Patent foramen ovale and stroke: prognosis and treatment in young adults.
A patent foramen ovale (PFO) is found with increased frequency in patients with stroke of undetermined origin but the significance and therapeutic implications of this observation remain unclear. Several lines of evidence suggest a role for the PFO in stroke pathophysiology for some cryptogenic stroke patients, such as those whose PFO is accompanied by a prothrombotic state, atrial septal aneurysm, or lower extremity/pelvic DVT. Diagnostic evaluation of the patient with cryptogenic stroke and PFO is directed at identifying these subgroups. Appropriate therapy for primary and secondary stroke prevention in a subject with a PFO remains unclear given current uncertainties as to the pathophysiological significance of PFO. Additional studies are needed, such as those focused on lower extremity veins or the cardiac interatrial septum, to guide therapy in specific stroke subpopulations.


Peer and adult companion helmet use is associated with bicycle helmet use by children.
To examine whether the helmet status of riding companions (child or adult) influences helmet use by children (5-14 years). This study is part of a larger prospective observational survey that was conducted in a defined urban region of Toronto, Canada (1990-1997, 1999, and 2001). Trained observers collected data on children who were riding bicycles in April through October each year. Observation sites included school yards, parks, major intersections, and residential streets. Of the 2094 children who were observed riding a bicycle, 50% were riding alone, 36% were riding with at least 1 child companion, and 14% were riding with at least 1 adult companion. Compared with riding alone, children were less likely to wear a helmet when riding with nonhelmeted child companions (relative risk [RR]: 0.29; 95% confidence interval [CI]: 0.22-0.38) and were more than twice as likely to wear a helmet when riding with either helmeted child (RR: 2.18; 95% CI: 1.97-2.42) or adult companions (RR: 2.67; 95% CI: 2.44-2.93). Compared with children who were riding with nonhelmeted child companions, children were more likely to wear a helmet when riding with nonhelmeted adults (RR: 3.93; 95% CI: 2.86-5.40), helmeted adults (RR: 9.18; 95% CI: 7.04-11.98), or helmeted children (RR: 7.49; 95% CI: 5.72-9.82). Adjusted analyses showed no difference between companion helmet status and helmet use by children before and after legislation. Helmeted and nonhelmeted adult riding companions were positively associated with child helmet use. The association between child riding companions and child helmet use was positive for helmeted child riding companions and negative for nonhelmeted child riding companions. Efforts need to be made toward improving adult helmet use and children's perceptions and attitudes toward helmet use.


Dural arteriovenous fistula presenting with stroke-like symptoms and regional cerebral hyperperfusion: a case report.
Non-hemorrhagic focal neurological deficit is one of the clinical manifestations of intracranial dural arteriovenous fistulas (DAVF). When symptoms appear suddenly, it is difficult to distinguish it from ischemic stroke in certain circumstances, which might easily lead to misdiagnosis. Here, we report a rare case of DAVF with sudden onset sensory aphasia mimicking hyperacute stroke but presented with unexpected regional hyperperfusion on the site corresponding to its symptoms. A 76-year-old male with histories of atrial fibrillation and hypertension was admitted to the emergency department due to sudden sensory aphasia. The diagnosis of ischemic stroke was made based on clinical experience after non-contrast CT excluding hemorrhage. As in the absence of clear contraindication, the patient received intravenous thrombolysis. On the cerebral CT perfusion, the left temporal lobe, where the sensory speech center is located, was manifested as regional hyperperfusion. Thrombolysis was subsequently halted, but scheduled cranial imaging indicated hemorrhagic transformation. According to the radiological hint from cranial MRI, the patient was suspected of having DAVF, which was finally confirmed by cerebral digital subtraction angiography. When DAVF is presented as sudden onset focal neurological deficit, cranial CT perfusion at an early stage might reveal an abnormal hyperperfusion pattern. Clinicians should be aware of the diagnostic possibility of DAVF in this situation and double-review the CT angiography image to reduce missed diagnoses.


Efficient diagnosis of hematologic malignancies using bone marrow microscopic images: A method based on MultiPathGAN and MobileViTv2.
Hematologic malignancies, including the associated multiple subtypes, are critically threatening to human health. The timely detection of malignancies is crucial for their effective treatment. In this regard, the examination of bone marrow smears constitutes a crucial step. Nonetheless, the conventional approach to cell identification and enumeration is laborious and time-intensive. Therefore, the present study aimed to develop a method for the efficient diagnosis of these malignancies directly from bone marrow microscopic images. A deep learning-based framework was developed to facilitate the diagnosis of common hematologic malignancies. First, a total of 2033 microscopic images of bone marrow analysis, including the images for 6 disease types and 1 healthy control, were collected from two Chinese medical websites. Next, the collected images were classified into the training, validation, and test datasets in the ratio of 7:1:2. Subsequently, a method of stain normalization to multi-domains (stain domain augmentation) based on the MultiPathGAN model was developed to equalize the stain styles and expand the image datasets. Afterward, a lightweight hybrid model named MobileViTv2, which integrates the strengths of both CNNs and ViTs, was developed for disease classification. The resulting model was trained and utilized to diagnose patients based on multiple microscopic images of their bone marrow smears, obtained from a cohort of 61 individuals. MobileViTv2 exhibited an average accuracy of 94.28% when applied to the test set, with multiple myeloma, acute lymphocytic leukemia, and lymphoma revealed as the three diseases diagnosed with the highest accuracy values of 98%, 96%, and 96%, respectively. Regarding patient-level prediction, the average accuracy of MobileViTv2 was 96.72%. This model outperformed both CNN and ViT models in terms of accuracy, despite utilizing only 9.8 million parameters. When applied to two public datasets, MobileViTv2 exhibited accuracy values of 99.75% and 99.72%, respectively, and outperformed previous methods. The proposed framework could be applied directly to bone marrow microscopic images with different stain styles to efficiently establish the diagnosis of common hematologic malignancies.


Assessing the inundation dynamics and its impacts on habitat suitability in Poyang Lake based on integrating Landsat and MODIS observations.
Poyang Lake, the largest freshwater lake in China, serves critical ecosystem function for water regulation and biodiversity conservation. However, it experienced dramatic changes in lake inundation due to recent climate change and human activities, causing ecological and economic problems. Here, we applied a multiple-index water detection rule to integrated Landsat and MODIS products to reconstruct surface water series at 30-m and 8-day resolutions and quantified the spatio-temporal inundation dynamics in Poyang Lake over the past 20 years (2000-2019). Furthermore, their influences on habitat suitability for herbivorous birds were also assessed from the perspectives of hydroperiod and vegetation growth threshold. The significant declining trend (-26.66 km2 yr-1, p < 0.001) for the annual minimum water areas throughout the 20 years implied that Poyang Lake was undergoing a continuous shrinkage in the low-water season. On the monthly scale, inundation frequency (IF) decreases were more significant in September-January, most of which occurred in the alluvial delta zones near the lake center. The altered water regime after the Three Gorges Dam (TGD) might be the dominant contributor responsible for the continuous lake shrinkage during the recent low-water period. The sub-lakes suffered from spring drought rather than winter drought, triggering vegetation successions regarding the reversed trend of the well-documented xerophilization in Poyang Lake. The recent earlier and prolonged dry seasons caused an increase of suitable habitat for herbivorous birds (13.92 km2 year-1, p < 0.1), but triggered a potential risk of food quality degradation when the migratory waterbirds peaked in December. These results provide a clear reference for optimizing the hydrologic management and biodiversity conservation of Poyang Lake.


Bioactive role of plant stress hormone methyl jasmonate against lipopolysaccharide induced arthritis.
The current investigation was carried out to screen antiarthritic potential of Methyl Jasmonate (MJ) against lipopolysaccharide (LPS) induced arthritis. Cartilage damage was induced in experimental animals by intraplantar administration of LPS (1 mg/kg) and antiarthritic effect of MJ was screened in two doses of MJ-1 (20 mg/kg), MJ-2 (40 mg/kg) by intraperitoneally administration. Indomethacin (30 mg/kg p.o.) was used as standard drug. The severity of arthritis was evaluated by assessing arthritis score, secondary lesions, motility test, stair climbing ability, and dorsal flexion pain score method. The estimation of blood cytokine tumor necrosis factor- aplha (TNF-α),interleukine (IL-2 and IL-6) and thymus/spleen index was carried out to access the severity of inflammation. Estimation of hepaticenzymatic antioxidant activity superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx)and radiological examination was carried out on 28th day. Results indicated that MJ showed significant reduction in severity of arthritis by decreasing arthritis score, secondary lesions where as significant increase in motility, climbing ability and flexion pain score was observed. Significant decreased in blood cytokine viz. TNF-α, IL-2, IL-6 andthymus/spleen index was observed in MJ treated animals in dose dependent manner. MJ treated animals showed significant increased and restoration of hepatic antioxidant enzymatic activityof SOD, CAT, GSH, GPx where asradiological examination indicates protective effect on joint structure as compared to LPS treated rats. These current studies conclude that MJ has protective role in arthritis.


Tracked ultrasound snapshots in percutaneous pedicle screw placement navigation: a feasibility study.
Computerized navigation improves the accuracy of minimally invasive pedicle screw placement during spine surgery. Such navigation, however, exposes both the patient and the staff to radiation during surgery. To avoid intraoperative exposure to radiation, tracked ultrasound snapshots-ultrasound image frames coupled with corresponding spatial positions-could be used to map preoperatively defined screw plans into the intraoperative coordinate frame. The feasibility of such an approach, however, has not yet been investigated. Are there vertebral landmarks that can be identified using tracked ultrasound snapshots? Can tracked ultrasound snapshots allow preoperative pedicle screw plans to be accurately mapped--compared with CT-derived pedicle screw plans--into the intraoperative coordinate frame in a simulated setting? Ultrasound visibility of registration landmarks was checked on volunteers and phantoms. An ultrasound machine with integrated electromagnetic tracking was used for tracked ultrasound acquisition. Registration was performed using 3D Slicer open-source software (www.slicer.org). Two artificial lumbar spine phantoms were used to evaluate registration accuracy of pedicle screw plans using tracked ultrasound snapshots. Registration accuracy was determined by comparing the ultrasound-derived plans with the CT-derived plans. The four articular processes proved to be identifiable using tracked ultrasound snapshots. Pedicle screw plans were registered to the intraoperative coordinate system using landmarks. The registrations were sufficiently accurate in that none of the registered screw plans intersected the pedicle walls. Registered screw plan positions had an error less than 1.28 ± 1.37 mm (average ± SD) in each direction and an angle difference less than 1.92° ± 1.95° around each axis relative to the CT-derived positions. Registration landmarks could be located using tracked ultrasound snapshots and permitted accurate mapping of pedicle screw plans to the intraoperative coordinate frame in a simulated setting. Tracked ultrasound may allow accurate computer-navigated pedicle screw placement while avoiding ionizing radiation in the operating room; however, further studies that compare this approach with other navigation techniques are needed to confirm the practical use of this new approach.


Clopidogrel Markedly Increases Plasma Concentrations of CYP2C8 Substrate Pioglitazone.
The glucose-lowering drug pioglitazone undergoes hepatic CYP2C8-mediated biotransformation to its main metabolites. The antiplatelet drug clopidogrel is metabolized to clopidogrel acyl-β-d-glucuronide, which was recently found to be a strong time-dependent inhibitor of CYP2C8 in humans. Therefore, we studied the effect of clopidogrel on the pharmacokinetics of pioglitazone. In a randomized crossover study, 10 healthy volunteers ingested either 300 mg of clopidogrel on day 1, and 75 mg on days 2 and 3, or placebo. Pioglitazone 15 mg was administered 1 hour after placebo and clopidogrel on day 1. Plasma concentrations of pioglitazone, clopidogrel, and their main metabolites were measured up to 72 hours. Clopidogrel increased the area under the plasma concentration-time curve (AUC0-∞) of pioglitazone 2.1-fold [P < 0.001, 90% confidence interval (CI) 1.8-2.6] and prolonged its half-life from 6.7 to 11 hours (P = 0.002). The peak concentration of pioglitazone was unaffected but the concentration at 24 hours was increased 4.5-fold (range 1.6-9.8; P < 0.001, 90% CI 3.17-6.45) by clopidogrel. The M-IV-to-pioglitazone AUC0-∞ ratio was 49% (P < 0.001, 90% CI 0.40-0.59) of that during the control phase, indicating that clopidogrel inhibited the CYP2C8-mediated biotransformation of pioglitazone. Clopidogrel increases the exposure to pioglitazone by inhibiting its CYP2C8-mediated biotransformation. In consequence, use of clopidogrel may increase the risk of fluid retention and other concentration-related adverse effects of pioglitazone.


Tetraglyme-mediated synthesis of Pd nanoparticles for dehydrogenation of ammonia borane.
Palladium nanoparticles (PdNPs) were conveniently prepared in tetraglyme (TG) solution using a variety of palladium precursors. At 140 °C, TG promoted Pd(3)(OAc)(6) to produce irregular shaped PdNPs with an average size of 4 nm. When these PdNPs were re-dispersed in TG and used for the dehydrogenation of ammonia borane (AB) at 85 °C, remarkably enhanced catalytic performance was achieved to release 2.3 equiv. of H(2) in 1 h.


Response to Comment on "Ancient origins of allosteric activation in a Ser-Thr kinase".
Park et al question one out of seven findings from Hadzipasic et al: whether TPX2 allosterically regulates the oldest Aurora. We had already addressed the two concerns raised-sparse sequence sampling and not forcing the gene to the species tree-before publication. Moreover, we believe their ancestral sequence reconstruction would be consistent with a nonallosteric common ancestor, and we show large sequence differences caused by species tree-enforced gene trees.


[Validation of the Spanish version of the Golombok Rust Inventory of Sexual Satisfaction].
Self-reports are one of the most used techniques in the evaluation of human sexuality. For this reason, valid and reliable evaluation instruments are necessary for high quality studies. The main purpose of this study was to translate and validate the Golombok Rust Inventory of Sexual Satisfaction for use in Spanish. A sample of 1,265 subjects (1,007 men, 258 women) completed the Golombok Rust Inventory of Sexual Satisfaction questionnaire. Two independent translators performed the translation and a group of experts unified the versions. The items showed adequate correlation, both in the men's version (0.306-0.440), and in the women's version (0.355-0.652). Reliability is high in both versions (men: 0.864; women: 0.924). Factor analysis adjusts to the theoretical dimensions proposed by the authors of the questionnaire, explaining 57.75% of the variance in men, and 66.67% in women. The Spanish version of the Golombok Rust Inventory of Sexual Satisfaction has the necessary psychometric properties to be used both in the clinic and in research.


PuzzleWalk: A theory-driven iterative design inquiry of a mobile game for promoting physical activity in adults with autism spectrum disorder.
Primary symptoms of adults with autism spectrum disorder (ASD), such as pervasive social deficits in social interaction and communication, cause adults with ASD to adopt a sedentary lifestyle. Meanwhile, gamified and behavioral theory-based interventions have been shown to improve physical activity in a fun and unobtrusive way. In this paper, we describe the iterative design inquiry process of PuzzleWalk, a gamified, physical activity-promoting mobile app designed for adults with ASD. We report the design rationales and lessons learned across four user-centered design phases with ASD experts and adults with ASD, including user requirement gathering, iterative participatory design, usability evaluation, and field deployment. The design insights generated from this work could inform future research focusing on designing sociotechnical systems, games, and interventions for people with ASD.


Ultra-high-precision time control system over any long time delay for laser pump and synchrotron x-ray probe experiment.
An ultra-high-precision clock system for long time delay has been developed for picosecond time-resolved x-ray diffraction measurements using synchrotron radiation (SR) pulses and synchronized femtosecond laser pulses. The time delay control between pump laser pulse and the probe SR pulse was achieved by combining an in-phase quadrature modulator and a synchronous counter. This method allowed us to change the delay time by a nearly infinite amount while maintaining the precision of +/-8.40 ps. Time-resolved diffraction measurements using the delay control system were demonstrated for precise measurement of an acoustic velocity in a single crystal of gallium arsenide.


COX2-derived primary and cyclopentenone prostaglandins are increased after asphyxial cardiac arrest.
Cyclopentenone prostaglandins have been identified as potential neurotoxic agents in the setting of hypoxia-ischemia. Cyclooxygenase-2 (COX-2), the upstream enzyme responsible for prostaglandin production is upregulated following hypoxic-ischemic brain injury. However, the temporal production and concentration of cyclopentenone prostaglandins has not been described following global brain ischemia. Global brain ischemia was induced in rats by asphyxial cardiac arrest (ACA) followed by resuscitation. Rats were sacrificed between 24h and 7 days following resuscitation and their brains removed. Western blot, immunohistochemistry, and mass spectroscopy were performed. A cohort of rats was pretreated with the COX-2 inhibitor SC58125. COX-2 is induced in hippocampus at 24h following ACA. Multiple prostaglandins, including cyclopentenone prostaglandin species, are increased in hippocampus as 24h following ACA. Prostaglandin and cyclopentenone prostaglandin concentrations are returned to baseline at 3 and 7 days post-ischemia. The COX-2 inhibitor SC58125 completely abrogates the post-ischemic increase in prostaglandins and cyclopentenone prostaglandins. Prostaglandins, including cyclopentenone prostaglandins, are increased in ischemic brain, peak at 24h and can be attenuated by the COX-2 inhibitor SC58125. These data establish the presence of potentially neurotoxic cyclopentenone prostaglandins in post-ischemic brains, thus identifying a target and therapeutic window for neuroprotective therapies.


Platelet-activating factor (PAF) receptor binding antagonists from Alpinia officinarum.
The bioassay-guided purification of ether extracts of Alpinia officinarum led to the isolation of two new compounds 6-hydroxy-1,7-diphenyl-4-en-3-heptanone (1) and 6-(2-hydroxy-phenyl)-4-methoxy-2-pyrone (4) as well as three known compounds 1,7-diphenyl-4-en-3-heptanone (2), 1,7-diphenyl-5-methoxy-3-heptanone (3), and apigenin (5). Their structures were established on the basis of spectral methods. All three diarylheptanoids 1, 2, and 3 exhibited potent PAF receptor binding inhibitory activities with an IC(50) of 1.3, 5.0, and 1.6 microM, respectively. These studies have identified diarylheptanoids as a novel class of potent PAF antagonists.


Impact of COVID-19 pandemic on hospital onset bloodstream infections (HOBSI) at a large health system.
The COVID-19 pandemic has had a considerable impact leading to increases in health care-associated infections, particularly bloodstream infections (BSI). We evaluated the impact of COVID-19 in 69 US hospitals on BSIs before and during the pandemic. Events associated with 5 pathogens (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida sp.) were stratified by community onset (CO) if ≤ 3 days from admission or hospital onset (HO) if > 3 days after admission. We compared pre-pandemic CO and HO rates with pandemic periods and the rates of BSI for those with and without COVID-19. COVID-19 patients were less likely to be admitted with COBSI compared to others (10.85 vs 22.35 per 10,000 patient days; P < .0001). There was a significant increase between pre-pandemic and pandemic HOBSI rates (2.78 vs 3.56 per 10,000 patient days; P < .0001). Also, COVID-19 infected patients were 3.5 times more likely to develop HOBSI compared to those without COVID-19 infection (9.64 vs 2.74 per 10,000 patient-days; P < .0001). The COVID-19 pandemic period was associated with substantial increases in HOBSI and largely attributed to COVID-19 infected patients. Future research should evaluate whether such measures would be beneficial to incorporate in evaluating infection prevention trends.


Human Alzheimer's disease reactive astrocytes exhibit a loss of homeostastic gene expression.
Astrocytes are one of the brain's major cell types and are responsible for maintaining neuronal homeostasis via regulating the extracellular environment, providing metabolic support, and modulating synaptic activity. In neurodegenerative diseases, such as Alzheimer's disease, astrocytes can take on a hypertrophic appearance. These reactive astrocytes are canonically associated with increases in cytoskeletal proteins, such as glial fibrillary acidic protein and vimentin. However, the molecular alterations that characterize astrocytes in human disease tissues have not been extensively studied with single cell resolution. Using single nucleus RNA sequencing data from normal, pathologic aging, and Alzheimer's disease brains, we identified the transcriptomic changes associated with reactive astrocytes. Deep learning-based clustering algorithms denoised expression data for 17,012 genes and clustered 15,529 astrocyte nuclei, identifying protoplasmic, gray matter and fibrous, white matter astrocyte clusters. RNA trajectory analyses revealed a spectrum of reactivity within protoplasmic astrocytes characterized by a modest increase of reactive genes and a marked decrease in homeostatic genes. Amyloid but not tau pathology correlated with astrocyte reactivity. To identify reactivity-associated genes, linear regressions of gene expression versus reactivity were used to identify the top 52 upregulated and 144 downregulated genes. Gene Ontology analysis revealed that upregulated genes were associated with cellular growth, responses to metal ions, inflammation, and proteostasis. Downregulated genes were involved in cellular interactions, neuronal development, ERBB signaling, and synapse regulation. Transcription factors were significantly enriched among the downregulated genes. Using co-immunofluorescence staining of Alzheimer's disease brain tissues, we confirmed pathologic downregulation of ERBB4 and transcription factor NFIA in reactive astrocytes. Our findings reveal that protoplasmic, gray matter astrocytes in Alzheimer's disease exist within a spectrum of reactivity that is marked by a strong loss of normal function.


Serum circulating egg antigen levels in two areas endemic for Schistosoma mansoni.
A monoclonal antibody-based enzyme-linked immunosorbent assay detecting Schistosoma mansoni circulating soluble egg antigen (CSEA) was applied in epidemiological studies. The serum CSEA levels were determined for 2 populations with a high prevalence (> 95%) and high intensity of infection as determined by faecal egg counts. In one population (Maniema, Zaire) transmission had been occurring for several decades, while in the other population (Ndombo, Senegal) transmission had started only recently. CSEA could be detected in 88% and 70% of the serum samples from Maniema and Ndombo, respectively. The sensitivity of the CSEA assay increased with rising egg count. The age-related CSEA profiles of the Maniema population followed a pattern similar to that of egg counts and of the adult worm antigen CAA (circulating anodic antigen). However, the recently infected Ndombo population showed a clearly different profile: while the CSEA prevalence reached a peak in children and adolescents, the mean CSEA levels did not vary significantly in the different age groups. CSEA levels were significantly lower in Ndombo than in Maniema. As egg antigens in serum are thought to be in part, or even primarily, derived from eggs in the tissues, these findings indicate a relatively smaller tissue egg load in Ndombo than in Maniema.


Self-Aligned Crystallographic Multiplication of Nanoscale Silicon Wedges for High-Density Fabrication of 3D Nanodevices.
High-density arrays of silicon wedges bound by {111} planes on silicon (100) wafers have been created by combining convex corner lithography on a silicon dioxide hard mask with anisotropic, crystallographic etching in a repetitive, self-aligned multiplication procedure. A mean pitch of around 30 nm has been achieved, based on an initial pitch of ∼120 nm obtained through displacement Talbot lithography. The typical resolution of the convex corner lithography was reduced to the sub-10 nm range by employing an 8 nm silicon dioxide mask layer (measured on the {111} planes). Nanogaps of 6 nm and freestanding silicon dioxide flaps as thin as 1-2 nm can be obtained when etching the silicon at the exposed apices of the wedges. To enable the repetitive procedure, it was necessary to protect the concave corners between the wedges through "concave" corner lithography. The produced high-density arrays of wedges offer a promising template for the fabrication of large arrays of nanodevices in various domains with relevant details in the sub-10 nm range.


Development and verification of a deep learning-based m6A modification model for clinical prognosis prediction of renal cell carcinoma.
The deep learning-based m6A modification model for clinical prognosis prediction of patients with renal cell carcinoma (RCC) had not been reported for now. In addition, the important roles of methyltransferase-like 14 (METTL14) in RCC have never been fully explored. A high-level neural network based on deep learning algorithm was applied to construct the m6A-prognosis model. Western blotting, quantitative real-time PCR, immunohistochemistry and RNA immunoprecipitation were used for biological experimental verifications. The deep learning-based model performs well in predicting the survival status in 5-year follow-up, which also could significantly distinguish the patients with high overall survival risk in two independent patient cohort and a pan-cancer patient cohort. METTL14 deficiency could promote the migration and proliferation of renal cancer cells. In addition, our study also illustrated that METTL14 might participate in the regulation of circRNA in RCC. In summary, we developed and verified a deep learning-based m6A-prognosis model for patients with RCC. We proved that METTL14 deficiency could promote the migration and proliferation of renal cancer cells, which might throw light on the cancer prevention by targeting the METTL14 pathway.


Nonenzymatic derived lipid peroxide, 8-iso-PGF2 alpha, participates in the pathogenesis of delayed cerebral vasospasm in a canine SAH model.
We studied whether 8-iso-PGF2alpha, nonenzymatic arachidonyl peroxide, participated in the pathogenesis of delayed vasospasm using a canine subarachnoid hemorrhage (SAH) model. Fourteen adult mongrel dogs were divided into two groups, two-hemorrhage SAH group (n = 8) and control group (n = 6). The contents of 8-iso-PGF2alpha in CSF, the basilar artery segment, and subarachnoid clot were measured by enzyme immunoassay kit. The CSF 8-iso-PGF2alpha content on Day 7 in the SAH group was 67.9+/-29.9 pg ml(-1) (n = 8), which was significantly higher than 27.1+/-13.8 (n = 8) on Day 0 in the SAH group, and 33.2+/-14.4 pg ml(-1) (n = 5) on Day 7 in the control group. The 8-iso-PGF2alpha content in the basilar artery segment with spasm on Day 7 in the SAH group was 13.5+/-1.9 pg mg(-1) wet weight (n = 8), significantly higher than 8.7+/-1.9 (n = 6) in the control group. The 8-iso-PGF2alpha content in subarachnoid clot was 1.7+/-1.4 ng g(-1) wet weight (n = 8). Significant elevation of the 8-iso-PGF2alpha contents in the CSF and the basilar artery segment occurred on Day 7 in the SAH group. The subarachnoid clot enclosed the basilar artery on Day 7, contained a considerable amount of 8-iso-PGF2alpha. These results suggested that 8-iso-PGF2alpha could play a crucial role in the pathogenesis of the delayed cerebral vasospasm.


Serum proteins in patients with benign prostatic hyperplasia.
Studies of serum protein patterns done in a group of 42 patients with benign prostatic hyperplasia (PBH) revealed the following: (1) prior to the operation significant hypalbuminaemia and increase of alpha 2-, beta- and gamma-globulins, IgG, IgA, IgM and CRP levels; (2) 12 days after operation a marked decrease of albumin concentration, increase of alpha 2-globulin and a sharp rise of CRP; (3) after 1 year a decrease of hypalbuminaemia and increase of alpha 2- and beta-globulins and CRP; in contrast to that, there was further increase of gamma-globulin concentration expressed also in the IgG, IgA and IgM levels.


Structural characterization and anticomplement activity of an acidic polysaccharide from Hedyotis diffusa.
An acidic homogeneous polysaccharide (HD-PS-1) was purified from Hedyotis diffusa (Willd.) Roxb. HD-PS-1 possessed a backbone chain of →[4)-β-Glcp-3-OAc-(1]6→[6)-β-Manp-(1]2→6)-α-Galp-(1→[4)-α-Galp-(1]2→, with three branches of β-Manp-(1→3)-β-GlcpA, α-Rhap-(1→3)-α-Rhap and α-Galp attached to the backbone chain at O-4 position of 1,4,6-linked β-Manp, O-3 position of 1,3,6-linked α-Galp and O-3 position of 1,3,4-linked α-Galp, respectively. HD-PS-1 exhibited significant anticomplement activity (CH50: 0.084 ± 0.009 mg/mL, AP50: 0.176 ± 0.013 mg/mL). It was found that the presence of uronic acids is important to anticomplement activity of HD-PS-1, given that the reduced HD-PS-1 showed weaker activity (CH50: 0.456 ± 0.008 mg/mL, AP50: 0.572 ± 0.010 mg/mL). Preliminary mechanism study indicated that HD-PS-1 interacted with C3 and C4 in the complement activation cascade. In addition, a neutral homogeneous polysaccharide (HD-PS-2) was also purified and characterized. HD-PS-2 displayed antioxidant activity by scavenging DPPH· radicals without anticomplement activity.


Dual-Energy CT-Derived Volumetric Iodine Concentration for the Assessment of Therapeutic Response after Microwave Ablation in a Rabbit Model with Intrahepatic VX2 Tumor.
To evaluate whether changes in volumetric iodine concentration (VIC) could serve as a suitable predictor of therapeutic response to microwave (MW) ablation in a rabbit intrahepatic VX2 tumor model. Sixteen intrahepatic VX2 tumors were transplanted in 8 New Zealand White rabbits treated with MW ablation. Contrast-enhanced dual-energy CT scans were obtained at baseline and follow-up. Therapeutic response assessment by modified Response Evaluation Criteria In Solid Tumors (mRECIST), Choi criteria, and VIC changes was performed. An intraclass correlation coefficient (ICC) was used to characterize consistency of assessment results among the criteria used. Technical success was evaluated with explant pathologic findings as a reference. Correlations between technical success and variations in diameter, CT density, and VIC were analyzed. Disease control was observed in 4, 8, and 10 of the 16 tumors per mRECIST, Choi criteria, and VIC changes, respectively. VIC exhibited strong consistency (ICC = 0.807, P < .0001) with Choi criteria. According to explant pathology, technical success was achieved in 10 of the 16 tumors. There was a moderate correlation between VIC changes and technical success (r = 0.532, P = .034), and no correlation was found between technical success and variations in diameter or CT density. Compared with mRECIST and Choi criteria, dual-energy CT-derived VIC allowed for better prediction of therapeutic response after MW ablation and could provide a potential imaging biomarker of tumor response to MW ablation in patients with hepatocellular carcinoma.


Adolescents' experiences of parental separation and divorce.
This paper reports preliminary results of interviews with 71 divorced parents and 50 of their adolescent children. The interviews took place five to six years after divorce, and the sample was reasonably representative of divorced Edinburgh families having children aged 10-13 at divorce. Qualitative analysis shows a lack of explanations to children about the reasons for their parents' separation. The children's feelings are described, together with their experiences of custody and of access or lack of access. Finally, the children's reactions are given to their parents' new partners. Some of the children remain unconvinced of the need for their parents to separate, and some are still sad and hurt.


Pathologic findings of multiple sulfatase deficiency reflect the pattern of enzyme deficiencies.
Multiple sulfatase deficiency is a rare metabolic storage disorder that manifests in childhood. It is probably an autosomal-recessive inherited condition, the gene for which has not yet been identified. Clinical features include mental deficiency and a dysmorphic appearance reminiscent of a mucopolysaccharidosis. Unlike most storage disorders, there are multiple deficient enzymes; all are sulfatases, hence the name of the disorder. Biochemical testing reveals accumulation of glycosaminoglycans, sulfatides, and gangliosides in the brain and other tissues of affected patients. In previous accounts of postmortem examinations, white matter histologic and biochemical pathologic findings similar to metachromatic leukodystrophy have been reported. Ganglioside accumulation, secondary to interference with degradative enzyme activity by the accumulating glycosaminoglycans also has been demonstrated. The authors report a case of multiple sulfatase deficiency with only mild deficiencies of the arylsulfatases but with severe deficiencies of iduronate sulfatase and heparan sulfamidase. Pathologic changes were more in keeping with a mucopolysaccharidosis, with minimal white matter changes and deposition of metachromatic material. The authors postulate that the mild leukodystrophic changes but striking features similar to a mucopolysaccharidosis are reflections of the pattern of enzyme deficiency. The pathology of multiple sulfatase deficiency therefore represents an overlap between a leukodystrophy and a mucopolysaccharidosis, with the relative contribution of each pattern apparently depending on the pattern of enzyme deficiency encountered in each patient.


Achievement of individualized treatment targets in patients with comorbid type-2 diabetes and hypertension: 6 months results of the DIALOGUE registry.
Patients with type-2 diabetes mellitus (T2DM) and hypertension have increased risk of cardiovascular disease (CVD). We studied individualized treatment targets and their achievement in clinical practice. DIALOGUE is a prospective, multi-center registry in patients with both T2DM and hypertension. Patients (n = 6,586) had a baseline fasting glucose (8.5 ± 2.8 mmol/l), postprandial glucose (10.9 ± 3.4 mmol/l), and HbA1c (7.8 ± 2.1%) levels indicated poor glycemic control. Baseline systolic and diastolic BP were 140.3 ± 15.7 and 82.6 ± 9.5, respectively. Patients were categorized by HbA1c treatment goals: ≤6.5% (strict), >6.5 to ≤7.0% (medium), and >7.0 to ≤7.5% (loose). When considering systolic BP (SBP) targets (≤130 mmHg [strict], >130 to ≤135 mmHg [medium], and >135 to ≤140 mmHg [loose]), patients with strict SBP treatment goals displayed similar characteristics to those with strict HbA1c targets. Although approximately 70% of patients received both strict HbA1c and SBP targeting, overall treatment goals remained unmet in all HbA1c target groups at the 6-month follow-up. SBP targets were not reached in the strict and medium groups, but were achieved in the loose treatment group. Specific predictors for choosing loose SBP or HbA1c treatment goals were identified, including SBP/HbA1c levels and various comorbidities. Individualized glucose and BP targets were selected by treating physicians based on patient characteristics and overall comorbidity. While treatment goals were not consistently met using various antidiabetic and antihypertensive therapies, our analyses indicated that the strictly targeted patient populations maintained lower overall HbA1c and SBP levels at 6 months.


Analysis of preservatives with different polarities in beverage samples by dual-phase dual stir bar sorptive extraction combined with high-performance liquid chromatography.
A new concept of "dual-phase dual stir bar sorptive extraction (SBSE)" was proposed to simultaneously extract six preservatives with different polarities (logKo/w values of 1.27-3.41), namely, benzoic acid (BA), sorbic acid (SA), methyl p-hydroxybenzoate (MP), ethyl p-hydroxybenzoate (EP), propyl p-hydroxybenzoate (PP), and butyl p-hydroxybenzoate (BP). The dual-phase dual SBSE apparatus was consisted of two differently coated stir bars, a 3-aminopropyltriethoxysilane (APTES)-hydroxy-terminated silicone oil (OH-TSO)-coated stir bar that was prepared by sol-gel technique and a C(18) silica (C(18))-polydimethylsiloxane (PDMS)-coated stir bar that was prepared by adhesion. In dual-phase dual SBSE, the two stir bars with different coatings were placed in the same sample solution for the simultaneous extraction of the target analytes with different polarities, and then the bars were desorbed in the same desorption solvent. The extraction performance of the dual-phase dual SBSE for the six preservatives was evaluated by comparing with the conventional SBSE (individual stir bar) with different coatings, including commercial PDMS, homemade PDMS, C(18)-APTES-OH-TSO, APTES-OH-TSO, and C(18)-PDMS. The experimental results showed that the dual-phase dual SBSE had the highest extraction efficiency for the six target preservatives. Based on this fact, a novel method by combining the dual-phase dual SBSE which was consisted of the APTES-OH-TSO-coated and C(18)-PDMS-coated stir bars with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) was developed for the simultaneous analysis of six target beverage preservatives in beverages. Under optimal conditions, the limits of detection (LODs) for six target preservatives ranged from 0.6 to 2.7 μgL(-1) with the relative standard deviations (RSDs) of 4.6-9.2% (C(BA,SA)=5 μgL(-1),C(MP)=20 μgL(-1),C(EP,PP,BP)=10 μgL(-1), n=7). The enrichment factors (EFs) were approximately 16-42-fold (theoretical EF was 50-fold). The proposed method was validated by the analysis of six target preservatives in three kinds of beverage samples, and the recoveries for the spiked samples were in the range of 76.6-118.6% for cola, 74.6-17.5% for orange juice, and 83.0-119.1% for herbal tea, respectively.


The value of a prognostic scoring system in the rehabilitation of elderly patients with proximal femoral fractures.
To evaluate a prognostic scoring system for elderly patients with hip fractures, which can, on admission, predict on the basis of pre-injury prognostic factors the possible length of stay in hospital, progress of rehabilitation, level of self-caring and rehousing needs at discharge. A prognostic scoring system, developed on the basis of pre-injury level of independence in activities of daily living (ADL) (Katz), medical comorbidities and Pfeiffer's mental scoring system was used (Svensson O et al. J Bone Joint Surg 1996; B78: 115-8). The study was conducted on a cohort of 63 patients prospectively recruited from consecutive admissions. Ninety percent of the patients (without comorbidities and mental score > 7; group 3/3) who were independently mobile pre-injury remained independently mobile at discharge (CI 95% 0.79-0.97). Pre-injury score was found to be significantly related to the level of ADL at 2 weeks after operation and at discharge from hospital (CI 95% 0.69-0.9). There was a pattern in duration of hospital stay in different groups (score 3/3 = 22 days, 2/3 = 31 days and 1/3 = 33 days). A pattern of community placement and housing after discharge was noticed in relation to the pre-injury score. 3/3 score groups are most likely to achieve independence with mobility and ADL on the acute orthopaedic ward and to be discharged directly to their pre-injury homes. They also were the least likely group to need rehabilitation in a dedicated orthogeriatric rehabilitation unit. 2/3 score groups are most likely to benefit from rehabilitation in a dedicated orthogeriatric rehabilitation unit. 1/3 and 0/3 score groups are least likely to benefit from rehabilitation in a dedicated orthogeriatric unit, in terms of achieving independence with mobility and ADL. They were also the most likely group to need long-term high dependency residential care. Early liaison with social and community services is essential for effective and timely planning of discharge.


Emergency revascularization for acute main-trunk occlusion in the anterior circulation.
We report the surgical results in patients with acute cerebral main-trunk occlusion in the anterior circulation. Between April 2004 and March 2005, 26 patients were surgically treated within 24h after the onset. The occlusion occurred in the internal carotid artery in 10 patients, in the middle cerebral artery in 15, and in the anterior cerebral artery in 1. We investigated the clinical characteristics and surgical treatment and evaluated the outcome using the modified Rankin Scale (mRS). Nine patients underwent anastomosis, 14 had an embolectomy, and 3 had a carotid endarterectomy. In all the patients, revascularization was achieved, and neurological improvement was obtained. At 6 months after the onset, eight (30.8%) patients showed a good recovery (defined as grade 1 on the mRS), seven (26.9%) were rated as grade 2, eight (30.8%) were grade 3, and three (11.5%) were grade 4. Manual muscle test on admission was significantly different between the good outcome and the poor outcome groups at 6 months after onset. None of the patients experienced any complications related to the surgery. Early surgical revascularization can be an effective and safe treatment modality in appropriately selected patients with acute cerebral main-trunk occlusion in the anterior circulation.


Thyroxine restores severely impaired cutaneous re-epithelialisation and angiogenesis in a novel preclinical assay for studying human skin wound healing under "pathological" conditions ex vivo.
Impaired cutaneous wound healing remains a major healthcare challenge. The enormity of this challenge is compounded by the lack of preclinical human skin wound healing models that recapitulate selected key factors underlying impaired healing, namely hypoxia/poor tissue perfusion, oxidative damage, defective innervation, and hyperglycaemia. Since organ-cultured human skin already represents a denervated and impaired perfusion state, we sought to further mimic "pathological" wound healing conditions by culturing experimentally wounded, healthy full-thickness frontotemporal skin from three healthy female subjects for three days in either serum-free supplemented Williams' E medium or in unsupplemented medium under "pathological" conditions (i.e. hypoxia [5% O2], oxidative damage [10 mM H2O2], absence of insulin, excess glucose). Under these "pathological" conditions, dermal-epidermal split formation and dyskeratosis were prominent in organ-cultured human skin, and epidermal reepithelialisation was significantly impaired (p < 0.001), associated with reduced keratinocyte proliferation (p < 0.001), cytokeratin 6 expression (p < 0.001) and increased apoptosis (p < 0.001). Moreover, markers of intracutaneous angiogenesis (CD31 immunoreactivity and the number of of CD31 positive cells and CD31 positive vessel lumina) were significantly reduced. Since we had previously shown that thyroxine promotes wound healing in healthy human skin ex vivo, we tested whether this in principle also occurs under "pathological" wound healing conditions. Indeed, thyroxine administration sufficed to rescue re-epithelialisation (p < 0.001) and promoted both epidermal keratinocyte proliferation (p < 0.01) and angiogenesis in terms of CD31 immunoreactivity and CD31 positive cells under "pathological" conditions (p < 0.001) ex vivo. This demonstrates the utility of this pragmatic short-term ex vivo model, which recapitulates some key parameters of impaired human skin wound healing, for the preclinical identification of promising wound healing promoters.


Humoral hypercalcaemia in a patient with renal-cell carcinoma.
In a patient with hypercalcaemia secondary to a renal-cell carcinoma, a concentration gradient of bioactivity was detected between the tumour effluent vein and the peripheral venous blood that was capable of stimulating adenylate cyclase in bone cells. Immuno-reactive PTH was undetectable in the tumour effluent and in the peripheral blood. It is concluded that a non-parathyroid humoral factor whose action involved cyclic AMP stimulation was responsible for the hypercalcaemia.


Effect of antimicrobial photodynamic therapy using toluidine blue on dual-species biofilms of Candida albicans and Candida krusei.
Although Candida albicans is the most frequent etiological agent of candidiasis, it has been reported a sizable number of infections related to the non-albicans Candida (NAC) species, Candida krusei. In addition, dual biofilms (biofilms composed by two species) may easily occur in vivo, becoming even more challenging the treatment of an infection. The fungicide effect of Photodynamic Therapy (PDT), using toluidine blue O (TBO) on both C. albicans and C. krusei development has been demonstrated. Thus, the objective of this study was to investigate the effects of PDT on dual-species biofilms of Candida albicans and Candida krusei. The effect of PDT was observed on the metabolic activity of mature dual-species biofilms of Candida albicans and Candida krusei by a metabolic assay based on the reduction of XTT (2,3-bis(2‑methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt) assay and the identification of Candida albicans and Candida krusei was performed on CHROMagar Candida medium. it was observed a reduction of ∼30% in the metabolic activity of a mature biofilm treated with PDT, using 0.05 mg·mL-1 TBO and during biofilm formation a predominance of C. albicans on C. krusei was observed. The inhibition observed was related to reduction in the number of Colony Forming Units (CFU) of Candida albicans from 31.33 ± 3.7 to 17.0 ± 1.5. The number of CFU of C. krusei was not significantly modified. These results demonstrated the efficiency of PDT in inhibiting the dual-species biofilms of Candida albicans and Candida krusei by reducing C. albicans development.


Clinically important differences in the intensity of chronic refractory breathlessness.
Clinically important differences in chronic refractory breathlessness are ill defined but important in clinical practice and trial design. To estimate the clinical relevance of differences in breathlessness intensity using distribution and patient anchor methods. This was a retrospective data analysis from 213 datasets from four clinical trials for refractory breathlessness. Linear regression was used to explore the relationship between study effect size and change in breathlessness score (0-100mm visual analogue scale) and to estimate the change in score equivalent to small, moderate, and large effect sizes. Pooled individual blinded patient preference data from three randomized controlled trials were analyzed. The difference between the mean change in Day 4 minus baseline scores between preferred and non-preferred arms was calculated. There was a strong relationship between change in score and effect size (P = 0.001; R(2) = 0.98). Values for small, moderate, and large effects were -5.5, -11.3, and -18.2mm. The participant preference change in score was -9mm (95% CI, -15.8, -2.1) (P = 0.008). This larger dataset supports a clinically important difference of 10mm. Studies should be powered to detect this difference.


MRI of the uterus, uterine cervix, and vagina: diagnostic performance of dynamic contrast-enhanced fast multiplanar gradient-echo imaging in comparison with fast spin-echo T2-weighted pulse imaging.
The aim of this study was to compare the diagnostic performance of contrast-enhanced fast multiplanar gradient-echo (GRE) and T2-weighted fast spin-echo (FSE) image sets in the assessment of uterus, cervix, and vagina. Fast (up to 20 contiguous sections in 23 s) multiplanar GRE and FSE images of 45 patients referred for imaging of the female pelvis were evaluated retrospectively with regard to overall image quality and the ability to detect normal anatomic structures, as well as lesion conspicuity. Results were compared with histologic findings (n = 29) or clinical follow-up. Furthermore, a quantitative assessment of contrast-to-noise ratios among normal uterine and cervical structures as well as uterine lesions was performed for both sequences. On GRE images, uterine and cervical differentiation was best seen on the image sets acquired 15 and 60 s following contrast enhancement and results were significantly better compared with delayed images (p < 0.05). Delineation of the junctional zone was significantly (p < 0.05) better on FSE compared with GRE images; no significant difference was seen for the other anatomic structures. Overall image quality of GRE and FSE images was similar. Sensitivity for lesion detection based on both GRE and FSE images was 96% with a sensitivity of 93% for GRE, and 81% for FSE images alone, respectively. Using the extended McNemar chi 2 test, the difference in diagnostic performance between FSE and GRE revealed no significant difference, whereas the combination of both techniques performed better than FSE imaging alone (p < 0.05). The presented data suggest that dynamic contrast-enhanced GRE imaging should be part of an MR examination of the female pelvis. Combined GRE and FSE imaging provide an excellent sensitivity in the assessment of uterine and vaginal pathologies.


Amino-Fe3O4-functionalized graphene oxide as a novel adsorbent of Methylene Blue: kinetics, equilibrium, and recyclability aspects.
Graphene oxide (GO) was synthetized from graphite oxidation via the modified Hummers method. Afterwards, the GO was functionalized with diethylenetriamine (DETA) and FeCl3 to obtain the novel amino-iron oxide functionalized graphene (GO-NH2-Fe3O4). FTIR, XRD, SEM with EDX, and Raman spectroscopy were performed to characterize both GO and GO-NH2-Fe3O4. The GO-NH2-Fe3O4 was then evaluated as adsorbent of the cationic dye Methylene Blue (MB); analysis of the point of zero net charge (pHPZC) and pH effect showed that the GO-NH2-Fe3O4 pHPZC was 8.2; hence, the MB adsorption was higher at pH 12.0. Adsorption kinetics studies indicated that the system reached the equilibrium state after 5 min, with adsorption capacity at equilibrium (qe) and kinetic constant (kS) of 966.39 mg g-1 and 3.17∙10-2 g mg-1 min-1, respectively; moreover, the pseudo-second-order model was better fitted to the experimental data. Equilibrium studies showed maximum adsorption capacity of 1047.81 mg g-1; furthermore, Langmuir isotherm better fitted the adsorption. Recycling experiments showed that the GO-NH2-Fe3O4 maintained the MB removal rate above 95% after 10 cycles. All the results showed sorbent high adsorption capacity and outstanding regeneration capability and evidenced the employment of novel GO-NH2-Fe3O4 as a profitable adsorbent of textile dyes.


The highly exposed loop region in mammalian purple acid phosphatase controls the catalytic activity.
Recombinant human purple acid phosphatase (recHPAP) provides a convenient experimental system for assessing the relationship between molecular structure and enzymatic activity in mammalian purple acid phosphatases (PAPs). recHPAP is a monomeric protein with properties similar to those of uteroferrin (Uf) and other PAPs isolated as single polypeptide chains, but its properties differ significantly from those of bovine spleen PAP (BSPAP) and other PAPs isolated as proteolytically "clipped" forms. Incubation of recHPAP with trypsin results in proteolytic cleavage in an exposed region near the active site. The product is a tightly associated two-subunit protein whose collective spectroscopic and kinetics properties resemble those of BSPAP. These results demonstrate that the differences in spectroscopic and kinetics properties previously reported for mammalian PAPs are the result of proteolytic cleavage. Mass spectrometry shows that a three-residue segment, D-V-K, within the loop region is excised by trypsin. This finding suggests that important interactions between residues in the excised loop and one or more of the groups that participate in catalysis are lost or altered upon proteolytic cleavage. Analysis of available structural data indicates that the most important such interaction is that between Asp 146 in the exposed loop and active-site residues Asn 91 and His 92. Loss of this interaction should result in both an increase in the Lewis acidity of the Fe(II) ion and an increase in the nucleophilicity of the Fe(III)-bound hydroxide ion. Proteolytic cleavage thus constitutes a potential physiological mechanism for regulating the activity of PAP in vivo.


Analysis of well-being and 24-hour blood pressure recording in a comparative study between indapamide and captopril.
The effects of indapamide and captopril on office and ambulatory blood pressure control and on general well-being were investigated in 30 active, randomly selected patients from 25 to 68 years old, with mild to moderate essential hypertension (diastolic blood pressure, 92 to 114 mm Hg). Twenty-four-hour ambulatory blood pressure monitoring using an ICR model 5200 portable recorder and evaluation of general well-being were performed prior to and at the end of three months of therapy with indapamide 2.5 mg given once daily, or captopril 12.5 to 50 mg given twice daily. Indapamide and captopril were equally effective in controlling blood pressures in clinic and during 24-hour activities. Although general well-being and subjective symptomatology improved with both treatments, the only significant difference between the two drugs was improvement in the sleep dysfunction scale with indapamide (p less than 0.02). The results shown in this study suggest that both indapamide (2.5 mg) once daily and captopril (12.5 to 50 mg) twice daily are suitable drugs for initial therapy of active patients with mild to moderate hypertension. A fixed once-daily dosage of an antihypertensive agent may, however, increase patient compliance and convenience.


Examining the mediating effect of work-to-family conflict on the associations between job stressors and employee psychological distress: a prospective cohort study.
The mediating effect of work-to-family conflict (WFC) on the associations between eight types of job stressors (measured based on the job demands-control, effort-reward imbalance and organisational justice models) and psychological distress in employees was examined. This study employed a prospective design. An occupational cohort study in Japan (Japanese Study of Health, Occupation, and Psychosocial Factors Related Equity; J-HOPE). 5859 men and 1560 women who were working for 11 firms and participated at three consecutive waves of J-HOPE, at 1-year intervals, from 2010 to 2013. Psychological distress, as measured by Kessler 6 scores. Mediation analysis using data on job stressors at baseline, WFC at 1-year follow-up and psychological distress at 2-year follow-up showed that WFC mediated 39.1% (95% CI 29.1% to 49.1%) and 44.5% (95% CI 31.4% to 51.7%) of the associations of psychological distress with job demands and effort, respectively, for men. The mediating effect of WFC was smaller for job stressors indicating reduced job resources, compared with job demands and effort. The mediating effect of WFC was somewhat larger for women than it was for men, with WFC mediating 47.5% (95% CI 22.5% to 72.6%) and 64.0% (95% CI 24.3% to 100.0%) of the associations of psychological distress with job demands and effort, respectively. WFC was a key mediator in the associations between most job stressors and employee psychological distress. Results suggest that policy measures and support from supervisors, to prevent job stressors from adding to WFC, are needed to reduce employee psychological distress.


The Charlson Comorbidity Index: problems with use in epidemiological research.
The Charlson Comorbidity Index (CCI) is a highly cited and well established tool for measuring comorbidity in clinical research, but there are problems with its use in practice. Like most comorbidity summary measures, the CCI was developed to adjust for prognostic comorbidities in statistical models, particularly those exploring associations between a risk of death or survival time and other patient-related and disease-related factors. Despite this, the CCI is often used in cancer research to measure all comorbidity, or as a multimorbidity measure, and CCI scores are often used to assess the prognostic importance of multiple health conditions. In the latter case, it is not at all surprising that researchers report a significant association between CCI scores and a risk of death or survival times because CCI scores provide a summary of the presence or absence of a set of prognostic comorbidities. Advances in multimorbidity research require specific attention to the methods used to develop relevant indices. Published literature on the association between the comorbidity and risk of death or survival time should be interpreted with caution, especially if the CCI was used to provide a measure of comorbidities.


Energy and electron transfer in photosystem II reaction centers with modified pheophytin composition.
Energy and electron transfer in Photosystem II reaction centers in which the photochemically inactive pheophytin had been replaced by 13(1)-deoxo-13(1)-hydroxy pheophytin were studied by femtosecond transient absorption-difference spectroscopy at 77 K and compared to the dynamics in untreated reaction center preparations. Spectral changes induced by 683-nm excitation were recorded both in the Q(Y) and in the Q(X) absorption regions. The data could be described by a biphasic charge separation. In untreated reaction centers the major component had a time constant of 3.1 ps and the minor component 33 ps. After exchange, time constants of 0.8 and 22 ps were observed. The acceleration of the fast phase is attributed in part to the redistribution of electronic transitions of the six central chlorin pigments induced by replacement of the inactive pheophytin. In the modified reaction centers, excitation of the lowest energy Q(Y) transition produces an excited state that appears to be localized mainly on the accessory chlorophyll in the active branch (B(A) in bacterial terms) and partially on the active pheophytin H(A). This state equilibrates in 0.8 ps with the radical pair. B(A) is proposed to act as the primary electron donor also in untreated reaction centers. The 22-ps (pheophytin-exchanged) or 33-ps (untreated) component may be due to equilibration with the secondary radical pair. Its acceleration by H(B) exchange is attributed to a faster reverse electron transfer from B(A) to. After exchange both and are nearly isoenergetic with the excited state.


Genomic variants exclusively identified in children with birth defects and concurrent malignant tumors predispose to cancer development.
Children with birth defects (BD) express distinct clinical features that often have various medical consequences, one of which is predisposition to the development of cancers. Identification of the underlying genetic mechanisms related to the development of cancer in BD patients would allow for preventive measures. We performed a whole genome sequencing (WGS) study on blood-derived DNA samples from 1566 individuals without chromosomal anomalies, including 454 BD probands with at least one type of malignant tumors, 767 cancer-free BD probands, and 345 healthy individuals. Exclusive recurrent variants were identified in BD-cancer and BD-only patients and mapped to their corresponding genomic regions. We observed statistically significant overlaps for protein-coding/ncRNA with exclusive variants in exons, introns, ncRNAs, and 3'UTR regions. Exclusive exonic variants, especially synonymous variants, tend to occur in prior exons locus in BD-cancer children. Intronic variants close to splicing site (< 500 bp from exon) have little overlaps in BD-cancer and BD-only patients. Exonic variants in non-coding RNA (ncRNA) tend to occur in different ncRNAs exons regardless of the overlaps. Notably, genes with 5' UTR variants are almost mutually exclusive between the two phenotypes. In conclusion, we conducted the first genomic study to explore the impact of recurrent variants exclusive to the two distinguished clinical phenotypes under study, BD with or without cancer, demonstrating enrichment of selective protein-coding/ncRNAs differentially expressed between these two phenotypes, suggesting that selective genetic factors may underlie the molecular processes of pediatric cancer development in BD children.


Individual variation in incentive salience attribution and accumbens dopamine transporter expression and function.
Cues (conditioned stimuli; CSs) associated with rewards can come to motivate behavior, but there is considerable individual variation in their ability to do so. For example, a lever-CS that predicts food reward becomes attractive and wanted, and elicits reward-seeking behavior, to a greater extent in some rats ('sign-trackers'; STs) than others ('goal-trackers'; GTs). Variation in dopamine (DA) neurotransmission in the nucleus accumbens (NAc) core is thought to contribute to such individual variation. Given that the DA transporter (DAT) exerts powerful regulation over DA signaling, we characterized the expression and function of the DAT in the accumbens of STs and GTs. STs showed greater DAT surface expression in ventral striatal synaptosomes than GTs, and ex vivo fast-scan cyclic voltammetry recordings of electrically evoked DA release confirmed enhanced DAT function in STs, as indicated by faster DA uptake, specifically in the NAc core. Consistent with this, systemic amphetamine (AMPH) produced greater inhibition of DA uptake in STs than in GTs. Furthermore, injection of AMPH directly into the NAc core enhanced lever-directed approach in STs, presumably by amplifying the incentive value of the CS, but had no effect on goal-tracking behavior. On the other hand, there were no differences between STs and GTs in electrically-evoked DA release in slices, or in total ventral striatal DA content. We conclude that greater DAT surface expression may facilitate the attribution of incentive salience to discrete reward cues. Investigating this variability in animal sub-populations may help explain why some people abuse drugs while others do not.


Psychogenic nonepileptic seizures: characterization of two distinct patient profiles on the basis of trauma history.
This prospective study investigated and compared psychiatric features of 25 consecutive patients with psychogenic nonepileptic seizures (PNES) on the basis of presence of reported trauma. The "trauma" group comprised 19 patients (76%) and the "no-trauma" group comprised 6 patients (34%). We compared history of PNES, psychiatric comorbidity, alexithymia, and symptoms of dissociation. The study clearly characterized two distinct profiles of patients with PNES on the basis of trauma history. Patients with trauma had at least one psychiatric comorbidity or antecedent (vs 0% in the no-trauma group NT, P<0.001) and a higher median score of dissociation (P<0.001). Patients without trauma had more frequent "frustration situations" as a factor triggering PNES and subsequent sick leaves as perpetuating factors (P=0.001). Trauma antecedents correlated with a high rate of psychiatric comorbidity and a strong dissociative mechanism. Patients without trauma had no psychiatric comorbidity and a weaker dissociative mechanism.


Supraventricular tachycardia in acquired rubella infection: a case report.
A 6-year-old boy developed supraventricular tachycardia nine days after onset of the exanthem of clinical rubella. The diagnosis of rubella virus infection was confirmed serologically. Except in the neonatal period, only eight cases of cardiac involvement in acquired rubella infection have been previously reported. During epidemics, rubella virus infection should be considered in patients who manifest cardiac symptoms and signs of unknown etiology.


Acetylator polymorphism in rheumatoid arthritis.
Acetylator phenotype has been determined with sulphamethazine (sulphadimidine) in 69 Spanish patients with rheumatoid arthritis (48 females), all of whom were on second line therapy, and in 96 age-matched normal controls (54 females). Thirty-two patients (46.4%) and 56 controls (58.3%) were classified as slow acetylators. On analysing separately the females in both groups, 37.5% of patients and 63% of controls were found to be slow acetylators. No difference was found in the males (patients 66.3% and controls 52.4% slow acetylators). Rapid acetylator phenotype may be a risk factor for the development of severe rheumatoid arthritis in women.


Proteomic study of human bronchoalveolar lavage fluids from smokers with chronic obstructive pulmonary disease by combining surface-enhanced laser desorption/ionization-mass spectrometry profiling with mass spectrometric protein identification.
Bronchoalveolar lavage fluid (BALF) is an important diagnostic source to investigate cellular and molecular changes in the course of lung disorders. The pattern of soluble proteins in BALF obtained from patients at different stages of respiratory disorders may provide deeper insights in the molecular mechanisms of the disease. We used surface-enhanced laser desorption/ionization mass spectrometry (MS) for differential protein display combined with reversed-phase chromatography and subsequent matrix-assisted laser desorption/ionization-MS or nanoliquid chromatography MS/MS analysis for protein identification to compare the protein pattern of BALF samples obtained from ten smokers suffering from chronic obstructive pulmonary disease (COPD), eight clinically asymptomatic smokers, and eight nonsmokers without pulmonary disease. In this context, we were able to identify small proteins and peptides, either differentially expressed or secreted in the course of COPD or in a direct response to cigarette smoke. The concentrations of neutrophil defensins 1 and 2, S100A8 (calgranulin A), and S100A9 (calgranulin B) were elevated in BALFs of smokers with COPD when compared to asymptomatic smokers. Increased concentrations in S100A8 (Calgranulin A), salivary proline-rich peptide P-C, and lysozyme C were detected in BALFs of asymptomatic smokers when compared to nonsmokers, whereas salivary proline-rich peptide P-D and Clara cell phospholipid-binding protein (CC10) were reduced in their concentration. The identified proteins and peptides might be useful in the future as diagnostic markers for smoke-induced lung irritations and COPD.


Localised Fusobacterium necrophorum infections: a prospective laboratory-based Danish study.
During a 3-year prospective laboratory-based study in Denmark from 1998 to 2001, all patients who were diagnosed with localised Fusobacterium necrophorum infections were registered with the purpose of describing the variety of localised infections caused by F. necrophorum, especially in the head. We found 267 patients, most of them previously healthy, with localised F. necrophorum infections in the head and neck. In children, F. necrophorum caused otitis media and solitary abscess formation in cervical lymphadenitis. In adolescents, F. necrophorum was found in 21% of peritonsillar abscesses. We also found F. necrophorum in young adults with tonsillitis and in middle-aged adults with sinusitis. F. necrophorum was found in substantial amounts and as the only bacterial pathogen in the majority of patients. All 267 patients recovered without sequelae. We found another 21 localised non-head-and-neck-associated F. necrophorum infections, mainly subcutaneous wound infections in adults. This study shows that F. necrophorum causes a variety of localised infections, especially in the head and neck region, with a characteristic age distribution. We recommend that anaerobic culture is performed on swabs from children with recurrent otitis media and adolescents with non-streptococcal group A tonsillitis.


Robotics in paediatric urology.
After the emergence of robotically assisted systems in laparoscopic surgery more than 15 years ago, several systems have been on the market. At the time being only one system, the da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA, USA), has survived in clinical use with an increasing spread particularly among adult urologists used primarily for radical prostatectomies. However, the reconstructive nature of paediatric urology makes the system interesting for the paediatric urologists, since its strength is laparoscopic suturing and difficult dissection. So far only few reports have been published about its clinical use in paediatric urology. The main advantages are the 3D magnified view, the wrist-like movements of the instruments, and the scaling and precision of instrument movements. The system has been used for upper tract reconstruction like pyeloplasties and heminephrectomies, both for the transperitoneal and, more technical challenging, the retroperitoneal approach. In the pelvic region, anti-reflux surgery (both extra- and intravesically) and surgery for malformations of the internal genitalia like utriculus cysts and gonadal streaks are feasible. More simple procedures like nephrectomies and the management of the intra-abdominal testis are not justified due to the high costs. In addition, no advantage for the patients related to standard laparoscopic procedures has been proofed yet. For the surgeon the minimally challenging invasive procedures become feasible with certainly improved ergonomics. The use of the system is much easier than standard laparoscopic surgery and its widespread will give more patients to access minimal invasive surgery.


The influence of aorta-aneurysm geometry upon stress in the aneurysm wall.
Finite element analysis (FEA), a computer-based method for solving complex structural problems, was used to determine the wall stress distribution in three cases of model infrarenal abdominal aortic aneurysms representing common problems in determining risk of aneurysm rupture. The point of maximum circumferential wall stress in a spherical model aneurysm was located near the junction of the aneurysm and the nondilated aorta, while maximum longitudinal wall stress was located at the point of maximum diameter of the aneurysm. FEA showed that cylindrically shaped constant thickness model aneurysms had a higher maximum circumferential stress (sigma c = 11.9 X 10(5) dyn/cm2) and a comparable maximum longitudinal wall stress (sigma L = 6.6 X 10(5) dyn/cm2) when compared with spherical model aneurysms of the same diameter (sigma c = 8.1 X 10(5) dyn/cm2 and sigma L = 6.2 X 10(5) dyn/cm2). Analysis of the aorta to aneurysm diameter ratio (A:a gradient) indicated that aortic size is important in determining aneurysm wall stress and that the relationship between aortic size and wall stress is dependent upon aneurysm wall thickness. We conclude that the ability of the aneurysm wall to withstand stress in the longitudinal as well as the circumferential direction is an important factor determining aneurysm rupture. Finally, this investigation showed that FEA is a versatile tool for use in studying the mechanics of vascular structures, making it potentially more useful than size alone in estimating the clinical significance of abdominal aortic aneurysms.


Stapedius muscle fiber characterization during postnatal development in the rat.
The stapedius muscle (SM) is reported to prevent cochlear damage by noise. Functional demands are then the ability of fast contraction with long endurance. At the end of the third postnatal week, the middle ear of the rat is completely pneumatized and according to electrophysiological data, the auditory function starts to match the adult. We investigated the developmental changes in myosin composition of SM fibres using consecutive complete SM cross-sections (taken from rats on post natal day (PND) 7, 14, 16, 21, 28, 42 and 84) which were processed by enzymehistochemistry to determine acid/alkali lability of myofibrillar adenosine triphosphatase (mATPase) and by immunohistochemistry using myosin heavy chain (MHC) antibodies (mAb). Fibres were assigned to mATPase type I, IIA, IIB, IIX or 'Miscellaneous' categories. Per mATPase category, the fibres were attributed to groups with specific MHC isoform compositions. Neonatal MHC expression could not be documented with the mAb used. However, embryonal (Emb) MHC was expressed at PND 7, very little at PND 14; at later PND fibres did not show Emb MHC. In general, the mATPase-based classification did not show large alterations after PND 21. Expression of MHC IIB, which was present in almost 50% of the fibres at PND 7 and 14, diminished to 3% at PND 84. A decrease in number of fibres expressing more than one MHC isoform was found. These results show that the SM is a precociously developing muscle compared to limb muscles and even to the diaphragm. Moreover, it is shown that the expression of the adult MHC isoform phenotype coincides with the onset of auditory function in the third postnatal week.


Magnesium metabolism in preterm infants: effects of calcium, magnesium, and phosphorus, and of postnatal and gestational age.
This study tests the hypothesis that increasing the calcium and phosphorus content of formulas for very low birth weight (VLBW) infants to the level required to decrease the incidence of rickets has a negative impact on magnesium balance. Using formulas variously supplemented with these minerals, we measured absorption and retention in two groups of preterm infants: (1) VLBW infants, less than 1500 gm and at less than 32 weeks of gestational age, with 3-day mineral balances begun at days 10, 20, 30, and 40; and (2) low birth weight infants appropriately grown and at 32 to 34 weeks of gestational age, with a single 3-day balance begun at day 10. Magnesium did not affect calcium balance in VLBW or low birth weight infants but promoted phosphorus retention in VLBW infants from day 20 onward. Absorption and retention of magnesium increased with postnatal age in VLBW infants, but this effect was obvious only when calcium or phosphorus intakes were low or when magnesium intake was high. Calcium and phosphorus supplementation further reduced magnesium absorption and retention in VLBW infants to the extent that they were in negative balance throughout the study; however, magnesium supplementation improved absorption and retention in VLBW infants. The low birth weight infants absorbed and retained more magnesium than VLBW infants at the same postnatal age whether or not magnesium was supplemented. We conclude that magnesium deficits occur at currently recommended intakes of 10 mg/kg/day for VLBW infants with calcium and phosphorus intakes that allow retentions equivalent to in utero accretions; however, with magnesium intakes approaching 20 mg/kg/day, appropriate retention can be achieved.


Direct ethanol fermentation of the algal storage polysaccharide laminarin with an optimized combination of engineered yeasts.
Laminarin is the algal storage glucan and represents up to 35% of the dry weight of brown macroalgae. In this study, a novel laminarinase, Gly5M, was first found using focused proteome analysis of a laminarin-assimilating marine bacterium, Saccharophagus degradans, and the encoding gene was isolated. A Gly5M-displaying yeast strain was prepared with the cell surface display system using Saccharomyces cerevisiae. It showed a laminarin-degrading activity on the cell surface and caused the dominant accumulation of gentiobiose. The obtained gentiobiose was converted into glucose and could be assimilated by an Aspergillus aculeatus β-glucosidase (BG)-displaying yeast strain. When Gly5M- and BG-displaying yeasts were anaerobically cultivated together in fermentation medium containing 20g/L laminarin as a sole carbon source, the coculture system with the combination of optimized ratios of the 2 yeast strains directly produced 5.2g/L ethanol. This coculture system of the 2 engineered yeast strains would be a platform for the use of laminarin and contribute to the complete utilization of brown macroalgae.


Acute green tea intake attenuates circulating microRNA expression induced by a high-fat, high-saturated meal in obese women: A randomized crossover study.
The objective of this study was to assess whether acute green tea (GT) supplementation attenuates inflammatory and oxidative stress biomarkers induced by high-fat, high-saturated (HFHS) meals in obese women, and to assess its ability to modulate circulating microRNA (miRNA) expression. This was a randomized, double-blind, crossover study. The study included obese women over 18 years old who had no comorbidities. In the first moment, patients were instructed to take 2 capsules of placebo or GT (738 mg) at 10:00 p.m. and to fast overnight. The next morning, a blood sample was collected, and an HFHS meal was offered to the patients. Another blood sample was collected 5 hours after the meal. In the second moment, patients who received placebo in the first moment now received the GT and vice-versa. Serum inflammatory and oxidative stress biomarkers were measured, and circulating levels of miRNA were evaluated. Fifteen women with mean age of 35.5±9.9 years were included in the final analysis. There was no difference regarding inflammatory and oxidative stress biomarkers. However, patients who consumed GT had lower circulating expression of 62 miRNAs compared with patients who did not consume GT. Predictive analysis of target genes showed 1,757 targets regulated by the 62 miRNAs. Notably, 5 miRNAs (miR-1297, miR-192-5p, miR-373-3p, miR-595 and miR-1266-5p) regulate genes associated with TGF-beta, CARM1, RSK, and BMP pathways. Our study showed that GT inhibited the expression of miRNAs induced by HFHS meal intake. These results shed light on the mechanisms involved in the beneficial effects of GT ingestion.


Hypertriglyceridemia and hyperuricemia: effects of two fibric acid derivatives (bezafibrate and fenofibrate) in a double-blind, placebo-controlled trial.
The effects of bezafibrate and fenofibrate on serum lipoproteins and serum urinary uric acid were compared. In a double-blind, placebo-controlled, cross-over study, each drug was administered in random order for 6 weeks followed by a 3-week drug-free phase to ten men with primary hypertriglyceridemia. Serum triglyceride and cholesterol concentrations decreased significantly with both fenofibrate and bezafibrate, although no significant change in serum apolipoprotein B, serum low density lipoprotein (LDL) cholesterol or serum high density lipoprotein (HDL) cholesterol concentrations was apparent. Serum uric acid levels, which were elevated on placebo and bezafibrate, were significantly reduced by 20% by fenofibrate. This was associated with an increase in renal uric acid clearance of 30% during fenofibrate therapy. Because it seems likely that hypertriglyceridemia and hyperuricemia are linked by a common carbohydrate inducibility, we studied the acute hyperuricemic response to orally administered fructose. Fructose (50 g) caused the anticipated rise in serum urate reaching a peak between 60 and 90 minutes, which was quantitatively greater in the men with hypertriglyceridemia than in healthy controls. The serum uric response to fructose was unaffected by bezafibrate, but was converted to normal by fenofibrate. The hyperuricemic action of fenofibrate is of sufficient magnitude to be of therapeutic value in the management of patients whose hypertriglyceridemia is associated with gout.


S100B and brain ultrasound: Novel predictors for functional outcome in acute ischemic stroke patients.
Stroke is a leading cause of mortality and disability worldwide. This study aimed to assess the prognostic value of serum S100B protein, transcranial color-coded duplex sonography (TCCD), and optic nerve sheath diameter (ONSD) in predicting functional outcomes in critically ill patients with acute ischemic stroke (AIS). In this prospective observational study, 80 adult AIS patients were evaluated. Serum S100B protein levels, ONSD, and middle cerebral artery pulsatility index (MCA PI) were measured on days 1 and 3. Functional outcomes at 90 days were assessed using the modified Rankin Scale (mRS) and categorized into favourable (mRS 0-2) or unfavourable (mRS 3-6) groups. The association of demographic, clinical, laboratory, and imaging parameters with mRS outcomes was analyzed. Poor mRS outcomes occurred in 82.5 % of patients. Factors significantly associated with poor outcomes were female sex, higher National Institutes of Health Stroke Scale (NIHSS) scores on days 1, 3, and 7, and larger stroke size. Receiver Operating Characteristic (ROC) curve analysis revealed that ONSD at days 1 and 3, serum S100B levels at day 1, and right MCA PI at day 1 had significant predictive value for poor mRS outcome. Multivariate analysis identified female sex, S100B on day 1, and NIHSS on days 1, 3, and 7 as independent predictors of poor mRS outcomes. The combination of S100B, ONSD, and MCA PI improved the prediction of functional outcomes in critically ill AIS patients. Early S100B measurement and brain ultrasound evaluation may serve as valuable prognostic tools for guiding therapeutic decision-making. This study provides novel insights into the role of S100B and brain ultrasound in stroke outcome prediction, particularly in critically ill AIS patients.


Assessment and treatment of Spanish-speaking sex offenders: special considerations.
While there is an expanding body of literature pertaining to the special considerations related to the treatment of Hispanic patients whose primary language is Spanish, there is virtually no information reported to aid in the assessment and treatment of Hispanic and primarily Spanish-speaking sex offenders. Beyond the obvious problems posed by differences in language, there are a host of transcultural factors that may impact on the evaluation and engagement of this patient population when they are also largely psychologically unsophisticated and from a low socioeconomic level. The experiences in modifying and implementing a special program to accommodate the needs of this patient group is presented. Reticence to discuss sexuality in a group setting, the relationship between therapists and patients as effected by rules of social etiquette, and the reluctance to criticize other members in the group were prominent features attributed to religious and cultural factors. The authors consider it a necessity to be sensitive to these subtle nuances in order to provide adequate treatment.


Characterisation of Staphylococcus aureus and Enterococcus faecalis mutants with reduced susceptibility to the investigational oxazolidinone RWJ-416457.
RWJ-416457 is a novel investigational oxazolidinone with minimum inhibitory concentrations (MICs) to staphylococci and enterococci that are two- to four-fold lower than those of linezolid. Single-step and serial passage in vitro resistance selection experiments were performed for RWJ-416457 and linezolid with Staphylococcus aureus and Enterococcus faecalis laboratory and clinical isolates. RWJ-416457 selected for resistant mutants in single-step selections at a frequency of ≤1×10(-10), similar to that of linezolid. In serial passage selection experiments, a G2576T transversion in the domain V region of the 23S rRNA gene was the predominant mutation observed for both oxazolidinones, suggesting similar 23S rRNA binding sites. The associated development of increasing oxazolidinone resistance in E. faecalis (four 23S rRNA alleles) required fewer passages than with S. aureus isolates (six 23S rRNA alleles), and resistance was generally proportionate to the number of mutated (G2576T) 23S rRNA alleles. Fold changes in MICs were similar for both compounds, and MICs for RWJ-416457 remained two- to four-fold lower than those of linezolid for mutants selected by either compound. Serial passage of linezolid with S. aureus OC 2878 yielded a novel A2572T 23S rRNA mutation, whilst the final passages of S. aureus OC 10517 with RWJ-416457 resulted in the apparent loss of a mutated (G2576T) allele 6.


Human antibodies recognizing the envelope glycoprotein of the baboon endogenous virus BaEV are of heterophil origin.
Human sera were previously shown to possess antibodies capable of recognizing purified retrovirus envelope glycoproteins. In an extension of earlier studies we investigated sera from various groups of patients for an immune reaction against purified glycoprotein of the baboon endogenous virus BaEV. Reproducible demonstrations of oncovirus-like particles in human teratocarcinomas focused our main interest on sera from patients with testicular tumors. The specificity of the positive immune reaction of sera from these patients against BaEV gp 70 was analyzed in a competition RIAs with haptens and different cell lysates and experiments employing deglycosylated BaEV envelope antigen. From these experiments we conclude that the sera from teratocarcinoma patients contain naturally occurring, heterophil antibodies that react with the carbohydrate moieties of retrovirus envelope antigens.


Increased hepatic capacity of urea synthesis in acute and chronic uraemia in rats.
We studied whole body nitrogen balance in female rats for 28 days after induction of experimental uraemia by 5 6 nephrectomy and at the same time the kinetics of hepatic urea synthesis by means of the in vivo capacity of urea synthesis. The N-balance of 5 uraemic rats kept in metabolic cages was negative on day 2, and positive but only half of control on day 28. In between, it was normal. The uraemic rats lost weight during the first week, and later only slowly regained their initial weight. The capacity for urea synthesis was determined during alanine loading in 5 unoperated controls, in uraemic rats in groups of 5 on days 2, 7, 14, 21, and 28, and correspondingly in sham operated rats. In the control rats the capacity was 8.9 +/- 0.7 micromol/(min 100 g BW) and the same in sham operated rats. In uraemic rats the capacity increased to 17.1 +/- 2.0 micromol/(min 100 g BW) (p < 0.01) 2 days after partial nephrectomy. On day 7, the capacity fell to 5.5 +/- 1.0 (not different from initial values), and thereafter again gradually increased to 16.5 +/- 1.5 micromol/(min 100g BW) on day 28. The early increase in the capacity may be related to glucagon, that nearly doubled on day 2, but not on day 28. The hepatic capacity for urea synthesis doubles biphasically: acutely and after 4 weeks of experimental uraemia. This may play a role in the reduction in N-balance, since an increase in the capacity implies larger hepatic amino-N conversion at any blood amino-acid concentration.


Risks and costs of end-stage renal disease after heart transplantation.
To estimate the risks and costs of end-stage renal disease (ESRD) after heart transplantation. Previous studies have shown high rates of ESRD among solid-organ transplant patients, but the relevance of these studies for current transplant practices and policies is unclear. Limitations of prior studies include relatively small, single-center samples and estimates made before implementing suggested practice changes to reduce ESRD risk. Medicare beneficiaries who underwent heart transplantation between 1989 and 1994 were eligible for study inclusion (n=2088). Thirty-four patients undergoing dialysis or who had the diagnosis of ESRD before or at transplantation were excluded from the study. ESRD was defined as any patient undergoing renal transplantation or requiring dialysis for more than 3 months. Mortality and ESRD events were recorded up to 1995. ESRD risk was estimated using the Kaplan-Meier product-limit estimator and logistic regression analyses. Linear regression was performed to determine expenditures for treating ESRD, and we developed long-term models of the risk and direct medical costs of ESRD care. The annual risk of ESRD was 0.37% in the first year after transplant and increased to 4.49% by the sixth posttransplant year. There was no significant trend in the risk of ESRD based on the year of transplantation, even after adjusting for patient characteristics. The average cumulative 10-year direct cost of ESRD per patient undergoing heart transplantation exceeded $13,000. In a large, national sample of patients undergoing heart transplantation, ESRD is not rare, even for patients undergoing transplant after the development of new practices intended to reduce its occurrence. ESRD remains an important component of the costs of heart transplantation.


Use of complementary and alternative medicine among children, adolescent, and young adult cancer survivors: a survey study.
The main objective of this study was to investigate the prevalence of complementary and alternative medicine (CAM) use, types and reasons for use, and determinants of use among survivors of childhood cancer. An interviewer-based survey of CAM use was administered to 197 survivors or their guardians. Demographic data, CAM therapies used, purpose and referral for use, and communication about use was collected. A total of 115 (58%) survivors reported using CAM in survivorship, 72% of which used biologically based therapies. The majority of therapies were used for relaxation and stress management (15%), referred for use by the parent (25%), reported as very effective (62%), and initiated 0 to 4 years after completion of cancer treatment (41%). Among CAM users, young adults used manipulative and body-based therapies [odds ratio (OR)=3.3; 95% confidence interval (CI), 1.4-7.8] and mind-body therapies (OR=2.8, 95% CI: 1.2-6.4) more than children. Use of mind-body therapies was associated with not attending religious services regularly (OR=2.4; P<0.01). Half (51%) of all CAM therapies were disclosed to the physician. Survivors of childhood cancer frequently use CAM for health promotion and mitigation of physical and psychological conditions. Clinicians should consider the role of CAM in the adoption of healthy lifestyles among this population.


Pregnancy outcomes in women with diabetes mellitus - the impact of diabetes type and treatment.
It has been estimated that approximately 16% of pregnancies worldwide are affected by pre-existing or gestational insulin-dependent (type 1) or independent (type 2) diabetes mellitus (DM). Diabetes mellitus in pregnancy remains a high-risk condition for both mother and child. This study aimed to investigate pregnancy outcomes regarding DM types. The study included 323 DM patients delivered for 6 years (2012-2017). General and obstetric history data and all complications throughout the pregnancy and the early neonatal period were noted. Based on DM type, women were divided into 4 groups: pre-pregnancy/pre-existing DM, insulin-dependent or independent, and gestational diabetes mellitus with or without insulin therapy. The majority of women had pre-existing insulin-independent DM (type II 62%). Some types of pregnancy/maternal complications were registered in almost 85% of examined pregnancies. However, all babies were live born and mostly with good outcome (36.85% with early neonatal complications). Diabetes mellitus type could not predict the occurrence of neonatal complications (p = 0.342). Pre-existing insulin-dependent DM increased the risk for pregnancy complications (p = 0.031; OR = 1.656). Diabetes mellitus type has a limited impact on pregnancy outcomes and the occurrence of maternal and neonatal complications. With adequate therapy the pregnancy outcome can be good regardless of DM type.


Morquio syndrome: diagnosis in an adult.
Morquio syndrome or mucopolysaccharidosis (MPS) type IV is a rare autosomal recessive disease in which keratan sulfate builds up in cells. There are two variants, A and B, corresponding to deficiencies of two different enzymes. Type A is usually severe, although considerable clinical variability occurs due to the existence of attenuated phenotypes, which may escape diagnosis until adulthood. We illustrate this little known possibility by reporting a case of MPS IV A diagnosed in a 38-year-old woman. We review the clinical and radiological features of this disease, with which pediatricians are more familiar than other physicians. Our case provides an opportunity to emphasize the need for management by a rheumatologist in addition to the standard surgical treatment.


Energy-Band Engineering by Remote Doping of Self-Assembled Monolayers Leads to High-Performance IGZO/p-Si Heterostructure Photodetectors.
Metal oxide semiconductors are of great interest for enabling advanced photodetectors. However, operational instability and the absence of an appropriate doping technique hinder practical development and commercialization. Here, a strategy is proposed to dramatically increase the conventional photodetection performance, having superior stability in operational and environmental atmospheres. By performing energy-band engineering through an octadecylphosphonic acid (ODPA) self-assembled-monolayer-based doping treatment, the proposed indium-gallium-zinc oxide (IGZO)/p-Si heterointerface devices exhibit greatly enhance the photoresponsive characteristics, including a photoswitching current ratio with a 100-fold increase, and photoresponsivity and detectivity with a 15-fold increase each. The observed ODPA doping effects are investigated through comprehensive analysis with X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and Kelvin probe force microscopy (KPFM). Furthermore, the proposed photodetectors, fabricated at a 4 in. wafer scale, demonstrate its excellent operation robustness with consistent performance over 237 days and 20 000 testing cycles.


Changes in the dietary habits of male workers in Warsaw plants over a period of four years.
At the Polish Trial on Ischaemic Heart Disease Prevention begun in 1976-77 the dietary habits of 5,484 male workers aged 40-59 years working in 14 Warsaw plants were assessed by 24-hour recall. After two and four years of follow-up in 1978-79 and 1980-81 this study was repeated in random samples of the previously screened population still in employment in these plants i.e., 652 men (response rate after two years=70.4%) and 574 men (response rate after four years=65.0%). In the initial screening the mean energy value of the reported daily food ration was 2,700 kcal/11,296 kJ. This energy derived 13.6% from protein, 37.1% from fat, and 49.3% from carbohydrate. After two years the mean energy value of the daily food ration as well as the amounts of the daily consumed fat and carbohydrate and vitamin B1 had decreased significantly. The amounts of the remaining nutrients were not significantly changed. After four years only the mean daily consumption of vitamin C was decreased significantly. The mean values of the total energy value of the food ration as well as of the amounts of nutrients were not significantly different. On the other hand, differences were found in the amount of food products--the reported consumption of cereals and bread as well as animal fat increased significantly, while the consumption of meat and meat products, vegetable fats, fruits and sugar decreased.


Changes in blood flow of growing experimental tumor determined by the clearance of 133Xe.
133Xe clearance method has been employed for measurement of the blood flow in 6C3HED lymphosarcoma implanted in flank of C3H mice. In small tumors (9-day old) the mean rate of blood flow was 9.4 +/- 5.0 ml/100g/min. but with progressing growth of tumors the rate of blood flow significantly decreased. In large tumors (14-day old) the mean rate of the blood flow was only 5.4 +/- 2.8. Our results demonstrate that this type of tumor, similarly as most of transplanted tumors are not well perfused and, that there is an inverse relationhip between the blood flow and the tumor size.


Open conversion after Nellix endovascular aneurysm sealing.
The Nellix endovascular aneurysm sealing system (Endologix, Irvine, Calif) was presented as a novel concept in the treatment of abdominal aortic aneurysm. After numerous adverse events, the device was voluntarily withdrawn from the market by the manufacturer. This video describes the technical approach of a successful explantation of the Nellix endograft in a patient who underwent endovascular aneurysm sealing for abdominal aortic aneurysm.