The role of mean platelet volume in nonalcoholic fatty liver disease without cardiovascular comorbidities, obesity and diabetes mellitus.
While the relation of mean platelet volume (MPV) with inflammatory diseases is obvious, its role in nonalcoholic fatty liver disease (NAFLD) without cardiovascular comorbidities, obesity and diabetes mellitus is not clear. A total of 249 patients (nonobese, nondiabetic and not having cardiac diseases) who underwent an abdominal ultrasonography assessment were enrolled. They were divided according to the absence (group 1) or presence (group 2) of hepatic steatosis. The patients with steatosis were further divided according to the severity of steatosis as group 2a (grade 1), 2b (grade 2) and 2c (grade 3). The demographic and laboratory features were compared between groups. Hepatic steatosis was absent in 120 patients and detected in 129 patients (grade 1, 2, 3 hepatic steatosis in 75, 49 and 5 patients, respectively). BMI, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and serum AST, ALT, triglyceride levels were significantly higher in group 2 than in group 1 (P < 0.001, P < 0.001, P < 0.001, P = 0.005, P < 0.001, respectively). BMI, serum AST and triglyceride levels were significant factors for NAFLD (P < 0.001, P = 0.018, P = 0.001). MPV was neither different between groups (P > 0.05) nor a predictor factor for NAFLD (P > 0.05). MPV is a useless parameter to detect NAFLD without cardiovascular comorbidities, obesity and diabetes mellitus.


The Impact of Facility Type and Volume on Outcomes in Head and Neck Mucosal Melanoma.
To evaluate differences in treatment outcomes for head and neck mucosal melanoma (HNMM) patients seen at academic versus nonacademic centers and high versus low volume facilities. Retrospective cohort study. National Cancer Database. Differences in treatment course and overall survival (OS) by facility type and volume were assessed for 2772 HNMM cases reported by the 2004 to 2017 National Cancer Database. A subgroup analysis was performed with a smaller cohort containing staging data. The analysis employed Kaplan-Meier and Cox proportional hazards models. A higher proportion of patients treated at academic centers within the HNMM cohort waited longer for surgery after diagnosis (p < .001), had negative surgical margins (p < .001), and were readmitted to the hospital within 30 days of surgery (p = .001); these relationships remained significant when controlling for cancer stage. Kaplan-Meier analysis demonstrated higher 5-year OS for patients treated at academic versus nonacademic facilities within the main cohort (32.5% ± 1.3% vs 27.3% ± 1.5%; p = .006) and within the stage-controlled subgroup (34.8% ± 2.1% vs 27.2% ± 2.6%; p = .003). Treatment at high volume versus low volume facilities was associated with improved 5-year OS for main cohort patients (33.5% ± 1.7% vs 28.8% ± 1.2%; p = .016) but not for subgroup patients (35.3% ± 2.7% vs 30.1% ± 2.1%; p = .100). Upon multivariate analysis controlling for demographic and oncologic factors, there was no significant difference in OS by facility type (main cohort: odds ratio [OR] = 1.07, 95% confidence interval [CI] = 1.01-1.21; subgroup: OR = 1.13, 95% CI = 0.97-1.32). Neither facility type nor surgical volume predicts overall survival in HNMM.


Lymphotoxin β receptor activation promotes mRNA expression of RelA and pro-inflammatory cytokines TNFα and IL-1β in bladder cancer cells.
The role of inflammation in tumorigenesis and development is currently well established. Lymphotoxin β receptor (LTβR) activation induces canonical and noncanonical nuclear factor (NF)‑κB signaling pathways, which are linked to inflammation‑induced carcinogenesis. In the present study, 5,637 bladder cancer cells were cultured and the activation of LTβR was induced by functional ligand, lymphotoxin (LT) α1β2, and silencing with shRNA. Reverse transcription‑quantitative polymerase chain reaction was utilized to detect the mRNA expression levels of NF‑κB family members RelA and RelB, cytokines including LTα, LTβ, tumor necrosis factor (TNF)α, TNF superfamily member 14, interleukin (IL)‑6 and IL‑1β, and proliferation‑related genes including CyclinD1 and Survivin. The expression of phospho‑p65 was determined by western blotting. Activation of LTβR on bladder cancer 5,637 cells was demonstrated to upregulate the mRNA expression levels of the RELA proto‑oncogene, RelA, by 2.5‑fold compared with unstimulated cells, while no significant change was observed in the RELB proto‑oncogene NF‑κB member mRNA levels. Expression of pro‑inflammatory cytokines tumor necrosis factor (TNF)α and interleukin (IL)‑1β mRNA levels were significantly increased nearly 5‑fold and 1.5‑fold, respectively, following LTβR activation compared with unstimulated cells. The LTβR‑induced upregulation of RelA, TNFα and IL‑1β was decreased by ~33, 27, and 26% respectively when LTβR was silenced via short hairpin RNA. Activation of LTβR had no effect on 5,637 cell growth, despite CyclinD1 and Survivin mRNA levels increasing by ~2.7 and 1.3‑fold, respectively, compared with unstimulated cells. In conclusion, activation of LTβR induced the expression of RelA mRNA levels. LTβR activation might be an important mediator in promoting an inflammatory microenvironment in bladder cancer, via the upregulation of TNFα and IL‑1β mRNA levels. LTβR may be a potential therapeutic target for bladder cancer.


Mindfulness and intimate relationship satisfaction in daily life: The role of empathy.
This study examined the role of empathy in the relationship between mindfulness and intimate relationship satisfaction (IRS). Using ecological momentary assessment, 100 pairs of university students who were in relationships participated in the study. The participants were invited to complete a questionnaire measuring their current states of mindfulness, IRS, and empathy three times a day for 14 days. The results showed that empathy at the within-person level played a mediating role in the relationship between acceptance and IRS. Empathy at the within-person level also moderated the relationship between monitoring and IRS. Findings illustrated the vital role of empathy in an intimate relationship. Limitations of the study were discussed.


[Health-economics of oncology care: changes in hospital bed capacity].
The aim of our study was to analyze the effect of hospital bed reforms on April 1, 2007 in Hungary, with special respect to the changes of acute care cancer beds. Data were derived from the database of the National Health Insurance Fund Administration (OEP). We identified cancer care hospital capacities (beds) with the following financial codes: code nr. 12 (oncology), code nr. 24 (radiotherapy) and code nr. 28 (hematology). We analyzed the changes of these beds before and after the reform. The total number of acute care hospital beds decreased by 25.7%, while in the field of cancer care beds we found different trends. The number of hospital beds for oncology care and hematology care decreased by 11.4% and 11.1%, respectively. The number of hospital beds for radiotherapy departments even increased by 16.3%. We did not find any changes in regional inequalities. We can conclude that during the hospital bed reform in 2007, the number of oncology and hematology care beds decreased less than the total number of acute care hospital beds, and the number of beds for radiotherapy even increased, without significantly affecting the regional inequalities.


Examining Tennessee's collateral source rule.
The common law collateral source rule was established to prevent the defendant from benefiting from their wrongful actions. Despite a trend in the United States to limit the effects of the collateral source rule, the rule remains in force in courts of the State of Tennessee. However, to assist with the malpractice crisis, the legislature prohibited this rule by statute in regards to the Medical Malpractice Act. Although this statutory prohibition of the collateral source rule worked to lessen verdicts in malpractice cases after passage, the availability of consortium damages resulting from Jordan v. Baptist Three Rivers Hospital in 1999 has worked to drive verdicts substantially higher. Regardless the Medical Malpractice Act has been held as constitutional and has been clarified through several recent Tennessee court decisions.


Do response options influence self-reports of alcohol use?
The influence of response options on self-reported frequency of alcohol use was evaluated in an experimental study of 350 students at a west coast university. Respondents were asked about their frequency of alcohol use in the last 7 days, 30 days, 90 days, and 180 days with three methodological factors randomized: 1) how quantitative the response options were; 2) order of presentation of close-ended response options; and 3) relative placement of alcohol use items in the questionnaire. Results indicate that the quantitativeness of response options and the location of items within the questionnaire have minimal effects on the average frequency of alcohol use and number of inconsistent responses over a wide range of time frames. However, presenting higher frequency response options prior to lower frequency response options increased self-reported frequency of having consumed 2 or more drinks in the last 30 days and frequency of alcohol use over the last 180 days.


[Evidence based medicine and mobbing].
The phenomenon of the physical, moral or psychical violence in the working environment, variously indicated as "mobbing", "workplace bullying" or "workplace harassment", is to date object of numerous studies, mostly of epidemiological type, which are yet to clear, in a sufficient way, the aspects of that phenomenon, the possible causes, risk factors, constituent characteristics and consequences. Our search, a systematic review of the existing studies in literature and a meta-analysis of the jobs chosen to such scope, has shown that only a small percentage of the researches conducted on the topic is represented from studies that collected original information on the subject. The results of the meta-analysis show that in the category of the mobbed workers the psychosomatic disturbs, stress, and anxiety are greater than in the group of controls and that the perception of the surrounding environment is more negative in the victims of mobbing compared with the not mobbed workers. The value of such results is reduced by the characteristics and the heterogeneity of the studies.


Toward the description of electrostatic interactions between globular proteins: potential of mean force in the primitive model.
Monte Carlo simulations are used to calculate the exact potential of mean force between charged globular proteins in aqueous solution. The aim of the present paper is to study the influence of the ions of the added salt on the effective interaction between these nanoparticles. The charges of the model proteins, either identical or opposite, are either central or distributed on a discrete pattern. Contrarily to Poisson-Boltzmann predictions, attractive, and repulsive direct forces between proteins are not screened similarly. Moreover, it has been shown that the relative orientations of the charge patterns strongly influence salt-mediated interactions. More precisely, for short distances between the proteins, ions enhance the difference of the effective forces between (i) like-charged and oppositely charged proteins, (ii) attractive and repulsive relative orientations of the proteins, which may affect the selectivity of protein/protein recognition. Finally, such results observed with the simplest models are applied to a more elaborate one to demonstrate their generality.


Extended field of view of light-sheet fluorescence microscopy by scanning multiple focus-shifted Gaussian beam arrays.
Light-sheet fluorescence microscopy (LSFM) facilitates high temporal-spatial resolution, low photobleaching and phototoxicity for long-term volumetric imaging. However, when a high axial resolution or optical sectioning capability is required, the field of view (FOV) is limited. Here, we propose to generate a large FOV of light-sheet by scanning multiple focus-shifted Gaussian beam arrays (MGBA) while keeping the high axial resolution. The positions of the beam waists of the multiple Gaussian beam arrays are shifted in both axial and lateral directions in an optimized arranged pattern, and then scanned along the direction perpendicular to the propagation axis to form an extended FOV of light-sheet. Complementary beam subtraction method is also adopted to further improve axial resolution. Compared with the single Gaussian light-sheet method, the proposed method extends the FOV from 12 μm to 200 μm while sustaining the axial resolution of 0.73 μm. Both numerical simulation and experiment on samples are performed to verify the effectiveness of the method.


[Rethinking the challenges of Ulysses and Faust: health, the individual and history].
Concentrating on two historical synecdoches, Ulysses and Faust, this article takes up the etymology of the Latin term salute as a unit lying somewhere between "existential needs" and "especially human needs", leading to the challenge of satisfying the need for "conservation of life" and at the same time to "surpass it, go beyond it". Both meanings are present in Ulysses attitude of not succumbing to the siren s melody and in Faust s desire to rise above everyday life. Some aspects of the Marxist conception of the philosophy of history and Althusser s Structuralist Marxism are criticized. Also, in light of Marxist-Hellerian theory, the article analyzes the hypothesis that the target of the final reports of the VIII National Health Conference was "particular man" and not the individual, since health is treated only as "an existential need", and does not envisage the generic human. As a theoretical challenge, the text, in search of the unfolding individual, finally recommends the construction of "epistemological sutures" between nature and society, everyday life and universality, and the young and old Marx.


Succinate mediates inflammation-induced adrenocortical dysfunction.
The hypothalamus-pituitary-adrenal (HPA) axis is activated in response to inflammation leading to increased production of anti-inflammatory glucocorticoids by the adrenal cortex, thereby representing an endogenous feedback loop. However, severe inflammation reduces the responsiveness of the adrenal gland to adrenocorticotropic hormone (ACTH), although the underlying mechanisms are poorly understood. Here, we show by transcriptomic, proteomic, and metabolomic analyses that LPS-induced systemic inflammation triggers profound metabolic changes in steroidogenic adrenocortical cells, including downregulation of the TCA cycle and oxidative phosphorylation, in mice. Inflammation disrupts the TCA cycle at the level of succinate dehydrogenase (SDH), leading to succinate accumulation and disturbed steroidogenesis. Mechanistically, IL-1β reduces SDHB expression through upregulation of DNA methyltransferase 1 (DNMT1) and methylation of the SDHB promoter. Consequently, increased succinate levels impair oxidative phosphorylation and ATP synthesis and enhance ROS production, leading to reduced steroidogenesis. Together, we demonstrate that the IL-1β-DNMT1-SDHB-succinate axis disrupts steroidogenesis. Our findings not only provide a mechanistic explanation for adrenal dysfunction in severe inflammation, but also offer a potential target for therapeutic intervention.


Acute renal failure in the 21st century: recommendations for management and outcomes assessment.
Acute renal failure (ARF) remains a common and potentially devastating disorder affecting as many of 5% of all hospitalized patients, with a higher prevalence in patients in critical care units. ARF is more frequently observed in the setting of multiorgan dysfunction syndrome (MODS) and in elderly patients with complex disease, where mortality is high. Numerous technical advances have not yet impacted favorably on this high mortality rate. This report summarizes recommendations from participants at the National Institutes of Health Conference: "Acute Renal Failure in the 21st Century," May 6 to 8, 1996, in Bethesda, MD. The focus is on categorizing recent clinically relevant developments in the field and on identification of new research initiatives to transfer a new body of knowledge derived from fundamental studies and laboratory investigation to the management of ARF in the new millennium. The development of a multicenter database through cooperative multicenter studies is advocated. Future studies should define the appropriate outcome measures to assess and emphasize the impact of hemodynamic monitoring, adjunctive agents, and adequacy and modality of renal replacement therapy on outcomes in ARF.


Semisynthesis of natural flavones inhibiting tubulin polymerization, from hesperidin.
Semisynthesis of 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (1), a natural flavone that binds with high affinity to tubulin, was performed from hesperidin, the very abundant Citrus flavanone, by a five-step sequence. The last step of the synthesis also gave rise to 5,3'-dihydroxy-3,6,7,4'-tetramethoxyflavone (= casticin or vitexicarpin) (10), 5,3'-dihydroxy-3,7,8,4'-tetramethoxyflavone (= gossypetin 3,7,8,4'-tetramethyl ether) (11), and, unexpectedly, 5,7,3'-trihydroxy-3,6,8,4'-tetramethoxyflavone (12) and 5,3'-dihydroxy-8-dimethylamino-3,6,7,4'-tetramethoxyflavone (= 8-dimethylaminocasticin) (13). Cytotoxicity and antitubulin activity of these five flavones, as well as 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (= ayanin) (14) and intermediate 6,8-dibromo-ayanin (8), were evaluated. Comparison of the responses confirmed and clarified the influence of the A-ring substitution pattern on the biological activity.


Molecular evolution of candidate genes involved in post-mating-prezygotic reproductive isolation.
Traits involved in post-copulatory interactions between the sexes may evolve rapidly as a result of sexual selection and/or sexual conflict, leading to post-mating-prezygotic (PMPZ) reproductive isolating barriers between diverging lineages. Although the importance of PMPZ isolation is recognized, the molecular basis of such incompatibilities is not well understood. Here, we investigate molecular evolution of a subset of Drosophila mojavensis and Drosophila arizonae reproductive tract genes. These include genes that are transcriptionally regulated by conspecific mating in females, many of which are misregulated in heterospecific crosses, and a set of male genes whose transcripts are transferred to females during mating. As a group, misregulated female genes are not more divergent and do not appear to evolve under different selection pressures than other female reproductive genes. Male transferred genes evolve at a higher rate than testis-expressed genes, and at a similar rate compared to accessory gland protein genes, which are known to evolve rapidly. Four of the individual male transferred genes show patterns of divergent positive selection between D. mojavensis and D. arizonae. Three of the four genes belong to the sperm-coating protein-like family, including an ortholog of antares, which influences female fertility and receptivity in Drosophila melanogaster. Synthesis of these molecular evolutionary analyses with transcriptomics and predicted functional information makes these genes candidates for involvement in PMPZ reproductive incompatibilities between D. mojavensis and D. arizonae.


Protein adsorption of dialdehyde cellulose-crosslinked chitosan with high amino group contents.
Crosslinked chitosan was prepared by Schiff base formation between the aldehyde groups of dialdehyde cellulose (DAC) and the amino groups of chitosan and a subsequent reduction. DAC was obtained through periodate oxidation of cellulose and solubilization in hot water at 100°C for 1h. Three grades of DAC-crosslinked chitosan were prepared by adding various amounts DAC. The degrees of crosslinking as determined by amino group content were 3.8, 8.3, and 12.1%, respectively. DAC-crosslinked chitosan showed higher stability in the pH 2-9 range and no cytotoxicity was identified over the course of a 21-day long-term stability test. Also, DAC-crosslinked chitosan showed remarkably high bovine serum albumin (BSA) adsorption capacity at pH 5.5 as a result of the increased amino group content, due to the reaction between DAC and chitosan molecular chains occurring at multiple points even though DAC-crosslinked chitosan showed a lower degree of crosslinking.


Periodic operation of immobilized live cell bioreactor for the production of candicidin.
A lumped model for cell growth and secondary metabolite production in an immobilized live cell bioreactor has been developed. This model is applied here to simulate the performance of an immobilized bioreactor under steady-state conditions and under conditions of periodically varying concentration of a growth-limiting substrate. The results of the simulation study were experimentally verified in the case of the production of the antibiotic candicidin by Streptomyces griseus in an immobilized bioreactor with forced periodic operation. The results of the studies suggest that periodically operated immobilized live cell bioreactors can provide a potent alternative for the production of non-growth-associated biochemicals, as compared to free cell fermentations, pulsed fermentations with process cycle regeneration, and nonregenerated bioreactors. This work has demonstrated that by frequent pulsing of the growth limiting nutrient, stable extended production can be obtained at high specific cellular productivities.


Suitability of scoring PCC rings and fragments for dose assessment after high-dose exposures to ionizing radiation.
Assessment of radiation doses through measurement of dicentric chromosomes may be difficult due to the inability of damaged cells to reach mitosis. After high-dose exposures, premature chromosome condensation (PCC) has become an important method in biodosimetry. PCC can be induced upon fusion with mitotic cells, or by treatment with chemicals such as calyculin A or okadaic acid. Several different cytogenetic endpoints have been measured with chemically induced PCC, e.g., via scoring of extra chromosome pieces or ring chromosomes. The dose-effect curves published with chemically induced PCC show differences in their coefficients and in the distribution of rings among cells. Here we present a study with calyculin A to induce PCC in peripheral blood lymphocytes irradiated at nine different doses of γ-rays up to 20Gy. Colcemid was also added in order to observe metaphase cells. During microscopical analysis the chromosome aberrations observed in the different cell-cycle phases (G2/M-PCC, M/A-PCC and M cells) were recorded. The proportion of G2/M-PCC cells was predominant from 3 to 20Gy, M cells decreased above 1Gy and M/A-PCC cells remained constant at all doses and showed the highest frequencies of PCC rings. Depending on the cell-cycle phase there was a difference in the linear coefficients in the dose-effect curves of extra fragments and rings. Poisson distribution among PCC rings was observed after calyculin A+colcemid treatment, facilitating the use of this methodology also for partial body exposures to high doses. This has been tested with two simulated partial exposures to 6 and 12Gy. The estimated doses in the irradiated fraction were very close to the real dose, indicating the usefulness of this methodology.


Renal masses: characterization with Doppler US.
The vascularity of indeterminate renal masses in 70 patients was investigated prospectively with duplex ultrasound. The peak-systolic Doppler shift frequency obtained from the renal mass was utilized to attempt distinction between benign and malignant lesions. With use of the criterion of a peak-systolic Doppler shift frequency of 2.5 kHz or greater as evidence of neovascularity, 26 of 37 malignant lesions demonstrated tumor signals (70% sensitivity). Thirty-one of 33 benign lesions lacked tumor signals (94% specificity). Both of the false-positive lesions were infections with inflammatory masses, with peak frequencies of 3.0 and 3.7 kHz. Tumor vascularity in most malignant renal mass lesions gives rise to abnormal, high-frequency, Doppler-shifted signals that can aid the differential diagnosis of renal masses.


Longevity regulation by NMD-mediated mRNA quality control.
Proper maintenance of biological components is crucial for longevity and healthy aging. Although the role of homeostatic maintenance systems for DNA and protein in longevity is established, it remains largely unknown for RNA. In our recent work, we show that nonsense-mediated mRNA decay (NMD) promotes longevity in the roundworm C. elegans by enhancing RNA quality control. We find that the activity of NMD decreases during aging, raising the possibility that RNA quality declines in old animals. We then show that key components of NMD complex are required for prolonged lifespan in C. elegans. In addition, animals with reduced insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS), a representative longevity model, display increased NMD activity. Thus, up-regulation of NMD appears to play crucial roles in longevity conferred by reduced IIS via enhancing mRNA quality control. As both IIS and NMD pathways are evolutionarily conserved, mammals including humans may be equipped with similar RNA quality control systems to achieve longevity. [BMB Reports 2017; 50(4): 160-161].


Medical oncology consultation and minimization of overtreatment in men with low-risk prostate cancer.
Specialist bias, in which specialists recommend the therapy that they are capable of delivering, is thought to influence the treatment of patients with localized prostate cancer and to contribute to overtreatment of men with limited life expectancy. Consequently, rates of active surveillance, the preferred management modality per the National Comprehensive Cancer Network (NCCN) for patients with low- and very low-risk disease and a life expectancy of less than 10 and less than 20 years, respectively, are low. We sought to determine whether consultation with a medical oncologist is associated with increased rates of active surveillance in men with low-risk prostate cancer. We identified 188 patients with low-risk prostate cancer undergoing active surveillance at one of three referral centers in Boston, MA in 2009. Multivariable logistic regression was used to determine whether consultation with a medical oncologist was associated with selection of active surveillance. The data were reanalyzed for patients with low- and very low-risk disease and a life expectancy of less than 10 and less than 20 years, respectively. Consultation with a medical oncologist was associated with increased rates of active surveillance (37% v 21%, P = .01), an association that remained significant on multivariable logistic regression (odds ratio [OR] = 2.70; 95% CI, 1.27 to 5.75; P = .01). When applied to patients with limited life expectancy, this finding remained significant (OR = 4.74; 95% CI, 1.17 to 19.25; P = .03). Consultation with a medical oncologist is associated with increased rates of active surveillance, adherence to NCCN guidelines, and minimization of overtreatment in men with early prostate cancer and limited life expectancy.


Effect of regulatory mechanism on hyperbolic reaction network properties.
The notion that the regulated and flux-controlling enzyme in a metabolic network need not correspond suggests that the purpose of regulation may not be flux homeostasis under all physiological circumstances. Additionally, the fact that diversity in the function of intact metabolic networks exists suggests that in addition to time constant separation, other kinetic structure/regulatory mechanism patterns exist. In order to compliment and expand prior work on identifying kinetic structure-property relationships in networks, the present work explores in a general way how the control, dynamic, and energetic properties of metabolic networks depend on operating point, kinetic structure, and regulatory mechanism. The basic feature of trade-offs between properties is illustrated and used as a basis for indicating how particular subsets of structure, regulatory mechanism, and operating point emphasize certain properties that can be associated with a physiological function. Examples of scavenging trace metabolites and amphibolite coordination are proposed. Microstructure logic in terms of turnover number distributions as well as a potential mixed polynomial network analysis approach are also discussed.


[The use of cytoflavin in the acute period of hemorrhagic stroke].
To evaluate the efficacy of cytoflavin in the dose of 10 ml/day in the complex therapy in acute period of hemorrhagic stroke. Sixty patients were examined in the acute period of hemorrhagic stroke (HS). The NIHSS, the Rivermead Mobility Index, the Rankin scale and the Barthel Index of Activities of Daily Living were used. Patients were divided into 2 groups: the main group included 30 patients who received cytoflavin in addition to basic therapy. The control group included 30 patients who received basic therapy. In the main group, there were a significant decrease in the severity of neurological symptoms assessed with the NIHSS in the 10th day of treatment and a more pronounced improvement in the indicators of functional activity on the Rankin scale and daily life on the Barthel index to the level of 'moderate dependence', while the level of 'pronounced dependence' remained in the control group. Thus, the probability of favorable outcome was higher in the main group. Inclusion of cytoflavin in the therapy scheme of patients in the acute period of HS increased the efficacy of treatment.


Peptidome profiling of human serum of uveal melanoma patients based on magnetic bead fractionation and mass spectrometry.
To find new biomarkers for uveal melanoma (UM) by analyzing the serum peptidome profile. Proteomic spectra in patients with UM before and after operation were analyzed and compared with those of healthy controls. Magnetic affinity beads were used to capture serum peptides and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer were used to compile serum peptide profiles. A panel of 49 peptides were differentially expressed between UM patients and controls, of which 33 peptides were of higher intensities in patient group and 16 peptides were of higher intensities in control group. Based on combined use of these potential markers, peptides with mean molecular masses of 1467 and 9289.0 Da provide high sensitivity (83.3%), specificity (100%) and accuracy rate (93.0%) together to differentiate melanoma patients from healthy controls. At the time point of 6mo postoperatively, the levels of many peptides differentially expressed before surgery showed no more statistical difference between the patients and the control group. Fibrinogen α-chain precursors were identified as potential UM markers. We have shown that a convenient and fast proteomic technique, affinity bead separation and MALDI-TOF analysis combined with bioinformatic software, facilitates the identification of novel biomarkers for UM.


Structural analysis of an N-glycan with "beta1-4 bisecting branch" from human serum IgG by negative-ion MSn spectral matching and exoglycosidase digestion.
A novel N-linked oligosaccharide (N-glycan) with "beta1-4 bisecting branch (galactose beta1-4 bisecting N-acetylglucosamine)" was found in human serum IgG. Its structure was efficiently analyzed by using beta-galactosidase digestion, a MSn spectral library database, and negative-ion MS2 spectral matching. For confirmation, the novel N-glycan was synthesized by using an expected standard N-glycan (acceptor), UDP-galactose (donor), and beta1-4 galactosyltransferase. This work also demonstrates that the MSn spectral library database, in particular, negative-ion MS2 spectral matching, can efficiently reduce the number of specific, sequential exoglycosidase digestions required and is useful for rapid structural analysis of unknown glycans not in the database.


Differential susceptibility of mitochondrial complex II to inhibition by oxaloacetate in brain and heart.
Mitochondrial Complex II is a key mitochondrial enzyme connecting the tricarboxylic acid (TCA) cycle and the electron transport chain. Studies of complex II are clinically important since new roles for this enzyme have recently emerged in cell signalling, cancer biology, immune response and neurodegeneration. Oxaloacetate (OAA) is an intermediate of the TCA cycle and at the same time is an inhibitor of complex II with high affinity (Kd~10(-8)M). Whether or not OAA inhibition of complex II is a physiologically relevant process is a significant, but still controversial topic. We found that complex II from mouse heart and brain tissue has similar affinity to OAA and that only a fraction of the enzyme in isolated mitochondrial membranes (30.2±6.0% and 56.4±5.6% in the heart and brain, respectively) is in the free, active form. Since OAA could bind to complex II during isolation, we established a novel approach to deplete OAA in the homogenates at the early stages of isolation. In heart, this treatment significantly increased the fraction of free enzyme, indicating that OAA binds to complex II during isolation. In brain the OAA-depleting system did not significantly change the amount of free enzyme, indicating that a large fraction of complex II is already in the OAA-bound inactive form. Furthermore, short-term ischemia resulted in a dramatic decline of OAA in tissues, but it did not change the amount of free complex II. Our data show that in brain OAA is an endogenous effector of complex II, potentially capable of modulating the activity of the enzyme.


Only a subset of C. canimorsus strains is dangerous for humans.
Capnocytophaga canimorsus are gram-negative bacteria living as commensals in the mouth of dogs and cats. C. canimorsus cause rare but life-threatening generalized infections in humans that have been in contact with a dog or a cat. Over the last years we collected 105 C. canimorsus strains from different geographical origins and from severe human infections or healthy dogs. All these strains were analyzed by 16S rDNA sequencing and a phylogenetic tree revealed two main groups of bacteria instead of one with no relation to the geographical origin. This branching was confirmed by the whole-genome sequencing of 10 strains, supporting the evidence of a new Capnocytophaga species in dogs. Interestingly, 19 out of 19 C. canimorsus strains isolated from human infections belonged to the same species. Furthermore, most strains from this species could grow in heat-inactivated human serum (HIHS) (40/46 tested), deglycosylate IgM (48/66) and were cytochrome-oxidase positive (60/66) while most strains from the other species could not grow in HIHS (22/23 tested), could not deglycosylate IgM (33/34) and were cytochrome-oxidase negative (33/34). Here, we propose to call Capnocytophaga canis (Latin: dog) the novel, presumably less virulent dog-hosted Capnocytophaga species and to keep the name C. canimorsus for the species including human pathogens.


Translating research into practice: the dissemination and initial implementation of an evidence-based HIV prevention program.
Substantial effort has gone into scientifically developing and evaluating HIV prevention interventions. These programs make only minor contributions to HIV prevention efforts until they are widely put into practice; however, little research has been conducted to study how evidence-based, community-level HIV prevention interventions diffuse from research into practice. This article explores how one such evidence-based intervention for young MSM, the Mpowerment Project (MP), is scaling up in the US. The goals of this article are threefold: (a) to describe our longitudinal study, currently underway, concerning issues regarding translating research to practice; (b) present detailed data from 69 CBOs that are implementing the MP regarding characteristics of their communities, agencies, and target populations; and (c) to present baseline data on how these agencies are attempting to implement the MP, focusing on which intervention components CBOs decided to implement, modify, or delete and the implications of these modifications.


Early-Onset Vemurafenib-Induced DRESS Syndrome.
Vemurafenib is a BRAF inhibitor indicated in metastatic or unresectable melanoma in patients with BRAF mutations. Vemurafenib is frequently toxic, but the toxicity is often not serious. The third case of vemurafenib-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is reported herein. The case is unusual in that the onset was early, with symptoms emerging as of day 8 of treatment. Treatment of DRESS syndrome is not currently based on precise recommendations, but systemic corticosteroid therapy is effective in serious cases. Severe toxidermias under vemurafenib are exceptional; immediate discontinuation of treatment upon diagnosis is imperative. Switching from vemurafenib to dabrafenib then seems to constitute an interesting therapeutic alternative, since its efficacy is the same but with fewer cutaneous adverse reactions. This case highlights the importance of awareness of the risk of DRESS syndrome associated with vemurafenib and monitoring for warning signs from treatment initiation.


Dissociations in visual attention deficits among persons with mild cognitive impairment.
Impairments in visual attention and visual information processing have been identified as part of the neuropsychological features of Alzheimer's disease (AD), even in its earliest stages. There is increasing recognition that these deficits may be selective rather than global, with some attentional subtypes being more vulnerable than others. The few studies that have investigated attentional deficits in mild cognitive impairment (MCI), a putatively prodromal phase of AD, have not satisfactorily addressed the possible selectivity in attentional deficits in MCI. This study examined potential dissociations in visual attention deficits in MCI using a measure that assesses simple, divided, and selective attention. The results indicated a hierarchy of attentional impairments, with divided attention being the most affected and simple attention the least. Among participants with MCI, 53% showed evidence of impairment in divided attention compared to 19% of controls (OR = 4.81, p < .001). Poorer visual attention was also associated with poorer overall cognitive status. The implications of these findings for early identification of MCI, prevention of functional decline in MCI, and delay/reversal of cognitive degradation in MCI are discussed.


Ab initio modeling of the motional Stark effect on MAST.
A multichord motional Stark effect (MSE) system has recently been built on the MAST tokamak. In MAST the pi and sigma lines of the MSE spectrum overlap due to the low magnetic field typical for present day spherical tokamaks. Also, the field curvature results in a large change in the pitch angle over the observation volume. The measured polarization angle does not relate to one local pitch angle but to an integration over all pitch angles in the observation volume. The velocity distribution of the neutral beam further complicates the measurement. To take into account volume effects and velocity distribution, an ab initio code was written that simulates the MSE spectrum on MAST. The code is modular and can easily be adjusted for other tokamaks. The code returns the intensity, polarized fraction, and polarization angle as a function of wavelength. Results of the code are presented, showing the effect on depolarization and wavelength dependence of the polarization angle. The code is used to optimize the design and calibration of the MSE diagnostic.


Therapeutic options in female sexual dysfunction.
To review the psychology and physiology of female sexual dysfunction (FSD) and explore current strategies for prevention and treatment. Articles identified through a MEDLINE search using the term female sexual dysfunction. Additional references were identified from the bibliographies of retrieved articles. Investigational studies, clinical trials, and review articles examining female sexual dysfunction. FSD is a widespread problem that can arise from disorders of any component of female sexual response. These disorders are classified as problems with sexual desire, arousal, orgasm, and sexual pain. The dysfunction that characterizes these disorders may stem from a variety of factors, including psychologic issues surrounding sex and the effects of medications on female sexual response. Although pharmacists are unlikely to be involved in counseling patients about the psychologic aspects of sexual dysfunction, they can play a vital role in screening for and managing sexual adverse effects of medications. A variety of nonprescription, prescription, and investigational products may be of benefit for addressing the various types of disorders. Pharmacists who have a thorough understanding of female sexual response, potential causes of dysfunction, and accepted treatment strategies can help detect FSD and advise women about their options for managing this common problem.


Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit.
Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL(CR)), such that a 30-ml/min increase in the estimated CL(CR) would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL(CR) of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL(CR) of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved.


Structure of sylvaticin, a new alpha-elicitin-like protein from Pythium sylvaticum.
The structure of sylvaticin, a 10 kDa major pythin protein excreted by the parasitic oomycete Pythium sylvaticum, has been determined. Although closely related to alpha-elicitins in its biological response, toxicity and overall structure, sylvaticin presents a number of structural features that make it an unusual member of the elicitin class. Elicitins possess a large hydrophobic cavity and the mechanism of the systemic acquired resistance induced in planta is known to proceed through lipid transport and complexation within this cavity. Unlike other elicitins, sylvaticin contains tryptophan residues, one of which points inwards towards the central cavity, thus limiting access to sterols. In the case of sylvaticin, the sterol-transport mechanism is likely to be of less importance compared with other members of the elicitin family and still remains to be fully characterized.


Electron-Transfer-Enhanced Cation-Cation Interactions in Homo- and Heterobimetallic Actinide Complexes: A Relativistic Density Functional Theory Study.
To provide deep insight into cation-cation interactions (CCIs) involving hexavalent actinyl species that are major components in spent nuclear fuel and pose important implications for the effective removal of radiotoxic pollutants in the environment, a series of homo- and heterobimetallic actinide complexes supported by cyclopentadienyl (Cp) and polypyrrolic macrocycle (H4L) ligands were systematically investigated using relativistic density functional theory. The metal sort in both parts of (THF)(H2L)(OAnVIO) and (An')IIICp3 from U to Np to Pu, as well as the substituent bonding to Cp from electron-donating Me to H to electron-withdrawing Cl, SiH3, and SiMe3, was changed. Over 0.70 electrons are unraveled to transfer from the electron-rich UIII to the electron-deficient AnVI of the actinyl moiety, leading to a more stable AnV-UIV isomer; in contrast, uranylneptunium and uranylplutonium complexes behave as electron-resonance structures between VI-III and V-IV. These were further corroborated by geometrical and electronic structures. The energies of CCIs (i.e., Oexo-An' bonds) were calculated to be -19.6 to -41.2 kcal/mol, affording those of OUO-Np (-23.9 kcal/mol) and OUO-Pu (-19.6 kcal/mol) with less electron transfer (ET) right at the low limit. Topological analyses of the electron density at the Oexo-An' bond critical points demonstrate that the CCIs are ET or dative bonds in nature. A positive correlation has been built between the CCIs' strength and corresponding ET amount. It is concluded that the CCIs of Oexo-An' are driven by the electrostatic attraction between the actinyl oxo atom (negative) and the actinide ion (positive) and enhanced by their ET. Finally, experimental syntheses of (THF)(H2L)(OUVIO)(An')IIICp3 (An' = U and Np) were well reproduced by thermodynamic calculations that yielded negative free energies in a tetrahydrofuran solution but a positive one for their uranylplutonium analogue, which was synthetically inaccessible. So, our thermodynamics would provide implications for the synthetic possibility of other theoretically designed bimetallic actinide complexes.


(Z)-7,4'-Dimethoxy-6-hydroxy-aurone-4-O-β-glucopyranoside exerts neuroprotective effects in vitro and anxiolytic activity in vivo.
This study investigated the neuroprotective effects of (Z)-7,4'-dimethoxy-6-hydroxy-aurone-4-O-β-glucopyranoside (DHG) against hydrogen peroxide-induced cell damage in PC12 cells and further evaluated its effects on doxorubicin-induced anxiety-like behavior in rats. PC12 cells were treated with different concentrations of DHG (1-10 µM) for 24 h and then exposed to 0.2 mM hydrogen peroxide for 12 h. Cell viability was measured using the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium-bromide and lactate dehydrogenase assay. The apoptosis was detected by annexin V-PI staining. Oxidative stress was confirmed in PC12 cells by enzyme-linked immunosorbent assay, real-time PCR, and western blot. The anxiolytic effects of DHG were evaluated in the elevated plus maze test. Our results showed that DHG treatment significantly increased cell viability and decreased PC12 cell apoptosis induced by hydrogen peroxide by increasing the mitochondrial membrane potential, decreasing the cytochrome c release, inhibiting the activities of caspase-3 and caspase-9, and regulating the expression of apoptosis-related proteins. Moreover, DHG treatment effectively attenuated the redox imbalance in PC12 cells by enhancing the activity of superoxide dismutase and increasing the level of glutathione, as well as decreasing levels of malondialdehyde and intracellular reactive oxygen species. Furthermore, DHG treatment significantly mitigated the doxorubicin-induced adverse behavioral changes in rats. These results indicate the neuroprotective and antiapoptotic properties of DHG exerted by counteracting the oxidative stress and highlight DHG as a potential therapeutic regimen for behavior impairment of anxiety.


Nanomicellar Topical Aqueous Drop Formulation of Rapamycin for Back-of-the-Eye Delivery.
The objective of this study was to develop a clear, aqueous rapamycin-loaded mixed nanomicellar formulations (MNFs) for the back-of-the-eye delivery. MNF of rapamycin (0.2%) was prepared with vitamin E tocopherol polyethylene glycol succinate (TPGS) (Vit E TPGS) and octoxynol-40 (Oc-40) as polymeric matrix. MNF was characterized by various parameters such as size, charge, shape, and viscosity. Proton nuclear magnetic resonance ((1)H NMR) was used to identify unentrapped rapamycin in MNF. Cytotoxicity was evaluated in human retinal pigment epithelial (D407) and rabbit primary corneal epithelial cells (rPCECs). In vivo posterior ocular rapamycin distribution studies were conducted in male New Zealand white rabbits. The optimized MNF has excellent rapamycin entrapment and loading efficiency. The average size of MNF was 10.98 ± 0.089 and 10.84 ± 0.11 nm for blank and rapamycin-loaded MNF, respectively. TEM analysis revealed that nanomicelles are spherical in shape. Absence of free rapamycin in the MNF was confirmed by (1)H NMR studies. Neither placebo nor rapamycin-loaded MNF produced cytotoxicity on D407 and rPCECs indicating formulations are tolerable. In vivo studies demonstrated a very high rapamycin concentration in retina-choroid (362.35 ± 56.17 ng/g tissue). No drug was identified in the vitreous humor indicating the sequestration of rapamycin in lipoidal retinal tissues. In summary, a clear, aqueous MNF comprising of Vit E TPGS and Oc-40 loaded with rapamycin was successfully developed. Back-of-the-eye tissue distribution studies demonstrated a very high rapamycin levels in retina-choroid (place of drug action) with a negligible drug partitioning into vitreous humor.


Novel systemic therapies in the management of tyrosine kinase inhibitor-pretreated patients with epidermal growth factor receptor-mutant non-small-cell lung cancer.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard first-line option for non-small-cell lung cancer (NSCLC) harboring active EGFR mutations. The overall survival of patients with advanced NSCLC has improved dramatically with the development of comprehensive genetic profiles and targeted therapies. However, resistance inevitably occurs, leading to disease progression after approximately 10-18 months of EGFR-TKI treatment. Platinum-based chemotherapy is the standard treatment for patients who have experienced disease progression while undergoing EGFR-TKI treatment, but its efficacy is limited. The management of extensively pretreated patients with EGFR-mutant NSCLC is becoming increasingly concerning. New agents have shown encouraging efficacy in clinical trials for this patient population, including fourth-generation EGFR-TKIs, EGFR-TKIs combined with counterpart targeted drugs, and novel agents such as antibody-drug conjugates. We review current efforts to manage extensively pretreated patients with EGFR-mutant NSCLC.


Access to Veterinary Drugs in Sub-Saharan Africa: Roadblocks and Current Solutions.
Access to veterinary drugs for livestock has become a major issue over the last decade. Analysis has tended to focus on the demand for these products, while studies looking at the drivers behind their use generally focus on farmer behavior and interactions between veterinarians and farmers. However, the use of drugs also depends on structural factors that determine the functioning of the drug supply chain and farmers' access to the drugs. This article presents an overview of the factors that limit access to veterinary drugs in sub-Saharan Africa (SSA) as well as the international policy tools and arrangements that claim to improve it. We have conducted a scoping review of the scientific and grey literature as well as the publicly-available data from both the animal health industry and international organizations. We aimed to gather information on the veterinary drugs market in SSA as well as on the international norms, recommendations, guidelines, and initiatives that impact SSA farmers' access to these drugs. We highlight numerous barriers to veterinary drug access in SSA. The SSA market is highly dependent on imports, yet the region attracts little attention from the international companies capable of exporting to it. It suffers from a high level of fragmentation and weak distribution infrastructures and services, and is driven by the multiplication of private non-professional actors playing a growing role in the veterinary drug supply chain. The distribution system is increasingly dualized, with on the one hand the public sector (supported by development organizations) supplying small scale farmers in rural areas, but with limited and irregular means; and on the other side a private sector largely unregulated which supplies commercial and industrial farming systems. Different innovations have been developed at the international and regional levels to try to reduce barriers, such as homogenizing national legislations, donations, and vaccine banks. Alongside decades-old inter-state cooperation, many new forms of public-private partnerships and other hybrid forums continue to emerge, signaling the private sector's increasing influence in global governance. Policies on animal health would be bolstered by a better understanding of the drivers behind and the components of access to veterinary drugs in different regional and national contexts. Inequalities in drug access need to be addressed and a market-driven approach adopted in order to strengthen our understanding of what determines veterinary drug use at the farm level. Policies should balance the interests of the various stakeholders, being careful not to reinforce bias toward certain diseases deemed "interesting" and neglect others that could prove to be highly important for veterinary public health.


The Association Between Maternal Age and the Prevalence of Congenital Heart Disease in Newborns from 2016 to 2018 in Single Cardiac Center in Jeddah, Saudi Arabia.
Congenital heart diseases (CHD) are suggested to be associated with advanced maternal age in different ethnicities and geographical locations. To provide a profound ground for comparison with Saudi Arabian population, in this study, we have assessed the association between maternal age and congenital heart diseases for different age groups during the period from 2016 to 2018 in King Abdul-Aziz Medical City in Jeddah. In this case-control study, we found no evidence relating maternal age to the incidence of CHD. However, an association between maternal age and the type of CHD was found. Mothers who are 35 years old or younger are more likely to have a baby with atrial septal defects, while babies of mothers who are older than 35 presented mostly with ventricular septal defects and patent ductus arteriosus. Therefore, no modification to the local clinical practice, including a referral of patients for fetal echocardiography based on maternal age, is recommended.


Catering for the Point-of-Care Testing Explosion.
The ease of performing a laboratory test near to the patient, at the point-of-care, has resulted in the integration of point-of-care tests into healthcare treatment algorithms. However, their importance in patient care necessitates regular oversight and enforcement of best laboratory practices. This review discusses why this oversight is needed, it's importance in ensuring quality results and processes that can be placed to ensure point-of-care tests are chosen carefully so that both oversight can be maintained and patient care is improved. Furthermore, it highlights the importance of delivering focused webinars and continuing education in a variety of formats.


Lipopolysaccharide (LPS)-induced macrophage activation and signal transduction in the absence of Src-family kinases Hck, Fgr, and Lyn.
Lipopolysaccharide (LPS) stimulates immune responses by interacting with the membrane receptor CD14 to induce the generation of cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6. The mechanism by which the LPS signal is transduced from the extracellular environment to the nuclear compartment is not well defined. Recently, an increasing amount of evidence suggests that protein tyrosine kinases especially the Src-family kinases Hck, Fgr, and Lyn, play important roles in LPS signaling. To directly address the physiological function of Hck, Fgr and Lyn in LPS signaling, a genetic approach has been used to generate null mutations of all three kinases in a single mouse strain. hck-/-fgr-/-lyn-/- mice are moderately healthy and fertile; macrophages cultured from these mice express normal levels of CD14 and no other Src-family kinases were detected. Although the total protein phosphotyrosine level is greatly reduced in macrophages derived from hck-/-fgr-/-lyn-/- mice, functional analyses indicate that both elicited peritoneal (PEMs) and bone marrow-derived macrophages (BMDMs) from triple mutant mice have no major defects in LPS-induced activation. Nitrite production and cytokine secretion (IL-1, IL-6, and TNF-alpha) are normal or even enhanced in hck-/-fgr-/-lyn-/- macrophages after LPS stimulation. The development of tumor cell cytotoxicity is normal in triple mutant BMDMs and only partially impaired in PEMs after LPS stimulation. Furthermore, the activation of the ERK1/2 and JNK kinases, as well as the transcription factor NF-kappaB, are the same in normal and mutant macrophages after LPS stimulation. The current study provides direct evidence that three Src-family kinases Hck, Fgr, and Lyn are not obligatory for LPS-initiated signal transduction.


Neonatal Aneurysm Rupture in a Child with a De Novo Variant to ANKRD17.
Ankyrin repeat domain 17 (ANKRD17) is postulated to play a role in the integrity of blood vessels and has been reported to be associated with developmental delays, epilepsy, and growth restriction. Whereas ANKRD17-deficient mice have been demonstrated to experience catastrophic hemorrhages, vascular malformations have not been reported in human patients with pathogenic variants to ANKRD17. We report a term male neonate with a heterozygous de novo variant to ANKRD17 (ANKRD17; c6988 C > G, P.[P2330a]) who experienced subarachnoid hemorrhage from a ruptured aneurysm involving the left middle cerebral artery. He experienced acute symptomatic seizures and required clipping of his aneurysm at 35 days of life, later progressing to developing multifocal drug-resistant epilepsy. To our knowledge, this case represents the first report of a cerebrovascular malformation from a patient with ANKRD17. Further work is needed to investigate whether pathogenic variants to ANKRD17 can lead to cerebral aneurysms or other cerebrovascular malformations in children.


Effects of pre-experimental knowledge on recognition memory.
The influence of pre-experimental autobiographical knowledge on recognition memory was investigated using as memoranda faces that were either personally known or unknown to the participant. Under a dual process theory, such knowledge boosted both recollection- and familiarity-based recognition judgements. Under an unequal variance signal detection model, pre-experimental knowledge increased both the variance and the separation of the target and foil memory strength distributions, boosting hits and correct rejections. Thus, pre-experimental knowledge has profound effects on the multiple, interacting processes that subserve recognition memory, and likely in the neural systems that underpin them.


Management of Acromioclavicular Osteoarthritis in Rotator Cuff Tears: A Scoping Review.
Purpose The treatment of acromioclavicular joint (ACJ) osteoarthritis during shoulder arthroscopy is a discussed topic. The aim of this scoping review is to report the current recommendations regarding the management of this disorder in patients undergoing surgery for rotator cuff tears. Methods A scoping review was performed in Pubmed\Medline and Embase in March 2017, restricted to English language literature. The following keywords were used: ("rotator cuff tear" OR " rotator cuff" OR "rotator cuff repair") AND ("acromioclavicular joint arthritis" OR "ac joint arthritis" OR "ac joint" OR "acromioclavicular joint"). Inclusion criteria were randomized controlled trials, prospective cohort studies, retrospective trials, and therapeutic case series. Exclusion criteria were reviews, meta-analyses, and expert opinions. Results Two retrospective studies and three randomized controlled trials were identified. Clinical studies reported results of 443 shoulders, with an average age of 60.48 years and a mean follow-up of 31.7 months. Many differences were found regarding the design of the studies, patient's selection, surgical procedures, and instrumental and clinical evaluations. No statistically significant differences were found in clinical outcome scores between patients that underwent rotator cuff repair in association with distal clavicular resection and patients with isolated rotator cuff repair. Conclusion Results of this scoping review underline a lack of evidence-based recommendations about the management of ACJ osteoarthritis in association with arthroscopic rotator cuff repair. Surgical procedures such as distal clavicle resection (DCR) should be performed carefully in this cohort of patients. More prospective randomized studies are needed to reach a consensus about the correct surgical approach to DCR in patients with signs of ACJ osteoarthritis and rotator cuff tears. Level of Evidence Level III.


An imbalance fault detection method based on data normalization and EMD for marine current turbines.
This paper proposes an imbalance fault detection method based on data normalization and Empirical Mode Decomposition (EMD) for variable speed direct-drive Marine Current Turbine (MCT) system. The method is based on the MCT stator current under the condition of wave and turbulence. The goal of this method is to extract blade imbalance fault feature, which is concealed by the supply frequency and the environment noise. First, a Generalized Likelihood Ratio Test (GLRT) detector is developed and the monitoring variable is selected by analyzing the relationship between the variables. Then, the selected monitoring variable is converted into a time series through data normalization, which makes the imbalance fault characteristic frequency into a constant. At the end, the monitoring variable is filtered out by EMD method to eliminate the effect of turbulence. The experiments show that the proposed method is robust against turbulence through comparing the different fault severities and the different turbulence intensities. Comparison with other methods, the experimental results indicate the feasibility and efficacy of the proposed method.


Evaluation of 0 ≤ M ≤ 8 earthquake data sets in African - Asian region during 1966-2015.
This article evaluates the occurrence of 0 [Formula: see text]M[Formula: see text] 8 earthquake data sets for the period of 50 years (that is, January 1, 1966 to December 31, 2015) in African and Western Asia region. It is bounded by latitude 40° S to 40° N and longitude 30° W to 60° E with the focal depth of 0-700 km. Seventy seven thousand, six hundred and ninety-six data points were presented for the analysis. The data used were extracted from earthquake catalog of Advanced National Seismic system via http://quake.geo.berkeley.edu/cnss/, an official website of the Northern California Earthquake Data Centre, USA. Each datum comprised the earthquake occurrence date, time of the earthquake occurrence, epicenter's coordinates, focal depth and magnitude. The Gutenberg-Richter's relationship being the longest observed empirical relationship in seismology, analysis of variance and time series were used to analyze the seismicity of the study area. Annual distributions of earthquake occurrence based on magnitude variations with the limit 0 [Formula: see text]M[Formula: see text] 8 were presented. The two constants a and b in the Gutenberg-Richter's equation, magnitude of completeness (MC) adjusted R-Square and F-value for the period of 1966-1975, 1976-1985, 1986-1995, 1996-2005, 2006-2015, and the entire period of investigation ranging from 1966 to 2015 were determined so as to investigate the variations of these parameters on earthquake occurrence over time. The histograms of earthquake occurrence against magnitude of earthquakes for the selected years (1966-1975, 1976-1985, 1986-1995, 1996-2005, 2006-2015, and 1966-2015), and the decadal frequency distributions of earthquake occurrence were also plotted. The focal depth occurrence for each magnitude bins (0-0.9, 1-1.9, 2-2.9, 3-3.9, 4-4.9, 5-5.9, 6-6.9, 7-7.9, 8-8.9) were grouped into shallow, intermediate, and deep depths ranging from 0 to 70, 71 to 300, and 301 to 700 km as being used in seismology. The neural network analysis was also applied to the magnitude of the earthquake. The network uses a time series magnitude data as input with the output being the magnitude of the following day. If the nature of the earthquakes time series is stochastic, modeling and prediction is possible. The earthquake data sets presented in this article can further be adopted in the study of seismicity pattern, b-value using series of models, earthquake prediction and variations of earthquake parameters on African and/or Arabian plates. When this approach is integrated with other technique(s), it can provide insights to stability of African lithospehric plates especially the coastal region of Africa.


Impaired circadian photosensitivity in mice lacking glutamate transmission from retinal melanopsin cells.
Intrinsically photoreceptive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin and convey retinal light inputs to the circadian system via the retinohypothalamic tract (RHT) projection to the suprachiasmatic nucleus (SCN). The principal neurotransmitter of this projection is glutamate, and ipRGCs use the vesicular glutamate transporter 2 (VGLUT2) to package glutamate into synaptic vesicles. However, these neurons contain other potential neurotransmitters, such as pituitary adenylate cyclase activating polypeptide (PACAP). To test the role of glutamate in mediating ipRGC light inputs into the SCN, we crossed mice in which Cre-recombinase expression is driven by the melanopsin promotor (Opn4(Cre/+)) with mice in which the second exon of VGLUT2 is flanked by loxP sites (VGLUT2(fl/fl)), producing ipRGCs that are unable to package glutamate into synaptic vesicles. Such mice had free-running circadian rhythms that did not entrain to a 12:12 light-dark (12:12 LD) cycle, nor did they show a phase delay after a 45-min light pulse administered at circadian time (CT) 14. A small subset of the mice did appear to entrain to the 12:12 LD cycle with a positive phase angle to lights-off; a similar entrainment pattern could be achieved in free-running mice if they were exposed to a 12:12 LD cycle with light of a greater intensity. Glutamate transmission from the ipRGCs is necessary for normal light entrainment of the SCN at moderate (0.35 W/m(2)) light levels, but residual transmission (possibly by PACAP in ipRGCs or by other RGCs) can weakly entrain animals, particularly at very high (6.53 W/m(2)) light levels, although it may be less effective at suppressing locomotor activity (light masking).


CRISPR/Cas9-mediated mutagenesis of Sex lethal (Sxl) gene impacts fertility of the Fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae).
Identification of novel approaches for managing the global pest, the Fall armyworm, Spodoptera frugiperda, is the need of the hour, as it defies many management strategies including synthetic chemicals, Bt transgenics, and so on. Recently CRISPR/Cas9-based genome editing opened up newer avenues to design novel pest management strategies such as precision-guided sterile insect technique (pgSIT). In this regard, genes governing sex determination, egg reproduction, and spermatogenesis could be the prime targets for genome editing. This requires validation of the target genes, preferably by a nontransgenic DNA-free editing, before the final application. One such important gene regulating sex determination in Drosophila is the Sex lethal (Sxl). However, the function of Sxl is not highly conserved in other insects and, in particular, we are beginning to comprehend its role in Lepidoptera with only one reference available in Spodoptera litura till date. In the present study, we have edited the sxl gene of S. frugiperda through the delivery of ribonucleoprotein complex (sgRNA + Cas9) at G0 stage embryo, targeting the conserved region of all the documented five splice variants. Results clearly showed that editing of sxl gene impacted the overall fecundity and hatching rate. Therefore, Sxl could be one of the target genes for developing pgSIT approach for the management of S. frugiperda.


HIV-1 CNS in vitro infectivity models based on clinical CSF samples.
The concentration of antiretrovirals in CSF is often utilized as a surrogate for CNS drug exposure. This measurement does not consider pharmacodynamic or combinative effects of ART. We have developed a novel endpoint measurement to assess antiretroviral activity of CSF from subjects on ART. CSF samples were obtained from patients receiving tenofovir/emtricitabine (245/200 mg once daily) with either rilpivirine (25 mg once daily) or lopinavir/ritonavir/maraviroc (400/100/150 mg twice daily) and HIV-uninfected controls. Antiviral activity of ART-containing CSF was assessed in cell cultures using PBMCs and neuro-derived glial (U87) and astrocyte (373) cell lines. Infectivity model half-maximal inhibitory concentration (IMIC50) values were calculated and expressed as -log2IMIC50. Results were correlated with CSF antiretroviral concentrations. Compared with controls, CSF from both ART studies demonstrated in vitro antiretroviral activity in all models. CSF antiretroviral activity of patients on lopinavir/ritonavir/maraviroc was significantly greater than that of patients on rilpivirine [-log2IMIC50 (95% CI) 4.82 (4.74-4.89) versus 3.43 (3.33-3.54) in PBMCs, 3.06 (2.98-3.15) versus 2.56 (2.46-2.65) in U87 cells and 6.00 (6.11-5.88) versus 4.90 (5.09-4.72) in 373 cells, respectively]. Positive correlations were observed for individual CSF antiretroviral activity in different cellular models with CSF concentrations of rilpivirine (P = 0.040 in 373 cells) and lopinavir (P = 0.048 in 373 cells), but not maraviroc. Antiviral activity of CSF from patients on ART was successfully calculated and was greater with a regimen containing four active drugs compared with three active drugs. The use of neuro-derived cell lines alongside PBMCs to assess the effect of ART on CSF may act as a useful future clinical research tool.


Weekly Teriparatide Administration and Preoperative Anterior Slippage of the Cranial Vertebra Next to Fusion Segment < 2 mm Promote Osseous Union After Posterior Lumbar Interbody Fusion.
A multicenter case-control study. The aim of this study was to investigate the independent predictors of osseous union after posterior lumbar interbody fusion (PLIF). PLIF is usually performed to treat lumbar degenerative diseases in elderly patients. Some patients exhibit intervertebral pseudoarthrosis. We analyzed 66 elderly patients with osteoporosis who underwent PLIF from 2011 to 2014 (all women, mean age 71 years, follow-up period ≥6 months). Patients were randomly allocated to receive either treatment with weekly teriparatide, starting at 1 week postoperatively, or no teriparatide. Preoperative lumbar spine radiographs were obtained, and the amount of anterior slippage was measured. Osseous union was assessed by computed tomography at 6 months postoperatively. Thirty-three patients (50%) showed complete osseous union, while 33 did not. Teriparatide was administered in 20 (61%) patients of the union group and in 9 (27%) patients of the nonunion group (P < 0.01). The preoperative anterior slippage of the cranial vertebra next to fusion segment < 2 mm was observed in 16 (49%) and 4 (12%) patients in the union and nonunion groups, respectively (P < 0.01). Multivariate regression analysis showed that teriparatide administration (odds ratio, 4.75; 95% confidence interval: 1.51-14.90; P < 0.01) and preoperative anterior slippage of the cranial vertebra next to fusion segment < 2 mm (odds ratio, 5.90; 95% confidence interval: 1.53-22.70; P < 0.01) were independently associated with osseous union within 6 months after PLIF. At 6 months postoperatively, the mean femoral neck bone mineral density significantly increased by 1.1% in the union group and decreased by 1.3% in the nonunion group (P < 0.05). Weekly teriparatide administration and preoperative anterior slippage of the cranial vertebra next to fusion segment < 2 mm were independent predictors of osseous union within 6 months after PLIF. Our findings suggest that biological and mechanical factors may influence the improvement of spinal fusion. 4.


PLD2 regulates microtubule stability and spindle migration in mouse oocytes during meiotic division.
Phospholipase D2 (PLD2) is involved in cytoskeletal reorganization, cell migration, cell cycle progression, transcriptional control and vesicle trafficking. There is no evidence about PLD2 function in oocytes during meiosis. Herein, we analyzed PLD2 expression and its relationship with spindle formation and positioning in mouse oocyte meiosis. High protein level of PLD2 was revealed in oocytes by Western blot, which remained consistently stable from prophase I with intact germinal vesicle (GV) up to metaphase II (MII) stage. Immunofluorescence showed that PLD2 appeared and gathered around the condensed chromosomesafter germinal vesicle breakdown (GVBD), and co-localized with spindle from pro-metaphase I (pro-MI) to metaphase I (MI) and at MII stage. During anaphase I (Ana I) to telophase I (Tel I) transition, PLD2 was concentrated in the spindle polar area but absent from the midbody. In oocytes incubated with NFOT, an allosteric and catalytic inhibitor to PLD2, the spindle was enlarged and center-positioned, microtubules were resistant to cold-induced depolymerization and, additionally, the meiotic progression was arrested at MI stage. However, spindle migration could not be totally prevented by PLD2 catalytic specific inhibitors, FIPI and 1-butanol, implying at least partially, that PLD2 effect on spindle migration needs non-catalytic domain participation. NFOT-induced defects also resulted in actin-related molecules' distribution alteration, such as RhoA, phosphatidylinosital 4, 5- biphosphate (PIP2), phosphorylated Colifin and, consequently, unordered F-actin dynamics. Taken together, these data indicate PLD2 is required for the regulation of microtubule dynamics and spindle migration toward the cortex in mammalian oocytes during meiotic progression.


Complex abdominal wall reconstruction after massive resection due to neoplastic invasion: a case report.
Complex reconstructions of the abdominal wall, necessary after resection of neoplasms, infection or trauma, are a challenge for the surgical team. Although ovarian carcinoma is commonly presented with peritoneal carcinomatosis and invasion of adjacent organs, it rarely can invade the abdominal wall. Invasion of the abdominal wall was documented on ultrasound and abdominal computed tomography. Surgery was discussed and performed in a multidisciplinary team and consisted of wide en bloc excision and reconstruction with open intraperitoneal onlay mesh with inorganic polypropylene-coated mesh (Bard/BD Sepramesh), a midweight macroporous mesh and abdominoplasty. Postoperative course was uneventful and the patient showed good evolution 1 year after the procedure. Our report highlights the main objectives in complex reconstructions, the importance of a multidisciplinary team and discusses the characteristics that the mesh must have in order to achieve the desired goal.


New Strategies to Increase the Abiotic Stress Tolerance in Woody Ornamental Plants in Mediterranean Climate.
The native flora of different Mediterranean countries, often woody species, was widely recognized for its ornamental potential. The shrubs, in particular, are a typology of plants very widespread in the Mediterranean environment and constituent the 'Macchia', the typical vegetation of this ecosystem. The use of native shrubs for the realization of ornamental green areas has been recently examined for their adaptability to abiotic stress. Abiotic stresses, in fact, are the major limiting growth factor in urban and peri-urban areas. The identification and use of tolerant ornamental species allow the reduction of management costs and preserve the aesthetical value of green areas. Tolerance to drought stress, for instance, in the Mediterranean climate can improve the ecosystem services of these plants in the urban environment. In this review, the possibility to early individuate different plant species' mechanisms to tolerate or avoid the stresses is analysed, as well as the possibility to increase abiotic stress tolerance through genetic and agronomic strategies. The exploration of wild or spontaneous species can be a good source for selecting tolerant plants to be used as ornamental plants in urban areas. Among agronomic strategies, biostimulants, mulching, and plant combination can provide a useful solution to counteract abiotic stress in the urban environment.


Quality Assessment of Domesticated Animal Genome Assemblies.
The era of high-throughput sequencing has made it relatively simple to sequence genomes and transcriptomes of individuals from many species. In order to analyze the resulting sequencing data, high-quality reference genome assemblies are required. However, this is still a major challenge, and many domesticated animal genomes still need to be sequenced deeper in order to produce high-quality assemblies. In the meanwhile, ironically, the extent to which RNAseq and other next-generation data is produced frequently far exceeds that of the genomic sequence. Furthermore, basic comparative analysis is often affected by the lack of genomic sequence. Herein, we quantify the quality of the genome assemblies of 20 domesticated animals and related species by assessing a range of measurable parameters, and we show that there is a positive correlation between the fraction of mappable reads from RNAseq data and genome assembly quality. We rank the genomes by their assembly quality and discuss the implications for genotype analyses.


Synovial chondromatosis presenting as an epidural mass.
Synovial chondromatosis is an uncommon disorder characterized by the formation of multiple cartilaginous nodules in the synovium of the facet joint. It most commonly affects large joints such as hip or shoulder. Commonly seen features are bony erosion and calcifications. Synovial chondromatosis is rare in the spine and there are few previous reports of extension into the spinal canal. A 58-year-old man presented with a 2 year history of progressive numbness in the right upper extremity without objective weakness. A several month course of conservative management, including physical therapy, failed to alleviate symptoms. Magnetic resonance imaging of the cervical spine demonstrated the erosion of the right facet C5-C6 joint with listhesis and foraminal enlargement secondary to a lesion. Treatment was offered to the patient in the form of surgical resection. The lesion was removed in piecemeal fashion using curettes and Cavitron ultrasonic surgical aspirator. Histological examination demonstrated atypical well-differentiated cartilaginous proliferation. This patient had an uncomplicated postoperative course and experienced complete resolution of right upper extremity sensory symptoms. Synovial chondromatosis may compromise cervical spinal cord and nerve roots if it extends into the spinal canal. Although it remains rare, it should be included in the differential diagnosis for upper extremity radiculopathy and myelopathy. Surgical resection is a viable treatment option for symptomatic patients with this pathology. In some cases, adequate resection may necessitate stabilization with instrumentation.


Obstructive nephropathy secondary to AA-type amyloidosis in ankylosing spondylitis.
AA-type amyloidosis of the genitourinary tract is a rare phenomenon and few cases are described in the literature. We report a 42-year-old man with ankylosing spondylitis, who developed hematuria, bilateral hydronephrosis, and renal failure caused by AA amyloidosis.


Does early intervention improve outcomes in physiotherapy management of lumbar radicular syndrome? A mixed-methods study protocol.
Lumbar radicular syndrome (LRS) can be a painful and debilitating condition. The optimum management strategies and their timing remain elusive despite extensive research. Surgery provides good short-term outcomes but has concomitant risks and costs. Physiotherapy is commonly practised for patients with LRS but its effects remain equivocal and there is a lack of consensus on the type, duration and timing of physiotherapy intervention. There is a lack of high-quality evidence into new and innovative management strategies and the timings of those strategies for LRS. This pilot trial is an essential preliminary to a definitive randomised controlled trial (RCT) assessing the effectiveness and cost-effectiveness of early physiotherapy intervention for patients with LRS. The study will test the protocol, the intervention, the use of outcome measures and the ability to set-up and run the trial to enable refinement of a future definitive RCT. This is a mixed-methods study encompassing an external pilot RCT with integrated qualitative interviews with patients, clinicians and other key stakeholders. 80 patients will be recruited from primary care and randomised, after consent into 1 of 2 groups. Both groups will receive individually tailored, goal orientated physiotherapy. The usual care group will begin their physiotherapy 6 weeks after randomisation and the intervention group at 2 weeks after randomisation. Outcome measures will primarily be feasibility parameters including the ability to recruit and retain patients and to deliver the intervention. Data will be collected at baseline, and 6, 12 and 26 weeks following randomisation. The study has received favourable ethical review from the East of Scotland Research Ethics Service (EoSRES) on the 20 August 2015 (15/ES/0130). Recruitment began on the 1 March 2016 and is expected to close in January 2017. Data collection is anticipated to be complete in July 2017. The study results will be made available to participants, clinicians involved in the study and the wider clinical community through publication in a peer reviewed journal and at conference presentations. ISRCTN: 25018352, Pre-results; Clinical Trials.Gov: NCT02618278 Document version V1.1 23.9.2016.


Promoter hypermethylation of cyclooxygenase-2 gene in esophageal squamous cell carcinoma.
Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies including esophageal squamous cell carcinoma (ESCC). However, a subset of ESCC either do not express COX-2 or show low level of expression. It is well established that promoter methylation is a major mechanism that mediates transcriptional silencing of COX-2 in gastric and colorectal cancer, but the data on ESCC are very limited. In this study, we attempted to determine whether COX-2 expression was also regulated by promoter methylation in human ESCC cell lines. We examined the methylation status of the COX-2 promoter in five human ESCC cell lines (EC109, EC9706, KYSE 410, KYSE 150, TE-1) using bisulfite sequencing analysis. Western blot analysis was used to determine COX-2 expression. Quantitative real-time polymerase chain reaction was used to determine COX-2 mRNA level. Prostaglandin (PG) E(2) was detected by ELISA. The promoter was densely methylated in TE-1 and KYSE 150, which had a low level of COX-2 expression and less methylated in other three cell lines (EC109, EC9706, KYSE 410), with high level of COX-2 expression. Treatment with 5-aza-deoxycytidine (5-aza-DC), a DNA methyltransferase inhibitor, demethylated the promoter and upregulated COX-2 expression, as well as PGE(2) production in TE-1 and KYSE 150. However, no such effects were observed in EC109. COX-2 protein was negative, but mRNA was positive in TE-1. After treatment with 5-aza-DC, both COX-2 mRNA and protein level had increased. These findings suggest that the promoter methylation may be one of the mechanisms that regulate COX-2 expression in ESCC.


Aligned Er-doped ZnO nanorod arrays with enhanced 1.54 microm infrared emission.
Vertically aligned Er-doped ZnO nanorod arrays with sharp and intense 1.54 microm infrared emission have been fabricated on Si substrates through a well controlled spin-coating and annealing process. The synthesis method is advantageous for synthesizing ZnO nanostructures free from structural defects, capability for large-scale production, minimum equipment requirement and product homogeneity. Er atoms were found to incorporate into ZnO lattice from XRD, ESCA, TEM, STEM/EDS and PL measurements. The single-crystal Er-doped nanorods maintained their high microstructural quality after annealing for 4 hr at 800 degreesC. The intensity of 1.54 microm infrared emission was found to be correlated with the deep level green emission. The enhanced luminescence intensity and best ever narrow wavelength distribution of Er-doped ZnO nanorod arrays at 1.54 microm emission will be conductive to applications in optoelectronic devices and optical communications.


[Colorectal cancer: assessment of two-yearly screening of the population in health care examination centres].
To present the first assessment of the two-yearly faecal occult blood test used to screen patients attending health care centres for examinations. Method The Hemoccult II test was proposed by correspondence to 26 530 subjects aged 52-74 years, having exhibited a negative test during their periodical check-up 2 years before. The test was performed by 20 590 subjects and the corrected participation rate, taking into account unjustified sending, was of 83.1%. The positivity rate was 3.5%. In the 519 colonoscopies performed (71% of positive Hemoccult II), 23 cancers and 91 adenomas (31 larger than 1 cm) were observed (positive predictive value=22%). In 213 subjects, the information on the follow-up of the positive Hemoccult II were unavailable or unexploitable (lost to follow-up, coloscopy refused, inappropriate examinations). These results show that the two-yearly screening for colorectal cancer in an informed population after a periodical check-up results in a good participation rate. The follow-up rate of positive subjects, fundamental for the assessment of the program, is lower than during the regular check-up but remains relatively satisfactory.


Reflection and transmission of coupled elastic waves by a semiconduction interlayer with consideration of photothermal effects.
The wave propagation problem through an inhomogeneous semiconduction slab sandwiched between two thermoelastic half-spaces is studied in this paper. Due to the photothermal effects and photoacoustic effects, the multiple physical fields coupled waves are generated in the semiconduction interlayer. For the inhomogenous semiconduction slab of finite thickness, the multiple physical fields coupled waves cannot be expressed explicitly. Instead, the state vector is defined, and the state transfer equation is derived to obtain the transfer matrix of the inhomogeneous slab. The reflection and transmission coefficients as well as the dissipation energy are estimated. The influences of the photothermal effects and photoacoustic effects are discussed based on the numerical results. It is found that the photothermal effects and photoacoustic effects result in some different vibration modes and associated propagation modes. The gradient profiles of the inhomogeneous interlayer have complicated influences on the reflection and transmission behaviors and can be well-designed to adjust the propagation behavior.


The Relationship of Serum Soluble Fas Ligand (sFasL) Level with the Extent of Coronary Artery Disease.
Fas/Fas ligand system contributes to the programmed cell death induced by myocardial ischemia. We investigated whether serum soluble Fas ligand (sFasL) level is independently related with the severity and extent of angiographically assessed coronary artery disease (CAD). We included 169 patients in this study. Two groups were formed based on the existence of a lesion on coronary angiography. First group included patients with normal coronary arteries (NCA; n = 53). Patients with atherosclerotic lesions were included in the second group (n = 116). We used the coronary vessel score (the number of the coronary arteries with a lesion leading to ≥ 50% luminal obstruction) and the Azar score to determine the extent and the severity of CAD. Standard enzyme-linked immunosorbent assay kits were used to measure serum sFasL levels. The serum sFasL level was higher in patients with CAD than in patients with NCA (0.52 ± 0.23 mU/mL vs. 0.45 ± 0.18 mU/mL, p = 0.023). The sFasL level correlated with Azar score (r = 0.231, p = 0.003) and with coronary vessel score (r = 0.269, p < 0.001). In the multivariate analysis, we found that age (beta: 0.188, p = 0.008), gender (beta: 0.317, p < 0.001), diabetes mellitus (DM; beta: 0.195, p = 0.008), and sFasL level (beta: 0.209, p = 0.003) were independently related with Azar score. When we used coronary vessel score as the dependent variable, we found that age (p = 0.020), gender (p < 0.001), DM (p = 0.006), and sFasL level (p = 0.001) were independent predictors. Serum sFasL level is associated with angiographically more severe CAD. Our findings suggest that sFasL level may be a biochemical surrogate of severe coronary atherosclerosis.


Bioavailability of Mineral-Bound Iron to a Snow Algal-Bacterial Coculture and Implications for Albedo-Altering Snow Algal Blooms.
Snow algae can form large-scale blooms across the snowpack surface and near-surface environments. These pigmented blooms can decrease snow albedo and increase local melt rates, and they may impact the global heat budget and water cycle. Yet, the underlying causes for the geospatial occurrence of these blooms remain unconstrained. One possible factor contributing to snow algal blooms is the presence of mineral dust as a micronutrient source. We investigated the bioavailability of iron (Fe)-bearing minerals, including forsterite (Fo90, Mg1.8Fe0.2SiO4), goethite, smectite, and pyrite as Fe sources for a Chloromonas brevispina-bacterial coculture through laboratory-based experimentation. Fo90 was capable of stimulating snow algal growth and increased the algal growth rate in otherwise Fe-depleted cocultures. Fo90-bearing systems also exhibited a decrease in the ratio of bacteria to algae compared to those of Fe-depleted conditions, suggesting a shift in microbial community structure. The C. brevispina coculture also increased the rate of Fo90 dissolution relative to that of an abiotic control. Analysis of 16S rRNA genes in the coculture identified Gammaproteobacteria, Betaproteobacteria, and Sphingobacteria, all of which are commonly found in snow and ice environments. Archaea were not detected. Collimonas and Pseudomonas, which are known to enhance mineral weathering rates, comprised two of the top eight (>1%) operational taxonomic units (OTUs). These data provide unequivocal evidence that mineral dust can support elevated snow algal growth under otherwise Fe-depleted growth conditions and that snow algal microbial communities can enhance mineral dissolution under these conditions.IMPORTANCE Fe, a key micronutrient for photosynthetic growth, is necessary to support the formation of high-density snow algal blooms. The laboratory experiments described herein allow for a systematic investigation of the interactions of snow algae, bacteria, and minerals and their ability to mobilize and uptake mineral-bound Fe. Results provide unequivocal and comprehensive evidence that mineral-bound Fe in Fe-bearing Fo90 was bioavailable to Chloromonas brevispina snow algae within an algal-bacterial coculture. This evidence includes (i) an observed increase in snow algal density and growth rate, (ii) decreased ratios of bacteria to algae in Fo90-containing cultures relative to those of cultures grown under similarly Fe-depleted conditions with no mineral-bound Fe present, and (iii) increased Fo90 dissolution rates in the presence of algal-bacterial cocultures relative to those of abiotic mineral controls. These results have important implications for the role of mineral dust in supplying micronutrients to the snow microbiome, which may help support dense snow algal blooms capable of lowering snow albedo and increasing snow melt rates on regional, and possibly global, scales.


Gravity and Magnetic Anomalies of the Sierra Madera, Texas, "Dome".
A geophysical traverse across the Sierra Madera "Dome" indicates a negative gravity anomaly of 1(1/2) milligals over the zone of brecciation in the center and a residual positive anomaly of (1/2) milligal associated with a positive magnetic anomaly of 25 x 10(-5) oersted to the southeast of the zone of brecciation. Areal surveys are needed before any definite conclusions can be drawn concerning the origin of Sierra Madera. However, gravity and magnetic data can be extremely valuable in establishing criteria for classifying terrestrial and lunar features according to meteoritic and cryptovolcanic origin.


The certitudes and uncertainties of health care reform.
The Patient Protection and Affordable Care Act (PPACA) of 2010 was signed into law by President Obama on March 23. This legislation has elicited much debate among policy experts and the public alike. No one knows exactly how this new complex law will play out, and objective evaluation of its effects is important. The American College of Physicians hopes that the legislation will advance key priorities on coverage, workforce, and payment and delivery system reform. The goal of the PPACA is to help provide affordable health insurance coverage to most Americans, improve access to primary care, and lower costs. This article discusses what the chances are that it will accomplish these objectives. It also explains many of the key provisions in the legislation and how they will affect both physicians and patients. Despite considerable uncertainty about the effects of this act, when compared with the status quo, it is an extraordinary achievement that will continue to evolve through its implementation.


[Clinical research of medicinal vesiculation for perennial allergic rhinitis].
To compare the efficacy differences between dog-days medicinal vesiculation and regular-day medicinal vesiculation for perennial allergic rhinitis (PAR), and observe their effects on serum immune globulin E (IgE) and interleukin-4 (IL-4). Seventy-two patients were randomly divided into a dog-days moxibustion group (34 cases) and a regular-day moxibustion group (38 cases). In the dog-days moxibustion group, medicinal vesiculation was applied on the 1st dog-day, 2nd dog-day and last dog-day in summer by lunar calendar, 3 treatments per dog-day for totally 9 times. In the regular-day moxibustion group, the moxibustion was given on the regular day for continuous 9 times. The symptom score, rhinoconjunctivitis quality of life questionnaire (RQLQ) and the level of IgE and IL-4 were compared before and after treatment in two groups; the short-term and two-year efficacy evaluation were performed too. The short-term total effective rate was 88.2% (30/34) in the dog-days moxibustion group, which was not significantly different to 86.8% (33/38) in the regular-day moxibustion group (P>0.05). The long-term total effective rate was 97.1% (33/34) in the dog-days moxibustion group, which was significantly superior to 81.6% (31/38) in the regular-day moxibustion group (P<0.05). After treatment, the serum IgE, IL-4 and RQLQ were significantly reduced (all P<0.01), but the difference between two groups was not significant (all P>0.05). Medicinal moxibustion could be taken as a regular treatment for PAR, which could be performed during the whole year, and dog-days moxibustion could be considered as an enhanced method for prevention and treatment of PAR.


A three-gene cluster in Trichoderma reesei reveals a potential role of dmm2 in DNA repair and cellulase production.
The ascomycete Trichoderma reesei is one of the most efficient industrial producers of cellulase. Gene targeting by homologous recombination is a key technique for improving strains and constructing mutants. In T. reesei, tku70 (homologous to human KU70) was deleted to block non-homologous end-joining, which led to 95% of transformants exhibiting homologous recombination. Two genes located in close proximity to tku70 were identified: the ferrochelatase gene hem8 (tre78582, homologous to Aspergillus niger hemH and Cryptococcus neoformans HEM15) and a putative DNA methylation modulator-2 gene dmm2 (tre108087, homologous to Neurospora crassa dmm-2). Genome-wide surveys of 324 sequenced fungal genomes revealed that the homologues of the three genes of interest are encoded in tandem in most Sordariomycetes. The expression of this three-gene cluster is regulated by blue light. The roles of these three genes were analyzed via deletion and complementation tests. The gene hem8 was originally described as a novel and highly distinct auxotrophic marker in T. reesei and we found that the product protein, HEM8, catalyzes the final step in heme biosynthesis from highly photoreactive porphyrins. The lethal phenotype of the hem8 deletion could be overcome by hematin supplementation. We also studied the functions of tku70 and dmm2 in DNA repair using mutagen sensitivity experiments. We found that the Δtku70 strain showed increased sensitivity to bleomycin, which induces DNA double-strand breaks, and that the Δdmm2 strain was sensitive to bleomycin, camptothecin (an inhibitor of type I topoisomerases), and hydroxyurea (a deoxynucleotide synthesis inhibitor). The double-mutant Δtku70&dmm2 showed higher sensitivity to hydroxyurea, camptothecin, and bleomycin than either of the single mutants. Knockout of dmm2 significantly increased cellulase production. Our data show, for the first time, that ferrochelatase encoded by hem8 catalyzes the final step in heme biosynthesis from highly photoreactive porphyrins and that dmm2 encodes a putative DNA methylation modulator-2 protein related to DNA repair and cellulase expression in T. reesei. Our data provide important insights into the roles of this three-gene cluster in T. reesei and other Sordariomycetes and show that the DNA methylation modulator DMM2 affects cellulase gene expression in T. reesei.