Effectiveness of early orthodontic treatment with the Twin-block appliance: a multicenter, randomized, controlled trial. Part 1: Dental and skeletal effects.

This study evaluated the effectiveness of early orthodontic treatment with the Twin-block appliance for the developing Class II Division 1 malocclusion. This multicenter trial was carried out in the United Kingdom. A total of 174 children, aged 8 to 10 years old, with Class II Division 1 malocclusion were randomly allocated to receive treatment with a Twin-block appliance or to an untreated, control group. Data were collected at the start of the study and 15 months later. Results showed that early treatment with Twin-block appliances resulted in reduction of overjet, correction of molar relationships, and reduction in severity of malocclusion. Most of this correction was due to dentoalveolar change, but some was due to favorable skeletal change. Early treatment with the Twin-block appliance is effective in reducing overjet and severity of malocclusion. The small change in the skeletal relationship might not be considered clinically significant.     

Diagnosing menstrual disorders: a qualitative study of the approach of primary care professionals

BACKGROUND: Menstrual disorders are a common presentation in primary care. Wide variations in management as well as discordance between patient and practitioners in relation to presenting problems have been described. AIMS: To explore the model of menstrual disorders used by practitioners in practice. DESIGN OF STUDY: Semi-structured interviews with primary care practitioners. SETTING: One inner London health authority area. METHOD: Constant comparative analysis. RESULTS: Medical practitioners were critical of the guidance provided by gynaecological definitions and texts. Practitioners put more emphasis on defining normality than on defining disorder. Practitioners used a wide range of criteria to judge their patients' complaints and decide on a course of action. Female practitioners had access to personal and professional experience and used this to develop an understanding of women's complaints. Male practitioners in particular were limited by problems in discussing menstruation in detail. Because of the difficulties in assessing patient history, other non-gynaecological factors such as patient age and consulting behaviour informed practitioners' judgements. CONCLUSION: This study draws attention to practitioners' problems in using current definitions of menstrual disorders. The combination of unhelpful medical definitions, lack of standards of normality and difficulties in discussing menstruation resulted in individual practitioners making judgements in idiosyncratic ways. In the absence of a useful gynaecological model, practitioners develop individual, often subjective and gendered models to use in practice.     

Dural Tissue Trauma and Cerebrospinal Fluid Leak after Epidural Needle Puncture: Effect of Needle Design, Angle, and Bevel Orientation

Background: The effects of epidural needle design, angle, and bevel orientation on cerebrospinal fluid leak after puncture have not been reported. The impact of these factors on leak rate was examined using a dural sac model. Dural trauma was examined using scanning electron microscopy.

Methods: Human cadaveric dura, mounted on a cylindrical model, was punctured with epidural needles using a micromanipulator. Tissue was punctured at 15 cm H2O (left lateral decubitus) system pressure, and leak was measured at 25 cm H2O (semisitting) pressure. Leak rates and trauma were compared for the following: (1) six different epidural needles at 90[degrees], bevel parallel to the dural long axis; (2) 18-gauge Tuohy and 18-gauge Special Sprotte(R) epidural needles, 30[degrees]versus 90[degrees]; (3) 18-gauge Tuohy, bevel perpendicular versus parallel to the dural long axis.

Results: With the 90[degrees] puncture, bevel parallel, the greatest leak occurred with a 17-gauge Hustead (516 +/- 319 ml/15 min), and the smallest leak occurred with a 20-gauge Tuohy (100 +/- 112 ml/15 min; P = 0.0018). A 20-gauge Tuohy puncture led to statistically significant reductions in leak (P value range, 0.0001-0.0024) compared with all needles except the Special Sprotte(R). With the 30[degrees]versus 90[degrees] angle, 30[degrees] punctures with an 18-gauge Tuohy produced nonstatistically significant leak reductions compared with the 18-gauge Tuohy at 90[degrees]. The puncture angle made no difference for the Special Sprotte(R). Nonsignificant reductions were found for the Special Sprotte(R) compared with the Tuohy. With the 18-gauge Tuohy bevel orientation, perpendicular orientation produced nonstatistically significant reductions in leak compared with parallel orientation.     

Laforin preferentially binds the neurotoxic starch-like polyglucosans, which form in its absence in progressive myoclonus epilepsy

Lafora disease (LD) is a fatal and the most common form of adolescent-onset progressive epilepsy. Fulminant endoplasmic reticulum (ER)-associated depositions of starch-like long-stranded, poorly branched glycogen molecules [known as polyglucosans, which accumulate to form Lafora bodies (LBs)] are seen in neuronal perikarya and dendrites, liver, skeletal muscle and heart. The disease is caused by loss of function of the laforin dual-specificity phosphatase or the malin E3 ubiquitin ligase. Towards understanding the pathogenesis of polyglucosans in LD, we generated a transgenic mouse overexpressing inactivated laforin to trap normal laforin's unknown substrate. The trap was successful and LBs formed in liver, muscle, neuronal perikarya and dendrites. Using immunogold electron microscopy, we show that laforin is found in close proximity to the ER surrounding the polyglucosan accumulations. In neurons, it compartmentalizes to perikaryon and dendrites and not to axons. Importantly, it binds polyglucosans, establishing for the first time a direct association between the disease-defining storage product and disease protein. It preferentially binds polyglucosans over glycogen in vivo and starch over glycogen in vitro, suggesting that laforin's role begins after the appearance of polyglucosans and that the laforin pathway is involved in monitoring for and then preventing the formation of polyglucosans. In addition, we show that the laforin interacting protein, EPM2AIP1, also localizes on the polyglucosan masses, and we confirm laforin's intense binding to LBs in human LD biopsy material.     

Injecting drug use among gay and bisexual men in Sydney: prevalence and associations with sexual risk practices and HIV and hepatitis C infection

Injecting drug use is commonly reported among gay and bisexual men in Australia. We examined the prevalence and covariates of injecting drug use among men participating in the Sydney Gay Community Periodic Survey between 2004–06 and 2011. In 2004–06, data was collected about which drugs were injected, while in 2011, data was collected about hepatitis C (HCV) and esoteric sexual practices. In 2004–06, 5.6 % of men reported injecting drugs in the previous 6 months; 3.4 % reported methamphetamine injection and 0.4 % heroin injection. In 2011, men who injected drugs were less likely to be employed full-time, and more likely to be HCV-positive, HIV-positive, to have used party drugs for sex, and to have engaged in esoteric sexual practices. The strong associations between injecting drug use, sexual risk practices and blood-borne virus infection suggests the need for combined sexual health and harm reduction services for gay and bisexual men who inject drugs.     

Diagnostic value of symptoms of oesophagogastric cancers in primary care: a systematic review and meta-analysis

Background

Selection of primary care patients for investigation of potential oesophagogastric cancer is difficult, as the symptoms may represent benign conditions, which are also more common.

Aim

To review systematically the presenting features of oesophagogastric cancers in primary care, including open-access endoscopy clinics.

Design and setting

Systematic review and meta-analysis.

Method

MEDLINE^®, Embase, the Cochrane Library, and CINAHL were searched for studies of adults who were symptomatic and presented in primary care or open-access endoscopy clinics. Exclusions were being asymptomatic, screening, or recurrent cancers. Data were extracted to estimate the diagnostic performance of features of oesophagogastric cancers and summarised in a meta-analysis.

Results

Fourteen studies were identified. The strongest summary sensitivity and specificity estimates were for: dyspepsia 0.42 (95% confidence interval [CI] 0.29 to 0.56) and 0.48 (95% CI = 0.31 to 0.65); pain 0.41 (95% CI = 0.24 to 0.62) and 0.75 (95% CI = 0.51 to 0.89); and dysphagia 0.32 (95% CI = 0.17 to 0.52) and 0.92 (95% CI = 0.81 to 0.97). Summary positive likelihood ratios (LR+) and diagnostic odds ratios were: dyspepsia 0.79 (95% CI = 0.55 to 1.15) and 0.65 (95% CI = 0.32 to 1.33); pain 1.64 (95% CI = 1.20 to 2.24) and 2.09 (95% CI = 1.57 to 2.77); and dysphagia 4.32 (95% CI = 2.46 to 7.58) and 5.91 (95% CI = 3.56 to 9.82). Corresponding LR+ were: anaemia 4.32 (95% CI = 2.64 to 7.08); nausea/vomiting/bloating 1.07 (95% CI = 0.52 to 2.19); reflux 0.78 (95% CI = 0.47 to 1.78) and; weight loss 5.46 (95% CI = 3.47 to 8.60).

Conclusion

Dysphagia, weight loss, and anaemia show the strongest association but with relatively low sensitivity and high specificity. The findings support the value of investigation of these symptoms, but also suggest that, in a population of patients who are low risk but not no-risk, investigation is not currently recommended.     

Toxicity profiles and solvent–toxicant interference in the planarian Schmidtea mediterranea after dimethylsulfoxide (DMSO) exposure

To investigate hydrophobic test compounds in toxicological studies, solvents like dimethylsulfoxide (DMSO) are inevitable. However, using these solvents, the interpretation of test compound‐induced responses can be biased. DMSO concentration guidelines are available, but are mostly based on acute exposures involving one specific toxicity endpoint. Hence, to avoid solvent–toxicant interference, we use multiple chronic test endpoints for additional interpretation of DMSO concentrations and propose a statistical model to assess possible synergistic, antagonistic or additive effects of test compounds and their solvents. In this study, the effects of both short‐ (1 day) and long‐term (2 weeks) exposures to low DMSO concentrations (up to 1000 µl l^?1) were studied in the planarian Schmidtea mediterranea. We measured different biological levels in both fully developed and developing animals. In a long‐term exposure set‐up, a concentration of 500 µl l^?1 DMSO interfered with processes on different biological levels, e.g. behaviour, stem cell proliferation and gene expression profiles. After short exposure times, 500 µl l^?1 DMSO only affected motility, whereas the most significant changes on different parameters were observed at a concentration of 1000 µl l^?1 DMSO. As small sensitivity differences exist between biological levels and developmental stages, we advise the use of this solvent in concentrations below 500 µl l^?1 in this organism. In the second part of our study, we propose a statistical approach to account for solvent–toxicant interactions and discuss full‐scale solvent toxicity studies. In conclusion, we reassessed DMSO concentration limits for different experimental endpoints in the planarian S. mediterranea. Copyright © 2014 John Wiley & Sons, Ltd.     

Endothelial hyperplasia and endothelial galectin-3 expression are prognostic factors in primary central nervous system lymphomas

Recently, considerable attention has been focused on the identification of clinically relevant prognostic markers for primary central nervous system lymphomas (PCNSL). The present study investigated whether three morphological features, i.e. necrosis, reactive perivascular T-cell infiltrate and endothelial hyperplasia, and galectin-1 and galectin-3 immunohistochemical expression have prognostic roles in a series of 58 PCNSL samples from 44 immunocompetent and 14 immunocompromised patients. The presence of endothelial hyperplasia (identified in 21% of the assessable cases) was identified as a bad prognostic factor for immunocompetent PCNSL patients, whereas the other morphological features were not associated with any prognostic value. Lymphomatous cells of eight PCNSL cases expressed galectin-3 without any prognostic value, and lymphomatous cells did not express galectin-1. In contrast, endothelial expression of galectin-3 was identified (by means of uni- and multi-variate analyses) as a bad prognostic factor for immunocompetent PCNSL patients. In addition, a combination of endothelial hyperplasia and/or endothelial galectin-3 expression was shown to be an independent prognostic factor for immunocompetent PCNSL patients treated with methotrexate-based chemotherapy. In summary, this study suggests that endothelial-related markers can identify risk groups of PCNSL patients and indicates that galectin-3 could be involved in PCNSL angiogenesis.     

Islets of Langerhans from prohormone convertase‐2 knockout mice show α‐cell hyperplasia and tumorigenesis with elevated α‐cell neogenesis

Antagonism of the effects of glucagon as an adjunct therapy with other glucose‐lowering drugs in the chronic treatment of diabetes has been suggested to aggressively control blood glucose levels. Antagonism of glucagon effects, by targeting glucagon secretion or disabling the glucagon receptor, is associated with α‐cell hyperplasia. We evaluated the influence of total glucagon withdrawal on islets of Langerhans using prohormone convertase‐2 knockout mice (PC2‐ko), in which α‐cell hyperplasia is present from a young age and persists throughout life, in order to understand whether or not sustained glucagon deficit would lead to islet tumorigenesis. PC2‐ko and wild‐type (WT) mice were maintained drug‐free, and cohorts of these groups sampled at 3, 12 and 18 months for plasma biochemical and morphological (histological, immunohistochemical, electron microscopical and image analytical) assessments. WT mice showed no islet tumours up to termination of the study, but PC2‐ko animals displayed marked changes in islet morphology from α‐cell hypertrophy/hyperplasia/atypical hyperplasia, to adenomas and carcinomas, these latter being first encountered at 6–8 months. Islet hyperplasias and tumours primarily consisted of α‐cells associated to varying degrees with other islet endocrine cell types. In addition to substantial increases in islet neoplasia, increased α‐cell neogenesis associated primarily with pancreatic duct(ule)s was present. We conclude that absolute blockade of the glucagon signal results in tumorigenesis and that the PC2‐ko mouse represents a valuable model for investigation of islet tumours and pancreatic ductal neogenesis.