Heart failure with reduced ejection fraction: comparison of patient characteristics and clinical outcomes within Asia and between Asia, Europe and the Americas.
Nearly 60% of the world's population lives in Asia but little is known about the characteristics and outcomes of Asian patients with heart failure with reduced ejection fraction (HFrEF) compared to other areas of the world. We pooled two, large, global trials, with similar design, in 13 174 patients with HFrEF (patient distribution: China 833, India 1390, Japan 209, Korea 223, Philippines 223, Taiwan 199 and Thailand 95, Western Europe 3521, Eastern Europe 4758, North America 613, and Latin America 1110). Asian patients were younger (55.0-63.9 years) than in Western Europe (67.9 years) and North America (66.6 years). Diuretics and devices were used less, and digoxin used more, in Asia. Mineralocorticoid receptor antagonist use was higher in China (66.3%), the Philippines (64.1%) and Latin America (62.8%) compared to Europe and North America (range 32.8% to 49.6%). The rate of cardiovascular death/heart failure hospitalization was higher in Asia (e.g. Taiwan 17.2, China 14.9 per 100 patient-years) than in Western Europe (10.4) and North America (12.8). However, the adjusted risk of cardiovascular death was higher in many Asian countries than in Western Europe (except Japan) and the risk of heart failure hospitalization was lower in India and in the Philippines than in Western Europe, but significantly higher in China, Japan, and Taiwan. Patient characteristics and outcomes vary between Asia and other regions and between Asian countries. These variations may reflect several factors, including geography, climate and environment, diet and lifestyle, health care systems, genetics and socioeconomic influences.


Cavernous haemangioma of the left nasal cavity.
Cavernous haemangioma of the nose is a rare lesion but it has to be added to the differential diagnosis of an intra-nasal bleeding mass. A high index of suspicion, upon computed tomography delineation of the extent of the mass, including the presence of bone remodelling plus histological evaluation can be usefully employed to define an accurate diagnosis. In the present case of an adult female with a huge cavernous haemangioma arising from the mucosa of the left middle nasal meatus, the two most interesting points were the rarity as a site of occurrence of this tumour and the successful extirpation of this lesion with the minimally invasive trans-nasal endoscopic technique. We recommend the minimal invasive trans-nasal endoscopic technique for adequate exposure, sufficient control of bleeding and for complete removal of a nasal haemangioma reaching the nasopharynx and paranasal sinuses.


The Saccharomyces cerevisiae Piccolo NuA4 histone acetyltransferase complex requires the Enhancer of Polycomb A domain and chromodomain to acetylate nucleosomes.
Chromatin modification complexes are key gene regulatory factors which posttranslationally modify the histone component of chromatin with epigenetic marks. To address what features of chromatin modification complexes are responsible for the specific recognition of nucleosomes compared to naked histones, we have performed a functional dissection of the Esa1-containing Saccharomyces cerevisiae Piccolo NuA4 histone acetyltransferase complex. Our studies define the Piccolo determinants sufficient to assemble its three subunits into a complex as well as Piccolo determinants sufficient to specifically acetylate a chromatin template. We find that the conserved Enhancer of Polycomb A (EPcA) homology region of the Epl1 component and the N-terminal 165 amino acids of the Yng2 component of Piccolo are sufficient with Esa1 to specifically act on nucleosomes. We also find that the Esa1 chromodomain plays a critical role in Piccolo's ability to distinguish between histones and nucleosomes. In particular, specific point mutations in the chromodomain putative hydrophobic cage which strongly hinder growth in yeast greatly reduce histone acetyltransferase activity on nucleosome substrates, independent of histone methylation or other modifications. However, the chromodomain is not required for Piccolo to bind to nucleosomes, suggesting a role for the chromodomain in a catalysis step after nucleosome binding.


Restoration of soft x-ray laser images of nanostructures.
We present advanced techniques for the restoration of images obtained by soft x-ray laser microscopy. We show two methods. One method is based on adaptive thresholding, while the other uses local Wiener filtering in the wavelet domain to achieve high noise gains. These wavelet based denoising techniques are improved using spatial noise modeling. The accurate noise model is built up from two consecutive images of the object and respective background images. To our knowledge, the results of both proposed approaches over-perform competitive methods. The analysis is robust to enable image acquisition with significantly lower exposure times, which is critical in samples that are sensitive to radiation damage as is the case of biological samples imaged by SXR microscopy.


The adolescent outcome of hyperactive girls: self-report of psychosocial status.
The aim of the study was to clarify the developmental risk associated with hyperactive behaviour in girls in a longitudinal epidemiological design. This was investigated in a follow-up study of girls who were identified by parent and teacher ratings in a large community survey of 6- and 7-year-olds as showing pervasive hyperactivity or conduct problems or the comorbid mixture of both problems or neither problem. They were later investigated, at the age of 14 to 16 years, with a detailed self-report interview technique. Hyperactivity was a risk factor for later development, even allowing for the coexistence of conduct problems. Hyperactivity predicted academic problems and interpersonal relationship problems. Relationships with parents, by contrast, were not portrayed to be as problematic as relationships with peers and the opposite sex. Their psychological, social and occupational functioning was objectively rated to be more deviant and their self-report showed them to be more ambivalent about their future. There was a trend for hyperactivity to be self-reported as a risk for the development of continuing symptomatology but neither hyperactivity nor conduct problems were self-reported to be a risk for antisocial behaviour, substance misuse or low self-esteem in adolescence. However, they were at risk for the development of state anxiety. The results suggested girls' pattern of functioning may differ from that of boys because girls self-report a more pervasive range of social dysfunction than that previously reported in boys.


Subarachnoid hemorrhage in a patient with Lyme disease.
Neuroborreliosis can cause a wide variety of seemingly unrelated neurologic abnormalities. Although the epidemiology, etiology, and pathology of this infection have been well documented, the pathogenesis and diagnosis continue to be problematic. In the current study we report a case of Lyme disease in which subarachnoid hemorrhage was the presenting feature of a patient with polyradiculoneuropathy and encephalopathy. Magnetic resonance imaging of the spine demonstrated diffuse pial and meningeal enhancement with more focal nodular areas of involvement.


Localized gray matter volume abnormalities in generalized anxiety disorder.
Generalized anxiety disorder (GAD) is characterized by excessive and persistent worrying. Neural substrates of this disorder are insufficiently understood, which relates to functional as well as to structural brain abnormalities. Especially, findings on the neuroanatomy of GAD have been inconsistent and were predominantly derived from pediatric samples. Therefore, we studied adult patients. Thirty-one women (16 patients with GAD and 15 healthy control participants) underwent structural MRI scanning. Gray matter volumes for specific brain regions involved in worrying, anticipatory anxiety, and emotion regulation were analyzed by means of voxel-based morphometry. Relative to controls, patients with GAD had larger volumes of the amygdala and the dorsomedial prefrontal cortex (DMPFC). Moreover, patients' self-reports on symptom severity were positively correlated with volumes of the DMPFC and the anterior cingulate cortex. Patients with GAD show localized gray matter volume differences in brain regions associated with anticipatory anxiety and emotion regulation. This abnormality may represent either a predisposition for GAD or a consequence of disorder-specific behavior, such as chronic worrying. This issue should be addressed in future MRI studies.


Feasibility of a radiation dose conserving CT protocol for myocardial function assessment.
Assessment of myocardial function can be performed at higher noise levels than necessary for coronary arterial evaluation. We evaluated image quality and radiation exposure of a dose-conserving function-only acquisition vs retrospectively electrocardiogram(ECG)-gated coronary CTA with automatic tube current modulation. Of 26 patients who underwent clinically indicated coronary CTA for coronary and function evaluation, 13 (Group I) underwent prospectively ECG-triggered coronary CTA, followed by low-dose retrospectively ECG-gated scan for function (128-slice dual-source, 80 kVp; reference tube current, 100 mA; 8-mm-thick multiplanar reformatted reconstructions) performed either immediately (n = 6) or after 5- to 10-min delay for infarct assessment (n = 7). 13 corresponding controls (Group II) underwent retrospectively ECG-gated protocols (automatic tube potential selection with CARE kV/CARE Dose 4D; Siemens Healthcare, Forchheim, Germany) with aggressive dose modulation. Image quality assessment was performed on the six Group I subjects who underwent early post-contrast dedicated function scan and corresponding controls. Radiation exposure was based on dose-length product. Contrast-to-noise ratio (CNR) was preserved throughout the cardiac cycle in Group I and varied according to dose modulation in Group II. Visual image quality indices were similar during end systole but were better in Group II at end diastole. Although the total radiation exposure was equivalent in Group I and Group II (284 vs 280 mGy cm), the median radiation exposure associated with only the dedicated function scan was 138 mGy cm (interquartile range, 116-203 mGy cm). A low-dose retrospective ECG-gated protocol permits assessment of myocardial function at a median radiation exposure of 138 mGy cm and offers more consistent multiphase CNR vs traditional ECG-modulation protocols. This is useful for pure functional evaluation or as an adjunct to single-phase scan modes. Radiation exposure can be limited with a tailored myocardial function CT protocol while maintaining preserved images.


Mixed messages: implications of social conflict and social support within close relationships for adjustment to a stressful life event.
The authors examined the impact of women's perceptions of negative (conflict) and positive (support) exchanges with their mothers, partners, and friends before having an abortion on negative (distress) and positive (well-being) indexes of adjustment after the abortion. Preabortion conflict and support from the partner predicted postabortion adjustment in the same affective domain: Conflict uniquely predicted distress, whereas support uniquely predicted well-being. Within-source interactions were observed between support and conflict from mothers and friends. Women who perceived high support from their mothers or friends were more distressed if they also perceived them as sources of high conflict than if they perceived them as sources of low conflict. Among women who perceived their mothers or friends as nonsupportive, no relationship was observed between conflict and distress. Cross-source buffering was not observed.


Resolution of ST-segment depression: A new prognostic marker in ST-segment elevation myocardial infarction.
To evaluate the prognostic impact of ST depression resolution among patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI in the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial. In this study, 4729 of 5745 patients had analysable ECGs demonstrating concomitant ST-segment depression. Resolution of summation operatorST elevation (STE-R) and summation operatorST depression (STD-R) on 30 min post-PCI ECGs was dichotomized into those with > or =50 vs. <50% ST-segment resolution. Overall, 1143 patients (24%) had STD-R<50%. These patients had higher risk characteristics including older age, female sex, diabetes, hypertension, prior CHF/MI, Killip class >I, triple vessel disease, and less frequent TIMI 3 flow in the culprit coronary vessel post-PCI. After multivariable adjustment and accounting for STE-R, STD-R<50% remained an independent predictor for 90 day death and the composite of death, cardiogenic shock, or CHF. When compared with patients with both STE-R and STD-R> or =50%, patients with both STE-R and STD-R<50% had the worst outcomes [hazard ratios (HR) 90 day death: 2.54; 95% confidence intervals (CI): 1.71-3.77; HR 90 day composite: 2.18; 95% CI: 1.63-2.91]. When ST depression is present in STEMI patients undergoing primary PCI, STD-R<50% provides independent prognostic value that is incremental to STE-R.


Potential role of the intestinal microbiota of the mother in neonatal immune education.
Mucosal dendritic cells are at the heart of decision-making processes that dictate immune reactivity to intestinal microbes. They ensure tolerance to commensal bacteria and a vigorous immune response to pathogens. It has recently been demonstrated that the former involves a limited migration of bacterially loaded dendritic cells from the Peyer's patches to the mesenteric lymph nodes. During lactation, cells from gut-associated lymphoid tissue travel to the breast via the lymphatics and peripheral blood. Here, we show that human peripheral blood mononuclear cells and breast milk cells contain bacteria and their genetic material during lactation. Furthermore, we show an increased bacterial translocation from the mouse gut during pregnancy and lactation and the presence of bacterially loaded dendritic cells in lactating breast tissue. Our observations show bacterial translocation as a unique physiological event, which is increased during pregnancy and lactation. They suggest endogenous transport of intestinally derived bacterial components within dendritic cells destined for the lactating mammary gland. They also suggest neonatal immune imprinting by milk cells containing commensal-associated molecular patterns.


Raloxifene decreases serum IGF-I in male patients with active acromegaly.
Most patients with acromegaly require additional treatments after trans-sphenoidal surgery. Although traditional methods of treatment aim at suppressing GH hypersecretion from the pituitary tumor, recent studies on the use of the GH receptor antagonist have shown that targeting the action of GH on peripheral tissues may be more effective. Estrogens and the selective estrogen receptor modulator tamoxifen have been used previously to suppress circulating IGF-I levels in patients with acromegaly. Positive effects of raloxifene in women with active acromegaly have been reported recently. This study was designed to examine the potential role of raloxifene in the treatment of acromegaly in male patients. We studied eight men with active acromegaly despite the fact that they were receiving traditional treatments. All subjects were treated with raloxifene (60 mg twice a day) for a median of 5 weeks. The effects of raloxifene on GH secretion were assessed by obtaining 24-h GH profiles and studying the response of GH to various stimuli before and after treatment with raloxifene. Serum IGF-I was measured before and after raloxifene treatment. Raloxifene did not affect basal GH secretion or response of GH to TRH, GHRH or glucose, but it decreased circulating IGF-I by 16+/-4% (P=0.001), and normalized plasma IGF-I in two patients. No changes in clinical parameters were observed. Prolactin levels, the prolactin response to TRH and free testosterone levels remained unchanged. Raloxifene was well tolerated. Raloxifene might be useful in the treatment of male patients with active acromegaly, but longer term studies are clearly needed.


Early effects of renal denervation in the anaesthetised rat: natriuresis and increased cortical blood flow.
A novel method of renal denervation was developed based on electro-coagulation of tissue containing most of the sympathetic fibres travelling towards the kidney. Kidney tissue noradrenaline was decreased to 4.7 % of the content measured in the contralateral innervated kidney when studied 3 days postdenervation. The method was utilised in anaesthetised rats to examine the effects of denervation within the heretofore unexplored first 75 min period postdenervation. Sodium excretion (UNaV) increased significantly (+82 %, P < 0.03) over the 25-50 min after denervation. In a parallel group, with a lower baseline UNaV, there was also a significant increase in UNaV (+54 %, P < 0.03) within the first 25 min. The renal perfusion pressure was maintained at a constant value and the glomerular filtration rate did not change after denervation. Renal cortical and medullary blood flows (CBF, MBF) were estimated as laser Doppler flux and medullary tissue ion concentration was estimated as electrical admittance (Y). Following denervation, in both groups CBF increased significantly within the first 25 min (+12 %, P < 0.01 and +8 %, P < 0.05, respectively) while MBF did not change or decreased slightly; Y did not change. The data document the development of natriuresis within the first 25-50 min after denervation. The increase in CBF indicated that, prior to denervation, the cortical, but not medullary, circulation was under a tonic vasoconstrictor influence of the renal nerves. Such a dissociation of neural effects on the renal cortical vs. medullary vasculature has not been previously described.


GaIN (Georgia Interactive Network for Medical Information) study on health professionals' search requests and continuing education needs.
Health sciences librarians are being called upon to be more proactive in their institutions' continuing education efforts. In an effort to identify whether search requests indicated CE needs, a study was conducted by a group of members of GaIN (Georgia Interactive Network for Medical Information). MEDLINE requests from health care professionals for subject specific clinical topics were collected during a six-month period via a standard search request form created for the study. Copies of all completed requests were collected and broad ICD-9 codes assigned to the search topics. Institutional reports were generated for each participating library to share with hospital CE coordinators. They were also compiled for the group as a whole, and reflected the "hottest" topics requested during the study period for physicians and for non-physicians (nurses, allied health, administrators). A survey to hospital librarians and CE educators showed some value in the reports, but greater potential for further collaboration between librarians and CE coordinators.


Altered localization of H-Ras in caveolin-1-null cells is palmitoylation-independent.
Caveolin-1 is a palmitoylated protein involved in the formation of plasma membrane subdomains termed caveolae, intracellular cholesterol transport, and assembly and regulation of signaling molecules in caveolae. Caveolin-1 interacts via a consensus binding motif with several signaling proteins, including H-Ras. Ras oncogene products function as molecular switches in several signal transduction pathways regulating cell growth and differentiation. Post-translational modifications, including palmitoylation, are critical for the membrane targeting and function of H-Ras. Subcellular localization regulates the signaling pathways engaged by H-Ras activation. We show here that H-Ras is localized at the plasma membrane in caveolin-1-expressing cells but not in caveolin-1-deficient cells. Since palmitoylation is required for trafficking of H-Ras from the endomembrane system to the plasma membrane, we tested whether the altered localization of H-Ras in caveolin-1-null cells is due to decreased H-Ras palmitoylation. Although the palmitoylation profiles of cultured embryo fibroblasts isolated from wild type and caveolin-1 gene-disrupted mice differed, suggesting that caveolin-1, or caveolae, play a role in the palmitate incorporation of a subset of palmitoylated proteins, the palmitoylation of H-Ras was not decreased in caveolin-1-null cells. We conclude that the altered localization of H-Ras in caveolin-1-deficient cells is palmitoylation-independent. This article shows two important new mechanisms by which loss of caveolin-1 expression may perturb intracellular signaling, namely the mislocalization of signaling proteins and alterations in protein palmitoylation.


Treating prison inmates with co-occurring disorders: an integrative review of existing programs.
The tremendous growth in state and federal correctional populations has focused greater attention on the needs of mentally ill and substance abusing inmates. Although an estimated 3-11% of prison inmates have co-occurring mental health (psychotic and major mood) disorders and substance abuse disorders, few treatment programs are described in the literature and there is little available information regarding effective treatment strategies for this population. The current study provides an integrative review of seven 'dual diagnosis' treatment programs that recently have been developed in state and federal prisons. Many of these have evolved from existing substance abuse treatment programs and approaches. Key program components include an extended assessment period, orientation/motivational activities, psychoeducational groups, cognitive-behavioral interventions such as restructuring of 'criminal thinking errors', self-help groups, medication monitoring, relapse prevention, and transition into institution or community-based aftercare facilities. Many programs use therapeutic community approaches that are modified to provide (a) greater individual counseling and support, (b) less confrontation, (c) smaller staff caseloads, and (d) cross-training of staff. Research is underway in three of the seven sites to examine the effectiveness of these new programs.


Metabolism of N-nitrosamines by cultured human and rat esophagus.
The metabolism of several N-nitrosamines (N-nitrosodimethylamine, N-nitrosoethylmethylamine, N-nitrosodiethylamine, N-nitrosobenzylmethylamine, and N-nitrosopyrrolidine) in cultured human and rat esophagus has been investigated by measuring (a) CO2, (b) metabolites with an oxo group, and (c) metabolites bound to DNA. Both acyclic and cyclic N-nitrosamines were metabolized by rat esophagus. The highest level of metabolite binding was seen with N-nitrosobenzylmethylamine, an organotrophic carcinogen for the rat esophagus. The binding level was about 100-fold higher than in human esophagus. This compound methylated rat esophageal DNA at positions 7 and O6 of guanine. The level of benzylation in rat was one-tenth of the level of methylation. Formation of benzaldehyde exceeded that of formaldehyde plus CO2 by a factor of six, indicating that the methylene group was preferentially oxidized. N-Nitrosoethylmethylamine, another unsymmetrical N-nitrosamine, was preferentially oxidized by rat esophagus in the ethyl group, as shown by higher formation of CO2 and acetaldehyde from the compound labeled in the ethyl group. The highest binding level to DNA from this compound was observed with the methyl group. No binding was detected to human esophagus. N-Nitrosopyrrolidine was oxidized by both rat and human esophagus in the alpha position, as measured by the formation of 2,4-dinitrophenylhydrazone derivative of 4-hydroxybutanal. Binding of metabolites of N-nitrosopyrrolidine to DNA was detected only in rat esophagus. As measured by the formation of both CO2 and formaldehyde, N-nitrosodimethylamine was metabolized by both human and rat esophagus. While most of the radioactivity associated with DNA was found to be incorporated into guanine and adenine, methylation of the guanine positions 7 and O6 was detected by chromatography of the hydrolyzed rat DNA. The results indicate significant quantitative and perhaps qualitative differences between cultured rat and human esophagus in their ability to activate N-nitrosamines, although unknown physiological differences after culture may contribute to this difference.


[Micromethod of ultracentrifugation in cesium chloride].
The micromethod of ultracentrifugation in cesium chloride is described. Band destributions have been analysed by the direct scanning of microtubes with the differential doublewave micro-spectrophotometer at 260 nm. The 10(-8)-10(-9) g of DNA or ribosomes are enough for one analysis, tube volume is 2 mul. The method described permits the simultaneous centrifugation of several probe scores. The error of the beyoant density determination is 0.001 g/sm3 relatively internal standard. DNA's from 5 types of Acetabularia were analysed by the developed technique.


Lead biosorption by waste biomass of Corynebacterium glutamicum generated from lysine fermentation process.
Biomass waste, mainly Corynebacterium glutamicum, is generated from large-scale lysine fermentation process. In this study, protonated C. glutamicum biomass was evaluated as a biosorbent for the removal of lead from synthetic wastewater. As Pb2+ were bound to the biomass, the solution pH deceased, indicating that protons in the biomass were exchanged with lead ions. The Corynebacterium biomass bound Pb2+ at up to 2.74 mmol g(-1) at pH 5, where lead does not precipitate. Compared with other biosorbents and conventional sorbents, such as natural zeolite, activated carbon and synthetic ion exchange resin, the protonated C. glutamicum biomass was considered to be a useful biomaterial for lead biosorption.


Mortality among 723,948 foreign- and native-born Swedes 1970-1999.
Mortality in a population is regarded as an accurate and valid measure of the population's health. There are a few international studies, predominantly cross-sectional, of mortality among all foreign-born compared with an indigenous population, and the results have varied. No Swedish longitudinal study describing and analysing mortality data was found in a literature review. This study describes and analyses the differences in mortality between foreign-born persons and native Swedes during the period 1970-1999, based on data from Statistics Sweden and the National Board of Health and Welfare. The database consisted of 723,948 persons, 361 974 foreign-born living in Sweden in 1970, aged > or = 16 years, and 361 974 Swedish controls matched for age, sex, occupation and type of employment, living in the same county in 1970. The results showed increased mortality for foreign-born persons compared with the Swedish controls [odds ratio (OR) 1.08; 95% confidence interval (CI) 1.07-1.08]. Persons who had migrated 'late' (1941-1970) to Sweden were 2.5 years younger at time of death than controls. In relation to country of birth, the highest risk odds were for men born in Finland (OR 1.21), Denmark (OR 1.11) and Norway/Iceland (OR 1.074). Age cohorts of foreign-born persons born between 1901 and 1920 had higher mortality at age 55-69 years than cohorts born between 1921 and 1944. Migrants had higher mortality than the native population, and migration may be a risk factor for health; therefore, this seems to be an important factor to consider when studying mortality and health.


Effects of speed on the hindlimb kinematics of the lizard dipsosaurus dorsalis
Lizards are the most diverse extant lineage of vertebrates believed to have retained the sprawling limb posture of ancestral tetrapods and, although the sprinting speeds of lizards are well documented, quantitative analyses of limb movements are lacking. We therefore examined a wide range of steady running speeds to quantify variation in the kinematics of a morphologically generalized hindlimb in the lizard Dipsosaurus dorsalis. From speeds of 50 to 350 cm s-1, stride length, step length and stride frequency all had significant curvilinear increases from 13.3 to 39.4 cm, from 8.9 to 12.8 cm and from 3.9 to 8.6 Hz, respectively, whereas duty factor (percentage of cycle when foot is on ground) decreased from 63 to 34 % with increased speed. For five standardized speeds ranging from 50 to 250 cm s-1, analyses of variance detected highly significant (P<0.001) effects of speed on 27 out of a total of 46 kinematic variables. The height of the hip at the time of footfall increased significantly with increased speed, whereas the amount of pelvic rotation in the horizontal plane (mean 36 degrees ) per stride was unaffected by speed. The orientation of the long axis of the foot changed by nearly 50 degrees with increased speed such that the foot was nearly straight forward at 250 cm s-1, and at high speeds the heel often did not touch the ground. The effective length of the limb at footfall nearly doubled with increased speed as a combined result of increased plantar flexion and knee extension and a more erect femur. The pervasive effects of speed on hindlimb kinematics observed for this species do not conform simply with previous generalizations of lizards as having plantigrade foot posture and sprawling limbs.


The incidence and implications of coccidioidouria.
To estimate the frequency and significance of isolating Coccidioides immitis from urine specimens, we reviewed the records of 75 patients with various forms of coccidioidomycosis of whom 29 had urine cultures for fungi. The 7 patients (24%) who had coccidioidouria appeared similar as a group to those whose cultured urine did not yield C. immitis. Over half of the patients had no other evidence of extrathoracic spread, and in 2 patients with coccidioidouria, illness resolved without treatment. Usually only a few colonies of the fungus were isolated from 200-ml specimens. Thus, our use of a concentrating technique and repeated sampling may account for the high incidence of coccidioidouria in this study. Isolating C. immitis from the urine may be helpful for diagnosis and should lead to further evaluation of the urinary tract for destructive parenchymal lesions. However, as an isolated finding, coccidioidouria does not always indicate the need for therapy.


In vitro leishmanicidal activity of monomeric and dimeric naphthoquinones.
A series of monomeric and dimeric naphthoquinones with potential for treatment of Leishmania infections was identified in vitro using both a direct cytotoxicity assay against extracellular promastigotes of Leishmania donovani, Leishmania infanturn, Leishmania enriettii, and Leishmania major and a test against intracellular amastigote L. donovani residing within murine macrophages. Several naphthoquinones proved to be active at concentrations in the microgram range (EC(50) 0.9-17.0 microg/ml). When tested against a panel of human cancer cell lines (KB, SKMel, A549, MDA) and murine bone marrow culture-derived macrophages (BMMPhi) as mammalian host cell controls, compounds with anti-Leishmania-activity showed moderate (EC(50)>25 microg/ml) to pronounced (EC(50)<10 microg/ml) toxic effects.


Attending rounds: microangiopathic hemolytic anemia with renal insufficiency.
The classification of thrombotic microangiopathy has evolved and expanded due to treatment and advances in understanding of the diseases associated with this clinical presentation. The three clinical forms of thrombotic microangiopathy-thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and disseminated intravascular coagulation-encompass a wide range of disorders that can be classified as either primary (idiopathic) or secondary to another identifiable disease or clinical context. Identification of an inhibitor to a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in the idiopathic and acute forms of TTP, recognition of the absence of ADAMTS13 inhibition in diarrheal HUS, identification of complement abnormalities in atypical HUS, and a better understanding of the role of plasma therapy, rituximab, and eculizumab therapy have all had a major effect on current understanding of the thrombotic microangiopathies. In this Attending Rounds, a patient with a thrombotic microangiopathy is presented, along with discussion highlighting the difficulty of differentiating TTP from HUS and disseminated intravascular coagulation, the need for a prompt diagnosis, and the role for plasma therapy in appropriately selected patients. The discussion attempts to provide a simple clinical approach to the diagnosis, treatment options, and future course of adults and children suffering from a thrombotic microangiopathy.


Duodenal perforation as presentation of gastric neuroendocrine tumour: A case report.
Neuroendocrine tumors (NETs) represent uncommon neoplasms with different characteristics. They can be asymptomatic and benign or they can also proliferate and manifest themselves with neoplastic mass symptoms such as intestinal occlusion or with carcinoid syndrome. Gastric neuroendocrine neoplasms (g-NENs) are the most frequent digestive NENs while duodenal neuroendocrine neoplasms (d-NENs) may be sporadic or associated with multiple endocrine neoplasia type 1 (MEN-1) and present a functional syndrome (e.g. gastrinoma with Zollinger-Ellison syndrome). We report a case of duodenal perforation due to a unknown gastrinoma responsible of Zollinger-Ellison Syndrome. He underwent an emergency contrast enhanced CT abdominal scan that showed a perforation. We performed a distal gastrectomy. The histopathological examination revealed a g-NET configuring a possible picture of Zollinger-Ellison Syndrome. The management of NETs is diffulcult and controversial because of their rarity. It is useful to know the pathologic assessment of tumor differentiation and/or grade, evaluate surgical resectability and control the carcinoid syndrome symptoms. This case report shows that gastric NETs can be found in cases of duodenal perforation. Our future goal is to evaluate the possibilities to diagnose the Zollinger Ellison Syndrome as early as possible and to treat it with targeted therapy in order to prevent its related complications.


The effect of shock loading on the performance of a thermophilic anaerobic contact reactor at constant organic loading rate.
The influences of organic loading disturbances on the process performance of a thermophilic anaerobic contact reactor treating potato-processing wastewater were investigated. For this purpose, while the reactor was operated at steady state conditions with organic loading rate of 5.5 kg COD/m(3) · day, an instant acetate concentration increase (1 g/L) was introduced to the reactor. During the shock loading test of acetate, it was observed that the overall process performance was adversely affected by all the shock loading, however, the system reached steady state conditions less than 24 hours of operation indicating that thermophilic anaerobic contact reactor is resistant to shock loading and be capable of returning its normal conditions within a short time period.


A posteriori dietary patterns: how many patterns to retain?
Principal component analysis (PCA) and cluster analysis are used frequently to derive dietary patterns. Decisions on how many patterns to extract are primarily based on subjective criteria, whereas different solutions vary in their food-group composition and perhaps association with disease outcome. Literature on reliability of dietary patterns is scarce, and previous studies validated only 1 preselected solution. Therefore, we assessed reliability of different pattern solutions ranging from 2 to 6 patterns, derived from the aforementioned methods. A validated food frequency questionnaire was administered at baseline (1993-1997) to 39,678 participants in the European Prospective Investigation into Cancer and Nutrition-The Netherlands (EPIC-NL) cohort. Food items were grouped into 31 food groups for dietary pattern analysis. The cohort was randomly divided into 2 halves, and dietary pattern solutions derived in 1 sample through PCA were replicated through confirmatory factor analysis in sample 2. For cluster analysis, cluster stability and split-half reproducibility were assessed for various solutions. With PCA, we found the 3-component solution to be best replicated, although all solutions contained ≥1 poorly confirmed component. No quantitative criterion was in agreement with the results. Associations with disease outcome (coronary heart disease) differed between the component solutions. For all cluster solutions, stability was excellent and deviations between samples was negligible, indicating good reproducibility. All quantitative criteria identified the 2-cluster solution as optimal. Associations with disease outcome were comparable for different cluster solutions. In conclusion, reliability of obtained dietary patterns differed considerably for different solutions using PCA, whereas cluster analysis derived generally stable, reproducible clusters across different solutions. Quantitative criteria for determining the number of patterns to retain were valuable for cluster analysis but not for PCA. Associations with disease risk were influenced by the number of patterns that are retained, especially when using PCA. Therefore, studies on associations between dietary patterns and disease risk should report reasons to choose the number of retained patterns.


New development on materials and techniques used in the heraldic designs of illuminated Manueline foral charters by multi-analytical methods.
In the illuminated foral charters commissioned by D. Manuel I, King of Portugal (1495-1521), heraldry played a prominent role. In this work, royal emblems corresponding to the third heraldic design, applied to the Charter of Couto de Teixedo, are studied by means of EDXRF, SEM-EDS, micro-Raman, micro-FTIR and HPLC-DAD to characterize the materials and techniques used to produce this masterpiece of Portuguese Renaissance. By comparing this data with the results previously obtained in other three charters, this research allows for the first time an accurate insight into the reformed manuscripts production, especially since the illuminated charters under consideration were all investigated on the basis of similar micro-spectroscopic techniques. Inks, metal coatings, pigments, organic dyes, fillers or extenders, and binding media are discussed, and their use enlightened by the politic and legal messages the foral charters had to convey. Parchment analysis allowed us to identify the animal species, and all undertaken processes along its preparation. HPLC-DAD allowed us to differentiate the gums used. CaSO4 was observed in the parchment as a degradation product of CaCO3 used in parchment production in the presence of metal sulfates coming from the ink. Pigments used in the different colors as well as some specific phases for some colors were identified. Silvering and gilding processes, metal caratage and silver oxidation compounds were also objects of the present study.


[Comparisons of epidemiological and clinical characteristics in children with hand-foot-mouth disease caused by Enterovirus 71 and Coxackievirus A16].
To compare the differences of epidemiological and clinical characteristics in children with hand-foot-mouth disease (HFMD) caused by Coxsackievirus A16 (CA16) and Enterovirus 71 (EV71). The samples of vesicle fluid and throat swabs of 108 children with HFMD were collected and detected for enterovirus by RT-PCR. The clinical data of children with EV71 and CA16 infection were retrospectively reviewed and compared. The total positive rate of enterovirus was 97.2% (105/108). Of the 105 cases, 56 cases were positive for EV71 (51.9%), 39 cases were positive for CA16 (36.1%), 2 cases were positive for other enterovirus (1.9%), and 8 cases were co-infected by EV71 and CA16 (7.4%). There were no significant differences in age and sex between EV71 and CV16 infected cases. The univariate analysis showed that the incidences of herpes of mouth, erythra of knees, and nose running in children infected by CA16 were higher than in those infected by EV71. The multivariate logistic regression analysis showed that the HFMD children who had erythra of knees had higher probability of CA16 infection. EV71 should be considered as the pathogen in children with HFMD who have no herpes of mouth, erythra of knees, and nose running.


Photoreceptor mutant of Drosophia: is protein involved in intermediate steps of phototransduction?
In norpA mutants of Drosophila melanogaster the phototransduction process is either partially or completely blocked. By using a temperature-sensitive allele, we have found that that norpA mutation has little or no effect on either the rhodopsin-metarhodopsin transition or the machinery of quantum bump production. Thus, the norpA lesion appears to be localized in the intermediate process of phototransduction. Because a temperature-sensitive allele of norpA has been isolated, the norpA gene probably encodes a protein involved in the process.


Container Type Affects Mosquito (Diptera: Culicidae) Oviposition Choice.
Larvae of container-breeding mosquitoes develop in a wide range of container habitats found in residential neighborhoods. Different mosquito species may exhibit preference for different container types and sizes. Due to phenological differences, species composition in container habitats may change over time. We first conducted weekly neighborhood container surveys to determine the types of container habitats found in residential neighborhoods, and to determine mosquito species composition over time within these habitats. We then conducted an oviposition choice field assay to determine whether female mosquitoes of different species preferentially oviposit in different container types commonly found in neighborhoods. Halfway through the experiment, the largest container was removed at half the sites to test the hypothesis that incomplete source reduction alters oviposition preference among the remaining containers. In the neighborhood surveys, large containers had the greatest mosquito densities and the highest species richness. Aedes albopictus (Skuse), the most commonly collected mosquito, was found in all container types. The oviposition experiment indicated that Culex spp. females preferentially oviposit in large containers. When the largest container was removed, the total number of egg rafts decreased. Aedes spp. females preferred to oviposit in large- and medium-sized containers, but the total number of eggs laid did not change when the large container was removed. These results confirm that understanding habitat preferences of container-breeding mosquitoes is important to control efforts targeting vector species and that incomplete removal of container habitats may have unpredictable consequences for the distribution of juveniles among remaining habitats.


Orlistat and L-carnitine compared to orlistat alone on insulin resistance in obese diabetic patients.
Our study wants to evaluate the effects of one year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight, glycemic and lipid control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). We observed a faster, and better decrease of body weight, HbA(1c), FPG, PPG, LDL-C, HOMA-IR with orlistat plus L-carnitine compared to orlistat. A faster improvement of TC, Tg, FPI, resistin, RBP-4, visfatin, and Hs-CRP was reached with orlistat plus L-carnitine compared to orlistat. We can safely conclude that the association of orlistat plus L-carnitine was better than orlistat in improving body weight, glycemic and lipid profile, insulin resistance, and inflammatory parameters and no significant adverse events were recorded.


Factors influencing arrival of patients with acute myocardial infarction at emergency departments: implications for community nursing interventions.
This paper identifies the characteristics of Greek patients with acute myocardial infarction who have long prehospital delays and identifies the factors that are specifically associated with these delays. The time between the first appearance of symptoms until the hospitalization of the patient with myocardial infarction correlates statistically significantly with in-hospital and long-term mortality. The study took place in two Greek coronary care units from 1 June 2007 to 31 July 2008. From 232 consecutive patients with myocardial infarction, 160 were enrolled. Data were collected by a trained hospital staff nurse, who interviewed all patients within 48 hours of hospital admission. Smokers arrived statistically significantly sooner at the hospital than non-smokers [smokers' prehospital time delay: 78.9 (sd = 3.2) minutes vs. non-smokers' prehospital time delay: 98.2 (sd = 4.1) minutes, Mann-Whitney U-test, Z = -2.5, P < 0.05]. Patients with hyperlipidaemia arrived with a mean delay of 13 minutes less than normolipidaemic patients. Those with inferior ST segment elevation myocardial infarction exhibited statistically significantly shorter delay times than those with anterior or lateral (inferior vs. anterior, P = 0.003, inferior vs. lateral, P = 0.024, anova with Bonferroni-Holm post hoc test, F = 7.5, P = 0.001). Community nurses should educate all patients about myocardial infarction, not only those at high risk but also those without known risk factors for ischaemic heart disease.


Arthroplasty by osteocartilaginous graft in primates.
Joint surface grafting has evolved from use of cadaveric materials preserved chemically and physically, to viable allogeneic and autogenic grafts in nearly a century of surgical history. Technical problems arising at the interface between foreign substances and living tissues has limited engineering arthroplasty such that a biological grafting process is eagerly sought. If successful with long periods of joint functioning, the scope of application to human victims of trauma, disease, and tumors of joints is wide. Whereas rabbits and dogs have been extensively used as models, primates have not. Whereas osteochondral allografts in Papio ursinus (the South African baboon) have been quite successful in hip, knee and shoulder joints, but the follow-up has been no more than a few years. Human autografts have been successful with periods of 10 and 15 years, but the present series is inadequate for statistical assessment. Further investigations of allografts and autografts in human joints are warranted.


Developing a Tool to Measure Person-Centered Care in Service Planning.
Background: Delivering person-centered care is a key component of health care reform. Despite widespread endorsement, medical and behavioral health settings struggle to specify and measure person-centered care objectively. This study presents the validity and reliability of the Person-Centered Care Planning Assessment Measure (PCCP-AM), an objective measure of the extent to which service planning is person-centered. Methods: Based upon the recovery-oriented practice of person-centered care planning, the 10-item PCCP-AM tool rates service plans on the inclusion of service user strengths, personal life goals, natural supports, self-directed actions and the promotion of community integration. As part of a large randomized controlled trial of person-centered care planning, service plans completed by community mental health clinic providers were rated using the PCCP-AM. Reliability was tested by calculating inter-rater reliability across 168 plans and internal consistency across 798 plans. To test concurrent validity, PCCP-AM scores for 84 plans were compared to expert rater scores on a separate instrument. Results: Interrater reliability for each of the 10 PCCP-AM items as measured by Kendall's W ranged from W = 0.77 to W = 0.89 and percent of scores within ± 1 point of each other ranged from 85.7 to 100%. Overall internal consistency as measured by Cronbach's alpha across 798 plans was α = 0.72. Concurrent validity as measured by Kendall's W ranged from W = 0.55 to W = 0.74 and percent of item scores within ± 1 point of expert rater scores ranged from 73.8 to 86.8%. Conclusions: Findings demonstrated that the 10-item PCCP-AM was a valid and reliable objective measure of person-centered care. Using the service plan as an indicator of multiple domains of person-centered care, the measure provides a valuable tool to inform clinical supervision and quality improvement across programs. More psychometric testing is needed to strengthen the measure for research purposes.


Assessment of vasodilator therapy in patients with severe congestive heart failure: limitations of measurements of left ventricular ejection fraction and volumes.
Although noninvasive techniques are often used to assess the effect of vasodilator therapy in patients with congestive heart failure, it is unknown whether changes in noninvasively determined left ventricular ejection fraction, volume, or dimension reliably reflect alterations in intracardiac pressure and flow. Accordingly, we compared the acute effect of sodium nitroprusside on left ventricular volume and ejection fraction (determined scintigraphically) with its effect on intracardiac pressure and forward cardiac index (determined by thermodilution) in 12 patients with severe, chronic congestive heart failure and a markedly dilated left ventricle. Nitroprusside (infused at 1.3 +/- 1.1 [mean +/- standard deviation] microgram/kg/min) caused a decrease in mean systemic arterial, mean pulmonary arterial, and mean pulmonary capillary wedge pressure as well as a concomitant increase in forward cardiac index. Simultaneously, left ventricular end-diastolic and end-systolic volume indexes decreased, but the scintigraphically determined cardiac index did not change significantly. Left ventricular ejection fraction averaged 0.19 +/- 0.05 before nitroprusside administration and increased by less than 0.05 units in response to nitroprusside in 11 of 12 patients. The only significant correlation between scintigraphically and invasively determined variables was that between the percent change in end-diastolic volume index and the percent change in pulmonary capillary wedge pressure (r = 0.68, p = 0.01). Although nitroprusside produced changes in scintigraphically determined left ventricular ejection fraction, end-systolic volume index, and cardiac index, these alterations bore no predictable relation to changes in intracardiac pressure, forward cardiac index, or vascular resistance. Furthermore, nitroprusside produced a considerably greater percent change in the invasively measured variables than in the scintigraphically determined ones.


Suppression of inflammatory corneal lymphangiogenesis by application of topical corticosteroids.
To analyze whether topical application of corticosteroids inhibits inflammatory corneal lymphangiogenesis and to study the potential underlying antilymphangiogenic mechanisms. Inflammatory corneal neovascularization was induced by suture placement, and the corneas were then treated with topical fluorometholone, prednisolone acetate, or dexamethasone sodium phosphate. After 1 week, the corneas were stained with lymphatic vessel endothelial hyaluronan receptor 1 for detection of pathological corneal lymphangiogenesis. The effect of these corticosteroids on macrophage recruitment was assessed via fluorescence-activated cell sorting analysis. The effect of these corticosteroids on proinflammatory cytokine expression by peritoneal exudate cells was tested via real-time polymerase chain reaction. Furthermore, the effect of steroid treatment on the proliferation of lymphatic endothelial cells was assessed via enzyme-linked immunosorbent assay. Treatment with corticosteroids resulted in a significant reduction of inflammatory corneal lymphangiogenesis. The antilymphangiogenic effect of fluorometholone was significantly weaker than that of prednisolone and dexamethasone. Corneal macrophage recruitment was also significantly inhibited by the application of topical steroids. Treatment of peritoneal exudate cells with corticosteroids led to a significant downregulation of the RNA expression levels of tumor necrosis factor and interleukin 1β. Additionally, proliferation of lymphatic endothelial cells was also inhibited. Corticosteroids are strong inhibitors of inflammatory corneal lymphangiogenesis, with significant differences between various corticosteroids in terms of their antilymphangiogenic potency. The main mechanism of the antilymphangiogenic effect seems to be through the suppression of macrophage infiltration, proinflammatory cytokine expression, and direct inhibition of proliferation of lymphatic endothelial cells. Steroids block corneal lymphangiogenesis, the main risk factor for immune rejections after corneal transplantation. The different antilymphangiogenic potency of these drugs should be taken into account when using steroids in clinical practice (eg, after keratoplasty).


Psychiatry and the death penalty.
Psychiatrists conducting forensic evaluations of defendants facing a potential death penalty must understand the legal and ethical parameters governing these assessments in addition to the important clinical issues. Important areas to review with each defendant include the role of the evaluator, the party requesting the evaluation, circumstances in which the evaluation is not confidential, the nature, scope, and purpose of the evaluation, and the parties to whom the results of the evaluation are to be forwarded. In those circumstances in which the defense attorney has not retained the psychiatrist, the defendant's attorney must be aware that an evaluation has been ordered by the court or requested by the prosecution. The psychiatrist also must be prepared for passionate challenges to their findings from the defense or prosecution and in some instances for vigorous attacks on their own personal ethics. To weather such storms, the mental health evaluator must base their opinion on objective evidence rather than letting any personal bias guide their assessment.


From ethnography to randomized controlled trial: an innovative approach to developing complex social interventions.
The evidence base for mental health social work is vastly under-developed in contrast to medicine and psychology. Without randomized controlled trial evidence of effectiveness, social work interventions are largely absent from UK clinical guidelines and are increasingly difficult to defend in multidisciplinary teams. This article will discuss an innovative and thorough approach to developing a social intervention which will be amenable to evaluation in a randomized controlled trial. Using ethnography to capture practice wisdom, underpinned by social capital theory with its own rich evidence base, the intervention will help people recovering from an episode of psychosis to connect, or reconnect, with other people. It is envisaged that by ensuring the intervention is grounded in the lived experience of workers and service users it will be more amenable to implementation in routine practice, and produce better outcomes.


Prevalence of Hepatitis C among Multi-transfused Thalassaemic Patients in Oman: Single centre experience.
Regular blood transfusions are essential for patients with thalassaemia major. However, infections with hepatotropic viruses remain a major concern. The objective of this study was to evaluate the prevalence and characteristics of hepatitis C viral (HCV) infection among patients with homozygous beta thalassaemia in a single centre in Oman. A retrospective chart review of 200 patients treated at the Thalassemia Unit of Sultan Qaboos University Hospital (SQUH) in Muscat, Oman, between August 1991 and December 2011 was performed. Relevant demographic and clinical characteristics were collected, including age, gender, HCV status and the presence of endocrinopathies. A total of 81 patients (41%) were found to be anti-HCV-antibody (anti-HCV)-positive. HCV ribonucleic acid tests were performed on 65 anti-HCV-positive patients and were positive among 33 (51%); the remaining 16 patients died before these tests were available. Anti-HCV-positive patients were significantly older than anti-HCV-negative patients (P <0.001) and were more likely to be diabetic than anti-HCV-negative patients (27% versus 8%; P <0.001). A total of 100 patients had been transfused before they were transferred to SQUH in 1991; of these, 70 (70%) were anti-HCV-positive. Only 11 (11.5%) of the 96 patients who were seronegative in 1991, or who were transfused later, became seropositive. It is likely that the high prevalence of HCV among multi-transfused thalassaemic patients in Oman is due to blood transfusions dating from before the implementation of HCV screening in 1991 as the risk of HCV-associated transfusions has significantly reduced since then. Additionally, results showed that anti-HCV-positive patients were more likely to be diabetic than anti-HCV-negative patients.


General resource for ionospheric transient investigations (GRITI): An open-source code developed in support of the Dinsmore et al. (2021) results.
The analysis techniques and the corresponding software suite GRITI (General Resource for Ionospheric Transient Investigations) are described. GRITI was used to develop the Dinsmore et al. [2] results, which found a novel classification of traveling ionospheric disturbances (TIDs) called semi-coherent ionospheric pulsing structures (SCIPS). The any-geographic range (local-to-global), any-azimuth angle keogram algorithm used to analyze SCIPS in that work is detailed. The keogram algorithm in GRITI is applied to detrended vTEC (vertical Total Electron Content) data, called delta-vTEC herein, in Dinsmore et al. [2] and the follow-on paper Dinsmore et al. [3], but is also applicable to any other two-dimensional dataset that evolves through time. GRITI's delta-vTEC processing algorithm is also described in detail, which is used to provide the delta-vTEC data for Dinsmore et al. [3]. •We detail a keogram algorithm for analysis of delta-vTEC data in Dinsmore et al. [2] and the follow-on paper Dinsmore et al. [3].•We detail a delta-vTEC processing algorithm that converts vTEC data to delta-vTEC through detrending that is used to provide the delta-vTEC data used in Dinsmore et al. [3].•GRITI is an open-source Python 3 analysis codebase that encompasses the delta-vTEC processing and keogram algorithms. GRITI has additional support for other data sources and is designed for flexibility in adding new data sources and analysis methods. GRITI is available for download at: https://github.com/dinsmoro/GRITI.


Patient derived renal cell carcinoma xenografts exhibit distinct sensitivity patterns in response to antiangiogenic therapy and constitute a suitable tool for biomarker development.
Systemic treatment is necessary for one third of patients with renal cell carcinoma. No valid biomarker is currently available to tailor personalized therapy. In this study we established a representative panel of patient derived xenograft (PDX) mouse models from patients with renal cell carcinomas and determined serum levels of high mobility group B1 (HMGB1) protein under treatment with sunitinib, pazopanib, sorafenib, axitinib, temsirolimus and bevacizumab. Serum HMGB1 levels were significantly higher in a subset of the PDX collection, which exhibited slower tumor growth during subsequent passages than tumors with low HMGB1 serum levels. Pre-treatment PDX serum HMGB1 levels also correlated with response to systemic treatment: PDX models with high HMGB1 levels predicted response to bevacizumab. Taken together, we provide for the first time evidence that the damage associated molecular pattern biomarker HMGB1 can predict response to systemic treatment with bevacizumab. Our data support the future evaluation of HMGB1 as a predictive biomarker for bevacizumab sensitivity in patients with renal cell carcinoma.


GSK3β Inhibition Prevents Macrophage Reprogramming by High-Dose Methotrexate.
Methotrexate (MTX) is an antifolate drug used as a chemotherapeutic agent for acute lymphoblastic leukemia, where MTX improves patients' prognosis. Macrophage reprogramming is being increasingly assessed as an antitumor therapeutic strategy. However, and although MTX limits the pathogenic action of macrophages in chronic inflammatory diseases, its effects on tumor-promoting macrophages have not been previously explored. We now report that MTX shapes the transcriptional and functional profile of M-CSF-dependent human macrophages, whose transcriptome is highly enriched in the gene signature that defines pathogenic tumor-associated macrophages ("large TAM"). Specifically, MTX prompted the acquisition of the gene signature of antitumoral "small TAM" and skewed macrophages toward an IL-6high IFNβ1high IL-10low phenotype upon subsequent stimulation. Mechanistically, the MTX-induced macrophage reprogramming effect correlated with a reduction of the M-CSF receptor CSF1R expression and function, as well as a diminished expression of MAF and MAFB transcription factors, primary determinants of pro-tumoral macrophages whose transcriptional activity is dependent on GSK3β. Indeed, the ability of MTX to transcriptionally reprogram macrophages toward an antitumoral phenotype was abrogated by inhibition of GSK3β. Globally, our results establish MTX as a macrophage reprogramming drug and indicate that its ability to modulate macrophage polarization may also underlie its therapeutic benefits. Since GSK3β inhibition abrogates the reprogramming action of MTX, our results suggest that the GSK3β-MAFB/MAF axis constitutes a target for the macrophage-centered antitumor strategies.


Non-invasive investigations of potential renal artery stenosis in renal insufficiency.
The diagnostic value of non-invasive methods for diagnosing renal artery stenosis in patients with renal insufficiency is incompletely known. Forty-seven consecutive patients with moderately impaired renal function and a clinical suspicion of renal artery stenosis were investigated with computed tomography angiography (CTA), gadolinium-enhanced magnetic resonance angiography (MRA), contrast-enhanced Doppler ultrasound and captopril renography. The primary reference standard was stenosis reducing the vessel diameter by at least 50% on CTA, and an alternative reference standard ('morphological and functional stenosis') was defined as at least 50% diameter reduction on CTA or MRA, combined with a positive finding from ultrasound or captopril renography. The frequency of positive findings, calculated on the basis of individual patients, was 70% for CTA, 60% for MRA, 53% for ultrasound and 30% for captopril renography. Counting kidneys rather than patients, corresponding frequencies were 53%, 41%, 29% and 15%, respectively. In relation to the CTA standard, the sensitivity (and specificity) at the patient level was 0.81 (0.79) for MRA, 0.70 (0.89) for ultrasound and 0.42 (1.00) for captopril renography, and at the kidney level 0.76 (0.82), 0.53 (0.81) and 0.30 (0.86), respectively. Relative to the alternative reference standard, corresponding values at the patient level were 1.00 (0.62) for CTA, 0.90 (0.69) for MRA, 0.91 (1.00) for ultrasound and 0.67 (1.00) for captopril renography, and at the kidney level 0.96 (0.76), 0.85 (0.79), 0.71 (0.97) and 0.50 (0.97), respectively. CTA and MRA are superior to ultrasound and captopril renography at diagnosing morphological stenosis, but ultrasound may be useful as a screening method and captopril renography for verifying renin-dependent hypertension.


Pericardial effusion associated with minoxidil therapy.
Pericardial effusions are occasionally observed in patients treated with the new oral vasodilator, minoxidil. Almost all of these cases are related to severe renal or congestive heart failure, but very rarely can be observed in patients without an identifiable cause. Such a case is reported herein, in which extensive investigation failed to reveal the cause. On further observation, the effusion subsided despite continuation of minoxidil therapy. Review of the literature suggests that pericardial effusion is uncommonly observed in patients treated with minoxidil unless accompanied by renal or cardiac failure, and that discontinuation of minoxidil therapy is not always indicated.


Risk factors and treatment of refractory anaphylaxis - a review of case reports.
Patients experiencing anaphylaxis who do not recover after treatment with intramuscular adrenaline are regarded as suffering from refractory anaphylaxis. The incidence of refractory anaphylaxis is estimated to range between 3-5% of anaphylaxis cases. The risk factors for refractory anaphylaxis are unknown. Areas covered: In the present analysis, we aimed to evaluate the management and risk factors of refractory anaphylaxis to highlight possible clinical implications for updating current management algorithms. Expert commentary: According to international guidelines, adrenaline given through the intramuscular (i.m.) route is a rapid and safe treatment but may be insufficient. Therefore, defined standardized treatment protocols for such cases of refractory anaphylaxis are needed to optimize the treatment. Point-of-care diagnostics may enable doctors to identify patients experiencing severe, refractory anaphylaxis early in order to initiate intensified critical care treatment.


Educators' working conditions in a day care centre on ownership of a non-profit organization.
Working conditions of nursery school teachers have not been scrutinized thoroughly in scientific research. Only a few studies have so far examined work-load and strain in this profession. Preferably, subjective perceptions should be corroborated by data that can be quantified more objectively and accurately. The aim of the present observational field study was to evaluate pedagogical staffs' workflow. In 2009 eleven educators in a day care centre were observed throughout three complete workdays. A total of 250 working hours were recorded. An educators' workday lasted on average 07:46:59 h (SD = 01:01:10 h). Within this time span, an average of 02:20:46 h (30.14%, SD = 00:28:07 h) were spent on caring, 01:44:18 h on playing (22.33%, SD = 00:54:12 h), 00:49:37 h on educational work (10.62%, SD = 00:40:09), and only 00:05:38 h on individual child contact (1.21%, SD = 00:04:58 h). For the first time, educators' workflow in day care centres was studied in real time. Some of the educators' self-reported problems were corroborated. The results of this study form a basis upon which further investigations can be built and measures can be developed for an overall improvement of child care.


[After the GEMINI-ACS-1 trial].
The GEMINI-ACS-1 trial has recently been published. It was designed to test whether low dose rivaroxaban as an antithrombotic agent is as safe as aspirin in patients with acute coronary syndromes (ACS). The trial is important to set light to future of ACS management.


Microfilariae of Brugia malayi contain a T cell mitogen.
We investigated the mechanisms that lead to polyclonal hypergammaglobulinemia in persons exposed to or infected with lymph-dwelling filarial parasites. Extracts of microfilariae of Brugia malayi induce the in vitro proliferation of lymphocytes from nonsensitized donors. The mitogenic factor(s) responsible for this effect is of low molecular weight (Mr) and acts on T4+ cells but not on T8+ T lymphocytes or on B cells. T4+ lymphocytes stimulated with filarial mitogen augment the in vitro production of immunoglobulins by autologous B lymphocytes.


Distribution in tissue and seasonal variation of norovirus genogroup I and II ligands in oysters.
Bivalve molluscan shellfish, such as oysters, filter large volumes of water as part of their feeding activities and are able to accumulate and concentrate different types of pathogens, particularly noroviruses, from fecal human pollution. Based on our previous observation of a specific binding of the Norwalk strain (prototype norovirus genogroup I) to the oyster digestive tract through an A-like carbohydrate structure indistinguishable from human blood group A antigen and on the large diversity between strains in terms of carbohydrate-binding specificities, we evaluated the different ligands implicated in attachment to oysters tissues of strains representative of two main genogroups of human norovirus. The GI.1 and GII.4 strains differed in that the latter recognized a sialic acid-containing ligand, present in all tissues, in addition to the A-like ligand of the digestive tract shared with the GI.1 strain. Furthermore, bioaccumulation experiments using wild-type or mutant GI.1 Viruslike particles showed accumulation in hemocytes largely, but not exclusively, based on interaction with the A-like ligand. Moreover, a seasonal effect on the expression of these ligands was detected, most visibly for the GI.1 strain, with a peak in late winter and spring, a period when GI strains are regularly involved in oyster-related outbreaks. These observations may explain some of the distinct epidemiological features of strains from different genogroups.


X-ray crystal structure of the yeast Kar3 motor domain complexed with Mg.ADP to 2.3 A resolution.
The kinesin family of motor proteins, which contain a conserved motor domain of approximately 350 amino acids, generate movement against microtubules. Over 90 members of this family have been identified, including motors that move toward the minus or plus end of microtubules. The Kar3 protein from Saccharomyces cerevisiae is a minus end-directed kinesin family member that is involved in both nuclear fusion, or karyogamy, and mitosis. The Kar3 protein is 729 residues in length with the motor domain located in the C-terminal 347 residues. Recently, the three-dimensional structures of two kinesin family members have been reported. These structures include the motor domains of the plus end-directed kinesin heavy chain [Kull, F. J., et al. (1996) Nature 380, 550-555] and the minus end-directed Ncd [Sablin, E. P., et al. (1996) Nature 380, 555-559]. We now report the structure of the Kar3 protein complexed with Mg.ADP obtained from crystallographic data to 2.3 A. The structure is similar to those of the earlier kinesin family members, but shows differences as well, most notably in the length of helix alpha 4, a helix which is believed to be involved in conformational changes during the hydrolysis cycle.


Complement (C1q) fixing solid-phase screening for HLA antibodies increases the availability of compatible platelet components for refractory patients.
Immune refractoriness to platelet (PLT) transfusion is primarily due to HLA antibody. Patients at our institution are identified as refractory due to HLA by a Luminex-based immunoglobulin (Ig)G-single-antigen-bead (SAB) assay, but in highly sensitized patients, antigen-negative compatible donors cannot be found due to the high sensitivity of the IgG-SAB method. We developed an assay that detects only HLA antibodies binding the first complement component (C1q). We hypothesized that the C1q-SAB method might be more relevant than the IgG-SAB method because the antibodies identified may activate the complement cascade causing PLT destruction. Thirteen highly sensitized refractory patients received 177 PLT units incompatible by the IgG-SAB method. They were retrospectively retested by the C1q-SAB method. Calculated percent reactive antibody (CPRA) and HLA antibody specificities were compared between the two methods and corrected count increment (CCI) values were analyzed. Additionally the impact of ABO compatibility on CCI responses was evaluated. The mean CPRA value was significantly lower by C1q-SAB (60%) than by IgG-SAB (94%; p < 0.05). Patients showed significantly better CCI (10.6 × 10(9) ± 0.8 × 10(9) /L) with C1q-compatible (n = 134) than with C1q-incompatible PLTs (n = 43) (2.5 × 10(9) ± 0.9 × 10(9) /L/m(2) ; p < 0.0001). ABO compatibility did not significantly impact the CCI values (p < 0.0001). Our results show that 75% of PLT units previously considered incompatible were actually compatible. For highly refractory patients to PLT transfusion, the C1q-based SAB binding assay may be a better method for identifying clinically relevant HLA antibodies and selecting PLT units that will result in acceptable CCI.


[Spiders and predatory mites in the canopies of organically managed Montenegrina tangerine trees, in Montenegro County, RS].
A survey was conducted to study the spider and predatory mite fauna occurring in the canopies of tangerine trees (Citrus deliciosa Tenore, cultivar Montenegrina) of an organically managed orchard, at Montenegro County, RS. During a year, fortnightly, 24 randomly trees were selected and sampled in two canopies areas, by using a sheet of white cloth (1 m(2)). A total of 3,129 arachnids were collected, being 2,559 spiders and 570 mites. Based on the adults, 53 species of Araneae were recognized, belonging to eight families. Among those, the most abundant were Sphecozone sp. (Linyphiidae) (21.8%) and Chrysso pulcherrima (Mello-Leitão) (Theridiidae) (9.9%). Autumn exhibited the greatest abundance of young and adults of Araneae (29.2%) and spring was the season richest in species (40). Margalef and Shannon-Wiener diversity indexes also showed the highest values in spring. The latter index did not show differences among seasons. Simpson complementary index was equal among seasons, reflecting the same degree of species dominance. In Acari, eight species were identified in three families. The most abundant species were the mites Leptus sp.1 (Erythraeidae) (59.4%) and Amblyseius saopaulus Denmark & Muma (Phytoseiidae) (30%). Autumn was the season richest in mite species (eight). The highest abundance (47%) was observed on winter and the lowest (0.88%) on summer. Among mites, Phytoseiidae showed the highest richness. Among the spiders, Anyphaenidae was the most abundant and Theridiidae had the highest species richness, following the patterns observed for the group.


Refinement of the Affordable Care Act: A Progressive Perspective.
The Affordable Care Act (ACA) was the most significant expansion of health coverage since Medicare and Medicaid were enacted. The law resulted in approximately 13-20 million uninsured persons gaining coverage. Despite these gains, the ACA has numerous shortcomings. For progressives, the ACA was a unique opportunity to provide access to high-quality, comprehensive, equitable health coverage to all persons living in the United States. Using this perspective as our framework, in this review we highlight some of the limitations of the ACA and potential areas for refinement. We conclude that the ACA fell far short of the goal of achieving universal coverage and that the coverage made available through the ACA was not equitable. In addition, the ACA expanded coverage by building onto a highly fragmented, inefficient, and costly health system. Thus, it did little to control health costs. A more fiscally prudent approach would have been built upon more successful existing programs, such as a Medicare for All.


Sexual and addictive risk behaviors and sexually transmitted infections in illegal gold miners in French Guiana: A multicenter observational study.
Common representations of the world of gold mining-especially illegal-are usually negative: the activity conjures up images of drug trafficking, human exploitation, the sex trade, environmental destruction, and infectious diseases, in particular sexually transmitted infections (STIs). The aim of the present article is to describe the levels of risk behaviors such as transactional sex, multiple sexual partners, and the frequency of condom use, addictive substance consumption, and the prevalence of STIs among the population of illegal gold miners in French Guiana (FG), a French overseas entity in Amazonia, in order to guide potential interventions. An observational multicenter cross-sectional study was carried out from October to December 2019 along the two borders of FG with Suriname and Brazil at rest sites used by the miners. Among the 499 participants, transactional sex was very prevalent, declared by 33.5% of men and 8.4% of women. Condoms were more frequently used for transactional sex than with a non-commercial partner (93.4% versus 42.1%). More women were tested for HIV than men (91.1% versus 55.2%). Excessive alcohol consumption (57.3%%) and tobacco use (41.2%) were very frequent, but cocaine or crack consumption was low (1.2%), which refuted our initial assumption. Consumers of alcohol had more sexual partners and reported condom use more frequently. Prevalence of HIV, HCV, HBV, and syphilis was respectively 0.5% (95% CI: 0.1-2.1), 2.1% (95% CI: 0.7-3.6), 1.6% (95% CI: 0.3-2.8), and 12.4% (95% CI: 9.0-15.7), which was higher than in the local population, especially for syphilis. This study documents for the first time the risk behaviors of gold miners in FG. Although the level of condom use was high, the prevalence of STIs combined with the high rate of transactional sex should encourage an increase in prevention and screening, in particular through rapid tests, given the mobility of the population concerned.


[Seroprevalence of cytomegalovirus infection in puerperal women and its impact on their newborns].
Cytomegalovirus (CMV) is the most frequent etiologic agent associated with perinatal infections. The incidence of this infection is higher in developing countries. The seroprevalence of CMV infection among pregnant women and its impact on newborns have not been studied in Panama and there are a few publications on this health problem in Latin America. The purpose of this study was to determine the seroprevalence of CMV infection in puerperal women and CMV-related morbidity in the neonates of seropositive mothers. A total of 316 blood samples from puerperal women and 317 urine samples from their newborns were obtained to determine CMV IgG and the polymerase chain reaction CMV test respectively. Risk factors such as parity, socioeconomic status and educational level were analyzed. The seroprevalence of CMV was 84 % and the incidence of congenital CMV infection in the newborns of seropositive women was 0.8 %. Two cases of congenital CMV infection were diagnosed, one of which showed clinical signs at birth, but neither of the newborns showed neurological or audiological sequels in the first 11 months of life. There were no correlations between positive serology and parity, socioeconomic status or educational level in the mothers studied. Although neither of the newborns diagnosed with congenital CMV infection showed clinical signs at the time of this report, we believe that the incidence of 0.8 % found in this study should be kept in mind with a view to evaluating the possibility of including CMV diagnostic tests in neonatal screening and introducing measures to prevent seronegative mothers from becoming infected.


Highly Deformable Origami Paper Photodetector Arrays.
Flexible electronics will form the basis of many next-generation technologies, such as wearable devices, biomedical sensors, the Internet of things, and more. However, most flexible devices can bear strains of less than 300% as a result of stretching. In this work, we demonstrate a simple and low-cost paper-based photodetector array featuring superior deformability using printable ZnO nanowires, carbon electrodes, and origami-based techniques. With a folded Miura structure, the paper photodetector array can be oriented in four different directions via tessellated parallelograms to provide the device with excellent omnidirectional light harvesting capabilities. Additionally, we demonstrate that the device can be repeatedly stretched (up to 1000% strain), bent (bending angle ±30°), and twisted (up to 360°) without degrading performance as a result of the paper folding technique, which enables the ZnO nanowire layers to remain rigid even as the device is deformed. The origami-based strategy described herein suggests avenues for the development of next-generation deformable optoelectronic applications.


Maturation of sympathetic neurotransmission in the rat heart. VII. Suppression of sympathetic responses by dexamethasone.
Effects of dexamethasone on development of sympathetic nerve function in the heart were evaluated by giving 1 mg/kg of dexamethasone s.c. daily for several days beginning the day after birth. Dexamethasone interfered with tyramine- and isoproterenol-induced tachycardia in the neonates but did not cause alterations in development of a marker for presynaptic sympathetic nerve terminals (synaptic vesicle uptake of [3H] norepinephrine) nor of postsynaptic beta adrenoceptor binding of [3H]dihydroalprenolol; the deficit was also unrelated to general cellular effects of the hormone. These data suggest that the subnormal chronotropic responses of the heart to sympathetic stimulation in dexamethasone-treated neonatal rats result from uncoupling of receptors from the organ response. The effects of dexamethasone on cardiac responses were specific to the neonate, as mature rats given dexamethasone did not show suppression of cardiac sympathetic action. Neonatal dexamethasone treatment also produced a deficit of adrenomedullary development with deficiencies in catecholamine levels and in catecholamine biosynthetic enzymes; deficits in phenylethanolamine N-methyltransferase activity persisted into young adulthood.


[Antilysozyme activity of microorganisms causing acute and chronic pyelonephritis].
Etiological structure of urine microflora was studied in patients with acute and chronic pyelonephritis. Gram-negative microorganisms dominated. Antilysozyme activity of 175 bacterial strains was studied. Detectability and potency of persisting potential were assessed regarding infectious-inflammatory process course. High antilysozyme activity of bacteria was revealed. This indicates potential ability of the bacteria to persist in the patients.


Synthesis, characterization and reactivity of single-site aluminium amides bearing benzotriazole phenoxide ligands: catalysis for ring-opening polymerization of lactide and carbon dioxide/propylene oxide coupling.
New aluminium complexes containing bis-BTP ligands (BTP = N,O-bidentate benzotriazole phenoxide) were synthesized and structurally characterized. Amine elimination of Al(NMe2)3 with (R)BTP-H ligands ((CMe2Ph)BTP-H = 2-(2H-benzotriazol-2-yl)-4,6-bis(1-methyl-1-phenylethyl)phenol, (t-Bu)BTP-H = 2-(2H-benzotriazol-2-yl)-4,6-di-tert-butylphenol and (TMCl)BTP-H = 2-tert-butyl-6-(5-chloro-2H-benzotriazol-2-yl)-4-methylphenol) (2.0 mol equiv.) in toluene or hexane afforded the penta-coordinated single-site amidoaluminium complexes [((R)BTP)2Al(NMe2)] (R = CMe2Ph for 1; R = t-Bu for 2; R = TMCl for 3) in satisfactory yields. With the addition of H2O (0.5 molar equiv.), the hydrolysis of Al amides 2 and 3 in a mixed solvent of THF/toluene at 25 °C produced oxo-bridged bimetallic aluminium complexes [{((R)BTP)2Al}2(μ-O)] (R = t-Bu for 4 and R = TMCl for 5) in ≥70% yield. According to single crystal X-ray diffraction studies, complex 2 shows a monomeric Al(iii) amide with bis((t-Bu)BTP) ligands and one -NMe2 group, whereas alumoxane 4 is a dinuclear species, in which the bonding mode of the Al-O-Al moiety from μ2-oxo assumes a linear type. Catalysis for ring-opening polymerization of lactide (LA) and CO2/propylene oxide (PO) coupling was systematically studied. Single-site Al amide 3 is an efficient initiator for LA polymerizations with a living character; the polymerization displays a first-order dependence on the concentration of l-LA. Bimetallic BTP-ligated alumoxane 5 is an active catalyst (TOF: 120 h(-1)) for the coupling of CO2 with PO in the presence of n-Bu4NBr to give propylene carbonate under mild conditions.


Analysis of the Health Information Needs of Diabetics in China.
According to the latest statistics of the China National Health Protection Commission, the prevalence of adult diabetics in China has reached 11.6%, and the number of patients has exceeded 114 million. Understanding the needs of diabetics and what kind of problems they are anxious about are crucial for doctors, hospitals and other health care providers, which can be used to ameliorate patient education services and help patients to improve their disease management skills. Hence we have conducted a study to analyze the questions about diabetes collected from a Chinese health website; the number of which is 151,589. We have divided these questions into 9 categories using a convolutional neural network. The shocking results showed that the questions about prevention only account for 1.23%. And a Chinese patented drug Xiaoke pill, the main component of which is glibenclamide, ranks fourth among the drugs the user cares most about due to the cheap price. However, patients know very little about its side effects.


Thalamic connections with limbic cortex. II. Corticothalamic projections.
The corticothalamic projections from the cat limbic cortex have been investigated with anterograde and retrograde axonal transport techniques. Five limbic cortical areas-the anterior limbic area, the cingular area, the granular and dysgranular retrosplenial areas, and the presubiculum-were identified on the basis of their cytoarchitecture. Emphasis was placed on determining the laminar distribution of the cells of origin of the efferent projections, the projection pathways, and the sites of termination within the thalamus. Projections to the thalamus originate in layers V and VI of limbic cortex. In the cingular region the cells of origin are predominantly in layer V and to a lesser extent in layer VI, while the majority of cells projecting from the more caudal retrosplenial areas and presubiculum are in layer VI. There are two fiber pathways from each cortical area to the thalamus. One system of fibers passes through the internal capsule and lateral thalamic peduncle, and a second system travels in the cingulate fasciculus before piercing the corpus callosum to join the postcommissural fornix. The lateral dorsal nucleus and the anterior nuclear group, including the anterior dorsal, anterior ventral, and anterior medial nuclei, are the major thalamic recipients of projections from limbic cortex. Corticothalamic projections also terminate sparsely in the midline and intralaminar nuclear complex, including the central lateral, central dorsal, paracentral, central medial, rhomboid, and reuniens nuclei. Projections from the anterior limbic area project predominantly to the anterior medial, central lateral, and paracentral nuclei. the anterior ventral nucleus, anterior medial nucleus, and lateral dorsal nucleus are the major thalamic recipients of projections from the cingular area, the granular and dysgranular retrosplenial areas, and the presubiculum. It appears that the anterior dorsal nucleus receives afferents only from the dysgranular retrosplenial area. Bilateral cortico-thalamic projections were found in the anterior medial, dorsal medial, central lateral, central medial, paracentral, and reuniens nuclei.


CLEC4F is an inducible C-type lectin in F4/80-positive cells and is involved in alpha-galactosylceramide presentation in liver.
CLEC4F, a member of C-type lectin, was first purified from rat liver extract with high binding affinity to fucose, galactose (Gal), N-acetylgalactosamine (GalNAc), and un-sialylated glucosphingolipids with GalNAc or Gal terminus. However, the biological functions of CLEC4F have not been elucidated. To address this question, we examined the expression and distribution of murine CLEC4F, determined its binding specificity by glycan array, and investigated its function using CLEC4F knockout (Clec4f-/-) mice. We found that CLEC4F is a heavily glycosylated membrane protein co-expressed with F4/80 on Kupffer cells. In contrast to F4/80, CLEC4F is detectable in fetal livers at embryonic day 11.5 (E11.5) but not in yolk sac, suggesting the expression of CLEC4F is induced as cells migrate from yolk cells to the liver. Even though CLEC4F is not detectable in tissues outside liver, both residential Kupffer cells and infiltrating mononuclear cells surrounding liver abscesses are CLEC4F-positive upon Listeria monocytogenes (L. monocytogenes) infection. While CLEC4F has strong binding to Gal and GalNAc, terminal fucosylation inhibits CLEC4F recognition to several glycans such as Fucosyl GM1, Globo H, Bb3∼4 and other fucosyl-glycans. Moreover, CLEC4F interacts with alpha-galactosylceramide (α-GalCer) in a calcium-dependent manner and participates in the presentation of α-GalCer to natural killer T (NKT) cells. This suggests that CLEC4F is a C-type lectin with diverse binding specificity expressed on residential Kupffer cells and infiltrating monocytes in the liver, and may play an important role to modulate glycolipids presentation on Kupffer cells.


Ant-inspired sorting by robots: the importance of initial clustering.
For engineers the prospect of scalable collective robot systems is very appealing. Such systems typically adopt a decentralized approach in their control and coordination mechanism, which employs local sensing and action as well as limited communication. Under these constraints and informed by research on Temnothorax ants, two puck sorting algorithms were tested in a combination of simulation and with real robots. Both algorithms employed puck density as a cue. Only the overall local density, irrespective of puck type, was found to be required which offers the prospect for a more simple mechanism than had been previously considered. For one algorithm, this density cue was used both for picking up and dropping items and is, therefore, referred to as the 'double density' algorithm (DD). In the second algorithm, density was used as a cue only for picking up. Depositing an item was governed by the distance travelled which was specific to the type of item being carried. This was referred to as the 'single density' algorithm (SD). Unlike the DD it was found that, for the SD, the clustering of items is a necessary pre-condition for sorting. Results from ant experiments also showed that sorting is carried out in two phases: a primary clustering episode followed by a spacing phase. This strongly suggests that clustering may also be a precondition for spacing in ants.


Modelling speed behaviour in rural highways: Safety analysis of driving under adverse road-weather conditions.
This study proposes a methodical approach to model desired speed distributions under different road-weather and traffic conditions followed by identification of road-weather conditions with potentially higher safety risks in rural divided highways located in extremely cold regions. Desired speed distributions encompassing unique combinations of adverse road-weather and traffic conditions are modelled as normal distributions characterized by their means and standard deviations formulated based on two principal statistical theorems and techniques i.e., Central Limit Theorem and Minimum Variance Unbiased Estimation. Combination of the precipitation conditions, road surface conditions, time of the day, temperature, traffic flow and the heavy vehicle percentage at the time of travel were considered in defining the combinations of road-weather and traffic conditions. The findings reveal that simultaneous occurrence of particular precipitation and pavement conditions significantly affect the characteristics of the desired speed distribution and potentially expose drivers to elevated safety risks. Jurisdictions experiencing extreme road-weather conditions may adapt the proposed methodology to assess speed behaviour under different road-weather conditions to establishing and deploying weather-responsive traffic management strategies such as variable speed limit to regulate speeding and improve traffic safety in winter.


Cryptococcus neoformans infections at Vancouver Hospital and Health Sciences Centre (1997-2002): epidemiology, microbiology and histopathology.
An outbreak of infections due to a rare subspecies of Cryptococcus neoformans (var. gattii) was recognized on Vancouver Island (VI), British Columbia, in 2002, which had affected 59, mostly immunocompetent, individuals since 1999. The objectives of this study were to: (1) determine if the outbreak had spread to Vancouver and its surrounding communities and (2) review the epidemiological, clinical and pathological features of all cryptococcal infections in patients admitted to the Vancouver Hospital and Health Sciences Centre (VHHSC) over a 5 year period. VHHSC microbiology and pathology databases were searched for cryptococcal infections from 1 June 1997 to 31 December 2002. Hospital charts of all identified patients were reviewed. Available cryptococcal isolates and histopathological specimens were reviewed. Twenty-six cases of cryptococcosis were identified in both HIV-positive (n = 15) and HIV-negative (n = 11) patients. C. neoformans var. grubii was cultured from 13 patients, of whom 10 were HIV-positive. The outbreak strain, C. neoformans var. gattii, was detected in three patients; all had travelled to VI. C. neoformans var. neoformans was cultured from two patients, Cryptococcus laurentii was cultured from one, and seven patients had cryptococcosis based on histopathology alone, without cultures. The majority (10/15) of the HIV-positive patients developed systemic disease whilst HIV-negative patients (8/11) presented with pulmonary cryptococcosis. Lung biopsies revealed necrotizing and/or fibrosing granulomas, with cryptococcal cells in 5 of 10 specimens. Brain biopsies showed cryptococcal organisms within leptomeninges and deeper structures with minimal associated inflammation. This retrospective study demonstrated a sharp increase in the total number of C. neoformans infections in both immunocompromised and immunocompetent patients at the VHHSC in 2002. There was no evidence of spread of the outbreak strain to the Greater Vancouver area. This is the first correlation of clinical and investigational findings of cryptococcosis in a region in North America where C. neoformans varieties gattii and grubii are endemic.


Evaluation of distinct freezing methods and cryoprotectants for human amniotic fluid stem cells cryopreservation.
Amniotic fluid (AF) was described as a potential source of mesenchymal stem cells (MSCs) for biomedicine purposes. Therefore, evaluation of alternative cryoprotectants and freezing protocols capable to maintain the viability and stemness of these cells after cooling is still needed. AF stem cells (AFSCs) were tested for different freezing methods and cryoprotectants. Cell viability, gene expression, surface markers, and plasticity were evaluated after thawing. AFSCs expressed undifferentiated genes Oct4 and Nanog; presented typical markers (CD29, CD44, CD90, and CD105) and were able to differentiate into mesenchymal lineages. All tested cryoprotectants preserved the features of AFSCs however, variations in cell viability were observed. In this concern, dimethyl sulfoxide (Me(2)SO) showed the best results. The freezing protocols tested did not promote significant changes in the AFSCs viability. Time programmed and nonprogrammed freezing methods could be used for successful AFSCs cryopreservation for 6 months. Although tested cryoprotectants maintained undifferentiated gene expression, typical markers, and plasticity of AFSCs, only Me(2)SO and glycerol presented workable viability ratios.


Stolonidiol: Synthesis, Target Identification, and Mechanism for Choline Acetyltransferase Activation.
Stolonidiol, a marine natural product, has been reported to potentiate the activity of choline acetyltransferase (ChAT), the enzyme that produces the neurotransmitter acetylcholine. Here we report the total synthesis of stolonidiol starting from (R)-(+)-limonene. To identify the mechanism by which ChAT activity is increased, we sought to identify the biological target of stolonidiol. We show that stolonidiol binds to the phorbol ester binding site of protein kinase C (PKC), induces translocation of PKC to the cell membrane, and activates kinase activity. Furthermore, we confirmed the increase in ChAT activity observed upon treatment of cells with stolonidiol and show that this effect is mediated by PKC. Collectively, our data strongly suggest that PKC activation by stolonidiol is responsible for the resulting potentiation of ChAT activity.


Influence of Preseason Antibodies Against Influenza Virus on Risk of Influenza Infection Among Healthcare Personnel.
The association of hemagglutination inhibition (HAI) antibodies with protection from influenza among healthcare personnel (HCP) with occupational exposure to influenza viruses has not been well-described. The Respiratory Protection Effectiveness Clinical Trial was a cluster-randomized, multisite study that compared medical masks to N95 respirators in preventing viral respiratory infections among HCP in outpatient healthcare settings for 5180 participant-seasons. Serum HAI antibody titers before each influenza season and influenza virus infection confirmed by polymerase chain reaction were studied over 4 study years. In univariate models, the risk of influenza A(H3N2) and B virus infections was associated with HAI titers to each virus, study year, and site. HAI titers were strongly associated with vaccination. Within multivariate models, each log base 2 increase in titer was associated with 15%, 26% and 33%-35% reductions in the hazard of influenza A(H3N2), A(H1N1), and B infections, respectively. Best models included preseason antibody titers and study year, but not other variables. HAI titers were associated with protection from influenza among HCP with routine exposure to patients with respiratory illness and influenza season contributed to risk. HCP can be reassured about receiving influenza vaccination to stimulate immunity.