miR-365 (microRNA): Potential Biomarker in Oral Squamous Cell Carcinoma Exosomes and Extracellular Vesicles.
miR-365 is a non-coding microRNA that regulates transcription and has been demonstrated to promote oncogenesis and metastasis in some cancers, while suppressing these effects in others. Many microRNAs are produced and then exported extracellularly in exosomes, which are small extracellular vesicles ranging from 30 to 100 nm that are found in eukaryotic fluids and facilitate many cellular functions. Exosomes and extracellular vesicles are produced by many cell types, including oral cancer cells-although no study to date has evaluated miR-365 and oral cancer exosomes or extracellular vesicles. Based on this information, our research question was to evaluate whether oral cancers produce exosomes or extracellular vesicles containing miR-365. Two commercially available oral cancer cell lines (SCC25 and CAL27) and a normal oral keratinocyte (OKF4) were grown in serum-free media, supplemented with exosome-depleted fetal bovine serum. Extracellular vesicles and exosomes were then isolated using the Invitrogen total exosome RNA and protein isolation kit for processing using the hsa-miR-365a-5p microRNA qPCR assay kit. RNA was successfully isolated from the exosome-depleted supernatant from each cell line-SCC9, SCC15, SCC25, and CAL27 (oral squamous cell carcinomas) and OKF4 (oral epithelial cell line). Relative concentrations of RNA were similar among each cell line, which were not significantly different, p = 0.233. RNA quality was established by A260:A280 absorbance using a NanoDrop, revealing purity ranging 1.73-1.86. Expression of miR-16 was used to confirm the presence of microRNA from the extracted exosomes and extracellular vesicles. The presence of miR-365 was then confirmed and normalized to miR-16 expression, which demonstrated an increased level of miR-365 in both CAL27 and SCC25. In addition, the normalized relative quantity (RQ) for miR-365 exhibited greater variation among SCC25 (1.382-4.363) than CAL27 cells (1.248-1.536). These results confirm that miR-365 is not only expressed in oral cancer cell lines, but also is subsequently exported into exosomes and extracellular vesicles derived from these cultures. These data may help to contextualize the potential for this microRNA to contribute to the phenotypes and behaviors of oral cancers that express this microRNA. Future research will begin to investigate these potential mechanisms and pathways and to determine if miR-365 may be useful as an oral cancer biomarker for salivary or liquid biopsies.


Radiance Saturation and Afterglow Emission of High Pressure 20-nsec Spark Channels in Argon and Helium.
Time functions of the radiance (ITT FW-114, spectral response S-4) were observed, as well as the radiant intensity of high pressure spark channels in argon and helium with pressures between 1 atm and 40 atm, and a constant gap of 0.65 mm. The radiance, as well as radiant intensity, first increases exponentially with pressure and breakdown voltage; later, the radiance curves bend into a saturation plateau in both gases. On the other hand, the radiant intensity does not reach saturation, but shifts its maximum up to 50 nsec after the 8-nsec current maximum. The shift of the radiant intensity and saturation are related and result from the increasing opacity of the channel. The observed 1.65 ratio of the saturation radiances of helium and argon agrees with values reported in microsecond spark channels which have a diameter approximately six times wider.


ACTIVATION (PercutAneous Coronary inTervention prIor to transcatheter aortic VAlve implantaTION): A Randomized Clinical Trial.
This study sought to determine if percutaneous coronary intervention (PCI) prior to transcatheter aortic valve replacement (TAVR) in patients with significant coronary artery disease would produce noninferior clinical results when compared with no PCI (control arm). PCI in patients undergoing TAVR is not without risk, and there are no randomized data to inform clinical practice. Patients with severe symptomatic aortic stenosis and significant coronary artery disease with Canadian Cardiovascular Society class ≤2 angina were randomly assigned to receive PCI or no PCI prior to TAVR. The primary endpoint was a composite of all-cause death or rehospitalization at 1 year. Noninferiority testing (prespecified margin of 7.5%) was performed in the intention-to-treat population. At 17 centers, 235 patients underwent randomization. At 1 year, the primary composite endpoint occurred in 48 (41.5%) of the PCI arm and 47 (44.0%) of the no-PCI arm. The requirement for noninferiority was not met (difference: -2.5%; 1-sided upper 95% confidence limit: 8.5%; 1-sided noninferiority test P = 0.067). On analysis of the as-treated population, the difference was -3.7% (1-sided upper 95% confidence limit: 7.5%; P = 0.050). Mortality was 16 (13.4%) in the PCI arm and 14 (12.1%) in the no-PCI arm. At 1 year, there was no evidence of a difference in the rates of stroke, myocardial infarction, or acute kidney injury, with higher rates of any bleed in the PCI arm (P = 0.021). Observed rates of death and rehospitalization at 1 year were similar between PCI and no PCI prior to TAVR; however, the noninferiority margin was not met, and PCI resulted in a higher incidence of bleeding. (Assessing the Effects of Stenting in Significant Coronary Artery Disease Prior to Transcatheter Aortic Valve Implantation; ISRCTN75836930).


Medial Temporal Lobe Subregional Atrophy in Aging and Alzheimer's Disease: A Longitudinal Study.
Medial temporal lobe (MTL) atrophy is a key feature of Alzheimer's disease (AD), however, it also occurs in typical aging. To enhance the clinical utility of this biomarker, we need to better understand the differential effects of age and AD by encompassing the full AD-continuum from cognitively unimpaired (CU) to dementia, including all MTL subregions with up-to-date approaches and using longitudinal designs to assess atrophy more sensitively. Age-related trajectories were estimated using the best-fitted polynomials in 209 CU adults (aged 19-85). Changes related to AD were investigated among amyloid-negative (Aβ-) (n = 46) and amyloid-positive (Aβ+) (n = 14) CU, Aβ+ patients with mild cognitive impairment (MCI) (n = 33) and AD (n = 31). Nineteen MCI-to-AD converters were also compared with 34 non-converters. Relationships with cognitive functioning were evaluated in 63 Aβ+ MCI and AD patients. All participants were followed up to 47 months. MTL subregions, namely, the anterior and posterior hippocampus (aHPC/pHPC), entorhinal cortex (ERC), Brodmann areas (BA) 35 and 36 [as perirhinal cortex (PRC) substructures], and parahippocampal cortex (PHC), were segmented from a T1-weighted MRI using a new longitudinal pipeline (LASHiS). Statistical analyses were performed using mixed models. Adult lifespan models highlighted both linear (PRC, BA35, BA36, PHC) and nonlinear (HPC, aHPC, pHPC, ERC) trajectories. Group comparisons showed reduced baseline volumes and steeper volume declines over time for most of the MTL subregions in Aβ+ MCI and AD patients compared to Aβ- CU, but no differences between Aβ- and Aβ+ CU or between Aβ+ MCI and AD patients (except in ERC). Over time, MCI-to-AD converters exhibited a greater volume decline than non-converters in HPC, aHPC, and pHPC. Most of the MTL subregions were related to episodic memory performances but not to executive functioning or speed processing. Overall, these results emphasize the benefits of studying MTL subregions to distinguish age-related changes from AD. Interestingly, MTL subregions are unequally vulnerable to aging, and those displaying non-linear age-trajectories, while not damaged in preclinical AD (Aβ+ CU), were particularly affected from the prodromal stage (Aβ+ MCI). This volume decline in hippocampal substructures might also provide information regarding the conversion from MCI to AD-dementia. All together, these findings provide new insights into MTL alterations, which are crucial for AD-biomarkers definition.


Simultaneous bilateral carotid endarterectomies.
Twelve patients with bilateral symptomatic lesions of internal carotid arteries have had bilateral carotid endarterectomy at single operations without complications. These were patients up to age 80 who had prior mycardial infarction, stroke with recovery, and hemispheric and nonhemispheric episodes. Neurologist's clearance and three- or four-vessel intracranial-extracranial angiography preceded all operations, which were performed with the patient under general anesthesia. Stump pressure measurements were the principal guideline of adequacy of collateral flow and predictor of safe outcome. The safety of this concept of bilateral operations during one anesthesia can eliminate uncertainties of sequence and timing, obviate delay and indecision, and avoid the hazards of a second anesthetic-operative experience.


Subacute osteomyelitis masquerading as primary bone sarcoma: report of six cases.
We report a series of six immunocompetent patients who were believed initially to have primary bone sarcomas, but turned out to have subacute osteomyelitis. Case report and review of relevant literature. All our patients were treated with antibiotics and recovered fully from the infection. Only one patient had a recurrence with the same offending microorganism, which resolved after a longer period of intravenous antibiotic. Subacute osteomyelitis and bone tumors can be similar in presentation, and the key to proper diagnosis is histopathological and microbiological confirmation in biopsy specimens.


Urinary pregnanetriol and delta 5-pregnentriol in women with idiopathic hirsutism.
Urinary pregnanetriol and delta 5-pregnenetriol were determined in 90 normal women and in 90 women with idiopathic hirsutism of comparable age group. When group Student's "t"-test was carried out, the mean steroid excretion values in hirsute women were found to be significant with delta 5-pregnenetriol more significant than pregnanetriol. Of the 90 women with hirsutism, 8 patients had pregnanetriol and delta 5-pregnenetriol values higher than normal. When, on the basis of these elevated values, the women were sent for a thorough gynaecological investigation, they were found to have the polycystic ovary syndrome. After wedge resection, the diagnosis was confirmed and the urinary excretion of pregnanetriol and delta 5-pregnenetriol came down to a normal level. This study shows that, in the case of women with idiopathic hirsutism suspected of any ovarian disorder, the measurement of these two steroids could be of diagnostic importance.


Associations between specific components of executive control and eating behaviors in adolescence: A study using objective and subjective measures.
A growing literature suggests that executive control (EC; also known as "executive functioning" or "EF") in adolescence may play an important role in the development of key health behaviors, including eating behaviors. However, existing literature has significant limitations in the conceptualization and measurement of EC. The current study aims to address these limitations by employing a multidimensional approach to conceptualizing and measuring adolescent EC, including both objective and subjective measures covering multiple components of EC, and examining links with specific eating behaviors. A community sample of adolescents (N = 208; mean age = 14.5 years) completed a battery of performance-based neuropsychological tasks assessing specific components of EC (i.e., working memory, inhibitory control, flexible shifting), a norm-referenced questionnaire covering problems with specific components of EC in daily life, and a measure assessing key eating behaviors (i.e., uncontrolled eating, emotional eating, cognitive restraint). Objectively-measured adolescent working memory was significantly and uniquely associated with cognitive restraint, with stronger working memory associated with less cognitive restraint. No other associations between performance-based EC tasks and eating behaviors were found. In contrast, using subjective reports of EC, problems with inhibitory control were associated with greater uncontrolled eating, and problems with flexible shifting were associated with greater emotional eating. The results suggest links between specific aspects of EC and specific eating behaviors in adolescence, as well as the potential importance of context for understanding the role of EC in eating behavior. Given evidence that EC is modifiable, the findings have potential implications for novel interventions addressing eating behaviors by targeting EC.


Quantitative brain microdialysis study on the mechanism of quinolones distribution in the central nervous system.
Brain interstitial fluid (ISF) concentrations, which regulate the toxicodynamic effect of quinolone antimicrobial agents (quinolones) in the central nervous system, have been determined for norfloxacin, ofloxacin, fleroxacin, and pefloxacin using a quantitative brain microdialysis technique. Steady-state brain ISF concentrations of the quinolones were 7-30 times lower than the unbound serum concentrations due to restricted distribution in the brain. Cerebrospinal fluid concentrations of the quinolones were approximately twice as high as the brain ISF concentrations, except for norfloxacin. Thus, it seems that an active efflux transport system across the blood-brain barrier is responsible for maintaining brain ISF concentrations lower than unbound serum concentrations at steady-state. A good correlation was observed for norfloxacin, ofloxacin, fleroxacin, and pefloxacin between brain ISF concentrations and total brain concentrations. Moreover, a relatively small difference was observed among the quinolones for the in vitro brain slice-to-medium concentration ratio, compared with an 11-fold difference in the in vivo brain-to-unbound serum concentration ratio after intravenous infusion. These results indicate that the different quinolones studied all exhibit similar apparent binding and/or uptake by brain parenchyma, with an average brain ISF-to-total brain concentration ratio of 0.688.


Bullous pemphigoid antigen expression in Pam 212 cells induced by the addition of platelet activating factor.
Platelet activating factor (Paf-acether) is a phospholipid which has various activities including platelet and neutrophil aggregation and eosinophil chemotaxis. We have previously reported that the blister fluids of bullous pemphigoid possess platelet aggregation activity and suggested that Paf-acether might be concerned with the accumulation and activation of neutrophils and eosinophils. In this study, we examined the influence of Paf-acether on BP antigen expression on Pam 212 cells. Paf-acether enhanced the expression of BP antigen on Pam 212 cells and this expression was blocked by Paf-acether antagonist. Our observations might suggest that Paf-acether contributes to the blister formation not only by the activation of inflammatory cells but the enhancement of BP antigen.


A machine learning approach identifies 5-ASA and ulcerative colitis as being linked with higher COVID-19 mortality in patients with IBD.
Inflammatory bowel diseases (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammation within the gastrointestinal tract. IBD patient conditions and treatments, such as with immunosuppressants, may result in a higher risk of viral and bacterial infection and more severe outcomes of infections. The effect of the clinical and demographic factors on the prognosis of COVID-19 among IBD patients is still a significant area of investigation. The lack of available data on a large set of COVID-19 infected IBD patients has hindered progress. To circumvent this lack of large patient data, we present a random sampling approach to generate clinical COVID-19 outcomes (outpatient management, hospitalized and recovered, and hospitalized and deceased) on 20,000 IBD patients modeled on reported summary statistics obtained from the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD), an international database to monitor and report on outcomes of COVID-19 occurring in IBD patients. We apply machine learning approaches to perform a comprehensive analysis of the primary and secondary covariates to predict COVID-19 outcome in IBD patients. Our analysis reveals that age, medication usage and the number of comorbidities are the primary covariates, while IBD severity, smoking history, gender and IBD subtype (CD or UC) are key secondary features. In particular, elderly male patients with ulcerative colitis, several preexisting conditions, and who smoke comprise a highly vulnerable IBD population. Moreover, treatment with 5-ASAs (sulfasalazine/mesalamine) shows a high association with COVID-19/IBD mortality. Supervised machine learning that considers age, number of comorbidities and medication usage can predict COVID-19/IBD outcomes with approximately 70% accuracy. We explore the challenge of drawing demographic inferences from existing COVID-19/IBD data. Overall, there are fewer IBD case reports from US states with poor health ranking hindering these analyses. Generation of patient characteristics based on known summary statistics allows for increased power to detect IBD factors leading to variable COVID-19 outcomes. There is under-reporting of COVID-19 in IBD patients from US states with poor health ranking, underpinning the perils of using the repository to derive demographic information.


Methemoglobinemia Caused by Portable Dialysis in the Critically Ill.
To evaluate the root cause of a series of methemoglobinemia cases in a medical ICU. We report a sentinel case of methemoglobinemia that was associated with dialysis sessions using a portable dialysis unit in our hospital. This led to the identification of four additional patients who developed methemoglobinemia while undergoing portable dialysis. We determined that these episodes were caused by inadequate clearance of chloramine from the tap water used for portable dialysis. Introduction of larger capacity carbon filters into the portable dialysis systems resulted in no further cases of methemoglobinemia at our institution. Clinicians should be aware of municipal tap water as a potential cause of methemoglobinemia and monitor for excessive levels of oxidants in dialysis water sources. The capacity of the hemodialysis equipment to clear chloramine can vary as a function of external factors. Using a reliable test method to identify chloramines in the water prior to entering the hemodialysis equipment is essential.


Crystal structure of Plasmodium falciparum spermidine synthase in complex with the substrate decarboxylated S-adenosylmethionine and the potent inhibitors 4MCHA and AdoDATO.
Plasmodium falciparum is the causative agent of the most severe type of malaria, a life-threatening disease affecting the lives of over three billion people. Factors like widespread resistance against available drugs and absence of an effective vaccine are seriously compounding control of the malaria parasite. Thus, there is an urgent need for the identification and validation of new drug targets. The enzymes of the polyamine biosynthesis pathway have been suggested as possible targets for the treatment of malaria. One of these enzymes is spermidine synthase (SPDS, putrescine aminopropyltransferase), which catalyzes the transfer of an aminopropyl moiety from decarboxylated S-adenosylmethionine (dcAdoMet) to putrescine, leading to the formation of spermidine and 5'-methylthioadenosine. Here we present the three-dimensional structure of P. falciparum spermidine synthase (pfSPDS) in apo form, in complex with dcAdoMet and two inhibitors, S-adenosyl-1,8-diamino-3-thio-octane (AdoDATO) and trans-4-methylcyclohexylamine (4MCHA). The results show that binding of dcAdoMet to pfSPDS stabilizes the conformation of the flexible gatekeeper loop of the enzyme and affects the conformation of the active-site amino acid residues, preparing the protein for binding of the second substrate. The complexes of AdoDATO and 4MCHA with pfSPDS reveal the mode of interactions of these compounds with the enzyme. While AdoDATO essentially fills the entire active-site pocket, 4MCHA only occupies part of it, which suggests that simple modifications of this compound may yield more potent inhibitors of pfSPDS.


Partial nucleotide sequence of Japanese encephalitis virus ling strain genome and comparison of the encoded structural proteins and nonstructural protein NS1 among Japanese encephalitis virus strains.
Approximately 4000 nucleotides of the 5'-terminal portion of Japanese encephalitis virus (JEV) Ling strain genome were cloned and sequenced. This nucleotide sequence and its encoded C-PrM-E-NS1 polyprotein sequences were also compared with the corresponding sequences of other JE virus strains. Results demonstrated that the nucleotide sequence homology varied from 97.1 to 99.3% and the amino acid homology 98.6 to 98.9%. Based on homology, the Ling strain was closer to the Beijing-1 strain than to the SA14 and JaOArS982 strains. However, only on comparison of the E sequence, which neutralization, hemagglutination-inhibition and complement fixation antigenic determinants are located, between Ling and other JEV strains demonstrated that nucleotide sequence homology varied from 97.1% to 99.3% and amino acid homology from 98.6% to 99.2%. The Ling strain JEV is more closely related to the Beijing-1 strain than to the Nakayama NIH, SA14 and JaOArS982 strains in that order. Based on this analysis, the Taiwanese JEV strain appears to be more closely related to the Chinese strain than to the Japanese strain. Also, JEV strains isolated in humans are more closely related to each other than to JEV strains of mosquito isolates.


Dynamics of intrarenal pressures and glomerular filtration rate after acetazolamide.
The dynamics of intrarenal pressures, early distal tubular fluid conductivity (EDC), and renal flood flow (RBF) were studied in rats given acetazolamide (ACZ), an inhibitor of proximal reabsorption. Glomerular filtration rate (GFR) and end-proximal flow were estimated by clearances of 51Cr-EDTA and lithium. Proximal tubular pressure (Pprox) increased initially by 1.7 +/- 0.1 mmHg after ACZ, causing a decrease in the hydrostatic pressure difference across the glomerular membrane (delta P). EDC increased, and then RBF, glomerular capillary pressure (Pgc), Pprox, and star vessel pressures (Psv) dropped as a result of afferent vasoconstriction. Pprox decreased less than Pgc, resulting in a further decrease in delta P, which after 25-30 s reached a constant level 3-4 mmHg below control. After a transient increase the pressures declined to a new steady state, in which Pprox was equal to control, Pgc was decreased, and distal tubular pressure, end-proximal flow, and EDC were increased. GFR was depressed by 29%. The results indicate that the tubuloglomerular feedback mechanism controls Pgc and Pprox by afferent vasoconstriction, as well as efferent vasodilation. The data also indicate that proximal reabsorption rate is important in determining the changes in delta P by its effect on Pprox at least in the early transient phase.


Digital interventions to promote physical activity among inactive adults: A study protocol for a hybrid type I effectiveness-implementation randomized controlled trial.
Physical inactivity is the fourth leading risk factor for global mortality, and inactive adults have a higher risk to develop lifestyle diseases. To date, there is preliminary evidence of the efficacy of fitness technologies and other digital interventions for physical activity (PA) promotion. Intervention studies are needed to test the effectiveness and implementation of innovative PA promotion strategies. The ONWARDS study is a hybrid type I effectiveness-implementation randomized control trial aiming at an inactive and presumably high-risk population living in Northern Norway. One hundred and eighty participants will be assigned to 3 groups in a 1:1:1 ratio and participate for 18 months. Participants in group A will be provided an activity tracker with the personalized metric Personal Activity Intelligence (PAI). Participants in group B will be provided with both an activity tracker with the personalized metric PAI and access to online training videos (Les Mills+) to perform home-based training. Participants in group C will be provided an activity tracker with the personalized metric PAI, home-based online training and additional peer support via social media. The primary objective is to test which combination of interventions is more effective in increasing PA levels and sustaining long-term exercise adherence. Secondary objectives include: proportion of participants reaching PA recommendations; exercise adherence; physical fitness; cardiovascular risk; quality of life; perceived competence for exercise; self-efficacy; social support; usability; users' perspectives on implementation outcomes (adoption, acceptability, adherence, sustainability). The study design will allow testing the effectiveness of the interventions while gathering information on implementation in a real-world situation. This study can contribute to reduce disparities in PA levels among inactive adults by promoting PA and long-term adherence. Increased PA might, in turn, result in better prevention of lifestyle diseases. Digital interventions delivered at home can become an alternative to training facilities, making PA accessible and feasible for inactive populations and overcoming known barriers to PA. If effective, such interventions could potentially be offered through national health portals to citizens who do not meet the minimum recommendations on PA or prescribed by general practitioners or specialists. https://clinicaltrials.gov/ct2/show/NCT04526444, Registered 23 April 2021, identifier: NCT04526444.


Categorical 12-step involvement and continuous abstinence at 2 years.
A longitudinal analysis of 12-step involvement was conducted among a U.S. sample of patients exiting treatment for substance dependence. Categorical involvement in a set of 12-step activities and summary scores of involvement from the Alcoholics Anonymous Affiliation Scale were examined in relation to continuous abstinence and aftercare (Oxford House or usual care) condition. Participants who were categorically involved in 12-step activities were significantly more likely to maintain continuous abstinence at 2 years compared with those who were less involved, predicting a greater likelihood of complete abstinence than summary scores of involvement. In addition, participants in the Oxford House condition were significantly more likely to remain continuously abstinent throughout the course of this randomized clinical trial. Findings suggest that categorical involvement in a set of 12-step activities and communal-living settings such as Oxford Houses are independent factors associated with continuous abstinence from both alcohol and illicit drugs among substance dependent persons.


Interleukin-17A+ cell counts are increased in systemic sclerosis skin and their number is inversely correlated with the extent of skin involvement.
Levels of interleukin-17A (IL-17A) have been found to be increased in synovial fluid from individuals with systemic sclerosis (SSc). This study was undertaken to investigate whether IL-17A-producing cells are present in affected SSc skin, and whether IL-17A exerts a role in the transdifferentiation of myofibroblasts. Skin biopsy samples were obtained from the involved skin of 8 SSc patients and from 8 healthy control donors undergoing plastic surgery. Immunohistochemistry and multicolor immunofluorescence techniques were used to identify and quantify the cell subsets in vivo, including IL-17A+, IL-4+, CD3+, tryptase-positive, α-smooth muscle actin (α-SMA)-positive, myeloperoxidase-positive, and CD1a+ cells. Dermal fibroblast cell lines were generated from all skin biopsy samples, and quantitative polymerase chain reaction, Western blotting, and solid-phase assays were used to quantify α-SMA, type I collagen, and matrix metalloproteinase 1 (MMP-1) production by the cultured fibroblasts. IL-17A+ cells were significantly more numerous in SSc skin than in healthy control skin (P = 0.0019) and were observed to be present in both the superficial and deep dermis. Involvement of both T cells and tryptase-positive mast cells in the production of IL-17A was observed. Fibroblasts positive for α-SMA were found adjacent to IL-17A+ cells, but not IL-4+ cells. However, IL-17A did not induce α-SMA expression in cultured fibroblasts. In the presence of IL-17A, the α-SMA expression induced in response to transforming growth factor β was decreased, while MMP-1 production was directly enhanced. Furthermore, the frequency of IL-17A+ cells was higher in the skin of SSc patients with greater severity of skin fibrosis (lower global skin thickness score). IL-17A+ cells belonging to the innate and adaptive immune system are numerous in SSc skin. IL-17A participates in inflammation while exerting an inhibitory activity on myofibroblast transdifferentiation. These findings are consistent with the notion that IL-17A has a direct negative-regulatory role in the development of dermal fibrosis in humans.


Insular erosion, isostasy, and subsidence.
Organic reefs and shore erosion record the intersection of sea level with islands. From this record it is possible to reconstruct the history of vertical movement of the islands and the adjacent deep sea floor, including midplate swells. As judged by coral thickness, islands with barrier reefs sink as though they were on thermally youthful crust regardless of the actual age. Reefless islands do not sink until truncated by erosion. Apparently, thermal subsidence is balanced by isostatic uplift in response to erosion. Barrier reefs prevent wave erosion of encircled volcanoes and capture products of stream erosion so that isostatic uplift is eliminated. Insular shelves widen initially at rates of 0.6 to 1.7 kilometers per million years; the rates decrease with time. Thus the subsidence of islands depends on the size of the is land and the presence of reefs, and it may not always be the same as that of the surrounding oceanic crust.


Site-directed mutagenesis of the leech-derived factor Xa inhibitor antistasin. Probing of the reactive site.
Antistasin (ATS) is a leech-derived 119-amino-acid protein which exhibits potent and highly selective inhibition of coagulation Factor Xa. It inhibits Factor Xa according to a common mechanism of serine-proteinase inhibitors in which a conformationally rigid substrate-like reactive site is presented to the enzyme. In this study a recombinant version of ATS was expressed and purified utilizing a yeast expression system in order to probe the reactive site P1 (Arg-34) and P1' (Val-35) residues by site-directed mutagenesis. The results demonstrate the requirement for a positively charged residue in the P1 position of ATS, with an arginine residue preferred over a lysine, yielding K1 values of 61 pM and 1.28 nM respectively. Mutation of the P1 arginine residue to the non-polar amino acid leucine abolished its inhibitory potency toward Factor Xa. The role of the C-terminal domain of ATS, which shares significant amino acid sequence identity with the N-terminal domain, was investigated by creating a second reactive site in the corresponding position of the C-terminal domain. The inhibitory activity of this mutant demonstrated that the C-terminal domain of ATS is not folded into the proper conformation necessary to create a functional inhibitory domain.


Understanding the financial impact of MS-DRGs.
Steps hospitals should take to prepare for changes to Medicare's inpatient prospective payment system include: Analyze the data within product lines to identify trends (by physician or by specific Medicare severity diagnosis-related group). Determine which product lines will be most affected. Develop action plans to proactively manage the resulting changes in revenue.


Genetic features of the Puumala virus (Hantaviridae: Orthohantavirus) identified in the Moscow region.
Puumala virus (family Hantaviridae, genus Orthohantavirus) is distributed in most regions of the European part of Russia. However, information about its genetic variants circulating on the territory of the Central Federal District is extremely scarce. Rodents' tissue samples were tested after reverse transcription by PCR for the presence of hantaviral RNA. The amplified fragments of the L segment were sequenced by the Sanger method. For two samples, sequences of all three segments were obtained using the NGS method. Phylogenetic trees were built in the MEGA-X software. Puumala virus was found in six samples. Based on the phylogenetic analysis of sequences of three segments, the obtained genetic variants belong to the sublineage previously designated as W-RUS. A genetic variant of the Puumala virus, belonging to the subline W-RUS, circulates on the territory of the Volokolamsk district of Moscow region.


Brief communication: Bone trabeculae are visible on periapical images.
It is traditionally believed that the radiographic image of bone striae is a reflection of the trabecular pattern of cancellous bone. Results of a 1999 paper by Cavalcanti et al. contradicted this paradigm, suggesting that the intraoral radiographic image of trabecular pattern in the mandible reflects the morphology of the endosteal surface of the cortical bone, rather than that of cancellous bone. Here, we conduct a simple experiment to assess the contribution of dry mandibular cancellous bone to the image of trabecular pattern seen on intraoral films. Standardized periapical-type radiographs centered on the same region of interest of a dry human mandible were acquired before and after removal of the buccal, then of both cortical plates, together with the endosteal cortical-trabecular bone interface. One oral and maxillofacial radiologist and 4 oral and maxillofacial radiology residents blindly assessed the presence or absence of bone striations on the acquired images. We find that bone striations are visible on periapical-type images of dry human mandibles in the absence of one or both cortical plates, and that their pattern is similar to that seen in the image of the intact specimen. We conclude that cancellous bone contributes significantly to the image of trabecular bone in dry human mandibles.


Luminol-dependent chemiluminescence of human phagocyte cell lines: comparison between DMSO differentiated PLB 985 and HL 60 cells.
The human promyelocytic leukemia HL 60 and PLB 985 cell lines can differentiate into terminally mature neutrophil-like cells via dimethyl sulfoxide (DMSO) induction. In this study the luminol-dependent chemiluminescence (LCL) of both neutrophil-like cells was analayzed and compared in response to phorbol myristate acetate (PMA) and opsonized zymosan (OZ) stimulants. It was shown that, like human blood neutrophils, both neutrophil-like cells expressed high levels of CD11b, but unlike human blood neutrophils these cells almost lack LCL-detectable intracellular oxidase activity. By studying the pattern of activation to OZ and PMA and priming with GM-CSF, we concluded that there is no difference between the percentage of differentiation and function of DMSO-induced HL 60 and PLB 985. However, the LCL capacity (area under the curve) of DMSO induced PLB 985 cells was higher than that of HL 60 cells in response to both PMA and OZ, which implies a higher capacity to generate reactive oxygen species in PLB 985 cells.


Satellite data identify decadal trends in the quality of Pygoscelis penguin chick-rearing habitat.
Pygoscelis penguins are experiencing general population declines in their northernmost range whereas there are reported increases in their southernmost range. These changes are coincident with decadal-scale trends in remote sensed observations of sea ice concentrations (SIC) and sea surface temperatures (SST) during the chick-rearing season (austral summer). Using SIC, SST, and bathymetry, we identified separate chick-rearing niche spaces for the three Pygoscelis penguin species and used a maximum entropy approach (MaxEnt) to spatially and temporally model suitable chick-rearing habitats in the Southern Ocean. For all Pygoscelis penguin species, the MaxEnt models predict significant changes in the locations of suitable chick-rearing habitats over the period of 1982-2010. In general, chick-rearing habitat suitability at specific colony locations agreed with the corresponding increases or decreases in documented population trends over the same time period. These changes were the most pronounced along the West Antarctic Peninsula where there has been a rapid warming event during at least the last 50 years.


Insights into gut microbiota metabolism of dietary lipids: the case of linoleic acid.
It has been recognized that, next to dietary fibre and proteins, gut microbiota can metabolize lipids producing bioactive metabolites. However, the metabolism of dietary lipids by human gut microbiota has been poorly explored so far. This study aimed to examine the change in lipids, particularly linoleic acid (LA), induced by the chemical form of lipids and the presence of the plant matrix. Short-chain fatty acid (SCFA) production was monitored to get an insight into microbial activity. Free LA, glyceryl trilinoleate and soybean oil as well as digested intact (DS) and broken (BS) soybean cells were subjected to in vitro fermentation using human faecal inoculums. Confocal microscopy was used to visualize the soybean cell integrity. Three LA metabolites, including two conjugated fatty acids (CLAs, 9z,11e and 9e,11e) and 12hydroxy, 9z C18:1, were identified and monitored. Free LA addition improved the LA metabolite production but reduced SCFA concentrations compared to trilinoleate and soybean oil. Breaking cell integrity had impacts on CLA, hydroxy C18:1 and SCFA production and free fatty acid release within the first 24 h of fermentation, but this effect vanished with time. In contrast, soybean oil only increased free LA release and hydroxy C18:1 production. The content of several FAs decreased during fermentation suggesting a substantial conversion in microbial metabolites. Besides, LA metabolites were also identified in the fermentation pellets suggesting the incorporation of microbial FA metabolites into bacterial cells. This study expands our understanding of microbial metabolism of dietary lipids with a special emphasis on the role of food- and diet-related factors.


Identification of a nonsynonymous polymorphism in the SVEP1 gene associated with altered clinical outcomes in septic shock.
Mortality from septic shock is highly heritable. The identification of causal genetic factors is insufficient. To discover key contributors, we first identified nonsynonymous single-nucleotide polymorphisms in conserved genomic regions that are predicted to have significant effects on protein function. We then test the hypothesis that these nonsynonymous single-nucleotide polymorphisms across the genome alter clinical outcome of septic shock. Genetic-association study plus in vitro experiment using primary cells plus in silico analysis using genomic DNA and protein database. Twenty-seven ICUs at academic teaching centers in Canada, Australia, and the United States. Patients with septic shock of European ancestry (n = 520). Patients with septic shock were genotyped for 843 nonsynonymous single-nucleotide polymorphisms in conserved regions of the genome and are predicted to have damaging effects from the protein sequence. The primary outcome variable was 28-day mortality. Secondary outcome variables were organ dysfunction. Productions of adhesion molecules including interleukin-8, growth-regulated oncogene-α, monocyte chemoattractant protein-1, and monocyte chemoattractant protein-3 were measured in human umbilical vein endothelial cells after SVEP1 gene silencing by RNA interference. Patients with septic shock having the SVEP1 C allele of nonsynonymous single-nucleotide polymorphism, SVEP1 c.2080A>C (p. Gln581His, rs10817033), had a significant increase in the hazard of death over the 28 days (hazard ratio, 1.72; 95% CI, 1.31-2.26; p = 9.7 × 10-5) and increased organ dysfunction and needed more organ support (p < 0.05). Silencing SVEP1 significantly increased interleukin-8, growth-regulated oncogene-α, monocyte chemoattractant protein-1, monocyte chemoattractant protein-3 production in human umbilical vein endothelial cells under lipopolysaccharide stimulation (p < 0.01). C allele of SVEP1 c.2080A>C (p. Gln581His) single-nucleotide polymorphism, a non-synonymous single-nucleotide polymorphism in conserved regions and predicted to have damaging effects on protein structure, was associated with increased 28-day mortality and organ dysfunction of septic shock. SVEP1 appears to regulate molecules of the leukocyte adhesion pathway.


Cellulose Elementary Fibrils Assemble into Helical Bundles in S1 Layer of Spruce Tracheid Wall.
The ultrastructural organization of cellulose elementary fibrils (EFs) in wood cell wall is considered to be the prime factor regulating the material characteristics of wood in micro to macro levels and the conversion of delignified wood fibers into various products. Specifically, the complex assembly of EFs in wood cell wall limits its swellability, solubility, and reactivity, for example, in dissolution of cellulose for regeneration of textile fibers, fibril separation for the manufacture of nanocellulose, and enzymatic hydrolysis of cellulose into sugars for their subsequent fermentation to various products, like ethanol for future fossil fuels replacement. Here cryo-transmission electron tomography was applied on ultrathin spruce wood sections to reveal the EF assembly in S1 layer of the native cell wall. The resolution of these tomograms was then further enhanced by computational means. For the first time, cellulose in the intact cell wall was visualized to be assembled into helical bundles of several EFs, a structural feature that must have a significant impact on the swelling, accessibility, and solubility of woody biomass for its conversion into the aforementioned value added products.


Secretory autophagy promotes Rab37-mediated exocytosis of tissue inhibitor of metalloproteinase 1.
Rab37-mediated exocytosis of tissue inhibitor of metalloproteinase 1 (TIMP1), an inflammatory cytokine, under serum-depleted conditions which leads to suppression of lung cancer cell metastasis has been reported. Starvation is also a stimulus of autophagic activity. Herein, we reveal that starvation activates Rab37 and induces autophagy. We used an overexpression/knockdown system to determine the relationship between autophagy and Rab37 in vitro and in vivo. The autophagy activity was detected by immunoblotting, transmission electron microscope, autophagosome purification, and immunofluorescence under the confocal microscope. Lung-to-lung metastasis mouse model was used to clarify the role of autophagy and Rab37 in lung cancer. Clinical lung cancer patient specimens and an online big database were analyzed. Initially, we demonstrated that active-form Rab37 increased LC3-II protein level (the marker of autophagosome) and TIMP1 secretion. Accordingly, silencing of Rab37 gene expression alleviated Rab37 and LC3-II levels as well as TIMP1 secretion, and induction of autophagy could not increase TIMP1 exocytosis under such conditions. Moreover, silencing the Atg5 or Atg7 gene of lung cancer cells harboring active-mutant Rab37 (Q89L) led to decreased autophagy activity and TIMP1 secretion. In the lung-to-lung metastasis mouse model, increased TIMP1 expression accompanied by amiodarone-induced autophagy led to decreased tumor nodules and cancer cell metastasis. These phenomena were reversed by silencing the Atg5 or Atg7 gene. Notably, increasing autophagy activity alone showed no effect on TIMP1 secretion under either Rab37 or Sec22b silencing conditions. We further detected colocalization of LC3 with either Rab37 or TIMP1, identified Rab37 and Sec22b proteins in the purified autophagosomes of the lung cancer cells harboring the active-form Rab37 gene, and confirmed that these proteins are involved in the secretion of TIMP1. We reveal that autophagic activity was significantly lower in the tumors compared to the non-tumor parts and was associated with the overall lung cancer patient survival rate. We are the first to report that autophagy plays a promoting role in TIMP1 secretion and metastasis in a Rab37-dependent manner in lung cancer cells and the lung-to-lung mouse model.


[Vaginal vault fluid collection after hysterectomy. Frequency and clinical significance].
Our aim was to investigate the prevalence of sonographically detectable vault fluid collection after hysterectomy and its relation to post-operative morbidity. We studied a group of 103 women below 60 years of age who had undergone abdominal or vaginal hysterectomy for benign causes apart from uterovaginal prolapse. A transvaginal ultrasound examination was carried out 24 to 72 hours after surgery. A telephone follow-up and a record review were done six to eight weeks later to determine the morbidity rate. Of the 103 women scanned, 39 (38%) had sonographically detected vaginal vault fluid collection. A haemoglobin concentration drop was observed in a significant number of patients (33% vs. 13%) who had fluid collection in the immediate post-operative period. At follow-up, a significant increase in the complaints of post-operative pain (15% vs. 42%) and re-presentation (32% vs. 55%) was seen in the fluid collection group. The increased risk of re-presentation was not accompanied by an increased risk of needing additional treatment. Sonographic detection of vaginal vault fluid collection is common after hysterectomy, but such a finding rarely indicates additional treatment. Vaginal ultrasound examination should not be performed routinely after hysterectomy.


A magneto-DNA nanoparticle system for the rapid and sensitive diagnosis of enteric fever.
There is currently no widely available optimal assay for diagnosing patients with enteric fever. Here we present a novel assay designed to detect amplified Salmonella nucleic acid (mRNA) using magneto-DNA probes and a miniaturized nuclear magnetic resonance device. We designed primers for genes specific to S. Typhi, S. Paratyphi A, and genes conserved among Salmonella enterica spp. and utilized strongly magnetized nanoparticles to enhance the detection signal. Blood samples spiked with in vitro grown S. Typhi, S. Paratyphi A, S. Typhimurium, and E. coli were used to confirm the specificity of each probe-set, and serial 10-fold dilutions were used to determine the limit of the detection of the assay, 0.01-1.0 CFU/ml. For proof of principle, we applied our assay to 0.5 mL blood samples from 5 patients with culture-confirmed enteric fever from Bangladesh in comparison to 3 healthy controls. We were able to detect amplified target cDNA in all 5 cases of enteric fever; no detectable signal was seen in the healthy controls. Our results suggest that a magneto-DNA nanoparticle system, with an assay time from blood collection of 3.5 hours, may be a promising platform for the rapid and culture-free diagnosis of enteric fever and non-typhoidal Salmonella bacteremia.


A comparison of the Yan and a dosimeter method for methacholine challenge in experienced and inexperienced subjects.
Bronchial reactivity is being measured with increasing frequency in epidemiological studies, but there debate continues about the relative merits of the different methods used to measure reactivity, particularly for subjects with no previous experience of reactivity testing as is the case in epidemiological studies. Repeatability is likely to improve with practice, and laboratory based studies on experienced subjects may overestimate the repeatability of a test in inexperienced subjects. We have compared the repeatability of the Yan method with a dosimeter (Mefar) method of administering methacholine to 40 asthmatic subjects: 20 with experience of methacholine challenge on at least six previous occasions and 20 with no previous experience. Subjects attended the laboratory on four days within a two week period, at the same time of day. A methacholine challenge was performed on two occasions using the Yan method and on two occasions using the dosimeter. Methacholine responsiveness was measured as the provocative dose causing a 20% reduction in forced expiratory volume in one second (PD20FEV1). Geometric mean PD20FEV1 values with the Yan method were 1.14 doubling doses (DD) of methacholine higher than with the dosimeter method. In the experienced subjects, the 95% range for a single estimate was +/- 1.56 DD for the Yan method and +/- 1.37 DD for the dosimeter method. In the inexperienced subjects, the 95% ranges were +/- 2.65 and +/- 1.87 DD for the Yan and dosimeter methods, respectively. Thus, the differences in repeatability between the Yan and dosimeter methods, were small; experienced subjects gave more repeatable values than inexperienced subjects.


A new species of Barbatula from the headwaters of the Bulgan River in western Mongolia (Teleostei: Nemacheilidae).
Barbatula karabanowi, new species, is described from the upper Bulgan River drainage in Mongolia. It is most similar to B. dsapchynensis from the Zavhan River basin (Lake Valley, Mongolia). The new species is distinguished from this and all other species of Barbatula in Asia by a combination of characters, none of them unique: nostrils widely spaced; snout broad, ratio between maximum head width and width of snout at anterior nare 1.4-1.6; lips smooth, upper lip with a short incision; lower lip with short, well developed lateral lobes, mental lobes oval, lacking conical protrusions; scales absent or isolated scales present on the flank between dorsal- and caudal-fin bases; 42-44 vertebrae (usually 43); 75-88 lateral line pores on flank; paired fins with rounded tips; pigmentation pattern with densely set and partially fused irregularly shaped blotches and streaks. Barbatula karabanowi occurs in syntopy with B. cf. altayensis. It is distinguished from this species by having widely separated nares (vs. closely-set), details in the mouth structure, few or no scales (vs. squamation well developed), less vertebrae and lateral line pores (42-44 and 75-88 vs. 44-45 and 89-105, respectively), "non-muscular" cheeks in both sexes (vs. thickened, especially in the males) and details in colour pattern. These two species were found to prey on different food items and were the only fish taxa found in the studied part of the river.


[Ehlers-Danlos syndrome type IV. Case study and clinical findings].
We describe Ehlers-Danlos syndrome type IV in adult patients with a confirmed diagnosis and a systematic review of expected clinical findings in the disease. Serious complications were found in four individuals, two with gastrointestinal perforation at the age of 32 years, two had died from an aortic rupture (34 and 44 years old) and one has been diagnosed with aortic root dilatation. Most had also less severe clinical features such as varicose veins, easy bruising, thin and translucent skin, chronic joint subluxation or dislocation or pes planus. None of the females had uterine rupture or premature birth. Management and surveillance options were reviewed.


Does one size fit all African American smokers? The moderating role of acculturation in culturally specific interventions.
There is a consensus that interventions for ethnic minority populations should be culturally specific (CS). A previous study found that although African American smokers indicated a preference for CS self-help materials over standard materials, several outcomes were superior for the standard information (Webb, 2008). The current study reports on a priori analyses that tested level of acculturation as a moderating variable for the efficacy of CS interventions in a sample of low-income African Americans. Participants (N = 182) completed the African American Acculturation Scale-Revised before receiving a CS smoking cessation guide or a standard guide. As hypothesized, level of acculturation predicted evaluations of the intervention content, readiness to quit smoking, and 24-hr point prevalence abstinence at the 3-month follow-up. Lower levels of acculturation (i.e., more engagement in traditional African American culture) predicted a preference for CS materials and greater readiness to quit smoking after receiving the CS guide. Yet, among participants who were less acculturated, 24-hr abstinence was greater after receiving the standard guide. Overall, these findings emphasize that individual differences in levels of acculturation to the dominant culture affect receptivity to CS written interventions. Intragroup differences should be considered prior to the provision of CS interventions.


Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides.
Insulin and IGF signaling are critical to numerous developmental and physiological processes, with perturbations being pathognomonic of various diseases, including diabetes. Although the functional roles of the respective signaling pathways have been extensively studied, the control of insulin production and release is only partially understood. Herein, we show that in Drosophila expression of insulin-like peptides is regulated by neprilysin activity. Concomitant phenotypes of altered neprilysin expression included impaired food intake, reduced body size, and characteristic changes in the metabolite composition. Ectopic expression of a catalytically inactive mutant did not elicit any of the phenotypes, which confirms abnormal peptide hydrolysis as a causative factor. A screen for corresponding substrates of the neprilysin identified distinct peptides that regulate insulin-like peptide expression, feeding behavior, or both. The high functional conservation of neprilysins and their substrates renders the characterized principles applicable to numerous species, including higher eukaryotes and humans.


The profile of nursing management graduates from the nursing programs in southern Brazil.
This is an exploratory-descriptive study, performed on a documental basis and using a quantitative approach. The objective was to describe the profile of graduates from the Nursing Graduate Programs from Southern Brazil, from 2006 to 2009, which titles revealed they were in the lines of research regarding nursing management. The data was collected using The CAPES Indicator Books and searches on the graduates' Curriculum Lattes/CNPq. The Nursing Graduate Programs in Southern Brazil totaled 409 students, 129 (31.5%) of which worked in the lines of research associated with nursing management/administration: 116 (89.9%) Masters and 13 (10.1%) Doctorates. Most graduates currently work as faculty. Of those with a master degree, two (1.7%) have already obtained a doctorate degree, and 39 (33.6%) are currently in the doctorate program. The intellectual production after obtaining the degree adds up to 501 published scientific articles, with an average 1.1 and 1.8 article/year among masters and doctorates, respectively. The study presents indicatives for the preparation of differentiated masters and doctorates to work in nursing and health management/administration.


Improved Biocompatible, Flexible Mesh Composites for Implant Applications via Hydroxyapatite Coating with Potential for 3-Dimensional Extracellular Matrix Network and Bone Regeneration.
Hydroxyapatite (HA)-coated metals are biocompatible composites, which have potential for various applications for bone replacement and regeneration in the human body. In this study, we proposed the design of biocompatible, flexible composite implants by using a metal mesh as substrate and HA coating as bone regenerative stimulant derived from a simple sol-gel method. Experiments were performed to understand the effect of coating method (dip-coating and drop casting), substrate material (titanium and stainless steel) and substrate mesh characteristics (mesh size, weave pattern) on implant's performance. HA-coated samples were characterized by X-ray diffractometer, transmission electron microscope, field-emission scanning electron microscope, nanoindenter, polarization and electrochemical impedance spectroscopy, and biocompatibility test. Pure or biphasic nanorod HA coating was obtained on mesh substrates with thicknesses varying from 4.0 to 7.9 μm. Different coating procedures and number of layers did not affect crystal structure, shape, or most intense plane reflections of the HA coating. Moduli of elasticity below 18.5 GPa were reported for HA-coated samples, falling within the range of natural skull bone. Coated samples led to at least 90% cell viability and up to 99.5% extracellular matrix coverage into a 3-dimensional network (16.4% to 76.5% higher than bare substrates). Fluorescent imaging showed no antagonistic effect of the coatings on osteogenic differentiation. Finer mesh size enhanced coating coverage and adhesion, but a low number of HA layers was preferable to maintain open mesh areas promoting extracellular matrix formation. Finally, electrochemical behavior studies revealed that, although corrosion protection for HA-coated samples was generally higher than bare samples, galvanic corrosion occurred on some samples. Overall, the results indicated that while HA-coated titanium grade 1 showed the best performance as a potential implant, HA-coated stainless steel 316 with the finest mesh size constitutes an adequate, lower cost alternative.


Assessing the Safety Attitudes Questionnaire (SAQ), German language version in Swiss university hospitals--a validation study.
Improving patient safety has become a major focus of clinical care and research over the past two decades. An institution's patient safety climate represents an essential component of ensuring a safe environment and thereby can be vital to the prevention of adverse events. Covering six patient safety related factors, the Safety Attitudes Questionnaire (SAQ) is a validated and widely used instrument to measure the patient safety climate in clinical areas. The objective of this study was to assess the psychometric properties of the German language version of the SAQ. A survey was carried out in two University Hospitals in Switzerland in autumn 2009 where the SAQ was distributed to a sample of 406 nurses and physicians in medical and surgical wards. Following the American Educational Research Association guidelines, we tested the questionnaire validity by levels of evidence: content validity, internal structure and relations to other variables. Confirmatory factor analysis was used to examine factor structure. Cronbach's alphas and inter-item correlations were calculated to examine internal consistency reliability. A total of 319 questionnaires were completed representing an overall response rate of 78.6%. For three items, the item content validity index was <0.75. Confirmatory factor analysis showed acceptable model fit (RMSEA = 0.045; CFI = 0.944) for the six-factor model. Additional exploratory factor analysis could not identify a better factor model. SAQ factor scores showed positive correlations with the Safety Organizing Scale (r = .56-.72). The SAQ German version showed moderate to strong internal consistency reliability indices (Cronbach alpha = .65-.83). The German language version of the SAQ demonstrated acceptable to good psychometric properties and therefore shows promise to be a sound instrument to measure patient safety climate in Swiss hospital wards. However, the low item content validity and large number of missing responses for several items suggest that improvements and adaptations in translation are required for select items, especially within the perception of management scale. Following these revisions, psychometric properties should reassessed in a randomly selected sample and hospitals and departments prior to use in Swiss hospital settings.


ImmunoDataAnalyzer: a bioinformatics pipeline for processing barcoded and UMI tagged immunological NGS data.
Next-generation sequencing (NGS) is nowadays the most used high-throughput technology for DNA sequencing. Among others NGS enables the in-depth analysis of immune repertoires. Research in the field of T cell receptor (TCR) and immunoglobulin (IG) repertoires aids in understanding immunological diseases. A main objective is the analysis of the V(D)J recombination defining the structure and specificity of the immune repertoire. Accurate processing, evaluation and visualization of immune repertoire NGS data is important for better understanding immune responses and immunological behavior. ImmunoDataAnalyzer (IMDA) is a pipeline we have developed for automatizing the analysis of immunological NGS data. IMDA unites the functionality from carefully selected immune repertoire analysis software tools and covers the whole spectrum from initial quality control up to the comparison of multiple immune repertoires. It provides methods for automated pre-processing of barcoded and UMI tagged immune repertoire NGS data, facilitates the assembly of clonotypes and calculates key figures for describing the immune repertoire. These include commonly used clonality and diversity measures, as well as indicators for V(D)J gene segment usage and between sample similarity. IMDA reports all relevant information in a compact summary containing visualizations, calculations, and sample details, all of which serve for a more detailed overview. IMDA further generates an output file including key figures for all samples, designed to serve as input for machine learning frameworks to find models for differentiating between specific traits of samples. IMDA constructs TCR and IG repertoire data from raw NGS reads and facilitates descriptive data analysis and comparison of immune repertoires. The IMDA workflow focus on quality control and ease of use for non-computer scientists. The provided output directly facilitates the interpretation of input data and includes information about clonality, diversity, clonotype overlap as well as similarity, and V(D)J gene segment usage. IMDA further supports the detection of sample swaps and cross-sample contamination that potentially occurred during sample preparation. In summary, IMDA reduces the effort usually required for immune repertoire data analysis by providing an automated workflow for processing raw NGS data into immune repertoires and subsequent analysis. The implementation is open-source and available on https://bioinformatics.fh-hagenberg.at/immunoanalyzer/ .


Sex Differences in the Prevalent Use of Oral Formulations of Cholinesterase Inhibitors in Older Adults with Dementia.
Cholinesterase inhibitors (ChEIs) are one of only two drug therapies available to manage cognitive decline in dementia. Given sex-specific differences in medication access and effects, it is important to understand how ChEIs are used by women and men. The objective of this study was to provide contemporary sex-stratified evidence on patterns of ChEI use by community-dwelling older adults with dementia to inform opportunities to optimize drug prescribing. We conducted a population-based cross-sectional study examining ChEI use in older adults with dementia in Ontario, Canada. We identified all community-dwelling individuals aged 66 years and older with a pre-existing diagnosis of dementia as of 1 April, 2016. We examined the prevalence of ChEI use among women and men separately, and explored the association between ChEI use and age, sex, income status, geographic location of residence, use of palliative care services, comorbidity, and polypharmacy. Concurrent use of drugs known to impair cognition (including antipsychotics, benzodiazepines, and medications with strong anticholinergic properties) was separately assessed among women and men using multivariable analyses and prevalence risk ratios. Of 74,799 women and 52,231 men living with dementia in the community, nearly 30% currently were using a ChEI (29.3% women, 28.6% men). Close to 70% of users were receiving the target therapeutic dose. Compared to men, women were less often taking the target therapeutic dose (67.8% women vs. 71.6% men, p < 0.001). Over 20% of users also were using drugs known to impair cognition, while being treated for cognitive decline using ChEIs. Compared to men, women were more often concurrently using drugs known to impair cognition (23.9% women vs. 21.8% men, p < 0.001). This is one of the first studies of ChEI use to account for important sex differences. The results remind clinicians and researchers that patterns of ChEI therapy use differ by sex, as women were less likely to receive target therapeutic doses and more vulnerable to potentially problematic polypharmacy than men.


[Emollients: benefits, key elements, and clinical application].
The skin is the largest organ in the human body. Among other components, it contains epidermal cells, which are modified epithelial cells that rest on a basal membrane that separates them from the dermis. When the epidermis presents variations in its structural composition and the distribution of its elements, the result is the loss of large amounts of water, which perpetuates these variations and leads to permanent dehydration. Emollients are the first line of treatment for pathologies that affect the hydration of the skin, such as atopic dermatitis, which is one of the most important ones. This document entails the description of the epidermal barrier with its main components and functions, the characteristics of an altered skin barrier, and the mechanisms for its repair. Subsequently, this paper includes the definition of emollient, hydration mechanisms for the recovery of the barrier, types of emollients, the situations that must be taken into account when the use of emollients is prescribed, evidence with or without connection with their advantages, and the key points at the time of its formulation.


Gut microbiota in the short-beaked echidna (Tachyglossus Aculeatus) shows stability across gestation.
Indigenous gut microbial communities (microbiota) play critical roles in health and may be especially important for the mother and fetus during pregnancy. Monotremes, such as the short-beaked echidna, have evolved to lay and incubate an egg, which hatches in their pouch where the young feeds. Since both feces and eggs pass through the cloaca, the fecal microbiota of female echidnas provides an opportunity for vertical transmission of microbes to their offspring. Here, we characterize the gut/fecal microbiome of female short-beaked echidnas and gain a better understanding of the changes that may occur in their microbiome as they go through pregnancy. Fecal samples from four female and five male echidnas were obtained from the Currumbin Wildlife Sanctuary in Queensland and sequenced to evaluate bacterial community structure. We identified 25 core bacteria, most of which were present in male and female samples. Genera such as Fusobacterium, Bacteroides, Escherichia-Shigella, and Lactobacillus were consistently abundant, regardless of sex or gestation stage, accounting for 58.00% and 56.14% of reads in male and female samples, respectively. The echidna microbiome remained stable across the different gestation stages, though there was a significant difference in microbiota composition between male and female echidnas. This study is the first to describe the microbiome composition of short-beaked echidnas across reproductive phases and allows the opportunity for this novel information to be used as a metric of health to aid in the detection of diseases triggered by microbiota dysbiosis.


[Phase III open-label study of nepafenac ophthalmic suspension 0.1% for inflammation and ocular pain following ophthalmic surgery].
To examine the efficacy and safety of nepafenac ophthalmic suspension 0.1% on postoperative inflammation and eye pain with intraocular surgery, other than cataract surgery. Patients scheduled to undergo vitreous surgery, trabeculectomy, laser iridotomy, laser trabeculoplasty and laser posterior capsulotomy were investigated in a multicenter, open-label study. The total rate of patients cured in all the intraocular surgery methods was 85.6% (95/111), and that of the patients who were pain free was 91.0% (101/111). The rate cured by vitreous surgery was 80.4% (45/56), by laser iridotomy 93.3% (14/15) and by laser posterior capsulotomy was 94.6% (35/37). The rate of patients free from pain following vitreous surgery was 85.7% (48/56), laser iridotomy 100.0% (15/15) and by laser posterior capsulotomy was 94.6% (35/37). A total of 23 adverse events were reported in 22 patients (19.6%). Allergic conjunctivitis was observed in one patient (0.9%) as an adverse event, in which the relationship cannot be denied. This allergic conjunctivitis was mild and resolved after treatment. Nepafenac ophthalmic suspension 0.1% is considered safe and efficious not only following cataract surgery but also for postoperative inflammation and eye pain in intraocular surgery.


Further analysis of the short-term inhibition of food intake in humans by the dipeptide L-aspartyl-L-phenylalanine methyl ester (aspartame).
It was reported previously that the dipeptide sweetener aspartame suppresses food intake in humans by a postingestive action. The present study examined the hypothesis that this is due to an effect of phenylalanine, one of the primary breakdown products of aspartame (phenylalanine is a potent releaser of the so-called satiety hormone cholecystokinin, CCK). Capsulated aspartame (400 mg) administered to human volunteers reduced food intake by 15% (253 kcal) in a lunchtime test meal begun 1 hour later. However, neither phenylalanine (200 mg) nor the other constituent amino acid of aspartame, aspartic acid (200 mg), altered intake compared with placebo. Despite the large effect on food intake there were no treatment differences in pre- or postmeal ratings of motivation to eat. This suggests that aspartame may act to intensify the satiating effects of ingested food. Although high doses of phenylalanine reduce food intake, an individual action of phenylalanine cannot account for the potent anorexic effect of aspartame. In discussing alternative mechanisms it is noted that the amino acid sequence of aspartame (Asp-Phe) is the same as the C-terminal dipeptide of CCK. A direct action of aspartame at CCK receptors appears to be unlikely; however, aspartame might act as CCK releaser. Further studies are required to elucidate the mechanism of aspartame's anorexic action and perhaps to evaluate its therapeutic potential as an antiobesity agent.


When fragments link: a bibliometric perspective on the development of fragment-based drug discovery.
Fragment-based drug discovery (FBDD) is a highly interdisciplinary field, rich in ideas integrated from pharmaceutical sciences, chemistry, biology, and physics, among others. To enrich our understanding of the development of the field, we used bibliometric techniques to analyze 3642 publications in FBDD, complementing accounts by key practitioners. Mapping its core papers, we found the transfer of knowledge from academia to industry. Co-authorship analysis showed that university-industry collaboration has grown over time. Moreover, we show how ideas from other scientific disciplines have been integrated into the FBDD paradigm. Keyword analysis showed that the field is organized into four interconnected practices: library design, fragment screening, computational methods, and optimization. This study highlights the importance of interactions among various individuals and institutions from diverse disciplines in newly emerging scientific fields.


Protective effects of exercise on heart and aorta in high-fat diet-induced obese rats.
We investigated the protective effects of swimming exercise on high-fat diet-induced heart and aorta damage by evaluating oxidative stress and the endothelial nitric oxide (NO) system. Sprague Dawley rats were fed either standard chow (STD, 6% fat) or high-fat diet (HFD; 45% fat) for 18 weeks, with half of the animals trained by daily swimming sessions (EXC; 1 h per day for 5 days/week) for the last 6 weeks of the experimental period and half kept sedentary (SED). Heart and aorta tissues were prepared for routine light and electron microscopy evaluation. Endothelial NOS (eNOS) and inducible NOS (iNOS) distribution in the tissue samples were examined by immunohistochemistry. Biochemical examinations, including blood serum lipid profiles, malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and tissue NO levels were measured. Deteriorated heart and aorta morphology, increased MDA levels and iNOS-immunoreactivity (iNOS-ir), as well as decreased GSH, NO, SOD, and eNOS-ir parameters were observed in the HFD + SED group. These morphological and biochemical parameters were ameliorated in the HFD + EXC group. Our study revealed that obesity-induced iNOS activation and increased oxidative stress in cardiac and aorta tissues. Exercise protected the obesity-induced cardiac and aortic tissue damage by modulating oxidant/antioxidant balance via involvement of the NO system.


Whole-Body [18F]FDG PET/CT Can Alter Diagnosis in Patients with Suspected Rheumatic Disease.
The 2-deoxy-d-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is widely utilized to assess the vascular and articular inflammatory burden of patients with a suspected diagnosis of rheumatic disease. We aimed to elucidate the impact of [18F]FDG PET/CT on change in initially suspected diagnosis in patients at the time of the scan. Thirty-four patients, who had undergone [18F]FDG PET/CT, were enrolled and the initially suspected diagnosis prior to [18F]FDG PET/CT was compared to the final diagnosis. In addition, a semi-quantitative analysis including vessel wall-to-liver (VLR) and joint-to-liver (JLR) ratios was also conducted. Prior to [18F]FDG PET/CT, 22/34 (64.7%) of patients did not have an established diagnosis, whereas in 7/34 (20.6%), polymyalgia rheumatica (PMR) was suspected, and in 5/34 (14.7%), giant cell arteritis (GCA) was suspected by the referring rheumatologists. After [18F]FDG PET/CT, the diagnosis was GCA in 19/34 (55.9%), combined GCA and PMR (GCA + PMR) in 9/34 (26.5%) and PMR in the remaining 6/34 (17.6%). As such, [18F]FDG PET/CT altered suspected diagnosis in 28/34 (82.4%), including in all unclear cases. VLR of patients whose final diagnosis was GCA tended to be significantly higher when compared to VLR in PMR (GCA, 1.01 ± 0.08 (95%CI, 0.95-1.1) vs. PMR, 0.92 ± 0.1 (95%CI, 0.85-0.99), p = 0.07), but not when compared to PMR + GCA (1.04 ± 0.14 (95%CI, 0.95-1.13), p = 1). JLR of individuals finally diagnosed with PMR (0.94 ± 0.16, (95%CI, 0.83-1.06)), however, was significantly increased relative to JLR in GCA (0.58 ± 0.04 (95%CI, 0.55-0.61)) and GCA + PMR (0.64 ± 0.09 (95%CI, 0.57-0.71); p < 0.0001, respectively). In individuals with a suspected diagnosis of rheumatic disease, an inflammatory-directed [18F]FDG PET/CT can alter diagnosis in the majority of the cases, particularly in subjects who were referred because of diagnostic uncertainty. Semi-quantitative assessment may be helpful in establishing a final diagnosis of PMR, supporting the notion that a quantitative whole-body read-out may be useful in unclear cases.


Nanocarbon materials in water disinfection: state-of-the-art and future directions.
Water disinfection practices are critical for supplying safe drinking water. Existing water disinfection methods come with various drawbacks, calling for alternative or complementary solutions. Nanocarbon materials (NCMs) offer unique advantages for water disinfection owing to their high antimicrobial activity, often low environmental/human toxicity, and tunable physicochemical properties. Nevertheless, it is a challenge to assess the research progress made so far due to the structure and property diversity in NCMs as well as their different targeted applications. Because of these, here we provide a broad outline of this emerging field in three parts. First, we introduce the antimicrobial activities of the different types of NCMs, including fullerenes, nanodiamonds, carbon (nano)dots, carbon nanotubes, and graphene-family materials. Next, we discuss the current status in applying these NCMs for different water disinfection problems, especially as hydrogel filters, filtration membranes, recyclable aggregates, and electrochemical devices. We also introduce the use of NCMs in photocatalysts for photocatalytic water disinfection. Lastly, we put forward the key hurdles of the field that hamper the realization of the practical applications and propose possible directions for future investigations to address those. We hope that this minireview will encourage researchers to tackle these challenges and innovate NCM-based water disinfection platforms in the near future.


Antitumour, Antimicrobial, Antioxidant and Antiacetylcholinesterase Effect of Ganoderma Lucidum Terpenoids and Polysaccharides: A Review.
Ganoderma lucidum (Reishi) is a popular medicinal mushroom and has been used in oriental medicine because of its promoting effects on health and life expectancy. G. lucidum contains various compounds with a high grade of biological activty, which increase the immunity and show antitumour, antimicrobial, anti-inflammatory, antioxidant and acetylcholinesterase inhibitory activity. Several of these substances belong to the triterpenoids and polysaccharides classes. Proteins, lipids, phenols, sterols, etc. are also present. In the present review, an extensive overview of the presence of antitumour, antimicrobial, antioxidant and antiacetylcholinesterase compounds in G. lucidum extracts will be given, along with an evaluation of their therapeutic effects.


Dry textile electrode for ambulatory monitoring after catheter ablation of atrial fibrillation: A pilot study of simultaneous comparison to the Holter electrocardiogram.
Background: Holter electrocardiogram (ECG) is the gold standard for ambulatory monitoring of atrial fibrillation (AF) but it is insufficient because of its limited recording time. Although several consumer ECG devices provide longer recording time, they generally do not undergo the regulatory process for medical use. Furthermore, current medical-grade devices for longer ECG monitoring are not continuous or too invasive for AF monitoring. A wearable ECG with a medical-grade dry textile electrode is a promising technology to remedy this limitation. This pilot study aimed to simultaneously compare the wearable and Holter ECGs for ambulatory monitoring in a clinical setting. Methods: This prospective observational study enrolled 18 patients who underwent AF ablation. One day after AF ablation, ambulatory ECG was obtained for three hours simultaneously using both the wearable and Holter ECG devices. Automatic ECG interpretations between devices were compared with correlation and agreement analyses. Results: Simultaneous ECG monitoring demonstrated a comparable analysis time and total heart beats between the two devices. Almost complete correlation and agreement were also demonstrated in all clinically relevant testing aspects except in R-wave amplitude (r = 0.743, p < .001). AF was detected in three patients. AF duration was the same in both ECG devices in two patients with continuous AF. In the remaining patient with intermittent AF, AF duration was shortened by 0.6% with the wearable ECG as compared to that with the Holter ECG. Conclusions: Simultaneous ECG comparison revealed a high consistency between the wearable and Holter ECG devices. The results of this study warrant further clinical studies for long-term monitoring of ambulatory ECG after AF ablation.


D-optimal mixture design for optimization of topical dapsone niosomes: in vitro characterization and in vivo activity against Cutibacterium acnes.
This study aimed to illustrate the use of D-optimal mixture design (DOMD) for optimization of an enhancer containing Dapsone niosomal formula for acne topical treatment. Mixture components (MixCs) studied were: Span 20, Cholesterol, and Cremophor RH. Different responses were measured. Optimized formula (OF) was selected to minimize particle size and maximize absolute zeta potential and entrapment efficiency. Optimized formula gel (OF-gel) was prepared and characterized. OF-gel in vivo skin penetration using confocal laser scanning microscopy and activity against Cutibacterium acnes in acne mouse model were studied. Based on DOMD results analysis, adequate models were derived. Piepel and contour plots were plotted accordingly to explain how alteration in MixCs L-pseudo values affected studied responses and regions for different responses' values. The OF had suitable predicted responses which were in good correlation with the actually measured ones. The OF-gel showed suitable characterization and in vivo skin penetration up to the dermis layer. In vivo acne mouse-model showed that OF-gel-treated group (OF-gel-T-gp) had significantly better recovery (healing) criteria than untreated (UT-gp) and Aknemycin®-treated (A-T-gp) groups. This was evident in significantly higher reduction of inflammation percent observed in OF-gel-T-gp than both UT-gp and A-T-gp. Better healing in OF-gel-T-gp compared with other groups was also verified by histopathological examination. Moreover, OF-gel-T-gp and A-T-gp bacterial loads were non-significantly different from each other but significantly lower than UT-gp. Thus, DOMD was an adequate statistical tool for optimization of an appropriate enhancer containing Dapsone niosomal formula that proved to be promising for topical treatment of acne.


Protective effects of aucubin isolated from Eucommia ulmoides against UVB-induced oxidative stress in human skin fibroblasts.
Ultraviolet-B (UVB) irradiation has been demonstrated to produce reactive oxygen species (ROS) in the cells and skin, which induces the synthesis of matrix metalloproteinases (MMPs), causing skin photoaging. Using the human skin fibroblast HS68 cell line in the present study, we investigated the photoprotective effects of aucubin from Eucommia ulmoides. Pretreatment with aucubin significantly inhibited the production of MMP-1 by 57% when compared to the UVB-irradiated cells. Additionally, the senescence-associated beta-galactosidase (SA beta-gal) activity was markedly decreased in the presence of aucubin, which indicates it as an antiphoto-induced aging compound. As the effect of aucubin was determined against ROS, the inhibited ROS formation and malondialdehyde (MDA) levels, and the increased cell viability and glutathione (GSH) level were observed with aucubin under UVB irradiation. Based upon these results, it was suggested that aucubin might play an important role in the cellular defense mechanism against UV radiation-induced photoaging. An understanding of the antioxidant properties of aucubin could, in part, act to elucidate its protective mechanism on the human skin photoaging.


A Stratified Algorithm for Skull Base Reconstruction With Endoscopic Endonasal Approach.
The authors presented our institutional experience with skull base reconstruction techniques and developed a stratified algorithm for different causes of cerebrospinal fluid (CSF) leak. This is a retrospective review of patients who were diagnosed as CSF leak treated with skull base reconstruction or who underwent endoscopic transsphenoidal surgery for sellar and parasellar lesions at our department from August 2012 to April 2017. The authors totally identified 57 (59 operations in total) patients who were divided into 3 groups according to the causes of CSF leak and different reconstruction techniques. All patients underwent skull base reconstruction with specific focus on diagnosis, reconstruction techniques and strategies, and clinical outcome. The reconstruction technique we adopted was the classical multiple-layer technique, as known as "sandwich" technique, with combination of fat tissue, septal bone, autologous fascia lata, artificial dura, and nasoseptal flap (NSF). The NSF was selectively harvested for large defects according to our protocol. The reconstruction failure rate is 4.4% (2 of 45) in patients underwent endoscopic surgery for sellar and parasellar lesions. Reconstruction for postoperative iatrogenic, traumatic, and spontaneous CSF leak achieved 100% success rate; 54.2% (32 of 59) operations were done with "sandwich" plus NSF. The overall failure rate of all reconstructions was 3.4% (2 of 59). A stratified approach with multiple-layer technique and NSF is reliable for skull base reconstruction.


Acute gastrointestinal bleeding from a submucosal gastric mass.
We report a case of a 44-year-old male patient who presented with melena and hemodynamic instability. The endoscopic investigation of the upper and lower gastrointestinal tract was initially negative, but a repeat gastroduodenoscopy revealed a submucosal mass in the lesser curvature of the stomach with central erosion, primarily perceived as ectopic pancreas, but it was later discovered that it pertained to a gastrointestinal stromal tumor.


[Risk and benefits of disclosing a diagnosis of dementia].
While dementias represent an important problem of social health, they remained underdiagnosed. Data from the literature suggests that only 30% of cognitive impairment are detected and correctly evaluated, while most of the patient (up to 90%) and caregivers (up to 70-80%) ask for a precise diagnosis. Proper evaluation increase diagnostic accuracy from 30% to 80% but 20% of diagnoses remains inexact. Diagnostic disclosure seems to have a positive impact on patient's affective symptoms but is associated to an increase of suicide during the following 3 months, and thus must be a progressive and controlled process. Accompanying a patient in this process necessitates complexes competencies from the primary care physician. Difficulties related to this disclosure are counterbalanced by benefits for both patient and families.


Cytokines chattering in pancreatic ductal adenocarcinoma tumor microenvironment.
Pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) consists of multiple cell types interspersed by dense fibrous stroma. These cells communicate through low molecular weight signaling molecules called cytokines. The cytokines, through their receptors, facilitate PDAC initiation, progression, metastasis, and distant colonization of malignant cells. These signaling mediators secreted from tumor-associated macrophages, and cancer-associated fibroblasts in conjunction with oncogenic Kras mutation initiate acinar to ductal metaplasia (ADM), resulting in the appearance of early preneoplastic lesions. Further, M1- and M2-polarized macrophages provide proinflammatory conditions and promote deposition of extracellular matrix, whereas myofibroblasts and T-lymphocytes, such as Th17 and T-regulatory cells, create a fibroinflammatory and immunosuppressive environment with a significantly reduced cytotoxic T-cell population. During PDAC progression, cytokines regulate the expression of various oncogenic regulators such as NFκB, c-myc, growth factor receptors, and mucins resulting in the formation of high-grade PanIN lesions, epithelial to mesenchymal transition, invasion, and extravasation of malignant cells, and metastasis. During metastasis, PDAC cells colonize at the premetastatic niche created in the liver, and lung, an organotropic function primarily executed by cytokines in circulation or loaded in the exosomes from the primary tumor cells. The indispensable contribution of these cytokines at every stage of PDAC tumorigenesis makes them exciting candidates in combination with immune-, chemo- and targeted radiation therapy.


Mineralization of sulfonated azo dyes and sulfanilic acid by Phanerochaete chrysosporium and Streptomyces chromofuscus.
Five 14C-radiolabeled azo dyes and sulfanilic acid were synthesized and used to examine the relationship between dye substitution patterns and biodegradability (mineralization to CO2) by a white-rot fungus and an actinomycete. 4-Amino-[U-14C]benzenesulfonic acid and 4-(3-sulfo-4-aminophenylazo)-[U-14C]benzenesulfonic acid were used as representative compounds having sulfo groups or both sulfo and azo groups. Such compounds are not known to be present in the biosphere as natural products. The introduction of lignin-like fragments into the molecules of 4-amino-[U-14C]benzenesulfonic acid and 4-(3-sulfo-4-aminophenylazo)-[U-14C]benzenesulfonic acid by coupling reactions with guaiacol (2-methoxyphenol) resulted in the formation of the dyes 4-(3-methoxy-4-hydroxyphenylazo)-[U-14C]benzenesulfonic acid and 4-(2-sulfo-3'-methoxy-4'-hydroxy-azobenzene-4-azo)-[U-14C]benzenesulf oni c acid, respectively. The synthesis of acid azo dyes 4-(2-hydroxy-1-naphthylazo)-[U-14C]benzenesulfonic acid and 4-(4-hydroxy-1-naphthylazo)-[U-14C]benzenesulfonic acid also allowed the abilities of these microorganisms to mineralize these commercially important compounds to be evaluated. Phanerochaete chrysosporium mineralized all of the sulfonated azo dyes, and the substitution pattern did not significantly influence the susceptibility of the dyes to degradation. In contrast, Streptomyces chromofuscus was unable to mineralize aromatics with sulfo groups and both sulfo and azo groups. However, it mediated the mineralization of modified dyes containing lignin-like substitution patterns. This work showed that lignocellulolytic fungi and bacteria can be used for the biodegradation of anionic azo dyes, which thus far have been considered among the xenobiotic compounds most resistant to biodegradation.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunization rates of pneumococcal, influenza and tetanus vaccines and knowledge and attitudes of adult patients who receive inpatient treatment at hospital: Point prevalence study.
The safety of vaccines, access to health care, the level of community's knowledge and the attention of physicians play a critical role in the rate of adult vaccination. This study aims to determine the immunization rate of pneumococcal, influenza and tetanus vaccines among the patients and their knowledge and attitudes in the hospital. The study is a cross-sectional point prevalence survey. The patients who agreed to participate in the study were interviewed using a questionnaire. Patients' gender, occupation, educational status, income level and risk factors (immunosuppressed and over 65 years old) were compared with the knowledge and attitudes about vaccinations. Of the 251 participants, 51.4% were female and 48.6% were male. The self-reported vaccination rate was 3.5% for pneumococcal, 8.6% for influenza and 26.6% for tetanus. Most of the patients have knowledge about influenza vaccination (90.3%). Patients with the high education level have significantly higher knowlege about tetanus vaccination and higher rate of tetanus vaccine compared to those with low education level (p = 0.04; p = 0.006). It was found that those with higher income levels had the more pneumococcal vaccination, more knowledge on tetanus vaccination, and more attitude that tetanus vaccine is necessary compared to those with lower income level (p < 0.05). Patients without risk factors have a higher rate of tetanus vaccination compared to those with risk factors (p < 0.001). It was inferred that the high level of education and income have a positive effect on the patients vaccination rates and their knowledge and attitude.


Fluvoxamine prevents recurrence of depression: results of a long-term, double-blind, placebo-controlled study.
This double-blind placebo-controlled study specifically tested the efficacy of fluvoxamine, at a dose of 100 mg a day, in reducing the risk of new episodes of depression. Out of 436 patients treated openly with fluvoxamine 283 patients fulfilled stringent criteria to define responders at 6 weeks. A total of 204 patients maintained their remission throughout a continuation treatment period of 18 weeks and then entered the prophylactic study. They were randomly assigned to receive either fluvoxamine 100 mg a day or placebo for 1 year. There were significantly fewer recurrences of new episodes of depression in the fluvoxamine group compared with the placebo group (p < 0.001). The significant advantage for fluvoxamine was also seen in the Kaplan-Meier analysis of time to recurrence (p < 0.001). The clear-cut efficacy of 100 mg of fluvoxamine and the good tolerability and side-effect profile demonstrated in this study support the view that fluvoxamine is particularly suitable for maintenance or prophylactic treatment.


Ancient diversity of Afrotropical Microborus: three endemic species - not one widespread.
The primarily Neotropical genus Microborus Blandford is represented with three species in Africa and Madagascar. The previously recorded species from this region, M. boops Blandford, is a Neotropical species restricted to Central America and is likely not found in the Afrotropics. The previously recognised species in western parts of Africa is M. camerunus (Eggers) and is resurrected from synonymy under M. boops. Molecular and morphological data revealed a second species of this complex in Madagascar, M. brevisetosus Jordal. Another new species, M. angustus Jordal, co-occurs with M. camerunus in Cameroon. Substantial genetic divergence indicate that Microborus was established in the Afrotropical region long before human transport across oceans. A key to Afrotropical species is provided.


[Total knee arthroplasty in a patient with meniscal transplantation].
The natural history of a knee subjected to total meniscectomy leads to poor outcomes, so we should be careful with these lesions. Meniscal transplantation may be a proper treatment for these patients as it involves a good medium-term survival. We report the case of a 52 year-old male who underwent meniscal transplantation and developed left gonarthrosis. The surgical approach consisted of medial longitudinal arthrotomy and implantation of a posterior stabilized prosthesis after releasing the soft tissues, which were very retracted. At the one year follow-up the operated knee had an articular range of 0-110 degrees, with no gap and no pain; no external support was required for walking. Despite the fact that most case series report good short- and medium-term results, some patients do not have good results and need a total knee prosthesis.


[Change in the level of quality of life in end-stage kidney patients during a 12 months follow-up].
Among chronic diseases, end-stage kidney disease (ESRD) is distinguished for its negative impact on quality of life (QoL). This study intended to verify change of QoL in ESRD patients on hemodialysis during 12 months and identify factors associated with worsening or improvement of QoL. The sample comprised a cohort of 93 patients from a single hospital located in the State of Ceará, Brazil. The Medical Outcomes Study Questionnaire 36-Item Short Form Health Survey (SF-36) was administered in 2004 and 2005 to measure QoL in 8 dimensions and 2 components (physical and mental) scaled from 0 (worst) to 100 (best). The sample was stratified into three categories: no change, improvement and worsening of QoL according to physical and mental components. There was positive mean variation (improvement) of the score due to the dimension Role-emotional (36.0 +/- 40.1 vs. 57.0 +/- 45.7; p=0.004) and Mental Component (53.4 +/- 22.2 vs. 61.6 +/- 23.5; p=0.021). Patients with a negative variation (worsening) due to Mental Component had been on hemodialysis for less time when compared to patients with no change (36.4 +/- 32.9 vs. 74.0 +/- 54.8 months; p=0.008). In ESRD patients a longer time on hemodialysis was associated with improvement in mental aspects of QoL. Psychological adaptation, which occurs in other chronic diseases, could be the explanation of this outcome.


Assessment of intratumoral micromorphology for patients with clear cell renal cell carcinoma using susceptibility-weighted imaging.
Multiple treatment options exist for the management of renal cell carcinomas. Preoperative evaluation of clear cell renal cell carcinoma (CRCC) grades is important for deciding upon the appropriate method of therapy. We hypothesize that susceptibility weighted imaging (SWI) is sensitive enough to detect intratumoral microvessles and microbleeding in renal cell carcinoma, which can be used to grade CRCC. Retrospective reviews of 37 patients with pathologically proven CRCCs were evaluated. All patients underwent SWI examinations. The characteristics of intratumoral susceptibility signal intensity (ITSS) includes the likelihood of the presence of ITSS, morphology of ITSS, dominant structure of ITSS and ratio of ITSS area to tumor area, which were all assessed on SWI. The results were compared using the nonparametric Mann-Whitney test. ITSS was seen in all patients except 4 patients with low-grade CRCCs. There was no significant difference between low and high-grade CRCCs when looking at the likelihood of the presence of ITSS. There was a significant difference in the mean score of dominant structures between low and high-grade CRCCs. Specifically, more dominant vascular structures and less hemorrhage were seen in low-grade tumors (2.15±1.05) compared to high-grade tumors (1.27±0.47) (P<0.005). The ratio of ITSS area to tumor area was also significantly higher for the high-grade group (1.55±0.52) than that for the low-grade group (0.88±0.43) on SWI (P<0.005). SWI is useful for grading CRCCs.


The impact of broadband noise on serial memory: Changes in band-pass frequency increase disruption.
Irrelevant sound consisting of bursts of broadband noise, in which centre frequency changes with each burst, markedly impaired short-term memory for order. In contrast, a sequence of irrelevant sound in which the same band-pass noise burst was repeated did not produce significant disruption. Serial recall for both visual-verbal (Experiment 1) and visual-spatial items (Experiment 2) was sensitive to the increased disruption produced by changing irrelevant noise. The results provide evidence that sounds that are largely aperiodic can produce marked disruption of serial recall in a similar manner to periodic sounds (e.g., speech, musical streams, and tones), and thus show a changing-state effect.