Meta-analysis and systematic review of population-based epidemiological studies in idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is positively associated with obesity, mostly in young women. The global increase in obesity may influence the burden of IIH. Using the PubMed, Embase, MEDLINE and Web of Science databases, a meta-analysis and systematic review of epidemiological studies of IIH were performed up to June 2017. Temporal changes in IIH incidence were measured, and incidence rates of IIH were correlated with country-specific World Health Organization obesity rates. Prevalence data and shunting rates of IIH were recorded. The quality of epidemiological studies was assessed using the Standards of Reporting of Neurological Disorders (STROND) criteria. In 15 identified studies, there were 889 patients (87% women), mean age 29.8 years. The incidence of IIH ranged from 0.03 to 2.36 per 100 000 per year. The pooled incidence of IIH was 1.20 per 100 000 per year although there was very high heterogeneity (I2 98%). The incidence rates of IIH were correlated with country-specific prevalence of obesity (Spearman's correlation 0.82, P < 0.01). The prevalence of IIH was rarely recorded. A shunting procedure was reported in 8% of patients. STROND criteria were variably reported, median of 26.5 of 43 (range 16-35). IIH is a public health concern as increased obesity prevalence is associated with increased incidence of IIH. A better quality of epidemiological studies is required to improve understanding of IIH and inform health policy for IIH management.

Are adult carpal angle measurements applicable to the pediatric population in the trauma setting?

OBJECTIVE: The aim of this study is to assess the applicability of standard adult carpal angle measurements, specifically the scapholunate and capitolunate angles, in the assessment of the pediatric wrist. MATERIALS AND METHODS: The study cohort comprised male and female children who underwent a wrist radiograph for the evaluation of suspected wrist injuries following trauma. A gender- and indication-matched adult cohort was also assessed. To ensure an accurate carpal angle measurement, only individuals with a sufficiently ossified carpus and an adequately positioned lateral wrist radiograph were included. RESULTS: Carpal angle measurements were performed on the lateral wrist radiographs of 256 individuals between the ages of 5 and 17 years (mean 11.2 years, SD ± 2.5 years) and 256 individuals between the ages of 18 and 40 years (mean 28.8 years, SD ± 6.2 years). The mean pediatric scapholunate angle was 47° (SD ± 8) and the mean pediatric capitolunate angle was 11° (SD ± 7). The mean adult scapholunate and capitolunate angles were 48° (SD ± 8°) and 10° (SD ± 6°) respectively. No statistically significant difference was observed between the scapholunate or capitolunate angle measurements in the two groups (p = 0.26 and p = 0.36). CONCLUSION: The study data supports the applicability of standard adult carpal angle values to the pediatric population provided the carpus is sufficiently ossified.

The physics of Martian weather and climate: a review.

The planet Mars hosts an atmosphere that is perhaps the closest in terms of its meteorology and climate to that of the Earth. But Mars differs from Earth in its greater distance from the Sun, its smaller size, its lack of liquid oceans and its thinner atmosphere, composed mainly of CO(2). These factors give Mars a rather different climate to that of the Earth. In this article we review various aspects of the martian climate system from a physicist's viewpoint, focusing on the processes that control the martian environment and comparing these with corresponding processes on Earth. These include the radiative and thermodynamical processes that determine the surface temperature and vertical structure of the atmosphere, the fluid dynamics of its atmospheric motions, and the key cycles of mineral dust and volatile transport. In many ways, the climate of Mars is as complicated and diverse as that of the Earth, with complex nonlinear feedbacks that affect its response to variations in external forcing. Recent work has shown that the martian climate is anything but static, but is almost certainly in a continual state of transient response to slowly varying insolation associated with cyclic variations in its orbit and rotation. We conclude with a discussion of the physical processes underlying these long- term climate variations on Mars, and an overview of some of the most intriguing outstanding problems that should be a focus for future observational and theoretical studies.

Unscheduled undergraduate teaching in surgery: a multi-institutional analysis.

A significant amount of valuable undergraduate medical teaching may be informal, unscheduled and delivered by non-consultant hospital doctors (NCHDs). 800 Questionnaires were distributed to consultants, NCHDs and medical students in Irish teaching hospitals. The aim was to quantify the level of unscheduled teaching carried out in these hospitals and the manner in which it was performed. The response rate was 46% (364/800). 71% of doctors who replied are independently teaching undergraduate medical students (77/109), including 71% of interns and senior house officers (48/68). Students tend to prefer small group teaching. Fifty-six percent of students suggest they would benefit from more surgical teaching time (144/255). No interns surveyed were scheduled to teach as part of a formal curriculum. A significant amount of unscheduled teaching by interns and senior house officers takes place in Irish hospitals. It may prove beneficial to incorporate interns into scheduled surgical teaching curricula.

Double trouble--duplication of the gallbladder requiring repeat laparoscopic cholecystectomy.

Duplication of the gallbladder is a surprisingly common phenomenon. Clinically, these patients present with straightforward gallbladder pathologies. It is a challenging preoperative diagnosis on ultrasound, and most cases are diagnosed intra-operatively. We present a case of gallbladder duplication, where the patient presented with biliary colic, had a straightforward laparoscopic cholecystectomy, and then represented with biliary colic four years later.

An outcome analysis of seventeen patients treated surgically for intractable extratemporal epilepsy.

We studied the outcomes of seventeen patients treated surgically for extratemporal lobe epilepsy. A retrospective case review of medical charts was performed. Seizure freedom post surgery was appraised using the Engel classification system. Post-operatively seven patients (41%) were seizure free (Engel class I), four patients were class II (23.5%), two in class III (11.76%) and four in class IV (23.5%). Three patients (17.6%) suffered traumatic injuries due to seizures. The mean duration of epilepsy prior to surgery was 12.2 years and the mean number of anti-epileptic medications given was 6.5. Seizure freedom rates for surgical treatment of extratemporal epilepsy in this centre are similar to those of other centres. Post-operative morbidity in this centre was similar to other centres. Any complications resolved with no lasting impairment.

Varicocele Embolization: An Assessment of the Quality and Readability of Online Patient Information.

AIMS AND OBJECTIVES: Varicocele embolization is a growing treatment modality owing to the safety, efficacy, and quick return to work following the procedure. The internet is the most dominant source of information for many. We aimed to assess the quality of information accessible by patients considering treatment. MATERIALS AND METHODS: A list of applicable, commonly used searchable terms was generated. Each term was assessed across the five most-used English language search engines to determine the two most commonly used terms. These two terms were then investigated across each search engine, with the first 25 web pages returned by each engine included for analysis. Duplicate web pages, nontext content such as video or audio, and web pages behind paywalls were excluded. Web pages were analyzed for quality and readability using validated tools including DISCERN score, JAMA Benchmark Criteria, HONcode Certification, Flesch Reading Ease Score, Flesch-Kincaid Grade Level, and Gunning-Fog Index. Secondary features including age, rank, author, and publisher were recorded. RESULTS: The most common applicable terms were "Testicular embolization" (378,300 results) and "Varicocele embolization" (375,800 results). Mean DISCERN quality of information provided by websites is "fair"; Adherence to JAMA Benchmark Criteria was 13.5%. Flesh-Kincaid readability tests demonstrated an average "9th grade" reading level. Scientific journals showed the highest quality scores, but were least up to date with an average web page age of 11.2 years. Web pages produced by "for-profit" organizations were the second most current (average age 2.7 years), but displayed the lowest quality of information scores. CONCLUSION: While quality of online information available to patients is "fair," adherence to JAMA benchmark criteria is poor. "For-profit" organization websites are far more numerous and significantly more up-to-date, yet showed significantly lower quality of information scores. Scientific journals were unsurprisingly of higher quality, yet more challenging for the general public to read. These findings call for the production of high-quality and comprehensible content regarding interventional radiology, where physicians can reliably direct their patients for information.

Tumor suppressor PTEN inhibits nuclear accumulation of beta-catenin and T cell/lymphoid enhancer factor 1-mediated transcriptional activation.

beta-Catenin is a protein that plays a role in intercellular adhesion as well as in the regulation of gene expression. The latter role of beta-catenin is associated with its oncogenic properties due to the loss of expression or inactivation of the tumor suppressor adenomatous polyposis coli (APC) or mutations in beta-catenin itself. We now demonstrate that another tumor suppressor, PTEN, is also involved in the regulation of nuclear beta-catenin accumulation and T cell factor (TCF) transcriptional activation in an APC-independent manner. We show that nuclear beta-catenin expression is constitutively elevated in PTEN null cells and this elevated expression is reduced upon reexpression of PTEN. TCF promoter/luciferase reporter assays and gel mobility shift analysis demonstrate that PTEN also suppresses TCF transcriptional activity. Furthermore, the constitutively elevated expression of cyclin D1, a beta-catenin/TCF-regulated gene, is also suppressed upon reexpression of PTEN. Mechanistically, PTEN increases the phosphorylation of beta-catenin and enhances its rate of degradation. We define a pathway that involves mainly integrin-linked kinase and glycogen synthase kinase 3 in the PTEN-dependent regulation of beta-catenin stability, nuclear beta-catenin expression, and transcriptional activity. Our data indicate that beta-catenin/TCF-mediated gene transcription is regulated by PTEN, and this may represent a key mechanism by which PTEN suppresses tumor progression.

Regression analyses of southern African ethnomedicinal plants: informing the targeted selection of bioprospecting and pharmacological screening subjects.

ETHNOPHARMACOLOGICAL RELEVANCE: Regression analyses of local medicinal floras are considered potentially useful when prioritising candidate plant taxa for pharmacological/bioprospecting investigations. AIM OF THE STUDY: To identify plant orders and subsequently families within the highly diverse ethnomedicinal flora of southern Africa, towards which biases by traditional healers are demonstrable. Taxa so identified can subsequently be weighted appropriately in semi-quantitative selection systems. METHODOLOGY: Plant data sourced from the SANBI MedList database, the most comprehensive inventory of ethnomedicinal plants for the Flora of southern Africa region were grouped by order. A least squares regression analysis was applied to test the null hypothesis that the use of these plants by traditional healers is strictly random. Of 'hot' orders subsequently identified, characteristics of taxa therein were assessed to better determine the roles played by (i) growth forms, and (ii) inherent chemical diversity, in plant selections by ethnomedicinal practitioners. RESULTS: Analyses identified seven principally 'hot' plant orders (Malpigiales, Fabales, Gentianales, Asteraceae, Solanales, Malvales and Sapindales) and 'hot' families therein from a total of 55 regional ethnomedicinal orders. Five 'cold' ethnomedicinal orders (Rosales, Proteales, Poales, Asparagales and Caryophyllales) were shown to be significantly less represented in the medicinal flora than predicted. No clear growth form preferences were identified across orders. The presence of highly diverse bioactives was evident in the 'hottest' plant families from 'hot' plant orders. CONCLUSIONS: These 12 outliers identified by the regression analyses allowed for the falsification of the null hypothesis. Indications are that 'hot' taxa are selected traditionally on the basis of bioactivity, which is reflected in chemical diversity.

The in vitro pharmacological activities of 12 South African Hermannia species.

Hermannia species are widely used in traditional medicine in southern Africa, however no extensive study has been conducted on this genus. The acetone extracts of 12 indigenous Hermannia species (flowers, stems and leaves combined) were evaluated for various pharmacological activities. All investigated species displayed promising antimicrobial activity, with Hermannia saccifera being the most active against Staphylococcus aureus (MIC=19.5 microg/ml), Bacillus cereus (MIC=19.5 microg/ml) and Enterococcus faecalis (MIC=125 microg/ml). Time-kill studies on H. saccifera against S. aureus indicated bacteriostatic activity at 1.25, 2.5 and 5.0%, and a concentration of 7.5% achieved complete bactericidal activity after 4h. Ten of the 12 species indicated good free radical scavenging activity, with H. cuneifolia demonstrating the most promising activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH():IC(50)=10.26 microg/ml) and 2,2'-azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS(+)/TEAC: IC(50)=10.32 microg/ml) assays. In addition, all species exhibited moderate anti-inflammatory activity in the 5-lipoxygenase assay with the exception of H. cuneifolia (IC(50)=15.32 microg/ml). Overall, the selected species were low in cytotoxicity, except for H. saccifera and H. trifurca. Several Hermannia species indicated promising in vitro biological activity which relate to their traditional use in treating a number of disease states.

PTEN and GSK3beta: key regulators of progression to androgen-independent prostate cancer.

Prostate cancer (PrCa) is characterized by progression from an androgen-dependent phenotype to one that is inevitably androgen independent (AI) and lethal. Recent evidence strongly suggests that the phosphatidylinositol-3-kinase/Akt (PI3K/Akt) and androgen receptor (AR) signalling pathways provide prostatic epithelium with the necessary signalling events to escape the apoptotic response associated with androgen withdrawal therapy. Silencing of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and glycogen synthase kinase beta (GSK3beta) are frequently associated with advanced PrCa systems and likely serve critical roles in promoting AR and PI3K/Akt gain-of-function. That PTEN negatively regulates AR and is sufficient to promote metastatic PrCa in murine models strongly implies its role as a gatekeeper of progressive PrCa. In human PrCa, PTEN loss is correlated with substantial increases in Akt(Ser473) and integrin-linked kinase expression, both of which promote Ser(9) phospho-inhibition of GSK3beta and inactivation of apoptotic factors. Sufficient evidence also suggests that GSK3beta is not only a critical regulator of proproliferative signalling but also a promiscuous one as PI3K/Akt pools of GSK3beta are, at least in part, functionally interchangeable with those of the Wnt/beta-catenin pathway. Thus, GSK3beta may serve not only as a mediator of PI3K/Akt activation but may also regulate the potent transactivation and proproliferative effects that Wnt3a and beta-catenin confer upon AR. These data suggest that prostate-specific activation of GSK3beta may serve as a viable pharmacological option. Thus, in this review, we emphasize that temporal changes in GSK3beta and PTEN expression during progression to AI PrCa are important factors when considering the potential for therapies targeting the oncogenic contributions of PI3K/Akt and AR signalling pathways.

Low antiplasmodial activity of alkaloids and amides from the stem bark of Zanthoxylum rubescens (Rutaceae).

The stem bark of Zanthoxylum rubescens (syn. Fagara rubescens) is used for treating fevers associated with malaria in the Ivory Coast. Three alkaloids: N-nornitidine, 7,9-dimethoxy-2,3-methylenedioxybenzophenanthridine, and bis[6-5,6-dihydrochelerythrinyl)] ether; and two amides: zanthomamide and lemairamide, were isolated from the stem bark of this plant. These compounds were screened in vitro against the chloroquine-sensitive 3D7 strain and the chloroquine-resistant FCM29 strain of P. falciparum. N-nornitidine was found to be inactive. 7,9-dimethoxy-2,3-methylenedioxybenzophenanthridine, lemairamide and zanthomamide showed weak activity with average IC50 values ranging from 45.6 microM to 149.9 microM. Bis[6-15,6-dihydrochelerythrinyl)] ether was the most active of the tested compounds with mean IC50s of 14.9 +/- 1.4 microM in FCM29 strain and 15.3 +/- 3.4 microM in 3D7 strain (approximately 58 to approximately 1130 times less active than chloroquine respectively). The anti-Plasmodium activities of the tested alkaloids of Z. rubescens were low; and do not encourage the use of this plant as antimalarial.

Predictors of poor self-rated health at area level in the Eastern Regional Health Authority: a multilevel analysis.

In this analysis, employing 2002 data from SLAN Survey of Lifestyles, Attitudes and Nutrition and mortality data from the Eastern region of the Republic of Ireland, we examined predictors of area level variability in self-rated health across 101 electoral divisions (ED)s. Overall 11.5% of 1500 participants reported fair or poor health. We found area level variation in poor self-rated health (0.0357 (SE 0.160), p = 0.03), which was related significantly to area-level standardised mortality ratio. Odds of poor self-rated health, adjusted for age and sex were 1.55 (95% CI 0.89, 2.71) in average SMR areas and 2.61 (95% CI 1.38, 4.92) in high SMR areas compared to low SMR areas. Adjusted models for age, sex, general medical services eligibility, an established proxy for income, problems in the neighbourhood and smoking rates largely explained any variability, suggesting a strong role for individual disadvantage in predicting health status, regardless of area, in Ireland.

Making health informatics competencies useful: an applied health informatics competency self-assessment system.

Years ago we undertook to define Health Informatics (HI) competencies. This effort resulted in the creation of a document that articulated HI roles, the challenges faced by HI professionals, the high-level tasks that they needed to undertake to address these challenges and the competencies (skills, knowledge, and experience) they needed to complete these tasks. Unfortunately, in so doing we created what is arguably the most boring book in history, shoes contents are very difficult to extract, use, maintain and improve. We report here the completion of a pilot of a system that we believe corrects this situation. It is a webbased tool that incorporates all of the material, from roles to detailed competencies, enabling them to be accessed and used for a variety of purposes, the most notable of which is professional self-assessment.

Investigations of the Malagasy species Tachiadenus longiflorus Grisebach (Gentianaceae): linking chemical finding and traditional usage.

A decoction of the aerial parts of Tachiadenus longiflorus, a Gentianaceae endemic to Madagascar, is drunk to relieve stomach pains and dyspepsia; while a leaf decoction is drunk as a purgative or to relieve gall bladder ailments in folk medicine in Madagascar. The stem and bark have yielded a large amount of the triterpenoid, oleanolic acid, and the coumarins, scoparone and scopoletin. These compounds have been isolated previously from other sources and have shown broad pharmacological properties. We report the possible link between the compounds isolated and the traditional use of Tachiadenus longiflorus.

Evaluation of the mutagenic and antimutagenic effects of South African plants.

Dichloromethane and 90% methanol extracts of 42 South African plants were screened for mutagenicity and antimutagenicity using the Salmonella/microsome mutagenicity assay (Ames) against Salmonella typhimurium TA98 and TA100 bacterial strains in the presence and absence of metabolic activator S9. The methanol extracts from whole plants of Helichrysum simillimum, Helichrysum herbaceum and Helichrysum rugulosum indicated mutagenicity. These are the first reported tests on the mutagenicity of Helichrysum species. Six species indicated antimutagenic properties, all in the presence of S9: methanol leaf extract of Bauhinia galpinii, and dichloromethane leaf extracts of Bauhinia galpinii, Clerodendrum myricoides, Datura stramonium, Buddleja saligna, Millettia sutherlandii and Sutherlandia frutescens.

HDAC inhibition impedes epithelial-mesenchymal plasticity and suppresses metastatic, castration-resistant prostate cancer.

PI3K (phosphoinositide 3-kinase)/AKT and RAS/MAPK (mitogen-activated protein kinase) pathway coactivation in the prostate epithelium promotes both epithelial-mesenchymal transition (EMT) and metastatic castration-resistant prostate cancer (mCRPC), which is currently incurable. To study the dynamic regulation of the EMT process, we developed novel genetically defined cellular and in vivo model systems from which epithelial, EMT and mesenchymal-like tumor cells with Pten deletion and Kras activation can be isolated. When cultured individually, each population has the capacity to regenerate all three tumor cell populations, indicative of epithelial-mesenchymal plasticity. Despite harboring the same genetic alterations, mesenchymal-like tumor cells are resistant to PI3K and MAPK pathway inhibitors, suggesting that epigenetic mechanisms may regulate the EMT process, as well as dictate the heterogeneous responses of cancer cells to therapy. Among differentially expressed epigenetic regulators, the chromatin remodeling protein HMGA2 is significantly upregulated in EMT and mesenchymal-like tumors cells, as well as in human mCRPC. Knockdown of HMGA2, or suppressing HMGA2 expression with the histone deacetylase inhibitor LBH589, inhibits epithelial-mesenchymal plasticity and stemness activities in vitro and markedly reduces tumor growth and metastasis in vivo through successful targeting of EMT and mesenchymal-like tumor cells. Importantly, LBH589 treatment in combination with castration prevents mCRPC development and significantly prolongs survival following castration by enhancing p53 and androgen receptor acetylation and in turn sensitizing castration-resistant mesenchymal-like tumor cells to androgen deprivation therapy. Taken together, these findings demonstrate that cellular plasticity is regulated epigenetically, and that mesenchymal-like tumor cell populations in mCRPC that are resistant to conventional and targeted therapies can be effectively treated with the epigenetic inhibitor LBH589.

Effect of pacing rate on the human atrial strength-duration curve.

The effect of rapid pacing on the atrial constant voltage stimulation threshold in humans has not been defined at rates applicable to those of antitachycardia pacing. The effect of pacing rate on the atrial strength-duration relation was determined in 10 patients at pacing rates between 125 and 300 beats/min to explore excitability over the range of rates used for permanent antitachycardia pacing systems. Two points that define the strength-duration curve were measured at each pacing rate: rheobase voltage--the lowest stimulus voltage that results in capture at a pulse duration of 2 ms; and chronaxie pulse duration--the threshold pulse duration at twice rheobase voltage. A permanent, tined, J-shaped pacing lead with a high current density and low polarization electrode was positioned in the right atrial appendage for cathodal stimulation. A constant voltage output, incorporating a fast recharge pulse designed to minimize electrode polarization, was used for stimulation. There was a significant increase in rheobase voltage (p = 0.009), chronaxie pulse duration (p = 0.001) and minimal threshold stimulus energy (p = 0.05) at pacing rates greater than 225 beats/min. A rheobase voltage greater than 5 V occurred in three patients at pacing rates greater than or equal to 275 beats/min. At a pacing rate of 300 beats/min, rheobase voltage had increased in 8 of 10 patients.(ABSTRACT TRUNCATED AT 250 WORDS)