Ab Initio Ligand-Field Theory Analysis and Covalency Trends in Actinide and Lanthanide Free Ions and Octahedral Complexes.
Actinide chemistry is gaining increased focus in modern research, particularly in the fields of energy research and molecular magnetism. However, the structure-function and structure-property relationships of actinides have still not been studied as intensely as those for transition metals. In this work, we report a detailed ab initio study of the spectroscopic, magnetic, and bonding properties of the trivalent actinide free ions and their associated hexachloride complexes in octahedral symmetry. The electronic structures of these systems are examined using complete active-space self-consistent-field calculations followed by second-order N-electron valence perturbation theory, including both scalar relativistic and spin-orbit-coupling effects. The computed energies and wave functions are further analyzed by means of ab initio ligand-field theory (AILFT) and finally chemically interpreted by means of the angular overlap model (AOM). The derived Slater-Condon and spin-orbit parameters have allowed us to systematically rationalize the spectroscopic and magnetic properties of the investigated free ions and complexes along the entire actinide series. Overall, the AILFT- and AOM-derived parameters accurately reproduce the multireference electronic structure calculations. The small observed discrepancies with respect to experimentally derived ligand-field parameters are essentially due to an underestimation of the electronic correlation, which arises from both the constrained size of the active space (restricted to the f orbitals) and the limit of the perturbation approach to account for dynamical correlation. Our analysis also provides insight into the metal-ligand covalency trends along the series. Consistent with natural population analysis, the nephelauxetic (Slater-Condon parameters) and relativistic nephelauxetic (spin-orbit-coupling) reductions determined for these complexes indicate a decrease in the covalency along the series. These trends also hold, to varying extents, for the corresponding tetravalent derivatives, as well as the lanthanide analogues.


Admixture analysis of plasma cholesterol levels in a Jewish population sample in Jerusalem.
The frequency distribution of total plasma cholesterol levels (TC) in 17-year-old Jerusalem youngsters and their parents (n = 6,170) was examined for evidence of admixture of normal distributions. Probability plots indicated bimodality of age-adjusted TC in both sexes. Using a maximum likelihood procedure, two normal distributions fitted the age- and sex-adjusted data significantly better than 1, with 0.9% males and 1.2% females coming from a lower distribution 2-3 standard deviations below the major mode and 0.2% males and 1.1% females belonging to the higher distribution. These results suggest that single genes may determine high as well as low cholesterol levels, but are open to other interpretations, and thus require confirmation by segregation analysis. Jews originating from Europe showed the highest TC levels followed by those from Israel, Asia, and Africa. Adjustment of TC for ethnicity did not alter the above estimates. Analysis of bimodality within countries of origin showed greater separation of the distributions in Asian and Israeli origin groups than in European and North African groups, in whom there was less evidence for admixture.


Distinct mechanisms of substrate selectivity in the DRE-TIM metallolyase superfamily: A role for the LeuA dimer regulatory domain.
The use of modular domains in proteins affords nature a simple route to the diversification of protein function, but co-evolution between domains can complicate large-scale functional annotation. The LeuA dimer regulatory domain is primarily responsible for allosteric feedback inhibition of the enzymes isopropylmalate synthase (IPMS) and citramalate synthase (CMS). In addition to this regulatory role, presence of the domain may also affect substrate selectivity in certain members of the enzyme family. To assess the role of the LeuA dimer regulatory domain in substrate selectivity, truncated versions of IPMS and CMS from Methanococcus jannaschii (MjIPMS and MjCMS, respectively) have been created that lack the LeuA dimer regulatory domain. In the case of MjIPMS, loss of the regulatory domain does not affect substrate selectivity, consistent with previous reports identifying conserved active site residues that play this role. Loss of the regulatory domain in MjCMS, however, results in increased functional promiscuity. Both truncated enzymes exhibit a shift in quaternary structure from tetrameric to monomeric forms as judged by size-exclusion chromatography. Kinetic isotope effects reveal that loss of the regulatory domain results in unique effects on catalysis with chemistry becoming more rate-determining in MjIPMS and less rate-determining in MjCMS. Finally, substitution of conserved active site residues in the promiscuous truncated MjCMS affect substrate selectivity while identical substitutions cause no changes in the wild-type enzyme. Overall, the data predicts a more complex role for the LeuA dimer regulatory domain in substrate selectivity through catalytic modulations rather than selectivity through differential binding as a result of extensive co-evolution between the catalytic and regulatory domains.


Focused VHEE (very high energy electron) beams and dose delivery for radiotherapy applications.
This paper presents the first demonstration of deeply penetrating dose delivery using focused very high energy electron (VHEE) beams using quadrupole magnets in Monte Carlo simulations. We show that the focal point is readily modified by linearly changing the quadrupole magnet strength only. We also present a weighted sum of focused electron beams to form a spread-out electron peak (SOEP) over a target region. This has a significantly reduced entrance dose compared to a proton-based spread-out Bragg peak (SOBP). Very high energy electron (VHEE) beams are an exciting prospect in external beam radiotherapy. VHEEs are less sensitive to inhomogeneities than proton and photon beams, have a deep dose reach and could potentially be used to deliver FLASH radiotherapy. The dose distributions of unfocused VHEE produce high entrance and exit doses compared to other radiotherapy modalities unless focusing is employed, and in this case the entrance dose is considerably improved over existing radiations. We have investigated both symmetric and asymmetric focusing as well as focusing with a range of beam energies.


Efficacy and safety of asenapine in Asian patients with an acute exacerbation of schizophrenia: a multicentre, randomized, double-blind, 6-week, placebo-controlled study.
Asenapine is a second generation anti-psychotic approved in the USA in 2009 for the treatment of schizophrenia, but its efficacy has not been proven in Asian patients. The objectives of this study are to evaluate the efficacy and tolerability of asenapine in Asian patients experiencing an acute exacerbation of schizophrenia. In this prospective, double-blind study, patients in Japan, Korea, and Taiwan were randomized (1:1:1) to asenapine 5 mg twice daily (bid), 10 mg bid or placebo for 6 weeks after a 3- to 7-day washout/screening period. The primary endpoint was the mean change in the positive and negative syndrome scale (PANSS) total score from baseline to day 42/treatment end. Of the 532 participants randomized, 530 received treatment. The primary endpoint was significantly greater with asenapine 5 and 10 mg bid than with placebo (-12.24 and -14.17 vs. -0.95; p < 0.0001). The results of secondary endpoints including PANSS negative subscale scores and PANSS responders at the end of treatment supported the results of the primary endpoint. There were no significant differences in the incidence of treatment-emergent adverse events reported with asenapine 5 and 10 mg bid and placebo (84.6, 80.7, and 81.6 %). There was a mean (± standard deviation) change in weight of -1.76 ± 2.45 kg for placebo, +0.42 ± 2.65 kg for asenapine 5 mg bid, and +0.81 ± 2.89 kg for asenapine 10 mg bid group. Asenapine was effective and generally well tolerated when used for the treatment of acute exacerbations of schizophrenia in Asian patients.


Estrogen receptor alpha-immunoreactive astrocytes are increased in the hippocampus in Alzheimer's disease.
Postmenopausal estrogen use may decrease the risk, and delay the onset and progression, of Alzheimer's disease (AD). By means of fluorescence immunocytochemistry, the present study investigated the distribution of estrogen receptor alpha (ERalpha) in the human hippocampus in controls and in AD cases. ERalpha immunoreactivity was observed in neurons and glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in the hippocampus both in controls and AD cases. The number and density of GFAP- and ERalpha-positive astrocytes was increased in AD. The number of GFAP-immunoreactive astrocytes, the number of nuclear ERalpha-staining astrocytes, and cytoplasmic ERalpha-staining astrocytes per unit area (1 mm(2)) significantly increased (P < 0.001, P < 0.05, P < 0.05, respectively) in CA1 in AD patients, while the percentage of ERalpha-immunoreactive astrocytes of the two groups did not differ (P > 0.05). These data suggest an important role for ERalpha-mediated effects of estrogens on neurons and astrocytes in the hippocampus of human and AD patients.


Neuropilin-2 expression promotes TGF-β1-mediated epithelial to mesenchymal transition in colorectal cancer cells.
Neuropilins, initially characterized as neuronal receptors, act as co-receptors for cancer related growth factors and were recently involved in several signaling pathways leading to cytoskeletal organization, angiogenesis and cancer progression. Then, we sought to investigate the ability of neuropilin-2 to orchestrate epithelial-mesenchymal transition in colorectal cancer cells. Using specific siRNA to target neuropilin-2 expression, or gene transfer, we first observed that neuropilin-2 expression endows HT29 and Colo320 for xenograft formation. Moreover, neuropilin-2 conferred a fibroblastic-like shape to cancer cells, suggesting an involvement of neuropilin-2 in epithelial-mesenchymal transition. Indeed, the presence of neuropilin-2 in colorectal carcinoma cell lines was correlated with loss of epithelial markers such as cytokeratin-20 and E-cadherin and with acquisition of mesenchymal molecules such as vimentin. Furthermore, we showed by surface plasmon resonance experiments that neuropilin-2 is a receptor for transforming-growth factor-β1. The expression of neuropilin-2 on colon cancer cell lines was indeed shown to promote transforming-growth factor-β1 signaling, leading to a constitutive phosphorylation of the Smad2/3 complex. Treatment with specific TGFβ-type1 receptor kinase inhibitors restored E-cadherin levels and inhibited in part neuropilin-2-induced vimentin expression, suggesting that neuropilin-2 cooperates with TGFβ-type1 receptor to promote epithelial-mesenchymal transition in colorectal cancer cells. Our results suggest a direct role of NRP2 in epithelial-mesenchymal transition and highlight a cross-talk between neuropilin-2 and TGF-β1 signaling to promote cancer progression. These results suggest that neuropilin-2 fulfills all the criteria of a therapeutic target to disrupt multiple oncogenic functions in solid tumors.


Toward Corneal Limbus In Vitro Model: Regulation of hPSC-LSC Phenotype by Matrix Stiffness and Topography During Cell Differentiation Process.
A functional limbal epithelial stem cells (LSC) niche is a vital element in the regular renewal of the corneal epithelium by LSCs and maintenance of good vision. However, little is known about its unique structure and mechanical properties on LSC regulation, creating a significant gap in development of LSC-based therapies. Herein, the effect of mechanical and architectural elements of the niche on human pluripotent derived LSCs (hPSC-LSC) phenotype and growth is investigated in vitro. Specifically, three formulations of polyacrylamide gels with different controlled stiffnesses are used for culture and characterization of hPSC-LSCs from different stages of differentiation. In addition, limbal mimicking topography in polydimethylsiloxane is utilized for culturing hPSC-LSCs at early time point of differentiation. For comparison, the expression of selected key proteins of the corneal cells is analyzed in their native environment through whole mount staining of human donor corneas. The results suggest that mechanical response and substrate preference of the cells is highly dependent on their developmental stage. In addition, data indicate that cells may carry possible mechanical memory from previous culture matrix, both highlighting the importance of mechanical design of a functional in vitro limbus model.


Elevated acute phase reactants in hemodialysis patients.
The incidence of elevated acute phase reactants, measured by nephelometry, was examined in 69 otherwise uncomplicated hemodialysis patients in comparison with 30 healthy subjects. Increased C-reactive protein was found in 40.6% of the patients (p less than 0.001 vs controls) and the degree of increase was correlated with the duration of hemodialysis. Haptoglobin was increased in 33.3% (p less than 0.01 vs controls). High levels of alpha-1-acid glycoprotein and alpha-1-proteinase inhibitor were present in 15.9% and 2.9%, respectively; these frequencies were not significantly different from controls. No differences between pre- and postdialysis values were observed. It is concluded that, unlike C-reactive protein, both alpha-1-acid glycoprotein and alpha-1-proteinase inhibitor maintain an excellent specificity in hemodialysis patients. Vice versa, haptoglobin may be unreliable as an acute phase reactant in these patients because of the unacceptably high false-positive rate.


Interrogating Bronchoalveolar Lavage Samples via Exclusion-Based Analyte Extraction.
Although average survival rates for lung cancer have improved, earlier and better diagnosis remains a priority. One promising approach to assisting earlier and safer diagnosis of lung lesions is bronchoalveolar lavage (BAL), which provides a sample of lung tissue as well as proteins and immune cells from the vicinity of the lesion, yet diagnostic sensitivity remains a challenge. Reproducible isolation of lung epithelia and multianalyte extraction have the potential to improve diagnostic sensitivity and provide new information for developing personalized therapeutic approaches. We present the use of a recently developed exclusion-based, solid-phase-extraction technique called SLIDE (Sliding Lid for Immobilized Droplet Extraction) to facilitate analysis of BAL samples. We developed a SLIDE protocol for lung epithelial cell extraction and biomarker staining of patient BALs, testing both EpCAM and Trop2 as capture antigens. We characterized captured cells using TTF1 and p40 as immunostaining biomarkers of adenocarcinoma and squamous cell carcinoma, respectively. We achieved up to 90% (EpCAM) and 84% (Trop2) extraction efficiency of representative tumor cell lines. We then used the platform to process two patient BAL samples in parallel within the same sample plate to demonstrate feasibility and observed that Trop2-based extraction potentially extracts more target cells than EpCAM-based extraction.


Access to hepatitis B vaccination among Korean American children in immigrant families.
This study examined social determinants affecting successful completion of the hepatitis B vaccination protocol among Korean American children in immigrant families. The effects of family characteristics, social support from support network, barriers to immunizations, and health beliefs concerning hepatitis B vaccination were examined using logistic regression analysis. Information support concerning parenting and child health (adjusted odds ratio [aOR] 2.55, 95% confidence interval [CI] 1.11-7.02) and perception that hepatitis B was a difficult disease from which to recover (aOR 2.11, 95% CI 1.20-3.72) appear to be the most important factors for vaccination compliance after adjusting for family income, mother's education level, and health insurance coverage. The burden of paying for immunizations (aOR 0.50, 95% CI 0.22-0.90) also had an impact on the vaccination status. These findings suggest that identifying the children at risk of undervaccination against hepatitis B maybe aided by focusing on these social determinants in addition to provider and sociodemographic characteristics.


Renovascular hypertension.
Renovascular hypertension is the most prevalent form of curable hypertension. Despite some unanswered questions, there is a growing consensus about the need to identify patients with renovascular hypertension so that a specific therapy can be recommended. The renin-angiotensin system is the chief pathophysiologic mechanism responsible for hypertension in patients with renal ischemia but other, yet poorly defined, mechanisms may be operative. Most patients with renovascular hypertension do not present with typical or discriminative clinical features. Thus, many physicians do not perform work-up to uncover renovascular disease even if diagnosis is dictated by patients' clinical course. It is difficult to make the proper diagnosis unless there is a high index of suspicion and certain procedures are performed. How can we, then, select a few patients for the work-up from the vast sea of people with hypertension? The identification of such patients and the pursuit of a renovascular etiology is a matter of clinical judgment. Delineation of renovascular hypertension should be undertaken only after careful deliberation. When clinical clues suggestive of renovascular hypertension are present, appropriate diagnostic tests should be undertaken in patients who are candidates for PTRA or surgery. Captopril-stimulated PRA test is done first. If the test is positive (and in some clinically relevant circumstances even if it is not done or is negative), DSA should be obtained. IV-DSA is being steadily replaced by the superior IA-DSA. The need for renal vein renin determination varies from center to center, but when carefully performed, it yields meaningful information. Ultimately, a conventional arteriogram is done to define the extent of renal artery stenosis and to assess intrarenal vascular anatomy. For selected patients, the benefit-risk ratio clearly outweighs the cost considerations. The spectrum of renovascular hypertension is variable, further compounding the diagnostic indications and contraindications. At one end of this spectrum are those patients in whom surgical therapy is likely to be beneficial, and at the other end are the patients who have relative contraindications to surgery. In between lies the vast gray zone that constitutes a great judgmental challenge in clinical medicine. What is to be done with the patients who have mild to moderate renovascular hypertension whose BP is controlled on medical therapy? There are some patients who may benefit from renovascular repair despite the nonlateralization of renal vein renins. What is the mechanism underlying their hypertension?(ABSTRACT TRUNCATED AT 400 WORDS)


A simple method for displaying recalcitrant proteins on the surface of bacteriophage lambda.
Bacteriophage lambda (lambda) permits the display of many foreign peptides and proteins on the gpD major coat protein. However, some recombinant derivatives of gpD are incompatible with the assembly of stable phage particles. This presents a limitation to current lambda display systems. Here we describe a novel, plasmid-based expression system in which gpD deficient lambda lysogens can be co-complemented with both wild-type and recombinant forms of gpD. This dual expression system permits the generation of mosaic phage particles that contain otherwise recalcitrant recombinant gpD fusion proteins. Overall, this improved gpD display system is expected to permit the expression of a wide variety of peptides and proteins on the surface of bacteriophage lambda and to facilitate the use of modified lambda phage vectors in mammalian gene transfer applications.


Tracking the development of professional values in undergraduate nursing students.
In the current nursing shortage, nurses are frequently making significant patient care decisions concerning value-laden clinical issues. A program evaluation study was conducted to track professional values over time from entry into a baccalaureate program to graduation. Nursing students completed a survey measuring professional values upon entry into and exit from the program. Comparative analysis of pretest and posttest group means demonstrated statistically significant increases in total scores. The highest pretest value items were also the highest on the posttest, with the addition of patient advocacy. Patient advocacy jumped 16 places from pretest to posttest to become the highest-ranked statement upon exit from the program. All of the values rated as least valued at pretest remained least valued at posttest; however, the means of all but two (participating in nursing research and providing consumer education about products/services) increased significantly. The value statements with mean scores that increased significantly centered on aspects of nursing practice less visible to the lay public and involving interaction with other health care providers.


The role of hormonal therapy in the management of hormonal-receptor-positive breast cancer with co-expression of HER2.
Approximately half of breast cancers that overexpress human epidermal growth factor receptor 2 (HER2) also express hormone receptors (HRs). Although HR positivity predicts efficacy of endocrine agents, preclinical and clinical data suggest that HER2 overexpression confers intrinsic resistance to hormonal treatment. In addition, HER2 overexpression is an independent adverse prognostic factor regardless of the hormonal status of the tumor, indicating that patients with HR+/HER2+ breast tumors might not derive a benefit from single-agent hormonal therapy. These data provided a strong rationale for exploring the targeting of both HR and HER2 signaling pathways in HR+/HER2+ breast tumors to optimize hormonal therapy and overcome resistance to anti-estrogen therapy. Results from a randomized clinical trial that combined hormonal treatment with targeted anti-HER2 therapy in postmenopausal women with HR+/HER2+ advanced breast cancer indicate that this novel dual-targeting strategy significantly improves outcomes compared with endocrine treatment alone. Nonetheless, other data suggest that it might achieve an inferior outcome compared with anti-HER2 therapy plus chemotherapy. Therefore, targeting both the HR and HER2 signaling pathways upfront might not be the most-effective therapeutic strategy in the management of HR+/HER2+ breast cancer. We discuss the clinical implication of resistance to endocrine therapy, and describe new insights into the management of HR+/HER2+ advanced breast cancer.


A family of Ca2+-dependent activator proteins for secretion: comparative analysis of structure, expression, localization, and function.
Ca2+-dependent activator protein for secretion (CAPS) 1 is an essential cytosolic component of the protein machinery involved in large dense-core vesicle (LDCV) exocytosis and in the secretion of a subset of neurotransmitters. In the present study, we report the identification, cloning, and comparative characterization of a second mammalian CAPS isoform, CAPS2. The structure of CAPS2 and its function in LDCV exocytosis from PC12 cells are very similar to those of CAPS1. Both isoforms are strongly expressed in neuroendocrine cells and in the brain. In subcellular fractions of the brain, both CAPS isoforms are enriched in synaptic cytosol fractions and also present on vesicular fractions. In contrast to CAPS1, which is expressed almost exclusively in brain and neuroendocrine tissues, CAPS2 is also expressed in lung, liver, and testis. Within the brain, CAPS2 expression seems to be restricted to certain brain regions and cell populations, whereas CAPS1 expression is strong in all neurons. During development, CAPS2 expression is constant between embryonic day 10 and postnatal day 60, whereas CAPS1 expression is very low before birth and increases after postnatal day 0 to reach a plateau at postnatal day 21. Light microscopic data indicate that both CAPS isoforms are specifically enriched in synaptic terminals. Ultrastructural analyses show that CAPS1 is specifically localized to glutamatergic nerve terminals. We conclude that at the functional level, CAPS2 is largely redundant with CAPS1. Differences in the spatial and temporal expression patterns of the two CAPS isoforms most likely reflect as yet unidentified subtle functional differences required in particular cell types or during a particular developmental period. The abundance of CAPS proteins in synaptic terminals indicates that they may also be important for neuronal functions that are not exclusively related to LDCV exocytosis.


A Nile blue based infrared fluorescent probe: imaging tumors that over-express cyclooxygenase-2.
The first Golgi-localized cyclooxygenase-2 (COX-2)-specific near-infrared (NIR) fluorescent probe, Niblue-C6-IMC, able to detect cancer cells, was designed. Importantly, Niblue-C6-IMC preferentially labeled the tumors in a mouse tumor model with deep tissue penetration capacity. It may be a promising molecular tool for guiding tumor resection during surgery.


Correlation between the dimensions of diaphragm movement, respiratory functions and pressures in accordance with the gross motor function classification system levels in children with cerebral palsy.
This study was executed as correlation study to investigate the correlation between the dimensions of diaphragm movement, and respiratory functions and pressures in accordance with the Gross Motor Function Classification System (GMFCS) levels on children with cerebral palsy as the participants. Forty-three children in the age range of 5-13 years diagnosed with cerebral palsy as the research participants were divided into three groups (levels I, II, and III) through systematic stratified random sampling in accordance with their GMFCS levels. Pearson correlation analysis was executed to examine the correlation between dimensions of diaphragm movement, and respiratory functions and pressures in accordance with the GMFCS levels of the participants. There was no significant correlation between the dimensions of diaphragm movement, and respiratory functions and pressures in all of the three groups in accordance with the GMFCS levels of the participants. Therefore, it is deemed that although measurement of the dimensions of diaphragm movement of children with cerebral palsy by using diagnostic ultrasonic M-mode imaging device can be considered as auxiliary tool in predicting the breathing capabilities, it cannot be used as independent measurement equipment.


[BRCA1/2 gene mutation and clinicopathologic features of triple negative breast cancer].
To investigate the incidence of BRCA1/2 gene mutation among triple negative breast cancer (TNBC) patients. Polymerase chain reaction and DNA sequencing were used to detect mutations of BRCA1 (exons 2, 11 and 20) and BRCA2 (exon 11) genes using paraffin-embedded tissue samples of 33 TNBC patients (21 Uyghur patients and 12 Han patients ) in Xinjiang Uygur Autonomous Region. Among 33 cases of TNBC, 5 cases (5/33, 15.2%) were found to have BRCA1 gene mutation. The exon 11 of BRCA1 gene mutation proportion was seen in 4/5 and exon 20 of BRCA1 gene mutation proportion was seen in 1/5. No germline mutation was found in exon 2 of BRCA1 gene and exon 11 of BRCA2 gene. The onset age of patients with BRCA1 mutations were younger than 50 years. Four BRCA1 mutation patients were premenopausal. The proportions of BRCA1 gene mutation of Uygur TNBC patients and Han TNBC patients were 2/12 and 3/21, respectively, without significant difference (P=0.854). BRCA mutations were mainly found in stageⅠtoⅡ (4/5) and only 1 case (1/5) was found with stage Ⅲ disease. No significant difference was found in fertility status, menstrual status and age at menarche between mutated and non-mutated patients (P>0.05) . Germline mutation of BRCA1 may be more often associated with TNBC than BRCA2 for its higher mutation rate. Compared with non-mutated TNBC cases, several clinicopathologic features could be identified among mutated cases.


A new kind of filter paper comprising ultralong hydroxyapatite nanowires and double metal oxide nanosheets for high-performance dye separation.
Simultaneous enhancement in water flux and removal efficiency during the filtration process remains a big challenge for separation membranes. The porous structure of the filter paper can provide many channels for water transportation, but the separation performance is generally poor. The purpose of this study is to develop a new kind of filter paper consisting of ultralong hydroxyapatite (HAP) nanowires, cellulose fibers (CFs) and double metal oxide (LDO) nanosheets, and to achieve the simultaneous enhancement of both water flux and removal efficiency for high-performance dye separation. In this work, a novel kind of LDO/HAP/CF nanocomposite filter paper consisting of ultralong HAP nanowires and CFs and LDO nanosheets has been developed for rapid water filtration and highly efficient dye adsorption. Positively charged LDO nanosheets can adsorb on the surface of negatively charged ultralong HAP nanowires and embed in the porous networked structure of the LDO/HAP/CF nanocomposite filter paper, which can provide a porous structure for rapid water transportation and can adjust the pore size of the nanocomposite filter paper. As a result, the pure water flux of the LDO/HAP/CF nanocomposite filter paper can be adjusted. The optimized pure water flux of the LDO/HAP/CF nanocomposite filter paper can reach 783.6 L m-2 h-1 bar-1, which is 1.51 times that of the HAP/CF filter paper without LDO nanosheets (518.6 L m-2 h-1 bar-1). More importantly, the adsorption capacity of LDO nanosheets is high for dye molecules, the rejection percentage of Congo red (CR) by the as-prepared HAP/CF filter paper is only 59.8%, and its water flux is 534.7 L m-2 h-1 bar-1. The optimized rejection percentage and water flux of the LDO/HAP/CF nanocomposite filter paper for CR are significantly enhanced (98.3% and 736.8 L m-2 h-1 bar-1, respectively) compared to those of the HAP/CF filter paper. The size of LDO nanosheets has a significant effect on the water flux and dye rejection percentage of the LDO/HAP/CF nanocomposite filter paper. The as-prepared LDO/HAP/CF nanocomposite filter paper is promising for the applications in highly efficient purification of wastewater containing dye molecules.


Manometric mapping of normal esophagus and definition of the transition zone.
The normal esophagus has not been manometrically mapped. The transition zone between esophageal smooth and skeletal muscles has also not been defined manometrically. To manometrically map the normal esophagus and to define the transition zone. Thirty normal adults [23 men; mean age 34.8 (10.4) years] underwent manometry using a water-perfused system. The lower esophageal sphincter (LES) was studied by station pull-through, and esophageal body musculature was evaluated at 1-cm intervals with five wet swallows at each level. The transition zone was identified as an area where the wave-forms did not resemble typical skeletal or smooth muscle wave-forms. The basal mid-expiratory LES pressure was 18.7 (7.2) mmHg, and its length was 3.6 (1.2) cm. Based on our findings, we defined the transition zone as an area where either the amplitude of contraction was < 40 mmHg or, if the amplitude was 40-50 mmHg, the rate of change of pressure from baseline to peak of the wave was < 50 mmHg/s. The lengths of the skeletal, transition and smooth muscle zones were 2.8 (1.2), 4.0 (1.7) and 12.5 (2.7) cm, respectively. The amplitude and dp/dt of contraction and transmission velocity were lowest in the transition zone (p < 0.05). We have manometrically mapped the normal esophageal muscle zones; the parameters obtained may be used as reference values. The manometric criteria for the transition zone have also been defined.


[Previous abortions exert favourable effects on the prognosis of breast cancer patients].
The effect of previous abortions, both induced and spontaneous, on the prognosis of breast cancer patients was analysed, applying the hazard regression model of 1190 radically mastectomized Japanese women. The 10-year disease-free survival rate of 800 patients without abortion, 312 with one or two abortions and 78 with 3 or more abortions was 64.8%, 69.8% and 77.3%, respectively. Previous abortions had a significantly favourable effect on the prognosis when the effects of 8 other co-variants were taken into account (p = 0.008). Histologic findings on resected materials showed that patients with previous abortions had a higher incidence of well-differentiated breast cancer (25%) than those without abortions (19%) (p = 0.026). The former group had significantly less metastasis to visceral organs (11.8%) than the latter (17.5%) (p = 0.011) when the first recurrence site was investigated.


How to write a case report? or...not write at all?
Case report is the oldest and the best-known type of publication in medicine. Many original observations, recognition of new diseases, novel diagnostic and therapeutic methods, unusual forms of common diseases, and complications were first published as case reports. Case reports have become a standard and indispensable part of the medical literature. However, getting a case report published in a respectable journal was never more troublesome. In this essay, pearls and pitfalls as well as the importance of writing a case report for a journal have been further discussed.


Effect of treatment support on preventing local recurrence of hepatocellular carcinoma directly adjacent to the diaphragm.
Treatment support is anticipated to improve the results of radiofrequency ablation (RFA) treatment in cases in which visualization of tumors using the conventional B-mode is unclear. In the present study, the effectiveness of treatment support for RFA reducing the local recurrence rate of hepatocellular carcinoma (HCC) that are located directly adjacent to the diaphragm, and which are difficult to visualize with B-mode ultrasound imaging, was investigated. A total of 103 HCC tumors measuring <5 cm, which were located abutting the diaphragm, and which were difficult to visualize using the B-mode, were treated using RFA. Thirty-three of those HCC tumors were treated using RFA without treatment support, whereas the remaining 70 HCC tumors were treated using RFA with treatment support, including artificial pleural effusion, contrast-enhanced ultrasonography (CEUS) with the contrasting agent, Sonazoid™, and fusion imaging, either alone or in combination to improve the visualization of the tumors. The rate of local recurrence, and factors affecting local recurrence, were analyzed. Local recurrences were confirmed in 17 of the 103 nodules (16.50%). The overall rate of local recurrence was 13.1% at 6 months, and 20.2% at 12 months. The rate of local recurrence using RFA with artificial pleural effusion was significantly lower compared with those cases of HCC tumors treated without artificial pleural effusion (P=0.008). Similarly, the rate of local recurrence for CEUS RFA with Sonazoid™ was significantly lower compared with those cases of HCC tumors treated without Sonazoid™ (P=0.00081). In a multivariate analysis, CEUS RFA with Sonazoid™ and artificial pleural effusion contributed to the decrease in the rate of local recurrence (hazard ratios, 0.075 and 0.143, respectively). Based on these results, it is possible to conclude that CEUS with Sonazoid™ as a treatment support was the most effective method for reducing the rate of local recurrences abutting the diaphragm that are difficult to visualize using B-mode ultrasonography.


Global transcriptome analysis of genetically identified neurons in the adult cortex.
The enormous cellular complexity of the brain is a major obstacle for gene expression profiling of neurological disease models, because physiologically relevant changes of transcription in a specific neuronal subset are likely to be lost in the presence of other neurons and glia. We solved this problem in transgenic mice by labeling genetically defined cells with a nuclear variant of GFP. When combined with laser-directed microdissection, intact RNA from unfixed, freeze-dried sections can be isolated, which is a prerequisite for high-quality global transcriptome analysis. Here, we compared gene expression profiles between pyramidal motor neurons and pyramidal somatosensory neurons captured from layer V of the adult neocortex. One striking feature of motor neurons is the elevated expression of ribosomal genes and genes involved in ATP synthesis. This suggests a molecular adaptation of the upper motor neurons to longer axonal projections and higher electrical activity. These molecular signatures were not detected when cortical layers and microareas were analyzed in toto. Additionally, we used microarrays to determine the global mRNA expression profiles of microdissected Purkinje cells and cellularly complex cerebellar cortex microregions. In summary, our analysis shows that cellularly complex targets lead to averaged gene expression profiles that lack substantial amounts of cell type-specific information. Thus, cell type-restricted sampling strategies are mandatory in the CNS. The combined use of a genetic label with laser-microdissection offers an unbiased approach to map patterns of gene expression onto practically any cell type of the brain.


Rare yeasts causing fungemia in immunocompromised and haematology patients: Case series from Delhi.
Systemic fungal infection related to fluconazole-resistant yeasts are emerging in immunocompromised patients. In this case-series, we report eight cases of fungemia caused by Trichosporon spp. (2), Stephanoascus ceferrii (1), Kodamaea ohmeri (1), Pichia kutrawersi (2), Candida rugosa (1) and Candida lusitianae (1) in immunocompromised patients. All the yeasts except (Trichosporon asahii) were sequenced. As these rare species are inherently resistant to antifungal agents and they may lead to the development of nosocomial outbreaks, therefore, accurate identification followed by antifungal susceptibility testing is crucial for proper treatment and management.


Central and peripheral neural responses in acromegaly.
To assess the function of the central and peripheral nervous systems in patients with untreated acromegaly. We recorded the somatosensory evoked potentials (SSEPs) and brain stem auditory evoked potentials (BAEPs) in 10 patients with untreated acromegaly of brief duration and in 20 age- and sex-matched healthy control subjects to evaluate the function of the central nervous system and at least the median and tibial components of the peripheral nerves. Electrophysiologic studies were done at the time of diagnosis and before the initiation of any treatment for acromegaly. We also studied the distal motor latency, nerve conduction velocity, compound muscle action potentials, and F response in the peroneal nerve; the sensory nerve conduction velocity and sensory potential amplitude were measured in the sural nerve. The mean duration of acromegaly (expressed as time elapsed since patients first recognized signs or symptoms) was 2.4 years. The N(9) and N(13) latencies in median SSEPs and the N(22) latency in tibial SSEPs were significantly prolonged in patients with acromegaly in comparison with the control group; however, central nervous system components of SSEPs and all components of BAEPs were normal. We also noted abnormalities in peroneal motor and sural sensory nerves. No correlation was found between the neurophysiologic data and the basal growth hormone level, the fasting blood glucose level, or the duration of disease. Our results suggest that peripheral, but not central, nervous system involvement exists in patients with untreated acromegaly of short duration.


Microcalorimetric monitoring of growth of Saccharomyces cerevisiae: osmotolerance in relation to physiological state.
The importance of the physiological state of a culture of Saccharomyces cerevisiae for tolerance to sudden osmotic dehydration was studied, and it was investigated whether specific osmotolerance factors were demonstrable. The microcalorimeter was used to monitor growth, and different physiological states of the culture were selected and their osmotolerance was tested. In addition to cells in the stationary phase, cells from the transition phase between respirofermentative and respiratory catabolism were osmotolerant. S. cerevisiae exhibited ever-changing metabolism during batch growth on either glucose or ethanol as the carbon source. Instantaneous heat production per biomass formation (dQ/dX) and specific activity of sn-glycerol 3-phosphate dehydrogenase (GPDH) (EC 188.8.131.52) were shown to differ for different physiological states. Neither high respiratory activity nor low total cellular activity, nor factors involved in osmoregulation, i.e., intracellular glycerol or activity of GPDH, correlated with the osmotolerant phenotype.


Does donor brain death influence acute vascular rejection in the kidney transplant?
There is increasing experimental evidence to suggest that donor brain death enhances susceptibility to early inflammatory responses such as acute rejection in the kidney transplant. The aim of the present study was to establish whether the injury induced or aggravated by donor brain death could exert an effect on recipient immunologic tolerance by comparing data from patients receiving a kidney from non-heart-beating donors (NHBD) or from brain-dead donors (BDD). We reviewed data corresponding to 372 renal transplants performed from January 1996 to May 2002. The data were stratified according to donor type as 197 (53%) brain-dead and 175 (47%) non-heart-beating donors, and the two groups were compared in terms of acute vascular rejection by Cox's regression analysis. The rate of vascular rejection was 28% in the BDD group and 21.7% in the NHBD (P=0.10). The following predictive variables for acute vascular rejection were established: brain death [RR 1.77 (95% CI 1.06-3.18)], presence of delayed graft function [RR 3.33 (1.99-5.55)], previous transplant [RR 2.35 (1.34-4.13)], recipient age under 60 years [RR 1.86 (0.99-2.28)], female recipient [RR 1.50 (0.99-2.28)], cerebrovascular disease as cause of donor death [RR 1.72 (1.02-2.91)], and triple therapy as immunosuppressive treatment. Donor brain death could be a risk factor for the development of vascular rejection in kidney recipients. This process could affect the quality of the graft and host alloresponsiveness. Delayed graft function in transplants from dead brain donors could be a reflection of severe autonomic storm, leading to a higher incidence of vascular rejection in these patients.


Ultrastructure of male reproductive accessory glands and ejaculatory duct in the Queensland fruit fly, Bactrocera tryoni (Diptera: Tephritidae).
Ultrastructure of male reproductive accessory glands and ejaculatory duct in the Queensland fruit fly (Q-fly), Bactrocera tryoni, were investigated and compared with those of other tephritid flies. Male accessory glands were found to comprise one pair of mesodermic glands and three pairs of ectodermic glands. The mesodermic accessory glands consist of muscle-lined, binucleate epithelial cells, which are highly microvillated and extrude electron-dense secretions by means of macroapocrine transport into a central lumen. The ectodermic accessory glands consist of muscle-lined epithelial cells which have wide subcuticular cavities, lined with microvilli. The electron-transparent secretions from these glands are first extruded into the cavities and then forced out through small pores of the cuticle into the gland lumen. Secretions from the two types of accessory glands then flow into the ejaculatory duct, which is highly muscular, with epithelial cells rich in rough endoplasmic reticulum and lined with a thick, deeply invaginated cuticle. While there are some notable differences, reproductive accessory glands of male Q-flies generally resemble those of the olive fruitfly, Bactrocera oleae, and to a lesser extent the Mediterranean fruit fly, Ceratitis capitata.


Smart Card Decontamination in a High-Containment Laboratory.
Validated procedures for decontamination of laboratory surfaces and equipment are essential to biosafety and biorisk programs at high-containment laboratories. Each high-containment laboratory contains a unique combination of surfaces, procedures, and biological agents that require decontamination methods tailored to specific facility practices. The Plum Island Animal Disease Center (PIADC) is a high-containment laboratory operating multiple biosafety level (BSL)-3, ABSL-3, and BSL-3 Ag spaces. The PIADC facility requires the use of federally issued smart cards, called personal identity verification (PIV) cards, to access information technology (IT) networks both outside and within the high-containment laboratory. Because PIV cards may require transit from the BSL-3 to office spaces, a validated procedure for disinfecting PIV card surfaces prior to removal from the laboratory is critical to ensure biosafety and biosecurity. Two high-risk select agents used in the PIADC high-containment laboratory are foot-and-mouth disease virus (FMDV) and swine vesicular disease virus (SVDV). We evaluated disinfection of PIV cards intentionally spotted with FMDV and SVDV using a modified quantitative carrier test and the liquid chemical disinfectant Virkon® S. Our experimental design modeled a worst-case scenario of PIV card contamination and disinfection by combining high concentrations of virus dried with an organic soil load and use of aged Virkon® S prepared in hard water. Results showed that FMDV and SVDV dried on PIV card surfaces were completely inactivated after immersion for 30 and 60 seconds, respectively, in a 5-day-old solution of 1% Virkon® S. Therefore, this study provided internal validation of PIADC biosafety protocols by demonstrating the efficacy of Virkon® S to inactivate viruses on contaminated smart cards at short contact times.


Exposing the {010} Planes by Oriented Self-Assembly with Nanosheets To Improve the Electrochemical Performances of Ni-Rich Li[Ni0.8Co0.1Mn0.1]O2 Microspheres.
A modified Ni-rich Li[Ni0.8Co0.1Mn0.1]O2 cathode material with exposed {010} planes is successfully synthesized for lithium-ion batteries. The scanning electron microscopy images have demonstrated that by tuning the ammonia concentration during the synthesis of precursors, the primary nanosheets could be successfully stacked along the [001] crystal axis predominantly, self-assembling like multilayers. According to the high-resolution transmission electron microscopy results, such a morphology benefits the growth of the {010} active planes of final layered cathodes during calcination treatment, resulting in the increased area of the exposed {010} active planes, a well-ordered layer structure, and a lower cation mixing disorder. The Li-ion diffusion coefficient has also been improved after the modification based on the results of potentiostatic intermittent titration technique. As a consequence, the modified Li[Ni0.8Co0.1Mn0.1]O2 material exhibits superior initial discharges of 201.6 mA h g-1 at 0.2 C and 185.7 mA h g-1 at 1 C within 2.8-4.3 V (vs Li+/Li), and their capacity retentions after 100 cycles reach 90 and 90.6%, respectively. The capacity at 10 C also increases from 98.3 to 146.5 mA h g-1 after the modification. Our work proposes a novel approach for exposing high-energy {010} active planes of the layered cathode material and again confirms its validity in improving electrochemical properties.


Inhibition of the nuclear transporter, Kpnβ1, results in prolonged mitotic arrest and activation of the intrinsic apoptotic pathway in cervical cancer cells.
The karyopherin β proteins are involved in nuclear-cytoplasmic trafficking and are crucial for protein and RNA subcellular localization. We previously showed that Kpnβ1, a nuclear importin protein, is overexpressed in cervical cancer and is critical for cervical cancer cell survival and proliferation, whereas non-cancer cells are less dependent on its expression. This study aimed to identify the mechanisms by which inhibition of Kpnβ1 results in cervical cancer cell death. We show that the inhibition of Kpnβ1 results in the induction of apoptosis and a prolonged mitotic arrest, accompanied by distinct mitotic defects in cervical cancer cells but not non-cancer cells. In cervical cancer cells, Kpnβ1 downregulation results in sustained degradation of the antiapoptotic protein, Mcl-1, and elevated Noxa expression, as well as mitochondrial membrane permeabilization resulting in the release of cytochrome C and activation of associated caspases. Although p53 becomes stabilized in Kpnβ1 knockdown cervical cancer cells, apoptosis occurs in a p53-independent manner. These results demonstrate that blocking Kpnβ1 has potential as an anticancer therapeutic approach.


Gender differences in public beliefs and attitudes about mental disorder in western countries: a systematic review of population studies.
While quite a number of theories and hypotheses about gender differences in public beliefs and attitudes about mental illness have been proposed, the empirical evidence, particularly evidence based on population studies, is rather scarce. A systematic review of population-based studies providing information on gender differences in beliefs about mental disorders and attitudes towards the mentally ill was carried out. While both genders are no different in their willingness to seek informal help for mental illness, women seem more ready to recommend professional help than men. They also evaluate treatment outcomes more favourably. Women are more likely to endorse psychosocial conceptualizations of mental illness than men, and, in consequence, are more in favour of psychotherapy. With a few exceptions, women do not seem to display more favourable attitudes than men towards people with mental disorder. Female patients seem to be rejected by the public less than male patients. Our review suggests that gender matters in public beliefs and attitudes about mental illness. Some theoretical assumptions are supported by empirical findings, others not. However, as evidence is rather scarce, further studies testing theory-driven hypotheses are needed.


Adenofibroma of the fimbria: a common entity that is indistinguishable from ovarian adenofibroma.
Fallopian tube adenofibromas (FTAs) are considered rare, but their frequency has never been determined by systematic sampling of this organ. To determine the morphological spectrum and prevalence of FTAs, we analyzed a consecutive series of fallopian tubes removed during surgery for a wide range of disorders. Fallopian tubes were completely evaluated with attention to the fimbriated end (sectioning and extensively examining the fimbria [SEE-FIM] protocol). Discrete localized subepithelial stromal proliferations with alterations in plical architecture and a glandular component were classified as FTAs. Fallopian tube adenofibromas less than 3 mm were classified as incipient adenofibromas (iFTAs). The association of FTAs with ovarian adenofibromas (OAs) was also evaluated. Twenty-six of 28 (30% overall frequency) consecutively examined bilateral fallopian tube specimens contained adenofibromas (FTAs and iFTAs); all confined to the fimbria. Twelve FTAs were identified (11 cases; 14% frequency), 3 of which exceeded 1 cm. Twenty-nine iFTAs were identified (18 cases; 20% frequency); iFTAs were multiple in 10, bilateral in 4, and associated with an FTA in 3 cases. Three (25%) of 12 OAs with completely examined fallopian tubes were associated with FTAs. Stroma in both iFTAs and FTAs was CD10 and inhibin positive, and the epithelial phenotype of both iFTAs and OAs was identical, composed of secretory and ciliated cells. The fimbrial endosalpinx and the ovarian cortex share the potential for similar specialized stromal expansions with the formation of biphasic tumors with endosalpingeal epithelial differentiation. Similar to reports of serous and endometrioid tumors in both the distal fallopian tube and ovary, FTAs highlight a shared epithelial-mesenchymal differentiation pathway in the fimbrial-ovarian region. Whether the shared tumor phenotype in these 2 organs is coincidental or interdependent bears further investigation.


Dynamic incompetent cervix uteri. Sonographic observations.
In 15 of 56 patients with incompetent cervix, rapid changes in the degree of dilatation of the cervical canal were observed during sonographic examination, with the same degree of bladder distension. In ten of those 15 patients, the canal was seen to be completely closed at some point during the examination. Because of these rapid dynamic changes in the dilatation of the cervical canal, it is necessary to observe the cervical portion of the uterus several times during the sonographic examination, especially in patients suspected to have incompetent cervix. It is possible for the cervical canal to remain closed for several minutes during the examination. Incompetent cervix can go undetected if the cervix is not observed frequently throughout the sonographic examination.


Axillary Ultrasound Identifies Residual Nodal Disease After Chemotherapy: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance).
The purpose of this study is to determine lymph node features on axillary ultrasound (US) images obtained after neoadjuvant chemotherapy that are associated with residual nodal disease in patients with initial biopsy-proven node-positive breast cancer. All patients had axillary US performed after neoadjuvant chemotherapy. Axillary US images were centrally reviewed for lymph node size, cortical thickness, and cortical morphologic findings (type I indicated no visible cortex; type II, a hypoechoic cortex ≤ 3 mm; type III, a hypoechoic cortex > 3 mm; type IV, a generalized lobulated hypoechoic cortex; type V, focal hypoechoic cortical lobulation; and type VI, a totally hypoechoic node with no hilum). Lymph node characteristics were compared with final surgical pathologic findings. Axillary US images obtained after neoadjuvant chemotherapy and surgical pathologic findings were available for 611 patients. Residual nodal disease was present in 373 patients (61.0%), and 238 (39.0%) had a complete nodal pathologic response. Increased cortical thickness (mean, 3.5 mm for node-positive disease vs 2.5 mm for node-negative disease) was associated with residual nodal disease. Lymph node short-axis and long-axis diameters were significantly associated with pathologic findings. Patients with nodal morphologic type I or II had the lowest rate of residual nodal disease (51 of 91 patients [56.0%] and 138 of 246 patients (56.1%), respectively), whereas those with nodal morphologic type VI had the highest rate (44 of 55 patients [80.0%]) (p = 0.004). The presence of fatty hilum was significantly associated with node-negative disease (p = 0.0013). Axillary US performed after neoadjuvant chemotherapy is useful for nodal response assessment, with longer short-axis diameter, longer long-axis diameter, increased cortical thickness, and absence of fatty hilum significantly associated with residual nodal disease after neoadjuvant chemotherapy.


A Data-Driven Approach For Better Assignment Of Clinical And Surgical Capacity In An Elective Surgical Practice.
This work analyzes strategies for better allocation of surgeon resources in an elective surgical practice. Among the metrics considered to evaluate the assignment of tasks are OR-to-Clinic ratio per provider, OR-to-Clinic ratio per day, patient access to clinic, and patient access to surgery. In addition, a simulation model is used to evaluate the clinical and surgical capacity of the calendar to identify potential inefficiencies and propose strategic changes to the calendar.


[Dendritic cell-regulatory T-cell interaction].
The one of the main modes of homeostasis protection is maintaining the balance between antimicrobial immunological reactions and mechanisms involved in immune response suppression. The interaction between dendritic and T cells plays a crucial role in inducing both an immune response and immunological tolerance. Dendritic cells are also able to affect the differentiation, migration, and activation of CD4+ T cells using cell-to-cell contact and/or cytokine production. The proper cytokine microenvironment can influence the induction of FoxP3 transcription factor in T cells, determining the regulatory properties of these cells. However, it is still unclear what is more substantial for Treg induction: the cytokines in the microenvironment, stimulation by a specific DC population, or the type of antigens presented by DC. Activated natural Treg as well as induced Treg cells use similar mechanisms to generate tolerance, for example by the production of such anti-inflammatory cytokines as TGF-beta or IL-10 and by direct contact with target cells. Recently, some reports have described the possibility that Treg cells lose FoxP3 expression followed by loss of suppressive function directed against proliferating T lymphocytes.


Characteristics of patients with healthcare-associated infection due to SCCmec type IV methicillin-resistant Staphylococcus aureus.
Methicillin-resistant Staphylococcus aureus (MRSA) with the staphylococcal cassette chromosome mec (SCCmec) type IV allele is most commonly associated with community-acquired MRSA (CA-MRSA) infection; however, such organisms have also been identified in the healthcare setting. The objective of the present study was to characterize the epidemiology of and clinical outcomes associated with SCCmec-IV MRSA infection acquired in the healthcare setting, compared with infection caused by MRSA of other SCCmec types. We evaluated a cohort of 100 inpatients with MRSA infection that met the Centers for Disease Control and Prevention definition for healthcare-associated infection and compared the patients' demographic characteristics, the antimicrobial susceptibilities of the MRSA isolates, the infection types, and the associated clinical and microbiological outcomes. For each MRSA isolate, the SCCmec type and the presence of Panton-Valentine leukocidin (PVL) were determined by polymerase chain reaction methods. SCCmec-IV MRSA isolates were isolated from 53 patients (42% of these isolates were positive for PVL), and SCCmec-II or SCCmec-III MRSA was isolated from 47 patients (3% of these isolates were positive for PVL). No differences were noted between the patients in the SCCmec-II/III group and the patients in the SCCmec-IV group with respect to age (median, 55 vs 50 years); sex (77% vs 64% of patients were male); medical service (surgical service, 60% in both groups; ICU admission, 55% vs 53%), Acute Physiology and Chronic Health Evaluation II score (median, 8 vs. 7); infection type; or underlying comorbidities, except for presence of a burn wound (13% vs 2%; P < .04). Patients in the SCCmec-II/III group were more likely to have multiple sites of infection (P = .006) and a longer length of stay (LOS) prior to detection of MRSA than were patients in the SCCmec-IV group (median, 4 vs 1 days; P < .001). Total LOS was significantly greater for patients in the SCCmec-II/III, compared with those in the SCCmec-IV group (P = .006). Multiple logistic regression identified liver disease and longer LOS prior to detection of MRSA as predictors of infection with SCCmec-II/III MRSA. Rates of susceptibility to clindamycin, gentamicin, ciprofloxacin, levofloxacin, and tetracycline was significantly greater among SCCmec-IV MRSA isolates, compared with type II/III isolates (P < or = .05). Compared with SCCmec-IV isolates acquired in the community, the susceptibility rates among healthcare-associated SCCmec-IV isolates was significantly less for clindamycin, gentamicin, and levofloxacin, indicating that these organisms may quickly acquire resistance to non- beta -lactam antibiotics, as do SCCmec-II/III strains. SCCmec-IV MRSA appears to have become established in hospitals. The onset of infection caused by SCCmec-IV strains is earlier than the onset of infection with SCCmec-II/III strains; however, associated types of infection are similar. Infection with SCCmec-II/III MRSA is currently associated with an adverse impact on outcome, compared with infection with SCCmec-IV MRSA. Further research is warranted to determine the impact of SCCmec type IV strains in hospital settings.


Single photon transient hot electron ionization of C60.
Recent experiments have demonstrated that C60 can ionize in a thermal process after absorption of a photon with energy far above the ionization energy. This indirect ionization mechanism is investigated here by calculating the total and singly charged ion yields, electron energy distributions, and effective electronic temperatures as a function of photon energy.


Tepidimonas aquatica sp. nov., a new slightly thermophilic beta-proteobacterium isolated from a hot water tank.
A bacterial isolate, with an optimum growth temperature of about 50 degrees C, was recovered from a domestic hot water tank in Coimbra. Phylogenetic analysis using 16S rRNA gene sequence indicated that strain CLN-1T is a member of the beta-Proteobacteria and represents a new species of the genus Tepidimonas. The major fatty acids of strain CLN-1T are 16:0, 17:0 cyclo and 16:1 omega7c. Ubiquinone 8 is the major respiratory quinone, the major polar lipids are phosphatidylethanolamine, and phosphatidylglycerol. The new isolate is aerobic and facultatively chemolithoheterotrophic. Thiosulfate and tetrathionate are oxidized to sulfate in the presence of a metabolizable carbon source. Strain CLN-1T grows on amino acids and organic acids, but this organism does not assimilate carbohydrates. Glycerol is the only polyol assimilated. Resinic acids, namely abietic acid, dehydroabietic acid and isopimaric acid are not degraded. On the basis of the phylogenetic analyses, physiological and biochemical characteristics, we propose that strain CLN-1T represents a new species for which we offer the name Tepidimonas aquatica.


Spotlights on extracellular vesicles in hepatocellular carcinoma diagnosis and treatment: an update review.
Hepatocellular carcinoma (HCC), one of the most prevalent cancers, with a high mortality rate worldwide, seriously impairs patient health. The lack of accurate targets impedes the early screening and diagnosis of HCC and is associated with a poor response to routine therapies. Extracellular vesicles (EVs), comprising exosomes, microvesicles, and apoptotic bodies, are lipid bilayer membrane-derived nanometer-sized vesicles. EVs can be secreted from various cancer cells and release diverse biomolecules, such as DNA, RNA, proteins, metabolites, and lipids, making them a potential source of biomarkers and regulators of the tumor microenvironment. Emerging evidence suggests that EVs are involved in intercellular communication by carrying biological information. These EVs elicit physiological functions and are involved in the oncogenesis of HCC, such as proliferation, invasion, metastasis, and chemoresistance of HCC. EVs have also been considered promising biomarkers and nanotherapeutic targets for HCC. Therefore, this review sheds light on the current understanding of the interactions between EVs and HCC to propose potential biomarkers and nanotherapeutic strategies.


Melatonin for prevention of erythema and oxidative stress in response to ultraviolet radiation.
Skin damage induced by UVR is an escalating problem in dermatology, and increasing incidence of skin cancer, especially for non-melanoma skin cancer, has been reported worldwide. UVR from sun exposure and the production of reactive oxygen species (ROS) is known to be a pivotal factor in the aetiology of skin cancer. The pineal hormone melatonin is recognized as the most potent endogenous antioxidant. Melatonin conducts its antioxidant effects acting directly as a radical scavenger and indirectly by up regulation of antioxidant enzymes. It has been proposed, that melatonin may have a protective effect against UVR-induced skin damage. The aim of this thesis was to: - Clarify melatonin's protective effect against UVR-induced skin damage in laboratory and clinical settings trough a systematic review of the literature. - To clinically assess the protective effect of topical treatment with melatonin against natural sun exposure, and determine the optimal concentration. - To clinically evaluate the degree of cognitive dysfunction with full body application of topical melatonin. Study 1: This was a systematic review using the databases Pubmed, EM-BASE and Cinahl. The databases were searched up to January 2013 to identify studies evaluating melatonin's protective effect against UVR-induced erythema in humans, and damage on a cellular level. Twenty studies were included, four human and 16 experimental. The results indicated that melatonin had a protective effect against UVR-induced erythema if applied before exposure, and this effect was probably obtained by melatonin acting directly as an antioxidant, and indirectly by regulating gene expression and inducing a DNA stabilizing effect. As these results were obtained using artificial UVR-sources and without investigating possible side effects, studies using natural sunlight and evaluating possible side effects of topical melatonin administration were warranted. Study 2: This study was a randomized, double-blind, placebo-controlled study. We evaluated the protective effect of three different doses of topical melatonin against erythema induced by natural sun-light. The primary outcome was reduction in erythema, evaluated by chromatography, after sun exposure, when treated with topi-cal melatonin (0.5%, 2.5%, 12.5%) versus placebo and no treatment. A significant difference in erythema formation was found between areas treated with melatonin 12.5% and areas receiving placebo or no treatment. However, this was only seen in participants with an erythema reaction to the sun exposure. Further-more, the treated skin areas were very small and studies assessing any potential adverse effects were necessary. Study 3: This also was a randomized, double-blind, placebo-controlled, cross-over study. We assessed the degree of cognitive dysfunction with full body application of topical melatonin 12.5%. Cognition was evaluated using a neuropsychological test battery consisting of Karolinska sleepiness scale (KSS), finger tapping test (FTT) and continuous reaction time (CRT). The impact on KSS was the primary outcome. We found no significant effect on cognition, however, large inter-individual variation was observed. These results support that melatonin is a safe drug for dermal application. The studies in this thesis may be valuable in the research field of melatonin's protective potential against UVR-induced oxidative skin damage. Increasing incidence of skin cancer is reported worldwide, and experts have suggested that the problem will only increase further, due to depletion of the ozone layer and the aging population. Furthermore, high-risk patient groups are emerging with the widely use of immunosuppressive medicine in various diseases, and this high-risk is in spite of use of protective measures known today. Therefore, development of new and more effective sun protective agents, with other qualities than simple chemical reflection of the UVR, is more important than ever. We have supported the suggestion of melatonin as a sun protective agent, and added the clinical relevant feature, that melatonin also has a protective effect against natural sunlight. Furthermore, we have supported the idea of melatonin being a safe drug for topical treatment, even in previous unknown high dosages. However, before any clinical implementation of melatonin as a sun protective agent can take place, further studies evaluating the long-term effects are warranted.


Imprinted X inactivation and reprogramming in the preimplantation mouse embryo.
X chromosome inactivation is a developmentally regulated process that causes one of the two X chromosomes in normal female mammals to become transcriptionally silenced, thus equalizing the expression of X-linked genes between the sexes. Such dosage compensation depends upon dynamic genetic and epigenetic events occurring very early in development. X inactivation is controlled by an X inactivation centre that is associated with the expression of non-coding RNAs required for the silencing. Also associated with the inactive X are repressive histone modifications and polycomb protein-mediated states, which are progressively acquired during the inactivation process. In mouse, two forms of X inactivation have been described. Random X inactivation happens in the derivatives of the inner cell mass (ICM) giving rise to embryos where the maternally inherited X(Xm) is inactive in some cells and the paternally derived X (Xp) is inactive in others. Random X inactivation occurs around the time of implantation. Imprinted X inactivation, the preferential inactivation of the Xp chromosome, occurs earlier and, although there has been some debate as to the precise timing of initiation of this event, is apparent in all cells early in preimplantation development, then is subsequently confined to the cells of the extraembryonic lineages. A picture is emerging whereby initial epigenetic asymmetry between the two parental X chromosomes is reprogrammed in a lineage specific manner resulting in a switch from imprinted to random inactivation in embryonic derivatives. Neither the underlying reason nor the full extent of these early lineage specific epigenetic changes is known, but they may be correlated with more genome-wide reprogramming events essential for normal development.


Total administered dose of ibandronate determines its effects on bone mass and architecture in ovariectomized aged rats.
Ibandronate is a highly potent nitrogen-containing bisphosphonate that can prevent bone loss in various animal models as well as in clinical trials. We evaluated the effects of different doses and treatment schedules in ovariectomized aged rats, a model of human osteoporosis. Eight-month-old female Wistar rats were ovariectomized or sham operated (n = 15/group). Doses of 0.1 to 30 microg/kg/day ibandronate were administered subcutaneously over a period of 20 weeks with or without a 5 times higher single loading dose starting one day postsurgery. In a subsequent experiment, the optimal preventive dose, which is the lowest dose that prevented bone loss completely, or a suboptimal preventive dose were administered over the same period, either daily or by 3 cyclical intermittent regimens (on/off weeks = 1/2, 1/4, and 1/6), resulting in the same cumulative total dose. Ovariectomy induced significant bone loss in the following primary endpoints: femoral radiographic density, dry weight/tissue volume, and calcium content/tissue volume. Histomorphometry in the tibia resulted in reduced trabecular bone mass, thickness, and number, and increased separation. The optimal dose was 1.0 microg/kg/day, while 0.1 microg/kg/day was suboptimal. Higher doses resulted in a plateau. The loading dose had no effect on the results. Cyclical intermittent administration dose-dependently prevented bone loss, providing equivalent results per total dose, irrespective of the administration schedule. There were no differences between the various regimens, suggesting that it is the total dose of ibandronate rather than the treatment schedule that is important for efficacy, at least within the tested dosing intervals.


Comparative study of active and inactive plasma renin in healthy infants and adults.
Active, inactive and total plasma renin activity (obtained after cryoactivation), active, inactive and total plasma renin concentration (obtained after acid activation) and plasma angiotensin II were measured in 20 healthy infants and in 20 healthy adults. Active plasma renin activity but not active plasma renin concentration or plasma angiotensin II were significantly higher in the infants. In the latter both cryoactivation and acid activation resulted in a nearly 100% increase of the mean active plasma renin activity or active plasma renin concentration. Therefore the active fraction represented 0.5 of total renin with both methods. This was different in adults, where acid activation was more effective than cryoactivation. In adults, plasma angiotensin II was correlated only with active plasma renin activity and active plasma renin concentration; in contrast, plasma angiotensin II of infants was correlated with both active plasma renin activity, and with inactive plasma renin activity.


The effect of collection method and housing system on semen production and fertility of Alabio drakes.
Three methods of semen collection from Alabio drakes were compared: the use of an artificial vagina (AV), electro ejaculation (EE) and manual massage (MM). For the latter two methods, drakes were housed in individual cages or in groups in floor pens, while for the AV method all drakes were kept in individual cages. Training success rates of drakes for the three collection methods were similar. Drakes housed in cages produced significantly more semen with a higher sperm concentration, which maintained fertility longer than semen from floor-penned drakes. The average semen volume per ejaculate, sperm concentration and total number of sperm per ejaculate were highest for the AV method while the other two methods did not differ. The average duration of fertility was significantly longer for the AV method (8.8 d) than the EE (6.5 d) or MM methods (5.1 d). The proportion of fertile eggs for 7 d following the insemination of 2 X 10(8) spermatozoa was also highest for the AV method. Although greater skill was required from the operator, the AV method is recommended for general use because of its significantly higher semen yield and longer duration of fertility.


[Anti-angina therapy of coronary heart disease. Mono- or combination treatment].
Applying a metaanalysis, it was examined whether a combination of drugs is superior to monotherapy in the treatment of angina pectoris. The three classical groups of anti-anginal drugs, nitrates, calcium channel blockers and beta-receptor blockers were investigated. For data analysis, patients were divided in those suffering from "angina pectoris" and those suffering from "angina pectoris despite monotherapy." In patients with the inclusion criterium "angina pectoris" combination of drugs is not superior to monotherapy. This applies to the evaluation criteria "improvement of symptoms" and "reduction of ischemia". In patients with the inclusion criterium "angina pectoris despite monotherapy" however, there is a clear superiority of drug combination as compared to monotherapy. Again this applies to the evaluation criteria "improvement of symptoms" and "reduction in myocardial ischemia". With respect to antianginal efficacy all three possible combinations appear to be similar. If the evaluation criterium is "improvement of prognosis" no data are available with regard to drug combination. Furthermore no data are available on the prognostic effect of an anti-anginal therapy in patients with stable angina pectoris. A significant improvement of prognosis could be demonstrated for beta-receptor blocking agents without ISA in unstable angina, acute myocardial infarction, and in the postinfarction period. The effect of calcium channel blockers on prognosis depends on the substance class applied and on the presence or absence of signs of congestive heart failure. Monotherapy with nifedipine in instable angina and acute myocardial infarction fails to improve prognosis, and there even may be a tendency to adverse effects. In the absence of signs of congestive heart failure verapamil has been demonstrated to improve prognosis in the post infarction period. Likewise, improvement of prognosis by the administration of diltiazem in acute myocardial infarction only could be demonstrated in patients without signs of heart failure. In contrast, in patients with signs of congestive heart failure diltiazem increased the rate of reinfarction and mortality. For nitrates only in acute myocardial infarction a trend towards improved prognosis has been shown. Especially for nitrates the data on prognosis in coronary heart disease available so far are not convincing.


Use of pulsed dye laser in the treatment of sulcus vocalis.
The pulsed dye laser (PDL) has been shown to be effective in the treatment of hypertrophic scars and keloids in dermatology. On the basis of histopathologic similarities between sulcus vocalis and scar tissue and numerous reports on the treatment of laryngeal lesions, especially scar tissue, with PDL, we evaluated the efficacy of treating sulcus vocalis with PDL. We named this surgical procedure PDL glottoplasty. Case series with planned data collection. A university-based, tertiary care medical center. This study was conducted on 25 patients diagnosed with sulcus vocalis by videostroboscopy at the Gangnam Severance Hospital Otorhinolaryngology Department between August 2006 and February 2012. Energy delivery was fixed at 0.75 Joules (J) per pulse, and each vocal fold was administered 60 to 110 pulses (average 72.5 pulses) during each procedure. Aerodynamic, stroboscopic, and acoustic voice analyses were performed pre- and postoperatively. Although assessment was necessarily subjective, our study indicated that vocal folds showed decreased stiffness and improved mucosal wave properties after treatment, resulting in improved vibration and dysphonia. In the objective assessments, most patients who underwent PDL glottoplasty showed improvement in several postoperative voice analysis indices. The differences between preoperative and some postoperative voice parameter indices were statistically significant. We found PDL glottoplasty to be beneficial in the treatment of sulcus vocalis. Objective measurements of voice quality and normalization of vocal fold vibration improved after PDL treatment in most cases. Our results warrant further studies with larger numbers of participants and longer follow-up periods.


Brain perfusion scintigraphy with 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT single-photon emission tomography in dementia of the Alzheimer-type and diffuse Lewy body disease.
Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive decline, variably combined with frontal lobe release signs, parkinsonian symptoms and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most common cause of degenerative dementia, include progressive cognitive deterioration, often associated with levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, psychotic symptoms (visual and auditory hallucinations, depression), hypersensitivity to neuroleptics and orthostatic hypotension. A recent report suggests that positron emission tomography studies in patients with degenerative dementia may be useful in the differential diagnosis of DAT and DLBD. However, the diagnostic role of single-photon emission tomography (SPET) studies remains to be established. The aim of this study was therefore to evaluate regional cerebral perfusion [with either technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPET] and striatal dopamine transporter density [using iodine-123 2 beta-carboxymethoxy-3 beta-[4-iodophenyl]tropane (123I-beta-CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and seven patients with probable DLBD were studied. Blinded qualitative assessment by four independent raters of 99mTc-HMPAO or 99mTc-ECD SPET studies revealed bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was additional frontal hypoperfusion in two patients and occipital hypoperfusion in one patient. In the DLBD group, regional cerebral perfusion had a different pattern. In addition to temporoparietal hypoperfusion there was occipital hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT group, the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was 2.5 +/- 0.4, with an increase to 5.5 +/- 1.1 18 h after tracer injection. In comparison, in the DLBD patients the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was significantly reduced to 1.7 +/- 0.3, with a modest increase to 2.1 +/- 0.4 18 h after tracer injection (P < 0.05, Scheffe test, ANOVA). These results suggest that 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT SPET may contribute to the differential diagnosis between DAT and DLBD, showing different perfusion patterns and more severe impairment of dopamine transporter function in DLBD than in DAT.


[Leucocyte histamine release assay and its use in the diagnosis of atopic extrinsic asthma (author's transl)].
Quantitative estimation of histamine, the most important mediator of immedite hypersensitivity reaction, is described. Leucocytes, isolated from the peripheral blood of patients suspected to suffer from atopic extrinsic asthma are washed and incubated with the antigens to be tested. The amount of histamine released is measured by a fluorometric method. The leucocyte histamine release assay is compared with several commonly used methods for the diagnosis of an atopic sensitisation (cutaneous skin test, inhalative provocation test, serum IgE concentration). The usefulness of the application of this relevant and reliable in vitro test especially in patients with advanced obstruction of the respiratory tract or with superelevated rate of sensitisation, in infants and in any acute or subacute state of disease is discussed.


A new method to retrieve phase information for equiangular fan beam differential phase contrast computed tomography.
Sample radiation damage is one of the main drawbacks limiting applications of the x-ray phase-contrast imaging method. Recently, for x-ray grating-based phase contrast imaging, the reverse projection (RP) method has been proposed by Zhu et al. [Proc. Natl. Acad. Sci. U.S.A. 107, 13576-13581 (2010)]. Compared to the conventional phase stepping technique, the RP method allows a strong reduction of the exposure time and minimization of the errors induced by mechanical vibrations. However, so far, it has only been considered for parallel beam illumination, typical of a synchrotron radiation source. In this paper, a generalization of the RP method from parallel beam geometry to fan beam geometry was presented and discussed. Within parallel beam geometry, the RP method utilizes the conjugate characteristic between reverse projection images. Nevertheless, this characteristic is not directly satisfied for fan beam geometry. In this study, a phantom composed of known materials was constructed and the projection images of the phantom were calculated in a fan beam geometry. By considering single ray, the conjugate images of the projection images were derived from the projection dataset. After that, using the modified RP method the authors retrieved phase and absorption information from paired images. Extracted phase and absorption information of the phantom were in good agreement with theoretical values. Additionally, the slice reconstruction was performed and the results turned out to be in the authors' expectation. Theoretical calculations and numerical simulations confirm both feasibility and validity of the RP method under fan beam illumination. Because this method is simple, fast, and releases a relatively low dose, the authors believe that this research is very useful for the x-ray phase contrast imaging applications in clinical diagnosis, bioresearch, and industrial nondestructive testing.


Relation between bispectral index measurements of anesthetic depth and postoperative mortality: a meta-analysis of observational studies.
The association between anesthesia depth and mortality is still controversial. There are a number of narrative reviews on this topic that affirm this association, but their conclusions were based only on qualitative analyses. The aim of this meta-analysis of observational studies was to examine the potential association between depth of anesthesia as a low bispectral index (BIS) and mortality using appropriate quantitative methods. The literature was systematically reviewed in three main electronic databases (MEDLINE, EMBASE, Google Scholar) to identify all articles from inception through December 2015 regarding the association between depth of anesthesia and mortality. Inclusion criteria were restricted to observational studies that used multivariable Cox proportional regression methodology and reported adjusted hazard ratios (aHR). Pooled effect size was measured using a random effects model. Subgroup analysis was performed post hoc based on follow-up duration (30 days and ≥ one year). Eight observational studies that included 40,317 patients were evaluated in this meta-analysis. The results showed a statistically significant association between the depth of anesthesia as measured by low BIS (< 40-45), and mortality (pooled aHR, 1.21; 95% CI, 1.07 to 1.38; P = 0.003). Subgroup analysis showed that the association between depth of anesthesia (measured by low BIS) and mortality was significant for studies with a follow-up duration of ≥ one year (n = 23,347; pooled aHR, 1.10; 95% CI, 1.00 to 1.21; P = 0.04) but was not significant for studies with a follow-up duration of 30 days (n = 16,970; pooled aHR, 1.38; 95% CI = 0.81 to 2.36; P = 0.24). Existing observational studies support a significant association between depth of anesthesia (as measured by BIS) and long-term mortality (≥ one year), although it was without statistical significance at 30 days. Larger prospective, randomized trials are necessary to establish a definitive conclusion about whether this association represents true causality or is an epiphenomenon.


Reward components of feeding behavior are preserved during mouse aging.
Eating behavior depends on associations between the sensory and energetic properties of foods. Healthful balance of these factors is a challenge for industrialized societies that have an abundance of food, food choices and food-related cues. Here, we were interested in whether appetitive conditioning changes as a function of age. Operant and pavlovian conditioning experiments (rewarding stimulus was a palatable food) in male mice (aged 3, 6, and 15 months) showed that implicit (non-declarative) memory remains intact during aging. Two other essential components of eating behavior, motivation and hedonic preference for rewarding foods, were also found not to be altered in aging mice. Specifically, hedonic responding by satiated mice to isocaloric foods of differing sensory properties (sucrose, milk) was similar in all age groups; importantly, however, this paradigm disclosed that older animals adjust their energy intake according to energetic need. Based on the assumption that the mechanisms that control feeding are conserved across species, it would appear that overeating and obesity in humans reflects a mismatch between ancient physiological mechanisms and today's cue-laden environment. The implication of the present results showing that aging does not impair the ability to learn stimulus-food associations is that the risk of overeating in response to food cues is maintained through to old age.


Patient adherence to medication for HIV.
It is important to identify health beliefs, barriers and priorities that may hinder adherence to a medication regimen. Explaining the rationale behind taking medication as prescribed is essential to gain optimal therapeutic benefits. The integration of medicine-taking into the patient's lifestyle is necessary for promoting adherence. This framework is transferable for use by nurses in other specialties.


Useful oriented immobilization of antibodies on chimeric magnetic particles: direct correlation of biomacromolecule orientation with biological activity by AFM studies.
The preparation and performance of a suitable chimeric biosensor based on antibodies (Abs) immobilized on lipase-coated magnetic particles by means of a standing orienting strategy are presented. This novel system is based on hydrophobic magnetic particles coated with modified lipase molecules able to orient and further immobilize different Abs in a covalent way without any previous site-selective chemical modification of biomacromolecules. Different key parameters attending the process were studied and optimized. The optimal preparation was performed using a controlled loading (1 nmol Ab g(-1) chimeric support) at pH 9 and a short reaction time to recover a biological activity of about 80%. AFM microscopy was used to study and confirm the Abs-oriented immobilization on lipase-coated magnetic particles and the final achievement of a highly active and recyclable chimeric immune sensor. This direct technique was demonstrated to be a powerful alternative to the indirect immunoactivity assay methods for the study of biomacromolecule-oriented immobilizations.


Psoriasis disease severity affects patient satisfaction with treatment.
Patients with psoriasis are often dissatisfied with available treatments, but contributing factors are not well defined. Examine relationships between psoriasis severity, patient characteristics, and treatment satisfaction. Patients with psoriasis were classified into mild and moderate-to-severe groups based on self-reported data. Demographics, comorbidities, symptoms, and multiple treatment satisfaction outcomes were compared between groups. Predictors of patient satisfaction with treatment were examined using linear regression models. The analyses included 773 patients (407 mild; 366 moderate-to-severe). The percentage of patients reporting satisfaction with treatment was low overall, ranging from 8.6% to 61.7% for the mild and 13.9% to 49.5% for the moderate-to-severe group. Satisfaction among biologics users was also low (≤53%; 50% of satisfaction rates <40%). Regression results consistently showed greater dissatisfaction with current treatment among moderately to severely affected patients. Many psoriasis patients were dissatisfied with their treatment; moderate-to-severe patients expressed significantly less satisfaction than mild patients.


Graded and ungraded expectation patterns: Prediction dynamics during active comprehension.
Language comprehension can be facilitated by the accurate prediction of upcoming words, but prediction effects are not ubiquitous, and comprehenders likely use predictive processing to varying degrees depending on task demands. To ascertain the processing consequences of prioritizing prediction, we here compared ERPs elicited when young adult participants simply read for comprehension with those collected in a subsequent block that required active prediction. We were particularly interested in frontally-distributed post-N400 effects for expected and unexpected words in strongly constraining contexts, which have previously been documented as two distinct patterns: an enhanced positivity ("anterior positivity") observed for prediction violations compared to words that are merely unpredictable (because they occur in weakly constraining sentences) and a distinction between expected endings in more constraining contexts and those same weakly constrained words ("frontal negativity" to the strongly predicted words). We found that the size of the anterior positivity effect was unchanged between passive comprehension and active prediction, suggesting that some processes related to prediction may engage state-like networks. On the other hand, the frontal negativity showed graded patterns from the interaction of task and sentence type. These differing patterns support the hypothesis that there are two separate effects with frontal scalp distributions that occur after the N400 and further suggest that the impact of violating predictions (as long as prediction is engaged at all) is largely stable across varying levels of effort/attention directed toward prediction, whereas other comprehension processes can be modulated by task demands.


Prevalence and risk factors associated with female anal sex in the context of HIV/AIDS in the selected districts of Tanzania.
Female anal sex is a receptive type of sexual practice among heterosexual couples where the penis is inserted into the anus of a female partner. In the Western world, a number of studies and interventions have been carried out on anal sex among men due to its potential risks to HIV transmission. In African countries, including Tanzania, there is dearth of information on the risks inherent in practices associated with female anal sex in the general population. The objective of this study was to determine the prevalence and risk factors associated with female anal sex in fuelling HIV transmission in selected districts of Tanzania. This study was conducted in four districts of Tanzania of Kinondoni, Tanga Urban, Makete and Siha. Both quantitative and qualitative methods i.e. household interviews and focus group discussions were employed in data collection. Study participants included community members of aged 15 and above such as heads of the household, adolescents, bar workers and commercial sex workers. A total of 903 individuals were interviewed, 60.6% of whom were females. When respondents were asked to indicate whether they had ever been tempted to practise FAS, 167 (18.5%) reported to have been tempted in the past 12 months. Of these, 44 (26.3%) respondents had at least practised FAS. Risky practices associated with FAS were forced sex, multiple partners, frequency of engaging in FAS, low use of condoms during FAS, low rates of HIV testing among partakers, poor perception of the risks to acquire HIV through FAS and use of lubricants. In this population, the frequency of FAS practice was rather low. And yet, FAS practice attendant risk factors are likely to exacerbate HIV transmission. As such, there is a need for further exploratory studies to determine and document drivers of FAS. In addition, public health education should be provided with regard to the risks of contracting HIV associated with FAS practices.


Indiplon: a nonbenzodiazepine sedative-hypnotic for the treatment of insomnia.
To review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of indiplon in the treatment of transient and chronic insomnia in adult and geriatric patients. A literature search was conducted using MEDLINE (1966-May 2008), International Pharmaceutical Abstracts (1970-May 2008), and Cochrane database (2007) for the key words indiplon or NBI-34060. References cited in the articles were reviewed for additional information. Abstract data were included only in the absence of significant published data. English-language literature reporting animal and human clinical studies was reviewed to evaluate data on the pharmacology, pharmacokinetics, pharmacodynamics, efficacy, and adverse effects of indiplon. Clinical trials selected for inclusion were limited to those with human subjects, with the accepted inclusion of pharmacology data in animals. Indiplon is a nonbenzodiazepine sedative-hypnotic that exhibits its sedating activity through its interaction with the gamma-aminobutyric acid alpha receptor complex. Indiplon immediate-release (IR) as well as modified-release (MR) forms have shown improvement compared with placebo in patients with DSM-IV-TR primary insomnia in various areas of subjective and objective sleep measurements. Specifically, improvements in total sleep time, latency to persistent sleep, latency to sleep onset, wake after sleep onset, and sleep quality have been noted in clinical trials. Trials evaluating both indiplon IR and MR have so far not identified any major serious adverse effects. Limited clinical trial data exist on use of indiplon in a "true" transient insomnia patient population. Based on recent Food and Drug Administration requests, clinical trial data assessing direct comparisons of indiplon IR with other approved nonbenzodiazepine sedative-hypnotics are needed to clearly define the differences among these agents.


Simultaneous Bilateral Spontaneous Pneumothorax in an Adult Patient With Pulmonary Langerhans Cell Histiocytosis: A Case Report.
We report a case of a young female with known history of pulmonary Langerhans cell histiocytosis who was initially presented in the emergency department of a university hospital with respiratory distress. Clinical assessment and diagnostic workup revealed left hemithorax subcutaneous emphysema, bilateral pneumothorax, and atelectasis in both lower lung lobes. The patient was treated with bilateral staged thoracoscopic bullectomy and mechanical abrasion of the parietal pleura combined with chemical pleurodesis with talc. A new occurrence of right-sided pneumothorax was noticed 3 days after surgery, which was treated with chest tube insertion and chemical pleurodesis. The aforementioned surgical approach resulted in complete lung expansion and the patient's full recovery. A review of pulmonary Langerhans cell histiocytosis and treatment options in cases of pneumothorax due to lung histiocytosis is also presented in this report.