Safety of hormone replacement therapy in women with a history of cervical adenocarcinoma.

OBJECTIVES: Studies investigating the safety of hormone replacement therapy in cervical cancer have predominantly included patients with squamous disease. Pathological studies have identified estrogen receptor positivity in cervical adenocarcinomas. A recent small case-control study suggested a trend towards reduced survival with hormone replacement therapy in cervical adenocarcinomas. Our objective was to determine if hormone replacement therapy use in patients treated for cervical adenocarcinomas is detrimental to survival. STUDY DESIGN: A retrospective review of all women under the age of 50 with stage 1B-2B cervical adenocarcinomas diagnosed between 1 November 2000 and 24 September 2019. Women were categorised into three groups: ovaries conserved (OVCON); or iatrogenic menopause with (IM-HRT) or without (IM-NOHRT) hormone replacement therapy. Hormone replacement therapy use was defined on an intention to treat basis. Statistical analysis was performed using Kaplan-Meier and Cox proportional hazards methods. MAIN OUTCOME MEASURES: Overall (OS), disease specific (DSS) and progression free (PFS) survival. RESULTS: A total of 58 women (mean age 38.5 ± 6.6) were included in the study of whom 25 (43.1%) had OVCON, 20 (34.4%) had IM-HRT and 13 (22.4%) had IM-NOHRT. No menopause-associated deaths occurred. Although five-year DSS was 73% in IM-NOHRT compared to 95% in IM-HRT and 95% in OVCON, these differences were not statistically significant. Five-year PFS was 68% in IM-NOHRT compared to 90% in IM-HRT and 81% in OVCON but again, these differences were not statistically significant. CONCLUSION: In this small study, hormone replacement therapy does not appear to be detrimental to survival in cervical adenocarcinomas. There is a trend towards improved survival with hormone replacement therapy. Larger studies are required to substantiate these findings.

Phosphoproteomics identifies microglial Siglec-F inflammatory response during neurodegeneration.

Alzheimer's disease (AD) is characterized by the appearance of amyloid-ß plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK-p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec-F which was upregulated on a subset of reactive microglia. The human paralog Siglec-8 was also upregulated on microglia in AD. Siglec-F and Siglec-8 were upregulated following microglial activation with interferon gamma (IFNγ) in BV-2 cell line and human stem cell-derived microglia models. Siglec-F overexpression activates an endocytic and pyroptotic inflammatory response in BV-2 cells, dependent on its sialic acid substrates and immunoreceptor tyrosine-based inhibition motif (ITIM) phosphorylation sites. Related human Siglecs induced a similar response in BV-2 cells. Collectively, our results point to an important role for mouse Siglec-F and human Siglec-8 in regulating microglial activation during neurodegeneration.

Efficacy and Molecular Effects of a Reduced Graphene Oxide/Fe3O4 Nanocomposite in Photothermal Therapy Against Cancer.

PURPOSE: Expanded research on the biomedical applications of graphene has shown promising results, although interactions between cells and graphene are still unclear. The current study aims to dissect the cellular and molecular effects of graphene nanocomposite in photothermal therapy against cancer, and to evaluate its efficacy. METHODS: In this study, a reduced graphene oxide and iron oxide (rGO-Fe3O4) nanocomposite was obtained by chemical synthesis. The nanocomposite was fully characterized by Raman spectroscopy, TEM, VSM and thermal profiling. Cell-nanocomposite interaction was evaluated by confocal microscopy and viability assays on cancer cell line HeLa. The efficacy of the thermal therapy and changes in gene expression of Bcl-2 and Hsp70 was assessed. RESULTS: The resulting rGO-Fe3O4 nanocomposite exhibited superparamagnetic properties and the capacity to increase the surrounding temperature by 18-20°C with respect to the initial temperature. The studies of cell-nanocomposite interaction showed that rGO-Fe3O4 attaches to cell membrane but there is a range of concentration at which the nanomaterial preserves cell viability. Photothermal therapy reduced cell viability to 32.6% and 23.7% with 50 and 100 µg/mL of nanomaterial, respectively. The effect of treatment on the molecular mechanism of cell death demonstrated an overexpression of anti-apoptotic proteins Hsp70 and Bcl-2 as an initial response to the therapy and depending on the aggressiveness of the treatment. CONCLUSION: The results of this study contribute to understanding the interactions between cell and graphene and support its application in photothermal therapy against cancer due to its promising results.

Patient-reported outcomes in Alberta: rationale, scope, and design of a database initiative.

Background: The collection of patient reported outcomes (pros) is a standard of care in many cancer organizations. In Alberta, pros have been integrated into routine clinical practice since 2012. This longitudinal collection of pros provides a wealth of data and a unique research opportunity to improve cancer care. The goal of this pro data initiative is to establish a robust repository of information for ongoing clinical care and research focused on pros. In this paper, we describe the rationale, scope, and design of this initiative. Implementation: The initiative consists of pros and other administrative health data from the province of Alberta. Retrieval of health data from a variety of provincially governed sources will create a platform of information on pros, health outcomes, cancer data, other health conditions, and demographics. The aims of the initiative are to use the data to inform best practices at the point of care; to conduct health services research, particularly clinical epidemiology studies; and to evaluate a variety of pro-related outcomes. Discussion: Because this effort represents our first to integrate routinely collected pros with other administrative health data, a unique and robust data repository will be created. The ability to integrate various types of data will provide a comprehensive mechanism to evaluate a variety of outcomes. Because cancer care in Alberta is governed by a single health care system, the data linkages will include population health and psychosocial cancer data. We anticipate that research related to this initiative will ultimately help to inform more patient-centred care.

Publication of scientific research presented at scientific meetings of the British Association of Oral and Maxillofacial Surgeons: 10 years on - have we published or perished?

In 2009 we evaluated the publication of research presented at annual scientific meetings of the British Association of Oral and Maxillofacial Surgeons (BAOMS) 2002-2006, inclusive. Since then, the format of these meetings has changed, there has been a rapid increase in the number of online-only journals, and restraints on time during training and consultant practice have continued. We have therefore investigated the pattern of publication after presentation at these meetings between 2010 and 2014. All abstracts accepted for oral presentations or posters were included, and publication had to follow no more than four years later. We searched PubMed for papers in peer-reviewed journals and compared the data with those from 2002-2006. A total of 975 abstracts were accepted (2010-2014) of which 221 (23%) went on to be published. The median (IQR) delay to publication was 13 (4-25) months. Most were clinical papers from groups based in the UK (p<0.001) and most were published in BJOMS (p<0.001). The rate of publication has not changed significantly between the two periods (23% compared with 24%), and patterns in the type of papers, delays, journals, and research groups, were similar. Despite consistent rates of publication within the specialty, OMFS produces fewer publications after presentation than other surgical specialties. Further research is required to evaluate this more fully.

Novel outreach settings to enhance sexually transmitted infection/HIV awareness, diagnosis and treatment in hard-to-reach populations.

Despite recent rises in the number of cases of sexually transmitted infections (STIs) such as syphilis and gonorrhoea in England and increasing rates of HIV diagnosis among several men who have sex with men populations, many individuals are still not engaging with sexual health services. The John Hunter Clinic for Sexual Health, Chelsea and Westminster Hospital, London set up outreach clinics at the two world's largest adult lifestyle exhibitions in 2013 and 2015. This was the first time that a sexual health screening and promotion service was available at these large-scale (over 10,000 attendees at each) adult lifestyle events. A total of 381 individuals underwent STI screening across the two events. Nineteen (5.0%) patients were diagnosed with an infection. Twelve (3.1%) patients with Chlamydia trachomatis, three (0.8%) patients with syphilis, one (0.3%) patient with Neisseria gonorrhoeae, one (0.3%) patient with HIV, one (0.3%) patient with hepatitis B and one (0.3%) patient with hepatitis C. All 19 patients were promptly contacted with their results and had arrangements made for treatment or were referred for specialist follow up. Where possible, contact tracing was also performed. Implementing such outreach-based projects is challenged by lack of on-site laboratory support, high staffing demands and potentially high costs. However, we achieved a total HIV screening uptake rate of 94.5% amongst our outreach clinic attendees (versus 67% nationally in conventional sexual health clinic attendees) with an HIV positivity rate of 0.3% (versus 0.2% nationally in high HIV prevalence band populations). Additionally, 30.7% had never been tested for HIV previously (versus 20.7% nationally). Our work demonstrates that these strategies can help to address issues related to lack of STI/HIV screening in hard-to-reach populations and promote risk reduction behaviour.

Inhibition of p25/Cdk5 Attenuates Tauopathy in Mouse and iPSC Models of Frontotemporal Dementia.

Increased p25, a proteolytic fragment of the regulatory subunit p35, is known to induce aberrant activity of cyclin-dependent kinase 5 (Cdk5), which is associated with neurodegenerative disorders, including Alzheimer's disease. Previously, we showed that replacing endogenous p35 with the noncleavable mutant p35 (Δp35) attenuated amyloidosis and improved cognitive function in a familial Alzheimer's disease mouse model. Here, to address the role of p25/Cdk5 in tauopathy, we generated double-transgenic mice by crossing mice overexpressing mutant human tau (P301S) with Δp35KI mice. We observed significant reduction of phosphorylated tau and its seeding activity in the brain of double transgenic mice compared with the P301S mice. Furthermore, synaptic loss and impaired LTP at hippocampal CA3 region of P301S mice were attenuated by blocking p25 generation. To further validate the role of p25/Cdk5 in tauopathy, we used frontotemporal dementia patient-derived induced pluripotent stem cells (iPSCs) carrying the Tau P301L mutation and generated P301L:Δp35KI isogenic iPSC lines using CRISPR/Cas9 genome editing. We created cerebral organoids from the isogenic iPSCs and found that blockade of p25 generation reduced levels of phosphorylated tau and increased expression of synaptophysin. Together, these data demonstrate a crucial role for p25/Cdk5 in mediating tau-associated pathology and suggest that inhibition of this kinase can remedy neurodegenerative processes in the presence of pathogenic tau mutation.SIGNIFICANCE STATEMENT Accumulation of p25 results in aberrant Cdk5 activation and induction of numerous pathological phenotypes, such as neuroinflammation, synaptic loss, Aß accumulation, and tau hyperphosphorylation. However, it was not clear whether p25/Cdk5 activity is necessary for the progression of these pathological changes. We recently developed the Δp35KI transgenic mouse that is deficient in p25 generation and Cdk5 hyperactivation. In this study, we used this mouse model to elucidate the role of p25/Cdk5 in FTD mutant tau-mediated pathology. We also used a frontotemporal dementia patient-derived induced pluripotent stem cell carrying the Tau P301L mutation and generated isogenic lines in which p35 is replaced with noncleavable mutant Δp35. Our data suggest that p25/Cdk5 plays an important role in tauopathy in both mouse and human model systems.

Characteristics of e-cigarette users and their perceptions of the benefits, harms and risks of e-cigarette use: survey results from a convenience sample in Ottawa, Canada. / Caractéristiques des utilisateurs de cigarettes électroniques et leurs perceptions des avantages, des dangers et des risques de la cigarette électronique : résultats d'un sondage auprès d'un échantillon de commodité à Ottawa (Canada).

INTRODUCTION: Although e-cigarette use ("vaping") is increasing in Canada, few attempts have been made to describe e-cigarette users ("vapers"). In this context, we conducted a study in Ottawa, Canada, to describe e-cigarette users' perceptions of the benefits, harms and risks of e-cigarettes. We also collected information on why, how and where they use e-cigarettes as well as information on side effects. METHODS: A 24-item online survey was administered to individuals who purchased e-cigarettes or e-cigarette-related supplies at one of Ottawa's 17 e-cigarette shops. Descriptive analyses characterized respondents, and logistic regression models were fitted to evaluate the relationship between respondents' characteristics and their perception of e-cigarette harms. RESULTS: The mean age of the 242 respondents was 38.1 years (range: 16-70 years); 66% were male. Nearly all had smoked 100 or more cigarettes in their lifetime (97.9%). More than 80% indicated that quitting smoking was a very important reason for starting to use e-cigarettes and 60% indicated that they intend to stop using e-cigarettes at some point. About 40% reported experiencing some side effects within 2 hours of using e-cigarettes. Those who did not report experiencing any of the listed side effects had approximately 3.2 times higher odds of perceiving e-cigarettes as harmless than those who reported having side effects (odds ratio = 3.17; 95% confidence interval: 1.75-5.73). CONCLUSION: Our findings suggest that most e-cigarette users are using them to reduce or stop smoking cigarettes and perceive them as harmless. Due to our use of convenience sampling, the reader should be cautious in generalizing our findings to all Canadian e-cigarette users.

INTRODUCTION: Bien que l'utilisation de la cigarette électronique (« vapotage ¼) soit en hausse au Canada, peu d'efforts ont été consacrés à la description des utilisateurs de cigarettes électroniques (« vapoteurs ¼). C'est dans ce contexte que nous avons mené une étude à Ottawa (Canada) afin de décrire les perceptions qu'ont les utilisateurs de cigarettes électroniques des avantages, des dangers et des risques de ces dernières. Nous avons également recueilli de l'information pour savoir pourquoi, comment et où ils utilisent la cigarette électronique ainsi que sur les effets secondaires. MÉTHODOLOGIE: Un sondage en ligne de 24 questions a été soumis à des personnes ayant acheté des cigarettes électroniques ou des fournitures connexes dans l'un des 17 commerces de cigarettes électroniques à Ottawa. On a caractérisé les répondants au moyen d'analyses descriptives, puis nous avons appliqué des modèles de régression logistique pour évaluer la relation entre ces caractéristiques et la perception par les répondants des dangers de la cigarette électronique. RÉSULTATS: L'âge moyen des 242 répondants était de 38,1 ans (plage : 16 à 70 ans) et, de ce nombre, 66 % étaient des hommes. Près de la totalité (97,9 %) des répondants avaient fumé 100 cigarettes ou plus au cours de leur vie. Plus de 80 % des répondants ont indiqué que la volonté d'arrêter de fumer constituait l'une des principales raisons de recourir à la cigarette électronique, et 60 % ont mentionné qu'ils avaient l'intention de cesser l'utilisation de la cigarette électronique un jour. Environ 40 % des répondants ont fait état d'effets secondaires au cours des 2 heures suivant l'utilisation des cigarettes électroniques. Les répondants ayant signalé n'avoir ressenti aucun des effets secondaires énumérés étaient environ 3,2 fois plus nombreux à ne percevoir aucun danger dans la cigarette électronique que les personnes ayant signalé des effets secondaires (rapport de cotes = 3,17; intervalle de confiance à 95 % : 1,75 à 5,73). CONCLUSION: D'après nos constatations, la majorité des utilisateurs de cigarettes électroniques ont recours à ces dernières pour réduire ou cesser leur consommation de tabac et ils les perçoivent comme inoffensives. Étant donné que nous avons utilisé un échantillonnage de commodité, le lecteur doit faire preuve de prudence dans la généralisation de nos constatations à tous les utilisateurs de cigarettes électroniques au Canada.

Emerging roles of ATRX in cancer.

ATRX was identified over 20 years ago as the gene responsible for a rare developmental disorder characterized by α-thalassemia and intellectual disability. Similarities to the sucrose nonfermentable SNF2 type chromatin remodelers initially suggested a role in transcriptional regulation. However, over the last years, our knowledge of the epigenetic activities of ATRX has expanded steadily. Recent exciting discoveries have propelled ATRX into the limelight of chromatin and telomere biology, development and cancer research. This review summarizes recent breakthroughs in understanding ATRX function in heterochromatin structure, genome stability and its frequent dysregulation in a variety of cancers.

Dual effect of CTCF loss on neuroprogenitor differentiation and survival.

An increasing number of proteins involved in genome organization have been implicated in neurodevelopmental disorders, highlighting the importance of chromatin architecture in the developing CNS. The CCCTC-binding factor (CTCF) is a zinc finger DNA binding protein involved in higher-order chromatin organization, and mutations in the human CTCF gene cause an intellectual disability syndrome associated with microcephaly. However, information on CTCF function in vivo in the developing brain is lacking. To address this gap, we conditionally inactivated the Ctcf gene at early stages of mouse brain development. Cre-mediated Ctcf deletion in the telencephalon and anterior retina at embryonic day 8.5 triggered upregulation of the p53 effector PUMA (p53 upregulated modulator of apoptosis), resulting in massive apoptosis and profound ablation of telencephalic structures. Inactivation of Ctcf several days later at E11 also resulted in PUMA upregulation and increased apoptotic cell death, and the Ctcf-null forebrain was hypocellular and disorganized at birth. Although deletion of both Ctcf and Puma in the embryonic brain efficiently rescued Ctcf-null progenitor cell apoptosis, it failed to improve neonatal hypocellularity due to decreased proliferative capacity of rescued apical and outer radial glia progenitor cells. This was exacerbated by an independent effect of CTCF loss that resulted in depletion of the progenitor pool due to premature neurogenesis earlier in development. Our findings demonstrate that CTCF activities are required for two distinct events in early cortex formation: first, to correctly regulate the balance between neuroprogenitor cell proliferation and differentiation, and second, for the survival of neuroprogenitor cells, providing new clues regarding the contributions of CTCF in microcephaly/intellectual disability syndrome pathologies.

Trophic ecology of Arapaima in Guyana: giant omnivores in Neotropical floodplains

Using stable nitrogen and carbon isotope signatures, we investigated the trophic ecology and identified potential prey fish groups supporting the giant Arapaima within floodplain lakes of the Essequibo River basin in southwestern Guyana. Morphological descriptions of feeding structures and digestive tract are presented together with preliminary data on Arapaima diets. Stable isotope results suggest that algivorous/detritivorous and omnivorous fishes contributed most to Arapaima biomass, and generally, that was consistent with what is known about Arapaima diets. Stable nitrogen isotope ratios for piscivorous fishes in these lakes were higher than nitrogen isotope ratios for Arapaima, indicating that piscivorous fishes are unlikely to constitute a major source of energy for Arapaima. This population of Arapaima has an intestine averaging 1.45 times total body length, relatively small teeth, and numerous, closely-spaced gill rakers. These morphological features, together with isotope data, support our inference that Arapaima are secondary consumers and may be better characterized as omnivores and not top predators.

Utilizando firmas de isotopos estables de nitrógeno y carbón, investigamos la ecología trófica e identificamos los grupos de peces que potencialmente mantienen a la Arapaima en los lagos inundables de la cuenca del río Essequibo, al suroeste de Guyana. Presentamos descripciones morfológicas de las estructuras alimentarias y tracto digestivo de la Arapaima, conjuntamente a datos preliminares de sus dietas. Los isotopos estables sugieren que peces algívoros/detritívoros y peces omnívoros son los principales contribuyentes de la biomasa de la Arapaima, y estos resultados son compatibles con lo que se conoce actualmente de la dieta de la Arapaima. A diferencia, las proporciones del isotopo estable de nitrógeno para peces piscívoros en estos lagos resultaron más altas que los valores obtenidos para el isotopo estable de nitrógeno en la Arapaima. Esto indica que es improbable que sean peces piscívoros los que constituyan la fuente energética principal de la Arapaima. La población de Arapaima estudiada presenta un intestino que promedia 1,45 veces la longitud total del cuerpo, dientes relativamente pequeños, y agallas con branquiespinas numerosas y cercanamente espaciadas. Estas características morfológicas, conjuntamente a los datos obtenidos a través del uso de isotopos estables apoyan nuestra inferencia que la Arapaima es un consumidor secundario y que puede ser caracterizada como un pez omnívoro y no como un depredador mayor.

Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced life span.

Human ATRX mutations are associated with cognitive deficits, developmental abnormalities, and cancer. We show that the Atrx-null embryonic mouse brain accumulates replicative damage at telomeres and pericentromeric heterochromatin, which is exacerbated by loss of p53 and linked to ATM activation. ATRX-deficient neuroprogenitors exhibited higher incidence of telomere fusions and increased sensitivity to replication stress-inducing drugs. Treatment of Atrx-null neuroprogenitors with the G-quadruplex (G4) ligand telomestatin increased DNA damage, indicating that ATRX likely aids in the replication of telomeric G4-DNA structures. Unexpectedly, mutant mice displayed reduced growth, shortened life span, lordokyphosis, cataracts, heart enlargement, and hypoglycemia, as well as reduction of mineral bone density, trabecular bone content, and subcutaneous fat. We show that a subset of these defects can be attributed to loss of ATRX in the embryonic anterior pituitary that resulted in low circulating levels of thyroxine and IGF-1. Our findings suggest that loss of ATRX increases DNA damage locally in the forebrain and anterior pituitary and causes tissue attrition and other systemic defects similar to those seen in aging.

Inherited polyglutamine spinocerebellar ataxias in South Africa.

OBJECTIVE: To determine the frequency and distribution of polyglutamine spinocerebellar ataxias (SCAs) from referrals over a 24-year period to the National Health Laboratory Service (NHLS) in South Africa (SA). METHODS: Paper-based clinical reports in the University of Cape Town laboratory and the NHLS electronic patient record database spanning a 24-year period were mined for information regarding the molecular diagnosis, ethnicity and CAG repeat length for individuals referred for molecular genetic testing for the polyglutamine SCAs. RESULTS: SCA1 and 7 are the most frequent types of polyglutamine SCA in the SA patient population, followed by SCA2, 3 and 6. SCA1 is the most common type in the coloured, white and Indian populations, whereas the majority of indigenous black African patients are affected with SCA7 and 2. Of individuals tested, 22% were found to be positive for one of the polyglutamine SCAs. CONCLUSION: Although trends in the frequency and distribution of the polyglutamine SCAs in SA have not changed significantly since our previous study in 2003, they differ remarkably from those reported elsewhere, and reflect the unique genetic and demographic background of SA. The provision of accurate and complete patient information and family history is crucial to the diagnostic process, to enable comprehensive epidemiological studies and assist in developing therapeutic and patient management strategies.

Role of HCT-comorbidity index, age and disease status at transplantation in predicting survival and non-relapse mortality in patients with myelodysplasia and leukemia undergoing reduced-intensity-conditioning hemopoeitic progenitor cell transplantation.

Reduced-intensity-conditioning (RIC) regimens have allowed older patients to have allogeneic hemopoietic progenitor cell transplantation (HCT). This retrospective study was done to assess the impact of the HCT-comorbidity index (HCT-CI) in addition to other pre-transplant factors on the outcome of RIC transplants. In all 121 such patients were transplanted between 2002 and 2008 at two centers using fludarabine, melphalan and alumtuzumab conditioning. The OS and non-relapse mortality (NRM) were 56% and 30% at 2 years, respectively. The NRM of patients with HCT-CI ≥ 3 was not significantly different from the NRM of those with HCT-CI 0-2 (P value 0.24). Age and disease status at transplantation were significant factors affecting OS (P value 0.07 and 0.008, respectively), with no impact on NRM (P value 0.14 and 0.24, respectively). Although HCT-CI on its own did not independently predict NRM or survival, taken together with age and disease status at transplantation, it can be utilized to further delineate RIC allograft recipients into groups with different outcomes. Patients with none or one of these three adverse factors (age ≥ 60 years, leukemia in second CR or PR/high-risk myelodysplasia (MDS) and HCT-CI ≥ 3) had a 2-year NRM and survival of 18% and 80%, respectively, which was significantly better than those of patients with two or more of these adverse factors with 2-year NRM and survival of 46% (P value 0.03) and 40% (P value 0.02), respectively. None of the patients with all three adverse factors (age ≥ 60 years, leukemia in second CR or PR/high-risk MDS and HCT-CI ≥ 3) had survived for 2 years (median survival 12 months). This information can be used to guide patient selection for RIC transplants and to appropriately counsel patients of the risks and benefits of this treatment.

Abdominal wall closure: resident education and human error.

PURPOSE: Secure abdominal wall closure for laparotomy incisions is paramount in prevention of hernia formation. Despite the importance, abdominal closure is often delegated to the resident surgeon. The purpose of this study was to assess residents' formal training, knowledge, and technique in abdominal wall closure. METHODS: All surgical residents in our training program participated in a skills laboratory and completed a questionnaire. The skills portion involved closure of a 10-cm incision on a simulated abdominal wall. Participants were timed, videotaped, and graded using a standardized grading system. Lengths of the suture bites were measured. Regression analysis was used to compare results based on number of closures. A P-value of <0.05 was considered significant. RESULTS: Ten surgical residents participated. The average time for closure was 4:23 min (range 3:08-5:65 min). The average distance between the bite and the incision was 0.9 cm and between bites was 0.8 cm. All knots were satisfactory and intact following closure. Participants' experience varied with a range from 0 to 230 previous abdominal closures. All residents chose to perform closure in a continuous fashion using a slowly absorbing suture. All but one resident stated that sutures should be placed 1 cm from the incision with 1 cm advances. Only one resident knew the correct suture-to-wound length ratio for closure, and only four residents were familiar with the literature about abdominal wall closure. With increasing closure experience, there was significant improvement in time and motion of suturing (P = 0.02), respect of tissue (P = 0.0002), instrument handling (P = 0.004), orientation of needle (P = 0.0076), and flow of closure (P = 0.046). Residents who had performed more closures took significantly larger suture bites (P = 0.03) with larger distances between bites (P = 0.03). CONCLUSIONS: Surgical technique improves with increased experience with abdominal closures; however, residents at all levels have the physical ability to adequately perform this task. Education regarding closure appears to be lacking, and further study warranted.

Thoracic outlet syndrome part 1: clinical manifestations, differentiation and treatment pathways.

Thoracic outlet syndrome (TOS) is a challenging condition to diagnose correctly and manage appropriately. This is the result of a number of factors including the multifaceted contribution to the syndrome, the limitations of current clinical diagnostic tests, the insufficient recognition of the sub-types of TOS and the dearth of research into the optimal treatment approach. This masterclass identifies the subtypes of TOS, highlights the possible factors that contribute to the condition and outlines the clinical examination required to diagnose the presence of TOS.

Immunostimulatory principles from Chlorella pyrenoidosa--part 1: isolation and biological assessment in vitro.

Our proprietary preparation obtained by extraction of Chlorella pyrenoidosa cells, ONC-107 (Respondin), was recently found to selectively boost antibody response to the influenza vaccine in a human clinical trial. Respondin is a potent stimulator of mouse B cell proliferation and an activator of macrophages. Bioactivity-guided resolution concluded that Respondin is composed of a mixture of immunostimulatory principles of different chemical nature. A combination of size exclusion, anion exchange and hydrophobic interaction chromatography revealed that the bulk of the immunostimulatory activity resides in polysaccharide/protein complexes with molecular masses larger than 100 kDa that are composed primarily of galactose, rhamnose and arabinose.

Predictors of COPD symptoms: does the sex of the patient matter?

Although chronic obstructive pulmonary disease (COPD) patients frequently report symptoms, it is not known which factors determine the course of symptoms over time and if these differ according to the sex of the patient. The current study investigated predictors for presence, development and remission of COPD symptoms in 816 males and 312 females completing 3-yr-follow-up in the European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP). The following were included in generalised estimating equations logistic regression analyses: explanatory variables of treatment; pack-yrs smoking; age, forced expiratory volume in one second % predicted (FEV1 % pred); annual increase in FEV1 and number of cigarettes smoked; body mass index; and phadiatop. Interaction terms of sex multiplied by explanatory variables were tested. Over 3 yrs, similar proportions of males and females reported symptoms. In males only, higher FEV1 % pred was associated with reduction in new symptoms of wheeze and dyspnoea, and symptom prevalence was reduced with annual FEV1 improvement and phlegm prevalence reduced with budesonide treatment (odds ratio 0.66; 95% confidence interval 0.52-0.83). Additionally an increase in the number of cigarettes smoked between visits increased the risk of developing phlegm (1.40 (1.14-1.70)) and wheeze (1.24 (1.03-1.51)) in males but not females. The current study shows longitudinally that symptom reporting is similar by sex. The clinical course of chronic obstructive pulmonary disease can differ by sex, as males show greater response to cigarette exposure and treatment.