A finite element model for predicting the distribution of drugs delivered intracranially to the brain.
Drug therapy to the central nervous system is complicated by the presence of the blood-brain barrier. The development of new drug delivery techniques to overcome this obstacle will be aided by a clear understanding of the transport processes in the brain. A rigorous theoretical framework of the transport of drugs delivered locally to the parenchyma has been developed using the finite element method. Magnetic resonance imaging has been used to track the transport of paramagnetic contrast markers in the brain. The information obtained by postprocessing spin-echo, T1-weighted, and proton density images has been used to refine the mathematical model that includes realistic brain geometry and salient anatomic features and allows for two-dimensional transport of chemical species, including both diffusive and convective contributions. In addition, the effects of regional differences in tissue properties, ventricular boundary, and edema on the transport have been considered. The model has been used to predict transport of interleukin-2 in the brain and study the major determinants of transport, at both early and late times after drug delivery.


Nonvalue of sputum culture in the management of lower respiratory tract infections.
Establishment of the microbiological etiology of bacterial pneumonia by sputum culture is confounded by both lack of recovery of fastidious pathogens and contamination of specimens with oropharyngeal flora. We reviewed the clinical records from 249 patients over a 3-month period for evidence of pneumonia. Gram staining and cultures were performed on 381 specimens isolated from this population of patients. Recovery of respiratory tract pathogens was accomplished with 354 specimens from 226 patients; 27 specimens yielded normal flora in culture but were smear positive. An additional 256 specimens submitted to our microbiology laboratory did not meet smear criteria for purulence nor did they yield respiratory tract pathogens in culture. A total of 637 specimens submitted to the microbiology laboratory were evaluated for sputum purulence by the criteria of Bartlett. Of the total 354 specimens which were positive in culture for a pathogen, 182 (52%) were submitted from 150 patients with no objective evidence of pneumonia. The majority of specimens obtained from patients without pneumonia were nonpurulent. However, 71 of 182 culture-positive specimens obtained from 50 patients without pneumonia were purulent. Approximately half of these patients (31 of 50) had other pulmonary or upper respiratory tract pathology which could account for the sputum purulence. Among the 172 culture-positive specimens from 76 patients with pneumonia, only 100 (58%) were acceptable by smear criteria. An additional 23 patients provided expectorated purulent sputum from which no respiratory tract pathogen could be isolated. Of these 23, 7 had pneumonia. We conclude that sputum culture and Gram staining are neither specific nor sensitive as diagnostic tools. Objective criteria for purulence of Gram-stained specimens must be applied before their inoculation into culture media. Specimens should be sought only from patients with objective evidence of pneumonia.


Extinction blunts paraventricular thalamic contributions to heroin relapse.
Here, we use optogenetics and chemogenetics to investigate the contribution of the paraventricular thalamus (PVT) to nucleus accumbens (NAc) pathway in aversion and heroin relapse in two different heroin self-administration models in rats. In one model, rats undergo forced abstinence in the home cage prior to relapse testing, and in the other, they undergo extinction training, a procedure that is likened to cognitive behavioral therapy. We find that the PVT→NAc pathway is both sufficient and necessary to drive aversion and heroin seeking after abstinence, but not extinction. The ability of extinction to reduce this pathway's contribution to heroin relapse is accompanied by a loss of synaptic plasticity in PVT inputs onto a specific subset of NAc neurons. Thus, extinction may exert therapeutic reductions in opioid seeking by altering synaptic plasticity within the PVT→NAc pathway, resulting in reduced aversion during opioid withdrawal as well as reduced relapse propensity.


Nursing diagnoses of culturally diverse patients.
As the world's people become more mobile and the record number of refugees seek new homes, nurses are being increasingly faced with the caring of people from a culture different than their own. More than ever, there is a need for nursing care planned around unique cultural healthcare beliefs, values and practices of patients. However, incorporating cross-cultural defining characteristics into nursing diagnoses has been slow and difficult, the main reason being that nursing diagnoses are built into a classification system based on "labelling" which is "unintentionally culturally insensitive and may even stereotype clients." To help nurses in caring for culturally diverse patients, additions suggested to the classification system of nursing diagnoses are given below.


[Mental Health Risks Among Managers - Results of a Qualitative Study and Implications for Stress Prevention].
Research on mental health shows that, compared to employees, managers have a high risk for exhaustion, fatigue, and sleep disturbances. However, the origins and the progress of psychological complaints among managers have not been systematically evaluated to date. Based on a work and health psychological research model, the present study aims to identify health-related risk and protective factors. 15 interviews with managers working on different management levels and economic sectors were conducted. Categories of the contents of transcribed interviews were developed. All managers reported psychological complaints, i. e. irritation, detachment problems, exhaustion, fatigue and sleep disturbances. However, a minority of them suffered chronic health problems. Whether psychological complaints persisted and became chronic or not, was associated with several conditions, among others managers' health-related risk perception and self-efficacy, recovery experiences as well as the health culture in the company. The findings indicate the need for specific prevention strategies. Especially, managers and companies must further increase their awareness for the mental health risks associated with leadership activities.


Bioactive glycans in a microbiome-directed food for malnourished children.
Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Designing effective microbiome-directed therapeutic foods to repair these perturbations requires knowledge about how food components interact with the microbiome to alter its expressed functions. Here we use biospecimens from a randomized, controlled trial of a microbiome-directed complementary food prototype (MDCF-2) that produced superior rates of weight gain compared to a conventional ready-to-use supplementary food (RUSF) in 12-18-month-old Bangladeshi children with moderate acute malnutrition (MAM)4. We reconstructed 1000 bacterial genomes (metagenome-assembled genomes, MAGs) present in their fecal microbiomes, identified 75 whose abundances were positively associated with weight gain (change in weight-for-length Z score, WLZ), characterized gene expression changes in these MAGs as a function of treatment type and WLZ response, and used mass spectrometry to quantify carbohydrate structures in MDCF-2 and feces. The results reveal treatment-induced changes in expression of carbohydrate metabolic pathways in WLZ-associated MAGs. Comparing participants consuming MDCF-2 versus RUSF, and MDCF-2-treated children in the upper versus lower quartiles of WLZ responses revealed that two Prevotella copri MAGs positively associated with WLZ were principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilization of its component glycans. Moreover, the predicted specificities of carbohydrate active enzymes expressed by polysaccharide utilization loci (PULs) in these two MAGs correlate with the (i) in vitro growth of Bangladeshi P. copri strains, possessing differing degrees of PUL and overall genomic content similarity to these MAGs, cultured in defined medium containing different purified glycans representative of those in MDCF-2, and (ii) levels of carbohydrate structures identified in feces from clinical trial participants. In the accompanying paper5, we use a gnotobiotic mouse model colonized with age- and WLZ-associated bacterial taxa cultured from this study population, and fed diets resembling those consumed by study participants, to directly test the relationship between P. copri, MDCF-2 glycan metabolism, host ponderal growth responses, and intestinal gene expression and metabolism. The ability to identify bioactive glycan structures in MDCFs that are metabolized by growth-associated bacterial taxa will help guide recommendations about use of this MDCF for children with acute malnutrition representing different geographic locales and ages, as well as enable development of bioequivalent, or more efficacious, formulations composed of culturally acceptable and affordable ingredients.


Rupture of the uterus in labor. A review of 96 cases.
Ninety-six cases of ruptured uterus in labor treated in the University Teaching Hospitals, Benghazi, Libya between 1977 and 1980 are reported. An incidence of 1 in 585 deliveries remained unchanged during the period of study. Twenty uterine ruptures occurred in a previously scarred uterus. Rupture of the unscarred uterus is a more catastrophic event. There is a marked difference in both fetal and maternal outcome between the group with a previously scarred uterus and the group without a previous scar. The incidence and causes of uterine rupture in Libya differ greatly from those in developed countries. High parity is a frequent cause. Other common etiological factors were cephalopelvic disproportion, fetal malpresentation, oxytocin stimulation of labor and unwise obstetrical interference. The fetal wastage was high, a perinatal mortality of 75% being recorded, but 95% of the mothers were saved. Hysterectomy was commonly performed in this group. Repair of the uterus and sterilization should only be performed when the rupture is simple and transverse in the lower segment and without any sign of infection.


Effect of antifungal agents, lysozyme and human antimicrobial peptide LL-37 on clinical Candida isolates with high biofilm production.
Introduction. Candida species can form biofilms on tissues and medical devices, making them less susceptible to antifungal agents.Hypothesis/Gap Statement. Antifungal combination may be an effective strategy to fight against Candida biofilm.Aim. In this study, we investigated the in vitro activity of fluconazole, caspofungin and amphotericin B, alone and in combination, against 17 clinical Candida tropicalis and 6 Candida parapsilosis isolates with high biofilm formation. We also tested LL-37 and lysozyme for anti-biofilm activity against a selected C. tropicalis isolate.Methodology. Candida biofilms were prepared using the 96-well plate-based method. The minimum biofilm eradication concentrations were determined for single and combined antifungal drugs. The activity of LL-37 and lysozyme was determined by visual reading for planktonic cells and using the XTT assay for biofilms.Results. Under biofilm conditions, fluconazole plus caspofungin showed synergistic effects against 60.9% (14 of 23) of the tested isolates, including 70.6% of C. tropicalis [fractional inhibitory concentration index (FICI), 0.26-1.03] and 33.3% of C. parapsilosis (FICI, 0.04-2.03) isolates. Using this combination, no antagonism was observed. Amphotericin B plus caspofungin showed no effects against 78.3% (18 of 23) of the tested isolates. Amphotericin B plus fluconazole showed no effects against 65.2% (15 of 23) of the tested isolates and may have led to antagonism against 2 C. tropicalis and 2 C. parapsilosis isolates. LL-37 and lysozyme had no effect on biofilms of the selected C. tropicalis isolate.Conclusions. We found that fluconazole plus caspofungin led to a synergistic effect against C. tropicalis and C. parapsilosis biofilms. The efficacy of the antifungal combination therapies of the proposed schemes against biofilm-associated Candida infections requires careful and constant evaluation.


Long-term culture of neonatal rat pancreatic endocrine cells as model for insulin-secretion and ion-channel studies.
So far, only freshly isolated cells or short-term cultures have been used to study ion-channel activity in pancreatic nontumor beta-cells. We report a procedure for the long-term cultivation of pancreatic endocrine cells to study the relationship between ion channels and insulin secretion. Using thimerosal to suppress fibroblastoid cell proliferation and a preliminary 2-day cell exposure to alternating normal (5.6 mM) and high (16.7 mM) glucose levels, we observed a significant secretory responsiveness of the cells to a glucose challenge for at least 4 wk in culture. Cells also responded to glucose or other secretagogues, such as quinine and the sulfonylurea glyburide, with membrane voltage oscillations. In the cell-attached configuration of the patch-clamp technique, a 65-pS-conductance K+ channel was observed, which was inhibited by glucose, quinine, and glyburide. In the inside-out configuration, the activity of this channel was suppressed by ATP applied to the cytoplasmic side of the membrane. A K+ channel with a conductance of 200 pS was also observed, which was activated by intracellular Ca2+. A 13-pS-conductance glucose-insensitive K+ channel was present in both cell-attached and inside-out patch recordings. Even after 3 wk, the characteristics of these currents and channels were comparable to those reported by other investigators with freshly dissociated or short-term-cultured beta-cells from neonatal and adult rats and adult mice. Therefore, the neonatal rat endocrine cell culture characterized herein provides an improved model for long-term investigations combining secretion and electrophysiological studies.


Incorporation of ultraviolet (UV) absorbing nanoparticles in contact lenses for Class 1 UV blocking.
Accumulated UV exposure over long durations could be a contributory factor for ocular complications including cataracts and retinal damage. UV blocking contact lenses offer excellent protection, however, only a few commercial UV blocking contact lenses are available. Thus there is a need to develop new approaches for imparting UV blocking to contact lenses. We incorporate highly UV absorbing nanoparticles into hydroxyethylmethacrylate (HEMA) and silicone hydrogels by polymerizing a mixture of monomers and nanoparticles. The nanoparticles are prepared by thermal free radical polymerization of an emulsion of hydrophobic UV absorbing components that contain a polymerizable vinyl group. The particle size is controlled to be less than 100 nm to minimize the scattering of visible light. The nanoparticles disperse well in the HEMA monomer leading to fully transparent gels with excellent UV blocking. The particle suspension does not disperse in the silicone-hydrogel formulations necessitating dialysis to reduce the surfactant concentration. The silicone-hydrogels loaded with the particles are excellent UV blockers but the transparency in the visible range is only about 60%. SEM imaging of the particle loaded gels show that the microstructure of the gels depend on the rate of polymerization, with a rapid rate leading to a more uniform distribution of the particles. UV blocking from the particle loaded gels is not impacted by processing such as autoclaving. Also UV exposure does not degrade UV absorption and the particles are retained in the lens during storage. Incorporation of nanoparticles into contact lenses by the addition of the polymerization mixture followed by curing is a promising approach for imparting UV protection to contact lenses.


Power Doppler sonography to differentiate tuberculous cervical lymphadenopathy from nasopharyngeal carcinoma.
Tuberculous lymphadenitis and metastatic nodes from nasopharyngeal carcinoma are common in Asians and are often indistinguishable clinically. Because their treatment depends on prompt diagnosis, we undertook this study to evaluate if power Doppler sonography could distinguish these two pathologic abnormalities. The intranodal vascular appearances of tuberculous neck nodes are compared with benign reactive neck nodes and metastatic nodes from nasopharyngeal carcinoma. The appearances of power Doppler sonograms of 42 tuberculous nodes were compared with 28 metastatic nodes from nasopharyngeal carcinoma and 27 benign reactive nodes. The intranodal distribution of vessels and the intranodal vascular resistance of vessels were compared among these three groups. All examinations were performed by the same sonologist (A.A.), who had more than 3 years' scanning experience, and all data analysis was performed by the same investigator (M.Y.). The intranodal vascular distribution in tuberculous nodes was varied and simulated both benign and malignant disease. Avascularity of nodes and displacement of hilar vascularity were frequent in tuberculous nodes. Metastatic nodes from nasopharyngeal carcinoma (resistive index [RI], 0.81+/-0.09; pulsatile index [PI], 1.91+/-0.81) had a higher vascular resistance than did tuberculous nodes (RI, 0.71+/-0.11; PI, 1.34+/-0.55). Tuberculous nodes had a higher vascular resistance than did reactive nodes (RI, 0.66+/-0.09; PI, 1.10+/-0.26). Avascularity, displaced hilar vessels, and low intranodal vascular resistance are clues that may suggest the tuberculous nature of neck nodes. However, there is overlap of appearance between tuberculous nodes, benign reactive neck nodes, and metastatic nodes. Thus, histologic analysis is often required for a definitive diagnosis.


Effectiveness of guided and unguided low-intensity internet interventions for adult alcohol misuse: a meta-analysis.
Alcohol misuse ranks within the top ten health conditions with the highest global burden of disease. Low-intensity, Internet interventions for curbing adult alcohol misuse have been shown effective. Few meta-analyses have been carried out, however, and they have involved small numbers of studies, lacked indicators of drinking within low risk guidelines, and examined the effectiveness of unguided self-help only. We therefore conducted a more thorough meta-analysis that included both guided and unguided interventions. Systematic literature searches were performed up to September 2013. Primary outcome was the mean level of alcohol consumption and drinking within low risk guidelines for alcohol consumption at post-treatment. We selected 16 randomised controlled trials (with 23 comparisons and 5,612 participants) for inclusion. Results, showed a small but significant overall effect size in favour of Internet interventions (g = 0.20, 95% CI: 0.13-0.27, p<.001). Participants in Internet interventions drunk on average 22 grams of ethanol less than controls and were significantly more likely to be adhering to low-risk drinking guidelines at post-treatment (RD 0.13, 95% CI: 0.09-0.17, p<.001). Subgroup analyses revealed no significant differences in potential moderators for the outcome of alcohol consumption, although there was a near-significant difference between comparisons with waitlist control and those with assessment-only or alcohol information control conditions (p = .056). Internet interventions are effective in reducing adult alcohol consumption and inducing alcohol users to adhere to guidelines for low-risk drinking. This effect is small but from a public health point of view this may warrant large scale implementation at low cost of Internet interventions for adult alcohol misuse. Moderator analyses with sufficient power are, however, needed in order to assess the robustness of these overall results and to assess whether these interventions may impact on subgroups with different levels of success.


[Precipitation reactions between secretory products in amphibian oviducts].
The existence of precipitin reactions between some molecules in egg jellies (oviduct secretions) of tailed amphibians (Amphibia caudata) has been demonstrated by double diffusion on agarose plates. These reactions do not exist in frogs and toads (Amphibia salientia). One precipitin reaction was related to compounds with a common molecular site of interaction for all A. caudata: all cross-species reactions were possible; a common antigenic rate has been shown. Another precipitin reaction, positively demonstrated in Pleurodeles waltl, probably exists in other A. caudata. The putative influence of these reactions on egg jelly-spermatozoon interactions has been discussed. An homology between these intra-egg jelly reactions and cortical granule content-egg jelly reactions in A. salientia has been suggested.


Neostigmine methylsulfate delays gastric emptying of particulate markers in horses.
Eight horses were allotted to 2 groups, each of 4 horses. All horses were given 100 plastic markers intragastrically via a nasogastric tube. One group of animals (control group) was not given medication after marker administration. The other group (test group) was given neostigmine methylsulfate (0.022 mg/kg of body weight) in the subcutaneous tissue at the time of marker administration and 30, 60, and 90 minutes later. All horses were killed 135 minutes after marker administration to locate the beads in the gastrointestinal tract. Gastric emptying of the markers was significantly delayed (P less than 0.05) in horses given neostigmine methylsulfate.


Lighting conditions used during visual shade matching in private dental offices.
To our knowledge, no data are available on the actual lighting that is used for visual shade matching in private dental offices. The purpose of this study was to determine the shade matching practices and interest in continuing education in dental practices and to determine the quantity and quality of the ambient lighting used during visual shade matching in a sample cohort of dentists in private practices. Thirty-two private practices were enrolled, and each completed a 1-page survey on the clinic's shade matching practices. A spectrophotometer was used to measure the ambient lighting in each practice, collecting data on color temperature (Kelvin), color rendering index (CRI), and light intensity (foot candles/fc). A 2-sided nonparametric sign test was used to compare the true median color temperature with the standard (5500°K). A 1-sided t test was used to compare the CRI with the standard (CRI >90) (α=.05 for all statistical analyses). All dental practitioners surveyed used mainly visual shade matching in their practices. Of those, 87.5% showed interest in attending continuing education on this topic, with 56.3% preferring a clinical demonstration course. The mean color temperature was 4152.9°K and was significantly different from the standard 5500°K (P<.001). The 1-sided t test indicated that the mean CRI was less than 90 (P=1). The 95% confidence interval for the intensity was 80.7 to 111.6 fc. The ambient light in the majority of the 32 dental private practices measured was not ideal for visual shade matching.


Risk factors for reflux esophagitis after eradication of Helicobacter pylori.
Objective: While there is an association between successful eradication of Helicobacter pylori (HP) and reflux esophagitis (RE), risk factors associated with RE remain obscure. The aim of this study is to determine risk factors associated with the development of RE after HP eradication.Materials and methods: Among all patients treated with successful HP eradication from 2008 to 2016, we retrospectively analyzed those who were free from RE at initial esophagogastroduodenoscopy (EGD) and who were followed up with EGD after eradication. Patients were classified according to the presence or absence of RE at the follow-up EGD. RE was defined as mucosal breaks proximal to the squamous-columnar junction. Demographic data, underlying diseases, medications and endoscopic findings at the initial EGD were compared between patients with and without RE.Results: Among 1575 patients, 142 (9.0%) had RE at the follow-up EGD. The time interval from HP eradication until EGD ranged from 4 to 24 months. The endoscopic grade of RE was higher in males than in females. Multivariate analysis revealed that male sex (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.24), body mass index ≥25 kg/m2 (OR, 2.91; 95% CI, 2.00-4.22), use of calcium channel blockers (OR, 1.70; 95% CI, 1.12-2.55), and hiatal hernia (OR, 3.46; 95% CI, 2.41-5.00) were associated with the development of RE.Conclusions: Calcium channel blocker use was found to be a risk factor for the development of RE after eradication of HP.


Spreading depolarizations in ischaemia after subarachnoid haemorrhage, a diagnostic phase III study.
Focal brain damage after aneurysmal subarachnoid haemorrhage predominantly results from intracerebral haemorrhage, and early and delayed cerebral ischaemia. The prospective, observational, multicentre, cohort, diagnostic phase III trial, DISCHARGE-1, primarily investigated whether the peak total spreading depolarization-induced depression duration of a recording day during delayed neuromonitoring (delayed depression duration) indicates delayed ipsilateral infarction. Consecutive patients (n = 205) who required neurosurgery were enrolled in six university hospitals from September 2009 to April 2018. Subdural electrodes for electrocorticography were implanted. Participants were excluded on the basis of exclusion criteria, technical problems in data quality, missing neuroimages or patient withdrawal (n = 25). Evaluators were blinded to other measures. Longitudinal MRI, and CT studies if clinically indicated, revealed that 162/180 patients developed focal brain damage during the first 2 weeks. During 4.5 years of cumulative recording, 6777 spreading depolarizations occurred in 161/180 patients and 238 electrographic seizures in 14/180. Ten patients died early; 90/170 developed delayed infarction ipsilateral to the electrodes. Primary objective was to investigate whether a 60-min delayed depression duration cut-off in a 24-h window predicts delayed infarction with >0.60 sensitivity and >0.80 specificity, and to estimate a new cut-off. The 60-min cut-off was too short. Sensitivity was sufficient [= 0.76 (95% confidence interval: 0.65-0.84), P = 0.0014] but specificity was 0.59 (0.47-0.70), i.e. <0.80 (P < 0.0001). Nevertheless, the area under the receiver operating characteristic (AUROC) curve of delayed depression duration was 0.76 (0.69-0.83, P < 0.0001) for delayed infarction and 0.88 (0.81-0.94, P < 0.0001) for delayed ischaemia (reversible delayed neurological deficit or infarction). In secondary analysis, a new 180-min cut-off indicated delayed infarction with a targeted 0.62 sensitivity and 0.83 specificity. In awake patients, the AUROC curve of delayed depression duration was 0.84 (0.70-0.97, P = 0.001) and the prespecified 60-min cut-off showed 0.71 sensitivity and 0.82 specificity for reversible neurological deficits. In multivariate analysis, delayed depression duration (β = 0.474, P < 0.001), delayed median Glasgow Coma Score (β = -0.201, P = 0.005) and peak transcranial Doppler (β = 0.169, P = 0.016) explained 35% of variance in delayed infarction. Another key finding was that spreading depolarization-variables were included in every multiple regression model of early, delayed and total brain damage, patient outcome and death, strongly suggesting that they are an independent biomarker of progressive brain injury. While the 60-min cut-off of cumulative depression in a 24-h window indicated reversible delayed neurological deficit, only a 180-min cut-off indicated new infarction with >0.60 sensitivity and >0.80 specificity. Although spontaneous resolution of the neurological deficit is still possible, we recommend initiating rescue treatment at the 60-min rather than the 180-min cut-off if progression of injury to infarction is to be prevented.


A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1.
The human mind and body respond to stress, a state of perceived threat to homeostasis, by activating the sympathetic nervous system and secreting the catecholamines adrenaline and noradrenaline in the 'fight-or-flight' response. The stress response is generally transient because its accompanying effects (for example, immunosuppression, growth inhibition and enhanced catabolism) can be harmful in the long term. When chronic, the stress response can be associated with disease symptoms such as peptic ulcers or cardiovascular disorders, and epidemiological studies strongly indicate that chronic stress leads to DNA damage. This stress-induced DNA damage may promote ageing, tumorigenesis, neuropsychiatric conditions and miscarriages. However, the mechanisms by which these DNA-damage events occur in response to stress are unknown. The stress hormone adrenaline stimulates β(2)-adrenoreceptors that are expressed throughout the body, including in germline cells and zygotic embryos. Activated β(2)-adrenoreceptors promote Gs-protein-dependent activation of protein kinase A (PKA), followed by the recruitment of β-arrestins, which desensitize G-protein signalling and function as signal transducers in their own right. Here we elucidate a molecular mechanism by which β-adrenergic catecholamines, acting through both Gs-PKA and β-arrestin-mediated signalling pathways, trigger DNA damage and suppress p53 levels respectively, thus synergistically leading to the accumulation of DNA damage. In mice and in human cell lines, β-arrestin-1 (ARRB1), activated via β(2)-adrenoreceptors, facilitates AKT-mediated activation of MDM2 and also promotes MDM2 binding to, and degradation of, p53, by acting as a molecular scaffold. Catecholamine-induced DNA damage is abrogated in Arrb1-knockout (Arrb1(-/-)) mice, which show preserved p53 levels in both the thymus, an organ that responds prominently to acute or chronic stress, and in the testes, in which paternal stress may affect the offspring's genome. Our results highlight the emerging role of ARRB1 as an E3-ligase adaptor in the nucleus, and reveal how DNA damage may accumulate in response to chronic stress.


[Syndrome of brain compression in cranio-cerebral trauma].
The work presents the data of complex clinical investigation and treatment of 371 patients with the syndrome of brain compression of traumatic etiology. Valid indications for using differentiated operative interventions have been developed and results of treatment of patients with intracranial hematomas, depressed fractures of the cranial bones inducing the symptoms of brain compression have been analyzed.


Laparoscopic radical trachelectomy or parametrectomy and pelvic and para-aortic lymphadenectomy for cervical or vaginal stump carcinoma: report of six cases.
The aim of this study was to investigate the feasibility and safety of laparoscopic radical parametrectomy and pelvic and para-aortic lymphadenectomy after previous supracervical or extrafascial hysterectomy. This is a prospective study of six patients with vaginal or cervical stump carcinoma after previous supracervical or extrafascial hysterectomy. The technique of radical parametrectomy with pelvic and para-aortic lymphadenectomy as used for open surgical cases for years was performed laparoscopically. The average operating time was 180 min, the estimated average blood loss was 220 mL, and the duration of hospitalization was 11.8 days. There was no intraoperative or postoperative complication. Laparoscopic radical parametrectomy with pelvic and para-aortic lymphadenectomy for cervical or vaginal stump carcinoma can be successfully and safely accomplished.


An interactive web application for the dissemination of human systems immunology data.
Systems immunology approaches have proven invaluable in translational research settings. The current rate at which large-scale datasets are generated presents unique challenges and opportunities. Mining aggregates of these datasets could accelerate the pace of discovery, but new solutions are needed to integrate the heterogeneous data types with the contextual information that is necessary for interpretation. In addition, enabling tools and technologies facilitating investigators' interaction with large-scale datasets must be developed in order to promote insight and foster knowledge discovery. State of the art application programming was employed to develop an interactive web application for browsing and visualizing large and complex datasets. A collection of human immune transcriptome datasets were loaded alongside contextual information about the samples. We provide a resource enabling interactive query and navigation of transcriptome datasets relevant to human immunology research. Detailed information about studies and samples are displayed dynamically; if desired the associated data can be downloaded. Custom interactive visualizations of the data can be shared via email or social media. This application can be used to browse context-rich systems-scale data within and across systems immunology studies. This resource is publicly available online at [Gene Expression Browser Landing Page ( https://gxb.benaroyaresearch.org/dm3/landing.gsp )]. The source code is also available openly [Gene Expression Browser Source Code ( https://github.com/BenaroyaResearch/gxbrowser )]. We have developed a data browsing and visualization application capable of navigating increasingly large and complex datasets generated in the context of immunological studies. This intuitive tool ensures that, whether taken individually or as a whole, such datasets generated at great effort and expense remain interpretable and a ready source of insight for years to come.


Abnormal bone remodeling in patients with spontaneous painful vertebral fracture.
The application of tetracycline-based iliac bone histomorphometry to the study of the pathogenesis of osteoporosis has given conflicting results. Accordingly, we performed this procedure in 78 postmenopausal white women with one or more vertebral fractures identified according to rigorous criteria that excluded other causes of vertebral deformity and 66 healthy postmenopausal white women recruited from the same geographic region; the groups did not differ in age or weight. In each subject, measurements were made separately on the cancellous (Cn), endocortical (Ec), and intracortical (Ct) subdivisions of the endosteal envelope. In the fracture patients, osteoblast surface was reduced substantially on each subdivision, most markedly on the Cn surface, where about 25% of the deficit was in cuboidal (type II) osteoblasts, suggesting impaired recruitment; the remaining 75% of the deficit was in intermediate (type III) cells, suggesting earlier transition from type III to type IV (flat) cells. On the Ec and Ct surfaces, the deficit was exclusively in type III cells. Mean bone formation rate was reduced by about 18% on the Cn but not on the Ec or Ct surfaces. The deficit was more significant in subjects matched for Cn BV/TV when adjusted for the inverse regression on osteocyte density and after logarithmic transformation. The difference in bone formation rate resulted from a corresponding reduction in wall thickness without a change in activation frequency. The frequency distribution of bone formation rate was more skewed to the left in the fracture patients than in the controls. Osteoclast surface was significantly lower on each subdivision. The variation in osteoblast surface, bone formation rate, and osteoclast surface was significantly greater in the fracture patients than in the controls, with more abnormally low and abnormally high values. The data suggest the following conclusions: (1) The histologic heterogeneity of postmenopausal osteoporosis is reaffirmed; (2) the different subdivisions of the endosteal envelope, although in continuity, behave differently in health and disease; (3) a combination of defective osteoblast recruitment and premature osteoblast apoptosis would account for the deficit in type II and III cells and the reductions in wall thickness and bone formation rate on the Cn surface and the previously reported osteocyte deficiency in Cn bone; (4) premature disaggregation of multinuclear to mononuclear resorbing cells could account for the osteoclast deficit; and (5) some patients with vertebral fracture have one or another disorder of bone remodeling that at present cannot be identified by noninvasive means.


Risk of daytime transmission of malaria in the French Guiana rain forest.
Between 2008 and 2014, there were 1070 malaria cases reported in French Guiana among members of the armed forces. Most of the malaria outbreaks investigated were multifactorial and followed missions conducted at illegal gold mining sites. For example, a malaria outbreak occurred in September 2013, three weeks after the deployment of 15 soldiers at Dagobert, which is such a site. The attack rate was 53%, with seven Plasmodium vivax infections and one coinfection with both Plasmodium vivax and Plasmodium falciparum. Two months later, an entomological investigation in the field caught 321 anopheles by the human landing catch method. Among them, 282 were Anopheles darlingi. One specimen was PCR-positive for P. vivax, for an infection rate of 0.4% (1/282). In 15.7% of these cases, the An. darlingi was caught during the day. The existence of daytime biting activity by An. darlingi in the Guianese forest might play a key role in malaria outbreaks among military personnel. This finding requires that the Army Health Service adapt its recommendations concerning malaria prevention in French Guiana.


Antibacterial Properties of Citric Acid/β-Alanine Carbon Dots against Gram-Negative Bacteria.
While multi-drug resistance in bacteria is an emerging concern in public health, using carbon dots (CDs) as a new source of antimicrobial activity is gaining popularity due to their antimicrobial and non-toxic properties. Here we prepared carbon dots from citric acid and β-alanine and demonstrated their ability to inhibit the growth of diverse groups of Gram-negative bacteria, including E. coli, Salmonella, Pseudomonas, Agrobacterium, and Pectobacterium species. Carbon dots were prepared using a one-pot, three-minute synthesis process in a commercial microwave oven (700 W). The antibacterial activity of these CDs was studied using the well-diffusion method, and their minimal inhibitory concentration was determined by exposing bacterial cells for 20 h to different concentrations of CDs ranging from 0.5 to 10 mg/mL. Our finding indicates that these CDs can be an effective alternative to commercially available antibiotics. We also demonstrated the minimum incubation time required for complete inhibition of bacterial growth, which varied depending on bacterial species. With 15-min incubation time, A. tumefaciens and P. aeruginosa were the most sensitive strains, whereas E. coli and S. enterica were the most resistant bacterial strains requiring over 20 h incubation with CDs.


A model for population growth of laboratory animals subjected to marker-assisted introgression: how many animals do we need?
This study provides methods for calculating the mean and variance of the number of animals with the desired genotype in each backcross generation for a marker-assisted introgression experiment. The ultimate goal is to produce animals which are homozygous for the desired loci. The methods have been developed specifically for experiments with inbred lines. The model assumes a Poisson distribution for litter size, and is similar to that used in stochastic versions of population dynamics models. Certain biological parameters must be specified as well as parameters under the control of the breeder. These methods can be utilized in designing an experiment to determine the number of founder animals required, given the number of animals required at the completion of the backcross process and vice versa. Consideration is given to minimizing the total amount of genotyping over the entire experiment, by varying the number of times each backcrossed male is used. In addition, an outline is given for an adaptive design that allows for changes in male usage to be made during the experiment.


Modulation of cytokine release and neutrophil function by granulocyte colony-stimulating factor during endotoxemia in humans.
In this double-blind, cross-over, placebo-controlled, randomized study, two groups of eight healthy male volunteers were challenged with endotoxin (4 ng/kg) on two occasions, once in conjunction with placebo and once with granulocyte colony-stimulating factor (G-CSF; 5 microg/kg). In group 1, G-CSF was administered intravenously 2 hours before endotoxin challenge; in group 2, G-CSF was administered subcutaneously 24 hours before endotoxin challenge. In group 1, G-CSF significantly enhanced the release of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, IL-1 receptor antagonist (IL-1ra), and soluble TNF receptors. In group 2, G-CSF significantly reduced IL-8 concentrations and modestly attenuated TNF and IL-6 levels. In this group, IL-1ra and soluble TNF receptors were enhanced by G-CSF pretreatment and lipopolysaccharide (LPS)-induced soluble TNF receptor release was further augmented, whereas LPS-induced IL-1ra concentrations remained unaltered. Both pretreatments with G-CSF increased LPS-induced peripheral neutrophilia; the expression of CD11b, CD18, and CD67; and the release of elastase and lactoferrin. Both pretreatments also down-regulated neutrophil L-selectin expression and prevented the endotoxin-induced pulmonary neutrophil accumulation during the first 2 hours after endotoxin challenge. These data indicate that two different pretreatments with G-CSF result in differential effects on LPS-induced cytokine release but similar effects on LPS-induced neutrophil activation and changes in expression of cell surface molecules. Finally, regardless of the effects of G-CSF on LPS-induced cytokine release, G-CSF blocks LPS-induced pulmonary granulocyte accumulation.


A simple technique to characterize proximal and peripheral nitric oxide exchange using constant flow exhalations and an axial diffusion model.
The most common technique employed to describe pulmonary gas exchange of nitric oxide (NO) combines multiple constant flow exhalations with a two-compartment model (2CM) that neglects 1) the trumpet shape (increasing surface area per unit volume) of the airway tree and 2) gas phase axial diffusion of NO. However, recent evidence suggests that these features of the lungs are important determinants of NO exchange. The goal of this study is to present an algorithm that characterizes NO exchange using multiple constant flow exhalations and a model that considers the trumpet shape of the airway tree and axial diffusion (model TMAD). Solution of the diffusion equation for the TMAD for exhalation flows >100 ml/s can be reduced to the same linear relationship between the NO elimination rate and the flow; however, the interpretation of the slope and the intercept depend on the model. We tested the TMAD in healthy subjects (n = 8) using commonly used and easily performed exhalation flows (100, 150, 200, and 250 ml/s). Compared with the 2CM, estimates (mean +/- SD) from the TMAD for the maximum airway flux are statistically higher (J'aw(NO) = 770 +/- 470 compared with 440 +/- 270 pl/s), whereas estimates for the steady-state alveolar concentration are statistically lower (CA(NO) = 0.66 +/- 0.98 compared with 1.2 +/- 0.80 parts/billion). Furthermore, CA(NO) from the TMAD is not different from zero. We conclude that proximal (airways) NO production is larger than previously predicted with the 2CM and that peripheral (respiratory bronchioles and alveoli) NO is near zero in healthy subjects.


Evaluation of Demographic and Clinical Characteristics of Patients who Attempted Suicide by Self-Inflicted Burn Using Catalyzer.
Our aim was to assess demographic and clinical characteristics of patients treated at our units who attempted suicide by self-incineration, and to compare the results of burns with or without catalyzer use. Twenty patients who attempted suicide by self-incineration were examined in terms of clinical and demographic characteristics. Average age of the study population was 35 years (range 13-85 years). Average percentage of total body surface area burn was 53% (9%-100%). Six (30%) patients used gasoline and 5 (25%) used paint thinner in order to catalyze burning. Of these 11 patients who used a catalyzer, 5 (45.4%) had inhalation injury and 7 (63.6%) died. Among 9 patients who did not use any catalyzer, 1 (11.1%) had inhalation injury and 4 (44.4%) died. In general, inhalation injury was diagnosed in 6 patients (30%) while 11 (55%) patients died. A high morbidity and mortality rate was found in patients who used a catalyzer.


The challenge of timing surgery in a complex case of endocarditis.
While the results of clinical trials are useful in guiding management of the "average" patient, physicians are often left to their own devices when confronted with cases that neither fulfil the entrance criteria for clinical trials nor conveniently match evidence-based guidelines. We present a teaching exercise, built around a complex case of endocarditis, in a branched self-assessment format that challenges the reader's clinical judgement. The case involves a woman aged 45 years with decompensated liver cirrhosis who presents with endocarditis complicated by heart failure and multiple systemic emboli. The risk-to-benefit ratio for urgent surgical intervention tilts as the complications accumulate.


Towards 4D printed scaffolds for tissue engineering: exploiting 3D shape memory polymers to deliver time-controlled stimulus on cultured cells.
Tissue engineering needs innovative solutions to better fit the requirements of a minimally invasive approach, providing at the same time instructive cues to cells. The use of shape memory polyurethane has been investigated by producing 4D scaffolds via additive manufacturing technology. Scaffolds with two different pore network configurations (0/90° and 0/45°) were characterized by dynamic-mechanical analysis. The thermo-mechanical analysis showed a Tg at about 32 °C (Tg = T trans), indicating no influence of the fabrication process on the transition temperature. In addition, shape recovery tests showed a good recovery of the permanent shape for both scaffold configurations. When cells were seeded onto the scaffolds in the temporary shape and the permanent shape was recovered, cells were significantly more elongated after shape recovery. Thus, the mechanical stimulus imparted by shape recovery is able to influence the shape of cells and nuclei. The obtained results indicate that a single mechanical stimulus is sufficient to initiate changes in the morphology of adherent cells.


Case report: GCA like picture-preceding inaugural MOGAD presentation: A patient with a sudden-onset uniocular blindness.
Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) represents a demyelinating neurological syndrome characterized by the presence of serum IgG antibodies directed against myelin oligodendrocyte glycoprotein (MOG-IgG). Concurrently, giant cell arteritis (GCA) constitutes a systemic autoimmune vasculitis. In this case, we describe an elderly female patient who presented with the sudden onset of a severe headache, unilateral blindness, and clinical manifestations resembling those of GCA. Upon conducting a comprehensive analysis of serum antibodies, the diagnosis of MOGAD was established due to the presence of detectable serum MOG-IgG. Subsequently, the patient was administered intravenous methylprednisolone therapy, commencing 27 days after the initial onset of symptoms. It is noteworthy that patients afflicted by MOGAD typically manifest severe visual impairment, which, in many instances, exhibits significant improvement following immunotherapeutic interventions. However, this particular patient did not experience any amelioration in visual function despite glucocorticoid therapy. This unique case illustrates that the clinical presentation resembling GCA may precede the inaugural manifestation of MOGAD. This suggests the possibility of immune-mediated arterial involvement. The significance of glucocorticoid therapy in the context of immune-related diseases warrants further scrutiny, particularly in cases where MOG-IgG screening should be promptly considered.


The factor V Leiden mutation: a possible contributor to the hepatic artery thrombosis encountered after liver transplantation in a child.
A 10-year-old girl has experienced 3 recurrences of hepatic artery thrombosis (HAT) after a liver transplantation. She responded to intraarterial administrations of urokinase after the first 2 attacks. However, the restoration of the arterial flow was not possible after the third attack. The child and her father were both heterozygous for factor V Leiden mutation. In addition to the technical factors, the factor V Leiden mutation should be considered as a factor that plays a role in HAT.


The role of posture in idiopathic oedema.
Idiopathic oedema is a common disorder in women, and is diagnosed by exclusion of known causes of oedema. In 26 of 31 patients studied, the oedema was shown to be orthostatic, i.e. induced by the upright posture and relieved by recumbency. Approximately half of the patients with orthostatic oedema are orthostatic sodium retainers owing to excessive transudation from presumably defecive capillaries with a consequent fall in plasma volume, reduction in glomerular filtration rate and, frequently, excessive renal tubular reabsorption of filtered sodium because of orthostatic hyperaldosteronism. The other patients are orthostatic water retainers, perhaps because of abnormal ADH secretion in the upright posture. Measurement of changes in sodium and water excretion in the recumbent and upright postures are described for the differentiation of these conditions. When conventional diuretic therapy and sodium restriction lose their effectiveness - as often happens after several months - orthostatic sodium retainers may be treated with a combination of the following sympathomimetic amines (dextroamphetamine or ephedrine) to reduce fluid transudation, spironolactone (Aldactone) to promote excretion during recumbency of sodium retained in the upright posture, the use of elastic stockings during the day, and a conventional diuretic together with recumbency from 20h00 most evenings. The last three measures are also useful in orthostatic water retention. Considerable symptomatic improvement can usually be accomplished by these means.


Enhancement of natural killer cytotoxicity by cis-diamminedichloroplatinum (II) in vivo and in vitro.
To investigate the immunomodulating properties of cis-diamminedichloroplatinum (II) (CDDP), we studied the drug's effects on natural killer (NK) lymphocyte cytotoxicity. i.p. injections of CDDP (2-6 mg/kg) into adult mice significantly enhanced cytolysis of YAC-1 and K562 targets mediated by peritoneal and spleen cells. Lysis of the NK-resistant targets P815, EL-4, MOT, and RAJI was not increased, nor was the lysis of a YAC variant which had been specifically rendered resistant to NK lysis. Activated cytotoxicity was first noted 24 h after injection and returned to baseline by 7 days. Although i.p. injection enhanced peritoneal and spleen cell lysis, i.v. injection only activated spleen cells. Two analogues of CDDP, carbo- and iproplatin, effectively enhanced NK activity, but transplatin had no effect. Activated effector cells were non-adherent to nylon wool and serum-coated plates; they co-separated with lymphocytes on Percoll gradients, and they expressed asialo GM1 determinants. Incubation of targets with CDDP for 1 or 18 h significantly increased their sensitivity to lysis by normal murine spleen cells. These data indicate that CDDP has potent effects on NK cytotoxicity.


Expression and function of CXCR7 in the mouse forebrain.
The chemokine CXCL12/CXCR4 signaling system is important for the regulation of neuron migration in the developing forebrain. In particular it is crucial for correct distribution of Cajal-Retzius cells and migration of cortical interneurons. Here we investigated the expression of CXCR7, the second receptor for CXCL12, in comparison to CXCR4. We found that shifts in the expression of both receptors in the above cited cell populations coincide with major changes in their migratory behavior. Furthermore, we demonstrated that postnatally generated olfactory interneuron precursors express CXCR7 but not CXCR4 and that their distribution in the rostral migratory stream is affected by CXCR7 downregulation. This suggests an involvement of CXCR7 in neuronal cell migration and indicates a possible action of CXCR7 independently of CXCR4 as a mediator of CXCL12 signaling.


Mode Profiling of Semiconductor Nanowire Lasers.
We experimentally determine the lasing mode(s) in optically pumped semiconductor nanowire lasers. The spatially resolved and angle-resolved far-field emission profiles of single InP nanowire lasers lying horizontally on a SiO2 substrate are characterized in a microphotoluminescence (μ-PL) setup. The experimentally obtained polarization dependent far-field profiles match very well with numerical simulations and enable unambiguous identification of the lasing mode(s). This technique can be applied to characterize lasing modes in other type of nanolasers that are integrated on a substrate in either vertical or horizontal configurations.


Systematic comparison of different techniques to measure hippocampal subfield volumes in ADNI2.
Subfield-specific measurements provide superior information in the early stages of neurodegenerative diseases compared to global hippocampal measurements. The overall goal was to systematically compare the performance of five representative manual and automated T1 and T2 based subfield labeling techniques in a sub-set of the ADNI2 population. The high resolution T2 weighted hippocampal images (T2-HighRes) and the corresponding T1 images from 106 ADNI2 subjects (41 controls, 57 MCI, 8 AD) were processed as follows. A. T1-based: 1. Freesurfer + Large-Diffeomorphic-Metric-Mapping in combination with shape analysis. 2. FreeSurfer 5.1 subfields using in-vivo atlas. B. T2-HighRes: 1. Model-based subfield segmentation using ex-vivo atlas (FreeSurfer 6.0). 2. T2-based automated multi-atlas segmentation combined with similarity-weighted voting (ASHS). 3. Manual subfield parcellation. Multiple regression analyses were used to calculate effect sizes (ES) for group, amyloid positivity in controls, and associations with cognitive/memory performance for each approach. Subfield volumetry was better than whole hippocampal volumetry for the detection of the mild atrophy differences between controls and MCI (ES: 0.27 vs 0.11). T2-HighRes approaches outperformed T1 approaches for the detection of early stage atrophy (ES: 0.27 vs.0.10), amyloid positivity (ES: 0.11 vs 0.04), and cognitive associations (ES: 0.22 vs 0.19). T2-HighRes subfield approaches outperformed whole hippocampus and T1 subfield approaches. None of the different T2-HghRes methods tested had a clear advantage over the other methods. Each has strengths and weaknesses that need to be taken into account when deciding which one to use to get the best results from subfield volumetry.


Structure and origin of a snapback defective interfering particle RNA of vesicular stomatitis virus.
The nucleotide sequence of the region which covalently links the complementary strands of the "snapback" RNA of vesicular stomatitis virus, DI011, is (Formula: see text). Both strands of the defective interfering (DI) particle RNA were complementary for their full length and were covalently linked by a single phosphate group. Because the strands were exactly the same length and complementary, template strand and daughter strand nucleocapsids generated during replication of DI 011 were undistinguishable on the basis of sequence, a property not shared by other types of DI particle RNAs. Treatment of the RNA with RNase T1 in high-ionic-strength solutions cleaved the RNA only between positions 1 and 1'. These results and the availability of the guanosine residue in position 1' to kethoxal, a reagent that specifically derivatizes guanosines of single-stranded RNA, suggest that steric constraints keep a small portion of the "turnaround" region in an open configuration. The sequence of the turnaround region was not related in any obvious way to the sequences at the 3' and 5' termini and limited the number of possible models for the origin of this type of DI particle RNA. Two models for the genesis of DI 011 RNA are discussed. We favor one in which the progenitor DI 011 RNA was generated by replication across a nascent replication fork.


Vitellogenesis as a biomarker for estrogenic contamination of the aquatic environment.
A rapidly increasing number of chemicals, or their degradation products, are being recognized as possessing estrogenic activity, albeit usually weak. We have found that effluent from sewage treatment works contains a chemical, or mixture of chemicals, that induces vitellogenin synthesis in male fish maintained in the effluent, thus indicating that the effluent is estrogenic. The effect was extremely pronounced and occurred at all sewage treatment works tested. The nature of the chemical or chemicals causing the effect is presently not known. However, we have tested a number of chemicals known to be estrogenic to mammals and have shown that they are also estrogenic to fish; that is, no species specificity was apparent. Many of these weakly estrogenic chemicals are known to be present in effluents. Further, a mixture of different estrogenic chemicals was considerably more potent than each of the chemicals when tested individually, suggesting that enhanced effects could occur when fish are exposed simultaneously to various estrogenic chemicals (as is likely to occur in rivers receiving effluent). Subsequent work should determine whether exposure to these chemicals at the concentrations present in the environment leads to any deleterious physiological effects.


Posttraumatic epilepsy: the endophenotypes of a human model of epileptogenesis.
Posttraumatic epilepsy is a common complication of traumatic brain injury (TBI), occurring in up to 15-20% of patients with severe brain trauma. Trauma accounts for approximately 5% of chronic epilepsy in the community. Because it is a common condition, and because of the relatively short latency period between injury and onset of chronic seizures, posttraumatic epilepsy represents a good model to test antiepileptogenic therapies. However, several well-conducted clinical trials have failed to demonstrate antiepileptogenic efficacy for several common anticonvulsants. Posttraumatic epilepsy can arise through a number of mechanisms, which often coexist within a single patient. Penetrating brain injury produces a cicatrix in the cortex and is associated with a risk of posttraumatic epilepsy of approximately 50%, whereas nonpenetrating head injury may produce focal contusions and intracranial hemorrhages, and is associated with a risk of posttraumatic epilepsy of up to 30%. Furthermore, closed head injury often produces diffuse concussive injury, with shearing of axons and selective damage to vulnerable brain regions, such as the hippocampus. The clinical, neurophysiologic, imaging, and neuropathologic features or epileptogenicity differ between these alternate mechanisms. It is likely that better understanding of the subtypes of epilepsy resulting from brain trauma will be required to successfully identify antiepileptogenic therapies.


Deficiency of ATP13A2 leads to lysosomal dysfunction, α-synuclein accumulation, and neurotoxicity.
The autophagy-lysosomal pathway plays an important role in the clearance of long-lived proteins and dysfunctional organelles. Lysosomal dysfunction has been implicated in several neurodegenerative disorders including Parkinson's disease and related synucleinopathies that are characterized by accumulations of α-synuclein in Lewy bodies. Recent identification of mutations in genes linked to lysosomal function and neurodegeneration has offered a unique opportunity to directly examine the role of lysosomes in disease pathogenesis. Mutations in lysosomal membrane protein ATP13A2 (PARK9) cause familial Kufor-Rakeb syndrome characterized by early-onset parkinsonism, pyramidal degeneration and dementia. While previous data suggested a role of ATP13A2 in α-synuclein misfolding and toxicity, the mechanistic link has not been established. Here we report that loss of ATP13A2 in human fibroblasts from patients with Kufor-Rakeb syndrome or in mouse primary neurons leads to impaired lysosomal degradation capacity. This lysosomal dysfunction results in accumulation of α-synuclein and toxicity in primary cortical neurons. Importantly, silencing of endogenous α-synuclein attenuated the toxicity in ATP13A2-depleted neurons, suggesting that loss of ATP13A2 mediates neurotoxicity at least in part via the accumulation of α-synuclein. Our findings implicate lysosomal dysfunction in the pathogenesis of Kufor-Rakeb syndrome and suggest that upregulation of lysosomal function and downregulation of α-synuclein represent important therapeutic strategies for this disorder.


Monophasic and biphasic synovial sarcoma. An immunohistochemical study.
Seven cases of synovial sarcoma (SS), two with biphasic and five with monophasic histology, were studied immunohistochemically using monoclonal antibodies to intermediate filaments, keratin, and vimentin. Slender spindle cells and plump cells were constant components of all the tumors. Epithelioid cells were present only in biphasic SS. Epithelioid cells and plump cells were positively stained by both keratin and vimentin. Slender spindle cells were stained positive for vimentin and negative for keratin. Staining manner of each cell type was similar irrespective of monophasic or biphasic pattern. Present immunohistochemical studies suggested that monophasic or biphasic patterns in SS should be regarded as a different expression of the same disease. In addition, immunohistochemistry proved to be a useful tool to detect plump cells which were difficult to find on routine staining.


Presenile because of presenilin: the presenilin genes and early onset Alzheimer's disease.
Alzheimer's disease is a neurodegenerative disorder characterized by the massive and invariant accumulation of amyloid plaques in the brains of affected patients. In many cases Alzheimer's disease occurs in the absence of a prior history of the disease in other family members and is designated as sporadic, whereas in approximately 10% of patients, dominantly transmitted mutations within one of three genes are found. A few mutations have been identified within the gene encoding the beta-amyloid precursor protein; however, these mutations account for only about 1-3% of cases with familial Alzheimer's disease. In the majority of autosomal dominant cases (40-50%), mutations have been found in a gene localized to chromosome 14. The responsible gene, now called presenilin-1, has recently been identified and shown to encode a putative seven transmembrane domain protein. Surprisingly, a second highly homologous gene (named presenilin-2) was cloned shortly thereafter. It is localized on human chromosome 1 and is also involved in a small number of cases with familial Alzheimer's disease. Early data suggest that mutations found within the two genes cause early onset Alzheimer's disease by influencing the proteolytic processing of amyloid beta-peptide in a pathological manner.


Mate Selection and Behavioral Thermoregulation in Fowler's Toads.
Male Fowler's toads produce mating calls that are affected by the body size and temperature of the caller. Females are able to discriminate between variations in these calls and select the largest available males. By thermoregulation, males are able to alter their calls to make them more attractive to females.


The 'bear trap': the colliding epidemics of tuberculosis and HIV in Russia.
In April, 2003 the World Bank approved a long-awaited $150 million loan to the Russian Federation to support tuberculosis (TB) and AIDS control. Although the Russian Federation accounts for a relatively small fraction of the global TB case-load the proportion of cases which are drug-resistant and particularly multidrug-resistant is very high in some regions. HIV incidence, principally associated with intravenous drug abuse, has also increased dramatically and this will impact upon TB control efforts. Federation-wide data are limited but a focus on one region shows something of the confluence of the epidemics of HIV and TB. Approaching 200 cases of HIV-associated TB have occurred in the past two years, and the age structure of the HIV-infected population and that with high rates of TB shows sizeable overlap. The region has high rates of multidrug-resistant TB which are likely to impact considerably on efforts to meet this emerging and complex public health challenge. Insights gained through the examination of this one region can tell us something of the magnitude of the challenge now faced by both the international community and Russia.


Transport of North Sea cod larvae into the Skagerrak coastal populations.
The Atlantic cod (Gadus morhua) is economically one of the world's most important marine species--a species presently suffering from heavy overexploitation throughout its range of distribution. Although not fully understood, the Atlantic cod is believed to be structured into populations in a rather complex manner, whereby both highly migratory and more confined ocean-spawning stocks coexist with stationary coastal populations. Owing to the complex population structure, little is presently known about how overexploitation of offshore stocks may affect other segments of the species. Here, we use microsatellite DNA analyses of coastal and offshore cod in combination with oceanographic modelling to investigate the population structure of Atlantic cod in the North Sea-Skagerrak area and evaluate the potential for larval transport into coastal populations. Our results suggest an extensive but temporally variable drift of offshore cod larvae into coastal populations. In a year (2001) with high inflow of North Sea waters into the Skagerrak we find that juvenile cod caught along the Skagerrak coast are predominantly of North Sea origin, whereas in a year (2000) with low inflow juveniles appear to be of local origin. These findings indicate that offshore cod may influence coastal cod populations over large distances.


Activation of ERK1/2 Causes Pazopanib Resistance via Downregulation of DUSP6 in Synovial Sarcoma Cells.
Synovial sarcoma (SS) is a rare high-grade malignant mesenchymal tumour with a relatively poor prognosis despite intensive multimodal therapy. Although pazopanib, a multi-kinase inhibitor, is often used for advanced SS, most cases eventually become resistant to pazopanib. In the present study, we investigated the mechanisms of acquired pazopanib resistance in SS. To examine acquired pazopanib resistance, two SS cell lines, SYO-1 and HS-SY-II, were isolated after multiple selection steps with increasing concentrations of pazopanib. SYO-1 was also used in vivo. Then, pazopanib-resistant clones were investigated to assess potential mechanisms of acquired pazopanib resistance. Stable pazopanib-resistant clones were established and exhibited enhanced cell cycle progression, cell growth with increased ERK1/2 phosphorylation, and higher sensitivity than parental cells to a MEK-inhibitor, trametinib, both in vitro and in vivo. Furthermore, addition of low-dose trametinib partially reversed the pazopanib resistance. In the pazopanib-resistant clones, dual specificity phosphatase 6 (DUSP6) was downregulated. Inhibition of DUSP6 expression in parental HS-SY-II cells partially recapitulated acquired pazopanib resistance. Acquired pazopanib resistance in SS was associated with activation of ERK1/2 through downregulation of DUSP6 expression. Simultaneous treatment with pazopanib and a MEK inhibitor could be a promising strategy to overcome pazopanib resistance in SS.


Label, nudge or tax? A review of health policies for risky behaviours.
This work proposes a critical, non systematic, review of the three main lines of health policy interventions to deal with risky behaviours, such as over-eating, smoking, sedentary lives, and excess alcohol drinking, namely: i) the release of information on health risks and consequences; ii) the use of incentives; and iii) direct policy intervention in markets, through regulation and taxation. First, the health and economic impact of the risky behaviours epidemics are briefly described. Then a critical review follows on the evidence existing on the effectiveness of each type of intervention. The review will also highlight the public health approach staying beyond each type of policy on risky behaviours and critically consider them within the context of more general health and social policy interventions.


Antiproliferative Effects of Recombinant Apoptin on Lung and Breast Cancer Cell Lines.
Selective therapy has always been the main challenge in cancer treatments. Various non-replicative oncolytic viral systems have revealed the safety and efficacy of using viruses and these products. The aim of this paper is to examine the impact of recombinant apoptin on the proliferation of lung cancer and breast cancer cell lines. The present study consisted of two steps of expression of recombinant apoptin and its anti-proliferative effects on normal and cancer cells. In the first step, following bioinformatics and optimizing apoptin gene sequencing and synthesis, it was expressed using vector PET28a and E. coli BL21 (DE3). The expressed recombinant apoptin was confirmed by analytical SDSPAGE and then purified using Ni affinity chromatography. In the second step, the antiproliferative effects of recombinant apoptin on lung cancer, breast cancer and primary cell lines were determined using MTT assay. According to the results of SDS-PAGE gel assay, recombinant apoptin was visible in the 14 kDa band. Also, the MTT assay results indicated that the antiproliferative effects of recombinant apoptin in cancer cell lines was different compared with the primary cell line, and followed a dose-dependent manner in both cell lines. The highest cytotoxicity (lowest cell viability) groups were 0.2 mg/mL in lung cancer (0.32 ± 0.015) (P<0.001), and in breast cancer (0.33 ± 0.031) (P<0.001) and 0.032 mg/mL in primary cells (0.17 ± 0.004) (P<0.01), as compared to the control groups. Our results confirmed that recombinant apoptin can induce antiproliferative effects in lung cancer and breast cancer cell lines, but not in normal monkey kidney cell line Vero; thus, it can be introduced as a promising novel specific antitumor agent after further evaluation in clinical trials.


Age-associated change in macronuclear DNA content in Paramecium caudatum.
Macronuclear DNA content in Paramecium caudatum was found to be almost unchanged with a mean of about 400C during the earlier two-thirds of the life span in terms of the number of fissions and then it dropped rapidly to about one-fifth of the initial content. The age when rapid DNA decline occurred corresponded to that when the characteristics of senescence appeared. This decreasing pattern of macronuclear DNA content contrasted with earlier observations in P. tetraurelia, P. bursaria and Tetrahymena thermophila. The data suggested that in P. caudatum the distribution pattern of macronuclear DNA to daughter cells changed from an almost equal distribution in younger cells to an unequal distribution in older cells, while the relative volume of the macronucleus to the whole cell remained almost constant throughout the life cycle.


Depressed REM Sleep Behavior Disorder Patients Are Less Likely to Recall Enacted Dreams than Non-Depressed Ones.
REM sleep behavior disorder (RBD) is associated with psychiatric symptoms, such as anxiety and alexithymia. However, only a few studies on the relationship between depression and RBD have been published. In this study, we investigated the occurrence of depression and associated factors in patients with RBD. In total 94 patients (mean age: 61.9±12.7 years, male: 70.2%) diagnosed as RBD were examined using detailed clinical histories, the Beck Depression Inventory (BDI), the Epworth Sleepiness Scale (ESS), and nocturnal polysomnography (PSG). The mean BDI score of all patients was 12.4±10.3 and 44.7% of RBD patients showed depressed mood (BDI >11 points). Depressed RBD patients were less able to recall enacted dreams than were non-depressed patients (61.9% vs. 86.5%, p=0.008). Logistic regression analysis showed that failure to recall enacted dreams was significantly associated with depression, after controlling for confounding variables including the respiratory disturbance index and a history of psychiatric disorders (odds ratio=0.323, p=0.041). In this study, 44.7% of RBD patients were found to suffer from depressed mood. And, depression was found to be associated with reduced ability to recall enacted dreams. We suggest that routine evaluation of depression be performed in RBD patients, particularly when failure to recall enacted dreams is evident. We speculate that such failure may be associated with emotional dysregulation or neurodegeneration.


Interdisciplinary communication in general medical and surgical wards using two different models of nursing care delivery.
To compare two models of care on nurses' perception of interdisciplinary communication in general medical and surgical wards. Effective interdisciplinary collaboration remains the cornerstone of efficient and successful functioning of health care teams and contributes substantially to patient safety. In May 2007, participants were recruited from a tertiary teaching hospital in Australia. The multifaceted Shared Care in Nursing (SCN) model of nursing care involved team work, leadership and professional development. In the Patient Allocation (PA) model one nurse was responsible for the care of a discrete group of patients. Differences in interdisciplinary communication were assessed at the 6-month follow-up. Completed questionnaires were returned by 125 participants. At the 6-month follow-up, there was a significant reduction in scores in the SCN group in the subscales relating to communication openness (P = 0.03) and communication accuracy (P = 0.02) when compared with baseline values. There were no significant differences in the two groups at the 6-month follow-up in any of the other subscales. There is a need for effective training programmes to assist nurses in working together within a nursing team and an interdisciplinary ward team. The SCN and the PA models of care have been found by nurses to support most aspects of interdisciplinary and intradisciplinary communication. The applicability of both models of care to wards with a varying skill mix of nurses is suggested. Further studies of larger samples with varying compositions of skill mix and varying models of care are required. Nurse managers can use varying models of care to support interdisciplinary communication and enhance patient safety.


The value of ProMED-mail for the Early Warning Committee in the Netherlands: more specific approach recommended.
This article describes a retrospective and descriptive study into the added value of ProMED-mail--the global electronic reporting system for outbreaks of emerging infectious diseases and toxins maintained by the International Society for Infectious Diseases--as an early warning system for The Netherlands Early Warning Committee (NEWC). Information about infectious disease events in foreign countries originating from ProMED-mail was retrieved from the reports of the NEWC between May 2006 and June 2007. Each event was analysed in depth in order to determine if it could have been a possible threat to public health in The Netherlands. It was determined whether these events were mentioned in other sources of information used by the NEWC besides ProMED-mail. In addition, we assessed the possible consequences of missing an event when not reading ProMED-mail or of being informed of the event with a time delay. Semi-structured interviews with stakeholders were conducted to explore other functions of ProMED-mail besides early warning. Five out of 25 events reported in ProMED-mail were assessed as a potential threat to The Netherlands, mainly because of the known vulnerability of The Netherlands for vaccine preventable diseases: an outbreak of measles in the United Kingdom and Japan, a case of poliomyelitis in Kenya, and two events concerning Highly Pathogenic Avian Influenza (HPAI) H5N1. The outbreak of measles in Japan and one case of HPAI H5N1 infection in a bird in Germany were only reported by ProMED-mail; the other potential threats were mentioned in other sources with a time delay. ProMED-mail has a limited but real added value over other sources in the early warning of threats. A more specific approach of using ProMED-mail by defining vulnerabilities of a country would be useful and efficient. ProMED-mail is appreciated for providing background and preliminary outbreak information.


In vivo morphological changes in animal models of amyotrophic lateral sclerosis and Alzheimer's-like disease: MRI approach.
Magnetic resonance imaging (MRI) is the only noninvasive technique that provides structural information on both cell loss and metabolic changes. After reviewing all the results obtained in clinical studies, reliable biomarkers in neurological diseases are still lacking. Diffusional MRI, MR spectroscopy, and the assessment of regional atrophy are promising approaches, but they cannot be simultaneously used on a single patient. Thus, for further research progress, reliable animal models are needed. To this aim, we have used the clinical MRI to assess neurodegenerative processes in the hSOD-1(G93A) ALS rat model and in the trimethyltin (TMT)-treated model of Alzheimer's-like disease. T2-weighted (T2W) hyperintensive neurodegenerative foci were found in the brainstem of the ALS rat with apparent lateral ventricle dilation (T1W-hypointensity vs. T2W-hyperintensity). Degenerative processes in these areas were also confirmed by confocal images of GFAP-positive astrogliosis. MRI after i.v.i. of magnetic anti-CD4 antibodies indicated an accumulation of inflammatory cells near dilated ventricles. TMT-treated rats also revealed the dilation of lateral ventricles. Expected deterioration in the hippocampus was not observed by clinical MRI, but immunocytochemistry could reveal significant redistribution of macro- and microglia in this structure. In both models, Gd-DTPA contrast revealed a compromised blood brain barrier that may serve as the passage for inflammatory immune cells in the vicinity of dilated lateral ventricles. Moreover, in both models the midbrain region of the dorsal hippocampus was the target of BBB compromise, thus revealing a potentially vulnerable point that can be the primary target of neurodegeneration in the central nervous system.


[A man with chest pain and dyspnoea].
A 60-year-old man presented with acute chest pain and dyspnoea, which was caused by pericarditis secondary to a neo-oesophago-pericardial fistula after previous oesophagectomy for oesophageal cancer. The fistula presumably originated from a penetrating peptic ulcer.


Postgraduate medical training, stress, and marriage.
In a pilot study, 20 interviews were conducted with married female interns and residents and their spouses in order to explore both positive effects of spousal support and negative effects of additional role obligations during medical training. The marital state has been shown to be related to lowered levels of stress. Past studies of medical marriage have focused on male physicians and their wives. However, marriage and parenthood impact differently on women than men, and thus on women physicians. To explore these differences, our findings are contrasted with findings on male medical students and their wives by R. Coombs. Compared to our subjects, Coombs found spouses were either housewives or held lower level jobs rather than demanding careers, and consequently our subjects experienced greater difficulty meeting demands of everyday life (cooking, cleaning, child care). Coombs' wives showed greater vicarious identification with the goals and satisfactions of the physician in-training; greater feelings of obligation to nurture, support and make sacrifices on behalf of their spouses; and less resentment toward the current system of medical training. They stressed the nurturing aspect of marital support rather than instrumental aspects. Subjects in both studies feared growing apart but while Coombs' wives feared being outgrown intellectually, our husbands were critical of their wives' narrowness of interests. Subjects in both studies believed marriage provided benefits (intimacy, support, affection, sex) but also complained of the negative impact of exhausting and emotionally draining medical training. Implications of findings for reducing the stress of medical training are discussed.


New techniques and tumor nomenclature.
New techniques in pathology can effect tumor nomenclature by leading to new concepts which may then give rise to new terms. Pathologists generate morphological data. They are obliged to provide consistent data for those who depend on standardized terms, eg, clinical trials, tumor registries and practising physicians and surgeons. They face the dilemma of when to replace a standard term with a new term. The following are recent examples of situations in which new techniques have had an impact on tumor nomenclature but which have raised questions about the applicability of new terms in routine diagnostic reports: --tumors of the lung, particularly when studied by electron microscopy: should the ultrastructural heterogeneity of lung tumor types be expressed or ignored in routine diagnosis? --the APUD and neuroendocrine carcinoma concepts: is there a need to rename carcinoids and small cell carcinomas? --endocrine elements in carcinomas: are the following terms useful for diagnosis: amphicrine carcinoma, argentaffin cell carcinoma, biphenotypic carcinoma? The recognition that conceptual terms and descriptive terms have separate functions may help pathologists deal with terminological change.


Distinct roles of cytochrome P450 reductase in mitomycin C redox cycling and cytotoxicity.
Mitomycin c (MMC), a quinone-containing anticancer drug, is known to redox cycle and generate reactive oxygen species. A key enzyme mediating MMC redox cycling is cytochrome P450 reductase, a microsomal NADPH-dependent flavoenzyme. In the present studies, Chinese hamster ovary (CHO) cells overexpressing this enzyme (CHO-OR cells) and corresponding control cells (CHO-WT cells) were used to investigate the role of cytochrome P450 reductase in the actions of MMC. In lysates from both cell types, MMC was found to redox cycle and generate H(2)O(2); this activity was greater in CHO-OR cells (V(max) = 1.2 +/- 0.1 nmol H(2)O(2)/min/mg protein in CHO-WT cells versus 32.4 +/- 3.9 nmol H(2)O(2)/min/mg protein in CHO-OR cells). MMC was also more effective in generating superoxide anion and hydroxyl radicals in CHO-OR cells, relative to CHO-WT cells. Despite these differences in MMC redox cycling, MMC-induced cytotoxicity, as measured by growth inhibition, was similar in the two cell types (IC(50) = 72 +/- 20 nmol/L for CHO-WT and 75 +/- 23 nmol/L for CHO-OR cells), as was its ability to induce G(2)-M and S phase arrest. Additionally, in nine different tumor cell lines, although a strong correlation was observed between MMC-induced H(2)O(2) generation and cytochrome P450 reductase activity, there was no relationship between redox cycling and cytotoxicity. Hypoxia, which stabilizes MMC radicals generated by redox cycling, also had no effect on the sensitivity of tumor cells to MMC-induced cytotoxicity. These data indicate that NADPH cytochrome P450 reductase-mediated MMC redox cycling is not involved in the cytotoxicity of this chemotherapeutic agent.


Occurrence of a myxozoan parasite Myxidium streisingeri n. sp. in laboratory zebrafish Danio rerio.
Over several years of screening diagnostic cases, the Zebrafish International Resource Center Health Services has encountered a myxozoan parasite of the ducts associated with the kidney in zebrafish, Danio rerio , from an average of 21% of facilities submitting specimens over 5 yr. The parasite is coelozoic and is associated with no appreciable histological changes. Plasmodia bear ovoid spores with 3 sutural ridges. Spores are consistent with the genus Myxidium, but they are distinct from any known species and are thus described as Myxidium streisingeri n. sp. Phylogenetically, this parasite is a member of the polyphyletic urinary bladder clade, which is consistent with the site of infection. The common occurrence of a myxozoan in this closed husbandry system is unexpected because these parasites are known to have complex life cycles, alternating between a vertebrate and invertebrate host. It may be that biofilters provide habitat for suitable invertebrate hosts or perhaps M. streisingeri n. sp. can be transmitted directly. Future control of this parasite in zebrafish research laboratories depends on a better understanding of this life cycle.


Post-treatment surveillance of patients with colorectal cancer with surgically treated liver metastases.
Little is known about current surveillance patterns after treatment of colorectal liver metastasis (CRLM) or whether the intensity of surveillance correlates with outcome. We sought to define current population-based patterns of surveillance and investigate whether intensity of surveillance impacted outcome. We queried the Surveillance, Epidemiology, and End Results-linked Medicare database for patients with CRLM diagnosed between 1991 and 2005 who underwent liver resection and/or tumor ablation. Frequency of post-treatment abdominal computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) was recorded for ≤ 5 years after treatment. The association between frequency of imaging with secondary interventions and long-term survival were analyzed. We identified 1,739 patients with CRLM treated with surgery; median age was 73 years, and the majority were male (52.6%). CRLM treatment consisted of liver resection (61%), ablation (32%), or both simultaneously (6%). CT (97%) was utilized more often for post-treatment surveillance compared with MRI (7%) and PET (18%). A temporal trend was noted with more frequent surveillance imaging obtained in post-treatment year 1 (2.4 scans/year) versus year 5 (0.6 scans/year; P = .01); 66% of living patients had no imaging after 2 years. Frequency of surveillance imaging correlated with procedure type (total number of scans/5 years: resection, 5.0; ablation, 4.6; resection and ablation, 6.2; P = .01). Other factors associated with a greater frequency of surveillance included younger age at diagnosis, geographic location in the South, and CRLM directed surgery in 2000 through 2005 (all P < .05). Overall survival did not differ by intensity of surveillance imaging (3-4 scans/yr, 43 months vs 2 scans/yr, 57 months vs 1 scan/yr, 54 months; P = .08). Marked heterogeneity exists in how often surveillance imaging is obtained after treatment of CRLM. Intensity of imaging does not affect time to second procedure or median survival duration. Surveillance guidelines for CRLM need to be refocused to provide the best value for healthcare resources.


A quantitative map of protein sequence space for the cis-defensin superfamily.
The cis-defensins are a superfamily of small, cationic, cysteine-rich proteins, sharing a common scaffold, but highly divergent sequences and varied functions from host-defence to signalling. Superfamily members are most abundant in plants (with some genomes containing hundreds of members), but are also found across fungi and invertebrates. However, of the thousands of cis-defensin sequences in databases, only have a handful have solved structures or assigned activities. Non-phylogenetic sequence-analysis methods are therefore necessary to use the relationships within the superfamily to classify members, and to predict and engineer functions. We show that the generation of a quantitative map of sequence space allows these highly divergent sequences to be usefully analyzed. This information-rich technique can identify natural groupings of sequences with similar biophysical properties, detect interpretable covarying properties, and provide information on typical or intermediate sequences for each cluster. The cis-defensin superfamily contains clearly-defined groups, identifiable based on their biophysical properties and motifs. The organization of sequences within this space also provides a foundation of understanding the ancient evolution of the superfamily. A webtool for exploring and querying the space is hosted at TS404.shinyapps.io/DefSpace. Supplementary data are available at Bioinformatics online.


Physicians, patients, and public knowledge and perception regarding hypertension and stroke: a review of survey studies.
Hypertension is the most common treatable risk factor for stroke. Efforts have been made to raise the awareness of both hypertension and stroke. There is a lack of clear understanding of the current state of knowledge, attitudes, and perceptions about hypertension and stroke among patients, the public, and physicians. To understand the level of knowledge, attitudes, and perceptions regarding hypertension and stroke among patients, the public, and physicians and to highlight the practices of physicians in managing hypertension given current hypertension guideline recommendations. Current Contents, Embase, and Medline databases were searched to identify manuscripts published between January 1994 and December 2004 reporting surveys concerning the knowledge and perceptions of patients, the public, and physicians regarding hypertension and stroke. Studies were summarized and collated into a spreadsheet. Of a total of 85 manuscripts identified, only 43 contained information meeting the study objectives. Based on the reported results, it was observed that patients and public alike are generally aware that hypertension is one of the risk factors of stroke, and that stroke could be a consequence of hypertension, but do not consider hypertension to be a serious health concern. Physicians appreciate the importance of managing hypertension to avoid future complications such as stroke. However, they do not conform to the recommendations made in various hypertension guidelines. They have higher thresholds than guideline recommendations for defining and categorizing hypertension, for starting antihypertensive therapy, and for target blood pressure goals. They do not aggressively manage hypertension in older people, considering that the elderly are at greater risk for developing stroke. Patients and public are aware of the link between hypertension and stroke but do not appreciate the consequences of uncontrolled hypertension. Physicians worldwide need to engage in patient communication regarding hypertension, stroke, and the dangers of uncontrolled hypertension, and need to implement guideline recommendations for hypertension diagnosis and management.


Does social capital promote physical activity? A population-based study in Japan.
To examine the association between individual-level social capital and physical activity. In February 2009, data were collected in a population-based cross-sectional survey in Okayama city, Japan. A cluster-sampling approach was used to randomly select 4,000 residents from 20 school districts. A total of 2260 questionnaires were returned (response rate: 57.4%). Individual-level social capital was assessed by an item inquiring about perceived trust of others in the community (cognitive dimension of social capital) categorized as low trust (43.0%), mid trust (38.6%), and high trust (17.3%), as well as participation in voluntary groups (structural dimension of social capital), which further distinguished between bonding (8.9%) and bridging (27.1%) social capital. Using logistic regression, we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for physical inactivity associated with each domain of social capital. Multiple imputation method was employed for missing data. Among total participants, 68.8% were physically active and 28.9% were inactive. Higher trust was associated with a significantly lower odds of physical inactivity (OR = 0.58, 95% CI = 0.42-0.79) compared with low trust. Both bridging and bonding social capital were marginally significantly associated with lower odds of physical inactivity (bridging, OR = 0.79, 95% CI = 0.62-1.00; bonding, OR = 0.71, 95% CI = 0.48-1.03) compared with lack of structural social capital. Low individual-level social capital, especially lower trust of others in the community, was associated with physical inactivity among Japanese adults.


Slow Breathing Exercise with Multimodal Virtual Reality: A Feasibility Study.
Many studies have shown that slow breathing training is beneficial for human health. However, several factors might discourage beginners from continuing their training. For example, a long training period is generally required for benefit realization, and there is no real-time feedback to trainees to adjust their breathing control strategy. To raise the user's interest in breathing exercise training, a virtual reality system with multimodal biofeedback is proposed in this work. In our system, a realistic human model of the trainee is provided in virtual reality (VR). At the same time, abdominal movements are sensed, and the breathing rate can be visualized. Being aware of the breathing rate, the trainee can regulate his or her breathing to achieve a slower breathing rate. An additional source of tactile feedback is combined with visual feedback to provide a more immersive experience for the trainees. Finally, the user's satisfaction with the proposed system is reported through questionnaires. Most of the users find it enjoyable to use such a system for mediation training.


Influence of Different Methods to Determine Maximum Heart Rate on Training Load Outcomes in Basketball Players.
Berkelmans, DM, Dalbo, VJ, Fox, JL, Stanton, R, Kean, CO, Giamarelos, KE, Teramoto, M, and Scanlan, AT. Influence of different methods to determine maximum heart rate on training load outcomes in basketball players. J Strength Cond Res 32(11): 3177-3185, 2018-The summated-heart-rate-zones (SHRZ) approach uses heart rate (HR) responses relative to maximum HR (HRmax) to calculate the internal training load (TL). Age-predicted, test-derived, and session-based approaches have all been used to determine HRmax in team sports. The purpose of this study was to determine the effects of using age-predicted, test-derived, and session-based HRmax responses on SHRZ TL in basketball players. Semiprofessional, male basketball players (N = 6) were analyzed during the preparatory training phase. Six age-based approaches were used to predict HRmax including Fox (220 - age); Hossack (206 - [0.567 × age]); Tanaka (208 - [0.7 × age]); Nikolaidis (223 - [1.44 × age]); Nes (211 - [0.64 × age]); and Faff (209.9 - [0.73 × age]). Test-derived HRmax was taken as the highest HR during the Yo-Yo intermittent recovery test (Yo-Yo IRT), whereas session-based HRmax was taken as the higher HR seen during the Yo-Yo IRT or training sessions. Comparisons in SHRZ TL were made at group and individual levels. No significant group differences were evident between SHRZ approaches. Effect size analyses revealed moderate (d = 0.60-0.79) differences between age-predicted, test-derived, and session-based methods across the group and individually in 2 players. The moderate differences between approaches suggest age-predicted, test-derived, and session-based methods to determine HRmax are not interchangeable when calculating SHRZ. Basketball practitioners are encouraged to use individualized HRmax directly measured during field-based tests supplemented with higher HR responses evident during training sessions and games when calculating the SHRZ TL to ensure greatest accuracy.


Nursing handover in the Indonesian hospital context: Structure, process, and barriers.
Nursing handover is an essential part of nursing practice to safe patient care, which occurs among nurses between shifts for transferring professional responsibility and accountability. However, there is limited information about the implementation and evaluation of nursing handover in Indonesian hospitals. This study aimed to describe the structures, processes, and barriers of the nursing handover in the Indonesian hospital context. This study employed a case study design in five inpatient units, especially in the medical-surgical wards of a referral hospital in Indonesia. The study was conducted from August to November 2018. A total of 100 handovers and 76 nurses were included. Focus group discussions were conducted in head nurses, nurse team leaders, and registered nurses. Observations were implemented to capture the handover process, including the number of the nurses in and out and the content of the information covered situation, background, assessment, and recommendations (SBAR). Data were analyzed using content analysis and fishbone analysis. The nursing handover consisted of three phases: before, during, and after. The handover barriers were divided into manpower, material, money, method, environment, and machine. The content of handover varied according to nurses' familiarity with the patients and their complexity. The nurses also actively participated during the handover process, although some nurses were absent in the handover time. About 75% of nurses had sufficient knowledge about the shift handover process using SBAR. The SBAR was adopted as a standard for handover, but no specific guideline or standard operating procedure. The results of this study can be used as basic information to develop a guideline of nursing handover and supervision in the context of hospitals in Indonesia and beyond.