The effects of multi-hospital systems on hospital prices.
US hospital prices are rising again after years of limited growth. We analyze trends in hospital prices during a period of significant price growth (1999-2003) to assess whether hospitals that are part of multi-hospital systems were able to increase their prices faster than non-system hospitals. We find hospitals that were members of multi-hospital systems were able to increase their prices substantially more than comparable non-systems hospitals (34% for large systems and 17% for small systems). Further, we find that the systems effect is not confined to hospitals that have other system member hospitals in their local markets. One possible explanation is that hospitals belonging to non-local multi-hospital systems have improved their bargaining position vis-à-vis health plans.


ACGME Clinical and Educational Work Hour Standards: Perspectives and Recommendations from Emergency Medicine Educators.
The American College of Emergency Physicians (ACEP) and the Council of Emergency Medicine Residency Directors (CORD) were invited to contribute to the 2016 Accreditation Council for Graduate Medical Education's (ACGME) Second Resident Duty Hours in the Learning and Working Environment Congress. We describe the joint process used by ACEP and CORD to capture the opinions of emergency medicine (EM) educators on the ACGME clinical and educational work hour standards, formulate recommendations, and inform subsequent congressional testimony. In 2016 our joint working group of experts in EM medical education conducted a consensus-based, mixed-methods process using survey data from medical education stakeholders in EM and expert iterative discussions to create organizational position statements and recommendations for revisions of work hour standards. A 19-item survey was administered to a convenience sample of 199 EM residency training programs using a national EM educational listserv. A total of 157 educational leaders responded to the survey; 92 of 157 could be linked to specific programs, yielding a targeted response rate of 46.2% (92/199) of programs. Respondents commented on the impact of clinical and educational work-hour standards on patient safety, programmatic and personnel costs, resident caseload, and educational experience. Using survey results, comments, and iterative discussions, organizational recommendations were crafted and submitted to the ACGME. EM educators believe that ACGME clinical and educational work hour standards negatively impact the learning environment and are not optimal for promoting patient safety or the development of resident professional citizenship.


Impaired systolic function by strain imaging in heart failure with preserved ejection fraction.
This study sought to determine the frequency and magnitude of impaired systolic deformation in heart failure with preserved ejection fraction (HFpEF). Although diastolic dysfunction is widely considered a key pathophysiologic mediator of HFpEF, the prevalence of concomitant systolic dysfunction has not been clearly defined. We assessed myocardial systolic and diastolic function in 219 HFpEF patients from a contemporary HFpEF clinical trial. Myocardial deformation was assessed using a vendor-independent 2-dimensional speckle-tracking software. The frequency and severity of impaired deformation was assessed in HFpEF, and compared to 50 normal controls free of cardiovascular disease and to 44 age- and sex-matched hypertensive patients with diastolic dysfunction (hypertensive heart disease) but no HF. Among HFpEF patients, clinical, echocardiographic, and biomarker correlates of left ventricular strain were determined. The HFpEF patients had preserved left ventricular ejection fraction and evidence of diastolic dysfunction. Compared to both normal controls and hypertensive heart disease patients, the HFpEF patients demonstrated significantly lower longitudinal strain (LS) (-20.0 ± 2.1 and -17.07 ± 2.04 vs. -14.6 ± 3.3, respectively, p < 0.0001 for both) and circumferential strain (CS) (-27.1 ± 3.1 and -30.1 ± 3.5 vs. -22.9 ± 5.9, respectively; p < 0.0001 for both). In HFpEF, both LS and CS were related to LVEF (LS, R = -0.46; p < 0.0001; CS, R = -0.51; p < 0.0001) but not to standard echocardiographic measures of diastolic function (E' or E/E'). Lower LS was modestly associated with higher NT-proBNP, even after adjustment for 10 baseline covariates including LVEF, measures of diastolic function, and LV filling pressure (multivariable adjusted p = 0.001). Strain imaging detects impaired systolic function despite preserved global LVEF in HFpEF that may contribute to the pathophysiology of the HFpEF syndrome. (LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction; NCT00887588).


[Surgical diagnosis and therapy in patients with mediastinal space-occupying lesions. A retrospective analysis of 223 intervention with special reference to long-term course].
The diagnostic and therapeutic approach in patients with mediastinal masses (MM) treated at our institute between 1983 and 1993 was retrospectively reviewed. 193 patients with MM (105 males and 88 females, average age 53, ranging from 16-81) underwent 223 interventions. Staging mediastinoscopies in lung cancer patients were ruled out. Long-term follow-up data were available in 123 of 162 cases with neoplastic MM (average follow-up time 5.5 years). Of all 223 surgical interventions 143 were diagnostic (53 parasternal mediastinotomies, 78 mediastinoscopies and 8 thoracoscopies) and 80 therapeutic (46 sternotomies and 34 posterolateral and a second half). The analysed period was splitted up in a first half (1983-1987) and second half (1988-1993) to study an eventual trend in the management of MM. The most frequent diagnoses were: thymoma (21%), malignant lymphoma (18%) and mediastinal sarcoidosis (14%). 43% of the MM were localized in the anterior, 46% in the middle and 7% in the posterior mediastinum. Thoracic pain, cough and dyspnoea represented the most common symptoms, leading to an invasive diagnostic procedure. 25% of the patients had no symptoms. The mortality and morbidity rate of all interventions was 3.4% and 18.7% respectively and concerned almost nerval injuries and postoperative respiratory failure. The percentage of direct tumor excisions increased from 21% during the first half of the period to 40% during the second half of the period, whereas diagnostic surgical interventions decreased from 57% to 44%. The percentage of total excisions after previous surgical biopsies decreased from 22% to 16%. In spite of the introduction of high resolution CT scan and MRI techniques during this time period no significant change in the use of presurgical diagnostic procedures was obvious. Fine needle biopsies and bronchoscopies were performed less frequent in the second half in comparison to the first half (11%, 7%, 29%, 13% respectively). From 123 patients with neoplastic disease data were available for long-term results. 35 had benign and 83 malignant histologies, in five cases dignity was unclear. 54% of these patients were disease-free at follow-up time, 10% had local recurrency or distant metastasis and 37% died during the observed time period. Surgical biopsy seems to remain the most important investigation for a successful interdisciplinary approach to MM. Overall morbidity and mortality rate of mediastinal surgery might appear remarkable but has to be related to the favorous long-term results after different individual treatment modalities in patients with mediastinal masses.


Plant genetics predicts intra-annual variation in phytochemistry and arthropod community structure.
With the emerging field of community genetics, it is important to quantify the key mechanisms that link genetics and community structure. We studied cottonwoods in common gardens and in natural stands and examined the potential for plant chemistry to be a primary mechanism linking plant genetics and arthropod communities. If plant chemistry drives the relationship between plant genetics and arthropod community structure, then several predictions followed. We would find (i) the strongest correlation between plant genetic composition and chemical composition; (ii) an intermediate correlation between plant chemical composition and arthropod community composition; and (iii) the weakest relationship between plant genetic composition and arthropod community composition. Our results supported our first prediction: plant genetics and chemistry had the strongest correlation in the common garden and the wild. Our results largely supported our second prediction, but varied across space, seasonally, and according to arthropod feeding group. Plant chemistry played a larger role in structuring common garden arthropod communities relative to wild communities, free-living arthropods relative to leaf and stem modifiers, and early-season relative to late-season arthropods. Our results did not support our last prediction, as host plant genetics was at least as tightly linked to arthropod community structure as plant chemistry, if not more so. Our results demonstrate the consistency of the relationship between plant genetics and biodiversity. Additionally, plant chemistry can be an important mechanism by which plant genetics affects arthropod community composition, but other genetic-based factors are likely involved that remain to be measured.


Single dose oral gabapentin for established acute postoperative pain in adults.
Gabapentin is an antiepileptic drug, also used in the treatment of neuropathic pain, which is the subject of a Cochrane review, currently under revision. Its efficacy in treating established acute postoperative pain has not been demonstrated. To assess the efficacy and safety of single dose oral gabapentin compared with placebo in established acute postoperative pain using methods that permit comparison with other analgesics. We searched Cochrane CENTRAL, MEDLINE, EMBASE, and the Oxford Pain Relief Database. Additional studies were sought from reference lists of retrieved articles and reviews. Clinical trials databases were searched for unpublished studies; clinical trial reports of several unpublished studies have been made public following litigation in the US. Single oral dose, randomised, double-blind, placebo-controlled trials of gabapentin for relief of established moderate to severe postoperative pain in adults. Studies were assessed for methodological quality and data extracted by two review authors independently. Numbers of participants with at least 50% of maximum possible total pain relief (TOTPAR) or summed pain intensity difference (SPID) with gabapentin or placebo were calculated and used to derive relative benefit (RB) or risk (RR), and number-needed-to-treat-to-benefit (NNT). Numbers of participants using rescue medication, and time to its use, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Four unpublished studies met inclusion criteria; in three, participants had pain following dental surgery, and one followed major orthopaedic surgery; 177 participants were treated with a single dose of gabapentin 250 mg, 21 with gabapentin 500 mg, and 172 with placebo. At least 50% pain relief over 6 hours was achieved by 15% with gabapentin 250 mg and 5% with placebo; giving a RB of 2.5 (95% CI 1.2 to 5.0) and an NNT of 11 (6.4 to 35). Significantly fewer participants needed rescue medication within 6 hours with gabapentin 250 mg than with placebo; NNT to prevent use 5.8. About one third of participants reported adverse events with both gabapentin 250 mg and placebo. No serious adverse events occurred with gabapentin. Gabapentin 250 mg is statistically superior to placebo in the treatment of established acute postoperative pain, but the NNT of 11 for at least 50% pain relief over 6 hours with gabapentin 250 mg is of limited clinical value and inferior to commonly used analgesics. Gabapentin 250 mg is not clinically useful as a stand-alone analgesic in established acute postoperative pain, though this is probably the first demonstration of analgesic effect of an antiepileptic in established acute pain.


A Unified Approach to Functional Principal Component Analysis and Functional Multiple-Set Canonical Correlation.
Functional principal component analysis (FPCA) and functional multiple-set canonical correlation analysis (FMCCA) are data reduction techniques for functional data that are collected in the form of smooth curves or functions over a continuum such as time or space. In FPCA, low-dimensional components are extracted from a single functional dataset such that they explain the most variance of the dataset, whereas in FMCCA, low-dimensional components are obtained from each of multiple functional datasets in such a way that the associations among the components are maximized across the different sets. In this paper, we propose a unified approach to FPCA and FMCCA. The proposed approach subsumes both techniques as special cases. Furthermore, it permits a compromise between the techniques, such that components are obtained from each set of functional data to maximize their associations across different datasets, while accounting for the variance of the data well. We propose a single optimization criterion for the proposed approach, and develop an alternating regularized least squares algorithm to minimize the criterion in combination with basis function approximations to functions. We conduct a simulation study to investigate the performance of the proposed approach based on synthetic data. We also apply the approach for the analysis of multiple-subject functional magnetic resonance imaging data to obtain low-dimensional components of blood-oxygen level-dependent signal changes of the brain over time, which are highly correlated across the subjects as well as representative of the data. The extracted components are used to identify networks of neural activity that are commonly activated across the subjects while carrying out a working memory task.


Long-term perspective on wildfires in the western USA.
Understanding the causes and consequences of wildfires in forests of the western United States requires integrated information about fire, climate changes, and human activity on multiple temporal scales. We use sedimentary charcoal accumulation rates to construct long-term variations in fire during the past 3,000 y in the American West and compare this record to independent fire-history data from historical records and fire scars. There has been a slight decline in burning over the past 3,000 y, with the lowest levels attained during the 20th century and during the Little Ice Age (LIA, ca. 1400-1700 CE [Common Era]). Prominent peaks in forest fires occurred during the Medieval Climate Anomaly (ca. 950-1250 CE) and during the 1800s. Analysis of climate reconstructions beginning from 500 CE and population data show that temperature and drought predict changes in biomass burning up to the late 1800s CE. Since the late 1800s , human activities and the ecological effects of recent high fire activity caused a large, abrupt decline in burning similar to the LIA fire decline. Consequently, there is now a forest "fire deficit" in the western United States attributable to the combined effects of human activities, ecological, and climate changes. Large fires in the late 20th and 21st century fires have begun to address the fire deficit, but it is continuing to grow.


Factors that influence attitude and enforcement of the smoke-free law in Turkey: a survey of hospitality venue owners and employees.
In 2009, Turkey extended the smoke-free legislation to hospitality venues. Compliance, however, remains low in some hospitality venues. We identified characteristics associated with knowledge of health effects that can be prevented by the smoke-free law, the attitude towards and enforcement of the law. In 2014, we conducted 400 interviews with hospitality venue owners and employees in 7 cities in Turkey. The venues were identified based on a random sampling strategy in a previous phase of the study. Over one-third (37.3%) of hospitality owners and employees had adequate knowledge of the health effects from secondhand smoke (SHS), 71.3% had a positive attitude towards the law and 19.5% had personally enforced the law. Participants who worked 70 hours or more per week were more likely to have a positive attitude towards the law. Older individuals, women, participants working in bars/nightclubs, venue owners receiving fines for non-compliance and current smokers were less likely to have a positive attitude towards the law. Participants working in traditional coffee houses, former smokers, and participants with a high school education or greater were more likely to enforce the law. Smokers who quit or reduced smoking because of the law were more likely to enforce the law compared with those who were not influenced by the law. Although the attitude towards the law was positive, interventions are needed to increase knowledge on the health effects of SHS and facilitate enforcement of the law, particularly among subgroups less likely to have a positive attitude and enforce the law.


The heterogeneous impact of targeted therapy on the prognosis of stage III/IV colorectal cancer patients with different subtypes of TP53 mutations.
The relationship between molecular characteristics and the prognosis of colorectal cancer (CRC) patients has not been fully understood. This study explored the impact of targeted therapy on the prognosis of CRC patients with different TP53 mutations, in the context of comprehensive treatment. This study included patients with stage III/IV primary CRC from the electronic medical record system. TP53 mutations were detected via next-generation sequencing (NGS) using formalin-fixed paraffin-embedded (FFPE) tissues. Applying two methods, we classified TP53 mutations as gain of function (GOF)/non-GOF mutations or known/likely loss of function (LOF) mutations. Kaplan-Meier plot and parametric survival analysis were performed to evaluate the prognosis of CRC patients and identify potential predictors. There were 286 patients included, of which 166 (58.04%) patients received targeted therapy and 120 (41.96%) did not. There were 286 patients in the TP53 GOF classification set and 247 in the TP53 LOF classification set. Parametric survival analysis, adjusted for sex, onset, KRAS mutation, sidedness, stage, and surgery, showed that receiving targeted therapy predicted better overall survival (OS) among patients who harbored TP53 GOF mutations (HR 0.40, 95% confidence interval (CI) [0.21, 0.76], p = 0.005) or known LOF mutations (HR 0.21, 95% CI [0.07, 0.60], p = 0.002). However, there was no significant impact of receiving targeted therapy on OS among patients harboring TP53 non-GOF mutations (HR 1.68, 95% CI [0.50, 5.63], p = 0.403) or likely LOF mutations (HR 0.90, 95% CI [0.34, 2.39], p = 0.837). Receiving targeted therapy had a heterogeneous impact on the prognosis of CRC patients harboring different TP53 mutations. These results provide promising value for future personalized treatment and precision medicine.


Alpha-methylacyl coenzyme A racemase overexpression in gallbladder carcinoma confers an independent prognostic indicator.
Increased β-oxidation of branched-chain fatty acids provides an additional metabolic advantage for cancer cells thereby enhancing tumour development and progression. Alpha-methylacyl coenzyme A racemase (AMACR) is an enzyme essential for the catabolism of branched-chain fatty acids that allows their subsequent β-oxidation and thus plays an important role in generating biological energy. However, the expression of AMACR has never been systemically investigated in gallbladder carcinoma. This study evaluated the expression status, associations with clinicopathological variables and prognostic implications of AMACR in a well-defined cohort of gallbladder carcinoma and confirmed their expression status in gallbladder carcinoma cells. AMACR immunostaining was assessable in 89 cases on tissue microarrays of gallbladder carcinoma, and it was correlated with clinicopathological factors and patient survival. In three gallbladder carcinoma cell lines and one non-tumorigenic cholangiocyte, AMACR mRNA expression was measured by real-time reverse transcription PCR and the endogenous expression of AMACR protein was analysed by western blotting. AMACR overexpression was significantly associated with an advanced primary tumour status (p=0.027) and American Joint Committee on Cancer stage (p=0.027), an increased histological grade (p=0.002) and vascular invasion (p=0.017). Importantly, AMACR overexpression independently predicted worse disease-specific survival (p=0.0452, RR 1.887). Expression levels of AMACR mRNA and total protein in various cells were comparable. The abundance of AMACR expression increased in tumour cells and was even higher in the metastatic cell line. In primary gallbladder carcinoma, AMACR overexpression was correlated with important prognosticators and independently portended worse outcomes, highlighting the potential prognostic and therapeutic utility of AMACR in gallbladder carcinoma.


Insulin and insulin-like growth factor-I receptors similarly stimulate deoxyribonucleic acid synthesis despite differences in cellular protein tyrosine phosphorylation.
Signal transduction pathways stimulated by insulin or insulin-like growth factor-I (IGF-I) were compared in transfected NIH3T3 fibroblast cell lines expressing the human insulin receptor, IGF-I receptor, or a chimeric IGF-I receptor with its carboxy-terminal tail replaced with that of the insulin receptor (approximately 1 x 10(6) receptors/cell). Although receptor autophosphorylation was very similar in the three cell lines overexpressing receptors (EC50 = 1-3 nM), there were differences detected in the protein tyrosine phosphorylation stimulated by insulin and IGF-I in these cells. Although no substrates specific for the insulin receptor were detected, phosphorylation of a 170-kilodalton (kDa; IRS-1) and a 70-kDa protein was 10 times more sensitive to insulin than to IGF-I (EC50 = 1.5-2.5 vs. 14-23 nM). The chimeric receptor stimulated significantly lower levels of phosphorylation of several proteins relative to the wild-type IGF-I receptor. Activation of phosphatidylinositol 3'-kinase paralleled phosphorylation of the 170- and 70-kDa proteins. Despite these differences in protein tyrosine phosphorylation, stimulation of mitogen-activated protein (MAP) kinase and DNA synthesis were very similar in the three cell lines overexpressing receptors. Little difference was detected in Shc phosphorylation or MAP kinase activation through the three receptors, although activation of MAP kinase was more efficiently coupled to the platelet-derived growth factor receptor than to any of the overexpressed receptors. All three receptors stimulated DNA synthesis to levels comparable to 10% serum, with similar sensitivities (EC50 = 1.5-3.5 nM).


Antitumor effects of the novel NF-kappaB inhibitor dehydroxymethyl-epoxyquinomicin on human hepatic cancer cells: analysis of synergy with cisplatin and of possible correlation with inhibition of pro-survival genes and IL-6 production.
We tested the novel NF-kappaB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) in the hepatic cancer (HCC) HepG2, HA22T/VGH and HuH-6 cells. The sensitivity to the cell growth inhibitory and apoptotic effects of the agent increased along with the levels of constitutively activated NF-kappaB, which were low in HepG2 and higher in HA22T/VGH and HuH-6. In HA22T/VGH, DHMEQ exhibited synergy with cisplatin. In the same cells, DHMEQ exerted dose-dependent decreases in the nuclear levels of activated NF-kappaB and attenuated NF-kappaB activation by cisplatin. It down-regulated Bcl-XL mRNA in a dose-dependent manner and up-regulated that of Bcl-XS. It also decreased interleukin 6 (IL-6), NAIP and, after 16 h of exposure to the higher concentration tested (10 microg/ml), c-IAP-1 mRNA levels. At 10 microg/ml it caused significant increase in Bax, XIAP, cyclin D1 and beta-catenin mRNAs. The combination of DHMEQ with cisplatin produced unexpected significant decrease in c-IAP-2 and Bcl-XS mRNAs as well as additive decrease (IL-6, NAIP and, after 16 h, Bcl-XL) or increase (XIAP at 8 h) in gene expression. HA22T/VGH produce IL-6; in agreement with the results on mRNA, DHMEQ inhibited such a process. HA22T/VGH lack the IL-6 receptor alpha chain, ruling out that in these cells the antitumor effects of DHMEQ may be attributed to an interference with a growth stimulatory autocrine loop based on IL-6. However, the use of DHMEQ in HCC might be beneficial to contrast the adverse systemic effects of the released cytokine.


Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): alternatively spliced, functionally distinct isoforms expressed during mammalian cardiovascular development.
The establishment of the cardiovascular system represents an early, critical event essential for normal embryonic development. An important component of vascular ontogeny is the differentiation and development of the endothelial and endocardial cell populations. This involves, at least in part, the expression and function of specific cell surface receptors required to mediate cell-cell and cell-matrix adhesion. Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) may well serve such a function. It is a member of the immunoglobulin superfamily expressed by the entire vascular endothelium in the adult. It is capable of mediating adhesion by a heterophilic mechanism requiring glycosaminoglycans, as well as by a homophilic, glycosaminoglycan independent, mechanism. It has been shown to regulate the expression of other adhesion molecules on naive T cells. This report documents by RT-PCR and immunohistochemical analysis the expression of PECAM-1 during early post implantation mouse embryo development. PECAM-1 was expressed by early endothelial precursors first within the yolk sac and subsequently within the embryo itself. Interestingly, embryonic PECAM-1 was expressed as multiple isoforms in which one or more clusters of polypeptides were missing from the cytoplasmic domain. The sequence and location of the deleted polypeptides corresponded to exons found in the human PECAM-1 gene. The alternatively spliced isoforms were capable of mediating cell-cell adhesion when transfected into L-cells. The isoforms differed, however, in their sensitivity to a panel of anti-PECAM-1 monoclonal antibodies. These data suggest that changes in the cytoplasmic domain of PECAM-1 may affect its function during cardiovascular development, and are consistent with our earlier report that systematic truncation of the cytoplasmic domain of human PECAM-1 resulted in changes in its ligand specificity, divalent cation and glycosaminoglycan dependence, as well as its susceptibility to adhesion blocking monoclonal antibodies. This is the first report of naturally occurring alternatively spliced forms of PECAM-1 having possible functional implications.


Different susceptibility of osteosarcoma cell lines and primary cells to treatment with oncolytic adenovirus and doxorubicin or cisplatin.
Despite improvements in treatment regimens for osteosarcoma (OS) patients, survival rate has not increased over the last two decades. New treatment modalities are therefore warranted. Preclinical results with conditionally replicative adenoviruses (CRAds) to treat OS are promising. One type of CRAd that was effective against OS cells is Ad5-Delta24RGD. In other types of cancer, CRAds have been shown to interact synergistically with chemotherapeutic agents. Chemotherapy for OS often includes doxorubicin and cisplatin. Therefore, we explored combination treatment of OS cell lines and primary OS cell cultures with Ad5-Delta24RGD and doxorubicin or cisplatin. On OS cell lines, combination treatment was additive to synergistic. Surprisingly, however, on seven of eight primary OS samples no such combination effects were observed. In contrast, in many cases chemotherapy even inhibited CRAd-mediated cell killing. The inhibitory effect of doxorubicin on Ad5-Delta24RGD in primary OS cells appeared to correlate with slow cell growth rate; reduced viral replication and absence of chemotherapy-induced G2 cell cycle arrest. Our results point to the possibility that, at least for OS, virotherapy and chemotherapy should best not be performed simultaneously. In general, our work underscores the importance of testing new genetic anticancer agents and treatment regimens on primary cancer specimens.


Endoscopic treatment of a third ventricle choroid plexus cyst.
Choroid plexus cysts are frequent benign intraventricular lesions that infrequently cause symptoms, usually in the form of obstructive hydrocephalus. These instances are even less common in the adult population. When warranted, treatment seeks to reestablish cerebrospinal fluid flow and does not necessarily require resection of the cyst itself. Hence, endoscopic exploration of the ventricles with subsequent cyst ablation is the current treatment of choice for these lesions. Herein we present the case of a 25-year-old female patient with a 3-week history of intermittent headaches. Investigation with computerized tomography (CT) of the head detected supratentorial hydrocephalus, with enlargement of the lateral and third ventricles. Magnetic resonance imaging revealed a homogeneous cystic lesion in the third ventricle. A right-sided, pre-coronal burr hole was carried out, followed by endoscopic exploration of the ventricular system. A third-ventriclostomy was performed. With the aid of the 30-degrees endoscope, a cyst arising from the choroid plexus was visualized along the posterior portion of the third ventricle, obstructing the aqueduct opening. The cyst was cauterized until significant reduction of its dimensions was achieved and the aqueduct opening was liberated. Postoperative recovery was without incident and resolution of the hydrocephalus was confirmed by CT imaging. The patient reports complete improvement of her headaches and has been uneventfully followed since surgery. The video can be found here: http://youtu.be/XBtj_SqY07Q. (http://thejns.org/doi/abs/10.3171/2013.V1.FOCUS12332)


Prediction and validation of total and regional skeletal muscle volume using B-mode ultrasonography in Japanese prepubertal children.
Very few effective field methods are available for accurate, non-invasive estimation of skeletal muscle volume (SMV) and mass in children. We aimed to develop regression-based prediction equations for SMV, using ultrasonography, in Japanese prepubertal children, and to assess the validity of these equations. In total, 145 healthy Japanese prepubertal children aged 6-12 years were randomly divided into two groups: the model development group (sixty boys, thirty-seven girls) and the validation group (twenty-nine boys, nineteen girls). Reference data in the form of contiguous MRI with 1-cm slice thickness were obtained from the first cervical vertebra to the ankle joints. The SMV was calculated by the summation of digitised cross-sectional areas. Muscle thickness was measured using B-mode ultrasonography at nine sites in different regions. In the model development group, strong, statistically significant correlations were observed between the site-matched SMV (total, arms, trunk, thigh and lower legs) measured by MRI and the muscle thickness×height measures obtained by ultrasonography, for both boys and girls. When these SMV prediction equations were applied to the validation groups, the measured total and regional SMV were also very similar to the values predicted for boys and girls, respectively. With the exception of the trunk region in girls, the Bland-Altman analysis for the validation group did not indicate any bias for either boys or girls. These results suggest that ultrasonography-derived prediction equations for boys and girls are useful for the estimation of total and regional SMV.


Patterns and Predictors of Adherence to Statin Therapy Among Older Patients: Protocol for a Systematic Review.
The benefits of statin therapy are significantly compromised by noncompliance. Although elderly patients may have particular challenges with medication adherence and persistence, previous reviews on statin adherence have not focused on this population. Additionally, comparisons of adherence and persistence specific to statin indication (primary or secondary prevention) have not been thoroughly explored. We aim to assess the extent of, and factors associated with, adherence and persistence to statin therapy among older populations (aged ≥65 years). A systematic review will be undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Searches will be performed using multiple electronic databases (Ovid MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and the National Health Service Economic Evaluation Database) to identify relevant randomized trials and observational studies that evaluated statin adherence and/or persistence as an outcome. Eligible studies will include those involving community-living or outpatient elderly individuals. The methodological quality of randomized controlled trials (RCTs) will be assessed via the Joanna Briggs Institute's critical appraisal checklist for RCTs, and the quality assessment of observational studies will be undertaken using a set of questions formulated with resort to the National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. When possible, meta-analyses will be conducted using random-effect modeling and generic inverse variance analyses for adjusted-effect estimates. Heterogeneity across studies will be quantified using the I2 statistic. The presence of publication bias will be assessed using funnel plots and Egger's regression tests. A leave-one-out sensitivity analysis will also be conducted to assess the impact of individual study results on pooled estimates. To explore possible sources of heterogeneity across studies, subgroup analyses will be performed based on covariates such as study design, statin indication, country of study, and length of patient follow-up. The electronic database searches were completed in December 2016. Retrieved articles are currently being screened and the entire study is expected to be completed by June 2017. This systematic review will provide further understanding of the patterns of, and barriers to, statin adherence and persistence among older patients. The findings will inform clinical practice and the design of appropriate interventions. PROSPERO CRD42016053191.


The virtue ethics approach to bioethics.
This paper discusses the viability of a virtue-based approach to bioethics. Virtue ethics is clearly appropriate to addressing issues of professional character and conduct. But another major remit of bioethics is to evaluate the ethics of biomedical procedures in order to recommend regulatory policy. How appropriate is the virtue ethics approach to fulfilling this remit? The first part of this paper characterizes the methodology problem in bioethics in terms of diversity, and shows that virtue ethics does not simply restate this problem in its own terms. However, fatal objections to the way the virtue ethics approach is typically taken in bioethics literature are presented in the second section of the paper. In the third part, a virtue-based approach to bioethics that avoids the shortcomings of the typical one is introduced and shown to be prima facie plausible. The upshot is an inviting new direction for research into bioethics' methodology.


Resolving genetic models for the transmission of schizophrenia.
Although family studies have consistently reported elevated rates of schizophrenia among the relatives of schizophrenics, the exact nature of the transmission of the disorder remains uncertain. Genetic models hypothesized to explain the transmission of schizophrenia include the generalized single locus and multifactorial threshold models. Here we briefly describe these models and test their goodness-of-fit to a single data set on the pooled morbid risks of schizophrenia among the relatives of schizophrenic probands in nine different classes of relatives with five different degrees of genetic relatedness. The generalized single locus model is rejected, while a pure polygenic threshold model does fit the observed risks. Allowance for environmental sources of familial resemblance under the multifactorial threshold model significantly improved the fit of the model to the data. An application of the multifactorial model to family data on tuberculosis is also reported. For tuberculosis, a strong familial environmental but not genetic effect was found, consistent with the known infectious etiology of this condition, showing that the finding of a strong genetic effect upon schizophrenia is not a necessary bias of these methods of analysis. The implications of these results for the search for major gene effects in schizophrenia are discussed.


Implications of pacemakers and implantable cardioverter defibrillators in urological practice.
Pacemakers and implantable cardioverter defibrillators are widely used and often encountered in urology practices worldwide. Safety and performance during electrosurgery, extracorporeal shock wave lithotripsy, magnetic resonance imaging, positron emission tomography and radiotherapy are not clearly defined. We reviewed the literature on their use and implications in urological practice. We performed a PubMed® search and all relevant articles were studied to understand the basic functioning of these devices along with the technological advances designed to reduce electromagnetic interference. A modern permanent pacemaker is comprised of a generator and leads connecting to the atrial or ventricular myocardium with sensing and pacing functions. Implantable cardioverter defibrillators respond to episodes of ventricular tachycardia and fibrillation by discharging a defibrillating current. From a device perspective, several protective mechanisms have been developed in the permanent pacemaker/implantable cardioverter defibrillator to reduce the effects of electromagnetic interference. These involve generator material changes, lead modification, and better sensing and pacing algorithms. Magnetic resonance imaging compatible pacemakers have now been developed and are approved for use in Europe. From a urologist's perspective 5 procedures require the close monitoring of permanent pacemaker/implantable cardioverter defibrillator function. 1) For electrosurgery modifications in the device and in the methods of use have been recommended. 2) For extracorporeal shock wave lithotripsy the European Association of Urology provides some guidance with regard to patients with these devices. 3) During positron emission tomography the pulse generator and the lead area should be covered with lead to protect the device. 4) Magnetic resonance imaging is contraindicated but currently trials are under way for a new pacing system for safe use in the magnetic resonance imaging environment. 5) Patients can undergo radiotherapy with standard precautions but those with an abdominal permanent pacemaker/implantable cardioverter defibrillator require careful planning. Finally, implanted devices should have a full evaluation before and after the procedure. Clear guidelines are essential given the rapid advances in technology to enhance patient safety. Magnetic resonance imaging should be avoided in patients without a magnetic resonance imaging compatible device. However, patients can undergo extracorporeal shock wave lithotripsy, radiotherapy and positron emission tomography as long as the device is not in the path.


Regulation of FGF-1 mitogenic activity by heparan sulfate oligosaccharides is dependent on specific structural features: differential requirements for the modulation of FGF-1 and FGF-2.
The interaction of heparan sulfate (HS) (and the closely related molecule heparin) with FGF-1 is a requirement for enabling the growth factor to activate its cell surface tyrosine kinase receptor. However, little is known about the regulatory role of naturally occurring cell surface HS in FGF-1 activation. We have addressed this issue by utilizing a library of HS oligosaccharides, which are defined in both length and sulfate content. Mitogenic activation assays using these oligosaccharides showed that HS contained both FGF-1 activatory and inhibitory sugar sequences. Further analysis of these oligosaccharides showed a clear correlation between FGF-1 promoting activity and their 6-O-sulfate content. The results, in particular with the dodecasaccharide sequences, suggested that specific positioning of 6-O-sulfate groups may be required for the promotion of FGF-1 mitogenic activity. This may also be true for 2-O-sulfate groups though the evidence was not as conclusive. Differential activation of FGF-1 and FGF-2 was also observed and found to be mediated by both oligosaccharide length and sulfation pattern, with different specific O-sulfate positioning being implicated for the promotion of different growth factors. These results suggest that variation and tight control of the fine structure of HS may allow cells to not only control their positive/negative responses to individual FGFs but also to change specificity towards promotion of different members of the FGF family.


Local softness, softness dipole, and polarizabilities of functional groups: application to the side chains of the 20 amino acids.
The values of molecular polarizabilities and softnesses of the 20 amino acids were computed ab initio (MP2). By using the iterative Hirshfeld scheme to partition the molecular electronic properties, we demonstrate that the values of the softness of the side chain of the 20 amino acids are clustered in groups reflecting their biochemical classification, namely: aliphatic, basic, acidic, sulfur containing, and aromatic amino acids. The present findings are in agreement with previous results using different approximations and partitioning schemes [P. Senet and F. Aparicio, J. Chem. Phys. 126, 145105 (2007)]. In addition, we show that the polarizability of the side chain of an amino acid depends mainly on its number of electrons (reflecting its size) and consequently cannot be used to cluster the amino acids in different biochemical groups, in contrast to the local softness. Our results also demonstrate that the global softness is not simply proportional to the global polarizability in disagreement with the intuition that "a softer moiety is also more polarizable." Amino acids with the same softness may have a polarizability differing by a factor as large as 1.7. This discrepancy can be understood from first principles as we show that the molecular polarizability depends on a "softness dipole vector" and not simply on the global softness.


A counterfactual simulation model of causal judgments for physical events.
How do people make causal judgments about physical events? We introduce the counterfactual simulation model (CSM) which predicts causal judgments in physical settings by comparing what actually happened with what would have happened in relevant counterfactual situations. The CSM postulates different aspects of causation that capture the extent to which a cause made a difference to whether and how the outcome occurred, and whether the cause was sufficient and robust. We test the CSM in several experiments in which participants make causal judgments about dynamic collision events. A preliminary study establishes a very close quantitative mapping between causal and counterfactual judgments. Experiment 1 demonstrates that counterfactuals are necessary for explaining causal judgments. Participants' judgments differed dramatically between pairs of situations in which what actually happened was identical, but where what would have happened differed. Experiment 2 features multiple candidate causes and shows that participants' judgments are sensitive to different aspects of causation. The CSM provides a better fit to participants' judgments than a heuristic model which uses features based on what actually happened. We discuss how the CSM can be used to model the semantics of different causal verbs, how it captures related concepts such as physical support, and how its predictions extend beyond the physical domain. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assaying neural activity of children during video game play in public spaces: a deep learning approach.
Understanding neural activity patterns in the developing brain remains one of the grand challenges in neuroscience. Developing neural networks are likely to be endowed with functionally important variability associated with the environmental context, age, gender, and other variables. Therefore, we conducted experiments with typically developing children in a stimulating museum setting and tested the feasibility of using deep learning techniques to help identify patterns of brain activity associated with different conditions. A four-channel dry EEG-based Mobile brain-body imaging data of children at rest and during videogame play (VGP) was acquired at the Children's Museum of Houston. A data-driven approach based on convolutional neural networks (CNN) was used to describe underlying feature representations in the EEG and their ability to discern task and gender. The variability of the spectral features of EEG during the rest condition as a function of age was also analyzed. Alpha power (7-13 Hz) was higher during rest whereas theta power (4-7 Hz) was higher during VGP. Beta (13-18 Hz) power was the most significant feature, higher in females, when differentiating between males and females. Using data from both temporoparietal channels to classify between VGP and rest condition, leave-one-subject-out cross-validation accuracy of 67% was obtained. Age-related changes in EEG spectral content during rest were consistent with previous developmental studies conducted in laboratory settings showing an inverse relationship between age and EEG power. These findings are the first to acquire, quantify and explain brain patterns observed during VGP and rest in freely behaving children in a museum setting using a deep learning framework. The study shows how deep learning can be used as a data driven approach to identify patterns in the data and explores the issues and the potential of conducting experiments involving children in a natural and engaging environment.


Evidence for causal links between education and maternal and child health: systematic review.
Numerous studies have documented an inverse association between years of schooling attained, particularly by women, and reduced maternal, infant and child mortality. However, if factors affecting educational attainment - many of which are unobservable, e.g. motivation and genetic endowment - also affect the likelihood of engaging in behaviours that enhance health, then assumed effects of schooling will be inflated in analyses that do not address this endogeneity. This systematic review assesses evidence for a causal link between education and maternal and child health in low and middle-income countries. Eligible studies controlled for observable and unobservable factors affecting both education and health. Reported effects were converted into partial correlations. When possible, we also conducted meta-analyses to estimate mean effects by outcome. Of 4952 papers identified, 16 met the inclusion criteria. The 15 child health papers examined neonatal, infant and child mortality, stunting and wasting. Significant effects of education on infant and child health were observed for 30 of 33 models that did not account for endogeneity. In contrast, only 18 of 46 effects were significant in models that addressed endogeneity. Notably, for only one outcome -child mortality measured dichotomously -was the effect of maternal educational attainment significant in a meta-analysis. The one maternal morbidity paper found significant effects for the two preventable outcomes considered. While we find evidence for a causal link between education and health, effects are weaker in models that address endogeneity compared to naïve models that do not account for unobservable factors affecting both education and health. Advances in women's educational outcomes have undoubtedly played a role in improving health in many settings; however, the effect is not as strong as some researchers and advocates have claimed.


Transcription factor ETV1 is essential for rapid conduction in the heart.
Rapid impulse propagation in the heart is a defining property of pectinated atrial myocardium (PAM) and the ventricular conduction system (VCS) and is essential for maintaining normal cardiac rhythm and optimal cardiac output. Conduction defects in these tissues produce a disproportionate burden of arrhythmic disease and are major predictors of mortality in heart failure patients. Despite the clinical importance, little is known about the gene regulatory network that dictates the fast conduction phenotype. Here, we have used signal transduction and transcriptional profiling screens to identify a genetic pathway that converges on the NRG1-responsive transcription factor ETV1 as a critical regulator of fast conduction physiology for PAM and VCS cardiomyocytes. Etv1 was highly expressed in murine PAM and VCS cardiomyocytes, where it regulates expression of Nkx2-5, Gja5, and Scn5a, key cardiac genes required for rapid conduction. Mice deficient in Etv1 exhibited marked cardiac conduction defects coupled with developmental abnormalities of the VCS. Loss of Etv1 resulted in a complete disruption of the normal sodium current heterogeneity that exists between atrial, VCS, and ventricular myocytes. Lastly, a phenome-wide association study identified a link between ETV1 and bundle branch block and heart block in humans. Together, these results identify ETV1 as a critical factor in determining fast conduction physiology in the heart.


High incidence of vertebral fractures in children with acute lymphoblastic leukemia 12 months after the initiation of therapy.
Vertebral fractures due to osteoporosis are a potential complication of childhood acute lymphoblastic leukemia (ALL). To date, the incidence of vertebral fractures during ALL treatment has not been reported. We prospectively evaluated 155 children with ALL during the first 12 months of leukemia therapy. Lateral thoracolumbar spine radiographs were obtained at baseline and 12 months. Vertebral bodies were assessed for incident vertebral fractures using the Genant semiquantitative method, and relevant clinical indices such as spine bone mineral density (BMD), back pain, and the presence of vertebral fractures at baseline were analyzed for association with incident vertebral fractures. Of the 155 children, 25 (16%; 95% CI, 11% to 23%) had a total of 61 incident vertebral fractures, of which 32 (52%) were moderate or severe. Thirteen (52%) of the 25 children with incident vertebral fractures also had fractures at baseline. Vertebral fractures at baseline increased the odds of an incident fracture at 12 months by an odds ratio of 7.3 (95% CI, 2.3 to 23.1; P = .001). In addition, for every one standard deviation reduction in spine BMD Z-score at baseline, there was 1.8-fold increased odds of incident vertebral fracture at 12 months (95% CI, 1.2 to 2.7; P = .006). Children with ALL have a high incidence of vertebral fractures after 12 months of chemotherapy, and the presence of vertebral fractures and reductions in spine BMD Z-scores at baseline are highly associated clinical features.


Is it wrong to deliberately conceive or give birth to a child with mental retardation?
This paper discusses the issues of deciding to have a child with mental retardation, and of terminating a pregnancy when the future child is known to have the same disability. I discuss these problems by criticizing a utilitarian argument, namely, that one should act in a way that results in less suffering and less limited opportunity in the world. My argument is that future parents ought to assume a strong responsibility towards the well-being of their prospective children when they decide to reproduce. The moral point in cases in which our acts affect the well-being of future children should be expressed strictly in terms of parents' culpability. Future children thus do not have current moral standing but presently living persons have current obligations to consider the presumable effects of their actions on future people. I will also argue that there are morally significant differences between 'selective contraception' and selective abortion.


Lifestyle modification counseling of patients with dyslipidemias by pharmacists and other health professionals.
To establish whether patients who are taking lipid-lowering medications receive information on lifestyle modifications from health care providers when originally prescribed and whether they continue to receive follow-up information on lifestyle modifications, and to establish where patients with dyslipidemias are receiving information about lowering their serum cholesterol levels through lifestyle modifications. Cross-sectional survey. Two community pharmacies and two hospitals in two medium-sized cities in the midwestern area of the United States. 234 patients taking medication to lower serum lipids. Paper-based survey. Responses to survey items. Nearly three quarters (73.9%) of participants received information about lowering their serum lipids through lifestyle modifications when they were first diagnosed with elevated serum cholesterol concentrations. Of these, most (83.8%) said that the information came from their physician. Fewer than one half (48.3%) of all participants said that they continued to receive this type of information. Those who received lifestyle modification information at their original diagnosis and who continued to receive this type of information were more likely to be actively trying to lower their serum lipid levels through diet (93.1%) and exercise (71.6%). Participants visited their pharmacy more often than their physician's office each year, yet they recalled pharmacists offering less patient counseling on lifestyle modifications than did physicians and nurses. Despite being well positioned to assist patients with elevated serum cholesterol concentrations, pharmacists offer less patient counseling about therapeutic lifestyle modifications compared with physicians and nurses.


Advances in Clinical Decision Support: Highlights of Practice and the Literature 2015-2016.
Introduction: Advances in clinical decision support (CDS) continue to evolve to support the goals of clinicians, policymakers, patients and professional organizations to improve clinical practice, patient safety, and the quality of care. Objectives: Identify key thematic areas or foci in research and practice involving clinical decision support during the 2015-2016 time period. Methods: Thematic analysis consistent with a grounded theory approach was applied in a targeted review of journal publications, the proceedings of key scientific conferences as well as activities in standards development organizations in order to identify the key themes underlying work related to CDS. Results: Ten key thematic areas were identified, including: 1) an emphasis on knowledge representation, with a focus on clinical practice guidelines; 2) various aspects of precision medicine, including the use of sensor and genomic data as well as big data; 3) efforts in quality improvement; 4) innovative uses of computer-based provider order entry (CPOE) systems, including relevant data displays; 5) expansion of CDS in various clinical settings; 6) patient-directed CDS; 7) understanding the potential negative impact of CDS; 8) obtaining structured data to drive CDS interventions; 9) the use of diagnostic decision support; and 10) the development and use of standards for CDS. Conclusions: Active research and practice in 2015-2016 continue to underscore the importance and broad utility of CDS for effecting change and improving the quality and outcome of clinical care.


An investigation of transmission ratio distortion in the central region of the human MHC.
Transmission ratio distortion (TRD) describes a significant departure from expected Mendelian inheritance ratios that is fundamental to both the biology of reproduction and statistical genetics. The relatively high fetal wastage in humans, with consequent selection of alleles in utero, makes it likely that TRD is prevalent in the human genome. The central region of the human major histocompatibility complex (MHC) is a strong TRD candidate, as it houses a number of immune and regulatory genes that may be important in pregnancy outcome. We used a nonhaplotype-based method to select 13 tagging SNPs from three central MHC candidate regions, and analysed their transmission in 380 newborns and their parents (1138 individuals). A TRD of 54:46 was noted in favour of the common allele of a promoter SNP in the CLIC1 gene (P = 0.025), with a similar distortion using haplotypes across the same gene region (P = 0.016). We also found evidence that markers in the CLIC1 gene region may have been subject to recent selection (P < 0.001). The study illustrates the potential benefits of screening for TRD and highlights the difficulties encountered therein.


Asterless is a scaffold for the onset of centriole assembly.
Centrioles are found in the centrosome core and, as basal bodies, at the base of cilia and flagella. Centriole assembly and duplication is controlled by Polo-like-kinase 4 (Plk4): these processes fail if Plk4 is downregulated and are promoted by Plk4 overexpression. Here we show that the centriolar protein Asterless (Asl; human orthologue CEP152) provides a conserved molecular platform, the amino terminus of which interacts with the cryptic Polo box of Plk4 whereas the carboxy terminus interacts with the centriolar protein Sas-4 (CPAP in humans). Drosophila Asl and human CEP152 are required for the centrosomal loading of Plk4 in Drosophila and CPAP in human cells, respectively. Depletion of Asl or CEP152 caused failure of centrosome duplication; their overexpression led to de novo centriole formation in Drosophila eggs, duplication of free centrosomes in Drosophila embryos, and centrosome amplification in cultured Drosophila and human cells. Overexpression of a Plk4-binding-deficient mutant of Asl prevented centriole duplication in cultured cells and embryos. However, this mutant protein was able to promote microtubule organizing centre (MTOC) formation in both embryos and oocytes. Such MTOCs had pericentriolar material and the centriolar protein Sas-4, but no centrioles at their core. Formation of such acentriolar MTOCs could be phenocopied by overexpression of Sas-4 in oocytes or embryos. Our findings identify independent functions for Asl as a scaffold for Plk4 and Sas-4 that facilitates self-assembly and duplication of the centriole and organization of pericentriolar material.


The use and impact of national confidential enquiries in high-income countries.
To describe the use and characteristics of national confidential enquiries (NCEs) into adverse outcomes of healthcare in high-income countries and to review the evidence of their impact. Systematic search of bibliometric databases plus review of cited references and search of websites. Eleven characteristics of NCEs were extracted. Studies evaluating the impact of three NCEs were searched for. Data were extracted and tabulated, and a narrative review conducted. Establishment of NCEs has been limited with only 27 examples identified in over 50 years and only nine currently functioning. They have been particularly popular in the nations of the UK (17 of the 27) and in services around childbirth (15/27). NCEs mostly include all cases (19/23) and include adverse outcomes both during and after the initial hospital episode (17/23). The annual volume of cases varies from four to over 6000. With one exception, NCEs make no attempt to use 'controls.' Research evidence of the impact of the recommendations from three of the largest and longest running NCEs is poor, with no time-series analyses or experimental studies, and is restricted to considering their impact on the structure and process rather than the outcome of care. The lack of scientific evidence on the impact of NCEs on improving safety, combined with uncertainty as to the validity of their recommendations and their high cost, suggests the need for rigorous evaluation and a reconsideration of their contribution. One option is to nest NCEs within prospective national clinical audits.


Primary measures of dependence among menthol compared to non-menthol cigarette smokers in the United States.
Previously published studies provide somewhat inconsistent evidence on whether menthol in cigarettes is associated with increased dependence. The National Health and Nutrition Examination Survey, National Survey on Drug Use and Health, National Health Interview Survey, and Tobacco Use Supplement to the Current Population Survey collect data on current cigarette type preference and primary measures of dependence, and thus allow examination of whether menthol smokers are more dependent than non-menthol smokers. Analyses based on combined data from multiple administrations of each of these four nationally representative surveys, using three definitions for current smokers (i.e., smoked ⩾1day, ⩾10days and daily during the past month), consistently demonstrate that menthol smokers do not report smoking more cigarettes per day than non-menthol smokers. Moreover, two of the three surveys that provide data on time to first cigarette after waking indicate no difference in urgency to smoke among menthol compared to non-menthol smokers, while the third suggests menthol smokers may experience a greater urgency to smoke; estimates from all three surveys indicate that menthol versus non-menthol smokers do not report a higher Heaviness of Smoking Index. Collectively, these findings indicate no difference in dependence among U.S. smokers who use menthol compared to non-menthol cigarettes.


Integrative Medicine for Cardiovascular Disease and Prevention.
Cardiovascular disease (CVD) is traditionally treated through medications and lifestyle modifications, yet adherence to these treatments is often poor. The use of complementary therapies is increasing, and it is vital for physicians to be aware of the risks and benefits of these options. This article summarizes the current evidence base on integrative therapies for the prevention and treatment of CVD, including hypertension, hyperlipidemia, coronary artery disease, heart failure, and arrhythmias. Where applicable, recommendations are included for therapies that may be used as an adjunct to traditional medical care to improve cardiovascular health and quality of life.


Effects of fiber-optic probe design and probe-to-target distance on diffuse reflectance measurements of turbid media: an experimental and computational study at 337 nm.
Fiber-optic probes are widely used in optical spectroscopy of biological tissues and other turbid media. Only limited information exists, however, on the ways in which the illumination-collection geometry and the overall probe design influence the interrogation of media. We have investigated both experimentally and computationally the effect of probe-to-target distance (PTD) on the diffuse reflectance collected from an isotropically (Lambertian) scattering target and an agar-based tissue phantom. Studies were conducted with three probes characterized by either common (single-fiber) or separate (two bifurcated multifiber probes) illumination and collection channels. This study demonstrates that PTD, probe design, and tissue scattering anisotropy influence the extent of the transport of light into the medium, the light-collection efficiency, and the sampling volume of collected light. The findings can be applied toward optimization of fiber-optic probe designs for quantitative optical spectroscopy of turbid media including biological tissues.


An international comparison of the deinstitutionalisation of mental health care: Development and findings of the Mental Health Services Deinstitutionalisation Measure (MENDit).
Despite its inclusion as a key aspect of successful mental health care service provision by the World Health Organization, there exists a lack of consensus regarding the definition, key components and implementation of deinstitutionalisation. This lack of consensus has also contributed to subjectivity in assessments of countries' progress towards deinstitutionalisation which act as a barrier to its evaluation and success. In order to provide for reliable within and cross country evaluations of the success of deinstitutionalisation we aimed to develop a quantitative measure of country-level progress towards deinstitutionalisation through the (1) identification of key markers of deinstitutionalisation; (2) development of an assessment tool based on the identified markers; (3) evaluation of the tool's psychometric properties; and (4) comparison of progress towards deinstitutionalisation across Europe. National care standards from 10 European countries and World Health Organization recommendations were used to identify items for the tool. A draft version was reviewed by an international expert panel and assessed for test-retest reliability and internal consistency. Once a final version had been agreed, progress towards deinstitutionalisation was assessed for 30 European countries. We used this opportunity to test convergent validity through comparison with local experts' assessments. Country total as well as individual item scores were described and compared. The five-item Mental Health Services Deinstitutionalisation Measure (MENDit) is an objective tool with moderate to very good test-retest reliability (Kappa range: 0.46-1.00) and internal consistency (α = 0.70, 95 % CI 0.25, 0.92). A statistically significant difference between groups was found by one-way ANOVA (F(3,26) = 6.77, p = 0.002). Post-hoc testing found significant differences between MENDit scores of countries categorised as having advanced levels of deinstitutionalisation and not started or just started. Across Europe, MENDit scores suggest substantial variety in progress towards deinstitutionalisation. The MENDit has good psychometric properties which support its use in research and as a benchmarking tool to measure national progress towards deinstitutionalisation by policy makers. Across Europe a high proportion of psychiatric beds are still located in psychiatric hospitals. Additionally, low numbers of mental health professionals in many countries may hinder further deinstitutionalisation. These findings corroborate previous mental health systems research and highlight some of the difficulties of deinstitutionalisation.


The [PSI+] prion modulates cytochrome c oxidase deficiency caused by deletion of COX12.
Cytochrome c oxidase (CcO) is a pivotal enzyme of the mitochondrial respiratory chain, which sustains bioenergetics of eukaryotic cells. Cox12, a peripheral subunit of CcO oxidase, is required for full activity of the enzyme, but its exact function is unknown. Here experimental evolution of a Saccharomyces cerevisiae Δcox12 strain for ∼300 generations allowed to restore the activity of CcO oxidase. In one population, the enhanced bioenergetics was caused by a A375V mutation in the cytosolic AAA+ disaggregase Hsp104. Deletion or overexpression of HSP104 also increased respiration of the Δcox12 ancestor strain. This beneficial effect of Hsp104 was related to the loss of the [PSI+] prion, which forms cytosolic amyloid aggregates of the Sup35 protein. Overall, our data demonstrate that cytosolic aggregation of a prion impairs the mitochondrial metabolism of cells defective for Cox12. These findings identify a new functional connection between cytosolic proteostasis and biogenesis of the mitochondrial respiratory chain.


Fast-twitch glycolytic skeletal muscle is predisposed to age-induced impairments in mitochondrial function.
The etiology of mammalian senescence is suggested to involve the progressive impairment of mitochondrial function; however, direct observations of age-induced alterations in actual respiratory chain function are lacking. Accordingly, we assessed mitochondrial function via high-resolution respirometry and mitochondrial protein expression in soleus, quadricep, and lateral gastrocnemius skeletal muscles, which represent type 1 slow-twitch oxidative muscle (soleus) and type 2 fast-twitch glycolytic muscle (quadricep and gastrocnemius), respectively, in young (10-12 weeks) and mature (74-76 weeks) mice. Electron transport through mitochondrial complexes I and III increases with age in quadricep and gastrocnemius, which is not observed in soleus. Mitochondrial coupling efficiency during respiration through complex I also deteriorates with age in gastrocnemius and shows a tendency (p = .085) to worsen in quadricep. These data demonstrate actual alterations in electron transport function that occurs with age and are dependent on skeletal muscle type.


Clinical Prediction Models for Patients With Nontraumatic Knee Pain in Primary Care: A Systematic Review and Internal Validation Study.
Study Design Systematic review and validation study. Background Many prognostic models of knee pain outcomes have been developed for use in primary care. Variability among published studies with regard to patient population, outcome measures, and relevant prognostic factors hampers the generalizability and implementation of these models. Objectives To summarize existing prognostic models in patients with knee pain in a primary care setting and to develop and internally validate new summary prognostic models. Methods After a sensitive search strategy, 2 reviewers independently selected prognostic models for patients with nontraumatic knee pain and assessed the methodological quality of the included studies. All predictors of the included studies were evaluated, summarized, and classified. The predictors assessed in multiple studies of sufficient quality are presented in this review. Using data from the Musculoskeletal System Study (BAS) cohort of patients with a new episode of knee pain, recruited consecutively by Dutch general medical practitioners (n = 372), we used predictors with a strong level of evidence to develop new prognostic models for each outcome measure and internally validated these models. Results Sixteen studies were eligible for inclusion. We considered 11 studies to be of sufficient quality. None of these studies validated their models. Five predictors with strong evidence were related to function and 6 to recovery, and were used to compose 2 prognostic models for patients with knee pain at 1 year. Running these new models in another data set showed explained variances (R2) of 0.36 (function) and 0.33 (recovery). The area under the curve of the recovery model was 0.79. After internal validation, the adjusted R2 values of the models were 0.30 (function) and 0.20 (recovery), and the area under the curve was 0.73. Conclusion We developed 2 valid prognostic models for function and recovery for patients with nontraumatic knee pain, based on predictors with strong evidence. A longer duration of complaints predicted poorer function but did not adequately predict chance of recovery. Level of Evidence Prognosis, levels 1a and 1b. J Orthop Sports Phys Ther 2017;47(8):518-529. Epub 16 Jun 2017. doi:10.2519/jospt.2017.7142.


Reduced spore germination explains sensitivity of reef-building algae to climate change stressors.
Reduced seawater pH and changes in carbonate chemistry associated with ocean acidification (OA) decrease the recruitment of crustose coralline algae (CCAcf.), an important coral-reef builder. However, it is unclear whether the observed decline in recruitment is driven by impairment of spore germination, or post-settlement processes (e.g. space competition). To address this, we conducted an experiment using a dominant CCA, Porolithon cf. onkodes to test the independent and combined effects of OA, warming, and irradiance on its germination success and early development. Elevated CO2 negatively affected several processes of spore germination, including formation of the germination disc, initial growth, and germling survival. The magnitude of these effects varied depending on the levels of temperature and irradiance. For example, the combination of high CO2 and high temperature reduced formation of the germination disc, but this effect was independent of irradiance levels, while spore abnormalities increased under high CO2 and high temperature particularly in combination with low irradiance intensity. This study demonstrates that spore germination of CCA is impacted by the independent and interactive effects of OA, increasing seawater temperature and irradiance intensity. For the first time, this provides a mechanism for how the sensitivity of critical early life history processes to global change may drive declines of adult populations of key marine calcifiers.


Biological inhibitory effects of the Chinese herb danggui on brain astrocytoma.
Previous studies have demonstrated the utility of the traditional Chinese herb danggui in the treatment of chronic myelogenous leukemia. Our aim was to examine whether it might similarly be used to treat glioblastoma multiforme. The lipid-soluble active ingredients of danggui were extracted with acetone (AS-AC) or chlorophenol (AS-CH) and their antiproliferative and proapoptotic effects were studiedin vitro on cultured GBM 8401 cells and in vivoon tumors in nude mice. After a 24-hour treatment, either AS-AC or AS-CH at a lower (50 micro g/ml) and a higher concentration (100 micro g/ml) significantly inhibited the proliferative activity of GBM 8401 cultured cells by 30-50%, as well as the expression of cathepsin B and vascular endothelial growth factor (VEGF). In nude mice, the growth of the tumor was inhibited by 30% by AS-CH or AS-AC (20 mg/kg; p < 0.05) and by 60% by AS-CH or AS-AC (60 mg/kg; p < 0.05). AS-AC and AS-CH also significantly inhibited microvessel formation in the tumors of nude mice. Danggui may inhibit tumor growth by reducing the level of VEGF and the proapoptotic protein, cathepsin B. Thus, danggui may be useful in the treatment of high-grade astrocytomas.


Activation of prefrontal cortex in children during a nonspatial working memory task with functional MRI.
Functional magnetic resonance imaging (fMRI) was used to examine the pattern of activity of prefrontal cortex in prepubertal children during performance of a nonspatial working memory task. The children observed sequences of letters and responded whenever a letter repeated with exactly one nonidentical letter intervening. In a comparison task, subjects monitored similar sequences of letters for any occurrence of a single, prespecified target letter. Location of activation closely approximated that observed in a recent fMRI study with adults using exactly the same task. Activation of the inferior and middle frontal gyri was reliably observed within individual subjects during performance of the working memory task relative to the comparison task. Activation increased and decreased with a time course that was highly consistent with the task manipulations and correlated with behavioral performance. To our knowledge, this study is one of the first to demonstrate the applicability of fMRI to a normative developmental population. Issues of age dependence of the hemodynamic responses of fMRI are discussed.


Early occurrence and prognostic significance of p53 alteration in primary carcinoma of the fallopian tube.
The pathogenesis of primary carcinoma of the fallopian tube (PCFT) is poorly understood. Tumor suppressor p53 gene alterations are common in human malignancies, but their role in the tumorigenesis and survival of PCFT is undefined. The objectives of this study were to define the occurrence and prognostic role of p53 alteration in PCFT and to examine the efficiency of immunohistochemistry (IHC) in detecting p53 alteration in PCFT. Fifty-two PCFT and 10 normal fallopian tubes were examined for p53 alteration by IHC and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). The Kaplan-Meier method was used to derive the survival function, while the log-rank test was used to compare curves for two or more groups. Other patients' characteristics were analyzed by two-tailed Fisher's exact tests. IHC correlated well with PCR-SSCP with 100% sensitivity and 83.3% specificity for detecting p53 alteration in this study. Thirty-one of 52 (57%) PCFT showed p53 alteration. Alteration of p53 occurred in all stages of PCFT with a similar incidence in carcinoma in situ and late-stage disease. Alteration of p53 was related to tumor histologic type. Significant survival difference was noted between advanced and early clinical stages but no such difference was identified among different tumor grades. Compared to the p53-nonaltered group, the presence of p53 alteration in PCFT was related to significantly decreased patient survival (RR = 6.8, 95% CI = 2.9-16.2) in multivariate analysis. In the subgroup of patients with residual tumor after surgery, those with p53-altered tumors had a significantly decreased survival compared to those with p53-nonaltered group (RR = 7.4, 95% CI = 1.9-28.2). Alteration of p53 is common and IHC is an efficient method to detect p53 alteration in PCFT. Shorter survival is associated with p53 alteration which is an independent marker for the disease in this study. Alteration of p53 may be an early event in tubal tumorigenesis and may play an important role in the development of PCFT. Whether detection of p53 alteration may serve as an indicator of high-risk patients for whom more aggressive adjuvant chemotherapy may be considered needs to be explored in the future.


Genetic pathways to glioblastoma: a population-based study.
We conducted a population-based study on glioblastomas in the Canton of Zurich, Switzerland (population, 1.16 million) to determine the frequency of major genetic alterations and their effect on patient survival. Between 1980 and 1994, 715 glioblastomas were diagnosed. The incidence rate per 100,000 population/year, adjusted to the World Standard Population, was 3.32 in males and 2.24 in females. Observed survival rates were 42.4% at 6 months, 17.7% at 1 year, and 3.3% at 2 years. For all of the age groups, younger patients survived significantly longer, ranging from a median of 8.8 months (<50 years) to 1.6 months (>80 years). Loss of heterozygosity (LOH) 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16(INK4a) deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations and was predictive of shorter survival. Primary (de novo) glioblastomas prevailed (95%), whereas secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hotspot codons 248 and 273, whereas in primary glioblastomas, mutations were more equally distributed. G:C-->A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas (56% versus 30%; P = 0.0208). This suggests that the acquisition of TP53 mutations in these glioblastoma subtypes occurs through different mechanisms.


Protection of Hamsters from Mortality by Reducing Fecal Moxifloxacin Concentration with DAV131A in a Model of Moxifloxacin-Induced Clostridium difficile Colitis.
Lowering the gut exposure to antibiotics during treatments can prevent microbiota disruption. We evaluated the effects of an activated charcoal-based adsorbent, DAV131A, on the fecal free moxifloxacin concentration and mortality in a hamster model of moxifloxacin-induced Clostridium difficile infection. A total of 215 hamsters receiving moxifloxacin subcutaneously (day 1 [D1] to D5) were orally infected at D3 with C. difficile spores. They received various doses (0 to 1,800 mg/kg of body weight/day) and schedules (twice a day [BID] or three times a day [TID]) of DAV131A (D1 to D8). Moxifloxacin concentrations and C. difficile counts were determined at D3, and mortality was determined at D12 We compared mortality rates, moxifloxacin concentrations, and C. difficile counts according to DAV131A regimen and modeled the links between DAV131A regimen, moxifloxacin concentration, and mortality. All hamsters that received no DAV131A died, but none of those that received 1,800 mg/kg/day died. Significant dose-dependent relationships between DAV131A dose and (i) mortality, (ii) moxifloxacin concentration, and (iii) C. difficile count were evidenced. Mathematical modeling suggested that (i) lowering the moxifloxacin concentration at D3, which was 58 μg/g (95% confidence interval [CI] = 50 to 66 μg/g) without DAV131A, to 17 μg/g (14 to 21 μg/g) would reduce mortality by 90%; and (ii) this would be achieved with a daily DAV131A dose of 703 mg/kg (596 to 809 mg/kg). In this model of C. difficile infection, DAV131A reduced mortality in a dose-dependent manner by decreasing the fecal free moxifloxacin concentration.


Sensitive and rapid detection of pathogenic bacteria from urine samples using multiplex recombinase polymerase amplification.
Bacterial infections may cause severe diseases such as tuberculosis, sepsis, nephritis and cystitis. The rapid and sensitive detection of bacteria is a prerequisite for the treatment of these diseases. The current gold standard for bacterial identification is bacteriological culture. However, culture-based identification takes 3-7 days, which is time-consuming and laborious. In this study, bacteria in urine samples were enriched using a portable filter-based pipette. Then, a centrifugal chip was constructed to detect multiple pathogenic bacteria from urine samples by integrating the DNA extraction, multiplex recombinase polymerase amplification (RPA) and fluorescent detection together. This eliminated the time-consuming cultivation step, and thus accelerated the diagnosis of the urinary tract infections (UTIs). The five major pathogenic bacteria in UTIs were detected in this study, which are Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus and Salmonella typhimurium. Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Staphylococcus aureus were successfully detected with limits of detection of 100 CFU mL-1 from urine samples within 40 min. Salmonella typhimurium was successfully detected with a limit of detection of 1000 CFU mL-1 from urine samples. The chip-based bacteria detection proposed in this study is a promising tool for sensitive, accurate, and multiplex identification of bacteria in clinical urine samples of UTIs and bacteriuria.


Salivary Chemical Factors in Relation with Oral Cancer in Smokers and Non-Smokers: a Literature Review.
Squamous cell carcinoma of oral cavity is of malignant tumors, which causes cancerous complications. DNA damage, mainly because of products of oxidative stress like reactive oxygen species, is a frequent mutagenic that triggers carcinoma. Smoking increases the probability of cancer incidence. Saliva is the first biological medium to interact with external compounds, especially smoking substances. The present study overviews the salivary level of some remarkable compounds in relation with smoking and squamous cell carcinoma. To collect data, English literature was searched in databases including PubMed, ScienceDirect and Google Scholar. The keywords used for search were as follows: 'Carcinoma, Squamous Cell', 'Smoking', 'Saliva', and 'Biomarkers'. The inclusion criteria were the presence of salivary chemical factors in relation with oral cancer and influence by smoking. Out of 239 found articles, only 56 were selected. Our results demonstrated the potential role of salivary biochemistry to predict and/or treat complications with cancer in both smoker and non-smoker individuals. Changes in concentrations of salivary chemicals including antioxidants, total antioxidant, glutathione and uric acid, epithelial growth factor, cytokine biomarkers, superoxide dismutase activity, and transcriptome were related to squamous cell carcinoma and could be used as potential biomarkers for cancer prognosis; moreover, enhancement of antioxidant level might be a potential treatment.


Poly(ε-caprolactone) nanocapsule carriers with sustained drug release: single dose for long-term glaucoma treatment.
Glaucoma is an eye-related disease accompanied by highly elevated intraocular pressure (IOP), which causes damage to the optic nerve and results in vision loss and even blindness. Although the treatment of glaucoma with eye drops may reduce the IOP, eye drops have some limitations, such as poor patient compliance and short duration. To develop drug carriers that facilitate the sustained and long-term release of drugs for glaucoma therapy, we synthesized poly(ε-caprolactone) nanoparticles (PCL NPs) capable of loading pilocarpine, a widely used drug for the treatment of dry eye and glaucoma. We prepared two types of PCL NPs, namely, nanospheres (NSs), which are solid spheres capable of harboring the drug in their solid mass, and nanocapsules (NCs), which are hollow spherical structures for encapsulating the drug. The influence of the vesicular structure of PCL NPs on the drug loading efficiencies and release was investigated. The loading of pilocarpine in the PCL NCs was approximately 3 times higher than that in the PCL NSs. In addition, pilocarpine-loaded PCL NCs (PILO-PCL NCs) exhibited a sustained drug release profile. Effective pharmacological responses (i.e., IOP reduction and pupillary constriction) were observed in rabbits intracamerally treated with pilocarpine-loaded PCL NPs. Moreover, the PILO-PCL NCs show long-term therapeutic ability in alleviating ocular hypertension-induced corneal and retinal injuries under physiological conditions, even after 42 days. The results of in vivo studies also reveal that the PCL NCs are advantageous for the treatment of chronic ocular hypertension in glaucomatous eyes.


Relationship between the impacted mandibular third molar and adjacent second molar' external root resorption by cone-bean computed tomography analysis.
The relationship between the impacted mandibular third molar (IMTM) and the external root resorption (ERR) of the mandibular second molar (MSM) was analysed with cone-beam computed tomography (CBCT). The risk factors affecting the ERR of the MSM were examined to provide a reference. A total of 327 patients (total: 578 teeth) admitted to the Affiliated Hospital of Yanbian University for IMTM extraction from January 2017 to December 2019 was chosen and divided according to gender and age. The correlation between the IMTM and ERR of MSM was analysed, including inclination angle, impaction direction and depth. The relationship of mandibular ascending ramus classification with ERR of MSM was also analysed. In addition, the correlation between the MTM impaction type and the severity of ERR was analysed. The incidence of ERR of MSM in male patients was higher than in females (27.9% vs.17.6%, p = 0.018). The occurrence and the site of ERR showed statistical differences in the inclination angle [(≤20°, 3.6%) vs. (21°-40°, 27.1%) vs. (41°-60°, 27.6%) vs. (61°-80°, 25.6%) vs. (>80°, 31.7%), p <0.001], impaction direction [(Vertical, 1.1%) vs. (Mesial, 32.7%) vs. (Horizontal, 25.3%), p <0.001] and depth of MTM [(Low position, 38.6%) vs. (Median position, 32.0%) vs. (High position, 13.7%), p <0.001]. Also, there was a significant difference in the mandibular ascending ramus type [(Class I, 17.4%) vs. (Class II, 32.3%) vs. (Class III, 44.9%), p <0.001]. In addition, the severity of ERR showed statistical differences in the mesial (40.9%, p<0.05), lower impaction (54.5%, p<0.05) depth of MTM and type III of mandibular ascending ramus (63.6%, p<0.05). The inclination angle, impaction direction, and depth of MTM were the influencing factors for the occurrence and site of ERR. Also, mandibular ascending ramus type was the impact fact. For MTM with mesioangular, lower impaction, and mandibular ascending ramus with type III, the ERR of the MSM was severer.


Tunable morphology and magnetic properties of Bi2Fe4O9 nanocrystal synthesized by hydrothermal method.
Bi2Fe4O9 nano and micron powders have been synthesized by a hydrothermal method. The as-obtained samples are pure phase and crystallize in the orthorhombic structure. Diverse particle morphologies, including nanoplates, nanospheres, microcubes, and microcylinders, are obtained under different synthesis conditions. The solvent N,N-Dimethylformamide (DMF), together with the mineralisers NaOH and NH4OH, are found to be the key factors for the formation of the particles with their diverse morphologies and sizes. The magnetization dependence of temperature (M-T), observed in a field of 1000 Oe from 10 to 340 K, and M-H loops measured at 10 K indicate that the Bi2Fe4O9 particles are paramagnetic at room temperature and undergo an antiferromagnetic transition at a Néel temperature (T(N)) of 250 K.


Glucocorticoid receptor polymorphisms and haplotypes associated with chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) is a significant public health problem of unknown etiology, the pathophysiology has not been elucidated, and there are no characteristic physical signs or laboratory abnormalities. Some studies have indicated an association of CFS with deregulation of immune functions and hypothalamic-pituitary-adrenal (HPA) axis activity. In this study, we examined the association of sequence variations in the glucocorticoid receptor gene (NR3C1) with CFS because NR3C1 is a major effector of the HPA axis. There were 137 study participants (40 with CFS, 55 with insufficient symptoms or fatigue, termed as ISF, and 42 non-fatigued controls) who were clinically evaluated and identified from the general population of Wichita, KS. Nine single nucleotide polymorphisms (SNPs) in NR3C1 were tested for association of polymorphisms and haplotypes with CFS. We observed an association of multiple SNPs with chronic fatigue compared to non-fatigued (NF) subjects (P < 0.05) and found similar associations with quantitative assessments of functional impairment (by the SF-36), with fatigue (by the Multidimensional Fatigue Inventory) and with symptoms (assessed by the Centers for Disease Control Symptom Inventory). Subjects homozygous for the major allele of all associated SNPs were at increased risk for CFS with odds ratios ranging from 2.61 (CI 1.05-6.45) to 3.00 (CI 1.12-8.05). Five SNPs, covering a region of approximately 80 kb, demonstrated high linkage disequilibrium (LD) in CFS, but LD gradually declined in ISF to NF subjects. Furthermore, haplotype analysis of the region in LD identified two associated haplotypes with opposite alleles: one protective and the other conferring risk of CFS. These results demonstrate NR3C1 as a potential mediator of chronic fatigue, and implicate variations in the 5' region of NR3C1 as a possible mechanism through which the alterations in HPA axis regulation and behavioural characteristics of CFS may manifest.


Standards for hospital libraries 2002.
The Medical Library Association's "Standards for Hospital Libraries 2002" have been developed as a guide for hospital administrators, librarians, and accrediting bodies to ensure that hospitals have the resources and services to effectively meet their needs for knowledge-based information. Specific requirements for knowledge-based information include that the library be a separate department with its own budget. Knowledge-based information in the library should be directed by a qualified librarian who functions as a department head and is a member of the Academy of Health Information Professionals. The standards define the role of the medical librarian and the links between knowledge-based information and other functions such as patient care, patient education, performance improvement, and education. In addition, the standards address the development and implementation of the knowledge-based information needs assessment and plans, the promotion and publicity of the knowledge-based information services, and the physical space and staffing requirements. The role, qualifications, and functions of a hospital library consultant are outlined. The health sciences library is positioned to play a key role in the hospital. The increasing use of the Internet and new information technologies by medical, nursing, and allied health staffs; patients; and the community require new strategies, strategic planning, allocation of adequate resources, and selection and evaluation of appropriate information resources and technologies. The Hospital Library Standards Committee has developed this document as a guideline to be used in facing these challenges.


Residue bone wax simulating spinal tumour: a case report.
Bone wax is primarily used in case of bleeding of the diploic vessels of the bones in surgical procedures. It is useful in neurosurgical procedures because of its inert, nonreactive characteristics. Bone wax is safe material and its use rarely leads to complications but there may be complications of over use. It can cause direct pressure of neural tissue as a mass, simulating tumour with the symptoms and on MRI. In the present case the authors evaluated the signs and symptoms, diagnosis, surgical treatment, and outcome in a patient with an unusual sequestered mass simulating a spinal tumour or another space-occupying lesion on preoperative MR imaging. A 64-year-old was woman admitted to the Neurosurgery Clinic with a 10 year history of low back pain, 1-year history of gait disorder, leg weakness, paraparesis, and 1-month history of urinary incontinence and weight loss. T1- weighted sagittal MRI showed the L3 hemilaminectomy, discectomy defect, heterogeneous hyperintense extradural mass and spinal stenosis extending from L2. A hypointense mass relative to the spinal structures was detected in T2- weighted axial MR images.The provisional diagnosis of a cauda equina syndrome and intra- or extradural spinal tumour was made. The patient underwent an L2 total laminectomy. In our case the fragment was seen in the epidural space, under the lamina of L2. The histopathology showed granulation tissue, inflammatory cells, macrophages and multinuclear giant cells. Postoperatively the patient's neurological findings recovered quickly and she began to walk more comfortably.


Antioxidant activity and phenolic compounds in organic red wine using different winemaking techniques.
Wine phenolic composition depends on the grapes used to make wine and on vinification conditions. The occurrence of these biological compounds has stimulated numerous studies focused on understanding the mechanisms that influence their concentrations in wine. This article studied the effect of different vinification techniques on the antioxidant activity and on the phenolic compounds of red wine made from the variety of Monastrell grapes obtained by organic culture. To this purpose, 3 different vinification procedures were carried out: vinification after prolonged maceration, vinification with the addition of enological enzymes, and traditional vinification procedures (used as control).The results showed similar values of antioxidant activity in all 3 types of wine elaborated and found no differences in the concentrations of the different types of phenolic compounds in wine made with the 3 different methods. The evolution of antioxidant activity and phenolic compounds tested in wines during 3 mo of storage showed a similar pattern. Organic wine has acquired an important role in the economic world and its important, working in oenology to research in this field.


Introgression among three rockfish species (Sebastes spp.) in the Salish Sea, northeast Pacific Ocean.
Interspecific hybridization is often seen as a major conservation issue, potentially threatening endangered species and decreasing biodiversity. In natural populations, the conservation implications of hybridization depends on both on anthropogenic factors and the evolutionary processes maintaining the hybrid zone. However, the timeline and patterns of hybridization in the hybrid zone are often not known. Therefore, species conservation becomes a concern when recent anthropogenic changes influence hybridization and not if hybridization is part of a long-term process. Here, we use sequence data from one mitochondrial gene, three nuclear introns and one nuclear exon to estimate the direction, geographic extent, frequency and possible timeline of hybridization between three rockfish species (Sebastes auriculatus, S. caurinus, S. maliger) in the Salish Sea, Washington, USA. We show that (i) introgression occurred much more frequently in the Salish Sea than on the outer coast, (ii) introgression was highly asymmetrical from S. maliger into the other two species, (iii) almost 40% of individuals in the Salish Sea were hybrids, with frequency of hybrids increasing with isolation from the coast, and (iv) all hybrids were later generation backcrosses rather than F1 hybrids. Our results suggest long-standing low-level hybridization rather than recent onset of interbreeding because of human induced environmental change, possibly facilitated by specific environmental conditions in the sub-basins of the Salish Sea, and by differences in population sizes during recolonization of the area after the last glaciation. This rockfish hybrid system, with asymmetrical introgression and the maintenance of parental species, may prove useful to study both mechanisms that maintain species boundaries and that facilitate speciation in the presence of rapid environmental change.