Tracheostomy reveals a rare aberrant right subclavian artery; a case report

BACKGROUND: Anomalies of vascular anatomy in the neck are well recognised. We present a case of a very rare aberrant artery discovered during tracheostomy. CASE PRESENTATION: Elective tracheostomy was performed in theatre for an elderly gentleman on long-term ventilation. Pre-operative examination of the neck revealed no obvious abnormality. During surgery, a large vessel was revealed overlying the tracheal fourth ring. This was found to be an anomalous right subclavian artery. The procedure was completed without complication. CONCLUSIONS: The vessel abnormality described has not been previously documented in this context. It illustrates the importance of thorough pre-operative assessment of the neck and a sound knowledge of the potential for vascular abnormalities. The increasing prevalence of percutaneous dilatational tracheostomy techniques makes this lesson increasingly relevant

Why alternative teenagers self-harm: exploring the link between non-suicidal self-injury, attempted suicide and adolescent identity

Background: The term ‘self-harm’ encompasses both attempted suicide and non-suicidal self-injury (NSSI). Specific adolescent subpopulations such as ethnic or sexual minorities, and more controversially, those who identify as ‘Alternative’ (Goth, Emo) have been proposed as being more likely to self-harm, while other groups such as ‘Jocks’ are linked with protective coping behaviours (for example exercise). NSSI has autonomic (it reduces negative emotions) and social (it communicates distress or facilitates group ‘bonding’) functions. This study explores the links between such aspects of self-harm, primarily NSSI, and youth subculture.<p></p> Methods: An anonymous survey was carried out of 452 15 year old German school students. Measures included: identification with different youth cultures, i.e. Alternative (Goth, Emo, Punk), Nerd (academic) or Jock (athletic); social background, e.g. socioeconomic status; and experience of victimisation. Self-harm (suicide and NSSI) was assessed using Self-harm Behavior Questionnaire and the Functional Assessment of Self-Mutilation (FASM).<p></p> Results: An “Alternative” identity was directly (r ≈ 0.3) and a “Jock” identity inversely (r ≈ -0.1) correlated with self-harm. “Alternative” teenagers self-injured more frequently (NSSI 45.5% vs. 18.8%), repeatedly self-injured, and were 4–8 times more likely to attempt suicide (even after adjusting for social background) than their non-Alternative peers. They were also more likely to self-injure for autonomic, communicative and social reasons than other adolescents.<p></p> Conclusions: About half of ‘Alternative’ adolescents’ self-injure, primarily to regulate emotions and communicate distress. However, a minority self-injure to reinforce their group identity, i.e. ‘To feel more a part of a group’

Mismatched single stranded antisense oligonucleotides can induce efficient dystrophin splice switching

<p>Abstract</p> <p>Background</p> <p>Antisense oligomer induced exon skipping aims to reduce the severity of Duchenne muscular dystrophy by redirecting splicing during pre-RNA processing such that the causative mutation is by-passed and a shorter but partially functional Becker muscular dystrophy-like dystrophin isoform is produced. Normal exons are generally targeted to restore the dystrophin reading frame however, an appreciable subset of dystrophin mutations are intra-exonic and therefore have the potential to compromise oligomer efficiency, necessitating personalised oligomer design for some patients. Although antisense oligomers are easily personalised, it remains unclear whether all patient polymorphisms within antisense oligomer target sequences will require the costly process of producing and validating patient specific compounds.</p> <p>Methods</p> <p>Here we report preclinical testing of a panel of splice switching antisense oligomers, designed to excise exon 25 from the dystrophin transcript, in normal and dystrophic patient cells. These patient cells harbour a single base insertion in exon 25 that lies within the target sequence of an oligomer shown to be effective at removing exon 25.</p> <p>Results</p> <p>It was anticipated that such a mutation would compromise oligomer binding and efficiency. However, we show that, despite the mismatch an oligomer, designed and optimised to excise exon 25 from the normal dystrophin mRNA, removes the mutated exon 25 more efficiently than the mutation-specific oligomer.</p> <p>Conclusion</p> <p>This raises the possibility that mismatched AOs could still be therapeutically applicable in some cases, negating the necessity to produce patient-specific compounds.</p

Circulating markers of arterial thrombosis and late-stage age-related macular degeneration: a case-control study.

PURPOSE: The aim of this study was to examine the relation of late-stage age-related macular degeneration (AMD) with markers of systemic atherothrombosis. METHODS: A hospital-based case-control study of AMD was undertaken in London, UK. Cases of AMD (n=81) and controls (n=77) were group matched for age and sex. Standard protocols were used for colour fundus photography and to classify AMD; physical examination included height, weight, history of or treatment for vascular-related diseases and smoking status. Blood samples were taken for measurement of fibrinogen, factor VIIc (FVIIc), factor VIIIc, prothrombin fragment F1.2 (F1.2), tissue plasminogen activator, and von Willebrand factor. Odds ratios from logistic regression analyses of each atherothrombotic marker with AMD were adjusted for age, sex, and established cardiovascular disease risk factors, including smoking, blood pressure, body mass index, and total cholesterol. RESULTS: After adjustment FVIIc and possibly F1.2 were inversely associated with the risk of AMD; per 1 standard deviation increase in these markers the odds ratio were, respectively, 0.62 (95% confidence interval 0.40, 0.95) and 0.71 (0.46, 1.09). None of the other atherothrombotic risk factors appeared to be related to AMD status. There was weak evidence that aspirin is associated with a lower risk of AMD. CONCLUSIONS: This study does not provide strong evidence of associations between AMD and systematic markers of arterial thrombosis, but the potential effects of FVIIc, and F1.2 are worthy of further investigation

Collagenous microstructure of the glenoid labrum and biceps anchor.

Submitted versio

Proactive and politically skilled professionals: What is the relationship with affective occupational commitment?

The aim of this study is to extend research on employee affective commitment in three ways: (1) instead of organizational commitment the focus is on occupational commitment; (2) the role of proactive personality on affective occupational commitment is examined; and (3) occupational satisfaction is examined as a mediator and political skills as moderator in the relationship between proactive personality and affective occupational commitment. Two connected studies, one in a hospital located in the private sector and one in a university located in the public sector, are carried out in Pakistan, drawing on a total sample of over 400 employees. The results show that proactive personality is positively related to affective occupational commitment, and that occupational satisfaction partly mediates the relationship between proactive personality and affective occupational commitment. No effect is found for a moderator effect of political skills in the relationship between proactive personality and affective occupational commitment. Political skills however moderate the relationship between proactive personality and affective organizational commitment

Amygdaloid Kindling and the GABA System

The effect of increased brain GABA levels on fully kindled amygdala seizures was investigated in Long-Evans rats. The newly synthesized GABA-transaminase inhibitor, -Γ-acetylenic GABA (GAG) administered on four consecutive days (100 mg/kg, followed by 50 mg/kg, i.p.) was found to either significantly reduce, or eliminate entirely, the behavioral seizures normally produced by amygdala stimulation. The effect is seen after the first injection of GAG although its magnitude was greater on subsequent days. Behavioral seizures reappeared 2 to 3 days after termination of GAG treatment. The duration of electrographic seizures (self-sustained amygdala after-discharge) was either unchanged or greater on the first day of GAG treatment, but was briefer on subsequent days. The duration of afterdischarges returned to normal levels 1 to 2 days earlier than the behavioral seizures after the termination of GAG. Picrotoxin (1.5-2 mg/kg, i.p.) did not antagonize either electrographic or behavioral effects of inhibition produced with GAG. Electrical stimulation of amygdala delivered during the initial sedation stage induced by picrotoxin resulted in further regression of kindled seizures in the majority of animals. Although in doses employed, GAG alleviates amygdaloid-kindled seizures its use requires caution in view of its ability to reduce arousal level. RÉSUMÉ L'effet de l'ÉlÉvation des taux cÉrÉbraux de GABA sur les crises amygdaliennes par effet d'embrasement complet a ÉtÉÉtudiÉ chez des rats Long-Evans. l'injection pendant 4 jours consÉcutifs de 100 mg/kg suivis de 50 mg/kg i.p. d'un inhibiteur de la GABA. Transaminase nouvellement synthÉtisÉ (Γ-acetylenic GABA ou GAG) a significativement rÉduit ou mÊme supprimÉ les crises normalement provoquÉes par la stimulation amygdalienne. l'effet est observÉ aprÈs la premiere injection de GAG, mais son importance s'accroit les jours suivants. Les crises rÉapparaissent 2 ou 3 jours aprÈs la fin du traitement au GAG. Du point de vue Électrographique, la durÉe de la postdÉcharge amygdalienne autoentretenue est inchingÉe ou accrue le premier jour du traitement, mais elle diminue les jours suivants pour retourner À la normale un ou deux jours avant que les crises ne rÉapparaissent aprÈs la fin de ('administration du GAG. l'injection de picrotoxine (1.5-2 mg/kg i.p.) ne s'oppose pas aux effets inhibiteurs du GAG sur les crises ou leur accompagnement EEG. La stimulation Électrique de l'amygdala pendant l'Étape sÉdative initiate induite par la picrotoxine provoque une rÉgression supplÉmentaire des crises d'embrasement chez la majoritÉ des animaux. Bien que, aux doses utilisÉes, le GAG attÉnue les crises amyg-daliennes d'embrasement, son utilisation nÉcessite des prÉcautions compte tenu de sa tendance À rÉduire le niveau d'Éveil. RESUMEN En ratas Long-Evans se ha investigado el efecto del aumento de los niveles cerebrales de GABA, sobre los ataques originados en la amÍgdala totalmente condicionada, (Kindling). El recientemente sintetizado in-hibidor de la GABA transaminasa, Γ-acetilÉnico GABA (GAG), redujo significativamente o eliminÓ totalmente las crisis de comportamiento que habitualmente se producen con la estimulaciÓn de la amÍgdala. El efecto se observa despuÉs de la primera in-yecciÓn de GAG pero su magnitud aumentÓ en dias subsiguientes. Las crisis de comportamiento reaparecieron a los 2–3 dÍas de la interrupciÓn del tratamiento con GAG. La duraciÓn de los ataques electrogrÁficos (perservaciÓn de la post-descarga de la amigdala) no se modificÓ, o incluso aumentÓ, en el primer dia de la administraciÓn de GAG pero se redujo en los dias siguientes. La duraciÓn de las post-descargas volviÓ a sus niveles normales 1 o 2 dias antes que la reapariciÓn de las crisis de comportamiento una vez terminado el tratamiento con GAG. La picrotoxina (1.5-2 mg/kg, i.p.) no antagonizÓ los efectos inhibitorios producidos por el GAG sobre el electroencefalograma o las crisis de comportamiento. La estimulaciÓn elÉctrica sobre la amÍgdala, aplicada durante la fase de sedaciÓn inicial inducida por la picrotoxina, condujo a una regresiÓn aÚn mÁs intensa de las crisis condicionadas, en la mayorÍa de los animales. A pesar de que, con las dosis utilizadas, el GAG alivia las crisis de la amÍgdala previamente condicionada, se requiere gran precauciÓn en su utilizaciÓn en vista de su propiedad de reducir el nivel del despertar. ZUSAMMENFASSUNG Die Wirkung erhÖhter GABA-Spiegel des Gehirns auf AmygdalonkrÄmpfe nach Kindling wurden bei Long-Evans-Ratten untersucht. Der neuerdings synthetisierte GABA-TYansaminasen-Inhibitor, Gamma-Acetylen-GABA (GAG) wurde an 4 aufeinander-folgenden Tagen in einer Dosis von 100 mg/kg und anschlieliend 50 mg/kg i.p. verabfolgt. Er reduzierte entweder signifikant oder eliminierte vÖllig die anfalls-weisen VerhaltensÄnderungen, die normalerweise durch Stimulation des Amygdalon produziert wurden. Die Wirkung ist nach der Erstinjektion des GAG zu beobachten, obgleich ihr Ausmaß an folgenden Tagen grÖßer war. Die VerhaltensanfÄlle kamen 2 bis 3 Tagen nach Beendigung der GAG-Behandlung wieder. Die Dauer der elektrographischen AnfÄlle (sich selbst un-terhaltende Amydalonnachentladungen) blieben entweder gleich oder sie wurden grÖßer am 1. Tag der GAG-Behandlung, wurden aber kÜrzer an folgenden Tagen. Die Dauer der Nachentladungen nor-malisierte sich 1 bis 2 Tage frÜher als die VerhaltensanfÄlle nach Beendigung des GAG verschwanden. Picrotoxin (1.5 bis 2 mg/kg i.p.) wirken nicht als Antagonist gegenÜber der durch GAG produzierten Hemmung der elektrographischen-oder Verhalten-seffekte. Die elektrische Stimulierung des Amygdalon wÄhrend der initialen Sedierung nach Picrotoxin ver-ursachte bei der Mehrzahl der Tiere einen weiteren RÜckgang der durch Kindling entstandenen AnfÄlle. Obgleich das GAG in den verwandten Dosen, die durch Kindling des Amygdalon erzeugten KrÄmpfe leichter ablaufen lUßt, erfordert seine Anwendung Vorsicht hinsichtlich seiner FÄhigkeit, das Erreg-barkeitsniveau zu senken.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66112/1/j.1528-1157.1980.tb04058.x.pd

Expression of the Axonal Membrane Glycoprotein M6a Is Regulated by Chronic Stress

It has been repeatedly shown that chronic stress changes dendrites, spines and modulates expression of synaptic molecules. These effects all may impair information transfer between neurons. The present study shows that chronic stress also regulates expression of M6a, a glycoprotein which is localised in axonal membranes. We have previously demonstrated that M6a is a component of glutamatergic axons. The present data reveal that it is the splice variant M6a-Ib, not M6a-Ia, which is strongly expressed in the brain. Chronic stress in male rats (3 weeks daily restraint) has regional effects: quantitative in situ hybridization demonstrated that M6a-Ib mRNA in dentate gyrus granule neurons and in CA3 pyramidal neurons is downregulated, whereas M6a-Ib mRNA in the medial prefrontal cortex is upregulated by chronic stress. This is the first study showing that expression of an axonal membrane molecule is differentially affected by stress in a region-dependent manner. Therefore, one may speculate that diminished expression of the glycoprotein in the hippocampus leads to altered output in the corresponding cortical projection areas. Enhanced M6a-Ib expression in the medial prefrontal cortex (in areas prelimbic and infralimbic cortex) might be interpreted as a compensatory mechanism in response to changes in axonal projections from the hippocampus. Our findings provide evidence that in addition to alterations in dendrites and spines chronic stress also changes the integrity of axons and may thus impair information transfer even between distant brain regions

Facilitators and barriers to hypertension self-management in urban African Americans: perspectives of patients and family members.

INTRODUCTION: We aimed to inform the design of behavioral interventions by identifying patients' and their family members' perceived facilitators and barriers to hypertension self-management. MATERIALS AND METHODS: We conducted focus groups of African American patients with hypertension and their family members to elicit their views about factors influencing patients' hypertension self-management. We recruited African American patients with hypertension (n = 18) and their family members (n = 12) from an urban, community-based clinical practice in Baltimore, Maryland. We conducted four separate 90-minute focus groups among patients with controlled (one group) and uncontrolled (one group) hypertension, as well as their family members (two groups). Trained moderators used open-ended questions to assess participants' perceptions regarding patient, family, clinic, and community-level factors influencing patients' effective hypertension self-management. RESULTS: Patient participants identified several facilitators (including family members' support and positive relationships with doctors) and barriers (including competing health priorities, lack of knowledge about hypertension, and poor access to community resources) that influence their hypertension self-management. Family members also identified several facilitators (including their participation in patients' doctor's visits and discussions with patients' doctors outside of visits) and barriers (including their own limited health knowledge and patients' lack of motivation to sustain hypertension self-management behaviors) that affect their efforts to support patients' hypertension self-management. CONCLUSION: African American patients with hypertension and their family members reported numerous patient, family, clinic, and community-level facilitators and barriers to patients' hypertension self-management. Patients' and their family members' views may help guide efforts to tailor behavioral interventions designed to improve hypertension self-management behaviors and hypertension control in minority populations