c-MET immunohistochemical expression in sporadic and inflammatory bowel disease associated lesions.

BACKGROUND: Post-colonoscopy colorectal cancer (CRC) rates for patients with inflammatory bowel disease (IBD) are unacceptably high. During colonoscopy, an intravenous fluorescent anti-c-MET probe may improve endoscopic detection of lesions. However, c-MET expression in IBD lesions is poorly defined, limiting translational studies. AIM: To comprehensively define c-MET expression in sporadic and IBD-associated colorectal carcinogenesis. METHODS: c-MET expression was immunohistochemically assessed in 319 formalin-fixed paraffin-embedded tissue specimens, colonoscopically or surgically retrieved between 1994-2017. Tissue included: 30 normal colorectal biopsies, 30 hyperplastic polyps (HP), 31 sessile serrated lesions (SSL), 55 tubular/tubulovillous adenomas with low (TA-LGD, n = 32) or high grade dysplasia (TA-HGD, n = 23), 26 sporadic (s)-CRCs, 16 quiescent IBD biopsies, 11 active/inflamed IBD biopsies, 18 IBD-associated dysplastic lesions (IBD-dys), and 102 IBD-CRCs. Expression was scored by two independent observers as: 0 = absent, 1 = weak, 2 = moderate or 3 = strong. Mann-Whitney U and Kruskal-Wallis tests were used to assess significance. RESULTS: Positive epithelial cytoplasmic and membranous c-MET expression was observed in all tissues, indicating there is ubiquitous expression in the colorectum. c-MET expression was weak in normal colonic epithelium compared with each of the sporadic colonic lesions, including TA-LGD (P < 0.001), TA-HGD (P = 0.004), HP (P < 0.001), SSL (P < 0.001), and s-CRC (P < 0.001). Specifically, in sporadic (non-IBD) lesions, expression was stronger in TA-LGD compared with normal mucosa (P < 0.001), and stronger in s-CRC compared with TA-HGD (P = 0.004). However, there was no significant difference between TA-LGD and TA-HGD (P = 0.852). Further, there was no difference in c-MET expression between HP and SSL (P = 0.065). In IBD, expression was weaker in quiescent colonic mucosa compared with inflamed colonic mucosa (P < 0.001). There was no difference between inflamed colonic mucosa and IBD-dys (P = 0.512) or IBD-CRC (P = 0.296). However, expression was stronger in IBD-dys (P < 0.001) and IBD-CRC (P < 0.001) compared with quiescent IBD colonic mucosa. CONCLUSION: The characterisation of c-MET expression suggest that an intravenous probe may improve the endoscopic detection of lesions in both non-IBD patients and IBD patients with quiescent disease.

Do They Really Work? Quantifying Fabric Mask Effectiveness to Improve Public Health Messaging.

The purpose of this study is to compare masks (non-medical/fabric, surgical, and N95 respirators) on filtration efficiency, differential pressure, and leakage with the goal of providing evidence to improve public health messaging. Masks were tested on an anthropometric face filtration mount, comparing both sealed and unsealed. Overall, surgical and N95 respirators provided significantly higher filtration efficiency (FE) and differential pressure (dP). Leakage comparisons are one of the most significant factors in mask efficiency. Higher weight and thicker fabric masks had significantly higher filtration efficiency. The findings of this study have important implications for communication and education regarding the use of masks to prevent the spread of COVID-19 and other respiratory illnesses, specifically the differences between sealed and unsealed masks. The type and fabric of facial masks and whether a mask is sealed or unsealed has a significant impact on the effectiveness of a mask. Findings related to differences between sealed and unsealed masks are of critical importance for health care workers. If a mask is not completely sealed around the edges of the wearer, FE for this personal protective equipment is misrepresented and may create a false sense of security. These results can inform efforts to educate health care workers and the public on the importance of proper mask fit.

Preliminary Evaluation of Filtration Efficiency and Differential Pressure ASTM F3502 Testing Methods of Non-Medical Masks Using a Face Filtration Mount.

Research surrounding the mandated use of non-medical fabric masks is inconsistent and often confusing when compared to the standard N95. A recently published standard from ASTM International and the Centers for Disease Control and Prevention attempts to normalize evaluation procedures. The purpose of this study is to conduct a preliminary evaluation of the new methods for testing filtration efficiency of masks outlined by ASTM International F3502, where results can be directly compared to standards outlined for non-medical fabric masks. Eleven consumer non-medical fabric masks were tested for filtration efficiency and airflow resistance using a face filtration mount in accordance with the newly released ASTM International standard for facial barriers. The mean FE% (SD) ranged from 0.46% (0.44) to 11.80% (2.76) with the 3-layer athletic mesh having the highest performance and the highest deviations. All the masks tested following the procedure failed to meet to minimum FE of 20%; however all masks performed below the minimum upper limits for airflow resistance. Using a non-medical fabric masks as the sole mitigation strategy may not be as effective, as previously reported. With efforts to standardize and regulate the non-medical fabric mask market, this study demonstrates a variety of currently available consumer mask products do not meet the minimum standards nor are these remotely close to the standards of surgical or N95 masks.

The impact of depression and anxiety treatment on biological aging and metabolic stress: study protocol of the MOod treatment with antidepressants or running (MOTAR) study.

BACKGROUND: Depressive and anxiety disorders have shown to be associated to premature or advanced biological aging and consequently to adversely impact somatic health. Treatments with antidepressant medication or running therapy are both found to be effective for many but not all patients with mood and anxiety disorders. These interventions may, however, work through different pathophysiological mechanisms and could differ in their impact on biological aging and somatic health. This study protocol describes the design of an unique intervention study that examines whether both treatments are similarly effective in reducing or reversing biological aging (primary outcome), psychiatric status, metabolic stress and neurobiological indicators (secondary outcomes). METHODS: The MOod Treatment with Antidepressants or Running (MOTAR) study will recruit a total of 160 patients with a current major depressive and/or anxiety disorder in a mental health care setting. Patients will receive a 16-week treatment with either antidepressant medication or running therapy (3 times/week). Patients will undergo the treatment of their preference and a subsample will be randomized (1:1) to overcome preference bias. An additional no-disease-no-treatment group of 60 healthy controls without lifetime psychopathology, will be included as comparison group for primary and secondary outcomes at baseline. Assessments are done at week 0 for patients and controls, and at week 16 and week 52 for patients only, including written questionnaires, a psychiatric and medical examination, blood, urine and saliva collection and a cycle ergometer test, to gather information about biological aging (telomere length and telomerase activity), mental health (depression and anxiety disorder characteristics), general fitness, metabolic stress-related biomarkers (inflammation, metabolic syndrome, cortisol) and genetic determinants. In addition, neurobiological alterations in brain processes will be assessed using structural and functional Magnetic Resonance Imaging (MRI) in a subsample of at least 25 patients per treatment arm and in all controls. DISCUSSION: This intervention study aims to provide a better understanding of the impact of antidepressant medication and running therapy on biological aging, metabolic stress and neurobiological indicators in patients with depressive and anxiety disorders in order to guide a more personalized medicine treatment. TRIAL REGISTRATION: Trialregister.nl Number of identification: NTR3460, May 2012.

Mutational Analysis Identifies Therapeutic Biomarkers in Inflammatory Bowel Disease-Associated Colorectal Cancers.

Purpose: Inflammatory bowel disease-associated colorectal cancers (IBD-CRC) are associated with a higher mortality than sporadic colorectal cancers. The poorly defined molecular pathogenesis of IBD-CRCs limits development of effective prevention, detection, and treatment strategies. We aimed to identify biomarkers using whole-exome sequencing of IBD-CRCs to guide individualized management.Experimental Design: Whole-exome sequencing was performed on 34 formalin-fixed paraffin-embedded primary IBD-CRCs and 31 matched normal lymph nodes. Computational methods were used to identify somatic point mutations, small insertions and deletions, mutational signatures, and somatic copy number alterations. Mismatch repair status was examined.Results: Hypermutation was observed in 27% of IBD-CRCs. All hypermutated cancers were from the proximal colon; all but one of the cancers with hypermutation had defective mismatch repair or somatic mutations in the proofreading domain of DNA POLE Hypermutated IBD-CRCs had increased numbers of predicted neo-epitopes, which could be exploited using immunotherapy. We identified six distinct mutation signatures in IBD-CRCs, three of which corresponded to known mechanisms of mutagenesis. Driver genes were also identified.Conclusions: IBD-CRCs should be evaluated for hypermutation and defective mismatch repair to identify patients with a higher neo-epitope load who may benefit from immunotherapies. Prospective trials are required to determine whether IHC to detect loss of MLH1 expression in dysplastic colonic tissue could identify patients at increased risk of developing IBD-CRC. We identified mutations in genes in IBD-CRCs with hypermutation that might be targeted therapeutically. These approaches would complement and individualize surveillance and treatment programs. Clin Cancer Res; 24(20); 5133-42. ©2018 AACR.

Mortality in type 1 diabetes diagnosed in childhood in Northern Ireland during 1989-2012: A population-based cohort study.

OBJECTIVE: To investigate long-term mortality rates and causes of death in individuals diagnosed with type 1 diabetes before the age of 15 years during the period 1989-2012 or known to paediatric diabetes teams in 1989, in Northern Ireland. METHODS: A cohort of 3129 patients from the Northern Ireland Childhood Diabetes Register was linked to death registrations and underlying causes, coded according to ICD-9 or ICD-10. Standardized mortality ratios (SMRs) were calculated as the ratio of observed to expected deaths by sex, attained age, time since diagnosis, calendar period, and cause of death. RESULTS: Subjects were followed to December 31, 2012 giving 39 764 person-years of follow-up (median 12.1 years). In total, 59 subjects had died (1.5 per 1000 person-years) compared with 19.9 deaths expected, an SMR of 296 (95% confidence interval (CI) 229-382). Women had a significantly higher excess risk of mortality than men with SMRs of 535 (95% CI 361-764) and 203 (95% CI 136-291), respectively. Over half of the deaths (56%) were judged to be related or possibly related to diabetes with most of these due to acute (n = 24) or late (n = 6) complications. CONCLUSIONS: Subjects with type 1 diabetes diagnosed less than 15 years of age had 3 times the mortality risk of the general population. Over half of the deaths were related to acute or chronic complications of diabetes.

Uric acid in major depressive and anxiety disorders.

BACKGROUND: Uric acid has neuroprotective effects, owing to its antioxidant properties. Lowered antioxidant capacity, causing increased oxidative stress, may be involved in affective disorders and might be altered by antidepressants. This study investigated the association of plasma uric acid, the greatest contributor to blood antioxidant capacity, with major depressive disorder (MDD) and anxiety disorders. METHODS: Data were from the Netherlands Study of Depression and Anxiety including patients with current (N = 1648), remitted (N = 609) MDD and/or anxiety disorders (of which N = 710 antidepressant users) and 618 controls. Diagnoses were established with the Composite International Diagnostic Interview. Symptom severity was assessed with the Inventory of Depressive Symptoms-Self Report, Beck Anxiety Inventory and Fear Questionnaire. Uric acid was measured in plasma. Analyses were adjusted for sociodemographic, health and lifestyle variables. RESULTS: Plasma uric acid adjusted mean levels were lower in current MDD and/or anxiety disorder(s) (289µmol/l) compared to remitted disorders (298µmol/l, p < .001) and controls (299µmol/l, p < .001; Cohen's d .10). This finding was independent of antidepressant use. Depressive (ß-.05, p = .0012), anxiety (ß-.04, p = .009) and phobic (ß-.03, p = .036) symptom severity, and symptom duration (ß-.04, p = .009) were negatively associated with uric acid. LIMITATIONS: Limitations include the lack of data on dietary intake which could be a potential confounding factor. From these cross-sectional findings, the association between uric acid and psychopathology cannot be inferred to be causal. CONCLUSION: This large scale study finds plasma uric acid levels are lower in current, but not remitted, MDD and/or anxiety disorders, according to a dose-response gradient. This suggests the involvement of decreased antioxidant status in affective disorders, and points to their potential as an avenue for treatment.

The association between three major physiological stress systems and oxidative DNA and lipid damage.

BACKGROUND: Increased activity of the three major physiological stress systems (immune-inflammatory system, hypothalamic-pituitary-adrenal-axis [HPA-axis], and autonomic nervous system [ANS]) is part of the pathophysiology of various somatic and psychiatric diseases. Oxidative damage is a key mechanism in both ageing and disease. Elucidating the relationship between these stress systems and oxidative damage would contribute to the understanding of the role of physiological stress in disease. This study therefore investigates associations between various measures of physiological stress and oxidative DNA (8-hydroxy-2'-deoxyguanosine, 8-OHdG) and lipid (F2-isoprostanes) damage. METHODS: Plasma 8-OHdG and F2-isoprostanes were measured using LC-MS/MS in 2858 subjects (aged 18-65). Plasma inflammation markers, salivary cortisol and ANS markers (three for each stress system) were determined. Linear regression analyses were adjusted for sociodemographics, sampling factors and medication. RESULTS: 8-OHdG was positively associated with all inflammation markers (ß=0.047-0.050, p<0.01), evening cortisol (ß=0.073, p<0.001), and unexpectedly with low respiratory sinus arrhythmia (RSA) reflecting low ANS stress (ß=0.073, p<0.001). F2-isoprostanes were associated with higher C-reactive protein (ß=0.072, p<0.001), high ANS stress reflected in heart rate (ß=0.064, p<0.001) and RSA (ß=-0.076, p=0.001), but not with cortisol. Analyses investigating the cumulative impact of the stress systems demonstrated that the number of systems with ≥1 marker in the high risk quartile showed a positive linear trend with both 8-OHdG (p=0.030) and F2-isoprostanes (p=0.009). CONCLUSION: This large-scale study showed that markers of inflammation, the HPA-axis and ANS are associated with oxidative DNA damage. Oxidative lipid damage is associated with inflammation and the ANS. Increased physiological stress across systems is associated with increasing oxidative damage in a dose-response fashion.

Oxidative stress and brain morphology in individuals with depression, anxiety and healthy controls.

Oxidative stress is a biological process, caused by an imbalance between reactive oxygen species (ROS) and antioxidants, in favour of the ROS. This imbalance leads to oxidative damage to lipids, proteins and DNA and ultimately cell death. Studies in rodents have shown that the brain, particularly the amygdala and hippocampus, is sensitive to oxidative stress, although studies on the association between oxidative stress and brain morphology in humans are lacking. Oxidative stress has also been associated with major depressive disorder (MDD) and may be related to volumetric abnormalities in the amygdala and hippocampus in MDD and anxiety disorders. In this study we aimed to examine the association between two robust measures of oxidative damage in plasma (8-OHdG and F2-isoprostanes) and volume of the hippocampus and amygdala in a large sample of individuals with and without MDD and/or anxiety (N=297). In secondary analyses, we examine whether this association is similar in patients and controls. 8-OHdG and F2-isoprostanes plasma levels were determined using liquid chromatography tandem mass spectrometry and volume of the hippocampus and amygdala and hippocampal subfields was determined using Freesurfer. We found no association between plasma markers (or interaction with MDD and/or anxiety disorder diagnosis) and subcortical volume, suggesting that peripheral oxidative stress damage is not associated with subcortical brain volume.

Sociodemographic and Lifestyle Determinants of Plasma Oxidative Stress Markers 8-OHdG and F2-Isoprostanes and Associations with Metabolic Syndrome.

Background. Oxidative stress is increasingly important in health research. Therefore, it is necessary to understand which factors determine basal oxidative stress. This study examines the associations of various determinants with markers of oxidative DNA and lipid damage: 8-hydroxy-2'-deoxyguanosine (8-OHdG) and F2-isoprostanes. Methods. Data are from the Netherlands Study of Depression and Anxiety; 1117 subjects (18-65 years) without a current psychiatric diagnosis. Multivariable regression analyses were conducted with plasma levels of 8-OHdG and F2-isoprostanes (measured by LC/MS-MS) including sociodemographic, lifestyle, and sampling variables. Associations with metabolic syndrome (MetS) and chronic disease were examined. Results. 8-OHdG and F2-isoprostanes were weakly correlated (r = 0.06, p = 0.045). Both were positively associated with age and cotinine (cigarette exposure); 8-OHdG was lower in females and after longer sample storage. F2-isoprostanes were higher in females, alcohol users, and in samples collected in spring and lower in supplement users and those with more education. Both markers were lower in fasting subjects. F2-isoprostanes, not 8-OHdG, were positively associated with MetS. Conclusion. The weak correlation between 8-OHdG and F2-isoprostanes suggests they reflect specific aspects of oxidative stress. Both markers are associated with a range of sociodemographic, lifestyle, and sampling determinants which should be considered in future research. F2-isoprostanes are associated with MetS.

Taiwanese farm workers' pesticide knowledge, attitudes, behaviors and clothing practices.

The purpose of this study was to assess Taiwanese fruit farm workers' knowledge, attitudes, behaviours, and clothing practices regarding pesticide activities. Seventy-seven fruit farm workers from four districts of Tainan City, Taiwan completed the questionnaire. Results indicated that farmer workers had a good overall level of knowledge of the adverse effects of pesticides on human health and most had experienced symptoms of pesticide poisoning. Farm workers' attitudes toward pesticide use and handling indicated that they saw pesticides useful in controlling pests. Farm workers indicated the limited availability of comfortable clothing designed for a hot and humid climate while still providing sufficient protection was the main reason for not wearing personal protective clothing (PPC) and personal protective equipment (PPE). Emphasis on safety precautions is needed when using pesticides, and the importance of PPC and PPE is essential for the health of farm workers.

Excess mortality in Type 1 diabetes diagnosed in childhood and adolescence: a systematic review of population-based cohorts.

AIMS: Systematic review of mortality in childhood-/adolescent-diagnosed Type 1 diabetes and examination of factors explaining the mortality variation between studies. METHODS: Relevant studies were identified from systematic searches of MEDLINE and EMBASE. Observed and expected numbers of deaths were extracted, and standardised mortality ratios (SMRs) and 95 % confidence intervals (CIs) were calculated. Negative binomial regression was used to investigate association between mortality and study/country characteristics. RESULTS: Thirteen relevant publications with mortality data were identified describing 23 independent studies. SMRs varied markedly ranging from 0 to 854 (χ (2) = 70.68, df = 21, P < 0.0001). Significant associations were observed between SMR and mid-year of follow-up [incidence rate ratio (IRR) 0.95, 95 % CI 0.91-0.99 equivalent to a 5 % decrease per year], between SMR and infant mortality rate (IRR 1.07, 95 % CI 1.02-1.12, a 7 % increase for each death per 1,000 live births) and, after omitting an outlier, between SMR and health expenditure as a percentage of gross domestic product (GDP) (IRR 0.79, 95 % CI 0.68-0.93, a 21 % decrease for each one percent increase in GDP). No relationship was detected between SMR and a country's childhood diabetes incidence rate or GDP. CONCLUSIONS: Excess mortality in childhood-/adolescent-diagnosed Type 1 diabetes is apparent across countries worldwide. Excesses were less marked in more recent studies and in countries with lower infant mortality and higher health expenditure.

Is depression associated with increased oxidative stress? A systematic review and meta-analysis.

BACKGROUND: It has been suggested that depressed persons have increased oxidative stress and decreased anti-oxidant defences. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and F2-isoprostanes, measures of oxidative DNA and lipid damage respectively, are among the most reliable oxidative stress markers, but studies on their association with depression show conflicting results. This meta-analysis quantifies the association between depression and these markers and explores factors that may explain inconsistencies in the results. METHODS: A systematic literature search was conducted in PubMed, EMBASE and PsycINFO. Studies assessing the association of 8-OHdG or F2-isoprostanes with elevated depressive symptoms, major depressive disorder (MDD) or bipolar disorder (BD) were pooled in two random-effect models. RESULTS: The pooled effect size (Hedges' g) for the association of depression with oxidative stress was 0.31 (p=0.01, I(2)=75%) for 8-OHdG (10 studies, 1308 subjects) and 0.48 (p=0.001, I(2)=73%) for F2-isoprostanes (8 studies, 2471 subjects), indicating that both markers are increased in depression. There was no indication of publication bias for either marker. The F2-isoprostane results did not differ by type of depression, biological specimen, laboratory method or quality, however subgroup analyses in the 8-OHdG studies showed significantly stronger associations in plasma/serum vs. urine samples (p<0.01), in measurements performed with immuno-assay vs. chromatography-mass spectrometry (p<0.01) and weaker associations in high quality studies vs. low (p=0.02). CONCLUSION: This meta-analysis finds that oxidative stress, as measured by 8-OHdG and F2-isoprostanes, is increased in depression. Larger-scale studies are needed to extend the evidence on oxidative stress in depression, and examine the potential impact of treatment.

Resistant nonalcoholic fatty liver disease amelioration with rosuvastatin and pioglitazone combination therapy in a patient with metabolic syndrome.

OBJECTIVE: To report a case describing resolution of persistently elevated aminotransferases in a patient with severe, resistant nonalcoholic fatty liver disease (NAFLD) using combination therapy. CASE SUMMARY: A 47-year-old obese male patient presented with a history of elevated aminotransferases and numerous statin intolerances. In addition to worsening control of diabetes and dyslipidemia, severe NAFLD was confirmed. Rosuvastatin was started, which induced short-term elevations in aminotransferases resulting in patient discontinuation. Biochemical markers of NAFLD worsened over time. Therefore, both rosuvastatin 20 mg daily and pioglitazone 15 mg daily were started simultaneously to potentially blunt the early increase in transaminases seen with rosuvastatin. At 2 weeks, the patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had decreased 57% and 56% from baseline, respectively. By 9 months, the patient's ALT and AST serum concentrations had normalized. Repeat liver ultrasound demonstrated improvement in steatosis grading and reduction in liver size. These improvements occurred despite a 4.5-kg weight gain since starting rosuvastatin and pioglitazone. DISCUSSION: Pharmacotherapy in NAFLD is not well validated, particularly combination therapy. Medications that target obesity-related consequences are commonly used, although evidence regarding biochemical and histological improvement is inconclusive. Consideration should be given to the use of combination of thiazolidinediones and statins for rapid biochemical improvement and long-term histological impact. CONCLUSIONS: The improvement in this patient's biochemical and ultrasonographic markers of resistant, severe NAFLD was rapid and sustained with combination therapy. This case represents a potential solution for initiating or maintaining statin therapy in patients with NAFLD who are at high cardiovascular risk.

Post-transplant plasmablastic lymphoma of the skin.

Plasmablastic lymphoma (PBL) is a recently described rare variant of diffuse large B-cell lymphoma characterised by its aggressive nature and plasmacytic differentiation. It most frequently arises in the oral cavity of human immunodeficiency virus (HIV)-infected patients. However extra-oral involvement is becoming increasingly recognised, particularly in HIV-negative patients. We report a case of PBL presenting as multiple violaceous nodules and plaques on the leg of a HIV-negative patient, 13-years post-renal transplant. To date, 20 cases of PBL presenting in the skin have been reported. We review and compare the clinico-pathological features of these cases.

Estimate or calculate? How surgeons rate volumes and surfaces.

PURPOSE: Surgeons frequently describe the shape of intraoperative findings using visual judgement and their own sense of proportion or describing these findings in comparison to commonly used or metaphoric subjects. The aim of the study was to analyse the reliability of surgeon's estimations of dimensions. METHODS: The study was performed in two phases. First, physicians had to estimate the metric proportions of four well-known objects. Second, surgeons were asked intraoperatively to estimate the liver resection surface after partial hepatectomy. The exact surface of the resection plane was measured using computed tomography-guided planimetry of the resection specimen. Physician's estimations and the exact measurements of the well-known objects and the liver resection surface were compared. Systematic error was defined by the natural logarithm of estimated/real size. RESULTS: We found a large individual discrepancy in estimating the metric proportions of commonly used objects and a tendency to underestimate both commonly used objects and liver resection surface. Experienced liver surgeons were more accurate in estimating liver resection surface compared with younger staff members. CONCLUSIONS: We found a large bias in estimating the dimension of both commonly used objects and the surface area of liver parenchyma transection. Obviously, estimating errors are more influenced by the individual subject who estimates than by the object itself. In clinical routine, surgeons should rely more on simple measuring devices than on their own sense of proportion. Education in how to estimate more correctly human liver resection surfaces can be achieved by ex vivo studies using porcine livers.

Drugs and pacemakers for vasovagal, carotid sinus and situational syncope.

BACKGROUND: Neurally mediated reflex syncope is the most common cause of transient loss of consciousness. In patients not responding to non-pharmacological treatment, pharmacological or pacemaker treatment might be considered. OBJECTIVES: To examine the effects of pharmacological therapy and pacemaker implantation in patients with vasovagal syncope, carotid sinus syncope and situational syncope. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 1, 2008), PubMed (1950 until February 2008), EMBASE on OVID (1980 until February 2008) and CINAHL on EBSCOhost (1937 until February 2008). No language restrictions were applied. SELECTION CRITERIA: We included parallel randomized controlled trials and randomized cross-over trials of pharmacological treatment (beta-blockers, fludrocortisone, alpha-adrenergic agonists, selective serotonine reuptake inhibitors, ACE inhibitors, disopyramide, anticholinergic agents or salt tablets) or dual chamber pacemaker treatment. Studies were included if pharmacological or pacemaker treatment was compared with any form of standardised control treatment (standard treatment), placebo treatment, or (other) pharmacological or pacemaker treatment. We did not include non-randomized studies. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the risk of bias. Using a standardised data extraction form, they extracted characteristics and results of the various studies. In a consensus meeting they discussed any disagreements that had occurred during data extraction. If no agreement could be reached, a third reviewer was asked to make a decision. Summary estimates with 95% confidence intervals of treatment effect were calculated using relative risks, rate ratios or weighted means differences depending on the type of outcome reported. MAIN RESULTS: We included 46 randomized studies, 40 on vasovagal syncope and six on carotid sinus syncope. No studies on situational syncope matched the criteria for inclusion in our review. Studies in general were small with a median sample size of 42. A wide range of control treatments were used with 22 studies using a placebo arm. Blinding of patients and treating physicians was applied in eight studies. Results varied considerably between studies and between types of outcomes.For vasovagal syncope, the occurrence of syncope upon provocational head-up tilt testing was lower upon treatment with beta-blockers, ACE-inhibitors and anticholinergic agents compared to standard treatment. For carotid sinus syncope, the occurrence of syncope upon carotid sinus massage was lower on midodrine treatment compared to placebo treatment in one study. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of any of the pharmacological or pacemaker treatments for vasovagal syncope and carotid sinus syncope. Larger studies using patient relevant outcomes are needed.

Laser acupuncture does not improve menopausal symptoms.

OBJECTIVE: Acupuncture is commonly used to treat menopausal symptoms and other gynecological conditions. Laser acupuncture, more accurately named "laser acupoint stimulation," has the advantages of being noninvasive, reproducible, and convenient. A few studies of conventional acupuncture have suggested a beneficial effect in treating menopausal symptoms. This study sought to investigate the effectiveness of laser acupoint stimulation in relieving symptoms associated with menopause. METHODS: A double-blind, randomized, placebo-controlled study was conducted in 40 women experiencing active symptoms of menopause. Outcome variables were numbers of diurnal and nocturnal flushes and symptom score, determined using a previously validated scale. A laser acupoint stimulation device was altered to produce identical flashing lights whether or not the laser was operating to allow for a placebo ("laser off") control. Participants received either active or placebo treatment on a fortnightly basis for 12 weeks. The acupoint selection in both groups was individualized to each participant, selected from a set of 10 acupoints. RESULTS: There were no significant differences between the active and placebo treatment groups in numbers of diurnal or nocturnal flushes or in nonflushing symptom scores. CONCLUSIONS: Laser acupoint stimulation chosen from a fixed set of acupoints is no more efficacious than manual stimulation with an inert laser probe in altering menopausal symptoms.

Ectopic pancreatic-type malignancy presenting in a Meckel's diverticulum: a case report and review of the literature.

BACKGROUND: Neoplasms arising from Meckel's diverticulae reported in the literature are mainly carcinoid tumours, gastrointestinal stromal tumours, and gastric or intestinal adenocarcinomas. CASE PRESENTATION: We describe a 50-year-old man who presented with rectal bleeding and anaemia, later found to be caused by a pancreatic adenocarcinoma arising from ectopic pancreatic tissue in a Meckel's diverticulum. The tumour was unfortunately highly aggressive, and the patient passed away within 5 months of symptom onset. CONCLUSION: We believe this is the first case of pancreatic adenocarcinoma in a Meckel's diverticulum to be reported in the literature. The diagnosis of Meckel's should be considered in patients with acute gastrointestinal complaints; when found incidentally at laparotomy, it should be carefully examined for any gross abnormality and resection should be considered.

Chest wall injuries following cardiopulmonary resuscitation.

The forensic records were reviewed of 1823 deaths referred to Edinburgh City Mortuary for autopsy over a 15-month period, 2000-2001; 499 cases (343 males, 156 females) that received CPR prior to death were studied. Rib fractures were found in 29%, sternal fracture in 14%, and 11% of cases showed external chest wall bruising or abrasion. More females sustained rib fractures than males (37% versus 26%; P <0.05). There was no significant gender difference for sternal fracture (females 17%, males 12%; P=0.051). The incidence of rib fractures increased with age (P <0.001). There was no significant difference in the number of left or right ribs fractured (P=0.631). This study incorporates all cases of in and out-of-hospital CPR and does not discriminate for the CPR provider or technique employed, therefore, providing a current and representative overview of the incidence of rib and sternal fractures in non-survivors of CPR.