four weeks prevented memory deficits and displayed a neuroprotective action. This is the first time that 11β-HSD1 inhibitors have been studied in this broadly-used mouse model of accelerated senescence and late-onset Alzheimer's disease. [ABSTRACT FROM AUTHOR]

A series of potent, competitive and highly selective kynurenine monooxygenase inhibitors have been discovered via a substrate-based approach for the treatment of acute pancreatitis. The lead compound demonstrated good cellular potency and clear pharmacodynamic activity in vivo . [ABSTRACT FROM AUTHOR]

Objectives: Hypertension (HTN) is a common cause of left ventricular hypertrophy (LVH). Sustained pressure overload induces a permanent myocardial switch from fatty-acid to glucose metabolism. In this study, we tested the hypothesis that metabolic remodeling, characterized by increased myocardial glucose uptake, precedes structural and functional remodeling in HTN-induced LVH. Methods: We recruited 31 patients: 11 with HTN only, 9 with HTN and LVH and 11 normotensive controls without LVH. Transthoracic echocardiography was performed to assess the function, mass, wall thickness and diastolic function of the left ventricle. Positron emission tomography imaging was performed, and the rate of myocardial 2-deoxy-2-[18F]fluoro-D-glucose uptake, Ki, was determined using a 3-compartment kinetic model. Results: The mean Ki values were significantly higher in HTN patients than in those with HTN and LVH (p < 0.001) and in controls (p = 0.003). The unexpected decrease in Ki with LVH may be secondary to a decreased Ki with diastolic dysfunction (DD), 0.039 ± 0.032 versus 0.072 ± 0.013 (p = 0.004). There was also a significant stepwise decrease in Ki with increasing DD grade (p = 0.04). Conclusion: Glucose metabolic remodeling is detectable in hypertensive patients before the development of LVH. Furthermore, lower glucose uptake rates are observed in patients with DD. The mechanism for this last finding requires further investigation. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A novel implicit integration scheme for the Discrete Element Method (DEM) based on the variational integrator approach is presented. The numerical solver provides a fully dynamical description that, notably, reduces to an energy minimisation scheme in the quasi-static limit. A detailed derivation of the numerical method is presented for the Hookean contact model and tested against an established open source DEM package that uses the velocity-Verlet integration scheme. These tests compare results for a single collision, long-term stability and statistical quantities of ensembles of particles. Numerically, the proposed integration method demonstrates equivalent accuracy to the velocity-Verlet method. • An implicit integration scheme for the Discrete Element Method based on the variational integrator approach is presented. • Numerically, the proposed integration method demonstrates equivalent accuracy to the established methods. • This work is inspired by the Quasicontinuum Method and is seen as a crucial step towards a granular Quasicontinuum Method. [ABSTRACT FROM AUTHOR]

Aims Genetically influenced aspects of adolescent behaviour can play a role in alcohol use and peer affiliation. We explored the correlations between friends' alcohol use and adolescent own use with a genetically sensitive design. Design Genetic and environmental factors were estimated on adolescent reports of their friends' alcohol use and their own use and problem use of alcohol. The correlations between the genetic and environmental factors that influence friends' alcohol use and adolescent own alcohol use and problem use were also estimated. Participants A total of 862 twin pairs aged 11–17 years sampled from the UK population-based Cardiff Study of All Wales and North-west of England Twins (CaStANET). Measurements Data on adolescent own alcohol use and problem use and the alcohol use of their three best friends were obtained using self-report questionnaires. Findings A significant genetic influence was found on adolescent friends' alcohol use (about 30%). Significant correlations of 0.60 and 0.70 were found between the genetic influences on friends' alcohol use and adolescents' own use and problem use of alcohol. Common environmental influences were almost completely correlated for friends' alcohol use and adolescents' own alcohol use and problem use (0.91 and 0.94). Conclusions There is considerable overlap in the common environmental and genetic factors that contribute to the relationship between adolescents' own alcohol use and that of their friends. These findings contribute to understanding of the mechanisms by which friends' alcohol use influences adolescent drinking behaviour. [ABSTRACT FROM AUTHOR]

Aims To examine the genetic and environmental contributions to the initiation of use and progression to more serious use of alcohol, cigarettes and marijuana during adolescence, and to examine the relationship between initiation and progression of substance use. Design The study used a twin-based design and a new theoretical model, the causal–common–contingent (CCC) model. This allows modelling of the relationship between initiation of use and progression to heavier use as a two-stage model and the examination of genetic and environmental influences on both stages, while taking into account their relationship. Participants The participants consisted of 1214 twin pairs (69% response rate) aged 11–19 years sampled from the UK population-based Cardiff Study of All Wales and North-west of England Twins (CaStANET). Measurements Data on adolescent initiation and progression to more serious use of alcohol, cigarettes and marijuana were obtained using self-report questionnaires. Findings Initiation of alcohol and progression to heavier alcohol use had separate but related underlying aetiologies. For cigarette and marijuana use the relation between initiation and progression to heavier use was stronger, suggesting greater overlap in aetiologies. For all three substances, environmental influences that make twins more similar (common environment) tended to be greater for initiation, while genetic influences were stronger for heavier use. Conclusions These findings have implications for policy decisions aimed at an adolescent and early adult age group. Specifically, these findings suggest that it may be more efficacious to focus alcohol interventions on risk factors for the development of heavier use rather than initiation of use. In contrast, interventions aimed at reducing the initiation of cigarettes and marijuana use may be more appropriate. [ABSTRACT FROM AUTHOR]

In continuum bone remodelling, bone is considered as continuous matter on the macroscale. Motivated by i) the underlying trabecular microstructure of bone resulting in size-dependence and ii) the non-local characteristics of osteocyte mechanosensing, a novel phenomenological approach based on a micromorphic formulation is proposed. Via illustrative benchmark examples, i.e. elementary unit cube, rod-shaped bone samples, and a 3D-femur sample, the novel approach is compared to the established local formulation, and the influence of the characteristic size of the microcontinuum and the coupling between macro- and microscale deformation is analysed. Taken together, the interaction between continuum points at the macroscale and their neighbourhood is effectively captured by the micromorphic formulation thus influencing the resulting distribution of nominal bone density at the macroscale.

Background: The treatment of shoulder osteoarthritis in the young patient remains challenging. The higher functional demands and higher expectations of the young patient cohort are often coupled with increased failure and revision rates. Consequently, shoulder surgeons are faced with a unique challenge with implant selection. The aim of this study was to compare the survivorship and reasons for revision of 5 classes of shoulder arthroplasty in patients aged <55 years with a primary diagnosis of osteoarthritis by use of data from a large national arthroplasty registry., Methods: The study population included all primary shoulder arthroplasty procedures undertaken for osteoarthritis in patients aged <55 years and reported to the registry between September 1999 and December 2021. Procedures were grouped into the following classes: total shoulder arthroplasty (TSA), hemiarthroplasty resurfacing (HRA), hemiarthroplasty stemmed metallic head (HSMH), hemiarthroplasty stemmed pyrocarbon head (HSPH), and reverse total shoulder arthroplasty (RTSA). The outcome measure was the cumulative percent revision, which was defined using Kaplan-Meier estimates of survivorship to describe the time to the first revision. Hazard ratios (HRs) were calculated from Cox proportional hazards models, adjusting for age and sex, to compare revision rates among groups., Results: There were 1564 shoulder arthroplasty procedures in patients aged <55 years, of which 361 (23.1%) were HRA, 70 (4.5%) were HSMH, 159 (10.2%) were HSPH, 714 (45.7%) were TSA, and 260 (16.6%) were RTSA. HRA had a higher rate of revision than RTSA after 1 year (HRA = 2.51 (95% CI 1.30, 4.83), P = .005), with no difference prior to that time. In addition, HSMH had a higher rate of revision than RTSA for the entire period (HR, 2.69 [95% confidence interval, 1.28-5.63], P = .008). There was no significant difference in the rate of revision for HSPH and TSA when they were compared with RTSA. Glenoid erosion was the most common cause of revision for HRA (28.6% of revisions) and HSMH (50%). Instability/dislocation was the leading cause of revision for RTSA (41.7%) and HSPH (28.6%), and for TSA, the majority of revisions were for either instability/dislocation (20.6%) or loosening (18.6%)., Conclusion: These results should be interpreted within the context of the lack of availability of long-term data on RTSA and HSPH stems. RTSA outperforms all implants regarding revision rates at mid-term follow-up. The high early dislocation rate associated with RTSA, as well as the lack of revision options available to address this, indicates that careful selection of patients and a greater appreciation of anatomic risk factors are needed in the future., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Shoulder replacement is a reliable treatment for the relief of pain and improvement of function in patients with glenohumeral arthritis, rotator cuff arthropathy, osteonecrosis and fracture. Limited data is available comparing revision rates for the different types of shoulder replacement when used in younger patients. This study aims to compare the survivorship of hemi resurfacing, stemmed hemiarthroplasty, total shoulder arthroplasty and reverse total shoulder arthroplasty in younger patients using data from a large national arthroplasty registry., Methods: Data from the Australian Orthopaedic Association National Joint Replacement Registry was obtained for the period 16 April 2004-31 December 2018. The study population included all shoulder arthroplasty patients aged <65 years. These were stratified into two groups: <55 years and 55-64 years. A total of 8742 primary shoulder arthroplasty procedures were analysed (1936 procedures in the <55 years and 6806 in the 55-64 years age group)., Results: In the <55 years age group, there was no difference in revision rate for total shoulder arthroplasty versus reverse total shoulder arthroplasty at any time point. Reverse total shoulder arthroplasty had a lower revision rate after six months when compared to hemi resurfacing (HRA) (p = 0.031). Also, reverse total shoulder arthroplasty had a higher early rate of revision in the first 12 months compared to hemiarthroplasty (p = 0.018). However, from 2 years reverse total shoulder arthroplasty had a lower revision rate overall (p = 0.029).In the 55-64 years patient age group, reverse total shoulder arthroplasty had a lower earlier revision rate. This was statistically significant compared to hemi resurfacing (HRA) (p = 0.028), hemiarthroplasty (p = 0.049) and total shoulder arthroplasty (p < 0.001)., Conclusion: This study demonstrated that for patients aged <55 years there was no significant difference in the rate of revision when total shoulder arthroplasty and reverse total shoulder arthroplasty were compared. reverse total shoulder arthroplasty had a lower rate of revision when compared to hemi resurfacing and hemiarthroplasty after 2 years. reverse total shoulder arthroplasty had the lowest comparative revision rate in patients aged 55-64 years overall., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: The most common complication with reverse shoulder arthroplasty Grammont based design with a 155° neck shaft angle (NSA) is scapular notching. Scapular notching has been associated with reduced clinical outcomes. Reducing the humeral NSA from 155° has been shown to reduce the incidence of scapular notching however it is unknown whether there is a difference in scapular notching between a 145° and 135° NSA. The purpose of this study was to evaluate the effect of decreasing the NSA on scapular notching rate and postoperative range of motion comparing 145° and 135° NSA stems at minimum 2 yr of follow-up., Methods: Consecutive patients undergoing primary reverse shoulder arthroplasty with a NSA of either 145° or 135° between January 2014 and February 2019 were retrospectively reviewed. Patients were included if they were over the age of 18, had minimum clinical follow-up of 24 mo with true postoperative anteroposterior radiographic view., Results: One hundred and three patients were included for the final analysis: 73 with a 145° NSA and 30 with a 135° NSA stem. The mean age and mean follow-up were respectively 70.9 yr (range, 52.0-89.0) and 32.1 mo. The overall incidence of scapular notching was 46.6 %. There was a statistically significant difference in scapular notching between the 145° (53.4%) and 135° (30%) NSA groups (P = .028). There was no difference in terms of postoperative Constant-Murley Score (mean, 66.1 vs. 68.2; P = .395), Subjective Shoulder Value (mean, 76.5 vs. 83.1%, P = .167), forward flexion (mean, 140° vs. 142°, P = .704), abduction (mean, 123.2° vs. 121.5°, P = .771), external rotation with the arm at the side (mean, 34.1° vs. 37.3°, P = .341) and internal rotation (mean, 5.3 vs. 5.4 pts P = .336) between the 2 groups., Conclusion: This is the first study to compare the effect of a 145° vs. 135° NSA on scapular notching rates. The key finding of this study is that scapular notching rate was significantly reduced from 53% to 30% in 135° NSA compared to 145° NSA, after at least 24 mo of follow-up. Our data also show that glenoid lateralization and inferiorization has an influence on scapular notching. We are unable to state that the reduced scapular notching rate was due to a reduction in NSA alone. Despite a lower rate of scapular notching, the 135° NSA group has not shown any significant better clinical and functional outcomes., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

The Trillat procedure has been described for the management of shoulder instability in younger patients but also for shoulder instability in older patients with irreparable rotator cuff tears. We describe an all-arthroscopic technique using screw fixation. This technique allows for safe dissection, clearance and osteotomy of the coracoid, and direct visualization during screw tensioning and fixation to minimize the risk of subscapularis impingement. We outline our stepwise approach to medialize and distalize the coracoid process using arthroscopic screw fixation and present pearls to avoid fracture through the superior bone bridge., (© 2023 The Authors.)