Laminin isoforms 8 and 10 are primary components of the subendothelial basement membrane promoting interaction with neoplastic lymphocytes.
To determine whether subendothelial laminins (LNs) could be implicated in the extravasation of neoplastic lymphocytes, we have examined the distribution of a number of LN isoforms in human vascular structures of adult individuals and have assayed the ability of the isolated LN molecules to promote adhesion of lymphoma and leukemic cells in vitro using a novel cell adhesion assay, CAFCA, Centrifugal Assay for Fluorescence-based Cell Adhesion (E. Giacomello et al., Biotechniques, 26: 758-762, 1999; P. Spessotto et al., Methods Mol. Biol., 139: 321-343, 2000). The use of previously characterized LN chain-specific antibodies showed that the vast majority of the smaller vascular compartments, known to correspond to sites of lymphocyte transmigration, expressed the subunits involved in the structuring of 9 of the 12 LN isoforms known to date. Eight LN isoforms (i.e., LN-1, -2, -4, -5, -8, -9, -10, and -11) and four naturally occurring LN complexes were isolated from various tissues and cultured cells by combined gel filtration, ion exchange, and immunoaffinity chromatographies, and the identity/composition of the isolated LNs/LN complexes was asserted by immunochemical means and amino-acid sequencing. Notwithstanding the widespread colocalization of LN isoforms, a panel of neoplastic B- and T-cell lines and lymphocytes isolated from patients affected by chronic lymphocytic B-cell leukemia attached preferentially and with high avidity to purified LN-8, purified LN-10, and LN-10-containing protein complexes, whereas lymphocytes derived from patients diagnosed with acute lymphocytic leukemia failed to bind to these LNs. All of the tested neoplastic lymphocytes failed to adhere to the isolated LN-1, LN-4, LN-9, and LN-11 and attached moderately well to purified LN-2 and LN-5. The interaction of transformed lymphocytes with LNs was cation-dependent and interchangeably mediated by the alpha3beta1 and alpha6beta1 integrins. The degree of engagement of the two LN receptors was dependent upon their relative levels of cell surface expression, whereas, irrespective of the phenotype, lymphocytes deprived of either of these receptors were incapable of LN binding. The findings suggest that LN-8 and LN-10 may act in an independent or complementary fashion as primary components of the endothelial basement membrane favoring the interaction of extravasating neoplastic lymphocytes. Thus, our results would demonstrate that different LN isoforms may evoke diverse cellular responses in different cell types and that this divergence may be the basis for the redundancy of LN distribution in a number of vascular structures.


Elucidating Compound Mechanism of Action by Network Perturbation Analysis.
Genome-wide identification of the mechanism of action (MoA) of small-molecule compounds characterizing their targets, effectors, and activity modulators represents a highly relevant yet elusive goal, with critical implications for assessment of compound efficacy and toxicity. Current approaches are labor intensive and mostly limited to elucidating high-affinity binding target proteins. We introduce a regulatory network-based approach that elucidates genome-wide MoA proteins based on the assessment of the global dysregulation of their molecular interactions following compound perturbation. Analysis of cellular perturbation profiles identified established MoA proteins for 70% of the tested compounds and elucidated novel proteins that were experimentally validated. Finally, unknown-MoA compound analysis revealed altretamine, an anticancer drug, as an inhibitor of glutathione peroxidase 4 lipid repair activity, which was experimentally confirmed, thus revealing unexpected similarity to the activity of sulfasalazine. This suggests that regulatory network analysis can provide valuable mechanistic insight into the elucidation of small-molecule MoA and compound similarity.


Somatosensory evoked response: application in neurology.
One technique used for short-latency somatosensory evoked response (SER) is described. SER following nerve stimulation is a unique non-invasive, clinical test used to evaluate the somatosensory pathways. It tests the physiological function of the median nerve, the brachial plexus, the C6-7 cervical roots, cervical spinal cord, the cuneate nuclei, the medial lemniscus, the thalamus, and the contralateral sensory cortex. It has been shown to be a reliable and useful clinical test particularly in multiple sclerosis and comatose patients. The promising technique of SER following peroneal nerve stimulation is mentioned.


[Chinese version of a face version of the modified child dental anxiety scale: transcultural adaptation and evaluation].
To develop the Chinese version of a face version of the modified child dental anxiety scale (MCDASf) and test the reliability and validity of MCDASf. The English version of MCDASf was translated and back-translated, as well as crosscultural adapted by the method of psychometrics to develop the Chinese version of MCDASf. Subsequently the Chinese version schedule was randomly investigated among 245 kindergarten children and school children aged greater than 4 and less than 12 years on two separate occasions 3 weeks apart to determine the reliability. A total of 248 children attending Pediatrics Dentistry of Peking University School and Hospital of Stomatology aged greater than 4 and less than 12 years old were selected and completed the Chinese version of MCDASf and the Chinese version of modified Children's fear survey schedule-dental subscale (CFSS-DS) before treatment to determine the validity. Then we rated the children's behavior during dental treatment by Venham's clinical anxiety rating scale and cooperative behavior rating scale to evaluate the relation between self-assessed dental anxiety scores and the behavioral reaction during the dental treatment. In reliability study, 98.0% of 250 children completed the MCDASf. In validity study, 99.2% of 248 children completed the MCDASf. Cronbach's alpha coefficient of the translated scale was 0.814 and the test-retest reliability was 0.907. Principal component analysis of the translated scale confirmed that the scale consisted of a single unidimensional construct. The Chinese version of MCDASf significantly was correlated with the Chinese version of modified CFSS-DS (r = 0.843, P < 0.01) . It was also correlated with Venham's clinic anxiety rating scale and cooperative behavior rating scale (r = 0.675, P < 0.01). The Chinese version of MCDASf demonstrated good reliability and validity and can be used as a simple self-report measurement of dental anxiety in Chinese children aged 4-11 years.


Aldosterone excess may inhibit insulin secretion: A comparative study on glucose metabolism pre- and post-adrenalectomy in patients with primary aldosteronism.
Conflicting data have been published on the effects of aldosterone excess on glucose metabolism. Specifically, there are limited data on whether adrenalectomy in patients with aldosterone-producing adenomas (APA) can improve glucose metabolism. In this study we evaluated changes in glucose metabolism, before and after surgery for APA. The subjects were 61 patients treated with unilateral adrenalectomy, localized by adrenal venous sampling. A 75g-oral glucose tolerance test (OGTT) was performed before and 1 year after adrenalectomy. Patients with diabetes mellitus or a serum cortisol level >3 μg/dL after a 1 mg dexamethasone suppression test, were excluded. Using the 75g-OGTT data, insulin secretion and insulin resistance (or sensitivity) indices were calculated. The results showed that immunoreactive insulin levels during the OGTT increased significantly after adrenalectomy, whereas plasma glucose levels, before and after surgery, were comparable. The insulinogenic index significantly increased after surgery (0.5 [0.4-0.8] to 0.8 [0.4-1.1], p < 0.001). The disposition index remained largely unchanged (806.2 [489.4-1,138.9] to 686.6 [479.4-922.1], p = 0.25). The homeostatic model assessment of insulin resistance increased significantly (1.0 [0.6-1.5] to 1.5 [1.0-2.2], p < 0.001) and the ISImatsuda decreased significantly (6.9 [4.5-10.4] to 5.2 [3.4-7.9], p < 0.001). Changes in these indices were not correlated with changes in potassium and aldosterone levels before and after surgery. In conclusion, insulin secretion increased after adrenalectomy for APA, indicating that aldosterone excess inhibits insulin secretion. However, because of a parallel increase in insulin resistance, plasma glucose levels remained unchanged.


Gabedit--a graphical user interface for computational chemistry softwares.
Gabedit is a freeware graphical user interface, offering preprocessing and postprocessing adapted (to date) to nine computational chemistry software packages. It includes tools for editing, displaying, analyzing, converting, and animating molecular systems. A conformational search tool is implemented using a molecular mechanics or a semiempirical potential. Input files can be generated for the computational chemistry software supported by Gabedit. Some molecular properties of interest are processed directly from the output of the computational chemistry programs; others are calculated by Gabedit before display. Molecular orbitals, electron density, electrostatic potential, nuclear magnetic resonance shielding density, and any other volumetric data properties can be displayed. It can display electronic circular dichroism, UV-visible, infrared, and Raman-computed spectra after a convolution. Gabedit can generate a Povray file for geometry, surfaces, contours, and color-coded planes. Output can be exported to a selection of popular image and vector graphics file formats; the program can also generate a series of pictures for animation. Quantum mechanical electrostatic potentials can be calculated using the partial charges on atoms, or by solving the Poisson equation using the multigrid method. The atoms in molecule charges can also be calculated. Gabedit is platform independent. The code is distributed under free open source X11 style license and is available at http://gabedit.sourceforge.net/.


Low prevalence of human papillomavirus in a geographic region with a high incidence of head and neck cancer.
The main purpose of this study was to determine the prevalence of human papillomavirus (HPV) infection in patients with head and neck carcinomas from Brazil. Forty-five patients with head and neck squamous cell carcinoma were included in the study, from 1995 to 1996. Forty-two were male and 3 female, with age ranging from 32 to 82 years (median 61). Five patients (11%) did not have previous history of use of tobacco and 38 (90.5%) were heavy smokers. Tumor sites were pyriform sinus, 10; tongue, 11 (oral, 6; base, 5); larynx, 7; floor of mouth, 3; tonsil, 6; retromolar area, 3; inferior gingiva 2; buccal mucosa, 2; and maxillary sinus in 1 patient. Twenty-five were stage IV, 17 stage III, and 3 stage II. The presence of HPV DNA was detected in 5 of 45 patients (11%), all of them with HPV 16. Two patients had HPV DNA in normal mucosa and tumor tissue, 1 patient had HPV DNA only in the normal mucosa and tumor tissue, 1 patient had HPV DNA only in the normal mucosa, and 2 patients were positive for HPV DNA in tumor tissue. Four patients were male and 1 was female; 2 patients were nonsmokers. Three patients had tonsil carcinoma, 1 patient had a tongue carcinoma, and 1 patient had a pyriform sinus cancer. The role of chemical carcinogens seems to be more important in the genesis of head and neck cancer than is HPV infection. The presence of HPV DNA in 5 of 45 patients stimulates further investigation to determine the role of HPV as a risk factor for head and neck carcinoma.


Pathophysiological mechanisms of persistent orofacial pain.
Nociceptive stimuli to the orofacial region are typically received by the peripheral terminal of trigeminal ganglion (TG) neurons, and noxious orofacial information is subsequently conveyed to the trigeminal spinal subnucleus caudalis and the upper cervical spinal cord (C1-C2). This information is further transmitted to the cortical somatosensory regions and limbic system via the thalamus, which then leads to the perception of pain. It is a well-established fact that the presence of abnormal pain in the orofacial region is etiologically associated with neuroplastic changes that may occur at any point in the pain transmission pathway from the peripheral to the central nervous system (CNS). Recently, several studies have reported that functional plastic changes in a large number of cells, including TG neurons, glial cells (satellite cells, microglia, and astrocytes), and immune cells (macrophages and neutrophils), contribute to the sensitization and disinhibition of neurons in the peripheral and CNS, which results in orofacial pain hypersensitivity.


Aggressive Behaviors in Young Siblings: Associations with Executive Functions and Maternal Characteristics.
Aggressive behaviors in early childhood are associated with multiple undesirable outcomes, including juvenile delinquency, academic failure, and substance abuse. This investigation employed a family study design to examine child, mother and sibling predictors of early-emerging aggressive behaviors. These predictors included several indices of executive functioning within children, depression symptoms and education level of mothers, and inhibitory control (IC) of siblings. The sample consisted of 95 families (191 children; boys = 100) with at least two, typically developing children between 30 and 66 months of age (M(age) = 45.93 months, SD = 12.40). Measures included laboratory-assessed working memory and IC, parent-reported aggressive behaviors, as well as self-reported maternal depression symptoms and education. Results revealed that children showed substantial sibling similarity in aggressive behaviors. Using multilevel regression analyses, low child IC and greater maternal depression symptoms were associated with increased child aggressive behaviors. Child working memory, maternal education, and sibling IC did not uniquely predict child aggressive behaviors. Moderation analyses revealed an interaction between maternal depression symptoms and maternal education, such that the effect of depression symptoms on child aggressive behaviors was particularly evident amongst highly educated mothers. The current analysis moved beyond a main effects model of maternal depression and extended previous findings on the importance of child IC to aggressive behaviors by using a multiple-child-per-family framework. A promising direction for future research includes assessing whether efforts to increase child IC are successful in reducing child aggressive behaviors.


Enhanced Chemo-Immunotherapy Strategy Utilizing Injectable Thermosensitive Hydrogel for The Treatment of Diffuse Peritoneal Metastasis in Advanced Colorectal Cancer.
Patients with colorectal cancer (CRC) and diffuse peritoneal metastasis (PM) are not eligible for surgical intervention. Thus, palliative treatment remains the standard of care in clinical practice. Systemic chemotherapy fails to cause drug accumulation at the lesion sites, while intraperitoneal chemotherapy (IPC) is limited by high clearance rates and associated complications. Given the poor prognosis, a customized OxP/R848@PLEL hydrogel delivery system has been devised to improve the clinical benefit of advanced CRC with diffuse PM. This system is distinguished by its simplicity, security, and efficiency. Specifically, the PLEL hydrogel exhibits excellent injectability and thermosensitivity, enabling the formation of drug depots within the abdominal cavity, rendering it an optimal carrier for IPC. Oxaliplatin (OxP), a first-line drug for advanced CRC, is cytotoxic and enhances the immunogenicity of tumors by inducing immunogenic cell death. Furthermore, OxP and resiquimod (R848) synergistically enhance the maturation of dendritic cells, promote the expansion of cytotoxic T lymphocytes, and induce the formation of central memory T cells. Moreover, R848 domesticates macrophages to an anti-tumor phenotype. OxP/R848@PLEL effectively eradicates peritoneal metastases, completely inhibits ascites production, and significantly prolongs mice lifespan. As such, it provides a promising approach to managing diffuse PM in patients with CRC without surgical indications.


Quantitative evaluation of diffusion-weighted imaging techniques for the purposes of radiotherapy planning in the prostate.
Diffusion-weighted imaging (DWI) is an important technique for the localization of prostate cancer, and its response assessment during treatment with radiotherapy (RT). However, it has known limitations in terms of distortions and artefacts using standard acquisition techniques. This study evaluates two alternative methods that offer the promise of improved image quality and the potential for more reliable and consistent diffusion data. Three DWI techniques were investigated; single-shot echoplanar imaging (EPI), EPI combined with reduced volume excitation (ZOOMit; Siemens Healthcare, Erlangen, Germany) and read-out segmentation with navigator-echo correction (RESOLVE; Siemens Healthcare). Daily measurements of apparent diffusion coefficient (ADC) value were made in a quality assurance phantom to assess the repeatability of each sequence. In order to evaluate the geometric integrity of these sequences, ten normal volunteers were scanned, and the prostate was contoured to compare its similarity with T2 weighted images. Phantom ADC values were significantly higher using the standard EPI sequence than those of the other two sequences. Differences were also observed between sequences in terms of repeatability, with RESOLVE and EPI performing better than ZOOMit. Overall, the RESOLVE sequence provided the best agreement for the in vivo data with smaller differences in volume and higher contour similarity than T2 weighted imaging. Important differences have been observed between each of the three techniques investigated with RESOLVE performing the best overall. We have adopted this sequence for routine RT simulation of prostate patients at Liverpool Cancer Therapy Centre. This work will be of interest to the increasing number of centres wanting to incorporate quantitative DWI in a clinical setting.


The use of intravenous neostigmine in palliation of severe ileus.
Neostigmine is a parasympathomimetic drug that acts as a reversible acetylcholinesterase inhibitor. Clinically it is used in patients with acute colonic pseudo-obstruction (ACPO or Ogilvie's syndrome, which is a gastrointestinal motility disorder characterized by marked dilatation of the colon in the absence of mechanical obstruction), postoperative ileus, urinary retention, myasthenia gravis, and in anesthesia to reverse the effects of nondepolarizing muscle relaxants. Both bolus and infusion are noted to be effective and lead to prompt evacuation of flatus or stool with a reduction in abdominal distention on physical examination. Median duration is noted to be 4-30 minutes in some trials. Here we present our experience of using 2 mg of intravenous neostigmine to help relieve the severe abdominal distention and ileus in a patient with severe fecal impaction when all conservative measures had been futile. The most frequent side effect of the drug is abdominal pain/cramping, which was noted in our patient as well. Other complications include bradycardia which is very infrequently symptomatic to require atropine. Overall, the drug is a simple, safe, and effective strategy; and as pointed out in the previous studies, the drug appears to be underused in patients who do not have a true contraindication to its use.


Leptin receptors in the adrenal medulla of the rat.
Leptin is the protein product of the recently cloned obesity gene. Leptin receptor mRNA is found in a number of central and peripheral locations. The hypothalamus is a presumed site of action. However, little is known about the specific locations of the receptor in peripheral organs. Epinephrine has potent anorectic effects and can cause weight loss by a variety of mechanisms. Excretion of epinephrine is reduced in the ob/ob mouse, which lacks leptin, suggesting an effect by leptin on the adrenal medulla. In the current study, the presence of the leptin receptor was identified on epinephrine-secreting cells in the adrenal medulla. Immunohistochemical studies found dense leptin receptor-like immunoreactivity in the adrenal medulla with no labeling in the adrenal cortex. Double immunofluorescent labeling confirmed that the leptin receptor was present on cells that were phenylethanolamine N-methyltransferase-like immunoreactive and therefore were epinephrine-secreting cells. Leptin receptor mRNA in the adrenal medulla was detected by reverse transcriptase-polymerase chain reaction, with the majority of the mRNA coding for the short isoform (Ob-Ra) of the receptor. Finally, autoradiography was performed using 125I-labeled leptin; specific binding was found in the adrenal medulla, with no specific binding in the adrenal cortex. These results suggest that leptin may have a direct effect on epinephrine-secreting cells in the adrenal medulla. Epinephrine may play a role in mediating the effects of leptin to reduce body weight.


Pathological narcissism: An analysis of interpersonal dysfunction within intimate relationships.
Pathological narcissism is marked by deficits in psychosocial functioning. Difficulties in relationships include instances of aggression, devaluation and control; however, few studies have examined these relationships from the perspective of partners and family members. We studied participants who were in relationships with relatives high in narcissistic traits (N = 436; current romantic partners [57.3%]; former romantic partners [21.1%]; family members [15.4%]). Participant responses were analysed thematically, and their underlying mental health problems were also measured. Thematic analysis of participant responses indicated themes of abuse from the relative with narcissism (physical, verbal, emotional and sexual) as well as the relative imposing challenging financial and sexual behaviours. There were complex interpersonal themes of mutual idealization but also devaluation. In response, participants reported high levels of anxiety, depression, self-aggression, sickness and somatic concerns. Further, participants expressed overt outward hostility towards their relative with narcissism, but also dependency strivings and frustrated dependency themes. Partners and their relative with narcissism appeared locked into interpersonal and intrapersonal dynamic conflicts. Clinical implications include specific attendance to alliance issues, dependency themes, and a focus on limit setting to establish personal safety.


Chinese nurses' relief experiences following two earthquakes: implications for disaster education and policy development.
Disasters require well trained nurses but disaster nursing education is very limited in China and evidence is urgently required for future planning and implementation of specialized disaster education. This describes the themes arising from narratives of Chinese registered nurses who worked in disaster relief after two major earthquakes. In-depth interviews were held with 12 registered nurses from Hubei Province. Riessman's narrative inquiry method was used to develop individual stories and themes, and socio-cultural theory informed this study. Five themes emerged: unbeatable challenges; qualities of a disaster nurse; mental health and trauma; poor disaster planning and co-ordination; and urgently needed disaster education. Participants were challenged by rudimentary living conditions, a lack of medical equipment, earthquake aftershocks, and cultural differences in the people they cared for. Participants placed importance on the development of teamwork abilities, critical thinking skills, management abilities of nurses in disasters, and the urgency to build a better disaster response system in China in which professional nurses could more actively contribute their skills and knowledge. Our findings concur with previous research and emphasize the urgency for health leaders across China to develop and implement disaster nursing education policies and programs.


Measurements of h(c)(1P(1)) in psi' decays.
We present measurements of the charmonium state h(c)(1P(1)) made with 106x10(6) psi' events collected by BESIII at BEPCII. Clear signals are observed for psi'-->pi0 h(c) with and without the subsequent radiative decay h(c)-->gamma eta(c). First measurements of the absolute branching ratios B(psi'-->pi0 h(c)) = (8.4+/-1.3+/-1.0) x 10(-4) and B(h(c)-->gamma eta(c)) = (54.3+/-6.7+/-5.2)% are presented. A statistics-limited determination of the previously unmeasured h(c) width leads to an upper limit Gamma(h(c))<1.44 MeV (90% confidence). Measurements of M(h(c)) = 3525.40+/-0.13+/-0.18 MeV/c2 and B(psi'-->pi0 h(c)) x B(h(c)-->gamma eta(c)) = (4.58+/-0.40+/-0.50) x 10(-4) are consistent with previous results.


Childhood deaths from external causes in Estonia, 2001-2005.
In 2000, the overall rate of injury deaths in children aged 0-14 was 28.7 per 100000 in Estonia, which is more than 5 times higher than the corresponding rate in neighbouring Finland. This paper describes childhood injury mortality in Estonia by cause and age groups, and validates registration of these deaths in the Statistical Office of Estonia against the autopsy data. The data on causes of all child deaths in Estonia in 2001-2005 were abstracted from the autopsy protocols at the Estonian Bureau of Forensic Medicine. Average annual mortality rates per 100,000 were calculated. Coverage (proportion of the reported injury deaths from the total number of injury deaths) and accuracy (proportion of correctly classified injury deaths) of the registration of causes of death in Statistical Office of Estonia were assessed by comparing the Statistical Office of Estonia data with the data from Estonian Bureau of Forensic Medicine. Average annual mortality from external causes in 0-14 years-old children in Estonia was 19.1 per 100,000. Asphyxia and transport accidents were the major killers followed by poisoning and suicides. Relative contribution of these causes varied greatly between age groups. Intent of death was unknown for more than 10% of injury deaths. Coverage and accuracy of registration of injury deaths by Statistical Office of Estonia were 91.5% and 95.3%, respectively. Childhood mortality from injuries in Estonia is among the highest in the EU. The number of injury deaths in Statistical Office of Estonia is slightly underestimated mostly due to misclassification for deaths from diseases. Accuracy of the Statistical Office of Estonia data was high with some underestimation of intentional deaths. Moreover, high proportion of death with unknown intent suggests underestimation of intentional deaths. Reduction of injury deaths should be given a high priority in Estonia. More information on circumstances around death is needed to enable establishing the intent of death.


Exercise prescription improves exercise tolerance in young children with CHD: a randomised clinical trial.
The main objective of this study was to ascertain if a structured intervention programme can improve the biophysical health of young children with congenital heart disease (CHD). The primary end point was an increase in measureable physical activity levels following the intervention. Patients aged 5-10 years with CHD were identified and invited to participate. Participants completed a baseline biophysical assessment, including a formal exercise stress test and daily activity monitoring using an accelerometer. Following randomisation, the intervention group attended a 1 day education session and received an individual written exercise plan to be continued over the 4-month intervention period. The control group continued with their usual level of care. After 4 months, all participants were reassessed in the same manner as at baseline. One hundred and sixty-three participants (mean age 8.4 years) were recruited, 100 of whom were male (61.3%). At baseline, the majority of the children were active with good exercise tolerance. The cyanotic palliated subgroup participants, however, were found to have lower levels of daily activity and significantly limited peak exercise performance compared with the other subgroups. One hundred and fifty-two participants (93.2%) attended for reassessment. Following the intervention, there was a significant improvement in peak exercise capacity in the intervention group. There was also a trend towards increased daily activity levels. Overall physical activity levels are well preserved in the majority of young children with CHD. A structured intervention programme significantly increased peak exercise capacity and improved attitudes towards positive lifestyle changes.


Osteochemonecrosis of the jaws due to bisphosphonate treatments. Update.
Bisphosphonates (BP),were initially used in industry and later as a drug due to their great affinity to osseous tissue, because of their powerful antiresorptive effect as a treatment in various osteopathies, such as osteoporosis, Paget disease or hypercalcemia associated with some malignant tumors, as myeloma or breast cancer. They are administered orally or intravenously, and although well tolerated, the most frequent side effects are gastrointestinal, in addition to osteonecrosis when they are administered via endovenous. The aim of this work has been to evaluate the existing publications in accredited scientific literature on biphosphonates and their action mechanism and the relationship with the appearance of osteonecrosis of the jaws. Although the mechanism by which osteonecrosis of the jaws develops is not known exactly, there seems to be influence by osteoclast inhibiton, antiangiogenic action, an inhibitory effect on the cellular cycle by the keratinocytes, as well as, reinforcement of the chemiotoxic action in oncological patients treated with other drugs. Clinically, it ranges from a non-specificity of symptoms to lesions such as osteomyelitis with necrosis and osseous sequesters that may be accompanied by fetor ex oris, with the appearance of many Actinomyces contaminated lesions. As for published antecedents on osteonecrosis due to bisphosphonate treatment found until 2006: 46.5% had a previous diagnosis of multiple myeloma; 38.8% were patients with metastatic breast cancer; 6.2% patients of metastatic prostate cancer; 4.1% suffered from osteoporosis; 3.5% from other metastatic diseases and 0.8% had Paget disease. The drugs that seem to have the highest incidence of osteochemionecrosis are: zoledronate, pamidronate, alendronate, risendronate and ibandronate, from the greatest to the least. Additionally, the risk of osteonecrosis being produced is accumulative and may reach 21% in the third year of intravenous bisphosphonate use.


The development of the use of long-term knowledge to assist short-term recall.
The influence of item familiarity upon memory span was examined in adults and children aged 5, 7, and 10 years by comparing the recall of words and nonwords. Using a probed recall task, both item recall and position recall were tested. The effect of familiarity upon item recall was found to develop with age, from no effects in the 5-year-olds to significant effects in the older children and adults. By contrast, no effect of familiarity was found at any age when recall of position was required. Dissociations between word length effects and familiarity effects supported the conclusion that the familiarity effect does not result from rehearsal. Several explanations for the source of the familiarity effect were examined, and the familiarity effect was attributed to a strategic redintegration or reconstruction process, which is necessary for item recall but not for position recall.


Effect of adsorbents on degradation of toxic organic compounds by coimmobilized systems.
The use of coimmobilized systems for treatment of toxic organic compounds has been proposed. The proposed approach combines the use of adsorbents and laboratory identified microorganisms immobilized in a protective permeable barrier to achieve a greater degree of control over the remediation process. This study was launched to understand the effect of adsorbents and changes in adsorption on the degradation of toxic compounds by coimmobilized systems. The specific case studied involved the degradation of pentachlorophenol (PCP) by Arthrobacter (ATCC 33790) coimmobilized with powdered activated carbon within calcium alginate capsules.The design parameters studied included adsorbent content and type as well as the effect of solution pH and surfactant concentration on adsorption and biodegradation. It was found that the equilibrium adsorption behavior of PCP was strongly influenced by solution pH and surfactant concentration. A mathematical model was developed that combined the physical processes of mass transfer and adsorption with biological degradation of PCP. The model was used to predict the effect of various parameters on the degradation of PCP. Based on model predictions, the degradation of PCP. Based on model predictions, the degradation of PCP was strongly dependent on variations in adsorbent capacity and affinity for this contaminant.


John Banister: an Elizabethan surgeon in Brazil.
In Brazil's sixteenth-century history, very few references are made to health professionals. On the expedition of Edward Fenton, dispatched by the English Crown in 1582 to set up a trading post in Asia, was the famous barber-surgeon and physician John Banister. The naval squadron, diverted from its original route to repeat the feats of Sir Francis Drake, stopped over in Africa, crossed the Atlantic and anchored off the Santa Catarina coast in Brazil. In these waters, the expedition degenerated into piracy and returned unsuccessful to Europe. John Banister is considered the person who liberated English anatomy from mediaeval slavery, shedding upon it the light of the Renaissance. It was the first time that anyone of this importance in the area of health had visited these latitudes.


Epidural Injections for Lumbar Radiculopathy and Spinal Stenosis: A Comparative Systematic Review and Meta-Analysis.
The prevalence of chronic low back pain and related disability is rapidly increasing as are the myriad treatments, including epidural injections. Even though epidural injections are one of the most commonly performed procedures in managing low back and lower extremity pain, starting in 1901 with local anesthetic alone, conflicting recommendations have been provided, despite the extensive literature. Recently Chou et al performed a technology assessment review for Agency for Healthcare Research and Quality (AHRQ) part of which was published in Annals of Internal Medicine showing lack of effectiveness of epidural steroid injections in managing lumbar radiculopathy and spinal stenosis. In contrast, multiple other publications have supported the efficacy and use of epidural injections. To assess the efficacy of 3 categories of epidural injections for lumbar and spinal stenosis: performed with saline with steroids, local anesthetic alone, or steroids with local anesthetic and separate facts from opinions. PubMed, Cochrane Library, US National Guideline Clearinghouse, prior systematic reviews, and reference lists. The literature search was performed through August 2015. Randomized trials, either placebo or active control, of epidural injections for lumbar radiculopathy and spinal stenosis. Data extraction and methodological quality assessment were performed utilizing Cochrane review methodologic quality assessment and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB). Evidence was summarized utilizing principles of best evidence synthesis. Thirty-nine randomized controlled trials met inclusion criteria. There were 9 placebo-controlled trials evaluating epidural corticosteroid injections, either with sodium chloride solution or bupivacaine, compared to placebo injections. There were 12 studies comparing local anesthetic alone to local anesthetic with steroid. A meta-analysis of 5 studies utilizing sodium chloride or bupivacaine with steroid showed a lack of efficacy.A comparison of lidocaine to lidocaine with steroids in 7 studies showed significant effectiveness from baseline to long-term follow-up periods. Meta-analysis showed a similar effectiveness for pain and function without non-inferiority of lidocaine compared to lidocaine with steroid at 3 months and 12 months. The review was restricted to the data available with at least 3 months of follow-up, which excluded some studies. The inclusion criteria were restricted to English language studies. Epidural corticosteroid injections for radiculopathy or spinal stenosis with sodium chloride solution or bupivacaine were shown to be ineffective. Lidocaine alone or lidocaine in conjunction with steroids were significantly effective.


Intensity discrimination and increment detection in cochlear-implant users.
Intensity difference limens (DLs) were measured in users of the Nucleus 22 and Clarion v1.2 cochlear implants and in normal-hearing listeners to better understand mechanisms of intensity discrimination in electric and acoustic hearing and to evaluate the possible role of neural adaptation. Intensity DLs were measured for three modes of presentation: gated (intensity increments gated synchronously with the pedestal), fringe (intensity increments delayed 250 or 650 ms relative to the onset of the pedestal), and continuous (intensity increments occur in the presence of a pedestal that is played throughout the experimental run). Stimuli for cochlear-implant listeners were trains of biphasic pulses; stimuli for normal-hearing listeners were a 1-kHz tone and a wideband noise. Clarion cochlear-implant listeners showed level-dependent effects of presentation mode. At low pedestal levels, gated thresholds were generally similar to thresholds obtained in the fringe and continuous conditions. At higher pedestal levels, however, the fringe and continuous conditions produced smaller intensity DLs than the gated condition, similar to the gated-continuous difference in intensity DLs observed in acoustic hearing. Nucleus cochlear-implant listeners did not show consistent threshold differences for the gated and fringe conditions, and were not tested in the continuous condition. It is not clear why a difference between gated and fringe thresholds occurred for the Clarion but not the Nucleus subjects. Normal-hearing listeners showed improved thresholds for the continuous condition relative to the gated condition, but the effect was larger for the 1-kHz tonal carrier than for the noise carrier. Findings suggest that adaptation occurring central to the inner hair cell synapse mediates the gated-continuous difference observed in Clarion cochlear-implant listeners and may also contribute to the gated-continuous difference in acoustic hearing.


Using co-design to develop interventions to address health literacy needs in a hospitalised population.
Health literacy describes the cognitive and social skills which determine the motivation and ability of individuals to gain access to, understand and use information in ways which promote and maintain good health. Suboptimal health literacy is common and is believed to impact up to 60% of Australians. Co-design is a participatory approach to the development of interventions that brings together to staff and patients to design local solutions to local problems. The aim of this study is to describe a staff and patient co-design process that will lead to the development of health literacy interventions in response to identified health literacy needs of hospital patients. A mixed methods, two-step sequential explanatory design. Step 1: hospitalised patients surveyed and data analysed using hierarchical cluster analysis to establish health literacy profiles. Step 2: clusters presented as vignettes to patients and clinicians to co-design interventions to address needs. Eight health literacy clusters were identified from surveys. Seven patients attended two patient workshops and 23 staff attended two staff workshops. Three key themes were identified: organisational, provider-patient, and patient self-care. Within these, five sub-themes emerged: "Good quality communication during hospital stay", "Social support for health", "A good discharge", "Care across the continuum" and "Accessing quality information when home". Fifteen potential interventions were produced, including changes to message design and delivery, staff training in assessing for understanding, social support to improve understanding, improving communication consistency across the care continuum, and strategic dissemination of web-based resources. This study identified fifteen strategies to address health literacy needs of a hospital population. Implementation and evaluation will identify sets of strategies that have the maximum patient, clinician and organisational benefit. This approach allows for the development of locally-driven, contextually-appropriate interventions to address health literacy needs.


Quantitative visualization of colloidal and intracellular gold nanoparticles by confocal microscopy.
Gold nanoparticles (AuNPs) have the potential to become a versatile biomarker. For further use of AuNPs labeled with functionalized molecules, their visualization in biological systems by routine laboratory tools such as light microscopy is crucial. However, the size far below the diffraction limit affords specialized parameters for microscopical detection, which stimulated the current study, aimed to determine from which size onward AuNPs, either in dispersion or cell-associated, can be reliably detected by standard confocal microscopy. First, gold colloids of size-restricted fractions are examined in dispersion. At a minimum particle size of 60 nm, detection appears to be reliable. Particle counts in dilution series confirm these results by revealing single particle detection of 60-nm colloids. Second, AuNPs are visualized and quantified in cells, which interestingly cause a phase shift in the reflection of AuNPs. Gold mass spectroscopy confirms the number of AuNPs counted microscopically inside cells. Furthermore, it demonstrates for the first time a very high diffusion rate of 15-nm particles into the cells. In conclusion, the results back the suitability of confocal microscopy for the quantitative tracking of colloidal and intracellular gold nanoparticles sized 60 nm.


Chorioretinitis and vitreitis due to Tropheryma whipplei after transplantation: case report and review.
Whipple's disease is a very rare chronic multisystemic bacterial disease characterized by diarrhea, malabsorption, fever, and polyarthritis. Ocular manifestations occur very rarely. Previous reports have suggested that the use of immunosuppressive drugs appears to accelerate or exacerbate the clinical course of Whipple's disease; however, the illness has yet to be reported in the setting of transplantation. Herein, we describe what we believe is the first reported case of Whipple's disease after transplantation. The patient is a 51-year-old woman who developed progressive visual floaters and blurring of vision 30 years after living-related kidney transplantation for an autosomal-dominant polycystic kidney disease. Her allograft was functioning well on maintenance immunosuppressive therapy with azathioprine and prednisone when she developed visual abnormalities. Transient weight loss, gastrointestinal symptoms, and migratory polyarthralgia predated the onset of ocular disease by several years. The diagnosis of Whipple's bilateral vitreitis and chorioretinitis was confirmed by polymerase chain reaction analysis demonstrating Tropheryma whipplei nucleic acid in vitreous fluid and peripheral blood sample as well as by demonstration of the bacilli by cytopathology. Intraocular vancomycin, intravenous ceftriaxone, and prolonged course of oral trimethoprim-sulfamethoxazole therapy led to clinical improvement and recovery of visual acuity.


The reducing incidence of respiratory tract infection and its relation to antibiotic prescribing.
There is good evidence of reduced prescribing of antibiotics in recent years, but the reason for this has not been established. To study the incidence of respiratory tract infections presenting to general practitioners (GPs) in England and Wales in relation to the incidence of other infections and to the prescription of antibiotics. Sentinel practices in England and Wales who contribute to the Weekly Returns Service (WRS) of the Royal College of General Practitioners. Time-series analysis of disease incidence data reported by the practices and of antibiotic prescription data from the Prescription Pricing Authority (PPA) during the years 1994-2000. Incidence data reported weekly from 73 practices in England and Wales, serving a population of 600,000, for acute respiratory tract infections, otitis media, infectious mononucleosis, shingles, urinary tract infections, and skin infections, were consolidated into quarterly datasets and examined graphically for evidence of secular and seasonal trends. Trends in antibiotic prescription items (data for England only were supplied by the PPA) were examined for association after adjustment for seasonal variation. The incidence of respiratory tract infections and antibiotic prescribing showed virtually identical seasonal variation, with both declining from 1995: respiratory tract infections by 48% in winter and 38% in summer, and antibiotic prescriptions by 34% and 21%, respectively. Trends in both were very highly correlated. The incidence of shingles and skin infections was constant. The incidence of urinary tract infections declined by 10%. The incidence of otitis media in children and acute bronchitis in the elderly followed the all-age trend in the reduction of respiratory tract infections. The considerable reduction in the incidence of respiratory tract infections between 1995 and 2000 is the main reason for the decline in antibiotic prescribing rather than changing prescribing thresholds for antibiotics.


Sleep-related breathing disorders in amyotrophic lateral sclerosis.
Sleep-related breathing events in patients with amyotrophic lateral sclerosis (ALS) have been reported in small case series, but the association with the clinical presentation--with (B) or without (nonB) bulbar symptoms--or the relevance for prognosis have not been investigated. We retrospectively analyzed sleep studies of 114 (46 nonB) ALS patients, aged 54 +/- 11 years. Respiratory function was better in nonB patients: forced vital capacity was 76 +/- 20% vs 55 +/- 23% in the bulbar group (p < 0.001); PaCO2 41 +/- 5 vs 44 +/- 6 mm Hg p < 0.05. The mean apnea/hypopnea index (AHI) was higher in nonB patients (22 +/- 12 vs 15 +/- 16 events per hour- p < 0.05); in this group 21 out of 46 patients (46%) had more than 20 events/hour versus 14 out of 68 (21%) in the nonB group (p < 0.005). On the contrary the oxygen desaturation index (ODI) was similar (10 +/- 11 vs 9 +/- 12 events per hour, p = NS). Most events had a central genesis and obstructive events were usually erratic, except in 7 patients (6 in group B) who had more than 10 obstructive events/hour. Data were stratified in three groups: with a disease duration below 1 year (< 1 yr), between 1 and 2 years (1-2 yr), and more than 2 years (> 2 yr). The occurrence of sleep-related respiratory disorders decreased with the increase of disease duration (23 +/- 15; 18 +/- 14; and 16 +/- 15 events per hour respectively), the decrease being significantly lower in the > 2 yr group than in the < 1 yr (p < 0.05). Again ODI was similar in the three groups. In conclusion the present study shows that sleep-related breathing events are more common than previously described in ALS patients, particularly in the first year following onset of the disease. Obstructive events occur rarely, although the prevalence of obstructive sleep apnea is higher than predicted, particularly when bulbar symptoms are present. Patients without bulbar signs show a higher prevalence of central events. The progressive decrease of events with the increase of disease duration could be due to a progressive weakness of respiratory muscles, but it could also suggest an independent role for nocturnal events which could be linked to a worse prognosis or to a more rapid decay of clinical status.


Religion and the brain: Jordan Grafman's contributions to religion and brain research and the special case of religious language.
Grafman and colleagues' papers in religion and brain research have documented the extent to which religious beliefs and behaviors are mediated by standard social cognitive networks in brain. Grafman's work however also points beyond treatments of religious cognition as merely a species of more general social cognitive processes. Data emerging from experiments targeting mystical states as well as reports of encounters with supernatural agents during controlled experiments with psychedelics, suggest that brain mediation of mystical encounters with supernatural agents involves both disruption/downregulation of social cognitive networks and activation of an additional as yet only partially identified neural process suggesting that a full neuroscience account of religious beliefs, behaviors and experiences must extend beyond treatment of religion as an ordinary social process.


Defining the ischemic penumbra using magnetic resonance oxygen metabolic index.
Penumbral biomarkers promise to individualize treatment windows in acute ischemic stroke. We used a novel magnetic resonance imaging approach that measures oxygen metabolic index (OMI), a parameter closely related to positron emission tomography-derived cerebral metabolic rate of oxygen utilization (CMRO2), to derive a pair of ischemic thresholds: (1) an irreversible-injury threshold that differentiates ischemic core from penumbra and (2) a reversible-injury threshold that differentiates penumbra from tissue not-at-risk for infarction. Forty patients with acute ischemic stroke underwent magnetic resonance imaging at 3 time points after stroke onset: <4.5 hours (for OMI threshold derivation), 6 hours (to determine reperfusion status), and 1 month (for infarct probability determination). A dynamic susceptibility contrast method measured cerebral blood flow, and an asymmetrical spin echo sequence measured oxygen extraction fraction, to derive OMI (OMI=cerebral blood flow×oxygen extraction fraction). Putative ischemic threshold pairs were iteratively tested using a computation-intensive method to derive infarct probabilities in 3 tissue groups defined by the thresholds (core, penumbra, and not-at-risk tissue). An optimal threshold pair was chosen based on its ability to predict infarction in the core, reperfusion-dependent survival in the penumbra, and survival in not-at-risk tissue. The predictive abilities of the thresholds were then tested within the same cohort using a 10-fold cross-validation method. The optimal OMI ischemic thresholds were found to be 0.28 and 0.42 of normal values in the contralateral hemisphere. Using the 10-fold cross-validation method, median infarct probabilities were 90.6% for core, 89.7% for nonreperfused penumbra, 9.95% for reperfused penumbra, and 6.28% for not-at-risk tissue. OMI thresholds, derived using voxel-based, reperfusion-dependent infarct probabilities, delineated the ischemic penumbra with high predictive ability. These thresholds will require confirmation in an independent patient sample.


Smoking quit rates among patients receiving pharmacist-provided pharmacotherapy and telephonic smoking cessation counseling.
Tobacco use is the nation's leading cause of preventable illness and death, causing a significant burden on the health care system. Many cessation pharmacotherapy treatment options are available to help smokers quit, including nicotine replacement therapies (NRTs) and prescription medications. Research indicates that pharmacists are able to provide a positive benefit to smokers who want to quit through pharmacologic and nonpharmacologic interventions. The aim of the present work was to examine the quit rates among participants who received smoking cessation pharmacotherapy and pharmacist-provided telephone-based quit counseling services. Retrospective database review of enrolled participants. Telephone-based pharmacotherapy and medication counseling services offered from a medication management center. State employees who voluntarily contacted a medication management center for smoking cessation services after receiving promotional flyers. Long-term quit rates at 7 and 13 months were determined by means of patient self-report in response to questioning. Smoking cessation was considered to be a success if the patient reported not smoking for the past 30 days. A total of 238 participants were included in the review. Thirty-nine participants completed the program after the first treatment, 12 participants after the second treatment, and 4 participants after the third treatment. Two patients completed the program more than once. Eighty-five participants (36%) reported results at 7-month follow-up; of these, 43 (51%) were smoking free. A total of 44 participants (18%) reported results at 13-month follow-up; of these, 24 participants (55%) reported being smoking free. There were no significant differences in the percentages of smoking-free participants at 7 or 13 months, regardless of their first treatment (P = 0.06 and 0.345, respectively). Successful quit rates were higher than previously demonstrated with other telephone-based smoking cessation programs. Therefore, pharmacist-provided telephone-based counseling may be beneficial in helping patients to quit smoking. Future research is warranted to examine the benefits of these types of programs.


A rational approach to nutritional assessment.
Consensus regarding definitions of malnutrition and methods to assess nutritional state is lacking. We propose a definition and its operationalization. A definition was formulated on the basis of the pathophysiology of malnutrition, while reviewing the metabolic and physiological characteristics of different populations, considered to be malnourished. The definition was operationalized to yield measures to perform nutritional assessment. Malnutrition was defined as "a subacute or chronic state of nutrition in which a combination of varying degrees of over- or undernutrition and inflammatory activity has led to a change in body composition and diminished function". Its operationalization led to four elements that may serve as the basis of nutritional assessment: (1) measurement of nutrient balance, (2) measurement of body composition, (3) measurement of inflammatory activity, and (4) measurement of muscle, immune and cognitive function. Most elements measured should be validated with gold standards; normal values should be obtained in different populations. Values obtained in people considered to be at nutritional risk should be related to outcome. A definition is proposed that reflects the pathophysiology of malnutrition and that, when operationalized, will lead to measures reflecting this pathophysiology. Such an approach may yield comparable and reproducible rates and degrees of malnutrition in populations as well as in individuals.


A novel tongue implant for tongue advancement for obstructive sleep apnea: feasibility, safety and histology in a canine model.
Obstructive sleep apnea (OSA) is a sleep related breathing disorder caused by partial or complete collapse of the upper airway during sleep. The disease is linked with important cardiovascular and cerebrovascular morbidity and mortality. Tongue base collapse is a major cause of upper airway occlusion in OSA and present surgical procedures to prevent this are invasive and inefficient. A novel implantable system to stabilize the tongue was evaluated in a canine model for feasibility, safety and histology. Successful implantation of the Advance System was performed in 21 canines and follow-up evaluations were performed at 30, 60, 90, 120 and 150 days. No technical or clinical adverse events were seen during the procedure. Minor clinical adverse events at some of the follow-up evaluations were treated successfully. Histologic evaluation of the implant was performed at different time points during follow-up and showed good biocompatibility, stability and osteointegration. The outcome of this study resulted in an implant for adjustable tongue advancement in humans with OSA.


Deregulation of VEGFR-2 and PDGFR Expression and Microvascular Density in a Triple-Negative Model of Canine Malignant Mammary Tumors with Lymph Node or Lung Metastasis.
Canine mammary tumors (CMT) represent the most common cancer in noncastrated female dogs. Interestingly, triple-negative tumors are the most common molecular subtype in female dogs. In this study, we proposed to evaluate the expression of vascular endothelial growth factor receptor 2 (VEGFR-2), Platelet-derived growth factor receptor (PDGFR), and microvascular density (MVD) in a group of metastatic and nonmetastatic triple-negative CMT and compare the expression based on clinical parameters. Twenty-six female dogs with triple-negative mammary tumors were divided into three groups: nonmetastatic tumors (NMT) (n = 11), tumors with lymph node metastasis (LNM) (n = 10), and tumors with lung metastasis (LM) (n = 5). We observed increased VEGFR-2 expression in LNM compared with NMT and a positive correlation between tumor grade and VEGFR-2 expression. A positive correlation was noted between VEGFR-2 and PDGFR expression. Regarding microvascular density (MVD), we identified a higher number of vessels in primary tumors with lymph node metastasis and lung metastasis compared with tumors with no metastasis. The primary tumors with lung metastasis exhibited an increased MVD compared with carcinoma with lymph node metastasis. Overall, our results suggest a deregulation of VEGFR-2 and PDGFR and high MVD in metastatic tumors, indicating a role for angiogenesis in tumor progression.


Irrelevant learned reward associations disrupt voluntary spatial attention.
Attention can be guided involuntarily by physical salience and by non-salient, previously learned reward associations that are currently task-irrelevant. Attention can be guided voluntarily by current goals and expectations. The current study examined, in two experiments, whether irrelevant reward associations could disrupt current, goal-driven, voluntary attention. In a letter-search task, attention was directed voluntarily (i.e., cued) on half the trials by a cue stimulus indicating the hemifield in which the target letter would appear with 100 % accuracy. On the other half of the trials, a cue stimulus was presented, but it did not provide information about the target hemifield (i.e., uncued). On both cued and uncued trials, attention could be involuntarily captured by the presence of a task-irrelevant, and physically non-salient, color, either within the cued or the uncued hemifield. Importantly, one week prior to the letter search task, the irrelevant color had served as a target feature that was predictive of reward in a separate training task. Target identification accuracy was better on cued compared to uncued trials. However, this effect was reduced when the irrelevant, and physically non-salient, reward-associated feature was present in the uncued hemifield. This effect was not observed in a second, control experiment in which the irrelevant color was not predictive of reward during training. Our results indicate that involuntary, value-driven capture can disrupt the voluntary control of spatial attention.


[Airway resistance in dialysis patients].
The oscillatory resistance to respiration ROS is not significantly influenced by the process of dialysis and thus does not allow a conclusion to a possible predialytic increase of the extravascular pulmonary water. The body-plethysmographically determined resistance of the respiratory tract Rt shows homogeneous behaviour. A functionally intact respiratory system is of vital importance for the patient with renal insufficiency.


Development of a versatile enrichment analysis tool reveals associations between the maternal brain and mental health disorders, including autism.
A recent study of lateral septum (LS) suggested a large number of autism-related genes with altered expression in the postpartum state. However, formally testing the findings for enrichment of autism-associated genes proved to be problematic with existing software. Many gene-disease association databases have been curated which are not currently incorporated in popular, full-featured enrichment tools, and the use of custom gene lists in these programs can be difficult to perform and interpret. As a simple alternative, we have developed the Modular Single-set Enrichment Test (MSET), a minimal tool that enables one to easily evaluate expression data for enrichment of any conceivable gene list of interest. The MSET approach was validated by testing several publicly available expression data sets for expected enrichment in areas of autism, attention deficit hyperactivity disorder (ADHD), and arthritis. Using nine independent, unique autism gene lists extracted from association databases and two recent publications, a striking consensus of enrichment was detected within gene expression changes in LS of postpartum mice. A network of 160 autism-related genes was identified, representing developmental processes such as synaptic plasticity, neuronal morphogenesis, and differentiation. Additionally, maternal LS displayed enrichment for genes associated with bipolar disorder, schizophrenia, ADHD, and depression. The transition to motherhood includes the most fundamental social bonding event in mammals and features naturally occurring changes in sociability. Some individuals with autism, schizophrenia, or other mental health disorders exhibit impaired social traits. Genes involved in these deficits may also contribute to elevated sociability in the maternal brain. To date, this is the first study to show a significant, quantitative link between the maternal brain and mental health disorders using large scale gene expression data. Thus, the postpartum brain may provide a novel and promising platform for understanding the complex genetics of improved sociability that may have direct relevance for multiple psychiatric illnesses. This study also provides an important new tool that fills a critical analysis gap and makes evaluation of enrichment using any database of interest possible with an emphasis on ease of use and methodological transparency.


The Effect of Prenatal Yoga on Pregnancy-Related Symptoms: A Pilot Quasi-Experimental Study.
In the last decade, yoga has attracted much attention from researchers. Although there are many studies on yoga, research on the effect of prenatal yoga on pregnancy-related symptoms is limited. This study aimed to determine the effect of prenatal yoga on pregnancy-related symptoms. The study was conducted at antenatal care services between June 2018 and October 2018 in Turkey. Simple random method was used to assign participants to the study arms. The yoga group attended a prenatal yoga program for 60 min once a week for 4 weeks. The control group received routine care. Data were collected before and after the intervention using the Descriptive Characteristics Form and Pregnancy Symptoms Inventory. Data analysis used descriptive statistics (mean, standard deviation/standard error, and percentages), χ2, Mann-Whitney, and Wilcoxon tests. Significance was set at p < 0.05. The study was completed with 70 participants (the yoga group: 35; the control group: 35). The yoga group had a significantly lower posttest Pregnancy Symptoms Inventory Symptom Frequency Total Score than the pretest score (38.42 ± 18.76 vs. 32.77 ± 16.55, p < 0.05). The total score of the yoga group's gastrointestinal, respiratory, and mental health symptoms was reduced after the intervention (respectively, 6.74 ± 4.32 vs. 5.31 ± 3.38; 1.48 ± 1.26 vs. 1.05 ± 1.13; 7.08 ± 4.59 vs. 5.22 ± 3.48, p < 0.05). The yoga group had significantly lower mental health symptom scores than the control group (5.22 ± 3.48 vs. 7.34 ± 4.02, p < 0.05). There was no significant difference between the control group's pretest and posttest Pregnancy Symptoms Inventory Symptom Frequency Scores. Pregnancy-related symptoms were significantly reduced in the yoga group. It is thought that prenatal yoga may be effective on pregnancy-related symptoms. Yoga can be recommended to cope with pregnancy-related symptoms and support activities of daily living.


The role of rotation-vibration coupling in symmetric and asymmetric isotopomers of ozone.
A theoretical framework and a computer code (SpectrumSDT) are developed for accurate calculations of coupled rotational-vibrational states in triatomic molecules using hyper-spherical coordinates and taking into account the Coriolis coupling effect. Concise final formulas are derived for the construction of the Hamiltonian matrix using an efficient combination of the variational basis representation and discrete variable representation methods with locally optimized basis sets and grids. First, the new code is tested by comparing its results with those of the APH3D program of Kendrick et al. [Kendrick, Pack, Walker, and Hayes, J. Chem. Phys. 110, 6673 (1999)]. Then, accurate calculations of the rovibrational spectra are carried out for doubly substituted symmetric (18O16O18O) and asymmetric (18O18O16O) ozone isotopomers for the total angular momentum up to J = 5. Together with similar data recently reported for the singly substituted symmetric (16O18O16O) and asymmetric (16O16O18O) ozone isotopomers, these calculations quantify the role of the Coriolis coupling effect in the large mass-independent isotopic enrichment of ozone, observed in both laboratory experiments and the atmosphere of the Earth. It is found that the Coriolis effect in ozone is relatively small, as evidenced by deviations of its rotational constants from the symmetric-top-rotor behavior, magnitudes of parity splittings (Λ-doubling), and ratios of rovibrational partition functions for asymmetric vs symmetric ozone molecules. It is concluded that all of these characteristics are influenced by the isotopic masses as much as they are influenced by the overall symmetry of the molecule. It is therefore unlikely that the Coriolis coupling effect could be responsible for symmetry-driven mass-independent fractionation of oxygen isotopes in ozone.


Diffusion-weighted imaging in Huntington's disease.
Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder that results from an expanded trinucleotide (CAG) repeat on the huntingtin gene. Neurodegeneration in HD affects most prominently the basal ganglia. Therefore, diffusivity was obtained in the basal ganglia and thalamus of 29 patients with early HD and 27 healthy volunteers by means of the trace of the diffusion tensor (Trace(D)). Putaminal, caudate, pallidal, and thalamic Trace(D) values were increased in patients with HD compared with controls. Increased diffusivity in the putamen and caudate nucleus correlated with global functional impairment, CAG repeat length, as well as bicaudate ratio. Diffusion-weighted imaging appears to be a promising surrogate marker for disease severity in HD. Sensitivity to change remains to be established longitudinally.


Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network.
Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, is characterized by chronic pain in the pelvic region or genitalia that is often accompanied by urinary frequency and urgency. Despite considerable research, no definite aetiological risk factors or effective treatments have been identified. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network uses a novel integrated strategy to characterize UCPPS as a systemic disorder that potentially involves multiple aetiologies. The first phase, MAPP I, included >1,000 participants who completed an intensive baseline assessment followed by a 12-month observational follow-up period. MAPP I studies showed that UCPPS pain and urinary symptoms co-vary, with only moderate correlation, and should be evaluated separately and that symptom flares are common and can differ considerably in intensity, duration and influence on quality of life. Longitudinal clinical changes in UCPPS correlated with structural and functional brain changes, and many patients experienced global multisensory hypersensitivity. Additionally, UCPPS symptom profiles were distinguishable by biological correlates, such as immune factors. These findings indicate that patients with UCPPS have objective phenotypic abnormalities and distinct biological characteristics, providing a new foundation for the study and clinical management of UCPPS.


Assessment of bone mineral density in tenofovir-treated patients with chronic hepatitis B: can the fracture risk assessment tool identify those at greatest risk?
Tenofovir disoproxil fumarate (TDF) is an established nucleotide analogue in the treatment of chronic hepatitis B. Bone mineral density loss has been described in TDF-treated patients with human immunodeficiency virus infection, but limited data exist for patients with chronic hepatitis B. Dual X-ray absorptiometry (DEXA) was used to determine bone mineral density changes in TDF-exposed patients. We evaluated the accuracy of the Fracture Risk Assessment Tool (FRAX) as an alternative to DEXA in clinical practice. A total of 170 patients were studied: 122 were exposed to TDF, and 48 were controls. All patients underwent DEXA, and demographic details were recorded. FRAX scores (before and after DEXA) were calculated. TDF was associated with a lower hip T score (P = .02). On univariate and multivariate analysis, advancing age, smoking, lower body mass index, and TDF exposure were independent predictors of low bone mineral density. In addition, the pre-DEXA FRAX score was an accurate predictor of the post-DEXA FRAX treatment recommendation (100% sensitivity and 83% specificity), area under the curve 0.93 (95% CI, .87-.97, P < .001). TDF-treated patients with chronic hepatitis B have reduced bone mineral density, but the reduction is limited to 1 anatomical site. Age and advanced liver disease are additional contributing factors, underlining the importance of multifactorial fracture risk assessment. FRAX can accurately identify those at greatest risk of osteoporotic fracture.


Immunologic aspects of monoclonal B-cell lymphocytosis.
Monoclonal B-cell lymphocytosis (MBL) is a preclinical hematologic condition wherein small numbers of clonal B cells can be detected in the blood of otherwise healthy individuals. Most MBL have a surface immunophenotype nearly identical to that of chronic lymphocytic leukemia (CLL), though other phenotypes can also be identified. MBL has been shown to be a precursor state for CLL, but most MBL clones are quite small and apparently have minimal potential to progress of CLL or other B-cell lymphoproliferative disorder (B-LPD). The investigation of MBL as a precursor state for CLL will likely lead to important insights into mechanisms of disease pathogenesis. The review will cover clinical and translational aspects of MBL, with a particular emphasis on the prevalence of MBL; the relationship between MBL, CLL, and other B-LPDs; and the capacity of MBL to modulate the normal B- and T-cell compartments.


Patient-Generated Data Analytics of Health Behaviors of People Living With Type 2 Diabetes: Scoping Review.
Complications due to type 2 diabetes (T2D) can be mitigated through proper self-management that can positively change health behaviors. Technological tools are available to help people living with, or at risk of developing, T2D to manage their condition, and such tools provide a large repository of patient-generated health data (PGHD). Analytics can provide insights into the health behaviors of people living with T2D. The aim of this review is to investigate what can be learned about the health behaviors of those living with, or at risk of developing, T2D through analytics from PGHD. A scoping review using the Arksey and O'Malley framework was conducted in which a comprehensive search of the literature was conducted by 2 reviewers. In all, 3 electronic databases (PubMed, IEEE Xplore, and ACM Digital Library) were searched using keywords associated with diabetes, behaviors, and analytics. Several rounds of screening using predetermined inclusion and exclusion criteria were conducted, after which studies were selected. Critical examination took place through a descriptive-analytical narrative method, and data extracted from the studies were classified into thematic categories. These categories reflect the findings of this study as per our objective. We identified 43 studies that met the inclusion criteria for this review. Although 70% (30/43) of the studies examined PGHD independently, 30% (13/43) combined PGHD with other data sources. Most of these studies used machine learning algorithms to perform their analysis. The themes identified through this review include predicting diabetes or obesity, deriving factors that contribute to diabetes or obesity, obtaining insights from social media or web-based forums, predicting glycemia, improving adherence and outcomes, analyzing sedentary behaviors, deriving behavior patterns, discovering clinical correlations from behaviors, and developing design principles. The increased volume and availability of PGHD have the potential to derive analytical insights into the health behaviors of people living with T2D. From the literature, we determined that analytics can predict outcomes and identify granular behavior patterns from PGHD. This review determined the broad range of insights that can be examined through PGHD, which constitutes a unique source of data for these applications that would not be possible through the use of other data sources.


Miniaturized extinction culturing is the preferred strategy for rapid isolation of fast-growing methane-oxidizing bacteria.
Methane-oxidizing bacteria (MOB) have a large potential as a microbial sink for the greenhouse gas methane as well as for biotechnological purposes. However, their application in biotechnology has so far been hampered, in part due to the relative slow growth rate of the available strains. To enable the availability of novel strains, this study compares the isolation of MOB by conventional dilution plating with miniaturized extinction culturing, both performed after an initial enrichment step. The extinction approach rendered 22 MOB isolates from four environmental samples, while no MOB could be isolated by plating. In most cases, extinction culturing immediately yielded MOB monocultures making laborious purification redundant. Both type I (Methylomonas spp.) and type II (Methylosinus sp.) MOB were isolated. The isolated methanotrophic diversity represented at least 11 different strains and several novel species based on 16S rRNA gene sequence dissimilarity. These strains possessed the particulate (100%) and soluble (64%) methane monooxygenase gene. Also, 73% of the strains could be linked to a highly active fast-growing mixed MOB community. In conclusion, miniaturized extinction culturing was more efficient in rapidly isolating numerous MOB requiring little effort and fewer materials, compared with the more widely applied plating procedure. This miniaturized approach allowed straightforward isolation and could be very useful for subsequent screening of desired characteristics, in view of their future biotechnological potential.


Adherence to cardiovascular medications in the South Asian population: A systematic review of current evidence and future directions.
To review methods of assessing adherence and strategies to improve adherence to cardiovascular disease (CVD) medications, among South Asian CVD patients. We conducted a systematic review of English language studies that examined CVD medication adherence in South Asian populations from 1966 to April 1, 2015 in SCOPUS and PubMed. Working in duplicate, we identified 61 studies. After exclusions, 26 studies were selected for full text review. Of these, 17 studies were included in the final review. We abstracted data on several factors including study design, study population, method of assessing adherence and adherence rate. These studies were conducted in India (n = 11), Pakistan (n = 3), Bangladesh (n = 1), Nepal (n = 1) and Sri Lanka (n = 1). Adherence rates ranged from 32%-95% across studies. Of the 17 total publications included, 10 focused on assessing adherence to CVD medications and 7 focused on assessing the impact of interventions on medication adherence. The validated Morisky Medication Adherence Scale (MMAS) was used as the primary method of assessing adherence in five studies. Three studies used validated questionnaires similar to the MMAS, and one study utilized Medication Event Monitoring System caps, with the remainder of the studies utilizing pill count and self-report measures. As expected, studies using non-validated self-report measures described higher rates of adherence than studies using validated scale measurements and pill count. The included intervention studies examined the use of polypill therapy, provider education and patient counseling to improve medication adherence. The overall medication adherence rates were low in the region, which suggest a growing need for future interventions to improve adherence.


Enterogenic metabolomics signatures of depression: what are the possibilities for the future.
An increasing number of studies indicate that the microbiota-gut-brain axis is an important pathway involved in the onset and progression of depression. The responses of the organism (or its microorganisms) to external cues cannot be separated from a key intermediate element: their metabolites. In recent years, with the rapid development of metabolomics, an increasing amount of metabolites has been detected and studied, especially the gut metabolites. Nevertheless, the increasing amount of metabolites described has not been reflected in a better understanding of their functions and metabolic pathways. Moreover, our knowledge of the biological interactions among metabolites is also incomplete, which limits further studies on the connections between the microbial-entero-brain axis and depression. This paper summarizes the current knowledge on depression-related metabolites and their involvement in the onset and progression of this disease. More importantly, this paper summarized metabolites from the intestine, and defined them as enterogenic metabolites, to further clarify the function of intestinal metabolites and their biochemical cross-talk, providing theoretical support and new research directions for the prevention and treatment of depression.


Oxycodone protects cardiac microvascular endothelial cells against ischemia/reperfusion injury by binding to Sigma-1 Receptor.
Endothelial dysfunction is an important mechanism involved in myocardial ischemia-reperfusion (I/R) injury. We aimed to explore the effects of Oxycodone on myocardial I/R injury in vivo and in vitro to reveal its mechanisms related to Sigma-1 Receptor (SIGMAR1). A rat model of I/R-induced myocardial injury was developed. The ischemic area and myocardial histopathological changes after oxycodone addition were evaluated by TTC staining and H&E staining. LDH, CK-MB and cTnI levels were used to assess myocardial function. Then, the endothelial integrity was reflected by the expressions of ZO-1, Claudin-1 and Occludin. Afterward, ELISA, RT-qPCR, western blot and immunofluorescence assays were adopted for the detection of inflammation-related genes. SIGMAR1 expression in myocardial tissues induced by I/R and cardiac microvascular endothelial cells (CMECs) under hypoxic/reoxygenation (H/R) was determined using RT-qPCR and western blotting. Subsequently, after SIGMAR1 silencing or BD1047 addition (a SIGMAR1 antagonist), cell apoptosis and endothelial integrity were analyzed in the presence of Oxycodone in H/R-stimulated CMECs. Results indicated that Oxycodone decreased the ischemic area and improved myocardial function in myocardial I/R injury rat. Oxycodone improved myocardial histopathological injury and elevated endothelial integrity, evidenced by upregulated ZO-1, Claudin-1 and Occludin expressions. Moreover, inflammatory response was alleviated after Oxycodone administration. Molecular docking suggested that SIGMAR1 could directly bind to Oxycodone. Oxycodone elevated SIGMAR1 expression and SIGMAR1 deletion or BD1047 addition attenuated the impacts of Oxycodone on apoptosis and endothelial integrity of CMECs induced by H/R. Collectively, Oxycodone alleviates myocardial I/R injury in vivo and in vitro by binding to SIGMAR1.


Prognosis for patients with cognitive motor dissociation identified by brain-computer interface.
Cognitive motor dissociation describes a subset of patients with disorders of consciousness who show neuroimaging evidence of consciousness but no detectable command-following behaviours. Although essential for family counselling, decision-making, and the design of rehabilitation programmes, the prognosis for patients with cognitive motor dissociation remains under-investigated. The current study included 78 patients with disorders of consciousness who showed no detectable command-following behaviours. These patients included 45 patients with unresponsive wakefulness syndrome and 33 patients in a minimally conscious state, as diagnosed using the Coma Recovery Scale-Revised. Each patient underwent an EEG-based brain-computer interface experiment, in which he or she was instructed to perform an item-selection task (i.e. select a photograph or a number from two candidates). Patients who achieved statistically significant brain-computer interface accuracies were identified as cognitive motor dissociation. Two evaluations using the Coma Recovery Scale-Revised, one before the experiment and the other 3 months later, were carried out to measure the patients' behavioural improvements. Among the 78 patients with disorders of consciousness, our results showed that within the unresponsive wakefulness syndrome patient group, 15 of 18 patients with cognitive motor dissociation (83.33%) regained consciousness, while only five of the other 27 unresponsive wakefulness syndrome patients without significant brain-computer interface accuracies (18.52%) regained consciousness. Furthermore, within the minimally conscious state patient group, 14 of 16 patients with cognitive motor dissociation (87.5%) showed improvements in their Coma Recovery Scale-Revised scores, whereas only four of the other 17 minimally conscious state patients without significant brain-computer interface accuracies (23.53%) had improved Coma Recovery Scale-Revised scores. Our results suggest that patients with cognitive motor dissociation have a better outcome than other patients. Our findings extend current knowledge of the prognosis for patients with cognitive motor dissociation and have important implications for brain-computer interface-based clinical diagnosis and prognosis for patients with disorders of consciousness.


Spatial Lipidomics of EPSPS and PAT Transgenic and Non-Transgenic Soybean Seeds Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging.
Herbicide-resistant soybeans are among the most widely planted transgenic crops. The in situ evaluation of spatial lipidomics in transgenic and non-transgenic soybeans is important for directly assessing the unintended effects of exogenous gene introduction. In this study, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI)-based non-targeted analytical strategies were used for the first time for in situ detection and imaging of endogenous lipid distributions in transgenic (EPSPS and PAT genes) herbicide-resistant soybean (Glycine max Merrill) (S4003.14) and non-transgenic soybean (JACK) seeds. Statistical analysis revealed significant differences in lipids between S4003.14 and JACK seeds. The variable importance of projection analysis further revealed that 18 identified lipids, including six phosphatidylcholines (PCs), four phosphatidylethanolamines (PEs), five triacylglycerols (TAGs), and three cytidine diphosphate-diacylglycerols (CDP-DAGs), had the strongest differential expression between S4003.14 and JACK seeds. Among those, the upregulated expressions of PC(P-36:1), PC(36:2), PC(P-36:0), PC(37:5), PE(40:2), TAG(52:1), TAG(55:5), and CDP-DAG(37:2) and the downregulated expressions of PC (36:1), TAG(43:0), and three PEs (i.e., PE(P-38:1), PE(P-38:0), and PE(P-40:3)) were successfully found in the S4003.14 seeds, compared to these lipids detected in the JACK seeds. Meanwhile, the lipids of PC (44:8), CDP-DAG(38:0), and CDP-DAG(42:0) were uniquely detected in the S4003.14 soybean seeds, and TAG(45:2) and TAG(57:10) were detected as the unique lipids in the JACK seeds. The heterogeneous distribution of these lipids in the soybean seeds was also clearly visualized using MALDI-MSI. MSI results showed that lipid expression was significantly up/downregulated in S4003.14 seeds, compared to that in JACK seeds. This study improves our understanding of the unintended effects of herbicide-resistant EPSPS and PAT gene transfers on spatial lipidomes in soybean seeds and enables the continued progression of MALDI-MSI as an emerging, reliable, and rapid molecular imaging tool for evaluating unintended effects in transgenic plants.


Structures and function of a tailoring oxidase in complex with a nonribosomal peptide synthetase module.
Nonribosomal peptide synthetases (NRPSs) are large modular enzymes that synthesize secondary metabolites and natural product therapeutics. Most NRPS biosynthetic pathways include an NRPS and additional proteins that introduce chemical modifications before, during or after assembly-line synthesis. The bacillamide biosynthetic pathway is a common, three-protein system, with a decarboxylase that prepares an NRPS substrate, an NRPS, and an oxidase. Here, the pathway is reconstituted in vitro. The oxidase is shown to perform dehydrogenation of the thiazoline in the peptide intermediate while it is covalently attached to the NRPS, as the penultimate step in bacillamide D synthesis. Structural analysis of the oxidase reveals a dimeric, two-lobed architecture with a remnant RiPP recognition element and a dramatic wrapping loop. The oxidase forms a stable complex with the NRPS and dimerizes it. We visualized co-complexes of the oxidase bound to the elongation module of the NRPS using X-ray crystallography and cryo-EM. The three active sites (for adenylation, condensation/cyclization, and oxidation) form an elegant arc to facilitate substrate delivery. The structures enabled a proof-of-principle bioengineering experiment in which the BmdC oxidase domain is embedded into the NRPS.


Fueling the engine: induction of AMP-activated protein kinase in trout skeletal muscle by swimming.
AMP-activated protein kinase (AMPK) is well known to be induced by exercise and to mediate important metabolic changes in the skeletal muscle of mammals. Despite the physiological importance of exercise as a modulator of energy use by locomotory muscle, the regulation of this enzyme by swimming has not been investigated in fish. We found that sustained swimming (40 days at 0.75 body lengths s(-1)) increased AMPK activity in red and white trout skeletal muscle (3.9- and 2.2-fold, respectively) as well as the expression of AMPK target genes involved in energy use: lipoprotein lipase and citrate synthase in red and white muscle and CPT1β1b and PGC-1α in red muscle. Furthermore, electrical pulse stimulation of cultured trout myotubes increased AMPK activity and glucose uptake (1.9- and 1.2-fold, respectively) in an AMPK-dependent manner. These results suggest that AMPK may play an important mediatory role in the metabolic adaptation to swimming in fish skeletal muscle.


Comparative Characteristics of the 2009 Pandemic Influenza A (H1N1) Virus and 2010-2011 Seasonal Influenza in Pediatric Patients.
In March 2009 the pandemic influenza A (H1N1) strain was identified. The disease initially appeared to be accompanied by complications and high mortality rates. It became an endemic virus during the influenza season in our region, along with the classical seasonal H3N2. To identify the burden of pandemic influenza, its effect in pediatric patients, and complicated hospitalizations, compared to seasonal influenza years after the pandemic. A retrospective observational study was conducted at a tertiary hospital. Data were collected from the medical records of all children who were hospitalized from April 2009 to 2011 with laboratory-confirmed influenza. Of 191 patients with influenza, 100 had the 2009 pandemic influenza, 62 had seasonal influenza, and 29 had H1N1 in 2010-2011. Patients with the 2009 H1N1 were characterized by older age, more co-morbidity conditions and more symptoms including fever, cough and rhinitis on admission. No significant differences in outcomes between the groups were recorded. Of patients hospitalized with pandemic influenza in 2009, 28% had complicated hospitalizations, compared with 17.7% of patients hospitalized with seasonal influenza in 2010-11. Children with pandemic influenza received more oseltamivir (Tamiflu®) (94% vs. 19.4%, P < 0.001) and more antibiotics than the other groups. The type of influenza had no effect on outcome. There were no significant differences between groups in the percentages of in-hospital mortality, admission to intensive care units, prolonged hospitalization (> 9 days), or the development of complications during hospitalization.


Surgical Treatment for Recurrent Benign Paroxysmal Positional Vertigo.
Introduction Benign paroxysmal positional vertigo is a generally benign condition that responds to repositioning maneuvers and frequently resolves spontaneously. However, for some patients it can become a disabling condition in which surgery must be considered. Two different surgical techniques exist, singular neurectomy and posterior semicircular canal occlusion. Objective The objective of this study is to review the current status of singular nerve section and posterior semicircular canal occlusion as treatments for intractable benign paroxysmal positional vertigo, and to determine if there are published data available that favors one over the other. Data Sources MEDLINE and OLDMEDLINE databases of the National Library of Medicine. Data Synthesis Four studies regarding singular neurectomy and 14 reports on semicircular canal occlusion were analyzed. Both techniques are reported to provide similar symptomatic benefit, with low risk of hearing loss and balance impairment. However, anatomical and clinical studies of singular neurectomy show it to be a more challenging technique, and considering that it is indicated in a very small number of cases, it may be difficult to master. Conclusions Both singular neurectomy and semicircular canal occlusion can be safe and effective in those few patients that require surgery for intractable positional vertigo. Although semicircular canal occlusion requires a postauricular transmastoid approach, it is ultimately easier to learn and perform adequately, and thus may be considered the best alternative.


Myeloid lineage cells evince distinct steady-state level of certain gene groups in dependence on hereditary angioedema severity.
Hereditary angioedema (HAE) is a rare genetic disorder with variable expressivity even in carriers of the same underlying genetic defect, suggesting other genetic and epigenetic factors participate in modifying HAE severity. Recent knowledge indicates the role of immune cells in several aspects of HAE pathogenesis, which makes monocytes and macrophages candidates to mediate these effects. Here we combined a search for HAE phenotype modifying gene variants with the characterization of selected genes' mRNA levels in monocyte and macrophages in a symptom-free period. While no such gene variant was found to be associated with a more severe or milder disease, patients revealed a higher number of dysregulated genes and their expression profile was significantly altered, which was typically manifested by changes in individual gene expression or by strengthened or weakened relations in mutually co-expressed gene groups, depending on HAE severity. SERPING1 showed decreased expression in HAE-C1INH patients, but this effect was significant only in patients carrying mutations supposedly activating nonsense-mediated decay. Pro-inflammatory CXC chemokine superfamily members CXCL8, 10 and 11 were downregulated, while other genes such as FCGR1A, or long non-coding RNA NEAT1 were upregulated in patients. Co-expression within some gene groups (such as an NF-kappaB function related group) was strengthened in patients with a severe and/or mild course compared to controls. All these findings show that transcript levels in myeloid cells achieve different activation or depression levels in HAE-C1INH patients than in healthy controls and/or based on disease severity and could participate in determining the HAE phenotype.


Endothelium-derived Cdk5 deficit aggravates air pollution-induced peripheral vasoconstriction through AT1R upregulation.
PM2.5 infiltrates into circulation and increases the risk of systemic vascular dysfunction. As the first-line barrier against external stimuli, the molecular mechanism of the biological response of vascular endothelial cells to PM2.5 exposure remains unclear. In this study, 4-week-old mice were exposed to Hangzhou 'real' airborne PM2.5 for 2 months and were found to display bronchial and alveolar damage. Importantly, in the present study, we have demonstrated that Cdk5 deficit induced peripheral vasoconstriction through angiotensin II type 1 receptor under angiotensin II stimulation in Cdh5-cre;Cdk5f/n mice. In the brain, Cdk5 deficit increased the myogenic activity in the medullary arterioles under external pressure. On the other hand, no changes in cerebral blood flow and behavior patterns were observed in the Cdh5-cre;Cdk5f/n mice exposed to PM2.5. Therefore, our current findings indicate that CDK5 plays an important role in endothelium cell growth, migration, and molecular transduction, which is also a sensor for the response of vascular endothelial cells to PM2.5.


Development of Metacognition in Adolescence: The Congruency-Based Metacognition Scale.
Previous studies on metacognitive ability were explored using self-report questionnaires that are difficult to adequately measure and evaluate when the capacity for self-reference is undeveloped. This study aimed to validate the Congruency-based Metacognition Scale (CMS) to measure metacognition and the feeling of confidence abilities and to investigate the development of metacognition during adolescence. The CMS was administered to 633 child-parent pairs in Japan (child, mean age = 16.0 years, 46.0% female; parent, mean age = 48.3 years, 94.9% mother). The CMS metacognition score was assessed based on congruency scores between the self-report of the child from a third-person perspective (3PP) and the parent's report from the first-person perspective (1PP). The CMS self-judgment accuracy score was assessed by the congruency scores between the children's self-report from the 1PP and 3PP. For both measures, the more distant the 3PP on the self-report was from the 1PP on the parent's report and child self-report means low ability. An exploratory factor analysis (EFA) was conducted to examine construct validity and then a confirmatory factor analysis (CFA) was used. Criterion validity was examined by calculating Pearson's correlation coefficients with scores on the Beck Cognitive Insight Scale (BCIS) and Autism Quotient (AQ). We used intraclass correlation and Cronbach's alpha to examine the test-retest and internal consistency reliability. Based on the results of the EFA and CFA, we adopted one factor structure with five items. The CMS metacognition and CMS self-judgment accuracy showed evidence criterion validity, exhibiting significant correlations with the BCIS self-reflectiveness (r = 0.16) and self-certainty scores (r = 0.17), respectively. Regarding to the AQ, only the CMS metacognition score had significant correlations with the social skills (r = 0.22) and total scale score (r = 0.20). The test-retest reliability showed adequate (intraclass correlation coefficient 0.70-0.81 and the Cronbach's alpha coefficient 0.63-0.59). Adolescents were found to have significantly lower metacognitive ability compared to young adults. CMS could be a valid and reliable measure to examine metacognitive abilities for adolescents.


[Clinical picture and diagnostic criteria of multiple system atrophy].
In 2013, European MSA Study Group demonstrated the prospective natural history of MSA. This study was greatly useful for better patients' management and future development of disease-modifying therapy. Although the diagnosis of early symptomatic stage is also an important factor for successful outcome of disease-modifying therapy, current diagnostic criteria for MSA, which has focused on the combination of motor and autonomic manifestations cannot diagnose MSA patients showing isolated autonomic failure in the early course of illness. We presented four premotor MSA patients who had sudden death prior to fulfilling the diagnostic criteria. 4 cases had very mild OPC and SN pathology, but significant autonomic system involvement including the intermediolateral nucleus, Onuf's nucleus, and medullary autonomic nucleus. Contrary, Petrovic et al reported four pathologically proven MSA patients with disease duration of 15 years or more. All patients presented isolated parkinsonism for a long time and mean duration from onset to dysautonomia was 9 years. Novel diagnostic biomarkers, which have a potential for evaluation of the component of glial cytoplasmic inclusion such as alpha-synuclein radiotracer and serum and CSF alpha-synuclein levels may be a key way to support the diagnosis of patients at the stage of "mono system atrophy".