Visualizing invisibility: metamaterials-based optical devices in natural environments.
Photorealistic ray tracing methods have been developed that allow us to see how devices such as imperfect invisible spheres and invisibility cloaks would appear if actually constructed and placed in outdoor environments. The methods developed allow photorealistic depiction of devices with gradient indices of refraction and birefringence or trirefringence in non-Cartesian coordinate systems (and hence accurately handle ray splitting/beam walkoff). The resulting images, which can be rendered in real time to produce animations as will be shown, allow subjective assessment of the performance of optical instruments such as invisibility devices in environments in which they are intended to ultimately be used.


Factors Associated with Knowledge and Awareness of Stroke Among the Jordanian Population: A Cross-Sectional Study.
Background and objective: Stroke is the second leading cause of death in Jordan and over the world. Knowledge and awareness towards stroke play a crucial role in the management and prevention of its complications. This study aims to assess the knowledge and awareness about stroke among the Jordanian population and determine factors associated with stroke awareness. Methods: This cross-sectional study through a web-based anonymous questionnaire that needed 10 minutes to be completed. It examined sociodemographic characteristics and recognition of the risk factors, warning signs, stroke consequences, and early response to stroke symptoms. Logistic regression analysis identified the factors associated with poor knowledge of stroke. Results: A total of 573 Jordanian adults participated in this study. The participant's ability to identify at least one early symptom of stroke and the proper response to the symptoms were significantly correlated with the educational level (OR of 3.4 and 2.5, respectively). At least one consequence of stroke was significantly associated with different demographic factors such as gender, socioeconomic income, females versus males and those with medium income versus low income had significantly higher odds (OR of 6.6 and 4.1, respectively). Conclusion: This study revealed a good knowledge and awareness level about stroke among Jordanians correlated mainly with their educational level. Therefore, new strategies should be considered to decrease the prevalence of stroke in Jordan, including the need for engagement in enhanced awareness campaigns.


Sympathetic activity in brown adipose tissue in lactating mice.
Sympathetic activity has been assessed, by measurements of norepinephrine turnover, in interscapular brown adipose tissue of mice during lactation. Norepinephrine turnover was reduced in brown adipose tissue from early lactation until weaning. The reduction in turnover occurred in dams suckling either large-or small-sized litters. Norepinephrine turnover returned to the control level after natural weaning and increased rapidly after abrupt weaning at peak lactation. Acute exposure to cold resulted in a large increase in norepinephrine turnover in brown adipose tissue of lactating mice, as in control animals. These results indicate that sympathetic activity is suppressed in brown adipose tissue during lactation, but sympathetic responsiveness is retained. The reduction in sympathetic activity is likely to be responsible for the decrease in brown adipose tissue thermogenesis in lactation. Norepinephrine turnover in the heart tended to be reduced at peak lactation, suggesting that there may be a general decrease in sympathetic activity in the lactating animal. In contrast to the normal animal, the hyperphagia of lactation does not lead to an activation of the sympathetic nervous system.


Severe, permanent orbital disease in herpes zoster ophthalmicus.
A 63-year-old man with HZO presented with involvement of cranial nerves II, III, IV, V, and VI, with proptosis, raised intraocular pressure, and chemosis. With the aid of orbital imaging, a diagnosis of orbital apex inflammation secondary to HZO was confirmed, and he was treated with intravenous acyclovir and oral steroids. Despite this, he made a minimal recovery at eight months following presentation. Severe, irreversible orbital disease may develop following HZO, and an ischemic vasculitis may play a role in the pathogenesis of the disease.


Suicide ideation and attempt in a community cohort of urban Aboriginal youth: a cross-sectional study.
There has been increasing attention over the last decade on the issue of indigenous youth suicide. A number of studies have documented the high prevalence of suicide behavior and mortality in Australia and internationally. However, no studies have focused on documenting the correlates of suicide behavior for indigenous youth in Australia. To examine the prevalence of suicide ideation and attempt and the associated factors for a community1 cohort of Koori2 (Aboriginal) youth. Data were obtained from the Victorian Aboriginal Health Service (VAHS) Young People's Project (YPP), a community initiated cross-sectional data set. In 1997/1998, self-reported data were collected for 172 Koori youth aged 12-26 years living in Melbourne, Australia. The data were analyzed to assess the prevalence of current suicide ideation and lifetime suicide attempt. Principal components analysis (PCA) was used to identify closely associated social, emotional, behavioral, and cultural variables at baseline and Cox regression modeling was then used to identify associations between PCA components and suicide ideation and attempt. Ideation and attempt were reported at 23.3% and 24.4%, respectively. PCA yielded five components: (1) emotional distress, (2) social distress A, (3) social distress B, (4) cultural connection, (5) behavioral. All were positively and independently associated with suicide ideation and attempt, while cultural connection showed a negative association. Suicide ideation and attempt were common in this cross-section of indigenous youth with an unfavorable profile for the emotional, social, cultural, and behavioral factors.


Activation of the c-Jun N-terminal kinase pathway by a novel protein kinase related to human germinal center kinase.
The c-Jun N-terminal kinase (JNK), or stress-activated protein kinase plays a crucial role in cellular responses stimulated by environmental stress and proinflammatory cytokines. However, the mechanisms that lead to the activation of the JNK pathway have not been elucidated. We have isolated a cDNA encoding a novel protein kinase that has significant sequence similarities to human germinal center kinase (GCK) and human hematopoietic progenitor kinase 1. The novel GCK-like kinase (GLK) has a nucleotide sequence that encodes an ORF of 885 amino acids with 11 kinase subdomains. Endogenous GLK could be activated by UV radiation and proinflammatory cytokine tumor necrosis factor alpha. When transiently expressed in 293 cells, GLK specifically activated the JNK, but not the p42/44(MAPK)/extracellular signal-regulated kinase or p38 kinase signaling pathways. Interestingly, deletion of amino acids 353-835 in the putative C-terminal regulatory region, or mutation of Lys-35 in the putative ATP-binding domain, markedly reduced the ability of GLK to activate JNK. This result indicates that both kinase activity and the C-terminal region of GLK are required for maximal activation of JNK. Furthermore, GLK-induced JNK activation could be inhibited by a dominant-negative mutant of mitogen-activated protein kinase kinase kinase 1 (MEKK1) or mitogen-activated protein kinase kinase 4/SAPK/ERK kinase 1 (SEK1), suggesting that GLK may function upstream of MEKK1 in the JNK signaling pathway.


Optimal duration for continuation of statin therapy in bacteremic patients.
Evidence suggests statins may improve survival in patients with bloodstream infections. However, there is no consensus on optimal timing and duration of exposure. To quantify statin therapy duration associated with decreased mortality in bacteremic statin users. We conducted a case-control study using OptumClinformatics™ with matched Premier hospital data (1 October 2009-31 March 2013). Cases who died during the hospitalization were matched 1:1 to survivors on disease risk scores (DRSs). Post-admission statin therapy duration was evaluated in patients with at least 90 days of pre-admission continuous statin use. Classification and regression tree (CART) analysis was conducted to identify the optimal duration of statin continuation which provided the lowest inpatient mortality. Logistic regression was used to calculate the odds of mortality. We included 58 DRS matched pairs of cases and controls: 47 patients (41%) continued statin therapy during the hospital admission, 15 (32%) cases and 32 (68%) controls. The CART analysis partitioned the continuation of statin therapy at ⩾2 days, representing lower mortality for patients who continued statins for 2 days or more and higher mortality for patients who did not continue or remained on statins for only 1 day. Inpatient mortality was 76% lower among those with at least 2 days of continued statin use (odds ratio 0.24, 95% confidence interval 0.11-0.55). Among matched cases and controls with at least 90 days of baseline statin use prior to the admission, the continuation of statins for at least 2 days after admission demonstrated a survival benefit among bacteremic patients.


Silica nanovehicles endow arsenic trioxide with an ability to effectively treat cancer cells and solid tumors.
Arsenic trioxide is a clinical drug that can be used to successfully treat acute promyelocytic leukemia. However, its therapeutic effect on solid tumors is limited because of the poor pharmacokinetics and dose-limiting toxicity. Here, we report a facile strategy to achieve high anticancer activity of arsenic trioxide by loading the nanoparticulate prodrug into hollow silica inorganic nanoparticles. Because of the appropriate size, pH sensitivity, and surface targeted modification, this smart nanosized drug system can deliver arsenic trioxide into cancer cells efficiently and exhibits much higher cytotoxicity to a variety of cancer cells than free arsenic trioxide. Moreover, this nanomedicine can further promote the differentiation and inhibit the migration of cancer cells. In vivo results suggest that this drug delivery system can significantly inhibit the growth of solid tumors without adverse side effects. This study highlights a feasible drug delivery strategy to expand the use of arsenic trioxide for the effective treatment of solid tumors.


Slow virus replication: the role of macrophages in the persistence and expression of visna viruses of sheep and goats.
Lentiviruses of sheep and goats cause slowly progressive diseases of the central nervous system (visna), lungs (maedi) and joints (arthritis) in their natural hosts. However, the virus target cell(s) in these diseases are still unknown. In this report, using laboratory-adapted Icelandic visna virus and several field strains recently obtained from sheep and goats with natural disease in the U.S.A., we show that macrophages became persistently infected when inoculated in culture. Furthermore, macrophages were an invariable source of virus from experimentally and naturally infected animals. Virus-producing macrophages developed minimal cytopathic changes and virus assembly occurred mainly intracellularly, accumulating in cytoplasmic vacuoles. In contrast to macrophages, sheep choroid plexus fibroblasts developed syncytial cytopathic changes after inoculation and virus maturation occurred at the cell surfaces. Replication of the Icelandic virus was highly productive in this system but that of the field viruses was very inefficient. In some cases these agents failed to replicate in the fibroblasts and no cytopathic effect occurred. This block in the field virus replication was, however, overcome when infected nonproducer fibroblasts were co-cultivated with macrophages. In these cases, virus production with attendant cytopathic effect in the fibroblasts required the continuous presence of macrophages because the cells reverted to a non-productive state when separated from macrophages and became productive again when subcultures were added to new macrophages. The roles of the macrophage as a virus target cell and virus inducer in the virus-macrophage-fibroblast interactions are discussed with inferences to the well-known phenomenon of restricted virus replication in infected animals and the immunopathological aspects of the diseases.


Outbreak of pertussis in Basra, Iraq.
A total of 133 pertussis cases were studied during an outbreak in Basra from June to December 1996. Most were females and were immunized. Bordetella spp. was isolated in 48.1% of the cases. The isolation rate was highest among infants and decreased with increasing age, and was highest during the catarrhal stage. B. pertussis was the most common species; however, B. parapertussis infection did occur. There were some severe cases of pertussis among infants caused mainly by B. pertussis and dual Bordetella infection. Infection was transmitted by close contact with a pertussis case.


Impeller behavior and displacement of the VentrAssist implantable rotary blood pump.
The VentrAssist implantable rotary blood pump, intended for long-term ventricular assist, is under development and is currently being tested for its rotor-dynamic stability. The pump is of the centrifugal type and consists of a shaftless impeller, also acting as the rotor of the brushless DC motor. The impeller remains passively suspended in the pump cavity by hydrodynamic forces, resulting from the small clearances between the impeller outside surfaces and the pump cavity. In the older version of the pump tested, these small clearances range from approximately 50 microm to 230 microm; the displacement of the impeller relative to the pump cavity is unknown in use. This article presents two experiments: the first measured displacement of the impeller using eddy-current proximity sensors and laser proximity sensors. The second experiment used Hall-effect proximity sensors to measure the displacement of the impeller relative to the pump cavity. All transducers were calibrated prior to commencement of the experiments. Voltage output from the transducers was converted into impeller movement in five degrees of freedom (x, y, z, theta(x), and theta(y)). The sixth degree of freedom, the rotation about the impeller axis (theta(z)), was determined by the commutation performed by the motor controller. The impeller displacement was found to be within the acceptable range of 8 micro m to 222 microm, avoiding blood damage and contact between the impeller and cavity walls. Thus the impeller was hydrodynamically suspended within the pump cavity and results were typical of centrifugal pump behavior. This research will be the basis for further investigation into the stiffness and damping coefficient of the pump's hydrodynamic bearing.


Characterization of cefotaxime-resistant urinary Escherichia coli from primary care in South-West England 2017-18.
Third-generation cephalosporin-resistant Escherichia coli from community-acquired urinary tract infections are increasingly reported worldwide. We sought to determine and characterize the mechanisms of cefotaxime resistance employed by urinary E. coli obtained from primary care, over 12 months, in Bristol and surrounding counties in South-West England. Cefalexin-resistant E. coli isolates were identified from GP-referred urine samples using disc susceptibility testing. Cefotaxime resistance was determined by subsequent plating onto MIC breakpoint plates. β-Lactamase genes were detected by PCR. WGS was performed on 225 isolates and analyses were performed using the Center for Genomic Epidemiology platform. Patient information provided by the referring general practices was reviewed. Cefalexin-resistant E. coli (n=900) isolates were obtained from urines from 146 general practices. Following deduplication by patient approximately 69% (576/836) of isolates were cefotaxime resistant. WGS of 225 isolates identified that the most common cefotaxime-resistance mechanism was blaCTX-M carriage (185/225), followed by plasmid-mediated AmpCs (pAmpCs) (17/225), AmpC hyperproduction (13/225), ESBL blaSHV variants (6/225) or a combination of both blaCTX-M and pAmpC (4/225). Forty-four STs were identified, with ST131 representing 101/225 isolates, within which clade C2 was dominant (54/101). Ciprofloxacin resistance was observed in 128/225 (56.9%) of sequenced isolates, predominantly associated with fluoroquinolone-resistant clones ST131 and ST1193. Most cefalexin-resistant E. coli isolates were cefotaxime resistant, predominantly caused by blaCTX-M carriage. The correlation between cefotaxime resistance and ciprofloxacin resistance was largely attributable to the high-risk pandemic clones ST131 and ST1193. Localized epidemiological data provide greater resolution than regional data and can be valuable for informing treatment choices in the primary care setting.


Hypertrophic synovial mass resulting in C8 radiculopathy--case report.
A 58-year-old man presented with a hypertrophic synovial mass manifesting as left C8 radiculopathy. Computed tomography revealed hypertrophic changes in the left C7-T1 facet joint and widening of the interarticular space. Magnetic resonance imaging showed left C7-T1 foraminal stenosis attributable to a periarticular mass enhanced with gadolinium. Decompression surgery of the left C8 nerve root was performed. During left C7-T1 facetectomy we detected inflamed soft tissue occupying the interarticular space with extension toward the intervertebral foramen. The mass markedly compressed the left C8 nerve root and was gross totally removed. The histological diagnosis was proliferated fibrous connective tissue compatible with hypertrophic synovial tissue. Postoperatively, his neurological condition improved remarkably. The surgical and pathological findings in our patient indicate that this clinical condition is important in the differential diagnosis in adult patients presenting with cervical radiculopathy.


Proteomic and Transcriptomic Responses Enable Clams to Correct the pH of Calcifying Fluids and Sustain Biomineralization in Acidified Environments.
Seawater pH and carbonate saturation are predicted to decrease dramatically by the end of the century. This process, designated ocean acidification (OA), threatens economically and ecologically important marine calcifiers, including the northern quahog (Mercenaria mercenaria). While many studies have demonstrated the adverse impacts of OA on bivalves, much less is known about mechanisms of resilience and adaptive strategies. Here, we examined clam responses to OA by evaluating cellular (hemocyte activities) and molecular (high-throughput proteomics, RNASeq) changes in hemolymph and extrapallial fluid (EPF-the site of biomineralization located between the mantle and the shell) in M. mercenaria continuously exposed to acidified (pH ~7.3; pCO2 ~2700 ppm) and normal conditions (pH ~8.1; pCO2 ~600 ppm) for one year. The extracellular pH of EPF and hemolymph (~7.5) was significantly higher than that of the external acidified seawater (~7.3). Under OA conditions, granulocytes (a sub-population of hemocytes important for biomineralization) were able to increase intracellular pH (by 54% in EPF and 79% in hemolymph) and calcium content (by 56% in hemolymph). The increased pH of EPF and hemolymph from clams exposed to high pCO2 was associated with the overexpression of genes (at both the mRNA and protein levels) related to biomineralization, acid-base balance, and calcium homeostasis, suggesting that clams can use corrective mechanisms to mitigate the negative impact of OA.


[Clinical experience with intravesical instillations of 5-aminolevulinic acid (5-ALA) for the photodynamic diagnosis using fluorescence cystoscopy for bladder cancer].
To report our clinical experience with intravesical instillations of 5-aminolevulinic acid (5-ALA) for the photodynamic diagnosis of bladder cancer and to assess any side-effects of the diagnostic method. Photodynamic diagnosis was performed in 18 patients of which 14 were men and 4 women with a median age of 71 years (range 44-84), 7 were primary cases and 11 were recurrent cases with bladder cancer. Two to two and half hours prior to endoscopy 1.5 g 5-ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate (NaHCO3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-LIGHT System, Karl Storz Endoscopy Japan K. K.) was used. Under white and fluorescence light guidance, tumor locations were recorded, cold cup biopsies were taken and tumors were resected. The levels in images of the 5-aminolevulinic acid-induced fluorescence were compared with the pathological results. The area under the receiver operative characteristic (ROC) curve (AUC) in blue light endoscopy was also compared with that in white light endoscopy. Among the 129 specimens obtained by transurethral biopsy 45 were obtained from polypoid lesion and 84 from non-polypoid lesion, and among the 76 malignant diseases 36 were obtained from polypoid lesion and 40 from non-polypoid lesion (including 19 carcinoma in situ), and 21 patients with dysplasia were detected pathologically, with a sensitivity of 89.5% and specificity of 58.5% with a predictive accuracy of 77.0%. The AUC in blue light endoscopy was more than that in white light endoscopy in not only all cases (p = 0.010) but also in cases with non-polypoid lesion (p = 0.007) and recurrent cases (p = 0.002). Duration of 5-ALA instillation with a median time of 80 (range 30-150) min. did not seem to affect the accuracy of photodynamic diagnosis. Procedures were well tolerated by all patients with mild bladder irritability but no systemic side effect. Photodynamic diagnosis with intravesically applied 5-ALA is more effective than observation by conventional cystoscopy in detecting bladder cancer without additional risk or complication, and is expected to become a golden standard in the detection program.


Promoter methylation analysis on microdissected paraffin-embedded tissues using bisulfite treatment and PCR-SSCP.
Methylation-sensitive single-strand conformation analysis (MS-SSCA) is a new method of screening for DNA methylation changes. The combination of bisulfite modification and PCR results in the conversion of unmethylated cytosines to thymines, whereas methylated cytosines remain unchanged. This sequence conversion can lead to methylation-dependent alterations of single-strand conformation, which can be detected by SSCA. An analysis of mixtures of methylated and unmethylated DNA at known ratios revealed that the relative intensities of the corresponding bands following MS-SSCA were maintained. MS-SSCA was applied for methylation analysis of human p16 promoter region using genomic DNA obtained from either frozen, fixed, or microdissected fixed tissue sections. MS-SSCA is a rapid, specific, and semiquantitative approach that allows the detection of methylation of the p16 gene promoter. In reconstruction experiments, the method permits the detection of 10% or less of cells harboring a methylated p16 promoter. We have been successful in analyzing by MS-SSCA almost all (96%) tumor samples microdissected from archival paraffin-embedded fixed tissue sections and obtaining reproducible results. In addition, when microdissection was performed, the clonality of this genetic alteration could be identified.


Biological richness of a large urban cemetery in Berlin. Results of a multi-taxon approach.
Urban green spaces can harbor a considerable species richness of plants and animals. A few studies on single species groups indicate important habitat functions of cemeteries, but this land use type is clearly understudied compared to parks. Such data are important as they (i) illustrate habitat functions of a specific, but ubiquitous urban land-use type and (ii) may serve as a basis for management approaches. We sampled different groups of plants and animals in the Weißensee Jewish Cemetery in Berlin (WJC) which is one of the largest Jewish cemeteries in Europe. With a total of 608 species of plants and animals, this first multi-taxon survey revealed a considerable biological richness in the WJC. In all, 363 wild-growing vascular plant, 72 lichen and 26 bryophyte taxa were recorded. The sampling also yielded 34 bird and 5 bat species as well as 39 ground beetle, 5 harvestman and 64 spider species. Some species are new records for Berlin.


Targeting LGR5 in Colorectal Cancer: therapeutic gold or too plastic?
Leucine-rich repeat-containing G-protein coupled receptor (LGR5 or GPR49) potentiates canonical Wnt/β-catenin signalling and is a marker of normal stem cells in several tissues, including the intestine. Consistent with stem cell potential, single isolated LGR5+ cells from the gut generate self-organising crypt/villus structures in vitro termed organoids or 'mini-guts', which accurately model the parent tissue. The well characterised deregulation of Wnt/β-catenin signalling that occurs during the adenoma-carcinoma sequence in colorectal cancer (CRC) renders LGR5 an interesting therapeutic target. Furthermore, recent studies demonstrating that CRC tumours contain LGR5+ subsets and retain a degree of normal tissue architecture has heightened translational interest. Such reports fuel hope that specific subpopulations or molecules within a tumour may be therapeutically targeted to prevent relapse and induce long-term remissions. Despite these observations, many studies within this field have produced conflicting and confusing results with no clear consensus on the therapeutic value of LGR5. This review will recap the various oncogenic and tumour suppressive roles that have been described for the LGR5 molecule in CRC. It will further highlight recent studies indicating the plasticity or redundancy of LGR5+ cells in intestinal cancer progression and assess the overall merit of therapeutically targeting LGR5 in CRC.


Family-size variability grows with collapse rate in a birth-death-catastrophe model.
Forest-fire and avalanche models support the notion that frequent catastrophes prevent the growth of very large populations and as such, prevent rare large-scale catastrophes. We show that this notion is not universal. A new model class leads to a paradigm shift in the influence of catastrophes on the family-size distribution of subpopulations. We study a simple population dynamics model where individuals, as well as a whole family, may die with a constant probability, accompanied by a logistic population growth model. We compute the characteristics of the family-size distribution in steady state and the phase diagram of the steady-state distribution and show that the family and catastrophe size variances increase with the catastrophe frequency, which is the opposite of common intuition. Frequent catastrophes are balanced by a larger net-growth rate in surviving families, leading to the exponential growth of these families. When the catastrophe rate is further increased, a second phase transition to extinction occurs when the rate of new family creations is lower than their destruction rate by catastrophes.


Individual Antigenic Specificity of Isolated Antibodies.
Antisera produced against certain isolated human antibodies showed clear antigenic differences between these antibodies. Individual antigenic specificity was demonstrated for two anti-A antibodies, one anti-dextran, and one anti-levan antibody. Failure to produce specific antisera in other instances appeared to be correlated with a greater heterogeneity of the antibody population used as antigen.


Resurgence following differential reinforcement of alternative behavior implemented with and without extinction.
In the clinic, differential reinforcement of alternative behavior (DRA) often involves programming extinction for destructive behavior while reinforcing an alternative form of communication (e.g., a functional communication response); however, implementing extinction can be unsafe or impractical under some circumstances. Quantitative theories of resurgence (i.e., Behavioral Momentum Theory and Resurgence as Choice) predict differences in the efficacy of treatments that do and do not involve extinction of target responding when reinforcement conditions maintaining alternative responding worsen. We tested these predictions by examining resurgence following two DRA conditions in which we equated rates of reinforcement. In DRA without extinction, target and alternative behavior produced reinforcement. In DRA with extinction plus noncontingent reinforcement, only alternative behavior produced reinforcement. We conducted this study in a reverse-translation sequence, first with participants who engaged in destructive behavior (Experiment 1) and then in a laboratory setting with rats (Experiment 2). Across both experiments, we observed proportionally lower levels of target responding during and following the DRA condition that arranged extinction for the target response. However, levels of resurgence were similar following both arrangements.


Specificity of chromosome damage caused by the Rex element of Drosophila melanogaster.
Rex is a multicopy genetic element that maps within an X-linked ribosomal RNA gene (rDNA) array of D. melanogaster. Acting maternally, Rex causes recombination between rDNA arrays in a few percent of early embryos. With target chromosomes that contain two rDNA arrays, the exchanges either delete all of the material between the two arrays or invert the entire intervening chromosomal segment. About a third of the embryos produced by Rex homozygotes have cytologically visible chromosome damage, nearly always involving a single chromosome. Most of these embryos die during early development, displaying a characteristic apoptosis-like phenotype. An experiment that tests whether the cytologically visible damage is rDNA-specific is reported here. In this experiment, females heterozygous for Rex and an rDNA-deficient X chromosome were crossed to males of two genotypes. Some of the progeny from the experimental cross entirely lacked rDNA, while all of the progeny from the control cross had at least one rDNA array. A significantly lower frequency of early-lethal embryos in the experimental cross, proportionate to the fraction of rDNA-deficient embryos, demonstrates that Rex preferentially damages rDNA.


Effects of whole body vibration training on body composition, skeletal muscle strength, and cardiovascular health.
Whole body vibration training (WBVT) has been used as a supplement to conventional exercise training such as resistance exercise training to improve skeletal muscle strength, specifically, in rehabilitation field. Recently, this exercise modality has been utilized by cardiovascular studies to examine whether WBVT can be a useful exercise modality to improve cardiovascular health. These studies reported that WBVT has not only beneficial effects on muscular strength but also cardiovascular health in elderly and disease population. However, its mechanism underlying the beneficial effects of WBVT in cardiovascular health has not been well documented. Therefore, this review highlighted the impacts of WBVT on cardiovascular health, and its mechanisms in conjunction with the improved muscular strength and body composition in various populations.


Mre11 and Rad50 from Pyrococcus furiosus: cloning and biochemical characterization reveal an evolutionarily conserved multiprotein machine.
The processing of DNA double-strand breaks is a critical event in nucleic acid metabolism. This is evidenced by the severity of phenotypes associated with deficiencies in this process in multiple organisms. The core component involved in double-strand break repair in eukaryotic cells is the Mre11-Rad50 protein complex, which includes a third protein, p95, in humans and Xrs2 in yeasts. Homologues of Mre11 and Rad50 have been identified in all kingdoms of life, while the Nbs1 protein family is found only in eukaryotes. In eukaryotes the Mre11-Rad50 complex has nuclease activity that is modulated by the addition of ATP. We have isolated the Mre11 and Rad50 homologues from the thermophilic archaeon Pyrococcus furiosus and demonstrate that the two proteins exist in a large, heat-stable complex that possesses single-strand endonuclease activity and ATP-dependent double-strand-specific exonuclease activity. These findings verify the identification of the P. furiosus Rad50 and Mre11 homologues and demonstrate that functional homologues with similar biochemical properties exist in all kingdoms of life.


Differences in post-disaster mental health among Vietnamese and African Americans living in adjacent urban communities flooded by Katrina.
Some communities recover more quickly after a disaster than others. Some differentials in recovery are explained by variation in the level of disaster-related community damage and differences in pre-disaster community characteristics, e.g., the quality of housing stock. But distinct communities that are similar on the above characteristics may experience different recovery trajectories, and, if so, these different trajectories must be due to more subtle differences among them. Our principal objective is to assess short-term and long-term post-disaster mental health for Vietnamese and African Americans living in two adjacent communities in eastern New Orleans that were similarly flooded by Hurricane Katrina. We employ data from two population-based cohort studies that include a sample of African American adults (the Gulf Coast Child and Family Health [GCAFH study]) and a sample of Vietnamese American adults (Katrina Impacts on Vietnamese Americans [KATIVA NOLA study]) living in adjacent neighborhoods in eastern New Orleans who were assessed near the second and thirteenth anniversaries of the disaster. Using the 12-Item Short Form Survey (SF-12) as the basis of our outcome measure, we find in multivariate analysis a significant advantage in post-disaster mental health for Vietnamese Americans over their African American counterparts at the two-year mark, but that this advantage had disappeared by the thirteenth anniversary of the Katrina disaster.


Oral hygiene and periodontal status among detainees in a juvenile detention center, India.
To assess the oral hygiene and periodontal status and analyse the influence of age, education, institutionalization, type of visit and oral health behaviour on oral hygiene and periodontal status among detainees in juvenile detention center in Udaipur city, Rajasthan, India. The total sample comprised 223 subjects (67.7% male and 32.3% female) aged 6 to 18 years. Clinical examination included assessment of oral hygiene and periodontal status using OHI-S (Oral Hygiene Index-Simplified) and CPI (Community Periodontal Index), respectively. Analysis of variance (ANOVA), chi-square, Student t-test and stepwise multiple linear and multiple logistic regression analysis were carried out to find the relation between oral hygiene/ periodontal status and different independent variables. The results showed that the oral hygiene status of detainees was poor, with only 28.1% of the subjects having good oral hygiene. Mean OHI-S scores were significantly associated with all independent variables. Overall periodontal disease prevalence was 80.2% with bleeding and calculus contributing a major part (71.9%). Stepwise multiple linear and logistic regression analysis revealed that oral hygiene practice and type of visit in the detention center were the best predictors for the oral hygiene index, and for periodontal disease it was oral hygiene practice alone. The findings confirmed that detainees in the juvenile detention center have poor oral hygiene and an increased prevalence of periodontal disease compared to that of similarly ages in the general population.


Using the matrixed multiple case study methodology to understand site differences in the outcomes of a Hybrid Type 1 trial of a peer-led healthy lifestyle intervention for people with serious mental illness.
Site differences in implementation trial outcomes are common but often not examined. In a Hybrid Type 1 trial examining the effectiveness-implementation of a peer-led group life-style balance (PGLB) intervention for people with serious mental illness (SMI) in three supportive housing agencies, we found that PGLB recipients' physical health outcomes differed by study sites. The matrixed multiple case study methodology was used to explore how implementation outcomes and changes in context of usual care (UC) services contributed to these site differences. Two implementation outcomes (i.e. PGLB fidelity ratings and intervention recipients' acceptability of PGLB and UC) and changes in healthcare services integration at the study sites were examined. ANOVAs were used to examine site differences in fidelity ratings and client satisfaction. Directed content analysis was used to analyze leadership interviews to identify changes in the context of UC services. Site 3 showed a trend approaching significance (P = .05) towards higher fidelity ratings. High levels of satisfaction with PGLB were reported at all sites. Significant differences in PGLB recipients' satisfaction with UC were found, with Site 3 reporting the lowest levels of satisfaction. Agency leaders reported an increase in prioritizing client's health throughout the trial with sites differing in how these priorities were put into action. Differences in PGLB recipients' satisfaction with UC, and changes in healthcare service integration seemed to have contributed to the site differences in our trial. The matrixed multiple case study methodology is a useful approach to identify implementation outcomes contributing to the heterogeneity of multisite implementation trial results.


Expression analysis of human salivary glands by laser microdissection: differences between submandibular and labial glands.
Both the major and minor salivary glands are the sources of saliva, a fluid vital for the maintenance of a healthy oral cavity. Here, the expression profiles of human submandibular (SMG) and labial glands (LG) were compared by RT-PCR analysis of laser microdissected mucous and serous cells, respectively. The focus was on trefoil factor family (TFF) genes, but also other genes encoding secretory proteins (mucins, lysozyme, amylase, statherin, and histatins) or aquaporin 5 were included. Immunofluorescence studies concerning TFF1-3, FCGBP, amylase, and lysozyme are also presented. It was shown that LGs clearly contain serous cells and that these cells differ in their expression profiles from serous SMG cells. Furthermore, all three TFF peptides, together with MUC5B, MUC7, MUC19, and FCGBP, were clearly detectable in mucous acini of both LGs and SMGs. In contrast, lysozyme was differentially expressed in LGs and SMGs. It can be expected that labial saliva may play a particularly important role for protecting the teeth.


Single-Trial Decoding of Visual Attention from Local Field Potentials in the Primate Lateral Prefrontal Cortex Is Frequency-Dependent.
Local field potentials (LFPs) are fluctuations of extracellular voltage that may reflect the physiological phenomena occurring within a volume of neural tissue. It is known that the allocation of spatial attention modulates the amplitude of LFPs in visual areas of primates. An issue that remains poorly investigated is whether and how attention modulates LFPs in executive brain areas, such as the lateral prefrontal cortex (LPFC), thought to be involved in the origins of attention. We addressed this issue by recording LFPs from multielectrode arrays implanted in the LPFC of two macaques. We found that the allocation of attention can be reliably decoded on a single-trial basis from ensembles of LFPs with frequencies >60 Hz. Using LFP frequencies <60 Hz, we could not decode the allocation of attention, but we could decode the location of a visual stimulus as well as the endpoint of saccades toward that stimulus. The information contained in the high-frequency LFPs was fully redundant with the information contained in the spiking activity of single neurons recorded from the same electrodes. Moreover, the decoding of attention using γ frequency LFPs was less accurate than using spikes, but it was twice more stable across time. Finally, decorrelating the LFP signals from the different electrodes increased decoding performance in the high frequencies by up to ∼14%. Our findings suggest that LFPs recorded from chronically implanted multielectrode arrays in the LPFC contain information about sensory, cognitive, and motor components of a task in a frequency-dependent manner.


Slc26a3 deficiency is associated with epididymis dysplasia and impaired sperm fertilization potential in the mouse.
Members of the solute carrier 26 (SLC26) family have emerged as important players in mediating anions fluxes across the plasma membrane of epithelial cells, in cooperation with the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Among them, SLC26A3 acts as a chloride/bicarbonate exchanger, highly expressed in the gastrointestinal, pancreatic and renal tissues. In humans, mutations in the SLC26A3 gene were shown to induce congenital chloride-losing diarrhea (CLD), a rare autosomal recessive disorder characterized by life-long secretory diarrhea. In view of some reports indicating subfertility in some male CLD patients together with SLC26-A3 and -A6 expression in the male genital tract and sperm cells, we analyzed the male reproductive parameters and functions of SLC26A3 deficient mice, which were previously reported to display CLD gastro-intestinal features. We show that in contrast to Slc26a6, deletion of Slc26a3 is associated with severe lesions and abnormal cytoarchitecture of the epididymis, together with sperm quantitative, morphological and functional defects, which altogether compromised male fertility. Overall, our work provides new insight into the pathophysiological mechanisms that may alter the reproductive functions and lead to male subfertility in CLD patients, with a phenotype reminiscent of that induced by CFTR deficiency in the male genital tract.


Atypical adenomatous hyperplasia of the prostate: a critical review.
The aim of this report is to review the literature concerning atypical adenomatous hyperplasia (AAH) with specific regard to evidence in support of or refuting its role as a precursor lesion for prostatic adenocarcinoma. The available literature was collected and critically reviewed. In addition, recently reported (abstract) but as yet unpublished data were included. Particular attention was focused on biological studies. There is considerable morphologic evidence suggesting that AAH is associated with low-grade (Gleason patterns 1 and 2) adenocarcinoma arising in the transition zone. Only limited biologic studies have been performed. There is weak and limited data to indicate that AAH has a proliferation rate higher than hyperplasia but lower than adenocarcinoma. AAH is diploid, as are most examples of low-grade adenocarcinoma. A few markers (blood group antigens, peanut agglutinin) show similar patterns of expression in AAH and adenocarcinoma while others (carbohydrate D-galactose-N-acetyl-D-galactosamine) do not. Recent cytogenetic analyses have detected abnormalities of chromosome 8 in a very small proportion (4-6%) of cases of AAH studied. Presently, the only strong evidence linking AAH to adenocarcinoma is morphologic. The few biologic and molecular/cytogenetic studies performed have not provided convincing evidence to support or refute this possibility. Additional studies are required. Finally, in comparative studies of AAH with adenocarcinoma, the latter should include low-grade transition zone tumors.


Rectal Diclofenac administration for prevention of post-Endoscopic Retrograde Cholangio-Pancreatography (ERCP) acute pancreatitis. Randomized prospective study.
Post-Endoscopic Retrograde Cholangio-Pancreatography pancreatitis (PEP) is a relevant (1-4%) complication of biliopancreatic operative endoscopy. Rectal nonsteroidal anti-inflammatory drugs (specifically, 100 mg of diclofenac) have shown promising prophylactic activity in PEP. The aim of our prospective study is to report whether prophylactic oral versus rectal suppository versus intramuscular diclofenac versus placebo are able to reduce the incidence and the severity of ERCP-induced pancreatitis. In this randomized, double-blinded, prospective study, 100 patients (49 male, 51 female), similar with regard to indication for ERCP, were enrolled between January 2016 and November 2017 to undergo ERCP in the Section of General and Thoracic Surgery of University Hospital of Palermo. They were randomized into five groups, respectively 20 patients with placebo by mouth; 20 patients with 50 mg diclofenac sodium enteric-coated capsules by mouth; 20 with 100 mg rectal suppository diclofenac, 20 with 75 mg/3 ml intramuscular diclofenac sodium, 20 with 75 mg/3 ml intramuscular diclofenac sodium and 20 with 75 mg/3 ml intravenous diclofenac. All drugs were administered 30 to 90 minutes before ERCP. All clinical data were collected one day before and 2, 12 and 24 hour after ERCP. Data were prospectively collected and to demonstrate the preventive effect of rectal diclofenac on PEP, a two-by-two table and chi-square test with Yates correction were used: the incidence of PEP was significantly lower (p < 0.001) in the rectal diclofenac group respect to other groups and, in the same way, the incidence of post-ERCP pain was significantly lower in the rectal diclofenac group than in the other groups (p = 0.001) and patients discharge was consequently earlier (p < 0.01). 100 mg dose rectal diclofenac administered 30-60 minutes before ERCP can effectively prevent PEP.


The prevalence of opioid-related major potential drug-drug interactions and their impact on health care costs in chronic pain patients.
Literature has shown that chronic pain patients prescribed opioids are at an increased risk for experiencing drug-drug interactions as a result of polypharmacy. In addition, chronic, noncancer pain patients who experience drug-drug interactions have been shown to have greater health care utilization and costs. However, no study has focused on the health economics of major clinically significant drug-drug interactions associated with long-acting opioids. To (a) estimate the prevalence of major drug-drug interactions among patients prescribed a long-acting opioid and (b) evaluate the potential impact of major drug-drug interactions on health care costs. This study was a retrospective cohort analysis using claims data from the MarketScan Commercial Claims and Encounter Database between 2008 and 2010. Patients with at least 1 prescription for a long-acting opioid for ≥ 30 days were placed into cohorts according to the expected clinical impact of the potential drug-drug interaction: major versus none. Propensity score matching was used to mitigate differences in baseline characteristics between the cohorts. Health care costs were based on payments for all covered health care services, which consisted of inpatient and outpatient medical, emergency department, and outpatient prescription costs. Among 57,752 chronic, noncancer pain patients who met all inclusion and exclusion criteria, 5.7% (3,302) were exposed to a potential major drug-drug interaction. The costs associated with a potential interaction versus no potential interaction were significantly more after baseline characteristics of the cohorts were normalized by propensity score matching. Monthly health care costs in the 90-day post-index period were significantly greater ($3,366 vs. $2,757, a $609 difference) in patients exposed to a potential drug-drug interaction of major clinical significance, compared with those not exposed to a drug-drug interaction. The higher health care costs were mainly driven by outpatient and inpatient medical costs. Exposure to potential drug-drug interactions may result in unnecessary and unintended health care costs. Physicians should be made aware of commonly administered cytochrome P450 (CYP450) metabolized drugs in the chronic pain patient and consider prescribing non-CYP450 metabolized opioid and nonopioid analgesics. Managed care's use of utilization management tools to avoid these exposures may reduce costs.


In vitro activities of oral antimicrobial agents against penicillin-resistant Streptococcus pneumoniae: implications for outpatient treatment.
We tested 83 penicillin-intermediate (Peni) and 50 penicillin-resistant (Penr) isolates of Streptococcus pneumoniae against eight oral antimicrobials. Clarithromycin's MICs (minimal inhibitory concentration) were generally the same or one to two dilutions less than those of azithromycin. Seventy-two percent of Peni isolates were susceptible to clarithromycin and azithromycin, in contrast to 42% and 40%, respectively, of Penr isolates. Cefuroxime activity exceeded that of cefprozil, which exceeded that of cefaclor, in Peni isolates. For all three cephalosporins, MICs of 90% of isolates tested were > or = 3 dilutions higher for Penr isolates than for Peni isolates. Percentages of Peni isolates susceptible to clindamycin and tetracycline were 92% and 83%, respectively, and 78% and 82% for Penr. Only 49% of Peni isolates and 4% of Penr isolates were susceptible to trimethoprim-sulfamethoxazole. Azithromycin, clarithromycin, cefuroxime, cefprozil, clindamycin, and tetracycline may be useful in treating infections caused by Peni S pneumoniae, but Penr isolates are frequently resistant to both old and newer agents.


Association of external cephalic version before term with late preterm birth.
While evidence suggests that beginning an external cephalic version (ECV) before term (340/7 to 366/7 weeks) compared with after term may be associated with an increase in late preterm birth (340/7 to 366/7 weeks), it remains unknown what might account for this risk. The objective of the present study is to further investigate the association between ECV before term and late preterm birth. Secondary analysis of data collected from the international, multicenter Early ECV trials. We evaluated the relation between ECV exposure and late preterm birth (340/7 to 366/7 weeks), as well as whether additional risk factors for preterm birth (such as maternal age, height, body mass index, parity, placental location, and perinatal mortality rate) moderated this relation. Generalized linear mixed methods were used to account for center effect and adjust for covariates. Among 1765 women with breech pregnancies and without a prior preterm birth, 749 (42.4%) received at least one ECV before term. Exposure to an ECV before term was not associated significantly independently with odds of preterm birth. However, placenta location moderated the association between early ECV exposure and late preterm birth. The odds of preterm birth in women who were exposed to an ECV before term and who also had an anterior placenta were doubled (OR 2.05; 95% CI 1.12-3.71; p = 0.02). In a large cohort of women without known risks for preterm birth, those with an anterior placenta who undergo an ECV before term constitute a subgroup at particular risk for late preterm birth.


NOTES: The question for minimal resection and sentinel node in early gastric cancer.
Surgical therapy for gastric cancer involves both removal of the cancer lesion and complete lymph node dissection. Natural orifice transluminal endoscopic surgery (NOTES) is considered to represent the next revolution in surgery. Many surgeons and endoscopists believe that NOTES may be a superior alternative for early gastric cancer treatment. Sentinel node (SN) navigation surgery for gastric cancer: Single institution results of SN mapping for early gastric cancer are increasingly being considered acceptable. Furthermore, a major large-scale clinical trial of SN mapping for gastric cancer has recently been completed by The Japan Society of SN Navigation Surgery study group. They reported false negative rate of 7.0% while the sensitivity of metastasis detection based on SN status was 93%. Combination of SN biopsy and NOTES: This concept was first described by Cahill et al who proved the feasibility of lymphatic mapping and SN biopsy by NOTES. Lymphatic channel filling was immediately observable via the intraperitoneal optics. Partial resection of the stomach by hybrid NOTES: Several centers have already reported gastrectomy assisted by NOTES using the transvaginal route. However, the main problem of full-thickness resection of gastric wall remains endoscopic gastric closure. Establishing an endoscopic suturing method would be an important step toward expanding potential indications. NOTES is met with both enthusiasm and skepticism but will gain its own place as human creativity eventually provides solutions to its technical limitations. In the near future, NOTES can evolve the capacity to complement the existing armamentarium for gastric cancer surgery.


[Pathogenic properties of Corynebacterium diphtheriae].
The main pathogenic properties of 73 C. diphtheriae strains (their adhesive, invasive and cytotoxic activity) were characterized in the cultures of cells HEp-2 and Vero. The quantitative determination of the toxigenicity of 381 strains in the indirect hemagglutination test was made, and the strains were distributed by the degree of their toxigenicity. The characteristics of C. diphtheriae obtained with the use of in vitro experimental models, coincided with the severity of clinical manifestations of the diphtheria in humans, which made it possible to regard the models used in this study as adequate. On the basis of the chosen criteria the characterized strains could be subdivided into highly, moderately and low virulent and the degree of their potential epidemic danger could be determined.


Mitochondria dysfunctions under Fe and S deficiency: is citric acid involved in the regulation of adaptive responses?
Within the last years, extensive information has been accumulated on the reciprocal influence between S and Fe nutrition at both physiological and molecular level in several plant species, but the mechanisms regulating S and Fe sensing and signaling are not fully understood. Fe and S interact for the building of Fe-S clusters, and mitochondria is one of the cellular compartments where Fe-S cluster assembly takes place. Therefore, it would be expected that mitochondria might play a central role in the regulation of Fe and S interaction. The Fe deficiency-induced alteration in the synthesis of mitochondria-derived carboxylic acids, such as citric acid, and the evidence that such molecules have already been identified as important players of metabolite signaling in several organisms, further support this hypothesis. Tomato plants were grown under single or combined Fe and S deficiency with the aim of verifying whether mitochondria activities played a role in Fe/S interaction. Both Fe and S deficiencies determined similar alteration of respiratory chain activity: a general decrease of Fe-S containing complexes as well as an increase of alternative NAD(P)H activities was observed in both Fe and S deficient-plants. However, the content of Krebs cycle-related organic acids in roots was substantially different in response to treatments, being the accumulation of citric acid always increased, while the others (i.e. succinic, malic, fumaric acids) always decreased. Interestingly, citric acid levels significantly correlated with the expression of some Fe and S deficiency induced genes. Our results contribute to existing knowledge on the complexity of the S/Fe interaction, suggesting a model in which endogenous alteration of citric acid content in plant tissues might act as signal molecule for the regulation of some nuclear-encoded and nutrient-responsive genes and also provide a basis for further study of the mechanism underlying S and Fe sensing and signalling.


[Diagnostic tactics in localized fibroadenomatosis of the breast].
Results of the examination and treatment of 203 patients with localized fibroadenomatosis of the mammary gland are described. The authors give an estimation of diagnostic algorithms used when detecting the physical signs of the disease. It was shown that the examination of patients with the palpation signs of nodular mastopathy should necessarily include mammography which can eliminate unwarranted risk of hypodiagnosing carcinoma of the mammary gland and determine the group of patients in whom the emergency operation is not necessary.


Bayesian nonlinear model selection and neural networks: a conjugate prior approach.
In order to select the best predictive neural-network architecture in a set of several candidate networks, we propose a general Bayesian nonlinear regression model comparison procedure, based on the maximization of an expected utility criterion. This criterion selects the model under which the training set achieves the highest level of internal consistency, through the predictive probability distribution of each model. The density of this distribution is computed as the model posterior predictive density and is asymptotically approximated from the assumed Gaussian likelihood of the data set and the related conjugate prior density of the parameters. The use of such a conjugate prior allows the analytic calculation of the parameter posterior and predictive posterior densities, in an empirical-Bayes-like approach. This Bayesian selection procedure allows us to compare general nonlinear regression models and in particular feedforward neural networks, in addition to embedded models as usual with asymptotic comparison tests.


The dopamine D4 receptor gene shows a gender-sensitive association with cognitive empathy: evidence from two independent samples.
Increasing evidence points to a role of dopaminergic pathways in modulating social behavior. Specifically, a polymorphic region in the third exon of the Dopamine D4 receptor (DRD4) has been associated with a host of social behaviors, often in an environment-sensitive manner. Empathy is thought to be an important motivator of prosocial behaviors and can be seen as multifaceted, combining cognitive empathy (CE) and emotional empathy (EE). In the current study, we analyzed the association between DRD4 and the 2 aspects of empathy, as well as the effect of gender on this association. In Study 1, a large sample of adult participants (N = 477) was inventoried for general empathy, CE, and EE and genotyped for the DRD4 exon 3 polymorphism. Women scored higher than men on all empathy measures and no main effect of genotype was observed. It is important that a significant interaction between genotype and gender emerged specifically for CE, with women carriers of the 7R-allele scoring higher than noncarriers, whereas in men 7R-carriers scored lower than -7R. Notably, these findings were replicated in an independently recruited sample (N = 121) in Study 2. The current report shows that the DRD4 exon3 polymorphism is associated with CE and the direction of the association is gender-sensitive.


Comparison of strategies using cefpirome and ceftazidime for empiric treatment of pneumonia in intensive care patients. The Cefpirome Pneumonia Study Group.
In an international, multicenter, open-label, randomized comparative study, adult patients in intensive care units were enrolled to receive cefpirome intravenously at 2 g twice daily or ceftazidime intravenously at 2 g three times daily for the empiric treatment of pneumonia. Randomization was performed after a double stratification according to the investigator's initial choice of monotherapy or combination therapy and then on the basis of the severity of disease. The primary endpoint was the clinical response at the end of treatment in the intent-to-treat population. Data for all patients were reviewed by a blinded observer. Of the 400 enrolled patients, 201 received cefpirome (monotherapy, 56%) and 199 received ceftazidime (monotherapy, 51%). Pneumonia was hospital acquired for 75% of the patients. Clinical failures rates were 34 versus 36% (odds ratio = 0.922; upper bound of 90% confidence interval = 1.301) in the intent-to-treat analysis for cefpirome and ceftazidime, respectively. For the cefpirome and ceftazidime groups, there were 35 versus 30% clinical failures among monotherapy-stratified patients, respectively, and 34 versus 42% clinical failures among combination therapy-stratified patients, respectively. The rates of clinical failures in the per-protocol analysis were 38 and 42%, respectively. In the population of patients evaluable for bacteriologic efficacy, eradication or presumed eradication was obtained for 71% (172 of 241) and 70% (162 of 230) of the pathogens isolated from the patients receiving cefpirome and ceftazidime, respectively. The mortality rates within 2 weeks after the end of treatment were similar (cefpirome group, 31%; ceftazidime group, 26%), as were the percentages of patients with at least one treatment-related adverse event (17 and 19%, respectively). An empiric treatment strategy with cefpirome at 2 g twice daily is equivalent in terms of efficacy and tolerance to ceftazidime at 2 g three times daily for the treatment of pneumonia in patients in intensive care units.


Sediment microbial communities in Great Boiling Spring are controlled by temperature and distinct from water communities.
Great Boiling Spring is a large, circumneutral, geothermal spring in the US Great Basin. Twelve samples were collected from water and four different sediment sites on four different dates. Microbial community composition and diversity were assessed by PCR amplification of a portion of the small subunit rRNA gene using a universal primer set followed by pyrosequencing of the V8 region. Analysis of 164 178 quality-filtered pyrotags clearly distinguished sediment and water microbial communities. Water communities were extremely uneven and dominated by the bacterium Thermocrinis. Sediment microbial communities grouped according to temperature and sampling location, with a strong, negative, linear relationship between temperature and richness at all taxonomic levels. Two sediment locations, Site A (87-80 °C) and Site B (79 °C), were predominantly composed of single phylotypes of the bacterial lineage GAL35 (\[pmacr]=36.1%), Aeropyrum (\[pmacr]=16.6%), the archaeal lineage pSL4 (\[pmacr]=15.9%), the archaeal lineage NAG1 (\[pmacr]=10.6%) and Thermocrinis (\[pmacr]=7.6%). The ammonia-oxidizing archaeon 'Candidatus Nitrosocaldus' was relatively abundant in all sediment samples <82 °C (\[pmacr]=9.51%), delineating the upper temperature limit for chemolithotrophic ammonia oxidation in this spring. This study underscores the distinctness of water and sediment communities in GBS and the importance of temperature in driving microbial diversity, composition and, ultimately, the functioning of biogeochemical cycles.


Expression of cancer/testis (CT) antigens MAGE-A1, MAGE-A3, MAGE-A4, CT-7, and NY-ESO-1 in malignant gammopathies is heterogeneous and correlates with site, stage and risk status of disease.
Cancer/testis (CT) antigens are expressed in several malignant tumors, but not in normal tissues except for testicular germ cells. The expression of CT antigenic proteins in malignant gammopathies has not been characterized. We examined the expression of a panel of CT antigenic proteins in 29 patients with malignant gammopathies by immunohistochemistry using the following monoclonal antibodies (mAbs): mAb MA454 to MAGE-A1, mAb M3H67 to MAGE-A3, mAb 57B to MAGE-A4, mAb CT7-33 to CT7/MAGE-C1 and mAb ES121 to NY-ESO-1. We could detect at least one CT antigen in tumors from 27 of 29 patients. The expression pattern of MAGE-A1, -A3, -A4 and NY-ESO-1 is heterogeneous in most cases, revealing staining in <25% of the tumor cells. Monoclonal antibodies CT7-33 and M3H67 show the highest incidence of immunoreactivity. Importantly, CT-7 can also be detected on the surface of some myeloma cells by flow cytometry, and in one plasmacytoma case by immunohistochemistry. Expression of CT antigens is greater in patients with stage III extramedullary plasmacytoma or high-risk myeloma relative to other cohorts. These data suggest that CT antigens may have important biological implications in malignant gammopathies and that CT-7 may be a suitable target for T cell-based and possibly antibody-mediated immunotherapy of myeloma.


Phylogenetic analysis in a recent controlled outbreak of Crimean-Congo haemorrhagic fever in the south of Iran, December 2008.
Crimean-Congo haemorrhagic fever (CCHF) is a viral zoonotic disease with a high mortality rate in humans. The CCHF virus is transmitted to humans through the bite of Ixodid ticks or contact with blood or tissues of CCHF patients or infected livestock. In December 2008, a re-emerging outbreak of CCHF occurred in the southern part of Iran. Five people were hospitalised with sudden fever and haemorrhaging, and CCHF was confirmed by RT-PCR and serological assays. One of the cases had a fulminant course and died. Livestock was identified as the source of infection; all animals in the incriminated herd were serologically analysed and more than half of them were positive for CCHFV. We demonstrated that two routes of transmission played a role in this outbreak: contact with tissue and blood of infected livestock, and nosocomial transmission. Phylogenetic analyses helped to identify the origin of this transmission. This outbreak should be considered as a warning for the national CCHF surveillance system to avoid further outbreaks through robust prevention and control programmes.


Invited review: effects of diet shifts on Escherichia coli in cattle.
Escherichia coli O157:H7 is a pathogenic bacterium that causes acute illness in humans, but mature cattle are not affected. E. coli O157:H7 can enter the human food supply from cattle via fecal contamination of beef carcasses at slaughter. Previous attempts to correlate the incidence of E. coli O157:H7 with specific diets or feeding management practices gave few statistically significant or consistent findings. However, recent work indicates that cattle diets may be changed to decrease fermentation acid accumulation in the colon. When fermentation acids accumulate in the colon and pH decreases, the numbers of acid-resistant E. coli increase; acid-resistant E. coli are more likely to survive the gastric stomach of humans. When cattle were fed hay for a brief period (<7 d), acid-resistant E. coli numbers declined dramatically. Other workers have shown that brief periods of hay feeding can also decrease the number of cattle shedding E. coli O157:H7, and a similar trend was observed if cattle were taken off feed and exposed to simulated transport. These observations indicate that cattle feeding management practices may be manipulated to decrease the risk of foodborne illness from E. coli, but further work will be needed to confirm these effects.


Phloretin promotes osteoclast apoptosis in murine macrophages and inhibits estrogen deficiency-induced osteoporosis in mice.
Bone-remodeling imbalance induced by increased osteoclast formation and bone resorption is known to cause skeletal diseases such as osteoporosis. The reduction of estrogen levels at menopause is one of the strongest risk factors developing postmenopausal osteoporosis. This study investigated osteoprotective effects of the dihydrochalcone phloretin found in apple tree leaves on bone loss in ovariectomized (OVX) C57BL/6 female mice as a model for postmenopausal osteoporosis. OVX demoted bone mineral density (BMD) of mouse femurs, reduced serum 17β-estradiol level and enhanced serum receptor activator of NF-κB ligand (RANKL)/osteoprotegerin ratio with uterine atrophy. Oral administration of 10 mg/kg phloretin to OVX mice for 8 weeks improved such effects, compared to sham-operated mice. Phloretin attenuated TRAP activity and cellular expression of β3 integrin and carbonic anhydrase II augmented in femoral bone tissues of OVX mice. This study further examined that osteogenic activity of phloretin in RANKL-differentiated Raw 264.7 macrophages into mature osteoclasts. Phloretin at 1-20 μM stimulated Smac expression and capase-3 activation concurrently with nuclear fragmentation of multi-nucleated osteoclasts, indicating that this compound promoted osteoclast apoptosis. Consistently, phloretin enhanced bcl-2 induction but diminished bax expression. Furthermore, phloretin activated ASK-1-diverged JNK and p38 MAPK signaling pathways in mature osteoclasts, whereas it dose-dependently inhibited the RANKL-stimulated activation of ERK. Therefore, phloretin manipulated ASK-1-MAPK signal transduction leading to transcription of apoptotic genes. Phloretin was effective in preventing estrogen deficiency-induced osteoclastogenic resorption.


The effects of wound lavage solutions on canine fibroblasts: an in vitro study.
The purpose of this study was to determine the effects of phosphate-buffered saline (PBS), sterile tap water, normal saline, and Ringer's lactate on wound healing in an in vitro model. The effects of PBS, sterile tap water, normal saline, and Ringer's lactate on a primary line of canine embryonic fibroblasts were determined. A primary line of canine embryonic fibroblasts. The effects of the various lavage solutions were determined by (1) vital staining of the treated cells with a 0.5% trypan blue solution, (2) evaluation of the amount of lactate dehydrogenase released by the treated cells, and (3) cytopathologic evaluation of hematoxylin and eosin-stained monolayers of treated canine fibroblasts. The cells were exposed to the lavage treatments for the following time intervals: 0.5 minute, 1 minute, 2.5 minutes, 5 minutes, and 10 minutes. PBS was used as the control. Sterile tap water significantly damaged canine fibroblasts at all time intervals (P = .05). This was attributed to the alkaline pH, hypotonicity, and presence of numerous cytotoxic trace elements in the tap water used. Cytotoxic effects were noted in fibroblasts after 10 minutes' exposure to normal saline; this may be because of the acidic pH of normal saline and lack of a buffering system. Ringer's lactate did not induce any significant fibroblast injury. PBS and Ringer's lactate do not induce any significant fibroblast injury, whereas normal saline and sterile tap water cause mild and severe cytotoxic effects in vitro. Further clinical investigation is indicated to establish whether Ringer's lactate is the wound lavage solution of choice compared with normal saline. Sterile tap water may cause considerable fibroblast injury.


Protective effects of Cinnamomum zeylanicum L. (Darchini) in acetaminophen-induced oxidative stress, hepatotoxicity and nephrotoxicity in mouse model.
Cinnamomum zeylanicum, a widely used spice and flavor, is used in the treatment and prevention of many diseases. In the current study, Balb/c mice were pretreated with cinnamon bark aqueous extract (200 mg/kg/day i.g.) 14 days prior to intragastrically administer single toxic dose of acetaminophen (200 mg/kg). Blood samples were collected for analysis of biochemical and oxidative stress parameters and liver and kidney samples were collected for histopathological analysis. The results indicate that cinnamon aqueous extract exhibit a highly significant preventive potential by ameliorating APAP-induced elevated levels of serum alanine aminotransferase, aspartate aminotransferase, creatinine, urea and macroscopic and histological alterations in liver and kidney. Moreover, significant increase in total oxidant status and decrease in total antioxidant capacity accompanied by APAP exposure, were restored by cinnamon pretreatment. We found that prior administration of cinnamon prevented the toxic changes induced by acetaminophen as confirmed by histopathological examination, more possibly owing to its antioxidant potential. In conclusion, the pretreatment with cinnamon provide potential therapeutic applications in acute liver and kidney injury induced by APAP in experimental animal model and it could have therapeutic potential in oxidative stress associated diseases.


NIDDK international conference report on diabetes and depression: current understanding and future directions.
Comorbid diabetes and depression are a major clinical challenge as the outcomes of each condition are worsened by the other. This article is based on the presentations and discussions during an international meeting on diabetes and depression convened by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in collaboration with the National Institute of Mental Health and the Dialogue on Diabetes and Depression. While the psychological burden of diabetes may contribute to depression in some cases, this explanation does not sufficiently explain the relationship between these two conditions. Shared biological and behavioral mechanisms, such as hypothalamic-pituitary-adrenal axis activation, inflammation, autonomic dysfunction, sleep disturbance, inactive lifestyle, poor dietary habits, and environmental and cultural risk factors, are important to consider in understanding the link between depression and diabetes. Both individual psychological and pharmacological depression treatments are effective in people with diabetes, but the current range of treatment options is limited and has shown mixed effects on glycemic outcomes. More research is needed to understand what factors contribute to individual differences in vulnerability, treatment response, and resilience to depression and metabolic disorders across the life course and how best to provide care for people with comorbid diabetes and depression in different health care settings. Training programs are needed to create a cross-disciplinary workforce that can work in different models of care for comorbid conditions.


Does perfusion computed tomography correlate to pathology in colorectal liver metastases?
Targeted therapy against tumor angiogenesis is widely used in clinical practice for patients with colorectal liver metastases (CRLM). Possible predictive biomarkers for tumor angiogenesis, such as, microvessel density (MVD), hypoxia and cell proliferation, can be determined using immunohistochemical staining. However, patients ineligible for surgical treatment need to undergo invasive diagnostic interventions in order to determine these biomarkers. CT perfusion (CTP) is an emerging functional imaging technique, which can non-invasively determine vascular properties of solid tumors. The purpose of this study was to evaluate CTP with histological biomarkers in CRLM. Patients with CRLM underwent CTP one day before liver surgery. CTP analysis was performed on the entire volume of the largest metastases in each patient. Dual-input maximum slope analysis was used and data concerning arterial flow (AF), portal flow (PF) and perfusion index (PI) were recorded. Immunohistochemical staining with CD34, M75/CA-IX and MIB-1 was performed on the rim in the midsection of the tumor to determine respectively MVD, hypoxia and cell proliferation. Twenty CRLM in 20 patients were studied. Mean size of the largest CRLM was 37 mm (95% CI 21-54 mm). Mean AF and PF were respectively 64 ml/min/100ml (95% CI 48-79) and 30 ml/min/100ml (95% CI 22-38). Mean PI was 68% (95% CI 62-73). No significant correlation was found between tumor growth patterns and CTP (p = 0.95). MVD did not significantly correlate to AF (r = 0.05; p = 0.84), PF (r = 0.17; p = 0.47) and PI (r = -0.12; p = 0.63). Cell proliferation also did not significantly correlate to AF (r = 0.07; p = 0.78), PF (r = -0.01; p = 0.95) and PI (r = 0.15; p = 0.52). Hypoxia did not significantly correlate to AF (r = -0.05; p = 0.83), however, significantly to PF (r = 0.51; p = 0.02) and a trend to negative correlation with PF (r = -0.43; p = 0.06). However, after controlling the false discovery rate, no significant correlation between CTP and used immunohistochemical biomarkers was found. In conclusion, this feasibility study found a trend to negative correlation between PI and hypoxia, CTP might therefore possibly evaluate this prognostic marker in CRLM non-invasively. However, CTP is not an appropriate technique for the assessment of microvessels or cell proliferation in CRLM.


Perceptions of spirituality and spiritual care among older nursing home residents at the end of life.
Spirituality is of particular importance in the lives of many older adults at the end of life. While the role of spirituality may differ among older adults, spirituality may offer a purpose and meaning toward the end of life and provides a framework for managing concerns and decisions at this time. Despite the increasingly evident role of spirituality in the United States, the spirituality of older adults has been neglected. Moreover, little research has been undertaken to determine how nurses may best help older adults improve spiritual health. The purpose of this analysis was to investigate perceptions of spirituality and spiritual care among older nursing home residents at the end of life. A total of 26 older long-term care residents were surveyed using the Spirituality and Spiritual Care Rating scale from 2 faith-based nursing facilities to better understand residents' spirituality and perception of spiritual care. Descriptive statistics were used to analyze the participant's perceptions of spirituality and spiritual care. The 2 samples in this study received a mean score of 51.36 (SD = 5.99) with a range of 43 to 68, indicating moderately high views of aspects of spirituality and spiritual care among the sample, supporting spirituality as a framework for life. The sample reported on several interventions that nurses could use to support spirituality, including arranging visits with religious personnel, showing kindness, spending time listening to residents (presence), and showing respect for resident's needs. The results of the study provide information that may be used to increase knowledge and improve spiritual interventions for nursing home residents at the end of life.


Comparison of Positive Screening for Obstructive Sleep Apnea in Patients With and Without Cleft Lip and Palate.
To compare the prevalence of increased risk of obstructive sleep apnea (OSA) in children with and without cleft lip and/or palate using a previously validated questionnaire and to examine the clinical and demographic variables that may lead to increased OSA risk. Prospective, cross-sectional study. One hundred fifty-five cleft lip palate and 155 noncleft children between 2 and 18 years old. The Pediatric Sleep Questionnaire (PSQ): Sleep Related Breathing Disorder Scale was used for screening of increased OSA risk. Age, body mass index (BMI), gender, breast-feeding, and bottle-feeding durations were recorded for all patients. Cleft type, lip and palate operation times, nasoalveolar molding, or nutrition plaque usage was documented for the cleft lip palate group. Pearson χ2 or Fisher exact test was used for the evaluation of the qualitative variables and independent samples t test or Mann Whitney U test for quantitative variables. P < .05 was accepted as statistically significant. The mean ages were 7.52 ± 3.91 and 7.50 ± 3.89 years for cleft lip palate and control groups, respectively. No significant differences were observed between the groups for age, gender, or BMI. Breast-feeding duration was significantly higher, and bottle-feeding duration was lower in the control group (P < .05). Mean PSQ score was significantly higher in cleft lip palate group (0.18 ± 0.12) than in control group (0.13 ± 0.1, P < .001); and prevalence of increased OSA risk was significantly higher in patients with both cleft lip and palate (P = .020). Positive OSA screening ratio of children with cleft lip and palate (12.2%) was significantly higher than the controls (4.5%).


Risk of osteoporosis among individuals with varicose veins: a multi-institution cohort study.
The present study showed a significant association between varicose veins and the development of osteoporosis, especially women and patients older than 50 years. Physicians should be alerted to this issue and consider screening for osteoporosis in patients with varicose veins. Osteoporosis might be associated with many skin diseases. However, only a paucity of data addressing the association between varicose veins and subsequent osteoporosis development. The study was aimed to evaluate whether there is an increased risk of osteoporosis among patients with varicose veins. This multi-institution database study was based on Chang Gung Research Database from January 1, 2003, to December 31, 2015. Patients aged 20 years and older with varicose veins were enrolled. Participants in the control group were selected by matching in a 4:1 ratio by sex, age, index date, and comorbidities. The hazard ratios associated with osteoporosis were estimated using Cox regression analysis with competitive risk model. Incidence rate of osteoporosis was assessed in individuals with and without varicose veins. A total of 11,959 patients with varicose veins and 47,633 matched controls were enrolled in the study. The varicose veins group had higher incidence rates than the control group for osteoporosis (46.40 vs 31.92 per 10,000 person-years; adjusted HR 1.481 [95%CI, 1.314-1.669; P < 0.001]). Compared with matched controls, varicose veins patients with or without venous ulcers had 1.711- and 1.443-times increased risk of developing osteoporosis, respectively. Subgroup analysis showed varicose veins were associated with osteoporosis in women and patients older than 50 years. The present study demonstrated individuals with varicose veins had an increased risk of osteoporosis. Physicians should be alerted to this issue and consider screening for osteoporosis in patients with varicose veins, especially among women and patients older than 50 years.


Ursolic acid abrogates depressive-like behavior and hippocampal pro-apoptotic imbalance induced by chronic unpredictable stress.
Emerging evidence has shown that ursolic acid exerts antidepressant-like effects, however, its ability to elicit an antidepressant-like response in rodents subjected to stress model that mimics behavioral and neurochemical alterations found in depression remains to be determined. Thus, this study investigated the possible antidepressant-like effect of ursolic acid in mice subjected to chronic unpredictable stress (CUS) for 14 days, and whether this effect could be associated with the modulation of serum corticosterone levels and hippocampal Bcl-2/Bax mRNA expression. Our results indicated that CUS induced a depressive-like behavior, as demonstrated by an increase in the immobility time and latency to first grooming in the tail suspension test and splash test, respectively. Conversely, the repeated administration of ursolic acid (0.1 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o.) in the last 7 days of CUS completely prevented CUS-induced behavioral alterations, suggesting an antidepressant-like effect. Additionally, CUS significantly increased the mRNA expression of Bax (pro-apoptosis marker), but not Bcl-2 (anti-apoptosis marker) in the hippocampus. Moreover, reduced hippocampal mRNA expression of Bcl-2/Bax ratio was detected in CUS-exposed mice. Ursolic acid, but not fluoxetine, prevented CUS-induced increase in the expression of Bax, but both ursolic acid and fluoxetine prevented CUS-induced reduction on Bcl-2/Bax ratio. Furthermore, neither CUS nor treatments with ursolic acid or fluoxetine altered serum corticosterone levels. Our study unveils the ability of ursolic acid to prevent the depressive-like behavior induced by stress and the modulation of Bcl-2/Bax expression could be associated with this response.


Frequency of late drug-eluting stent thrombosis with non-cardiac surgery.
Drug-eluting stents (DES) are highly effective in reducing restenosis but have a small but significant risk for late stent thrombosis (LAST). Cessation of antiplatelet drugs for noncardiac surgery has been implicated in precipitating LAST, prompting surgery to be done on antiplatelet therapy, with all the attendant bleeding risks, or deferred until 12 months after DES implantation, despite limited data defining the risk for LAST. Using billing data from 2 large health funds, members who had DES insertion (n = 9,321) with subsequent noncardiac surgery (n = 4,126) were mailed a questionnaire regarding their noncardiac procedures, antiplatelet use, and subsequent coronary events. From 1,086 returned, 710 were suitable for inclusion, identifying 11 patients (1.5%) with perioperative myocardial infarctions confirmed by medical records. Angiography showed that only 2 had stent thromboses, while 7 had new culprit lesion (2 patients did not undergo angiography). Before their noncoronary procedures, 66% were receiving dual-antiplatelet therapy, and 30% were taking single agents. Surgery was performed on dual therapy in 18%, on single agents in 23%, and with no antiplatelet therapy in 59%. The mean time to surgery from stent implantation was 348 days, with 56% <12 months. In conclusion, noncardiac surgery after DES implantation is frequent and appears to have low cardiac morbidity despite variable antiplatelet cessation. Perioperative myocardial infarctions occur because of narrowings in nonstented coronary arteries rather than from LASTs.


Critical factors influencing visitor emotions: analysis of "restorativeness" in urban park visits in Fuzhou, China.
To date, a comprehensive analysis of urban green space (UGS) visitors' emotional remains largely unexplored. In this study, we focus on how UGS environmental preferences, restorativeness, other physical factors (sound, air, and thermal environments), and individual characteristics affecting visitor emotions. Such a comprehensive analysis would allow relevant practitioners to check the environmental quality of UGSs and improve certain conditions to promote visitor emotions. A total of 904 questionnaire responses with concurrently monitored physical factors were analyzed by independent sample t-tests, one-way ANOVA and path analysis. The thermal evaluation had the largest impact on positive emotions (β = 0.474), followed by perceived restorativeness (β = 0.297), which had β values of -0.120 and -0.158, respectively, on negative emotions. Air evaluation was more effective for increasing positive emotions (β = 0.293) than reducing negative emotions (β = -0.115). Sound evaluation also had similar results (β = 0.330 vs. β = -0.080). Environmental preference significantly influenced only positive emotions (β = 0.181) but could still indirectly impact negative emotions. Moreover, objective physical factors can indirectly affect visitors' emotions by enhancing their evaluations.. The influence of different UGS environmental factors on visitors' emotions vary, as does their impacts on positive versus negative emotions. Positive emotions were generally more affected than negative emotions by UGS. Visitor emotions were mainly influenced by physical and psychological factors. Corresponding suggestions are proposed for UGS design and management in this study.


Stroke Risk and Antithrombotic Treatment During Follow-up of Patients With Ischemic Stroke and Cortical Superficial Siderosis.
In patients with ischemic stroke (IS) or transient ischemic attack (TIA) and cortical superficial siderosis (cSS), there are few data regarding the risk of future cerebrovascular events and also about the benefits and safety of antithrombotic drugs for secondary prevention. We investigated the associations of cSS and stroke risk in patients with recent IS or TIA. We retrospectively analyzed the Microbleeds International Collaborative Network (MICON) database. We selected patients with IS or TIA from cohorts who had MRI-assessed cSS, available data on antithrombotic treatments, recurrent cerebrovascular events (intracranial hemorrhage [ICrH], IS, or any stroke [ICrH or IS]), and mortality. We calculated incidence rates (IRs) and performed univariable and multivariable Cox regression analyses. Of 12,669 patients (mean age 70.4 ± 12.3 years, 57.3% men), cSS was detected in 273 (2.2%) patients. During a mean follow-up of 24 ± 17 months, IS was more frequent than ICrH in both cSS (IR 57.1 vs 14.6 per 1,000 patient-years) and non-cSS (33.7 vs 6.3 per 1,000 patient-years) groups. Compared with the non-cSS group, cSS was associated with any stroke on multivariable analysis {IR 83 vs 42 per 1,000 patient-years, adjusted hazard ratio [HR] for cSS 1.62 (95% CI: 1.14-2.28; p = 0.006)}. This association was not significant in subgroups of patients treated with antiplatelet drugs (n = 6,554) or with anticoagulants (n = 4,044). Patients with cSS who were treated with both antiplatelet drugs and anticoagulants (n = 1,569) had a higher incidence of ICrH (IR 107.5 vs 4.9 per 1,000 patient-years, adjusted HR 13.26; 95% CI: 2.90-60.63; p = 0.001) and of any stroke (IR 198.8 vs 34.7 per 1,000 patient-years, adjusted HR 5.03; 95% CI: 2.03-12.44; p < 0.001) compared with the non-cSS group. Patients with IS or TIA with cSS are at increased risk of stroke (ICrH or IS) during follow-up; the risk of IS exceeds that of ICrH for patients receiving antiplatelet or anticoagulant treatment alone, but the risk of ICrH exceeds that of IS in patients receiving both treatments. The findings suggest that either antiplatelet or anticoagulant treatment alone should not be avoided in patients with cSS, but combined antithrombotic therapy might be hazardous. Our findings need to be confirmed by randomized clinical trials.


The role of learning in improving functional writing in stroke aphasia.
Improving writing in people with aphasia could improve ability to communicate, reduce isolation and increase access to information. One area that has not been sufficiently explored is the effect of impairment based spelling therapies on functional writing. A multiple case study was conducted with eight participants with aphasia subsequent to stroke. This aimed to measure the effects of spelling therapy on functional writing and perception of disability. Participants engaged in 10 sessions of copy and recall spelling therapy. Outcome measures included spelling to dictation of trained and untrained words, written picture description, spelling accuracy within emails, a disability questionnaire and a writing frequency diary. All participants made significant gains on treated words and six demonstrated improvements to untreated words. Group analyses showed significant improvements to written picture description, but not email writing, writing frequency or perceptions of disability. These results show that small doses of writing therapy can lead to large gains in specific types of writing. These gains did not extend to improvements in frequency of writing in daily living, nor ecological measures of email writing. There is a need to develop bridging interventions between experimental tasks towards more multi-faceted and ecological everyday writing tasks. Implications for Rehabilitation Acquired dysgraphia can restrict people from participating in social, educational and professional life. This study has shown that copy and recall spelling therapies can improve the spelling of treated words, untreated words and written picture description in people with a range of types and severities of dysgraphia following stroke. The results of this study suggest that more specific additional training is required for other writing activities such as email writing.


An Insight into the Mechanism of Holamine- and Funtumine-Induced Cell Death in Cancer Cells.
Holamine and funtumine, steroidal alkaloids with strong and diverse pharmacological activities are commonly found in the Apocynaceae family of Holarrhena. The selective anti-proliferative and cell cycle arrest effects of holamine and funtumine on cancer cells have been previously reported. The present study evaluated the anti-proliferative mechanism of action of these two steroidal alkaloids on cancer cell lines (HT-29, MCF-7 and HeLa) by exploring the mitochondrial depolarization effects, reactive oxygen species (ROS) induction, apoptosis, F-actin perturbation, and inhibition of topoisomerase-I. The apoptosis-inducing effects of the compounds were studied by flow cytometry using the APOPercentageTM dye and Caspase-3/7 Glo assay kit. The two compounds showed a significantly greater cytotoxicity in cancer cells compared to non-cancer (normal) fibroblasts. The observed antiproliferative effects of the two alkaloids presumably are facilitated through the stimulation of apoptosis. The apoptotic effect was elicited through the modulation of mitochondrial function, elevated ROS production, and caspase-3/7 activation. Both compounds also induced F-actin disorganization and inhibited topoisomerase-I activity. Although holamine and funtumine appear to have translational potential for the development of novel anticancer agents, further mechanistic and molecular studies are recommended to fully understand their anticancer effects.


Is the oral contraceptive or hormone replacement therapy a risk factor for cholelithiasis: A systematic review and meta-analysis.
Association between exogenous estrogen intake and cholelithiasis risk has been reported in several epidemiological studies, including oral contraceptive (OC) and hormone replacement therapy (HRT), while the results were controversial. This study aimed to perform a comprehensive meta-analysis of this issue. PUBMED, EMBASE, and Cochrane library database were searched up to October 2016. Two reviewers independently extracted data from eligible studies, relative risks (RRs), and/or odds ratios (ORs) with 95% confidence intervals (95% CIs) for the highest versus lowest categories of intake were adopted. Either a fixed- or a random-effects model was adopted to estimate overall RRs or ORs. Besides, subgroup and publication bias analyses were applied to explain the heterogeneity. An original study was also conducted to verify our conclusion. A total of 19 studies with approximately 556,620 participants were included in this meta-analysis. The pooled RR of cholelithiasis for the highest versus the lowest categories was 1.59 (95% CI: 1.44-1.75), indicating that exogenous estrogen was positive associated with the intake of exogenous estrogen. However, the pooled RR of OC intake and cholelithiasis risk was 1.19 (95% CI: 0.97-1.45), and the RR for HRT was 1.79 (95% CI: 1.61-2.00). The HRT was positively associated with the cholelithiasis risk, and the OC will not increase the risk of cholelithiasis.


Multivariate analysis of correlated selection and kin selection, with an ESS maximization method.
Kin selection coefficients are used in two distinct ways. First, these coefficients measure phenotypic correlations that affect the marginal costs and benefits of behaviors. For example, the phenotypic correlation in sex ratio produced by two females in an isolated patch influences the favoured sex ratio. Second, kin selection coefficients describe genotypic correlations that measure fidelity of transmission. For example, a female values daughters vs. nieces according to genotypic correlations. It is widely known that kin selection coefficients may be interpreted as phenotypic or genotypic correlations in different contexts. However, these different interpretations have never been fully separated, and their different role have not been clearly explained. I provide proofs of a generic analytical approach. The technique automatically separates phenotypic correlations among social partners from genotypic components of transmission. The result is a general method that can be derived from first principles and applied to multivariate problems in social evolution. I emphasize a simple, practical maximization method that can be used to calculate equilibrium conditions for complex social interactions.