Gastroesophageal reflux disease (GERD): a review of conventional and alternative treatments.
Gastroesophageal reflux disorder (GERD), a common disorder in the Western world, can lead to complications that include esophageal stricture and esophageal adenocarcinoma. Multiple challenges are associated with GERD treatment. First, lack of symptoms does not correlate with the absence of or the healing of esophageal lesions. Second, proton pump inhibitors, the current standard of care for GERD, are ineffective for the majority of GERD patients who have non-erosive disease. This article discusses these challenges, investigates the mechanisms of damage in GERD, and explores the existing data on unconventional forms of treatment, including melatonin, acupuncture, botanicals, and dietary interventions.


Stromal-Interacting Molecule 1 (Stim1)/Orai1 Modulates Endothelial Permeability in Ventilator-Induced Lung Injury.
BACKGROUND Increased endothelial permeability is involved in ventilator-induced lung injury (VILI). Stim1/Orai1 mediates store-operated Ca2+ activation, which modulates endothelial permeability. However, the underlying mechanisms of the Stim1/Orai1 pathway in VILI are poorly understood. MATERIAL AND METHODS Wistar rats were exposed to low tidal volume (7 mL/kg) or high tidal volume (40mL/kg) ventilation. Human Lung Microvascular Endothelial Cells (HULEC) were subjected to 8% or 18% cyclic stretching (CS). BTP2 pretreatment was performed. Lung wet/dry weight ratio, histological changes of lung injury, and bronchoalveolar lavage fluid (BALF) protein were measured. Endothelial permeability and intracellular calcium concentration were evaluated in HULECs. Protein expression was determined by Western blotting. RESULTS High tidal volume mechanical ventilation-induced lung injury (such as severe congestion and hemorrhage) and BTP2 pretreatment protected lungs from injury. The expression of Stim1, Orai1, and PKCα, lung wet/dry weight ratio, and BALF protein level significantly increased in the high tidal volume group compared to the control group and low tidal volume group. Importantly, BTP2 pretreatment alleviated the above-mentioned effects. Compared with exposure to 8% CS, the protein levels of Stim1, Orai1, and PKCα in HULECs significantly increased after exposure to 18% CS for 4 h, whereas BTP2 pretreatment significantly inhibited the increase (P<0.05). BTP2 pretreatment also suppressed increase of endothelial permeability and the intracellular calcium induced by 18% CS (P<0.05). CONCLUSIONS When exposed to high tidal volume or large-magnitude CS, Stim1 and Orai1 expression are upregulated, which further activates calcium-sensitive PKCα and results in calcium overload, endothelial hyperpermeability, and, finally, lung injury.


Spotlight on copanlisib and its potential in the treatment of relapsed/refractory follicular lymphoma: evidence to date.
The importance of the phosphatidylinositol-3-kinase (PI3K) pathway in cell survival and proliferation has made it an attractive target in cancer therapy. The development of small molecule inhibitors for the PI3K pathway continues to provide treatment alternatives across a range of malignancy types. Several agents, including idelalisib, copanlisib and duvelisib, not only inhibit the PI3K pathway, but also have effects on associated mechanisms including the ATK and mTOR pathways. The advent of PI3K-specific small molecular inhibitors has led to increased efficacy with avoidance of an excessive toxicity profile. Key enzymes of the PI3K pathway exhibit differing expression in tissue types and roles in tumor pathogenesis. Copanlisib (BAY 80-6946) is a pan-specific PI3K small molecule inhibitor for four key isoforms with increased activity against PI3Kα and PI3Kδ, both important in B-cell malignancies. Follicular lymphoma is one of the most common indolent B-cell non-Hodgkin lymphomas worldwide. Follicular lymphoma like other indolent B-cell non-Hodgkin lymphomas is beleaguered by high relapse rates and the need for subsequent therapy options. Based on efficacy and a limited toxicity profile, copanlisib received accelerated US Food and Drug Administration approval for the treatment of adult patients with relapsed follicular lymphoma following two lines of therapy. Here, we review the development of copanlisib and the role of this agent in the treatment of follicular lymphoma.


Simultaneously increased TxA(2) activity in isolated arterioles and platelets of rats with hyperhomocysteinemia.
We aimed to elucidate the effect of hyperhomocysteinemia (HHcy) on the synthesis of prostaglandins in rat skeletal muscle arterioles and platelets. Male Wistar rats were divided into 2 groups: (1) control rats, with plasma Hcy levels of 6.5+/-0.5 micromol/L (n=50) and (2) rats with HHcy, induced by daily intake of 1 g/kg body weight methionine in the drinking water for 4 weeks (plasma Hcy levels were 20.6+/-3.0 micromol/L, P<0.01 versus controls; n=50). Arterioles (diameter approximately 130 micrometer) were isolated from the gracilis muscle, cannulated, and pressurized (at 80 mm Hg), and changes in their diameters were followed by video microscopy. Constrictions to bradykinin (BK; 10(-10) to 10(-7) mol/L) were significantly greater in HHcy than in control rat arterioles (at 10(-9) mol/L BK, changes were 11+/-3% in control and 41+/-9% in HHcy rats). The cyclooxygenase inhibitor indomethacin (10(-5) mol/L), the prostaglandin H(2)/thromboxane A(2) (PGH(2)/TxA(2)) receptor antagonist SQ 29,548 (10(-6) mol/L), or the TxA(2) synthase inhibitor furegrelate (5x10(-6) mol/L) significantly decreased constrictions to BK in both groups but more so in HHcy arterioles, thus eliminating the difference between responses of HHcy and control arterioles. Constrictions to U46619 (a TxA(2) analogue) were significantly greater in HHcy than in control arterioles (at 10(-8) mol/L U46619, values for controls were 33+/-2% and 54+/-3% for HHcy). Endothelium removal or indomethacin treatment attenuated constrictions to U46619 in HHcy arterioles and eliminated the difference in responses. Also, aggregation of platelets from HHcy rats to collagen and ADP was significantly enhanced compared with controls (with 5 microgram/mL collagen: controls, 23+/-5%; HHcy, 49+/-5%; with 10(-7) mol/L ADP: controls, 25+/-3%; HHcy, 35+/-3%). Indomethacin or SQ 29,548 caused greater inhibition of aggregation of HHcy platelets compared with controls, thereby eliminating the differences between the 2 groups. Thus, HHcy enhances TxA(2) synthesis both in the arteriolar endothelium and platelets. By promoting vascular constriction and platelet aggregation simultaneously, these alterations are likely to contribute to the atherothrombotic vascular diseases described in HHcy.


Efficacy of fine needle aspiration cytology in the diagnosis of tuberculous cervical lymphadenopathy.
The results of a consecutive series of 1,349 fine needle aspiration (FNA) biopsies from the head and neck region of 1,193 patients has been reviewed in order to evaluate the efficacy of this method in the diagnosis of tuberculous lymphadenopathy (TBLN). Of the 108 patients whose fine needle aspiration cytology (FNAC) showed granulomatous changes, 68 had subsequent surgery and histological confirmation of the cytological appearance. Sixty-three had TBLN, thus the specificity of FNAC was 93 per cent in diagnosing tuberculous related granulomatous lymphadenopathy. One false positive FNAC was reported histologically to be metastatic mucoepidermal carcinoma. Of the 1,193 patients, 90 patients had subsequently TBLN confirmed histologically. Of these 90 patients, FNA from 69 showed granulomatous changes or acid fast bacilli (AFB), thus the sensitivity of FNAC in detecting tuberculous lymphadenopathy was 77 per cent. Fifty-two cytological smears were stained for acid fast bacilli. Nineteen (37 per cent) contained AFB. It is evident from this review that FNAC is an efficient way to detect cervical tuberculous lymphadenopathy.


Dynamics of Fusarium solani cutinase investigated through structural comparison among different crystal forms of its variants.
In characterizing mutants and covalently inhibited complexes of Fusarium solani cutinase, which is a 197-residue lipolytic enzyme, 34 variant structures, crystallizing in 8 different crystal forms, have been determined, mostly at high resolution. Taking advantage of this considerable body of information, a structural comparative analysis was carried out to investigate the dynamics of cutinase. Surface loops were identified as the major flexible protein regions, particularly those forming the active-site groove, whereas the elements constituting the protein scaffold were found to retain the same conformation in all the cutinase variants studied. Flexibility turned out to be correlated with thermal motion. With a given crystal packing environment, a high flexibility turned out to be correlated with a low involvement in crystal packing contacts. The high degree of crystal polymorphism, which allowed different conformations with similar energy to be detected, made it possible to identify motions which would have remained unidentified if only a single crystal form had been available. Fairly good agreement was found to exist between the data obtained from the structural comparison and those from a molecular dynamics (MD) simulation carried out on the native enzyme. The crystallographic approach used in this study turned out to be a suitable tool for investigating cutinase dynamics. Because of the availability of a set of closely related proteins in different crystal environments, the intrinsic drawback of a crystallographic approach was bypassed. By combining several static pictures, the dynamics of the protein could be monitored much more realistically than what can be achieved on the basis of static pictures alone.


Phosphatidylinositol 3 kinase pathway and 4-hydroxy-2-nonenal-induced oxidative injury in the RPE.
4-Hydroxy-2-nonenal (4-HNE) is a major lipid peroxidation product in the retina and the retinal pigment epithelium. The purpose of the present study was to investigate how NF-E2-related factor-2 (Nrf2) and phosphatidylinositol 3 (PI3K) pathways affect the responses of cultured human retinal pigment epithelial (RPE) cells to 4-HNE. Cultured ARPE-19 cells were treated with different concentrations of 4-HNE and a PI3K inhibitor, LY294002. Intracellular glutathione (GSH) was measured by high-performance liquid chromatography (HPLC). The transcriptional activity of Nrf2 was measured by dual luciferase assay after transient transfection with reporter plasmids. The mRNA level of glutamate cysteine ligase (GCL) was quantified by real-time RT-PCR. Formation of HNE adduct on heat shock cognate protein 70 (Hsc70) was measured by immunoprecipitation and Western blot analyses. Treatment with 4-HNE increased Nrf2 activity and GSH synthesis in a dose-dependent manner in cultured RPE cells. The modulatory subunit of GCL was upregulated by 4-HNE. Antioxidant responses were largely abolished by pretreatment with LY294002. The modification of Hsc70 by 4-HNE was increased when PI3K was inhibited. The Nrf2-dependent antioxidant response protects against 4-HNE toxicity, and this protective mechanism is dependent on the functions of the PI3K pathway.


Ethical obligations and counseling challenges in cancer genetics.
Cancer genetics is creating new practice opportunities in medical genetics, oncology, and primary care. The ethical and counseling challenges of this new area of practice are not unique but sometimes take new form in the context of genetic risk. This article uses cases to explore the issues associated with shared family risk, including competing concerns of family members, duty to warn relatives of genetic risk, and testing of children and other relatives. The ethical obligations of clinicians start with the need to maintain competence in the face of rapidly evolving science. Clinicians should be able to identify patients within their practice who are candidates for genetic testing. When genetic susceptibility to cancer is identified, patients should be offered counseling and follow-up, with referral as appropriate, to ensure delivery of care consistent with current standards. When patients experience barriers to needed health care, clinicians should advocate for their needs. Clinicians must ensure the autonomy and informed decision-making of all members of cancer-prone families. Clinicians must also provide emotional support and accurate information about cancer risks and cancer risk reduction measures, including uncertainties. Teamwork among different specialties is important in addressing these challenges.


IL-9 as a mediator of Th17-driven inflammatory disease.
We report that like other T cells cultured in the presence of transforming growth factor (TGF) beta, Th17 cells also produce interleukin (IL) 9. Th17 cells generated in vitro with IL-6 and TGF-beta as well as purified ex vivo Th17 cells both produced IL-9. To determine if IL-9 has functional consequences in Th17-mediated inflammatory disease, we evaluated the role of IL-9 in the development and progression of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. The data show that IL-9 neutralization and IL-9 receptor deficiency attenuates disease, and this correlates with decreases in Th17 cells and IL-6-producing macrophages in the central nervous system, as well as mast cell numbers in the regional lymph nodes. Collectively, these data implicate IL-9 as a Th17-derived cytokine that can contribute to inflammatory disease.


Practice Paper of the Academy of Nutrition and Dietetics: Selecting Nutrient-Dense Foods for Good Health.
The 2015 Dietary Guidelines for Americans encourage selection of nutrient-dense foods for health promotion and disease prevention and management. The purpose of this Academy of Nutrition and Dietetics practice paper is to provide an update regarding the science and practice of nutrient-dense food identification and selection. Characterization of tools used to identify nutrient density of foods is provided and recommendations for how registered dietitian nutritionists and nutrition and dietetics technicians, registered, might use available profiling tools to help consumers select nutrient-dense foods is discussed.


Spatial covert attention increases contrast sensitivity across the CSF: support for signal enhancement.
This study is the first to report the benefits of spatial covert attention on contrast sensitivity in a wide range of spatial frequencies when a target alone was presented in the absence of a local post-mask. We used a peripheral precue (a small circle indicating the target location) to explore the effects of covert spatial attention on contrast sensitivity as assessed by orientation discrimination (Experiments 1-4), detection (Experiments 2 and 3) and localization (Experiment 3) tasks. In all four experiments the target (a Gabor patch ranging in spatial frequency from 0.5 to 10 cpd) was presented alone in one of eight possible locations equidistant from fixation. Contrast sensitivity was consistently higher for peripherally- than for neutrally-cued trials, even though we eliminated variables (distracters, global masks, local masks, and location uncertainty) that are known to contribute to an external noise reduction explanation of attention. When observers were presented with vertical and horizontal Gabor patches an external noise reduction signal detection model accounted for the cueing benefit in a discrimination task (Experiment 1). However, such a model could not account for this benefit when location uncertainty was reduced, either by: (a) Increasing overall performance level (Experiment 2); (b) increasing stimulus contrast to enable fine discriminations of slightly tilted suprathreshold stimuli (Experiment 3); and (c) presenting a local post-mask (Experiment 4). Given that attentional benefits occurred under conditions that exclude all variables predicted by the external noise reduction model, these results support the signal enhancement model of attention.


Comparison of the effectiveness of five different antibiotic regimens on infection with Rickettsia typhi: therapeutic data from 87 cases.
This study estimated the clinical effectiveness of five different antibiotic regimens (doxycycline, chloramphenicol, ciprofloxacin, doxycycline plus chloramphenicol, and doxycycline plus ciprofloxacin) administered for infection with Rickettsia typhi in terms of the duration of the fever. Eighty-seven patients with endemic typhus were hospitalized between 1993 and 1998 at the General Hospital of Chania in Chania, Crete, Greece. The mean time to defervescence was 2.9 days for doxycycline, 4.0 days for chloramphenicol, and 4.2 days for ciprofloxacin. In patients receiving combinations of doxycycline plus chloramphenicol and doxycycline plus ciprofloxacin, fever subsided in 3.4 and 4.0 days, respectively. The outcome was favorable in all patients, and no deaths or relapses were observed within two months.


The Malaria in Pregnancy Library: a bibliometric review.
The Malaria in Pregnancy (MiP) Library is a bibliographic database that was created by the MiP Consortium in 2005 and is updated every four months using a standardized search protocol. A bibliometric review was conducted of the contents of the Library to determine dynamics in the type, content and volume of literature on malaria in pregnancy over time. Data on year of publication, type, language, country of first-author affiliation and content (topic) were extracted from entries in the MiP Library and plotted over time. By January 2012, the MiP Library contained 5,346 entries, consisting of 3,721 journal articles (69.6%), 697 reports (13.0%), 219 academic theses (4.1%), 92 books or book chapters (1.7%), 487 conference proceedings (9.1%), 68 registered studies (1.3%) and 62 'other' (1.2%). Most of the sources were in English language (87.3%), followed by French (7.5%) and Spanish (1.5%). Over 40% of source material was publicly available online (42.4%) and the remaining with restricted access (35.0%) or otherwise unavailable (22.7%). The number of journal articles related to malaria in pregnancy increased from 41 in the 1960s, to 708 in the 1990s, and 1,895 between 2000 and 2009, and the variety of themes has increased over time. English-language articles were sourced from 737 different journals. The top three journals were the American Journal of Tropical Medicine and Hygiene (184), Malaria Journal (158) and the Transactions of the Royal Society of Tropical Medicine and Hygiene (131). The last decade has seen a dramatic increase in publications related to malaria in pregnancy, and an increasing proportion of these are publically available online. The MiP Library is a useful, scholarly source for literature and systematic reviews related to malaria in pregnancy.


Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials.
External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland-Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was -4.4% with limits of agreement of -37.1% to 28.2%. Limits of agreement for randomisation rates were -47.8% to 77.5%. Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate.


Evaluation of suprapubic bladder aspiration for detection of group B streptococcal antigen by latex agglutination in neonatal urine.
Our objective was to determine whether urine collection by suprapubic bladder aspiration (SBA) improves the specificity of the group B streptococcal (GBS) latex agglutination (LA) test by avoiding contamination of urine with GBS from perineal and rectal colonization that can result in a positive LA test in an uninfected infant when the urine is collected by bag. Part 1 consists of a retrospective review of the medical records of 113 infants who had urine collected by SBA for GBS LA testing as part of evaluation for possible sepsis. The sensitivity and specificity of the urine LA test was assessed by comparing it with blood culture results. In part 2, a prospective analysis was performed of 19 newborns who had rectal and vaginal/penile cultures as well as urine by SBA and bag for GBS cultures and LA. Results of LA testing on urine collected by both of these methods were compared with results of urine, perineal, and rectal cultures. In the retrospective review of GBS LA testing performed on 113 consecutive urine specimens collected by SBA from neonates being evaluated for suspected sepsis, the sensitivity and specificity were 67% and 89%, respectively, when compared with blood culture results. Twelve infants who had a positive LA test result but a sterile blood culture (BC-,LA+) were compared with 95 infants with both blood cultures and urine LA tests negative for GBS (BC-, LA-). BC-, LA+ infants were more likely than those with BC-, LA- to have an immature to total neutrophil (I/T) ratio > or = 0.16 at 12 and 24 hours (p = 0.04 and 0.02, respectively). In the prospective study, we found that a positive GBS LA test can be due to perineal contamination and possibly to gastrointestinal absorption of GBS antigen. No false positive LA test results occurred on urine obtained by SBA; however, use of this method failed to detect the one infant with GBS bacteremia. Because of suboptimal sensitivity and specificity, use of the GBS LA test on urine obtained either by SBA or bag cannot be recommended for diagnosis of early onset GBS disease.


Hypnotic Olfactory Hallucinations.
Olfactory hallucinations (smelling odors that are not present) are intrusive and disruptive yet challenging to investigate because they cannot be produced on demand. In this study, the authors attempted to model olfactory hallucinations using hypnotic suggestions. We gave some subjects a suggestion to smell an odor in the absence of a real odor (positive hallucination) and gave others a suggestion to smell nothing in the presence of a real odor (negative hallucination). High hypnotizable individuals who received the positive hallucination reported intense smells whereas those who received the negative hallucination reported a reduction in intensity. These suggestions also influenced later recall about frequency of odor presentation. Findings are discussed in terms of reality monitoring and differences between positive and negative hallucinations.


Imatinib ameliorates neuroinflammation in a rat model of multiple sclerosis by enhancing blood-brain barrier integrity and by modulating the peripheral immune response.
Central nervous system (CNS) disorders such as ischemic stroke, multiple sclerosis (MS) or Alzheimers disease are characterized by the loss of blood-brain barrier (BBB) integrity. Here we demonstrate that the small tyrosine kinase inhibitor imatinib enhances BBB integrity in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS). Treatment was accompanied by decreased CNS inflammation and demyelination and especially reduced T-cell recruitment. This was supported by downregulation of the chemokine receptor (CCR) 2 in CNS and lymph nodes, and by modulation of the peripheral immune response towards an anti-inflammatory phenotype. Interestingly, imatinib ameliorated neuroinflammation, even when the treatment was initiated after the clinical manifestation of the disease. We have previously shown that imatinib reduces BBB disruption and stroke volume after experimentally induced ischemic stroke by targeting platelet-derived growth factor receptor -α (PDGFR-α) signaling. Here we demonstrate that PDGFR-α signaling is a central regulator of BBB integrity during neuroinflammation and therefore imatinib should be considered as a potentially effective treatment for MS.


Statistical thermodynamics of non-stoichiometric ceria and ceria zirconia solid solutions.
The thermodynamic redox properties of ceria and ceria zirconia solid solutions are analysed with a new methodology for modelling such systems based on the statistical mechanics of lattice configurations. Experimental thermogravimetric equilibrium data obtained for small non-stoichiometry measurements are combined with literature data to cover a large range of non-stoichiometry (CeO2-δ, δ = 0.001-0.32), temperature (1073-1773 K) and oxygen partial pressure (1-10(-13) bar). A dilute species model of defect clusters , obeying the law of mass action, was sufficient to describe the system over the whole range of conditions, leading to a simple analytical equation of state for the system. This offers new physical insight into the redox properties of ceria based materials, and the theoretical methods developed should also be of great interest for other materials which exhibit continuous oxygen non-stoichiometry similar to ceria, such as perovskite oxides.


Increasing age and severe intraoperative hypotension associated with nonsurvival in dogs with gallbladder mucocele undergoing cholecystectomy.
To identify prognostic indicators and inflammatory markers associated with nonsurvival in dogs with gallbladder mucoceles (GBMs) following cholecystectomy and to evaluate C-reactive protein (CRP) and haptoglobin concentrations in dogs with GBMs compared to healthy controls. 25 dogs that underwent cholecystectomy for removal of GBM and 20 healthy control dogs. A prospective, multicenter cohort study. Survival outcomes to hospital discharge and 2 weeks postdischarge were recorded from medical records. Laboratory variables, inflammatory markers (CRP and haptoglobin), and 25-hydroxyvitamin(OH) D (25[OH]D) concentrations were measured preoperatively. Associations between signalment, clinicopathologic variables, acute patient physiologic and laboratory evaluation (APPLEFAST) scores, inflammatory markers, 25(OH)D concentration, and survival were analyzed using logistic regression. 76% (19/25) and 68% (17/25) of dogs survived to hospital discharge and 2 weeks postdischarge, respectively. For each additional year of age, the odds of nonsurvival in hospital and 2 weeks postdischarge increased by 2.2 (P = .01; 95% CI, 1.2 to 5.0) and 1.7 (P = .04; 95% CI, 1.0 to 3.2), respectively. Intraoperative systolic blood pressure ≤ 65 mm Hg increased the probability of nonsurvival in hospital (P < .04). Gallbladder perforation, APPLEFAST scores, and preoperative serum concentrations of CRP, haptoglobin, and 25(OH)D were not associated with survival. Serum CRP and haptoglobin concentrations were greater in dogs with GBM compared to controls (P < .001). Increasing age and intraoperative systolic blood pressure ≤ 65 mm Hg were associated with nonsurvival in dogs with GBM undergoing cholecystectomy. Serum CRP, haptoglobin, and 25(OH)D were not associated with nonsurvival postcholecystectomy in this sample population.


What are the ethical issues in relation to the role of the family in intensive care?
A large proportion of patients admitted to the intensive care unit (ICU) are unable to express themselves, often due to acute illness, shock or trauma, and this precludes any communication and/or consent for care that might reflect their wishes and opinions. In such cases, the only solution for the ICU physician is to include the patient's family in the healthcare decisions. This can represent a significant burden on the family, on top of the psychological distress of the ICU environment and hospitalisation of their relatives, and many family members may suffer from anxiety, depression or symptoms of post-traumatic stress disorder (PTSD) during or after the hospitalisation and/or death of a loved one in the ICU. Good communication remains the cornerstone of family satisfaction in the ICU. Information imparted to the patient and/or family should cover diagnosis, prognosis and treatment. Information should be given orally, in person, using accessible language. Several other measures that can lessen the burden on the families of patients in the ICU and help to reduce anxiety and stress are also detailed in this review. Overall, family-centred care in the ICU requires a systematic communication strategy within the healthcare team, combined with an environment that is as amenable as possible to the family's presence and involvement, in order to maximize family satisfaction with ICU care, and ensure that the patient's values and preferences are respected.


High Altitude and Cancer Mortality.
Thiersch, Markus, and Erik R. Swenson. High altitude and cancer mortality. High Alt Med Biol 19:116-123, 2018.-Humans living at high altitude (HA) are exposed to chronic (hypobaric) hypoxia. Despite the permanent stress of hypoxic exposure, humans populating HA areas have reduced cancer mortality over a broad spectrum of cancer types. In fact, the majority of the physiological adaptive processes at HA occurring in response to hypoxia might be the driving force for reduced cancer mortality at HA. In this review, we summarize epidemiological and animal studies that compare cancer incidence and cancer mortality between HA and low altitude or between hypoxia and normoxia, respectively. We discuss the potential role of oxygen-independent and oxygen-dependent mechanisms that might contribute to reduced cancer mortality at HA. Reactive oxygen species and their detoxification as well as the hypoxia-inducible factors are especially promising targets and may be related to why cancer mortality is reduced at HA. In addition, we briefly discuss two aspects with a proven impact on tumorigenesis, namely the immune system and tumor surveillance as well as HA-induced metabolic changes. Further animal and clinical studies are clearly needed to explain why cancer mortality is reduced at HA and to decide whether HA or hypoxia-based therapeutic approaches could be implemented for cancer treatment. However, exposure to HA activates multiple adaptive mechanisms (oxygen independent and oxygen dependent) sharing common pathways as well as activating counteracting pathways, which complicate the identification of specific HA-induced mechanisms of tumor suppression.


Plasmodium Cysteine Repeat Modular Proteins 3 and 4 are essential for malaria parasite transmission from the mosquito to the host.
The Plasmodium Cysteine Repeat Modular Proteins (PCRMP) are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. Analysis of mutants of the rodent parasite Plasmodium berghei lacking expression of PCRMP1 or 2 showed that these proteins are essential for targeting of P. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse. In this work, the role of the remaining PCRMP family members, PCRMP3 and 4, has been investigated throughout the Plasmodium life cycle by generation and analysis of P. berghei gene deletion mutants, Δpcrmp3 and Δpcrmp4. The role of PCRMP members during the transmission and hepatic stages of the Plasmodium lifecycle has been evaluated by light- and electron microscopy and by analysis of liver stage development in HEPG2 cells in vitro and by infecting mice with mutant sporozoites. In addition, mice were immunized with live Δpcrmp3 and Δpcrmp4 sporozoites to evaluate their immunization potential as a genetically-attenuated parasite-based vaccine. Disruption of pcrmp3 and pcrmp4 in P. berghei revealed that they are also essential for transmission of the parasite through the mosquito vector, although acting in a distinct way to pbcrmp1 and 2. Mutants lacking expression of PCRMP3 or PCRMP4 show normal blood stage development and oocyst formation in the mosquito and develop into morphologically normal sporozoites, but these have a defect in egress from oocysts and do not enter the salivary glands. Sporozoites extracted from oocysts perform gliding motility and invade and infect hepatocytes but do not undergo further development and proliferation. Furthermore, the study shows that immunization with Δcrmp3 and Δcrmp4 sporozoites does not confer protective immunity upon subsequent challenge. PCRMP3 and 4 play multiple roles during the Plasmodium life cycle; they are essential for the establishment of sporozoite infection in the mosquito salivary gland, and subsequently for development in hepatocytes. However, although Δpcrmp3 and Δpcrmp4 parasites are completely growth-impaired in the liver, immunization with live sporozoites does not induce the protective immune responses that have been shown for other genetically-attenuated parasites.


Branched CdO/ZnO Core/Shell Heterogeneous Structure and Its Enhanced Photoelectrocatalytic Performance.
Branched nanostructures of semiconductors based on one-dimensional heterostructures have many promising applications in optoelectronics, supercapacitors, photocatalysts, etc. Here, we report a novel branched core/shell CdO/ZnO hetero-nanostructure that resembles a Crimson bottlebrush (Callistemon Citrinus) but with intriguing hexagonal symmetry. The nanomaterials were fabricated via an improved one-step chemical vapor deposition method and consist of a CdO wire as the core and ZnO as the shell. With cadmium acting as a catalyst, ZnO nanowires grow as perpendicular branches from the CdO/ZnO one-dimensional core/shell structure. The nanostructures were characterized with X-ray diffraction scanning and transmission electron microscopy. A homogeneous epitaxial growth mechanism has been postulated for the formation of the nanostructure. The materials show a broad and strong absorption ranging from visible to ultraviolet and a better photoelectrocatalytic properties in comparison to pure ZnO or CdO. Our synthetic strategy may open up a new way for controlled preparation of one-dimensional nanomaterials with core/shell heterostructure, which could find potential applications in solar cells and opto-electrochemical water-splitting devices.


BioCreative V BioC track overview: collaborative biocurator assistant task for BioGRID.
BioC is a simple XML format for text, annotations and relations, and was developed to achieve interoperability for biomedical text processing. Following the success of BioC in BioCreative IV, the BioCreative V BioC track addressed a collaborative task to build an assistant system for BioGRID curation. In this paper, we describe the framework of the collaborative BioC task and discuss our findings based on the user survey. This track consisted of eight subtasks including gene/protein/organism named entity recognition, protein-protein/genetic interaction passage identification and annotation visualization. Using BioC as their data-sharing and communication medium, nine teams, world-wide, participated and contributed either new methods or improvements of existing tools to address different subtasks of the BioC track. Results from different teams were shared in BioC and made available to other teams as they addressed different subtasks of the track. In the end, all submitted runs were merged using a machine learning classifier to produce an optimized output. The biocurator assistant system was evaluated by four BioGRID curators in terms of practical usability. The curators' feedback was overall positive and highlighted the user-friendly design and the convenient gene/protein curation tool based on text mining.Database URL: http://www.biocreative.org/tasks/biocreative-v/track-1-bioc/.


Thoracic Involvement in IgG4-Related Disease.
Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that has been recognized to involve virtually any organ in the body and typically manifests mass-like lesions (tumefactive). Although initial reports of this disease (autoimmune pancreatitis [AIP]) were described in the Japanese population, it has since been reported worldwide. It is most commonly seen in adults of middle age or older, more often men than women. The pathogenesis of IgG4-RD is largely unknown, but genetic factors, microorganisms, and autoimmunity are thought to play important roles. Serum IgG4 concentration is elevated in the majority of patients with IgG4-RD but is a nonspecific finding. Characteristic histopathologic features include dense lymphoplasmacytic infiltrate, fibrosis (often in storiform pattern), and obliterative phlebitis. Lung involvement in IgG4-RD was first reported in 2004 in two patients with AIP and coexisting interstitial lung disease. Since then, a wide spectrum of intrathoracic involvement has been reported and includes not only parenchymal lung diseases but also pleural, airway, vascular, and mediastinal lesions. Thoracic involvement in IgG4-RD is often found incidentally during the workup of extrathoracic lesions but can sometimes be the presenting abnormality. The diagnosis of IgG4-RD requires correlation of clinical, laboratory, imaging, and histopathologic features. Glucocorticoids are the first-line therapy but other options including B cell depletion are being investigated. IgG4-RD is generally associated with an indolent clinical course and most patients improve with glucocorticoid therapy.


Determinants of hemodynamic compromise with severe right ventricular infarction.
To elucidate determinants of hemodynamic compromise in patients with acute right ventricular (RV) infarction, we studied 16 patients with hemodynamically severe RV infarction by right heart catheterization and two-dimensional ultrasound. Severe RV systolic dysfunction, evident by ultrasound in all patients as RV dilatation and depressed RV free wall motion, was associated with a broad sluggish RV waveform, diminished peak RV systolic pressure (27.6 +/- 4.5 mm Hg), and depressed RV stroke work (4.6 +/- 2.4 g.m/m2). Paradoxical septal motion was consistently noted. In some cases, the septum bulged into the right ventricle in a pistonlike fashion and appeared to mediate systolic ventricular interaction through which left ventricular septal contraction contributed to RV pressure generation. RV diastolic dysfunction was indicated by elevated RV end-diastolic pressures (13.7 +/- 2.7 mm Hg), RV "dip and plateau," equalization of diastolic filling pressures, and reversal of diastolic septal curvature toward the volume-deprived left ventricle. A prominent right atrial (RA) X and blunted Y descent, indicative of impairment of RV filling throughout diastole, were confirmed in all patients by their relation to RV systolic events. Patients manifested one of two distinct RA waveform morphologies differentiated by A wave amplitude and associated with disparate clinical courses. In eight patients, an RA W pattern was evident, characterized by augmented A waves; eight others manifested an M pattern constituted by depressed A waves. Compared with those with an M pattern, patients with a W pattern had higher peak RV pressures (29.6 +/- 3.8 versus 25.5 +/- 4.3 mm Hg, p less than 0.05), better cardiac output (3.4 +/- 0.3 versus 2.9 +/- 0.7 l/min, p less than 0.05), more favorable response to volume and inotropes, and less frequently required emergency revascularization for refractory shock (none versus five for those with an M pattern). Patients with a W pattern were more severely compromised if atrioventricular dyssynchrony developed and were more dramatically improved by restoration of physiological rhythm. Angiography in patients with depressed A waves demonstrated more proximal coronary obstruction leading to ischemic compromise of RA function, whereas in those with augmented A waves, the culprit lesion was proximal to the RV but distal to the RA branches. These results indicate that hemodynamic compromise in patients with RV infarction is exacerbated by decreased preload reserve that is dependent on atrial systole. The amplitude of the RA A wave, an indication of the status of RA function, is an important determinant of RV performance and hemodynamic compromise.


The large-scale organization of shape processing in the ventral and dorsal pathways.
Although shape perception is considered a function of the ventral visual pathway, evidence suggests that the dorsal pathway also derives shape-based representations. In two psychophysics and neuroimaging experiments, we characterized the response properties, topographical organization and perceptual relevance of these representations. In both pathways, shape sensitivity increased from early visual cortex to extrastriate cortex but then decreased in anterior regions. Moreover, the lateral aspect of the ventral pathway and posterior regions of the dorsal pathway were sensitive to the availability of fundamental shape properties, even for unrecognizable images. This apparent representational similarity between the posterior-dorsal and lateral-ventral regions was corroborated by a multivariate analysis. Finally, as with ventral pathway, the activation profile of posterior dorsal regions was correlated with recognition performance, suggesting a possible contribution to perception. These findings challenge a strict functional dichotomy between the pathways and suggest a more distributed model of shape processing.


Neurophysiologic and neuroradiologic features of intractable epilepsy after traumatic brain injury in adults.
There is controversy regarding the precise mechanism by which epilepsy results after traumatic brain injury (TBI). Previous reports have suggested that mesial temporal lobe epilepsy may result from TBI only in young children, while neocortical epilepsy arises from TBI in later life. These conclusions were based on surgical series and may be biased because of patient selection. To determine the frequency of mesial temporal lobe as opposed to neocortical epilepsy in patients with intractable epilepsy resulting from TBI after the age of 10 years. We identified 23 patients with intractable epilepsy who had TBI after the age of 10 years, preceding the onset of epilepsy. Patients were studied by simultaneous videotape and scalp electroencephalographic recording of typical seizures; magnetic resonance imaging; neuropsychologic studies; and, when appropriate, intracarotid amobarbital testing. Two patients underwent anterior temporal lobectomies. Of the 23 patients, 8 (35%) had mesial temporal lobe epilepsy, based on the finding of hippocampal sclerosis on a magnetic resonance imaging scan, consistent interictal and ictal electroencephalographic recordings, evidence of temporal lobe dysfunction on neuropsychologic testing, and characteristic seizure semiology. Two of these patients underwent anterior temporal lobectomies with clinical benefit, and hippocampal sclerosis was confirmed pathologically. In 2 cases, patients were not treated surgically because of bilateral temporal lobe dysfunction noted on intracarotid amobarbital testing. Eleven patients had neocortical epilepsy; 1 had primary generalized epilepsy; and, in 3, the site of seizure onset was not localized. Mesial temporal lobe epilepsy can result from TBI in adolescents and adults as well as in children, and can often be bilateral and associated with multifocal injury. This information may be useful in developing prophylactic therapy for posttraumatic epilepsy.


Breast cancer risk factor knowledge among nurses in teaching hospitals of Karachi, Pakistan: a cross-sectional study.
Breast cancer is the most common cancer among women in both the developed and the developing world. The incidence of breast cancer in Karachi, Pakistan is 69.1 per 100,000 with breast cancer presentation in stages III and IV being common (>or= 50%). The most pragmatic solution to early detection lies in breast cancer education of women. Nurses constitute a special group having characteristics most suited for disseminating breast cancer information to the women. We assessed the level of knowledge of breast cancer risk factors among registered female nurses in teaching hospitals of Karachi. We also identified whether selected factors among nurses were associated with their knowledge of breast cancer risk factors, so that relevant measures to improve knowledge of nurses could be implemented. A cross-sectional survey was conducted in seven teaching hospitals of Karachi using stratified random sampling with proportional allocation. A total of 609 registered female nurses were interviewed using a structured questionnaire adapted from the Stager's Comprehensive Breast Cancer Knowledge Test. Knowledge of breast cancer risk factors was categorized into good, fair and poor categories. Ordinal regression was used to identify factors associated with risk knowledge among nurses. Thirty five percent of nurses had good knowledge of risk factors. Graduates from private nursing schools (aOR = 4.23, 95% CI: 2.93, 6.10), nurses who had cared for breast cancer patients (aOR = 1.41, 95% CI: 1.00, 1.99), those having received a breast examination themselves (aOR = 1.56, 95% CI: 1.08, 2.26) or those who ever examined a patient's breast (aOR = 1.87, 95% CI: 1.34, 2.61) were more likely to have good knowledge. A relatively small proportion of the nursing population had good level of knowledge of the breast cancer risk factors. This knowledge is associated with nursing school status, professional breast cancer exposure and self history of clinical breast examination. Since only about one-third of the nurses had good knowledge about risk factors, there is a need to introduce breast cancer education in nursing schools particularly in the public sector. Continuing nursing education at the workplace can be of additional benefit.


A neurologist's perspective on serum neurofilament light in the memory clinic: a prospective implementation study.
Neurofilament light in serum (sNfL) is a biomarker for axonal damage with elevated levels in many neurological disorders, including neurodegenerative dementias. Since within-group variation of sNfL is large and concentrations increase with aging, sNfL's clinical use in memory clinic practice remains to be established. The objective of the current study was to evaluate the clinical use of serum neurofilament light (sNfL), a cross-disease biomarker for axonal damage, in a tertiary memory clinic cohort. Six neurologists completed questionnaires regarding the usefulness of sNfL (n = 5-42 questionnaires/neurologist). Patients that visited the Alzheimer Center Amsterdam for the first time between May and October 2019 (n = 109) were prospectively included in this single-center implementation study. SNfL levels were analyzed on Simoa and reported together with normal values in relation to age, as part of routine diagnostic work-up and in addition to cerebrospinal fluid (CSF) biomarker analysis. SNfL was perceived as useful in 53% (n = 58) of the cases. SNfL was more often perceived as useful in patients < 62 years (29/48, 60%, p = 0.05) and males (41/65, 63%, p < 0.01). Availability of CSF biomarker results at time of result discussion had no influence. We observed non-significant trends for increased perceived usefulness of sNfL for patients with the diagnosis subjective cognitive decline (64%), psychiatric disorder (71%), or uncertain diagnosis (67%). SNfL was mostly helpful to neurologists in confirming or excluding neurodegeneration. Whether sNfL was regarded as useful strongly depended on which neurologist filled out the questionnaire (ranging from 0 to 73% of useful cases/neurologist). Regardless of the availability of CSF biomarker results, sNfL was perceived as a useful tool in more than half of the evaluated cases in a tertiary memory clinic practice. Based on our results, we recommend the analysis of the biomarker sNfL to confirm or exclude neurodegeneration in patients below 62 years old and in males.


The impact of intuition and supervisor-nurse relationships on empowerment and affective commitment by generation.
This article reports a generational cohort and leader-member exchange theoretical frameworks-guided study of the influence of the supervisor-subordinate relationship on three generational nurse cohorts' use of intuition, perceptions of empowerment and affective commitment. Within a global context of nurse shortages, knowledge about factors influencing nurse retention is urgently sought. We postulated that nurses' use of intuition is the key to their empowerment and consequent commitment to the organization, and that impact would vary among the three large nurse generations. A self-report survey was used to gather data in 2008, which were then analysed using correlations, regression analysis, manova and path analysis. Data were obtained from 900 Baby Boomer and Generations X and Y nurses, randomly chosen from seven private hospitals across Australia. The findings confirm the important impact of supervisor-nurse relationships upon all three generations' use of intuition. The findings add new knowledge about the differing importance of using intuition for Generation X, Generation Y and Baby Boomer nurses' perceptions of empowerment, suggesting it is more important to Baby Boomers and Generation X than to Generation Y. Further, the impact of using intuition differs significantly among the generational cohorts. The findings suggest the need for a more differentiated tailored style - sensitive to varying needs of the generations. Improving supervisor-nurse relationships is also critical, because of their impact upon nurses' use of intuition, perceptions of empowerment and affective commitment. Poor relationships lead to increased nurse replacement costs.


Species mtDNA genetic diversity explained by infrapopulation size in a host-symbiont system.
Understanding what shapes variation in genetic diversity among species remains a major challenge in evolutionary ecology, and it has been seldom studied in parasites and other host-symbiont systems. Here, we studied mtDNA variation in a host-symbiont non-model system: 418 individual feather mites from 17 feather mite species living on 17 different passerine bird species. We explored how a surrogate of census size, the median infrapopulation size (i.e., the median number of individual parasites per infected host individual), explains mtDNA genetic diversity. Feather mite species genetic diversity was positively correlated with mean infrapopulation size, explaining 34% of the variation. As expected from the biology of feather mites, we found bottleneck signatures for most of the species studied but, in particular, three species presented extremely low mtDNA diversity values given their infrapopulation size. Their star-like haplotype networks (in contrast with more reticulated networks for the other species) suggested that their low genetic diversity was the consequence of severe bottlenecks or selective sweeps. Our study shows for the first time that mtDNA diversity can be explained by infrapopulation sizes, and suggests that departures from this relationship could be informative of underlying ecological and evolutionary processes.


Trabecular Bone Score-An Emerging Tool in the Management of Osteoporosis.
Areal bone mineral density (aBMD) is currently the gold standard for the diagnosis of osteoporosis, however, it has its own pitfalls. Trabecular bone score (TBS), a novel tool in the evaluation of osteoporosis is an indirect indicator of bone microarchitecture. It is a textural index that evaluates pixel gray-level variations in the lumbar spine DXA (dual energy X-ray absorptiometry) image. Both cross-sectional and longitudinal studies have demonstrated that TBS may independently predict fragility fractures. TBS can also be used to adjust FRAX probabilities of fracture, though data available till date doesn't support any additional benefit. TBS also shows an improving trend with anti-osteoporotic treatment; however, the least significant change (LSC) is high that it takes more than 2 years for the change to manifest. TBS is also used in the evaluation of bone strength in cases of secondary osteoporosis. Though TBS predicts fracture risk independently in both genders, with the currently available data, it cannot be recommended as a standalone tool for decision regarding treatment of osteoporosis. TBS can be used as a tool to complement BMD in assessment of bone health. Additional studies are needed to assess its utility in clinical practice.


Soft Matter Technology at KIT: Chemical Perspective from Nanoarchitectures to Microstructures.
Bioinspiration has emerged as an important design principle in the rapidly growing field of materials science and especially its subarea, soft matter science. For example, biological cells form hierarchically organized tissues that not only are optimized and designed for durability, but also have to adapt to their external environment, undergo self-repair, and perform many highly complex functions. Being able to create artificial soft materials that mimic those highly complex functions will enable future materials applications. Herein, soft matter technologies that are used to realize bioinspired material structures are described, and potential pathways to integrate these into a comprehensive soft matter research environment are addressed. Solutions become available because soft matter technologies are benefitting from the synergies between organic synthesis, polymer chemistry, and materials science.


The evolving concept of the healthy worker survivor effect.
The "healthy worker survivor effect" describes a continuing selection process such that those who remain employed tend to be healthier than those who leave employment. In an analysis of exposure-response patterns in an occupational study, the healthy worker survivor effect generally attenuates an adverse effect of exposure. In practical terms, such attenuation will be more problematic when evaluating subtle rather than strong associations. The use of an internal referent does not guarantee elimination of this effect, since by definition, it manifests within an occupational cohort. Although documented over 100 years ago, there is little consensus regarding the most appropriate method to control for the healthy worker survivor effect. Four methods have been proposed for its control: (1) restriction of the cohort to survivors of a fixed number of years of follow-up, (2) lagging the exposure to exclude recent exposure incurred by those who remained on the job, (3) adjusting for employment status as a confounder, and (4) treating the healthy worker survivor effect simultaneously as an intermediate and confounding variable by means of the G-null test or its extension, G-estimation analysis, using structurally nested failure time models. This paper reviews the concept of the healthy worker survivor effect and the four methods to control for it.


Fitness to fly testing in term and ex-preterm babies without bronchopulmonary dysplasia.
During air flight, cabin pressurisation produces an effective fraction of inspired oxygen (FiO(2)) of 0.15. This can cause hypoxia in predisposed individuals, including infants with bronchopulmonary dysplasia (BPD), but the effect on ex-preterm babies without BPD was uncertain. The consequences of feeding a baby during the hypoxia challenge were also unknown. Ex-preterm (without BPD) and term infants had fitness to fly tests (including a period of feeding) at 3 or 6 months corrected gestational age (CGA) in a body plethysmograph with an FiO(2) of 0.15 for 20 min. A 'failed' test was defined as oxygen saturation (SpO(2)) <90% for at least 2 min. 41 term and 30 ex-preterm babies (mean gestational age 39.8 and 33.1 weeks, respectively) exhibited a significant median drop in SpO(2) (median -6%, p<0.0001); there was no difference between term versus ex-preterm babies, or 3 versus 6 months. Two term (5%) and two ex-preterm (7%) babies failed the challenge. The SpO(2) dropped further during feeding (median -4% in term and -2% in ex-preterm, p<0.0001), with transient desaturation (up to 30 s) <90% seen in 8/36 (22%) term and 9/28 (32%) ex-preterm infants; the ex-preterm babies desaturated more quickly (median 1 vs 3 min, p=0.002). Ex-preterm babies without BPD and who are at least 3 months CGA do not appear to be a particularly at-risk group for air travel, and routine preflight testing is not indicated. Feeding babies in an FiO(2) of 0.15 leads to a further fall in SpO(2), which is significant but transient.


[Assessment of Reduction Abilities of an Expandable Stent in Treating Osteoporosis-Related Fractures of Th/L (Thoracolumbar) Spine].
PURPOSE OF THE STUDY The method of stabilising the osteoporosis-related spinal fractures using an expandable stent (vertebral body stent - VBS) and bone cement is generally accepted for its minimal invasiveness, a low risk of complications and confirmed analgesic effect. The efficiency of reduction of a compressed vertebra is, however, still discussed in the literature. Our hypothesis was that the stent expansion in the vertebral body can achieve a statistically significant reduction in the anterior, middle and posterior part of the vertebra. MATERIAL AND METHODS The patients in whom the VBS technique was used to treat an osteoporosis-related fracture of Th/L spine in the period 2010-2014 were included in the study, namely 29 patients with 31treated fractures. The following radiographic parameters were monitored - anterior, middle and posterior vertebral body height, kyphotic angle between the upper and lower endplates of the vertebral body. Also, the radiation burden, painfulness according to VAS score and occurrence of complications were monitored. The minimum follow-up was 12 months. RESULTS The mean height of the anterior part of the vertebral body before the surgery, on the 1st postoperative day and at 6 weeks, 3 months, 6 months and 12 months was 23.5/25.4/23.9/23.6/23.6 mm respectively. The mean height of the middle part of the vertebral body at the same intervals was 17.9/24.0/23.4/22.9/22.9/22.9 mm. The mean height of the posterior part of the vertebral body was 29.6/29.8/29.4/29.3/29.2/29.2 mm. The kyphotic angle between the endplates of the vertebral body was 8.6/5.3/7.4/7.9/8.0/8.0°. The mean VAS values were 8.2/2.4/2.0/1.9/1.8/1.7. The mean duration of surgery was 54.3 minutes. The mean time of fluoroscopy was 33.4 s. The mean radiation dose was 443.1 cGycm2. The observed complications comprised 2 cases of dilatation balloon rupture, one case of a failure to expand the stents in a healed fracture due to incorrect indication. In total, four cases of cement leakage outside the vertebral body were reported, always with no clinical response. DISCUSSION All the authors agree that the method brings immediate analgesic effect, comparable to kyphoplasty or vertebroplasty. In our cohort, good reduction ability of the implant in the middle part of the vertebral body was confirmed. This has been confirmed also by other authors. Nonetheless, at a longer time interval the loss of correction was observed, which was reported only by Hartmann (5). The other authors mostly did not take into account the longer-term outcomes. CONCLUSIONS The hypothesis that the stent is capable of a statistically significant reduction in the anterior, middle and posterior portion of the vertebral body was only partially confirmed. A statistically significant reduction was seen only in the middle portion of the vertebral body. In the anterior portion of the vertebral body the reduction was demonstrable only immediately after the surgery, while the later follow-up checks revealed the loss of correction. The statistically significant improvement of the kyphotic angle between the endplates of the injured vertebra was also seen only on the first postoperative radiographs and at later follow-up checks the improvement was no more significant. The change in the height of the posterior portion of the vertebral body was not statistically significant at any of the follow-up intervals. Key words:osteoporosis, vertebral fracture, vertebral body augmentation, stentoplasty, vertebral body stent.


A model electronic Hamiltonian for the self-assembly of an octahedron-shaped coordination capsule.
A model electronic Hamiltonian to describe ligand exchange reactions of palladium(ii) complexes with pyridine (Py) and tridentate (L) ligands was developed. It was shown that the model Hamiltonian can adequately reproduce the structures and potential energies of the reactant/product, intermediate, and transition state of the ligand exchange reaction of [PdPy4]2+ with free Py. The model Hamiltonian was extended to describe reactions of multi-metal complexes and was adequately applied to describe various clusters, [PdaLbPyc]2a+, in the self-assembly of an octahedron-shaped coordination capsule, [Pd6L8]12+. The heterogeneity in the energetics of intermediate species [PdaLbPyc]2a+ was strongly suggested by the calculations, and the underlying microscopic interactions were clarified with the geometrical motif. The present framework provides a way to examine the reaction mechanisms of complex metal ligand self-assembly, which can be complementary microscopic information to the recently investigated novel experimental results for the real time evolutions.


Irritable bowel symptoms, use of healthcare, costs, sickness and disability pension benefits: A long-term population-based study.
Objectives: Irritable bowel syndrome (IBS) is associated with increased healthcare use and work absenteeism. We aimed to investigate long-term use of healthcare services and social benefits across IBS symptom groups. Additionally, we estimated excess healthcare costs. Methods: A longitudinal population-based study comprising two 5-year follow-up studies: The Danish part of the Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (Dan-MONICA) 1 (1982-1987) and Inter99 (1999-2004) recruited from the western part of Copenhagen County. The total study population (n = 7278) was divided into symptom groups according to degree of IBS definition fulfillment at baseline and/or 5-year follow-up and was followed until 31 December 2013 in Danish central registries. Poisson regression was used for the analyses adjusting for age, sex, length of education, comorbidity, cohort membership and mental vulnerability. Results: IBS symptom groups compared to no IBS symptoms were associated with an increased number of contacts with primary and secondary healthcare, as well as weeks on sickness and disability benefits. Accounting for mental vulnerability decreased the estimates and all but two associations between IBS symptom groups and outcomes remained statistically significant. The two associations that became insignificant were contacts with psychiatric hospitals and weeks on disability pension. The excess unadjusted healthcare costs for IBS were 680 Euros per year and the overall association between symptom groups and total healthcare costs were statistically significant. Conclusions: IBS symptoms influence the long-term use and costs of healthcare, as well as the use of social benefits in the general population. Mental vulnerability explained some, but not all, of the use of healthcare and social benefits.


Periodontal repair in dogs: recombinant human bone morphogenetic protein-2 significantly enhances periodontal regeneration.
This study evaluated bone and cementum regeneration following periodontal reconstructive surgery using recombinant human bone morphogenetic protein-2 (rhBMP-2) in six beagle dogs. Surgically created mandibular supraalveolar premolar tooth defects in contralateral jaw quadrants were randomly assigned to receive rhBMP-2 or control vehicle. Clinical defect height was prepared to 5 mm. rhBMP-2 was applied with synthetic bioerodable particles and autologous blood using 20 micrograms rhBMP-2 per 100 microliters implant volume. Flaps were advanced to submerge the teeth and sutured. The dogs were sacrificed 8 weeks postsurgery. Histometric recordings included defect height, height and area of alveolar bone regeneration, height of cementum regeneration, root resorption, and ankylosis. Group means, standard deviations, and P values are shown (Student t test; n = 6). Histometric defect height for rhBMP-2 and control defects was 3.7 +/- 0.3 and 3.9 +/- 0.4 mm, respectively (P = 0.446). Height of alveolar bone regeneration amounted to 3.5 +/- 0.6 and 0.8 +/- 0.6 mm for rhBMP-2 and control defects, respectively (P = 0.000). Corresponding values for bone area were 8.4 +/- 4.5 and 0.4 +/- 0.5 mm2, respectively (P = 0.006). Cementum regeneration was observed in all experimental defects (17/17) and in 15 out of 17 controls, averaging 1.6 +/- 0.6 and 0.4 +/- 0.3 mm for rhBMP-2 and control defects, respectively (P = 0.005). Small amounts of root resorption were seen in rhBMP-2 defects, whereas controls exhibited substantial resorption (0.2 +/- 0.1 and 1.1 +/- 0.3 mm, respectively; P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Purcell-factor-enhanced scattering from Si nanocrystals in an optical microcavity.
Scattering processes in an optical microcavity are investigated for the case of silicon nanocrystals embedded in an ultra-high-Q toroid microcavity. Using a novel measurement technique based on the observable mode splitting, we demonstrate that light scattering is highly preferential: more than 99.8% of the photon flux is scattered into the original doubly degenerate cavity modes. The large capture efficiency is shown to result from the Purcell enhancement of the optical density of states over the free space value, an effect that is more typically associated with spontaneous emission. The experimentally determined Purcell factor has a lower bound of 171.


Molecular typing and evaluation of Sidr honey inhibitory effect on virulence genes of MRSA strains isolated from catfish in Egypt.
Fish represent a worldwide significant source of animal protein. In order to investigate the prevalence of MRSA in catfish as well as the inhibitory effect of Sidr honey on virulence genes of MRSA, fish were collected from Bahr Elbaker canal at Sharkia Governorate, Egypt. Swab samples were collected under complete aseptic conditions from internal organs (pancreas, liver, kidney and intestine), gills and skin then subjected to bacteriological examination. A total of 70 S. aureus strains were isolated from catfish, out of them 15 (21.42%) strains were identified as MRSA as a first record in Egypt. PCR was used for detection of meca, coa and spa genes in the isolated MRSA strains before and after the exposure to sidr honey. Before exposure to sider honey, all the selected MRSA strains showed positive results for meca, coa and spa genes with specific amplicon size of 310 bp, 430 bp and 226 bp, respectively. After exposure to sidr honey, MRSA strains showed inhibition of coa and spa genes, but has no effect on meca gene. In addition, scanning electron microscopy was used for detection of the morphological characters of MRSA strains before and after treatment with sidr honey. After exposure of MRSA strains to 30% (w/v) Sidr honey for 48 hours, cells surfaces were observable irregular with the appearance of cell debris. In conclusion, MRSA strains could be isolated from fresh water catfish in Egypt which may be attributed to the contamination of water and fish food. Sider honey showed a significant inhibitory effect on the growth of isolated MRSA strains. Moreover, it could inhibit spa and coa genes. SEM is a valuable tool revealing the abnormal morphological changes that take place in MRSA strains after exposure to Sidr honey.


Systemic sarcoidosis complicated of acute renal failure: about 12 cases.
The sarcoidosis is a systemic granulomatosis affecting most frequently the lungs and the mediastinum. An acute renal failure reveals exceptionally this disease. It's a retrospective study implicating 12 cases of sarcoidosis complicated of acute renal failure. The aim of this study is to determine epidemiological, clinical, biological and histological profile in these cases and then to indicate the interest to consider the diagnosis of sarcoidosis in cases of unexplained renal failure. Extra-renal complications, therapeutic modalities and the outcome were determined in all patients. Our series involved 12 women with an average age of 40 years. Biological investigations showed an abnormal normocalcemia in 7 cases, a hypercalcemia in 5 cases, a hypercalciuria in 10 cases and polyclonal hypergammaglobulinemia in 7 cases. An acute renal failure was found in all patients with a median creatinin of 520 umol/L. For all patients, the renal echography was normal however, the kidney biopsy showed tubulo-interstitial nephritis. The extra-renal signs highlighting pulmonary interstitial syndrome in 5 cases, a sicca syndrome in 4 cases, mediastinal lymph nodes in 2 cases, a lymphocytic alveolitis in 3 cases, an anterior granulomatous uveitis in 2 cases and a polyarthritis in 5 cases. Five patients benefited of hemodialysis. The treatment consisted of corticosteroid in all cases. The follow up was marked by complete resolution of clinical and biological signs. The diagnosis of renal sarcoidosis must be done quickly to prevent renal failure.


Evaluation of Lymphatic Filariasis and Onchocerciasis in Three Senegalese Districts Treated for Onchocerciasis with Ivermectin.
In Africa, onchocerciasis and lymphatic filariasis (LF) are co-endemic in many areas. Current efforts to eliminate both diseases are through ivermectin-based mass drug administration (MDA). Years of ivermectin distribution for onchocerciasis may have interrupted LF transmission in certain areas. The Kédougou region, Senegal, is co-endemic for LF and onchocerciasis. Though MDA for onchocerciasis started in 1988, in 2014 albendazole had not yet been added for LF. The objective of this study was to assess in an integrated manner the LF and onchocerciasis status in the three districts of the Kédougou region after ≥10 years of ivermectin-based MDA. The study employed an African Programme for Onchocerciasis Control (APOC) onchocerciasis-related methodology. In the three districts, 14 villages close to three rivers that have Simulium damnosum breeding sites were surveyed. Convenience sampling of residents ≥5 years old was performed. Assessment for LF antigenemia by immunochromatographic testing (ICT) was added to skin snip microscopy for onchocerciasis. Participants were also tested for antibodies against Wb123 (LF) and Ov16 (onchocerciasis) antigens. In two districts, no participants were ICT or skin snip positive. In the third district, 3.5% were ICT positive and 0.7% were skin snip positive. In all the three districts, Wb123 prevalence was 0.6%. Overall, Ov16 prevalence was 6.9%. Ov16 prevalence among children 5-9 years old in the study was 2.5%. LF antigenemia prevalence was still above treatment threshold in one district despite ≥10 years of ivermectin-based MDA. The presence of Ov16 positive children suggested recent transmission of Onchocerca volvulus. This study showed the feasibility of integrated evaluation of onchocerciasis and LF but development of integrated robust methods for assessing transmission of both LF and onchocerciasis are needed to determine where MDA can be stopped safely in co-endemic areas.


Unexpected selection to retain high GC content and splicing enhancers within exons of multiexonic lncRNA loci.
If sequencing was possible only for genomes, and not for RNAs or proteins, then functional protein-coding exons would be recognizable by their unusual patterns of nucleotide composition, specifically a high GC content across the body of exons, and an unusual nucleotide content near their edges. RNAs and proteins can, of course, be sequenced but the extent of functionality of intergenic long noncoding RNAs (lncRNAs) remains under question owing to their low nucleotide conservation. Inspired by the nucleotide composition patterns of protein-coding exons, we sought evidence for functionality across lncRNA loci from diverse species. We found that such patterns across multiexonic lncRNA loci mirror those of proteincoding genes, although to a lesser degree: Specifically, compared with introns, lncRNA exons are GC rich. Additionally we report evidence for the action of purifying selection to preserve exonic splicing enhancers within human multiexonic lncRNAs and nucleotide composition in fruit fly lncRNAs. Our findings provide evidence for selection for more efficient rates of transcription and splicing within lncRNA loci. Despite only a minor proportion of their RNA bases being constrained, multiexonic intergenic lncRNAs appear to require accurate splicing of their exons to transact their function.


Effects of Meal Timing on Postprandial Glucose Metabolism and Blood Metabolites in Healthy Adults.
We examined the effects of meal timing on postprandial glucose metabolism, including the incretin response and metabolites in healthy adults. Nineteen healthy young men completed two trials involving blood collection in a fasting state and at 30, 60 and 120 min after meal provision in a random order: (1) morning (~0900 h) and (2) evening (~1700 h). The blood metabolome of eight participants was analyzed using capillary electrophoresis-mass spectrometry. Postprandial glucose concentrations at 120 min (p = 0.030) and glucose-dependent insulinotropic polypeptide concentrations (p = 0.005) at 60 min in the evening trials were higher than those in the morning trials. The incremental area under the curve values of five glycolysis, tricarboxylic acid cycle and nucleotide-related metabolites and 18 amino acid-related metabolites were higher in the morning trials than those in the evening trials (p < 0.05). Partial least-squares analysis revealed that the total metabolic change was higher in the morning. Our study demonstrates that a meal in the evening exacerbates the state of postprandial hyperglycemia in healthy adults. In addition, this study provides insight into the difference of incretion and blood metabolites between breakfast and dinner, indicating that the total metabolic responses tends to be higher in the morning.


A yeast artificial chromosome contig that spans the RB1-D13S31 interval on human chromosome 13 and encompasses the frequently deleted region in B-cell chronic lymphocytic leukemia.
Abnormalities involving chromosome 13 have been reported as the only cytogenetic change in B-cell chronic lymphocytic leukemia (BCLL). Deletions are the most common cytogenetic abnormality and always involve 13q14, but when translocations are seen, the consistent breakpoint is always in 13q14. It is now established that deletions, distal to the RB1 gene in 13q14, are invariably associated with these translocations. We have recently described the smallest such deletion from a series of rearrangements from these tumors isolated in somatic cell hybrids, which spans approximately 1 Mb. In this report, we present the results of a series of a chromosome walking experiments using YACs and have been able to span this small deletion, which must contain the gene that is frequently deleted in BCLL. Four probes from 13q14 (RB1-mgg15-D13S25-D13S31) were used to isolate corresponding YACs for each of the markers. The chromosomal location of these YACs was verified using FISH, which also demonstrated their nonchimeric nature. Vectorette end rescue was then used to demonstrate the overlap of the YACs and to isolate new clones to complete the contig. The extremes of the contig were shown to cross the chromosome 13 translocation breakpoints isolated in somatic cell hybrids that carry the derivatives of chromosome 13 involved in the smallest BCLL deletion. This YAC contig covers the entire deletion and will prove a valuable resource to begin isolating genes from this region. In addition, we have isolated YACs corresponding to the RB1 locus, which extends the contig over a 3.8-cM distance on the chromosome.


Redox chemistry of vanadium in soils and sediments: Interactions with colloidal materials, mobilization, speciation, and relevant environmental implications- A review.
Vanadium (V), although serving as an important component of industrial activities, has bioinorganic implications to pose highly toxic hazards to humans and animals. Soils and sediments throughout the world exhibit wide ranges of vanadium concentrations. Although vanadium toxicity varies between different species, it is mainly controlled by soil redox potential (EH). Nonetheless, knowledge of the redox geochemistry of vanadium lags in comparison to what is known about other potentially toxic elements (PTEs). In particular, the redox-induced speciation and mobilization of vanadium in soils and sediments and the associated risks to the environment have not been reviewed to date. Therefore, this review aims to address 1) the content and geochemical fate of vanadium in soils and sediments, 2) its redox-induced release dynamics, 3) redox-mediated chemical reactions between vanadium and soil organic and inorganic colloidal materials in soil solution, 4) its speciation in soil solution and soil-sediments, and 5) the use of advanced geochemical and spectroscopic techniques to investigate these complex systems. Vanadium (+5) is the most mobile and toxic form of its species while being the thermodynamically stable valence state in oxic environments, while vanadium (+3) might be expected to be predominant under euxinic (anoxic and sulfidic) conditions. Vanadium can react variably in response to changing soil EH: under anoxic conditions, the mobilization of vanadium can decrease because vanadium (+5) can be reduced to relatively less soluble vanadium (+4) via inorganic reactions such as with H2S and organic matter and by metal-reducing microorganisms. On the other hand, dissolved concentrations of vanadium can increase at low EH in many soils to reveal a similar pattern to that of Fe, which may be due to the reductive dissolution of Fe(hydr)oxides and the release of the associated vanadium. Those differences in vanadium release dynamics might occur as a result of the direct impact of EH on vanadium speciation in soil solution and soil sediments, and/or because of the EH-dependent changes in soil pH, chemistry of (Fe)(hydr)oxides, and complexation with soil organic carbon. Release dynamics of vanadium in soils may also be affected positively by soil pH and the release of aromatic organic compounds. X-ray absorption spectroscopy (XAS) is a powerful tool to investigate the speciation of vanadium present in soil. X-ray absorption near edge structure (XANES) is often used to constrain the average valence state of vanadium in soils and sediments, and in limited cases extended X-ray absorption fine structure (EXAFS) analysis has been used to determine the average molecular coordination environment of vanadium in soil components. In conclusion, this review presents the state of the art about the redox geochemistry of vanadium and thus contributes to a better understanding of the speciation, potential mobilization, and environmental hazards of vanadium in the near-surface environment of uplands, wetlands, and agricultural ecosystems as affected by various colloidal particles. Further research is needed to elucidate the geochemistry and speciation of vanadium in the dissolved, colloidal, and soil sediments phases, including the determination of factors that control the redox geochemistry of vanadium.


Checkers is solved.
The game of checkers has roughly 500 billion billion possible positions (5 x 10(20)). The task of solving the game, determining the final result in a game with no mistakes made by either player, is daunting. Since 1989, almost continuously, dozens of computers have been working on solving checkers, applying state-of-the-art artificial intelligence techniques to the proving process. This paper announces that checkers is now solved: Perfect play by both sides leads to a draw. This is the most challenging popular game to be solved to date, roughly one million times as complex as Connect Four. Artificial intelligence technology has been used to generate strong heuristic-based game-playing programs, such as Deep Blue for chess. Solving a game takes this to the next level by replacing the heuristics with perfection.


Clinical efficacy of one stage posterior debridement joint graft fixation for lumbar vertebral fractures in spinal tuberculosis patients with compression.
Spinal tuberculosis, though destructive, can be cured in many patients by chemotherapy, though surgery is often necessary for decompression and deformity correction. Our aim of this study was to investigate the clinical efficacy of posterior debridement joint graft fixation therapy for lumbar vertebral fractures in patients with spinal tuberculosis with a compression fracture. We prospectively included 48 patients diagnosed with spinal tuberculosis and lumbar compression fracture in our hospital from June 2010 to June 2013. The patients were randomly divided into observation group (n = 27) and control group (n = 21). The patients in the control group underwent an anterior debridement joint bone fixation therapy, whereas, the patients in the observation group underwent one stage posterior debridement joint bone fixation therapy. The patients in the both groups were followed-up for about 2 years and the postoperative complications were recorded and analyzed. Incision length, operative time and blood loss in patients of the observation group were significantly lower than the control group (p < 0.05). The kyphosis Cobb's angle was found to be reduced in a time-dependent manner in both groups, however, patients in the observation group achieved a significant reduction than the control (p < 0.05). The ASIA grade of few patients in the observation group significantly (p < 0.05) improved to class E from D at the time of the end of follow-up. The patients under the class 'excellent' and 'good' of Kirkaldy-Willis criteria were significantly (p < 05) higher in the observation group (92.6%) than the control group (85.7%). Also, the patients in the Bridwell grade I and II in the observation group (88.9%) were significantly (p < 0.05) higher in comparison with control group (81%). The prevalence of postoperative complications was significantly lower in the observation group (18.5%) when compared with the control group (28.6%). Our results indicate that one-stage posterior debridement joint bone fixation therapy is an effective and safe procedure for patients with spinal tuberculosis and lumbar compression; this method is worthy of clinical application.


Effectiveness and efficiency of search methods in systematic reviews of complex evidence: audit of primary sources.
To describe where papers come from in a systematic review of complex evidence. Method Audit of how the 495 primary sources for the review were originally identified. Only 30% of sources were obtained from the protocol defined at the outset of the study (that is, from the database and hand searches). Fifty one per cent were identified by "snowballing" (such as pursuing references of references), and 24% by personal knowledge or personal contacts. Systematic reviews of complex evidence cannot rely solely on protocol-driven search strategies.


How ubiquitous are physical and psychological complaints in young and middle adulthood? A longitudinal perspective.
To investigate continuity and change of self-reported physical and psychological complaints in young adults over a period of 20 years. The Zurich Study--a long-term panel survey in psychiatric epidemiology--is based on a stratified sample of 591 subjects born in 1958 (women) and 1959 (men). The sample strata combine SCL-90-R high-scorers and low-scorers in a 2:1 ratio. Up to now, the Zurich Study has included six interviews between 1979 and 1999, i.e. 20 years of life in young adults. We analysed the longitudinal frequency data of a variety of physical and psychological complaints, as well as information about subjective suffering and use of professional help. The analyses utilised on the McNemar's test, the Q-test and Markov chain models. Sleep disorders, depression, menstruation, backache, headache, stomach and bowel complaints yielded cumulative prevalence rates of 80% or higher. Physical and psychological complaints systematically differ with respect to the change patterns between 1979 and 1999. Moreover, strong differences were found in view of subjective suffering and use of professional help. Even though many self-reported physical and psychological complaints are very common in young adulthood, the underlying dynamics and the implications largely differ. It seems to be crucial whether respondents use somatic glasses or psychological lenses.


A genetic screen for hedgehog targets involved in the maintenance of the Drosophila anteroposterior compartment boundary.
The development of multicellular organisms requires the establishment of cell populations with different adhesion properties. In Drosophila, a cell-segregation mechanism underlies the maintenance of the anterior (A) and posterior (P) compartments of the wing imaginal disc. Although engrailed (en) activity contributes to the specification of the differential cell affinity between A and P cells, recent evidence suggests that cell sorting depends largely on the transduction of the Hh signal in A cells. The activator form of Cubitus interruptus (Ci), a transcription factor mediating Hh signaling, defines anterior specificity, indicating that Hh-dependent cell sorting requires Hh target gene expression. However, the identity of the gene(s) contributing to distinct A and P cell affinities is unknown. Here, we report a genetic screen based on the FRT/FLP system to search for genes involved in the correct establishment of the anteroposterior compartment boundary. By using double FRT chromosomes in combination with a wing-specific FLP source we screened 250,000 mutagenized chromosomes. Several complementation groups affecting wing patterning have been isolated, including new alleles of most known Hh-signaling components. Among these, we identified a class of patched (ptc) alleles exhibiting a novel phenotype. These results demonstrate the value of our setup in the identification of genes involved in distinct wing-patterning processes.


Electron microscopy of the tapetum lucidum of the cat.
The fine structure of the tapetum of the cat eye has been investigated by electron microscopy. The tapetum is made up of modified choroidal cells, seen as polygonal plates grouped around penetrating blood vessels which terminate in the anastomosing capillary network of the choriocapillaris. The tapetal cells are rectangular in cross-section, set in regular brick-like rows, and attain a depth of some thirty-five cell layers in the central region. This number is gradually reduced peripherally, and is replaced at the margin of the tapetum by normal choroidal tissue. The individual cells are packed with long slender rods 0.1 micro by 4 to 5 micro. The rods are packed in groups and with their long axes oriented roughly parallel to the plane of the retinal surface. Each cell contains several such groups. Cells at the periphery or in the outer layers of the tapetum are frequently seen to contain both tapetal rods and melanin granules, the latter typical of the choroidal melanocytes. Also melanocyte granules may have intermediate shapes. These observations plus the similar density of the two inclusions lead to the belief that the tapetal rods may be melanin derivatives. A fibrous connective tissue layer lies between the tapetum and the retina. The subretinal capillary network, the choriocapillaris, rests on this layer and is covered by the basement membrane of the retinal epithelium. The cytoplasm of the retinal epithelium exhibits marked absorptive modifications where it comes in contact with the vessels of the choriocapillaris. This fibrous layer and the basement membrane of the retinal epithelium apparently comprise the structural elements of Bruch's membrane.


Stable xenon CT CBF measurements in prevalent cerebrovascular disorders (stroke).
Local cerebral blood flow (LCBF) and local tissue: blood partition coefficient (L lambda) values were measured for small volumes of gray or white matter by CT CBF. Single compartment analysis was used but fitted to infinity in normal volunteers aged between 20 to 100 years (N = 20). Hemispheric LCBF and L lambda values were compared to those of 61 age matched patients with transient ischemic attacks (TIAs, N = 10), reversible ischemic neurologic deficits (RINDS, N = 10), acute and chronic cerebral infarctions associated with emboli from atherosclerotic plaques or complete occlusion of internal carotid or middle cerebral arteries (n = 9) or of cardiac origin (N = 3), cerebral hemorrhage (N = 1), multi-infarct dementia (MID) (N = 11) and arteriovenous malformations (AVM) (N = 17). In normal aging, L lambda s were normal, but LCBF showed diffuse age-related declines. Symptomatic cerebrovascular disease was characterized by accentuation of age-related LCBF declines. TIAs with unilateral ICA occlusion showed bilateral reductions of LCBF more evident in ischemic hemispheres. TIAs due to fibrino-platelet emboli from ulcerated, non-occlusive ICA plaques were characterized by transient unilateral, localized LCBF reductions. All TIAs showed normal L lambda values. RINDS showed both LCBF and L lambda reductions. Larger embolic infarctions of ICA origin, whether acute or chronic, showed zones of zero flow with surrounding reductions of LCBF and L lambda values. Recent cerebral embolism of cardiac origin likewise exhibited zones of zero flow surrounded by reduced LCBF and L lambda values; but in chronic stages LCBF and L lambda values adjacent to zero flow zones were normal. MID was characterized by patchy reductions of LCBF and L lambda values throughout both hemispheres. Brain tissues surrounding AVM showed normal L lambda values but LCBF values were reduced due to steal.


Sterol Methyl Oxidases Affect Embryo Development via Auxin-Associated Mechanisms.
Sterols are essential molecules for multiple biological processes, including embryogenesis, cell elongation, and endocytosis. The plant sterol biosynthetic pathway is unique in the involvement of two distinct sterol 4α-methyl oxidase (SMO) families, SMO1 and SMO2, which contain three and two isoforms, respectively, and are involved in sequential removal of the two methyl groups at C-4. In this study, we characterized the biological functions of members of the SMO2 gene family. SMO2-1 was strongly expressed in most tissues during Arabidopsis (Arabidopsis thaliana) development, whereas SMO2-2 showed a more specific expression pattern. Although single smo2 mutants displayed no obvious phenotype, the smo2-1 smo2-2 double mutant was embryonic lethal, and the smo2-1 smo2-2/+ mutant was dwarf, whereas the smo2-1/+ smo2-2 mutant exhibited a moderate phenotype. The phenotypes of the smo2 mutants resembled those of auxin-defective mutants. Indeed, the expression of DR5rev:GFP, an auxin-responsive reporter, was reduced and abnormal in smo2-1 smo2-2 embryos. Furthermore, the expression and subcellular localization of the PIN1 auxin efflux facilitator also were altered. Consistent with these observations, either the exogenous application of auxin or endogenous auxin overproduction (YUCCA9 overexpression) partially rescued the smo2-1 smo2-2 embryonic lethality. Surprisingly, the dwarf phenotype of smo2-1 smo2-2/+ was completely rescued by YUCCA9 overexpression. Gas chromatography-mass spectrometry analysis revealed a substantial accumulation of 4α-methylsterols, substrates of SMO2, in smo2 heterozygous double mutants. Together, our data suggest that SMO2s are important for correct sterol composition and function partially through effects on auxin accumulation, auxin response, and PIN1 expression to regulate Arabidopsis embryogenesis and postembryonic development.


Applying the chronic care model to homeless veterans: effect of a population approach to primary care on utilization and clinical outcomes.
We compared a population-tailored approach to primary care for homeless veterans with a usual care approach. We conducted a retrospective prolective cohort study of homeless veterans enrolled in a population-tailored primary care clinic matched to a historical sample in general internal medicine clinics. Overall, 177 patients were enrolled: 79 in the Homeless-Oriented Primary Care Clinic and 98 in general internal medicine primary care. Homeless-oriented primary care-enrolled patients had greater improvements in hypertension, diabetes, and lipid control, and primary care use was higher during the first 6 months (5.96 visits per person vs 1.63 for general internal medicine) but stabilized to comparable rates during the second 6 months (2.01 vs 1.31, respectively). Emergency department (ED) use was also higher (2.59 vs 1.89 visits), although with 40% lower odds for nonacute ED visits than for the general internal medicine group (95% confidence interval = 0.2, 0.8). Excluding substance abuse and mental health admissions, hospitalizations were reduced among the homeless veterans between the 2 periods (28.6% vs 10.8%; P < .01) compared with the general internal medicine group (48.2% vs 44.4%; P = .6; difference of differences, P < .01). Tailoring primary care to homeless veterans can decrease unnecessary ED use and medical admissions and improve chronic disease management.


Estimating the Global Incidence of Aneurysmal Subarachnoid Hemorrhage: A Systematic Review for Central Nervous System Vascular Lesions and Meta-Analysis of Ruptured Aneurysms.
There is increasing acknowledgement that surgical care is important in global health initiatives. In particular, neurosurgical care is as limited as 1 per 10 million people in parts of the world. We performed a systematic literature review to examine the worldwide incidence of central nervous system vascular lesions and a meta-analysis of aneurysmal subarachnoid hemorrhage (aSAH) to define the disease burden and inform neurosurgical global health efforts. A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to estimate the global epidemiology of central nervous system vascular lesions, including unruptured and ruptured aneurysms, arteriovenous malformations, cavernous malformations, dural arteriovenous fistulas, developmental venous anomalies, and vein of Galen malformations. Results were organized by World Health Organization regions. After literature review, because of a lack of data from particular World Health Organization regions, we determined we could only provide an estimate of aSAH. Using data from studies with aSAH and 12 high-quality stroke studies from regions lacking data, we meta-analyzed the yearly crude incidence of aSAH per 100,000 persons. Estimates were generated via random-effects models. From an initial yield of 1492 studies, 46 manuscripts on aSAH incidence were included. The final meta-analysis included 58 studies from 31 different countries. We estimated the global crude incidence for aSAH to be 6.67 per 100,000 persons with a wide variation across WHO regions from 0.71 to 12.38 per 100,000 persons. Worldwide, almost 500,000 individuals will suffer from aSAH each year, with almost two-thirds in low- and middle-income countries.


Missed by an inch or a mile? Predicting the size of intention-behaviour gap from measures of executive control.
Failing to achieve healthy intentions can have a direct impact on subsequent health. The extent of this impact is partially determined by the size of the discrepancy between intentions and behaviour, that is, on whether an unachieved behavioural target is missed by an inch or a mile. Over two studies, measures of 'executive control' ability were used to predict the size of the intention-behaviour gap for two dietary behaviours - eating fruits and vegetables and snacking. In Study 1, participants (n=50) reported intended dietary intake, completed objective and self-report measures of executive control ability and recorded actual dietary intake over 3 days with computerised diaries. Using multiple regression, general executive control ability was found to account for 16-23% of the variance in the size of intention-behaviour gap for both the dietary behaviours. In Study 2 (n=52), deviation from intentions about snacking was significantly related to individual differences in prepotent response inhibition. Overall, individuals with weak executive control ate less fruits and vegetables and more snacks than intended. Intention-behaviour 'failures' are not homogenous, but instead vary predictably with the availability of executive control resources. This suggests that individuals with large intention-behaviour shortfalls may benefit from interventions designed to reduce the demands on executive control.