Use of tobramycin-impregnated antibiotic beads in frontal sinus osteomyelitis.

OBJECTIVE: Osteomyelitis of the frontal bone is a rare but devastating complication of frontal sinusitis. Treatment involves aggressive surgery to remove all sequestra in combination with long-term antibiotic therapy. However, systemic antibiotics may struggle to penetrate any remaining infection in devascularised areas, and the morbidity associated with surgical resection of some areas of the skull base is too high. In contrast, locally implanted antibiotics provide a reliable, high concentration of treatment to these areas while also minimising potential systemic side effects. The clinical application of tobramycin beads has primarily been used in orthopaedics as an adjunct to the treatment of tibial osteomyelitis or prosthetic joint infection. CASE REPORT: To the best of the authors' knowledge, the two cases discussed here represent the first use of tobramycin antibiotic beads in frontal sinus osteomyelitis secondary to chronic rhinosinusitis. CONCLUSION: These cases show promising use of tobramycin beads in recalcitrant frontal osteomyelitis.

How does climate variability affect water quality dynamics in Canada's oil sands region?

In Canada's oil sands region, classic boreal hydrology (i.e., winter low flow followed by peaks during spring freshet and then summer flow recession) combined with erosion of both natural and anthropogenically-exposed bitumen results in seasonal and inter-annual variability in stream water chemistry. Using data collected from all seasons over three years (2012-2015), we investigated the mechanisms driving spatial and temporal change in the concentration of 26 water quality parameters for six rivers draining Canada's oil sands region. Mantel tests showed a strong spatial aggregation of climatic drivers (average daily precipitation, accumulated precipitation, snow water equivalent) associated with west versus east discharge patterns. Wavelet analysis highlighted unique watershed attributes, in particular the importance of developed area in lowering responsiveness to seasonal precipitation. Concentrations of most chemical parameters (20 of 23) showed distinct temporal patterns that were correlated with seasonal changes in hydrology which, in turn, were related to changes in weather. Comparison of concentrations observed in this study with those reported in the scientific literature for the same watersheds showed 81% of comparisons differed significantly. This was likely due to the short duration of previous field campaigns and thus the sampling of a very narrow window of the annual streamflow regime.

How to Investigate the Origins of Novelty: Insights Gained from Genetic, Behavioral, and Fitness Perspectives.

Biologists are drawn to the most extraordinary adaptations in the natural world, often referred to as evolutionary novelties, yet rarely do we understand the microevolutionary context underlying the origins of novel traits, behaviors, or ecological niches. Here we discuss insights gained into the origins of novelty from a research program spanning biological levels of organization from genotype to fitness in Caribbean pupfishes. We focus on a case study of the origins of novel trophic specialists on San Salvador Island, Bahamas and place this radiation in the context of other rapid radiations. We highlight questions that can be addressed about the origins of novelty at different biological levels, such as measuring the isolation of novel phenotypes on the fitness landscape, locating the spatial and temporal origins of adaptive variation contributing to novelty, detecting dysfunctional gene regulation due to adaptive divergence, and connecting behaviors with novel traits. Evolutionary novelties are rare, almost by definition, and we conclude that integrative case studies can provide insights into this rarity relative to the dynamics of adaptation to more common ecological niches and repeated parallel speciation, such as the relative isolation of novel phenotypes on fitness landscapes and the transient availability of ecological, genetic, and behavioral opportunities.

Como Investigar as Origens da Novidade: Ideias Obtidas a Partir de Perspectivas da Genética, do Comportamento e de Fitness (How to Investigate the Origins of Novelty: Insights Gained from Genetic, Behavioral, and Fitness Perspectives) Biólogos são atraídos pelas adaptações mais extraordinárias do mundo natural, muitas vezes chamdas de novidades evolutivas, mas raramente entendemos o contexto microevolutivo subjacente às origens de novas características, novos comportamentos ou nichos ecológicos. Aqui discutimos ideias obtidas sobre as origens da novidade evolutiva a partir de um programa de pesquisa abrangendo níveis biológicos de organização de genótipo para fitness em pupas do Caribe. Nós nos concentramos em um estudo de caso sobre as origens de novos especialistas tróficos na ilha de São Salvador, Bahamas, e colocamos essa radiação no contexto de outras radiações rápidas. Destacamos questões que podem ser abordadas sobre as origens da novidade evolutiva em diferentes níveis biológicos, como medir o isolamento de novos fenótipos no cenário adaptativo, localizando as origens espaciais e temporais da variação adaptativa que contribuem para a novidade evolutiva, detectando a regulação gênica disfuncional devido à divergência adaptativa, e conectando comportamentos com novas características. As novidades evolutivas são raras, quase por definição, e concluímos que estudos de caso integrativos podem fornecer ideias sobre essa raridade em relação à dinâmica de adaptação a nichos ecológicos mais comuns e especiação paralela repetitiva, como o relativo isolamento de novos fenótipos em cenários adaptativos e a disponibilidade transitória de oportunidades ecológicas, genéticas, e comportamentais. Translated to Portuguese by G. Sobral (gabisobral@gmail.com).

Author Correction: Composition and Use of Cannabis Extracts for Childhood Epilepsy in the Australian Community.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Composition and Use of Cannabis Extracts for Childhood Epilepsy in the Australian Community.

Recent surveys suggest that many parents are using illicit cannabis extracts in the hope of managing seizures in their children with epilepsy. In the current Australian study we conducted semi-structured interviews with families of children with diverse forms of epilepsy to explore their attitudes towards and experiences with using cannabis extracts. This included current or previous users of cannabis extracts to treat their child's seizures (n = 41 families), and families who had never used (n = 24 families). For those using cannabis, extracts were analysed for cannabinoid content, with specific comparison of samples rated by families as "effective" versus those rated "ineffective". Results showed that children given cannabis extracts tended to have more severe epilepsy historically and had trialled more anticonvulsants than those who had never received cannabis extracts. There was high variability in the cannabinoid content and profile of cannabis extracts rated as "effective", with no clear differences between extracts perceived as "effective" and "ineffective". Contrary to family's expectations, most samples contained low concentrations of cannabidiol, while Δ9-tetrahydrocannabinol was present in nearly every sample. These findings highlight profound variation in the illicit cannabis extracts being currently used in Australia and warrant further investigations into the therapeutic value of cannabinoids in epilepsy.

Knockdown and recovery of malaria diagnosis and treatment in Liberia during and after the 2014 Ebola outbreak.

Setting: The malaria-endemic country of Liberia, before, during and after the 2014 Ebola outbreak. Objective: To describe the consequences of the Ebola outbreak on Liberia's National Malaria Programme and its post-Ebola recovery. Design: A retrospective cross-sectional study using routine countrywide programme data. Results: Malaria caseloads decreased by 47% during the Ebola outbreak and by 11% after, compared to the pre-Ebola period. In those counties most affected by Ebola, a caseload reduction of >20% was sustained for 12 consecutive months, while this lasted for only 4 consecutive months in the counties least affected by Ebola. Linear regression of monthly proportions of confirmed malaria cases-as a proxy indicator of programme performance-over the pre- and post-Ebola periods indicated that the malaria programme could require 26 months after the end of the acute phase of the Ebola outbreak to recover to pre-Ebola levels. Conclusions: The differential persistence of reduced caseloads in the least- and most-affected counties, all of which experienced similar emergency measures, suggest that factors other than Ebola-related security measures played a key role in the programme's reduced performance. Clear guidance on when to abandon the emergency measures after an outbreak may be needed to ensure faster recovery of malaria programme performance.

Contexte : Le Liberia, pays d'endémie palustre, avant, pendant et après l'épidémie d'Ebola de 2014.Objectif : Décrire les conséquences de l'épidémie d'Ebola sur le programme national de lutte contre le paludisme et sa récupération après Ebola.Schéma : Étude rétrospective transversale utilisant des données de routine du programme dans tout le pays.Résultats : Le nombre de cas de paludisme déclarés a baissé de 47% pendant et de 11% après l'épidémie d'Ebola, comparé à la période pré-Ebola. Dans les comtés les plus affectés par Ebola, une réduction de plus de 20% a été maintenue pendant plus de 12 mois consécutifs, tandis que celle-ci n'a duré que pendant 4 mois consécutifs dans les comtés les moins affectés par Ebola. Une régression linéaire des proportions mensuelles de cas de paludisme confirmés­comme indicateur indirect de la performance du programme­sur les périodes pré- et post-Ebola a montré que le programme paludisme pourrait avoir besoin de 26 mois après la fin de la phase aiguë de l'épidémie d'Ebola pour revenir aux niveaux d'avant Ebola.Conclusion: La persistance différentielle de réduction des cas déclarés dans les comtés les moins et les plus affectés, qui ont tous expérimenté des mesures d'urgence similaires, suggère que des facteurs autres que les mesures de sécurité liées à Ebola ont joué des rôles clés dans la réduction de la performance du programme. Des recommandations claires sur le moment auquel il faut abandonner les mesures d'urgence après une flambée pourraient être nécessaires pour assurer une récupération plus rapide de la performance du programme.

Marco de referencia: El país de Liberia, con una situación endémica de paludismo, antes de la epidemia de fiebre hemorrágica del Ébola, durante el brote y después del mismo en el 2014.Objetivos: Describir las consecuencias del brote epidémico del Ébola sobre el programa nacional contra el paludismo y su recuperación después de la epidemia.Método: Fue este un estudio transversal retrospectivo a partir de los datos corrientes del programa en todo el país.Resultados: La carga de morbilidad por paludismo disminuyó un 47% durante la epidemia y un 11% después de la misma, en comparación con el período anterior. En las provincias más afectadas por el brote se observó una disminución constante de más del 20% durante 12 meses consecutivos, comparada con 4 meses en las provincias menos afectadas. La regresión lineal de la proporción mensual de casos confirmados de paludismo, utilizada como indicador indirecto del desempeño del programa durante los períodos anterior y posterior a la epidemia del Ébola, puso de manifiesto que el programa precisó 26 meses después del final de la fase aguda de la epidemia hasta recuperar su nivel de desempeño anterior al brote.Conclusiones: La recuperación diferencial de la notificación en las provincias menos afectadas y las más afectadas por la epidemia, pese a que en todas las regiones se ejecutaron intervenciones de emergencia equivalentes, indica que factores diferentes a las medidas de seguridad desencadenadas por la epidemia influyeron de manera importante en la disminución del desempeño del programa. Se precisan orientaciones claras con respecto al momento más oportuno para interrumpir las intervenciones de emergencia después de los brotes epidémicos, con el propósito de facilitar una recuperación más rápida del funcionamiento del programa contra el paludismo.

Mercury levels in herring gulls and fish: 42 years of spatio-temporal trends in the Great Lakes.

Total mercury levels in aquatic birds and fish communities have been monitored across the Canadian Great Lakes by Environment and Climate Change Canada (ECCC) for the past 42 years (1974-2015). These data (22 sites) were used to examine spatio-temporal variability of mercury levels in herring gull (Larus argentatus) eggs, lake trout (Salvelinus namaycush), walleye (Sander vitreus), and rainbow smelt (Osmerus mordax). Trends were quantified with dynamic linear models, which provided time-variant rates of change of mercury concentrations. Lipid content (in both fish and eggs) and length in fish were used as covariates in all models. For the first three decades, mercury levels in gull eggs and fish declined at all stations. In the 2000s, trends for herring gull eggs reversed at two sites in Lake Erie and two sites in Lake Ontario. Similar trend reversals in the 2000s were observed for lake trout in Lake Superior and at a single station in Lake Ontario. Mercury levels in lake trout continued to slowly decline at all of the remaining stations, except for Lake Huron, where the levels remained stable. A post-hoc Bayesian regression analysis suggests strong trophic interactions between herring gulls and rainbow smelt in Lake Superior and Lake Ontario, but also pinpoints the likelihood of a trophic decoupling in Lake Huron and Lake Erie. Continued monitoring of mercury levels in herring gulls and fish is required to consolidate these trophic shifts and further evaluate their broader implications.

The role of adipokines in the rapid antidepressant effects of ketamine.

We previously found that body mass index (BMI) strongly predicted response to ketamine. Adipokines have a key role in metabolism (including BMI). They directly regulate inflammation and neuroplasticity pathways and also influence insulin sensitivity, bone metabolism and sympathetic outflow; all of these have been implicated in mood disorders. Here, we sought to examine the role of three key adipokines-adiponectin, resistin and leptin-as potential predictors of response to ketamine or as possible transducers of its therapeutic effects. Eighty treatment-resistant subjects who met DSM-IV criteria for either major depressive disorder (MDD) or bipolar disorder I/II and who were currently experiencing a major depressive episode received a single ketamine infusion (0.5 mg kg-1 for 40 min). Plasma adipokine levels were measured at three time points (pre-infusion baseline, 230 min post infusion and day 1 post infusion). Overall improvement and response were assessed using percent change from baseline on the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. Lower baseline levels of adiponectin significantly predicted ketamine's antidepressant efficacy, suggesting an adverse metabolic state. Because adiponectin significantly improves insulin sensitivity and has potent anti-inflammatory effects, this finding suggests that specific systemic abnormalities might predict positive response to ketamine. A ketamine-induced decrease in resistin was also observed; because resistin is a potent pro-inflammatory compound, this decrease suggests that ketamine's anti-inflammatory effects may be transduced, in part, by its impact on resistin. Overall, the findings suggest that adipokines may either predict response to ketamine or have a role in its possible therapeutic effects.

The meaning of participation for children in Malawi: insights from children and caregivers.

BACKGROUND: Global rates of childhood disability are high and are estimated through tools that focus on impairment, functioning and activity. The International Classification of Functioning, Disability and Health has promoted a framework to define disability more broadly and to include participation. New outcome measures have now been created to assess participation of children with disabilities for use in research and clinical practice. In order to use these in other cultural contexts, the validity of concepts and tools developed should be evaluated prior to use. We aim to create a tool that would be relevant and valid to the cultural context of Malawi, but to do so, we first need to understand what participation means to children in Malawi. AIM: The aim of this study is to explore what participation means for children (including those with and without disability) in rural Northern Malawi. METHODS: We used semi-structured interviews, focus group discussions, participatory action research and direct observations. Sixty-four participants were involved including children (8-18 years) with (14) and without disabilities (17), carers of children with (8) and without (6) disabilities, community members (14) and professionals/healthcare workers (5). Data analysis was carried out using the 'framework' approach. RESULTS: Activities reported by children, carers and community members fell within seven main themes or areas of participation. These include contribution to family life (chores and work), social activities (communicating and being with others), social activities (unstructured play), structured and organized activities, activities of daily living, education and schooling and entertainment (listening to and watching media). CONCLUSIONS: This study provides concepts and ideas that may be utilized in developing a suitable measure of participation of children with disabilities for rural African settings. Many of the most important activities for all children relate to family and day-to-day social life.

cAMP signaling in brain is decreased in unmedicated depressed patients and increased by treatment with a selective serotonin reuptake inhibitor.

Basic studies exploring the importance of the cyclic adenosine monophosphate (cAMP) cascade in major depressive disorder (MDD) have noted that the cAMP cascade is downregulated in MDD and upregulated by antidepressant treatment. We investigated cAMP cascade activity by using 11C-(R)-rolipram to image phosphodiesterase-4 (PDE4) in unmedicated MDD patients and after ~8 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI). 11C-(R)-rolipram positron emission tomographic (PET) scans were performed in 44 unmedicated patients during a major depressive episode and 35 healthy controls. Twenty-three of the 44 patients had a follow-up 11C-(R)-rolipram PET scan ~8 weeks after treatment with an SSRI. Patients were moderately depressed (Montgomery-Åsberg Depression Rating Scale=30±6) and about half were treatment naïve. 11C-(R)-rolipram binding was measured using arterial sampling to correct for individual differences in radioligand metabolism. We found in unmedicated MDD patients widespread, ~20% reductions in 11C-(R)-rolipram binding compared with controls (P=0.001). SSRI treatment significantly increased rolipram binding (12%, P<0.001), with significantly greater increases observed in older patients (P<0.001). Rolipram binding did not correlate with severity of baseline symptoms, and increased rolipram binding during treatment did not correlate with symptom improvement. In brief, consistent with the results of basic studies, PDE4 was decreased in unmedicated MDD patients and increased after SSRI treatment. The lack of correlation between PDE4 binding and depressive symptoms could reflect the heterogeneity of the disease and/or the heterogeneity of the target, given that PDE4 has four subtypes. These results suggest that PDE4 inhibitors, which increase cAMP cascade activity, may have antidepressant effects.

Effect of stress on heat shock protein levels, immune response and survival to fungal infection of Mamestra brassicae larvae.

Although the utilisation of fungal biological control agents to kill insect pests is desirable, it is known that the outcome of infection may be influenced by a number of criteria, including whether or not the target insect is stressed. In the current work, topical treatment of larvae of the lepidopteran pest, Mamestra brassicae, with conidia of Beauveria bassiana, followed by a heat stress (HS; 37°C for 1h) 48h later, resulted in a similar level of larval survival to that occurring for no heat stress (No-HS), fungus-treated larvae. By contrast, when the HS was applied 24h after fungal treatment, larval survival was significantly increased, indicating that the HS is protecting the larvae from B. bassiana. Similarly, exposure of larvae to a HS provided protection against Metarhizium brunneum (V275) at 48h (but not 24h) after fungal treatment. To elucidate the mechanism(s) that might contribute to HS-induced increases in larval survival against fungal infection, the effects of a HS on key cellular and humoral immune responses and on the level of selected heat shock proteins (HSP) were assessed. When larvae were kept under control (No HS) conditions, there was no significant difference in the haemocyte number per ml of haemolymph over a 24h period. However, exposure of larvae to a HS, significantly increased the haemocyte density immediately after (t=0h) and 4h after HS compared to the No HS controls, whilst it returned to control levels at t=24h. In addition, in vitro assays indicated that haemocytes harvested from larvae immediately after (0h) and 4h (but not 24h) after a HS exhibited higher rates of phagocytosis of FITC-labelled B. bassiana conidia compared to haemocytes harvested from non-HS larvae. Interestingly, the HS did not appear to increase anti-fungal activity in larval plasma. Western blot analysis using antibodies which cross react with Drosophila melanogaster HSP, resulted in a relatively strong signal for HSP 70 and HSP 90 from extracts of 50,000 and 100,000haemocytes, respectively, harvested from No-HS larvae. By contrast, for HSP 60, a lysate derived from 200,000haemocytes resulted in a relatively weak signal. When larvae were exposed to a HS, the level of all three HSP increased compared to the No HS control 4h and 16h after the HS. However, 24h after treatment, any heat stress-mediated increase in HSP levels was minimal and not consistently detected. Similar results were obtained when HSP 90, 70, and 60 levels were assessed in fat body harvested from heat stressed and non-heat stressed larvae. With regard to HSP 27, no signal was obtained even when a lysate from 200,000haemocytes or three times the amount of fat body were processed, suggesting that the anti-HSP 27 antibody utilised does not cross-react with the M. brassicae HSP. The results suggest that a HS-mediated increase in haemocyte density and phagocytic activity, together with an upregulation of HSP 90 and 70, may contribute to increasing the survival of M. brassicae larvae treated with B. bassiana and M. brunneum (V275).

Immune reconstitution inflammatory syndrome in HIV infection: taking the bad with the good.

In this review, we will describe the immunopathogies of immune reconstitution inflammatory syndrome, IRIS. IRIS occurs in a small subset of HIV patient, initiating combination antiretroviral therapy (ART), where immune reconstitution becomes dysregulated, resulting in an overly robust antigen-specific inflammatory reaction. We will discuss IRIS in terms of the associated coinfections: mycobacteria, cryptococci, and viruses.

Baseline vitamin B12 and folate levels do not predict improvement in depression after a single infusion of ketamine.

INTRODUCTION: Deficiencies in both vitamin B12 and folate have been associated with depression. Recently, higher baseline vitamin B12 levels were observed in individuals with bipolar depression who responded to the antidepressant ketamine at 7 days post-infusion. This study sought to -replicate this result by correlating peripheral vitamin levels with ketamine's antidepressant efficacy in bipolar depression and major depressive disorder (MDD). METHODS: Baseline vitamin B12 and folate levels were obtained in 49 inpatients with treatment-resistant MDD and 34 inpatients with treatment-resistant bipolar depression currently experiencing a major depressive episode. All subjects received a single intravenous ketamine infusion. Post-hoc Pearson correlations were performed between baseline vitamin B12 and folate levels, as well as antidepressant response assessed by percent change in Hamilton Depression Rating Scale (HDRS) scores from baseline to 230 min, 1 day, and 7 days post-infusion. RESULTS: No significant correlation was observed between baseline vitamin B12 or folate and percent change in HDRS for any of the 3 time points in either MDD or bipolar depression. DISCUSSION: Ketamine's antidepressant efficacy may occur independently of baseline peripheral vitamin levels.

Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer.

MicroRNA-155 (miR-155) is frequently upregulated in various types of human cancer; however, its role in cancer angiogenesis remains unknown. Here, we demonstrate the role of miR-155 in angiogenesis through targeting von Hippel-Lindau (VHL) tumour suppressor in breast cancer. Ectopic expression of miR-155 induced whereas knockdown of miR-155 inhibited human umbilical vein endothelial cell network formation, proliferation, invasion and migration. Furthermore, mammary fat pad xenotransplantation of ectopically expressed miR-155 resulted in extensive angiogenesis, proliferation, tumour necrosis and recruitment of pro-inflammatory cells such as tumour-associated macrophages. Expression of VHL abrogated these miR-155 effects. Moreover, miR-155 expression inversely correlates with VHL expression level and is associated with late-stage, lymph node metastasis and poor prognosis, as well as triple-negative tumour in breast cancer. These findings indicate that miR-155 has a pivotal role in tumour angiogenesis by downregulation of VHL, and provide a basis for miR-155-expressing tumours to embody an aggressive malignant phenotype, and therefore miR-155 is an important therapeutic target in breast cancer.

Clinical effectiveness of first-line chemoradiation for adult patients with locally advanced non-small cell lung cancer: a systematic review.

BACKGROUND: The National Institute for Health and Clinical Excellence has issued guidelines on the treatment of non-small cell lung cancer (NSCLC) and recommends that patients with stage IIIA-IIIB disease who are not amenable to surgery be treated with potentially curative chemoradiation (CTX-RT). This review was conducted as part of a larger systematic review of all first-line chemotherapy (CTX) and CTX-RT treatments for patients with locally advanced or metastatic NSCLC. However, it was considered that patients with potentially curable disease (e.g. stage IIIA) are different from those with advanced disease, who are suitable for palliative treatment only, and therefore the results should be reported separately. OBJECTIVE: To evaluate the clinical effectiveness of first-line CTX in addition to radiotherapy (RT) (CTX-RT vs CTX-RT) for adult patients with locally advanced NSCLC who are suitable for potentially curative treatment. DATA SOURCES: Three electronic databases (MEDLINE, EMBASE and The Cochrane Library) were searched from January 1990 to September 2010. REVIEW METHODS: Inclusion criteria comprised adult patients with locally advanced NSCLC, trials that compared any first-line CTX-RT therapy (induction, sequential, concurrent and consolidation) and outcomes of overall survival (OS) and/or progression-free survival (PFS). The results of clinical data extraction and quality assessment were summarised in tables and with narrative description. Direct meta-analyses using OS data were undertaken where possible: sequential CTX-RT compared with concurrent CTX-RT; sequential CTX-RT compared with concurrent/consolidation CTX-RT; and sequential CTX-RT compared with concurrent CTX-RT with or without consolidation. There were not sufficient data to perform meta-analysis on PFS. RESULTS: Of the 240 potentially relevant studies that were published post 2000, 19 met the inclusion criteria and compared CTX-RT with CTX-RT. The results from the OS meta-analysis comparing sequential CTX-RT with concurrent CTX-RT appear to show an OS advantage for concurrent CTX-RT arms over sequential arms; this result is not statistically significant [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.50 to 1.25)]. The results from the OS meta-analysis comparing sequential CTX-RT with concurrent/consolidation CTX-RT appear to show a statistically significant OS advantage for concurrent/consolidation CTX-RT treatment over sequential treatment (HR 0.68; 95% CI 0.55 to 0.83). The results from the OS meta-analysis comparing sequential CTX-RT with concurrent CTX-RT with or without consolidation appear to show a statistically significant OS advantage for concurrent CTX-RT with or without consolidation over sequential treatment (HR 0.72; 95% CI 0.61 to 0.84). LIMITATIONS: This report provides a summary and critical appraisal of a comprehensive evidence base of CTX-RT trials; however, it is possible that additional trials have been reported since our last literature search. It is disappointing that the quality of the research in this area does not meet the accepted quality standards regarding trial design and reporting. CONCLUSIONS: This review identified that the research conducted in the area of CTX-RT was generally of poor quality and suffered from a lack of reporting of all important clinical findings, including OS. The 19 trials included in the systematic review were too disparate to form any conclusions as to the effectiveness of individual CTX agents or types of RT. The focus of primary research should be good methodological quality; appropriate allocation of concealment and randomisation, and comprehensive reporting of key outcomes, will enable meaningful synthesis and conclusions to be drawn. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Immunosuppressive properties of a protein (rVPr1) from the venom of the endoparasitic wasp, Pimpla hypochondriaca: Mechanism of action and potential use for improving biological control strategies.

Previously, it was determined that the presence of rVPr1 (a recombinant Pimpla hypochondriaca venom protein), in the haemocoel of two lepidopteran larvae, significantly increases their susceptibility to the biological control agents (BCAs), Bacillus thuringiensis (Bt) and Beauveria bassiana (Richards and Dani, 2010; Richards et al., 2011). The current work examines the mechanism of action of rVPr1 and demonstrates that it binds to the surface of some haemocytes and disrupts the organization of the haemocyte cytoskeleton. This binding is associated with a reduction in the ability of haemocytes to extend pseudopods, and to move and form aggregates in vitro over an 18 h period. Moreover, rVPr1 exerts these effects after a relatively short incubation period (1.5 h) and the haemocytes do not recover their ability to form aggregates after rVPr1 has been removed. In addition, rVPr1 significantly reduces haemocyte-mediated phagocytosis of Bt and B. bassiana in vitro (p < 0.05) and, following injection into the insect haemocoel, rVPr1 reduces the number of circulating haemocytes per ml of haemolymph (this being significantly different to the controls 3 h after injection [p = 0.05]). The finding that rVPr1 has an adverse effect on haemocyte function and number in vivo, supports the hypothesis that this wasp protein significantly increases the susceptibility of lepidopteran larvae to Bt and B. bassiana, by suppressing haemocyte-mediated immune responses in the insects which otherwise would be directed against these BCAs.

Effect of thoracic epidural anaesthesia on splanchnic blood flow.

BACKGROUND: Thoracic epidural anaesthesia (TEA) is used widely in colorectal surgery. However, there is increasing concern that epidurals are associated with postoperative hypotension, mediating a potential reduction in splanchnic flow. The aim was to review the literature on the effects of TEA on splanchnic blood flow. METHODS: PubMed and Cochrane databases were searched. Search terms used were: English language, 'thoracic epidural splanchnic flow', 'thoracic epidural gut blood flow', 'thoracic epidural intestinal blood flow' and 'thoracic epidural colonic blood flow'. Abstracts were reviewed by two independent researchers and irrelevant studies excluded. The full text of the remaining articles was then retrieved. RESULTS: Twenty-two abstracts were reviewed and three excluded. Nineteen papers were reviewed in full and seven irrelevant articles excluded. Five human studies investigated the effects of TEA on splanchnic flow. Two studies measured splanchnic flow directly and found an epidural-mediated fall in flow, unresponsive to intravenous fluids and requiring vasopressors or inotropes to restore baseline flow. The remaining three studies had inconsistent findings and haemodynamic stability was maintained. The seven animal studies identified were heterogeneous in both methodology and findings. Three suggested a protective role for thoracic epidurals in septic shock and pancreatitis. CONCLUSION: These findings are inconsistent; however, the two studies that investigated the effects of vasoconstrictors on splanchnic blood flow directly both found a significant epidural-mediated reduction in splanchnic blood flow that was unresponsive to fluid therapy.

Stapled diverticulectomy for solitary caecal diverticulitis.

Caecal diverticulitis is an uncommon phenomenon in western countries. The clinical diagnosis is often difficult as it mimics other acute abdominal conditions like appendicitis, colitis or neoplasia. Diagnosis is often made at operation. Operative strategy has been controversial and there is no broad consensus emerging. We report the case of a 71-year-old woman, known to have chronic obstructive pulmonary disease, who presented acutely with right iliac fossa pain. A clinical diagnosis of appendicitis was made. At laparoscopy, a solitary, inflamed, gangrenous caecal diverticulum was found. A laparoscopic stapled diverticulectomy was performed. The patient made a steady post-operative recovery. Histology confirmed diverticulitis. We conclude that stapled diverticulectomy for solitary caecal diverticulitis is a safe and effective surgical strategy when confronted with this scenario.