Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development

Peer reviewedPublisher PD

Electromyographic Analysis of the Shoulder Girdle Musculature during External Rotation Exercises

Background: Implementation of overhead activity, a key component of many professional sports, requires an effective and balanced activation of shoulder girdle muscles particularly during forceful external rotation motions. Purpose: The study aimed to identify activation strategies of 16 shoulder girdle muscles/muscle segments during common shoulder external rotational exercises. Study Design: Cross-Sectional Study Method: EMG was recorded in 30 healthy subjects from 16 shoulder girdle muscles/muscle segments (surface electrode: anterior, middle and posterior deltoid, upper, middle and lower trapezius, serratus anterior, teres major, upper and lower latissimus dorsi, upper and lower pectoralis major; fine wire electrodes: supraspinatus, infraspinatus, subscapularis and rhomboid major) using a telemetric EMG system. Five external rotation (ER) exercises (standing ER at 0o and 90o of abduction, and with under-arm towel roll, prone ER at 90o of abduction, side-lying ER with under-arm towel) were studied. Exercise EMG amplitudes were normalised to EMGmax (EMG at maximal ER force in a standard position). Univariate analysis of variance (ANOVA) and post-hoc analysis applied on EMG activity of each muscle to assess the main effect of exercise condition. Results: Muscular activity differed significantly among the ER exercises (P<0.05 – P<0.001). The highest activation for anterior and middle deltoid, supraspinatus, upper trapezius, and serratus anterior occurred during standing ER at 90o of abduction; for posterior deltoid, middle trapezius, and rhomboid during side-lying ER at 0° of abduction; for lower trapezius, upper and lower latissimus dorsi, subscapularis, and teres major during prone ER at 90o of abduction, and for clavicular and sternal part of pectoralis major during standing ER with Under-Arm Towel. Conclusion: Key glenohumeral and scapular muscles can be optimally activated during the specific ER exercises particularly in positions that stimulate athletic overhead motions. Clinical Relevance: These results enable sport medicine professionals to target specific muscles during shoulder rehabilitation protocols while minimising the effect of others, providing a foundation for optimal evidence-based exercise prescription. They also provide information for tailored muscle training and injury prevention in overhead sports

Risk of subsequent primary neoplasms in survivors of adolescent and young adult cancer (Teenage and Young Adult Cancer Survivor Study): a population-based, cohort study.

Background Few studies have investigated the risks of subsequent primary neoplasms after adolescent and young adult (AYA) cancer. We investigated the risks of specific subsequent primary neoplasms after each of 16 types of AYA cancer. Methods The Teenage and Young Adult Cancer Survivor Study is a population-based cohort of 200 945 survivors of cancer diagnosed when aged 15–39 years in England and Wales from Jan 1, 1971, to Dec 31, 2006. The cohort was established using cancer registrations from the Office for National Statistics and the Welsh Cancer registry. Follow-up was from 5-year survival until the first occurrence of death, emigration, or study end date (Dec 31, 2012). In this analysis, we focus on the risk of specific subsequent primary neoplasms after 16 types of AYA cancer: breast; cervical; testicular; Hodgkin lymphoma (female); Hodgkin lymphoma (male); melanoma; CNS (intracranial); colorectal; non-Hodgkin lymphoma; thyroid; soft-tissue sarcoma; ovarian; bladder; other female genital; leukaemia; and head and neck cancer. We report absolute excess risks (AERs; per 10 000 person-years) and cumulative incidence of specific types of subsequent primary neoplasm after each type of AYA cancer. Findings During the 2 631 326 person-years of follow-up (median follow-up 16·8 years, IQR 10·5–25·2), 12 321 subsequent primary neoplasms were diagnosed in 11 565 survivors, most frequently among survivors of breast cancer, cervical cancer, testicular cancer, and Hodgkin lymphoma. AERs of any subsequent primary neoplasms were 19·5 per 10 000 person-years (95% CI 17·4–21·5) in survivors of breast cancer, 10·2 (8·0–12·4) in survivors of cervical cancer, 18·9 (16·6–21·1) in survivors of testicular cancer, 55·7 (50·4–61·1) in female survivors of Hodgkin lymphoma, and 29·9 (26·3–33·6) in male survivors of Hodgkin lymphoma. The cumulative incidence of all subsequent primary neoplasms 35 years after diagnosis was 11·9% (95% CI 11·3–12·6) in survivors of breast cancer, 15·8% (14·8–16·7) in survivors of cervical cancer, 20·2% (18·9–21·5) in survivors of testicular cancer, 26·6% (24·7–28·6) in female survivors of Hodgkin lymphoma, and 16·5% (15·2–18·0) in male survivors of Hodgkin lymphoma. In patients who had survived at least 30 years from diagnosis of cervical cancer, testicular cancer, Hodgkin lymphoma in women, breast cancer, and Hodgkin lymphoma in men, we identified a small number of specific subsequent primary neoplasms that account for 82%, 61%, 58%, 45%, and 41% of the total excess number of neoplasms, respectively. Lung cancer accounted for a notable proportion of the excess number of neoplasms across all AYA groups investigated. Interpretation Our finding that a small number of specific subsequent primary neoplasms account for a large percentage of the total excess number of neoplasms in long-term survivors of cervical, breast, and testicular cancer, and Hodgkin lymphoma provides an evidence base to inform priorities for clinical long-term follow-up. The prominence of lung cancer after each of these AYA cancers indicates the need for further work aimed at preventing and reducing the burden of this cancer in future survivors of AYA cancer. Funding Cancer Research UK, National Institute for Health Research, Academy of Medical Sciences, and Children with Cancer UK

Stent Design, Restenosis and Recurrent Stroke After Carotid Artery Stenting in the International Carotid Stenting Study

BACKGROUND AND PURPOSE: Open-cell carotid artery stents are associated with a higher peri-procedural stroke risk than closed-cell stents. However, the effect of stent design on long-term durability of carotid artery stenting (CAS) is unknown. We compared the medium- to long-term risk of restenosis and ipsilateral stroke between patients treated with open-cell stents versus closed-cell stents in the ICSS (International Carotid Stenting Study). METHODS: Patients with symptomatic carotid stenosis were randomized to CAS or endarterectomy and followed with duplex ultrasound for a median of 4.0 years. We analyzed data from patients with completed CAS procedures, known stent design, and available ultrasound follow-up. The primary outcome, moderate or higher restenosis (≥50%) was defined as a peak systolic velocity of >1.3 m/s on ultrasound or occlusion of the treated internal carotid artery and analyzed with interval-censored models. RESULTS: Eight hundred fifty-five patients were allocated to CAS. Seven hundred fourteen patients with completed CAS and known stent design were included in the current analysis. Of these, 352 were treated with open-cell and 362 with closed-cell stents. Moderate or higher restenosis occurred significantly less frequently in patients treated with open-cell (n=113) than closed-cell stents (n=154; 5-year risks were 35.5% versus 46.0%; unadjusted hazard ratio, 0.68; 95% CI, 0.53–0.88). There was no significant difference in the risk of severe restenosis (≥70%) after open-cell stenting (n=27) versus closed-cell stenting (n=43; 5-year risks, 8.6% versus 12.7%; unadjusted hazard ratio, 0.63; 95% CI, 0.37–1.05). The risk of ipsilateral stroke beyond 30 days after treatment was similar with open-cell and closed-cell stents (hazard ratio, 0.78; 95% CI, 0.35–1.75). CONCLUSIONS: Moderate or higher restenosis after CAS occurred less frequently in patients treated with open-cell stents than closed-cell stents. However, both stent designs were equally effective at preventing recurrent stroke during follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com/. Unique identifier: ISRCTN25337470

Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Optimal cut-off criteria for duplex ultrasound for the diagnosis of restenosis in stented carotid arteries: Review and protocol for a diagnostic study

Background: Carotid angioplasty with stenting is a relatively new, increasingly used, less-invasive treatment for the treatment of symptomatic carotid artery stenosis. It is being evaluated in ongoing and nearly finished randomized trials. An important factor in the evaluation of stents is the occurrence of in-stent restenosis. An un-stented carotid artery is likely to have a more elastic vessel wall than a stented one, even if stenosis is present. Therefore, duplex ultrasound cut-off criteria for the degrees of an in-stent stenosis, based on blood velocity parameters, are probably different from the established cut-offs used for un-stented arteries. Routine criteria can not be applied to stented arteries but new criteria need to be established for this particular purpose. Methods/Design: Current literature was systematically reviewed. From the selected studies, the following data were extracted: publication year, population size, whether the study was prospective, which reference test was used, and if there was an indication for selection bias and for verification bias in particular. Previous studies often were retrospective, or the reference test (DSA or CTA) was carried out only when a patient was suspected of having restenosis at DUS, which may result in verification bias. Results: In general, the cut-off values are higher than those reported for unstented arteries. Previous studies often were retrospective, or the reference test (DSA or CTA) was carried out only when a patient was suspected of having restenosis at DUS, which may result in verification bias. Discussion: To address the deficiencies of the existing studies, we propose a prospective cohort study nested within the International Carotid Stenting Study (ICSS), an international multi-centre trial in which over 1,700 patients have been randomised between stenting and CEA. In this cohort we will enrol a minimum of 300 patients treated with a stent. All patients undergo regular DUS examination at the yearly follow-up visit according to the ICSS protocol. To avoid verification bias, an additional computed tomography angiography (CTA) will be performed as a reference test in all consecutive patients, regardless of the degree of stenosis on the initial DUS test

HIV self-testing intervention experiences and kit usability: results from a qualitative study among men who have sex with men in the SELPHI (Self-Testing Public Health Intervention) randomized controlled trial in England and Wales.

OBJECTIVES: SELPHI (HIV Self-Testing Public Health Intervention) is the largest randomized controlled trial (RCT) of HIV self-testing (HIVST) in a high-income setting to date, and has recruited 10 000 men who have sex with men (cis- and transgender) and transgender women who have sex with men. This qualitative substudy aimed to explore how those utilizing self-tests experience HIVST and the implications for further intervention development and scale-up. This is the first qualitative study in Europe investigating experiences of HIVST among intervention users, and the first globally examining the experience of using blood-based HIVST. METHODS: Thirty-seven cisgender MSM SELPHI participants from across England and Wales were purposively recruited to the substudy, in which semi-structured interviews were used to explore testing history, HIVST experiences and intervention preferences. Interviews were audio-recorded, transcribed and analysed through a framework analysis. RESULTS: Men accessed the intervention because HIVST reduced barriers related to convenience, stigma and privacy concerns. Emotional responses had direct links to acceptability. Supportive intervention components increased engagement with testing and addressed supportive concerns. HIVST facilitated more frequent testing, with the potential to reduce sexually transmitted infection (STI) screening frequency. Substudy participants with an HIV-positive result (n = 2) linked to care promptly and reported very high acceptability. Minor adverse outcomes (n = 2; relationship discord and fainting) did not reduce acceptability. Ease of use difficulties were with the lancet and the test processing stage. CONCLUSIONS: Intervention components shaped acceptability, particularly in relation to overcoming a perceived lack of support. The intervention was broadly acceptable and usable; participants expressed an unexpected degree of enthusiasm for HIVST, including those with HIV-positive results and individuals with minor adverse outcomes

Improving tribological properties of cast Al-Si alloys through application of wear-resistant thermal spray coatings

Flame Spray Thermal Spray coatings are low-cost, high-wear surface-treatment technologies. However, little has been reported on their potential effects on cast automotive aluminum alloys. The aim of this research was to investigate the tribological properties of as-sprayed NiCrBSi and WC/12Co Flame Spray coatings applied to two cast aluminum alloys: high-copper LM24 (AlSi8Cu3Fe), and low-copper LM25 (AlSi7Mg). Potential interactions between the mechanical properties of the substrate and the deposited coatings were deemed to be significant. Microstructural, microhardness, friction, and wear (pin-on-disk, microabrasion, Taber abrasion, etc.) results are reported, and the performance differences between coatings on the different substrates were noted. The coefficient of friction was reduced from 0.69-0.72 to 0.12-0.35. Wear (pin-on-disk) was reduced by a factor of 103-104, which was related to the high surface roughness of the coatings. Microabrasion wear was dependent on coating hardness and applied load. Taber abrasion results showed a strong dependency on the substrate, coating morphology, and homogeneity

The phenotypic spectrum associated with OTX2 mutations in humans

OBJECTIVE: The transcription factor OTX2 is implicated in ocular, craniofacial, and pituitary development. DESIGN: We aimed to establish the contribution of OTX2 mutations in congenital hypopituitarism patients with/without eye abnormalities, study functional consequences, and establish OTX2 in the human brain, with a view to investigating the mechanism of action. METHODS: We screened patients from the UK (n=103), international centers (n=24), and Brazil (n=282); 145 were within the septo-optic dysplasia spectrum, and 264 had no eye phenotype. Transactivation ability of OTX2 variants was analysed in murine hypothalamic GT1-7 neurons. In situ hybridization was performed on human embryonic brain sections. Genetically engineered mice were generated with a series of C-terminal OTX2 variants. RESULTS: Two chromosomal deletions and six haploinsufficient mutations were identified in individuals with eye abnormalities; an affected relative of one patient harboured the same mutation without an ocular phenotype. OTX2 truncations led to significant transactivation reduction. A missense variant was identified in another patient without eye abnormalities, however studies revealed it was most likely not causative. In the mouse, truncations proximal to aa219 caused anophthalmia, while distal truncations and the missense variant were tolerated. During human embryogenesis, OTX2 was expressed in the posterior pituitary, retina, ear, thalamus, choroid plexus, and partially in the hypothalamus, but not in the anterior pituitary. CONCLUSIONS: OTX2 mutations are rarely associated with hypopituitarism in isolation without eye abnormalities, and may be variably penetrant, even within the same pedigree. Our data suggest that the endocrine phenotypes in patients with OTX2 mutations are of hypothalamic origin

A zoo-led study of the great ape bushmeat commodity chain in Cameroon

Current levels of bushmeat hunting in west and central Africa are largely unsustainable, and will lead to the loss of an important natural resource and cause the extinction of threatened species. Worryingly, great apes are hunted for their meat despite being protected across their range. In this paper, we highlight the main actors involved in the trafficking of great ape meat around the Dja Biosphere Reserve (DBR) in Cameroon, and describe the commodity chain associated with the trade. In total, 78 hunters, porters, traders and consumers were interviewed. Hunters, all men, were primarily driven by profit, encouraged by middlemen, though some hunt for their own consumption. However, we identify that great ape hunting is undertaken by specialised hunters along a relatively short supply chain. Gorilla and chimpanzee meat is sold to restaurants and wealthy buyers via few intermediaries. The price of great ape meat varied at different stages of the chain. Middlemen obtained the greatest financial gain, whereas wholesale traders profited least. Movement of ape meat to markets was predominantly by public transport and facilitated by drivers who can pass through checkpoints unnoticed. Based on our study we recommend potential interventions, including support of law enforcement, investments in conservation and development initiatives, and monitoring and research