Harvesting of Scenedesmus obliquus in wastewaters: auto- or bioflocculation?
Autoflocculation and bioflocculation are considered to be the most promising means for the economical harvesting of microalgae. We have therefore studied these phenomena with cultures of Scenedesmus obliquus produced during biological tertiary wastewater treatment. The quantity of extracellular polymers produced during ageing of the cultures proved insufficient to initiate bio-flocculation while the concentration of Ca(2+) and PO(4) (3-) of the treated effluent were too low to induce autoflocculation. It has been shown, however, that the algae sediment more readily upon ageing, possibly as a result of increased cell density. The use of density gradients made with Percoll (a colloidal solution of silica particles) allowed measurement of the true cell density and showed that this increases when cultures enter the declining growth phase. The quality of the biomass thus harvested is, however, considerably impaired, protein content decreasing from 62.7% (dry wt) during the exponential growth phase (day 5) to 14% at the end of cultures (day 21).


A novel strategy against ischemia and reperfusion injury: cytoprotection with heme oxygenase system.
Much interest has recently been focused on the physiological/pathological role of the heme oxygenase (HO) system, the rate-limiting step in the conversion of heme, in inflammatory events. The HO system may be instrumental in mediating a number of cytoprotective effects, because of its end products, biliverdin, carbon monoxide (CO) and ferrous free iron (Fe2+). As each of the byproducts acts dependently and/or co-operatively with each other, their in vivo effects are complex. In general, the HO system is thought to exert three major functions in ischemia/reperfusion injury: (1) anti-oxidant effects; (2) maintenance of microcirculation; and (3) modulatory effects upon the cell cycle. The anti-oxidant functions depend on heme degradation, oxygen consumption and the production of biliverdin/ferritin via iron accumulation. On the other hand, the production of CO, which has vasodilatory and anti-platelet aggregative properties, can maintain tissue microcirculation. Strikingly, CO may also be instrumental in anti-apoptotic and cell arrest mechanisms. The HO system prevents early injury in the re-perfused organ, and inhibits the function of immune reactive cells, such as neutrophils, macrophages and lymphocytes. The role of the HO system as a novel strategy to mitigate an antigen-independent ischemia/reperfusion injury has been documented in a number of transplantation models.


Influence of intracoronary shunt on myocardial ischemic injury during off-pump coronary artery bypass surgery.
The aim of the study was to evaluate the role of intracoronary shunt during off-pump coronary artery bypass surgery in patients with isolated left anterior descending coronary artery lesion. Forty patients undergoing off-pump coronary artery bypass using the left internal mammary artery to bypass the left anterior descending coronary artery were randomly assigned to have the bypass performed with intracoronary shunt or by occlusive snaring. Potential damage from the shunt or from snaring was monitored by clinical follow-up, monitoring of cardiac enzymes (cardiac troponin I, CK, CK-MB), electrocardiography, and echocardiography before and 24 h. after the surgery. Left ventricular myocardial biopsies were performed during surgery for histopathological analysis. None of the patients in this study died during or after the surgery. Duration of the anastomosis was significantly longer in the shunt group. No significant difference concerning the preoperative and postoperative CK levels between groups. The preoperative CK-MB levels of the groups were not significantly different, whereas postoperative levels was significantly lower in the shunt group. The preoperative troponin I levels of the groups were not significantly different, whereas postoperative levels was significantly higher in the snare group. Myocardial edema was significantly less in shunt group compared with snare group. There were no electrocardiographic abnormalities, severe CK-MB elevation, or hemodynamic deterioration after the operation in both groups. Intracoronary shunt may have beneficial effects due to the reduction of postoperative troponin I levels and myocardial edema during grafting of the left anterior descending coronary artery. However, further trials need to be performed for the documentation of their impacts precisely.


Tumors and tumor-like lesions of the heart valves.
Valvular tumors and tumor-like lesions may have similar morphological and clinical characteristics, and may place the patients at a high risk of stroke in different ways. From January 2004 to June 2008, 11 patients underwent surgery for a suspected valvular tumor. Valvular tumor and tumor-like lesions accounted for 0.32% of adult cardiac operations. Five (45.5%) valvular lesions were papillary fibroelastomas, one (9.1%) was myxoma, 2 (18.2%) were organized thrombi, and 3 (27.3%) were calcification lesions. There was a total of 5 (45.5%) atrioventricular valve lesions, 4 arising from the atrial side of the leaflets, and one from the ventricular side. All 5 (45.5%) semilunar valvular lesions were from the aortic valve. One (9.1%) lesion originated from the chorda tendinea of the mitral valve. All leaflet lesions were resected by a simple shave technique, and all the patients recovered favorably. Valvular tumor and tumor-like lesions are rare. Pre-operative differential diagnoses among these valvular lesions pose important clinical implications for appropriate treatment for the underlying diseases. Prompt therapeutic measures in view of the underlying diseases of the valvular lesions are essential to prevent potential embolic events.


[Intracardial migration of a bullet: diagnosis and management].
Venous pellet embolism to the cardia after shotgun wound is a very rare occurrence. Number and size of pellets, at the impact make this migration easier; embolism is asymptomatic and may occur 15 years after the injury. Many problems must be mentioned: mechanics of entry into the heart (own velocity, venous flow), topographic diagnosis (chest X-ray, transthoracic, transoesophageal ultrasound and CT-scan), local outcomes of this projectile (local erosion, clot, endocarditis), destination of a new migration (pulmonary embolism, left heart), indications of extraction, supervision. Extraction musn't be systematic, but only in the event of a patent foramen ovale with a risk of systemic embolism, which clinical outcomes are most serious or in the event of complications. The authors report on a 22 years old patient observation whose treatment was abstention and supervision.


Lysobacter terrae sp. nov. isolated from Aglaia odorata rhizosphere soil.
A Gram-stain negative, facultatively anaerobic, non-motile, rod-shaped bacterium, designated strain THG-A13(T), was isolated from Aglaia odorata rhizosphere soil in Gyeonggi-do, Republic of Korea. Based on 16S rRNA gene sequence comparisons, strain THG-A13(T) had close similarity with Lysobacter niabensis GH34-4(T) (98.5 %), Lysobacter oryzae YC6269(T) (97.9 %) and Lysobacter yangpyeongensis GH19-3(T) (97.3 %). Chemotaxonomic data revealed that strain THG-A13(T) possesses ubiquinone-8 (Q8) as the predominant isoprenoid quinone and iso-C15 : 0, iso-C16 : 0 and iso-C17 : 1ω9c as the major fatty acids. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol) and diphosphatidylglycerol. The G+C content was 66.3 mol%. The DNA-DNA relatedness values between strain THG-A13(T) and its closest phylogenetic neighbours were below 18.0 %. These data corroborated the affiliation of strain THG-A13(T) to the genus Lysobacter. These data suggest that the isolate represents a novel species for which the name Lysobacter terrae sp. nov. is proposed, with THG-A13(T) as the type strain ( = KACC 17646(T) = JCM 19613(T)).


Newly divided eosinophils limit ozone-induced airway hyperreactivity in nonsensitized guinea pigs.
Ozone causes vagally mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs, where they mediate ozone-induced hyperreactivity 1 day after exposure but are paradoxically protective 3 days later. We aimed to test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and nonsensitized guinea pigs. Nonsensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 h. Later (1 or 3 days later), vagally induced bronchoconstriction was measured, and inflammatory cells were harvested from bone marrow, blood, and bronchoalveolar lavage. Ozone induced eosinophil hematopoiesis. One day after ozone, mature eosinophils dominate the inflammatory response and potentiate vagally induced bronchoconstriction. However, by 3 days, newly divided eosinophils have reached the lungs, where they inhibit ozone-induced airway hyperreactivity because depleting them with antibody to IL-5 or a TNF-α antagonist worsened vagally induced bronchoconstriction. In sensitized guinea pigs, both ozone-induced eosinophil hematopoiesis and subsequent recruitment of newly divided eosinophils to lungs 3 days later failed to occur. Thus mature eosinophils dominated the ozone-induced inflammatory response in sensitized guinea pigs. Depleting these mature eosinophils prevented ozone-induced airway hyperreactivity in sensitized animals. Ozone induces eosinophil hematopoiesis and recruitment to lungs, where 3 days later, newly divided eosinophils attenuate vagally mediated hyperreactivity. Ozone-induced hematopoiesis of beneficial eosinophils is blocked by a TNF-α antagonist or by prior sensitization. In these animals, mature eosinophils are associated with hyperreactivity. Thus interventions targeting eosinophils, although beneficial in atopic individuals, may delay resolution of airway hyperreactivity in nonatopic individuals.


[In vivo evaluation of cellular immunity in melanoma patients against melanoma].
Evaluation of cellular immunity against human melanoma was performed in an in vivo model using Balb/c nude mice bearing the human melanoma. Intraperitoneal injection of 1 X 10(7) melanoma cells produced peritonitis carcinomatosa which lead to death of the mice at 23.8 +/- 2.6 days (N = 12). Peripheral blood lymphocytes (PBL) from healthy donors and the melanoma cells cultured on the back of the nude mouse were given to nude mice intraperitoneally, and survival times of 22.0 +/- 2.3 days were observed (N = 8). PBL from four of the five healthy donors which have been presensitized on monolayers of the melanoma tissue culture cells in flask failed to prolong host survival times. In contrast, PBL from 15 of 20 melanoma patients were found to prolong the survival of the tumor bearing nude mice. Of these 15 patients, 8 were treated with specific active immunotherapy, but 7 had not been sensitized except by the disease process. The ability of PBL from patients to prolong survival of the melanoma bearing nude mice did not seem to correlate with either the stage of the disease or the clinical course. The possible mechanisms for the prolonged survival and the usefulness of this in vivo model were discussed.


Selection bias from sampling frames: telephone directory and electoral roll compared with door-to-door population census: results from the Blue Mountains Eye Study.
Many Australian public health research studies use the telephone directory or the electoral roll as a sampling frame from which to draw study subjects. The sociodemographic, disease-state and risk-factor characteristics of subjects who could be recruited using only the telephone directory or only the electoral roll sampling frames were compared with the characteristics of subjects who would have been missed using only these sampling frames, respectively. In the first phase of the Blue Mountains Eye Study we interviewed and examined 2557 people aged 49 and over living in a defined postcode area, recruited from a door-to-door census. This represented a participation rate of 80.9 per cent and a response rate of 87.9 per cent. The telephone directory was searched for each subject's telephone number and the electoral roll was searched for each subject. Subject characteristics for those who were present in each of these sampling frames were compared with the characteristics of those subjects not included in the sampling frames. The telephone directory listed 2102 (82.2 per cent) of the subjects, and 115 (4.5 per cent) had no telephone connected. The electoral roll contained 2156 (84.3 per cent) of the subjects, and 141 subjects (5.5 per cent) could not be found in either the electoral roll or the telephone directory. Younger subjects, subjects who did not own their own homes and subjects born outside of Australia were significantly less likely to be included in either of these sampling frames. The telephone directory was also more likely to exclude subjects with higher occupational prestige, while the electoral roll was more likely to exclude unmarried persons and males. Researchers using the telephone directory and electoral roll to select subjects for study should be aware of the potential selection bias these sampling frames incur and need to take care when generalising their findings to the wider community.


Two different mitotic checkpoint inhibitors of the anaphase-promoting complex/cyclosome antagonize the action of the activator Cdc20.
The mitotic checkpoint system ensures the fidelity of chromosome segregation by preventing the completion of mitosis in the presence of any misaligned chromosome. When activated, it blocks the initiation of anaphase by inhibiting the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C). Little is known about the biochemical mechanisms by which this system inhibits APC/C, except for the existence of a mitotic checkpoint complex (MCC) inhibitor of APC/C composed of the APC/C activator Cdc20 associated with the checkpoint proteins Mad2, BubR1, and Bub3. We have been studying the mechanisms of the mitotic checkpoint system in extracts that reproduce its downstream events. We found that inhibitory factors are associated with APC/C in the checkpoint-arrested state, which can be recovered from immunoprecipitates. Only a part of the inhibitory activity was caused by MCC [Braunstein I, Miniowitz S, Moshe Y, Hershko A (2007) Proc Natl Acad Sci USA 104:4870-4875]. Here, we show that during exit from checkpoint, rapid disassembly of MCC takes place while APC/C is still inactive. This observation suggested the possible involvement of multiple factors in the regulation of APC/C by the mitotic checkpoint. We have separated a previously unknown inhibitor of APC/C from MCC. This inhibitor, called mitotic checkpoint factor 2 (MCF2), is associated with APC/C only in the checkpoint-arrested state. The inhibition of APC/C by both MCF2 and MCC was decreased at high concentrations of Cdc20. We propose that both MCF2 and MCC inhibit APC/C by antagonizing Cdc20, possibly by interaction with the Cdc20-binding site of APC/C.


Formaldehyde-limited cultivation of a newly isolated methylotrophic bacterium, Methylobacterium sp. MF1: enzymatic analysis related to C1 metabolism.
Formaldehyde is a highly toxic compound to most living organisms. We have isolated a bacterial strain that is able to efficiently degrade formaldehyde and use it as a sole carbon source. The isolated strain was identified as Methylobacterium sp. MF1, which could grow on formaldehyde and methanol. Methylobacterium sp. MF1 was grown in batch culture using 1.2 g/l formaldehyde as a sole carbon source, which was all consumed within 200 h. In order to decompose formaldehyde more efficiently, formaldehyde-limited chemostat cultivation of Methylobacterium sp. MF1 was investigated. Formaldehyde was consumed at 1.7 g/l/d when the dilution rate was 0.012 h(-1). Under these conditions, the cell turbidity (OD610) reached 2.0. Furthermore, when the initial turbidity was adjusted to 3.0 using methanol-grown cells, continuous cultivation could be started at an initial dilution rate of 0.008 h(-1). Using these conditions, consumption of formaldehyde could be continued for at least 600 h. The enzyme activities of cells growing as a chemostat culture, using methanol or formaldehyde as a sole carbon source, were compared to that of C1 metabolism. No difference was detected in the enzyme activities for the oxidation and assimilation of C1 compounds between the two cell-free extracts. Furthermore, methanol dehydrogenase activity was detected at the same level when formaldehyde was used as a sole carbon source. These results suggest that the resistance to the toxic effects of formaldehyde exhibited by Methylobacterium sp. MF1 is related to factors other than C1 metabolism.


The role of the long non-coding RNA HOXA11-AS in promoting proliferation and metastasis of malignant tumors.
Long non-coding RNA (lncRNA) is one of the focuses and hotspots of biological research in recent years. At the same time, tumors have become the main disease that endangers human health. In recent years, a large number of researchers have explored the relationship between lncRNA and tumors. HOXA11-AS is one of these lncRNAs. The long non-coding RNA HOXA11 antisense RNA (HOXA11-AS) is a novel lncRNA recently discovered. It is found in a variety of tumors such as ovarian cancer, glioma, and gastric cancer (GC) and so on, and is defined as an oncogene. It promotes tumor proliferation and metastasis by interacting with proteins such as miRNA and EZH2. In this paper, we review the mechanism of interaction between HOXA11-AS and various tumors in recent years, and believe that it can be a potential tumor marker and therapeutic target in the future prevention and treatment of tumors.


Oral bisphosphonates in polyostotic fibrous dysplasia.
The bisphosphonates inhibit osteoclastic bone resorption and have been used as an intravenous infusion in fibrous dysplasia of the bone. Oral bisphosphonates are cheaper and also easy to administer. We report a case of polyostotic fibrous dysplasia in a three-year-old child who showed significant improvement in bone mineral density after treatment with oral alendronate.


Cholera toxin inhibits lethal hit stage of natural killer cell-mediated cytotoxicity.
Cytolytic process which was affected by cholera toxin (CT) resulting in the loss of natural killer (NK) cell activity was analyzed. Conjugate formation assay, membrane phospholipid methylation assay and serine esterase (granzyme A) release assay were used to determine the stage of the CT-induced inhibition of NK cell-mediated cytotoxicity. A human NK cell line YT cell-mediated cytotoxicity was completely abolished by CT pretreatment or addition of CT to the assay system. The conjugate formation assay revealed that the binding between YT cells and target cells was not affected by CT. The defined triggering stage which is coupled with membrane phospholipid methylation was not affected by CT treatment, either. On the other hand, the lethal hit stage which is represented by serine esterase (SE) release was completely inhibited by CT treatment of YT cells. Therefore, CT inhibits the stage after binding and triggering--i.e., lethal hit stage of NK cell-mediated cytotoxicity. The results also suggest that there exists a CT-sensitive negative cytotoxic signal transduction pathway as well as usual positive signal transduction pathway and these pathways might cross talk each other in the NK cell cytotoxic process.


Proteinase-activated receptor 2 (PAR2) in hepatic stellate cells - evidence for a role in hepatocellular carcinoma growth in vivo.
Previous studies have established that proteinase-activated receptor 2 (PAR2) promotes migration and invasion of hepatocellular carcinoma (HCC) cells, suggesting a role in HCC progression. Here, we assessed the impact of PAR2 in HCC stromal cells on HCC growth using LX-2 hepatic stellate cells (HSCs) and Hep3B cells as model. PAR2 expression and function in LX-2 cells was analysed by RT-PCR, confocal immunofluorescence, electron microscopy, and [Ca(2+)]i measurements, respectively. The impact of LX-2-expressed PAR2 on tumour growth in vivo was monitored using HCC xenotransplantation experiments in SCID mice, in which HCC-like tumours were induced by coinjection of LX-2 cells and Hep3B cells. To characterise the effects of PAR2 activation in LX-2 cells, various signalling pathways were analysed by immunoblotting and proteome profiler arrays. Following verification of functional PAR2 expression in LX-2 cells, in vivo studies showed that these cells promoted tumour growth and angiogenesis of HCC xenografts in mice. These effects were significantly reduced when F2RL1 (encoding PAR2) was downregulated by RNA interference (RNAi). In vitro studies confirmed these results demonstrating RNAi mediated inhibition of PAR2 attenuated Smad2/3 activation in response to TGF-β1 stimulation in LX-2 cells and blocked the pro-mitotic effect of LX-2 derived conditioned medium on Hep3B cells. Furthermore, PAR2 stimulation with trypsin or a PAR2-selective activating peptide (PAR2-AP) led to activation of different intracellular signalling pathways, an increased secretion of pro-angiogenic and pro-mitotic factors and proteinases, and an enhanced migration rate across a collagen-coated membrane barrier. Silencing F2RL1 by RNAi or pharmacological inhibition of Src, hepatocyte growth factor receptor (Met), platelet-derived growth factor receptor (PDGFR), p42/p44 mitogen activated protein kinase (MAPK) or matrix-metalloproteinases (MMPs) blocked PAR2-AP-induced migration. PAR2 in HSCs plays a crucial role in promoting HCC growth presumably by mediating migration and secretion of pro-angiogenic and pro-mitotic factors. Therefore, PAR2 in stromal HSCs may have relevance as a therapeutic target of HCC.


Retrospective correction of frequency drift in spectral editing: The GABA editing example.
GABA levels can be measured using proton MRS with a two-step editing sequence. However due to the low concentration of GABA, long acquisition time is usually needed to achieve sufficient SNR to detect small differences in many psychiatric disorders. During this long scan time the frequency offset of the measured voxel can change because of magnetic field drift and patient movement. This drift will change the frequency of the editing pulse relative to that of metabolites, leading to errors in quantification. In this article we describe a retrospective method to correct for frequency drift in spectral editing. A series of reference signals for each metabolite was generated for a range of frequency offsets and then averaged together based on the history of frequency changes over the scan. These customized basis sets were used to fit the in vivo data. Our results demonstrate the effectiveness of the correction method and the remarkable robustness of a GABA editing technique with a top hat editing profile in the presence of frequency drift.


Episodes of elevated methylmercury concentrations in prairie streams.
Methylmercury (MeHg) and total mercury (THg) concentrations were determined weekly from late March through mid-December 2000 in unfiltered water samples from two prairie streams in south-central Minnesota. The Little Cobb River and County Ditch 86 drain predominantly agricultural watersheds, but riparian areas along much of the Little Cobb River are forested, whereas County Ditch 86 is a utilitarian drainage waterway with grassed riparian areas. Episodes of elevated MeHg concentration (1.3 ng/L) were observed in both streams in early May during a period of algal bloom. Between late May and late September, MeHg concentrations varied between 0.05 and 0.39 ng/L in the Little Cobb River and between 0.03 and 0.29 ng/L in County Ditch 86. Precipitation was well below average in August and September, and discharge in both streams ceased by late September. MeHg concentrations in the Little Cobb River increased dramatically in early October after autumnal leaf fall, increasing from 0.44 to 4.90 ng/L over a 5-week period. In contrast, MeHg concentrations in County Ditch 86 varied between 0.22 and 0.48 ng/L over the same time frame. The observed differences are thoughtto reflect differences in the amounts of litterfall entering the two streams. These results show that algal bloom and leaf fall events can result in elevated MeHg concentrations in surface waters, potentially leading to increased MeHg accumulation in fish.


Research and the future of intensive psychotherapy.
Several factors have altered our view of intensive psychotherapy-the most important, perhaps, having done so without real scientific basis or scrutiny. Shouldn't we take a careful look?


Spin-charge separation and quantum spin Hall effect of [Formula: see text]-bismuthene.
Multiple works suggest the possibility of classification of quantum spin Hall effect with magnetic flux tubes, which cause separation of spin and charge degrees of freedom and pumping of spin or Kramers-pair. However, the proof of principle demonstration of spin-charge separation is yet to be accomplished for realistic, ab initio band structures of spin-orbit-coupled materials, lacking spin-conservation law. In this work, we perform thought experiments with magnetic flux tubes on [Formula: see text]-bismuthene, and demonstrate spin-charge separation, and quantized pumping of spin for three insulating states, that can be accessed by tuning filling fractions. With a combined analysis of momentum-space topology and real-space response, we identify important role of bands supporting even integer invariants, which cannot be addressed with symmetry-based indicators. Our work sets a new standard for the computational diagnosis of two-dimensional, quantum spin-Hall materials by going beyond the [Formula: see text] paradigm and providing an avenue for precise determination of the bulk invariant through computation of quantized, real-space response.


[Correlation between the mRNA expression of tissue inhibitor of metalloproteinase-1 and apparent diffusion coefficient on diffusion-weighted imaging in rats' liver fibrosis].
To explore the correlation between the apparent diffusion coefficient (ADC) and mRNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in different stages of liver fibrosis in rats. Methods: A model of liver fibrosis in rats was established by intraperitoneal injection of high-fat diet combined with porcine serum. After drug administration for 4 weeks, 48 rats served as a model group and 12 rats served as a control group, then they underwent diffusion weighted imaging (DWI) scanning. The value of ADC was calculated at b value=800 s/mm2. The rats were sacrificed and carried out pathologic examination after DWI scanning immediately. The mRNA expression of TIMP-1 was detected by real time-polymerase chain reaction (RT-PCR). The rats of hepatic fibrosis were also divided into a S0 group (n=4), a S1 group (n=11), a S2 group (n=12), a S3 group (n=10), and a S4 group (n=9) according to their pathological stage. The value of ADC and the expression of TIMP-1 mRNA among the different stage groups of liver fibrosis were compared, and the correlation between ADC and the TIMP-1 mRNA were analyzed. Results: The ADC value and the TIMP-1 mRNA expression were significantly different between the control group and the liver fibrosis group (F=46.54 and 53.87, P<0.05). There were significant differences in the value of ADC between every two groups (all P<0.05), except the control group vs the S1 group, the S1 group vs the S2 group, and the S2 group vs the S3 group (all P>0.05). For the comparison of TIMP-1 mRNA, there was no significant difference between the S1 group and the S2 group, the S3 group and the S4 group (both P>0.05). There were significant differences among the rest of the groups (all P<0.05). Rank correlation analysis showed that there was a negative correlation between the ADC value and the TIMP-1 mRNA expression (r=-0.76, P<0.01). Conclusion: When the value of ADC decreases in the progress of rats' liver fibrosis, the mRNA expression of TIMP-1 increases gradually, and there is a negative correlation between them.


[Large accessory spleen torsion with a distorted fascicular structure; a case report].
A 37-year-old woman was admitted with left upper quadrant pain. Imaging examinations revealed a cystic mass with a diameter of 70 mm near the tail of the pancreas. The mass had a distorted fascicular structure adjacent to the hilum of the spleen. On operation the distorted fascicular structure was revealed to be connective tissue including vessels. On histopathological examination, the mass was strongly suspected to be an accessory spleen because spleen-like stroma was recognized, in spite of degeneration due to infarction.


Does the efficacy of asenapine in bipolar disorder increase in the presence of comorbidity with a substance use disorder? A naturalistic study.
Asenapine is a second-generation antipsychotic approved in Europe for treating moderate-to-severe manic episodes in adults affected by type I bipolar disorder (BD-I). We aimed to compare its efficacy in psychiatric inpatients with BD-I, with or without substance use disorder (SUD). We administered flexible asenapine doses ranging from 5-20 mg/day to 119 voluntarily hospitalized patients with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) BD-I diagnosis, with or without SUD. Patients were assessed with clinician-rated questionnaires [i.e. Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Global Assessment of Functioning (GAF)]. Assessments were carried out at baseline (T0, prior to treatment), and 3 (T1), 7 (T2), 15 (T3), and 30 days (T4) after starting treatment for all clinical scales and at T0 and T4 for the GAF. Patients improved on all scales (p < 0.001) across all timepoints, as shown both by paired-sample comparisons and by applying a repeated-measures, generalized linear model (GLM). Patients without comorbid SUD showed greater reductions in BPRS scores at T2 and T3, greater reduction in YMRS scores at T3, and lower HARS scores at all timepoints. HDRS scores did not differ between the two groups at any timepoint. However, the reduction in HARS scores in the comorbid group was stronger than in the BD-I only group, albeit not significantly. Side effects were few and mild-to-moderate. The open-label design and the relatively short observation period may expose to both type I and type II statistical errors (false positive and false negatives). Asenapine showed effectiveness and safety in hospitalized BD-I patients. Its effect was stronger in patients without comorbid SUD.


Fasting induces CART down-regulation in the zebrafish nervous system in a cannabinoid receptor 1-dependent manner.
Central and peripheral mechanisms modulate food intake and energy balance in mammals and the precise role of the type 1 cannabinoid receptor (CB1) in these processes is still being explored. Using the zebrafish, Danio rerio, we show that rimonabant, a CB1-specific antagonist with an EC(50) of 5.15 × 10(-8) m, decreases embryonic yolk sac reserve use. We reveal a developmental overlap between CART genes and CB1 expression in the hypothalamus and medulla oblongata, two brain structures that play crucial roles in appetite regulation in mammals. We show that morpholino knockdown of CB1 or fasting decreases cocaine- and amphetamine-related transcript (CART)-3 expression. Strikingly, this down-regulation occurs only in regions coexpressing CB1 and CART3, reinforcing the link between CB1, CART, and appetite regulation. We show that rimonabant treatment impairs the fasting-induced down-regulation of CART expression in specific brain regions, whereas vehicle alone-treated embryos do not display this rescue of CART expression. Our data reveal that CB1 lies upstream of CART and signals the appetite through the down-regulation of CART expression. Thus, our results establish the zebrafish as a promising system to study appetite regulation.


Early childhood pneumonia in Aborigines of Bourke, New South Wales.
We carried out a retrospective survey of all children born in the district of Bourke , New South Wales, over a three-year period to determine the frequency of lobar pneumonia in the first three years of life. Although more non-Aboriginal children (167) than Aboriginal children (103) were born during this period, there was a striking difference between these groups in the frequency of pneumonia. Twenty-six (25.2%) Aboriginal children had one or more episodes of lobar pneumonia, compared with only five (3%) non-Aboriginal children born during the same period. Characteristic features of the disease in the Aboriginal children included a high rate of recurrent pneumonia (35%), frequent involvement of the upper lobe of the right lung (77%), and often a family history of pneumonia in early childhood. Of those with siblings, 39% of the affected infants had siblings who had suffered from pneumonia in early childhood. No perinatal factors which correlated with the subsequent development of lobar pneumonia could be identified. However, a greater proportion of the affected than of the non-affected children lived in substandard housing conditions.


Transduodenal exploration of the common bile duct in a district general hospital.
In an 8 year period 214 transduodenal explorations were undertaken in a district general hospital. These were performed on 208 patients and in 40 instances a combined supraduodenal and transduodenal approach was employed. There were 23 deaths in 208 patients, a mortality of 11%. Twelve deaths occurred in 64 patients who underwent negative exploration. Postoperative pancreatitis was the most common cause of death and the occurrence resulted in a 53% mortality. We conclude that the transduodenal operation should only be performed by experienced surgeons with definite proof of common bile duct stone, and when the standard supraduodenal approach is unsatisfactory.


Induction of antioxidant enzyme activity by hyperoxia (60 % O2) in the developing chick embryo.
1. At premature birth, man and animals are exposed to relatively high oxygen levels, compared with intra-uterine conditions, at a time when their antioxidant enzyme (AOE) system is still immature. Using the chick embryo as a study model, we investigated changes in the AOE system in response to hyperoxia applied at different time points during the incubation period. Relations between hyperoxia and AOE activity were studied in selected organs (brain, heart, liver, intestine and lungs) of developing chick embryos (during the second half of the incubation period). 2. Incubated White Leghorn eggs were divided into four groups: control (n = 100) and three test groups exposed for 48 h to 60 % O2 on day 10 (test group 1, n = 80), day 14 (test group 2, n = 60) and day 18 (test group 3, n = 30). Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) enzyme activities were measured in homogenates of the brain, heart, liver, intestine and lungs. 3. Exposure to hyperoxia at different time points during incubation resulted in a 2- to 10-fold increase in SOD activity in all organs except the brain. Catalase and GPx enzyme activities were only induced in test group 1, 48 h after initiation of hyperoxia. 4. In the developing chick embryo, hyperoxia can produce a temporary induction of AOE activity, which is dependent on the AOE, organ, incubation time and time point of exposure.


Effects of a Designated Note Writing Hour on Pediatric Intern Adherence to Duty Hours.
Interns spend an inordinate amount of the workday writing notes, leading to less time in direct patient care. Since the introduction of the 80-h workweek, it has been shown that interns spend 12% of the workday in direct patient care, compared to 40% at the computer. A dedicated note-writing hour was introduced into the pediatric intern shift to evaluate its effects on note writing behaviors. Within 1 year of implementation in July 2019, we aimed to establish that 80% of all pediatric intern notes were completed prior to the end of their shift. Time stamps from EPIC electronic health record (EHR) database were reviewed for all notes written by pediatric interns during three periods of interest: prior to the implementation of the hour (Jan-May 2019), immediately after implementation (July-Nov 2019), and a year after (May-Aug 2020). Prior to implementation, 67.9% of notes were completed by sign out. In the period immediately following implementation, and at a year post implementation, percentages increased to 72.5% and 73.5%, respectively. The percentage of notes completed prior to the end of the protected hour improved from 34.0% to 49.5% and 53.7%, respectively. The percentage of notes completed in less than 1 h also increased from 13.9% to 50.6% and 24.9%, respectively. These results indicate that a designated note writing hour for interns offer an effective intervention to improve note writing efficiency, however, the goal of 80% note completion by sign out was not met.


[Pancoast tumor with rheumatic symptoms without Pancost's syndrome--case report].
About 5% of pulmonary lesions are the apical lung tumors, which can be divided in tumors producing and non-producing Pancoast's syndrome. The authors present a case of a 45-year-old male with ambulatory non-diagnosed Pancoast tumor demonstrating with rheumatic symptoms without typical signs of Pancoast's syndrome. Performing a routine chest X-ray after complete treatment of pulmonary inflammatory diseases, as well as in rheumatic disorders was proved fundamental.


Activator role of the pneumococcal Mga-like virulence transcriptional regulator.
Global transcriptional regulators that respond to specific environmental signals are crucial in bacterial pathogenesis. In the case of the Gram-positive pathogen Streptococcus pneumoniae (the pneumococcus), the sp1800 gene of the clinical isolate TIGR4 encodes a protein that exhibits homology to the Mga "stand-alone" response regulator of the group A Streptococcus. Such a pneumococcal protein was shown to play a significant role in both nasopharyngeal colonization and development of pneumonia in murine infection models. Moreover, it was shown to repress the expression of several genes located within the rlrA pathogenicity islet. The pneumococcal R6 strain, which derives from the D39 clinical isolate, lacks the rlrA islet but has a gene (here named mga(Spn)) equivalent to the sp1800 gene. In this work, and using in vivo approaches, we have identified the promoter of the mga(Spn) gene (Pmga) and demonstrated that four neighboring open reading frames of unknown function (spr1623 to spr1626) constitute an operon. Transcription of this operon is under the control of two promoters (P1623A and P1623B) that are divergent from the Pmga promoter. Furthermore, we have shown that the Mga(Spn) protein activates the P1623B promoter in vivo. This activation requires sequences located around 50 to 120 nucleotides upstream of the P1623B transcription start site. By DNase I footprinting assays, we have also demonstrated that such a region includes an Mga(Spn) binding site. This is the first report on the activator role of the pneumococcal Mga-like protein.


[National second opinion network for testicular cancer patients - transferring guidelines into practice!].
The second opinion network for testicular cancer is an internet-based platform addressed to physicians treating testicular cancer patients. They are offered a second opinion before determining further therapy after orchiectomy and completion of staging procedures. The platform has been used in more than 3,000 cases of testicular cancer to date. The rate of discrepancies between first and second opinions is higher than 30%. This suggests a deficit in the implementation of published therapy guidelines. According to our present interim analysis, the second opinion platform helps in avoiding overtreatment of testicular cancer. The high acceptance of the project and the encouraging results of this interim analysis open the door for expansion of the second opinion model to other diseases, e. g., penile carcinoma.


Blood Pressure Management in Hemodialysis Patients: What We Know And What Questions Remain.
Despite having thousands of blood pressure (BP) readings on individual dialysis patients over the course of a year, our knowledge about the optimal assessment of BP, the mechanisms underlying hypertension and its management remain incomplete. Observational studies reveal that BP is lower at home than when measured in the dialysis unit. However, we do not know if using home vs. in-center measurements to guide treatment decisions improves BP control and/or clinical outcomes. Moreover, a recent US study suggests that typical hemodialysis patients are unlikely to adhere to home monitoring over the long term. Volume excess is one of probably many factors mediating hypertension in this population. A randomized clinical trial of aggressively challenging dry weight in patients without overt signs of fluid overload was shown to reduce BP, but there was an increase in vascular access thrombosis and intradialytic hypotension episodes. Long-term studies have not been done; thus, we do not know whether "squeezing dry weight" as a means to control BP is of more benefit than harm. Daily or prolonged nocturnal dialysis consistently has been shown to lower BP. To what extent this is a result of enhanced solute clearance vs. removal of excess volume is not clear. Use of bioimpedance or relative blood volume monitoring to guide fluid management has been tested in small studies, but more data are needed to determine whether their use impacts clinical outcomes. Well-designed clinical trials to determine whether a specific antihypertensive drug class is of benefit, independent of BP lowering, are lacking. The BP target that optimizes outcomes HD patients is also unknown. Observational studies consistently show poorer survival with predialysis BP <140/90 mmHg, although such studies likely are confounded by low BP due to cardiovascular disease and other comorbidities. In this review, we discuss what is known and the questions that remain regarding the epidemiology, diagnosis, etiology, and management of hypertension in hemodialysis patients.


Idarubicin administered during pregnancy: its effects on the fetus.
Acute myeloblastic leukemia, subtype M1, was diagnosed in a 39-year-old G2P1 Japanese woman at 21 weeks' gestation. Remission-induction polychemotherapy, including daunorubicin, performed for one cycle, did not lead to remission. Second-line chemotherapy, including idarubicin, performed for one cycle, was administrated during the early third trimester of pregnancy. Septic shock occurred due to severe myelosuppression. An emergent cesarean section was performed in response to a nonreassuring pattern of the fetal heart rate and a rapid decrease in fetal amniotic fluid. The neonate delivered at 32 weeks' gestation showed no signs of cardiac failure but did show signs of transient myelosuppression, hepatopathy, and elevated creatine kinase. Complete remission was established with idarubicin including chemotherapy.


Biological risk in Italian prisons: data analysis from the second to the fourth wave of COVID-19 pandemic.
The management of COVID-19 in Italian prisons triggered considerable concern at the beginning of the pandemic due to numerous riots which resulted in inmate deaths, damages and prison breaks. The aim of this study is to shed some light, through analysis of the infection and relevant disease parameters, on the period spanning from the second to the fourth wave of the outbreak in Italy's prisons. Reproductive number (Rt) and Hospitalisation were calculated through a Eulerian approach applied to differential equations derived from compartmental models. Comparison between trends was performed through paired t-test and linear regression analyses. The infection trends (prevalence and Rt) show a high correlation between the prison population and the external community. Both the indices appear to be lagging 1 week in prison. The prisoners' Rt values are not statistically different from those of the general population. The hospitalisation trend of inmates strongly correlates with the external population's, with a delay of 2 weeks. The magnitude of hospitalisations in prison is less than in the external community for the period analysed. The comparison with the external community revealed that in prison the infection prevalence was greater, although Rt values showed no significant difference, and the hospitalisation rate was lower. These results suggest that the consistent monitoring of inmates results in a higher infection prevalence while a wide vaccination campaign leads to a lower hospitalisation rate. All three indices demonstrate a lag of 1 or 2 weeks in prison. This delay could represent a useful time-window to strengthen planned countermeasures.


Mixed hemimicelles solid-phase extraction of cephalosporins in biological samples with ionic liquid-coated magnetic graphene oxide nanoparticles coupled with high-performance liquid chromatographic analysis.
A novel mixed hemimicelles solid phase extraction based on magnetic graphene oxide (Fe3O4/GO) and ionic liquid (IL) was developed for the simultaneous extraction and determination of trace cephalosporins in spiked human urine. The high surface area and excellent adsorption capacity of the graphene oxide after modification with1-hexadecyl-3-methylmidazoliumbromide(C16mimBr) were utilized adequately in the solid phase extraction(SPE) process. A comprehensive study of the parameters affecting the extraction recovery, such as the zeta-potential of magnetic graphene oxide, amounts of magnetic graphene oxide and surfactant, pH of solution, ionic strength, extraction time, and desorption condition were optimized. A comparative study on the use of different surfacant-coated Fe3O4/GO NPs as sorbents was presented. Good linearity (R(2)>0.9987) for all calibration curves was obtained. The LODs were ranged between 0.6 and 1.9ng mL(-1) for the cephalosporins and the LOQs were 1.5 to 5.5, respectively. Satisfactory recoveries(84.3% to 101.7%)and low relative standard deviations from 1.7% to 6.3% in biological matrices were achieved. The mixed hemimicelles magnetic SPE (MSPE) method based on ILs and Fe3O4/GO NPs magnetic separation has ever been successfully used for pretreatment of complex biological samples.


[Diagnosis and surgical methods in primary varicose veins].
Modern surgery of varicose veins depends on a differentiated diagnostics. The planning and the type of operation have to take the particular hemodynamics into consideration. The main prerequisites are early operation to prevent secondary popliteal and femoral vein insufficiency and, on the other hand, a restrained tissue-sparing technique in order to preserve transplantable vein segments. Paratibial fasciotomy is a low-risk and technically uncomplicated method for the treatment of severe chronic venous congestion.


Factors influencing evaluations of web site information.
This study investigated the effect of first-person and third-person perceptions of web site information. Responses from a telephone survey of 226 participants in a stratified random sample indicated that (1) most participants had higher evaluations for television news than for news received on the Internet; (2) a third-person effect was present in that most respondents generally thought that other people found the Internet easier to use than they did, and that other people were more likely to believe Internet information and trust the sources of Internet information than they would. Also, (3), evaluations of information on a particular web site could be increased by providing links to other web sites on the same topic. Perhaps links to other web sites may serve as either a "referencing" function or a social confirmation function to increase evaluations of web site information.


Regulatory T cells in a spectrum of HPV-induced cervical lesions: cervicitis, cervical intraepithelial neoplasia and squamous cell carcinoma.
Thriving of tumors amidst rich immune infiltrates is an unexplained paradox. Immune markers on lymphocytic infiltrates in HPV-positive cervicitis, cervical intraepithelial neoplasia III (CIN III), squamous cell carcinoma (SCC) and normal cervices were characterized immunohistochemically. Regulatory T cells were enumerated and phenotypically characterized using antibodies to FOXP3. SCCs had higher numbers of CD4 and CD8 cells; infiltrates expressed more CD25, TGFbeta, and IL10 but had significantly lower IL2 compared with cervicitis and CIN III. Expression of CD25 and IL2 correlated well in cervicitis and CIN III but not in SCC. FOXP3 expression was also higher and ratios of CD4/FOXP3 and CD8/FOXP3 were lower in SCC. A fraction of cervicitis, CIN I, CIN II and CIN III had natural (n) regulatory T cells (Tregs); their lesional distribution was predominantly intraepithelial in cervicitis, while in CIN they were also present in the stroma. The proportion of FOXP3(+) CD25(+); FOXP3(+) CD25(-) and TGFbeta(+) CD25(+) in invasive tumors was 17; 19 and 22 respectively. Cervical tumors are marked by the presence of an immunoregulatory environment, and harbor equal proportions of 'inactive' n Tregs; activated n Tregs; and Tregs operating via TGFbeta. nTregs in cervicitis and CIN may be a potential marker of persistence.


Influence of fixation point of latissimus dorsi tendon transfer for irreparable rotator cuff tear on glenohumeral external rotation: A cadaver study.
Latissimus dorsi tendon transfer is a surgical option for treating irreparable posterosuperior rotator cuff tears, notably when attempting to reconstruct active external rotation. We hypothesized that the positioning of the transfer's point of fixation would differ depending on the desired elbow-to-body external rotation or external rotation with the elbow abducted. Seven shoulders from four whole frozen cadavers were used. We created two systems to install the subject in a semi-seated position to allow external rotation elbow to body and the arm abducted 90°. Traction sutures were positioned on the latissimus dorsi muscle and a massive tear of the rotator cuff was created. We tested six different transfer positions. Muscle contraction of the latissimus dorsi was stimulated using 10-N and 20-N suspended weights. The point of fixation of the latissimus dorsi on the humeral head had an influence on the elbow-to-body external rotation and with 90° abduction (P<0.001). The fixation point for a maximum external rotation with the elbow to the body was the anterolateral position (P<0.016). The fixation point for a maximum external rotation at 90° abduction was the position centered on the infraspinatus footprint (P<0.078). The optimal point of fixation differs depending on whether external rotation is restored at 0° or 90° abduction. Fundamental study, anatomic study.


Role of photodynamic therapy in the treatment of esophageal cancer.
Photodynamic therapy (PDT), a treatment of choice for cancer, induces a photochemical reaction, thereby eradicating tumor cells. This is achieved through the administration of a photosensitizer drug, which is activated with a laser after localization to the tumor mass, and is an approved curative endoscopic ablative treatment for superficial esophageal squamous cell carcinoma (ESCC) in Japan. PDT has been approved for dysplastic Barrett's esophagus and as a palliative treatment for patients with symptomatic obstructive esophageal cancer in US. However, its adverse events and complicated procedure and the development of alternative endoscopic procedures such as endoscopic submucosal dissection, radiofrequency ablation and cryotherapy, have largely limited the practice of PDT in esophageal cancer worldwide. Recently, owing to the invention of second-generation PDT using talaporfin sodium and diode laser, PDT can be performed with less phototoxicity and therefore has regained popularity in the treatment of ESCC. As a salvage treatment for patients with local failure after chemoradiotherapy (CRT), PDT has shown promising complete response with less phototoxicity and shorter sun shade period. In addition, the efficacy and safety of PDT in patients with local failure of ESCC after CRT were shown in several clinical trials. The direction of the study interest of the next-generation PDT is the safety and potential expansion of the indications for its application in the future. This review covers the PDT for the treatment of ESCC and dysplastic Barrett's esophagus, with special focus on the role of PDT in practice for esophageal cancer.


General ion recombination effect in a liquid ionization chamber in high-dose-rate pulsed photon and electron beams.
Liquid ionization chambers (LICs) are highly sensitive to dose irradiation and have small perturbations because of their liquid-filled sensitive volume. They require a sensitive volume much smaller than conventional air-filled chambers. However, it has been reported that the collection efficiency has dependencies on the dose per pulse and the pulse repetition frequency of a pulsed beam. The purpose of this study was to evaluate in detail the dependency of the ion collection efficiency on the pulse repetition frequency. A microLion (PTW, Freiburg, Germany) LIC was exposed to photon and electron beams from a TrueBeam (Varian Medical Systems, Palo Alto, USA) linear accelerator. The pulse repetition frequency was varied, but the dose per pulse was fixed. A theoretical evaluation of the collection efficiency was performed based on Boag's theory. Linear correlations were observed between the frequency and the relative collection for all energies of the photon and electron beams. The decrease in the collected charge was within 1% for all the flattened photon and electron beams, and they were 1.1 and 1.8% for the 6 and 10 MV flattening filter-free photon beams, respectively. The theoretical ion collection efficiency was 0.990 for a 10 MV flattened photon beam with a dose rate of 3 Gy·min-1. It is suggested that the collected charge decreased because of the short time intervals of the beam pulse compared with the ion collection time. Thus, it is important to correctly choose the pulse repetition frequency, particularly when flattening filter-free mode is used for absolute dose measurements.


Taxonomic value of morphological and morphometrical characters in the immature stages of four species of Kampimodromus Nesbitt (Acari: Phytoseiidae) from Italy and Croatia.
The immature stages of four species of Kampimodromus Nesbitt (Acari: Phytoseiidae) from Italy and Croatia have been studied and identified both at stage and species level. Larval stages of Kampimodromus corylosus Kolodochka and all immature stages of Kampimodromus ericinus Ragusa di Chiara & Tsolakis and Kampimodromus langei Wainstein & Arutunjan are described for the first time. The relative length of the posterior dorsal setae Z4 make the larvae of Kampimodromus aberrans (Oudemans) easy to separate from those of the other three species. Nymphs of each species had similar diagnostics to the adults of the respective species. Ontogeny of the idiosomal and leg setation of the Kampimodromus immatures studied in comparison to the available data from immatures of other phytoseiid species is discussed. The length of seta Z4 in the K. aberrans larva, and the number of setae on leg IV of the deutonymphs of the four Kampimodromus species, are proposed as additional taxonomic traits for Phytoseiidae.


[Family environment of the dependent elderly].
Dependency of an aged person, whatever its nature, places the subject in an infantile situation. The interaction of this new situation with the family background will create attitudes and dynamic forces that are apparently irrational and justify, as well as condition, the intervention of a third party. First steps in understanding what is observed can be made with reference to the pressure of the relationship which the patient implicitly exerts on his environment, and which seems to constitute the mainspring of the relationships and attitudes which progressively develop; these can feed a mechanism of increasing disability.


Development and validation of a risk-adjustment model for mortality and hospital length of stay for trauma patients: a prospective registry-based study in Australia.
Adequate risk adjustment for factors beyond the control of the healthcare system contributes to the process of transparent and equitable benchmarking of trauma outcomes. Current risk adjustment models are not optimal in terms of the number and nature of predictor variables included in the model and the treatment of missing data. We propose a statistically robust and parsimonious risk adjustment model for the purpose of benchmarking. This study analysed data from the multicentre Australia New Zealand Trauma Registry from 1 July 2016 to 30 June 2018 consisting of 31 trauma centres. The primary endpoints were inpatient mortality and length of hospital stay. Firth logistic regression and robust linear regression models were used to study the endpoints, respectively. Restricted cubic splines were used to model non-linear relationships with age. Model validation was performed on a subset of the dataset. Of the 9509 patients in the model development cohort, 72% were male and approximately half (51%) aged over 50 years . For mortality, cubic splines in age, injury cause, arrival Glasgow Coma Scale motor score, highest and second-highest Abbreviated Injury Scale scores and shock index were significant predictors. The model performed well in the validation sample with an area under the curve of 0.93. For length of stay, the identified predictor variables were similar. Compared with low falls, motor vehicle occupants stayed on average 2.6 days longer (95% CI: 2.0 to 3.1), p<0.001. Sensitivity analyses did not demonstrate any marked differences in the performance of the models. Our risk adjustment model of six variables is efficient and can be reliably collected from registries to enhance the process of benchmarking.


Effect of Tamarindus indica. L on the bioavailability of ibuprofen in healthy human volunteers.
The influence of Tamarindus indica L fruit extract incorporated in a traditional meal on the bioavailability of Ibuprofen tablets 400 mg dose when given concurrently was studied in 6 healthy human volunteers. There was a statistically significant increase in the plasma levels of Ibuprofen and its metabolites hydroxy-ibuprofen and carboxy-ibuprofen respectively, when the meal containing Tamarindus indica fruit extract was administered with the ibuprofen tablets than when taken under fasting state or with the meal without the fruit extract. The C(max), AUC(0-6 hr) and Ka for ibuprofen increased from 38 +/- 0.70 microg/ml to 42 +/- 0.98 microg/ml (p > 0.05); and 28.03 +/- 2.40 microg/ml x hr to 56.51 +/- 0.16 microg/ml x hr (p < 0.05) and 1.048 +/- 0.02hr(-1) to 2.781 +/- 0.11 hr(-1) (p < 0.05) respectively. There was no change in the t(max) (120.00 +/- 0.43m) but there was a decrease in the k(el) from 0.63 +/- 0.20 hr(-1) to 0.46 +/- 0.11 hr(-1) (p<0.05). Similarly the C(max), AUC(0-6 h) and Ka for hydroxy-ibuprofen rose from 43 +/- 0.76 microg/ml to 45 +/- 0.16 microg/ml (p < 0.05); 39.04 +/- 2.30 microg/ml x hr to 59.49 +/- 2.39 microg/ml.hr in (p < 0.05) and 1.498 +/- 0.79hr(-1) to 3.442 +/- 0.23 hr(-1) (p < 0.05) respectively; while the C(max), AUC(0-6 h) and Ka for carboxy-ibuprofen rose from 48 +/- 0.7 microg/ml to 51 +/- 0.16 microg/ml (p < 0.05); 41.972 +/- 0.68 microg/ml x hr to 63.948 +/- 0.12 microg/ml x hr (p < 0.05) and 1.649 +/- 0.08 hr(-1) to 4.187 +/- 0.42 hr(-1) (p < 0.05) respectively. The study has indicated that Tamarindus indica L. fruit extract significantly increased the bioavailability of Ibuprofen.


Long-term treatment with Pilogel/beta-blocker in glaucoma patients.
In a multicentre clinical trial thirteen patients with primary open angle glaucoma or ocular hypertension were followed during at least six months while selfinstilling Pilogel (once daily) and topical beta-blocker (twice daily). After six months of combination therapy there was an average decrease in intra-ocular pressure (IOP) of 33.6% 9.5 hours after Pilogel administration and an IOP decrease of 23.4% 22.5 hours after Pilogel administration. With topical beta-blocker alone, an average IOP decrease of 15% was measured. Throughout the study we observed in six patients (46.1%) a superficial punctate keratitis which mostly spontaneously cleared. We did not see any serious side-effects after six months of combination therapy.


Use of the Draw-A-Person with conduct-disordered children.
The Draw-A-Person test was administered to 40 conduct-disordered and 40 nonconduct-disordered children and adolescents. There were 20 boys and 20 girls, ages 10 to 16 years, in each group. Two independent judges rated the drawings for presence or absence of indicators of aggressiveness that should accompany a conduct disorder, but no significant differences were found between groups or sexes.


Wigner surmise for Hermitian and non-Hermitian chiral random matrices.
We use the idea of a Wigner surmise to compute approximate distributions of the first eigenvalue in chiral random matrix theory, for both real and complex eigenvalues. Testing against known results for zero and maximal non-Hermiticity in the microscopic large- N limit, we find an excellent agreement valid for a small number of exact zero eigenvalues. Compact expressions are derived for real eigenvalues in the orthogonal and symplectic classes and at intermediate non-Hermiticity for the unitary and symplectic classes. Such individual Dirac eigenvalue distributions are a useful tool in lattice gauge theory, and we illustrate this by showing that our results can describe data from two-color quantum chromodynamics simulations with chemical potential in the symplectic class.


Low-p_{T} e^{+}e^{-} Pair Production in Au+Au Collisions at sqrt[s_{NN}]=200 GeV and U+U Collisions at sqrt[s_{NN}]=193 GeV at STAR.
We report first measurements of e^{+}e^{-} pair production in the mass region 0.4<M_{ee}<2.6 GeV/c^{2} at low transverse momentum (p_{T}<0.15 GeV/c) in noncentral Au+Au collisions at sqrt[s_{NN}]=200 GeV and U+U collisions at sqrt[s_{NN}]=193 GeV. Significant enhancement factors, expressed as ratios of data over known hadronic contributions, are observed in the 40%-80% centrality of these collisions. The excess yields peak distinctly at low p_{T} with a width (sqrt[⟨p_{T}^{2}⟩]) between 40 and 60 MeV/c. The absolute cross section of the excess depends weakly on centrality, while those from a theoretical model calculation incorporating an in-medium broadened ρ spectral function and radiation from a quark gluon plasma or hadronic cocktail contributions increase dramatically with an increasing number of participant nucleons. Model calculations of photon-photon interactions generated by the initial projectile and target nuclei describe the observed excess yields but fail to reproduce the p_{T}^{2} distributions.


Pneumonia caused by diesel fuel aspiration.
An 18 years old Turkish boy was admitted to hospital due to cough, chest pain and shortness of breath for 4 days. Twentyfour hours before the onset of symptoms, the patient had accidentally aspirated diesel while siphoning from the fuel tank of a car. On admission, he was febrile and tachypnoeic. There were fine crackles on auscultation of the lungs. Chest X-ray revealed bilateral infiltration in the lower lung zones. Arterial blood gas analysis showed pH of 7.42, PaO2 of 45.6 mmHg, PaCO2 of 41.3 mmHg and oxygen saturation of 85.2%. He was treated with course of corticosteroid, antibiotic and oxygen supplementation. Chest X-ray showed near-complete resolution 2 weeks after discharge.


Women's psychosocial outcomes of breast augmentation with silicone gel-filled implants: a 2-year prospective study.
This study examined the experiences of 360 women receiving bilateral breast augmentation with Dow Corning's Silastic MSI (textured) or Silastic II (smooth) gel-filled mammary implants. Before surgery, the women completed a quantitative assessment of their surgical expectations and concerns. At 6, 12, and 24 months postoperatively, they rated their satisfaction with surgery and its specific psychosocial outcomes, their concerns, and benefits-to-risks appraisals of the augmentation. The women reported very high levels of satisfaction with the procedure and its psychosocial outcomes, which did not change over time. Throughout the 2-year period, over 90 percent of the women were satisfied with surgery and their resultant body-image changes. Their concerns about risks, reported by 19 percent before surgery, declined after surgery and remained subsequently stable. Most participants (75 to 85 percent) reported that the benefits of surgery exceeded its risks. Postoperative events such as significant capsular contracture that compromised aesthetic results diminished aspects of satisfaction, whereas less obvious events did not. Systematic analysis of attrition (i.e., missing assessments) did not indicate any biases because of complications or psychosocial outcomes. Evaluation of a possible impact of the publicity surrounding the Food and Drug Administration's voluntary moratorium on the use of silicone gel-filled breast implants, which occurred during the study, revealed a limited effect, if any, on women's psychosocial outcomes. Findings are discussed in relation to the study's methodological strengths and limitations and with respect to the broader context of patient care.


Subpopulation-proteomics reveal growth rate, but not cell cycling, as a major impact on protein composition in Pseudomonas putida KT2440.
Population heterogeneity occurring in industrial microbial bioprocesses is regarded as a putative effector causing performance loss in large scale. While the existence of subpopulations is a commonly accepted fact, their appearance and impact on process performance still remains rather unclear. During cell cycling, distinct subpopulations differing in cell division state and DNA content appear which contribute individually to the efficiency of the bioprocess. To identify stressed or impaired subpopulations, we analyzed the interplay of growth rate, cell cycle and phenotypic profile of subpopulations by using flow cytometry and cell sorting in conjunction with mass spectrometry based global proteomics. Adjusting distinct growth rates in chemostats with the model strain Pseudomonas putida KT2440, cells were differentiated by DNA content reflecting different cell cycle stages. The proteome of separated subpopulations at given growth rates was found to be highly similar, while different growth rates caused major changes of the protein inventory with respect to e.g. carbon storage, motility, lipid metabolism and the translational machinery. In conclusion, cells in various cell cycle stages at the same growth rate were found to have similar to identical proteome profiles showing no significant population heterogeneity on the proteome level. In contrast, the growth rate clearly determines the protein composition and therefore the metabolic strategy of the cells.


Rapid and efficient genotype analysis of the COL1a1 Sp1 binding site dimorphism, a genetic marker for bone mineral density.
A biallelic G/T polymorphism within the first intron of COL1A1 gene at a recognition site for the transcription factor Sp1 has been shown to be significantly related to bone mass and osteoporotic fracture. To date this polymorphism has been detected by conventional genomic DNA amplification followed by restriction enzyme digestion and polyacrylamide gel electrophoresis. We have designed a rapid and efficient genotyping method based on allele-specific polymerase chain reaction


Alginate Microfiber System for Expansion and Direct Differentiation of Human Embryonic Stem Cells.
Pluripotent human embryonic stem cells (hESCs) are a potential renewable cell source for regenerative medicine and drug testing. To obtain adequate cell numbers for these applications, there is a need to develop scalable cell culture platforms to propagate hESCs. In this study, we encapsulated hESCs in calcium alginate microfibers as single cells, for expansion and differentiation under chemically defined conditions. hESCs were suspended in 1% (w/v) alginate solution at high cell density (>10(7) cells/mL) and extruded at 5 m/min into a low calcium concentration bath (10 mM) for gelation. Mild citrate buffer (2.5 mM), which did not affect hESCs viability, was used to release the cells from the calcium alginate hydrogel. Encapsulation as single cells was critical, as this allowed the hESCs to grow in the form of relatively small and uniform aggregates. This alginate microfiber system allowed for expansion of an hESC line, HUES7, for up to five passages while maintaining pluripotency. Immunohistochemistry, polymerase chain reaction, and other analyses showed that passage 5 (P5) HUES7 cells expressed proteins and genes characteristic of pluripotent stem cells, possessed normal karyotype, and were able to form representative tissues of the three embryonic germ layers in vitro and in vivo. Encapsulated HUES7 cells at P5 could also be induced to directly differentiate into liver-like cells. Collectively, our experiments show that the alginate microfiber system can be used as a three-dimensional cell culture platform for long-term expansion and differentiation of hESCs under defined conditions.


Suppressor PAQR3 associated with the clinical significance and prognosis in esophageal squamous cell carcinoma.
Progestin and adipoQ receptor family member 3 (PAQR3) is a novel tumor suppressor; however, its function in esophageal cancer is not well understood. The present study explored the association between PAQR3, and the survival and clinical phenotype in patients with esophageal squamous cell carcinoma (ESCC). The expression of PAQR3 in 80 cases of ESCC and its corresponding adjacent tissues was detected by reverse transcription-quantitative polymerase chain reaction. The results demonstrated that PAQR3 expression in cancer tissues was significantly lower compared with that in adjacent tissues. Clinicopathological analysis indicated that PAQR3 expression was significantly correlated with ethnicity (P=0.032), tumor length (P=0.019), lymph node metastasis (P=0.011) and local recurrence (P=0.009). Notably, the Kaplan-Meier survival curve demonstrated that a decrease in PAQR3 expression was associated with poor prognosis in patients with ESCC. Multivariate analysis indicated that PAQR3 expression was an independent prognostic indicator for patients with ESCC. PAQR3 may serve an important role in the progress of ESCC and become a potential candidate for ESCC targeted therapy.


Circle of Life Awards.
This years winners of the AHAs annual awards for outstanding end-of-life care learned from the past, building lean, flexible programs that can survive the roller-coaster of health care financing and that are adaptable by nearly any hospital with a minimal investment.


Nuclear transcription of long hairpin RNA triggers innate immune responses.
RNA interference (RNAi) is one of the most promising tools for deciphering the human genome and has great therapeutic potential. However, its high target specificity limits its efficiency for therapeutic protection from viruses with high rates of genetic mutation. This limitation may be overcome by the expression of long hairpin RNAs (lhRNAs). Indeed, lhRNAs have been shown recently to have increased efficacy over short interfering RNAs (siRNAs) as protective antiviral agents. Here, we investigate the expression of lhRNAs and demonstrate unintended effects. We show that overexpressed lhRNAs are exported to the cytoplasm. As a consequence, we detect activation of innate immune signaling pathways by lhRNAs. With growing concerns about the complexity of cytoplasmic detection of dsRNAs by the innate immune machinery, this work highlights the need for closer scrutiny when using lhRNAs as potential antiviral agents.


Transcriptomics and venomics: implications for medicinal chemistry.
Over the last three decades, transcriptomic studies of venom gland cells have continuously evolved, opening up new possibilities for exploring the molecular diversity of animal venoms, a prerequisite for the discovery of new drug candidates and molecular phylogenetics. The molecular complexity of animal venoms is much greater than initially thought. In this review, we describe the different technologies available for transcriptomic studies of venom, from the original individual cloning approaches to the more recent global Next Generation Sequencing strategies. Our understanding of animal venoms is evolving, with the discovery of complex and diverse bio-optimized cocktails of compounds, including mostly peptides and proteins, which are now beginning to be studied by academic and industrial researchers.


Ingested bony foreign body abutting thoracic aorta.
The authors present the case of a 38-year-old female who presented with an ingested oesophageal foreign body (lamb bone) following consumption of a casserole. The bone was initially not seen on plain x-ray but CT imaging revealed a 21×20 mm pyramid shaped bone distending the proximal oesophageal mucosa and lodged only 2 mm from the aortic arch. Cardiothoracic surgery services were available on standby to perform an emergency thoracotomy in the event of any haemorrhage. However, the bone was removed successfully with rigid oesophagoscopy and the patient made a full recovery.


The site-specific distribution of atheromatous plaques in the coronary arteries.
The etiology of atherosclerosis is still unknown, but there are several hypotheses trying to explain this complex disease. Most consider atherosclerosis as a cholesterol storage disease. However, hypercholesterolemia is not a cause but a risk factor. Besides, like other well-known systemic risk factors, it does not explain the uneven distribution of atheromatous plaques in the vasculature. Atherosclerotic lesions develop mainly at vulnerable "risk points" of the arterial wall such as curvatures and near side branches, and predominantly in the left anterior descending (LAD), while the left circumflex (LCx) artery is relatively spared. Furthermore, atheromatous plaques are present mainly in the proximal segments in the LAD and LCx, in contrast to the right coronary artery (RCA), where plaques are more evenly distributed. The hemodynamic theory explains to some extent the distribution of atherosclerotic lesions and considers atherosclerosis as a reactive biological response of endothelial cells to wall shear stress. In this review, we discuss the interplay of concentration of low-density lipoproteins at the luminal surface and local hemodynamic forces (disturbed flow) that reduce wall shear stress in the process of plaque formation. Moreover, we present the distribution of atheromatous plaques in the coronary arteries in autopsy studies and imaging methods such as cardiac computed tomography angiography and invasive coronary angiography.


Delayed diagnosis of congenital factor IX deficiency (Christmas disease) in a girl with Turner's Syndrome.
Patients with Turner's syndrome are at risk of X-linked recessive disorders. We report a case of a young girl with Turner's syndrome with persistent mildly abnormal coagulation studies associated with a mild to moderate bleeding diathesis. The abnormalities were initially attributed to intrahepatic cholestasis and were partially responsive to vitamin K. After an interval of several years an episode of unexplained iron deficiency anaemia prompted re-investigation of the mild coagulopathy. Disproportionate reduction in the factor IX concentration and restoration of haemostasis with factor IX concentrate lead to a revised provisional diagnosis of mild haemophilia B which was subsequently confirmed by sequencing the factor IX gene.


Cardiovascular disease in obesity hypoventilation syndrome - A review of potential mechanisms and effects of therapy.
Cardiovascular disease is common in patients with obesity hypoventilation syndrome (OHS) and accounts in part for their poor prognosis. This narrative review article examines the epidemiology of cardiovascular disease in obesity hypoventilation syndrome, explores possible contributing factors and the effects of therapy. All studies that included cardiovascular outcomes and biomarkers were included. Overall, there is a higher burden of cardiovascular disease and cardiovascular risk factors among patients with obesity hypoventilation syndrome. In addition to obesity and sleep-disordered breathing, there are several other pathophysiological mechanisms that contribute to higher cardiovascular morbidity and mortality in OHS. There is evidence emerging that positive airway pressure therapy and weight loss have beneficial effects on the cardiovascular system in obesity hypoventilation syndrome patients, but further research is needed to clarify whether this translates to clinically important outcomes.


Molecular modeling studies of 4,5-dihydro-1H-pyrazolo[4,3-h] quinazoline derivatives as potent CDK2/Cyclin a inhibitors using 3D-QSAR and docking.
CDK2/cyclin A has appeared as an attractive drug targets over the years with diverse therapeutic potentials. A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) followed by molecular docking studies were performed on a series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent CDK2/cyclin A inhibitors. The CoMFA and CoMSIA models, using 38 molecules in the training set, gave r(2) (cv) values of 0.747 and 0.518 and r(2) values of 0.970 and 0.934, respectively. 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. Molecular docking was applied to explore the binding mode between the ligands and the receptor. The information obtained from molecular modeling studies may be helpful to design novel inhibitors of CDK2/cyclin A with desired activity.


Antigen-specific, major histocompatibility complex-restricted T cell receptors.
In this paper we have summarized our work on the structure of the receptor for Ag/MHC on 3 T cell hybridomas. In each case, these receptors have been identified by their reaction with antibodies, thought to be directed against Ag/MHC receptors because of their clone-specificity, and their ability to interfere with Ag/MHC recognition by the relevant hybridoma. The antibodies precipitate approximately 85 kd molecular weight heterodimeric glycoproteins from these cells. These reduce to 2 chains of 40-43 kd, one of acidic and the other of basic pI. These bulk characteristics apply to receptors from Class II-restricted, as well as Class I-specific T cells. There is evidence of molecular weight heterogeneity for both alpha and beta-chains in the mouse, both having 40 and 43 kd forms. Isoelectric focussing patterns suggest that both chains vary in amino acid sequence between clones. Peptide maps show that the receptor varies in amino acid sequence between clones, but that some peptides appear common, i.e., the receptor seems to have both variable and constant amino acid sequences. It is even possible that allotypic differences between the peptide maps of BALB/c and C57BL/6-derived receptors have been identified, though more data will be needed to confirm this. Finally we have recently shown that reaction with an anti-idiotype predicts both the Ag and MHC specificity of the T cell hybridoma bearing it, suggesting that a single receptor, responsible for binding both Ag and MHC, is identified by the anti-idiotypic antibody. The similarities between these T cell-bourne molecules, and immunoglobulin are inescapable. Both are disulphide-linked glycoproteins made up of 2 chains, both of which may vary in amino acid sequence. Secreted immunoglobulin is, of course, polyvalent, being composed of two or more of each type of chain, this contributes to the efficiency with which the molecule can bind polyvalent antigen or build precipitable lattices. Similar constraints do not apply to T cell-bound receptors, which do not seem to have a secreted form.


Cavernous sinus syndrome as the presentation of malignant lymphoma: case report and review of the literature.
Cavernous sinus syndrome (CSS) is an unusual presentation of malignant lymphoma. We report a patient with lymphoma that presented with CSS, and we review the literature on nine other reported cases. Sharp retroorbital pain, paraesthesia around the orbit, and complete 6th nerve palsy were dominant presenting symptoms. In all cases, the tumor developed on the right side. The computed tomographic scan was abnormal in only two of the nine patients during the early stages of the disease. The dominant histological type was large cell lymphoma. The mean age of the patients was 45 years. The mean survival time after the first presenting symptom was 8.7 months. Two of the reported patients as well as our patient had disseminated disease, which became evident at autopsy.


[Mechanism of Proliferation and Apoptosis of Acute Promyelocytic Leukemia Cell Line NB4 Induced by TPA].
To investigate the effect of phorbol-12-myristate-13-ace-tate (TPA) on the proliferation and apoptosis of acute promyelocytic leukemia cell line NB4 and its molecular mechanism. The effect of different concentrations of TPA on the proliferation of NB4 cells at different time points was detected by CCK-8 assay. The morphological changes of NB4 cells were observed by Wright-Giemsa staining. The cell cycle and apoptosis of NB4 cells after TPA treatment were detected by flow cytometry. The mRNA expressions of NB4 cells after TPA treatment were analyzed by high-throughput microarray analysis and real-time quantitative PCR. Western blot was used to detect the protein expression of CDKN1A, CDKN1B, CCND1, MYC, Bax, Bcl-2, c-Caspase 3, c-Caspase 9, PIK3R6, AKT and p-AKT. Compared with the control group, TPA could inhibit the proliferation of NB4 cells, induce the cells to become mature granulocyte-monocyte differentiation, and also induce cell G1 phase arrest and apoptosis. Differentially expressed mRNAs were significantly enriched in PI3K/AKT pathway. TPA treatment could increase the mRNA levels of CCND1, CCNA1, and CDKN1A, while decrease the mRNA level of MYC. It could also up-regulate the protein levels of CDKN1A, CDKN1B, CCND1, Bax, c-Caspase 3, c-Caspase 9, and PIK3R6, while down-regulate MYC, Bcl-2, and p-AKT in NB4 cells. TPA induces NB4 cell cycle arrest in G1 phase and promotes its apoptosis by regulating PIK3/AKT signaling pathway.


Steric zipper formed by hydrophobic peptide fragment of Syrian hamster prion protein.
Steric zippers, where the residues of two neighboring β-sheet layers are tightly interdigitated, have been proposed as fundamental structural units of amyloid fibrils by Eisenberg and co-workers. The steric zipper formed by polypeptides containing the palindromic sequence AGAAAAGA has a distinctive feature that the distance between two interdigitated β-sheet layers is comparable to the interstrand distance of the individual β-sheet. This structural motif is of great interest in the study of prion disease because the AGAAAAGA sequence is highly conserved in prion proteins of different species. In this work, the amyloid fibrils formed by the polypeptides of PrP(113-127), viz. Ac-AGAAAAGAVVGGLGG-NH(2), are taken as the model compound to investigate the biophysical principles governing the steric zipper formation. The target fibrils adopt the structural motif of class 7 steric zipper, which is formed by stacking of antiparallel β-sheet layers with residue 117 + k forming backbone hydrogen bonds to residue 120 - k. Implication of our results in the infectivity of scrapie prion is briefly discussed.


Association between fat content of breast milk and maternal nutritional status and infants' weight in tabriz, iran.
The aim of this study was to investigate the relationship between breast milk fat content with maternal anthropometric status, energy and macronutrient intake and weight for age Z-score of exclusively breastfed infants. Breast milk samples and information on energy and macronutrients intake (using 24-hour recall method for 3 days) were collected from 182 lactating women. Weight and height of mothers and infants were measured and the body mass index (BMI) and weight for age Z-score (WAZ) were calculated. The fat content of the milk samples was measured by the Gerber method. The mean daily energy intake was 2390 ± 405 kcal which was lower than the recommended values for mothers. The mean fat content of the milk samples was 3.52 ± 1.41 g/dl, which was significantly associated with dietary carbohydrate consumption (β= 0.39, P<0.004) and BMI (β= 0.28, P<0.02). A significant association between the WAZ of infants and maternal BMI (β= 0.36, P<0.001) was recorded. The WAZ of infants whose mothers' breast milk lipid content was more than 3 g/dl was significantly higher than those whose mothers had lower breast milk lipid content (P<0.031). Further studies need to be done on the effect of fat content of breast milk on infant's weight and how maternal factors regulate the composition of breast milk.


Acute episodic inflammatory lesions of the mucous membrane and skin.
The first consideration in the treatment of erythema multiforme is to search for and eliminate a possible underlying cause. Mild cases require little treatment. Severe forms of the disease must receive prompt, active therapeutic measures. Fluid and electrolyte imbalance must be corrected, secondary bacterial infections must be combated with topical or systemic antibiotics, and large doses of systemic corticosteroids are used for short periods. Without treatment, lesions can persist for many weeks. Mild forms of the disease, which constitute most of the cases, usually subside in a few days to two to three weeks without sequelae. Severe forms persist for three to six weeks longer; sequelae include neurologic changes, corneal opacities, blindness, conjunctival, vaginal, or preputial synechiae, and esophageal strictures. Mortality of all forms has been reported as less than 0.5% but severe cases, at approximately 10%. Recurrences are likely in approximately 25% of the cases; the pattern is variable, chronic, and episodic.


Randomized, controlled trial of high-dose influenza vaccine among frail residents of long-term care facilities.
Despite vaccination, residents of long-term-care facilities (LTCFs) remain at high risk of influenza-related morbidity and mortality. More-effective vaccine options for this population are needed. We conducted a single-blinded, randomized, controlled trial comparing high-dose (HD) to standard-dose (SD) inactivated influenza vaccine (IIV) in 205 frail, elderly residents of LTCFs during the 2011-2012 and 2012-2013 influenza seasons. Hemagglutination inhibition (HI) antibody titers were measured at baseline and 30 and 180 days following vaccination. A total of 187 subjects (91%) completed the study. The mean age was 86.7 years. Geometric mean titers (GMTs) were significantly higher (P < .05) at day 30 for HD recipients, compared with SD recipients, for all comparisons except influenza A(H1N1) during 2012-2013 (the HD formulation was noninferior to the SD formulation for influenza A[H1N1] during 2012-2013). GMTs for HD and SD recipients during 2011-2012 were as follows: influenza A(H1N1), 78 (95% confidence interval [CI], 45-136) and 27 (95% CI, 17-44), respectively; influenza A(H3N2), 26 (95% CI, 17-40) and 10 (95% CI, 7-15), respectively; and influenza B, 26 (95% CI, 19-35) and 14 (95% CI, 11-18), respectively. During 2012-2013, GMTs for HD and SD recipients were as follows: influenza A(H1N1), 46 (95% CI, 33-63) and 50 (95% CI, 37-67); influenza A(H3N2), 23 (95% CI, 18-31) and 14 (95% CI, 11-18), respectively; and influenza B, 26 (95% CI, 21-32) and 17 (95% CI, 14-22), respectively. GMTs were significantly higher at day 180 for HD recipients, compared with SD recipients, for influenza A(H3N2) in both years (P < .001). Among frail, elderly residents of LTCFs, HD influenza vaccine produced superior responses for all strains except influenza A(H1N1) in 2012-2013. NCT01654224.


Coupling Between Cell Cycle Progression and the Nuclear RNA Polymerases System.
Eukaryotic life is possible due to the multitude of complex and precise phenomena that take place in the cell. Essential processes like gene transcription, mRNA translation, cell growth, and proliferation, or membrane traffic, among many others, are strictly regulated to ensure functional success. Such systems or vital processes do not work and adjusts independently of each other. It is required to ensure coordination among them which requires communication, or crosstalk, between their different elements through the establishment of complex regulatory networks. Distortion of this coordination affects, not only the specific processes involved, but also the whole cell fate. However, the connection between some systems and cell fate, is not yet very well understood and opens lots of interesting questions. In this review, we focus on the coordination between the function of the three nuclear RNA polymerases and cell cycle progression. Although we mainly focus on the model organism Saccharomyces cerevisiae, different aspects and similarities in higher eukaryotes are also addressed. We will first focus on how the different phases of the cell cycle affect the RNA polymerases activity and then how RNA polymerases status impacts on cell cycle. A good example of how RNA polymerases functions impact on cell cycle is the ribosome biogenesis process, which needs the coordinated and balanced production of mRNAs and rRNAs synthesized by the three eukaryotic RNA polymerases. Distortions of this balance generates ribosome biogenesis alterations that can impact cell cycle progression. We also pay attention to those cases where specific cell cycle defects generate in response to repressed synthesis of ribosomal proteins or RNA polymerases assembly defects.


Effect of the initiation of noninvasive bi-level positive airway pressure on haemodynamic stability.
Noninvasive ventilation using noninvasive bilevel positive airway pressure (Bi-PAP) has been shown to be an effective means of improving oxygenation and respiratory status in patients with obstructive pulmonary disease (COPD) and acute congestive heart failure (CHF). However, it is uncertain what effects this positive airway pressure has on the haemodynamic condition of these patients. This study examines the acute changes in basic circulatory parameters with the initiation of Bi-PAP. Noninvasive measurements of the heart rate, systolic and diastolic arterial pressure, cardiac index, total peripheral resistance, ventricular ejection time, and total diastolic time were determined by impedance cardiography before and after the institution of Bi-PAP (pressures 15/5) in a group of healthy volunteers. In a collateral study, the same measurements were made in COPD patients in whom Bi-PAP was initiated for therapeutic reasons. Changes in the haemodynamic parameters were analysed using a paired t-test (p < 0.05). In the 12 healthy volunteers studied there were no significant differences in any of the haemodynamic parameters measured (average cardiac index: 2.75 +/- 0.78) over a period of 15 minutes after the placement of Bi-PAP. Similar results for most haemodynamic parameters were found in the 7 COPD patients with imminent respiratory failure (average respiratory rate 24.8 +/- 3.2) when Bi-PAP was utilized with the exception of significant but small increases in the cardiac index, stroke volume and oxygen saturation (p<0.05). While Bi-PAP is frequently used in the treatment of patients with acute respiratory failure, little is known about its effect on haemodynamics. This study suggests that the effects of the initiation of Bi-PAP on the general circulation and cardiac output may be of minor relevance.


Multi-technique approach for qualitative and quantitative characterization of furazidin degradation kinetics under alkaline conditions.
Degradation of drug furazidin was studied under different conditions of environmental pH (11-13) and temperature (30-60°C). The novel approach of hybrid hard- and soft-multivariate curve resolution-alternating least squares (HS-MCR-ALS) method was applied to UV-vis spectral data to determine a valid kinetic model and kinetic parameters of the degradation process. The system was found to be comprised of three main species and best characterized by two consecutive first-order reactions. Furazidin degradation rate was found to be highly dependent on the applied environmental conditions, showing more prominent differences between both degradation steps towards higher pH and temperature. Complimentary qualitative analysis of the degradation process was carried out using HPLC-DAD-TOF-MS. Based on the obtained chromatographic and mass spectrometric results, as well as additional computational analysis of the species (theoretical UV-vis spectra calculations utilizing TD-DFT methodology), the operating degradation mechanism was proposed to include formation of a 5-hydroxyfuran derivative, followed by complete hydrolysis of furazidin hydantoin ring.


The inter-relationship between mandibular autorotation and maxillary LeFort I impaction osteotomies.
The purposes of the present investigation were to: 1)locate the instantaneous rotation center of mandible autorotation during maxillary surgical impaction; 2) identify the discrepancies between the resultant mandibular position following by maxillary surgical impaction and presurgical predictions, which use the radiographic condylar center as the rotation center for mandibular autorotation; and 3)find the interrelation between the magnitude of maxillary surgical impaction and the sagittal change of mandible. Ten patients underwent maxillary LeFort I impaction without concomitant major mandibular ramus split osteotomies were included. The preoperative (T0) and postoperative (T1) lateral cephalograms were used to evaluate the surgical changes and locate the center of rotation of mandibular autorotation with Reuleaux method. Prediction errors were measured by comparing the predicted (Tp) and postoperative (T1) cephalometric tracings. The magnitude of the maxillary surgical impaction was compared to the positional changes of mandible after mandibular autorotation with correlation and regression analysis. The results demonstrated that the centers of mandibular autorotation located 2.5 mm behind and 19.6 mm below the radiographic condylar center of the mandible in average with large individual variations. By using the radiographic condylar center of the mandible to predict the mandibular autorotation would overestimate the horizontal position of chin by 2 mm and underestimate the vertical position of chin by 1.3 mm following an average of 5 mm surgical maxillary impaction. The magnitude of maxillary impaction was highly and positively correlated to the horizontal displacement of chin position. The rotation centers of mandibular autorotation following by maxillary LeFort I impaction osteotomies might not usually locate at the radiographic condylar center of the mandible also with large individual variations in their positions. Surgeons and orthodontists should be aware of the horizontal and vertical discrepancies of chin positions while planning a two-jaw surgery by using the radiographic center of mandibular condyle as the rotation center in mandibular autorotation.


Occupational obstructive airway diseases in Germany.
In industrialized countries, occupational asthma caused by allergens and irritants due to workplace exposure is increasing. More than 8,000 such claims were made in Germany (10.5% of all decided occupational disease claims) in 1995; 1,900 were confirmed (6.5% of all confirmed claims). The legal basis and the occupational disease-related regulations of trade-assigned statutory accident insurance institutions ('Berufsgenossenschaften') in Germany are described. Hitherto, three occupational disease categories for obstructive airway disorders existed: due to sensitizing agents, due to chemical-irritative or toxic agents, and due to isocyanates. Approximately 40% of accepted claims for occupational asthma and rhinitis result from exposure to flour. Ongoing changes in the recognition of work-related airway disease symptoms account for differences in the incidence and prevalence as reported over the years. Recently, chronic obstructive bronchitis and/or emphysema of hard coal miners have been included in the German list of occupational diseases.


Antibodies directed to envelope proteins of hepatitis C virus outside of hypervariable region 1.
The relatively high variability of the hepatitis C virus (HCV) envelope proteins E1 and E2 suggests that parts of these proteins other than the hypervariable region 1 (HVR1) might be involved in the induction of virus neutralizing antibodies. To test this hypothesis, two HCV proteins, pE1 and pE2 delta, were generated by in vitro translation. They represent amino acids 174-337 of E1 and 411-688 of E2, respectively, of isolate HCV-AD78; the protein pE2 delta contained no HVR1. As a control, protein pG.HVR1, which represents amino acids 384-410 of HVR1 of isolate HCV-AD78, was expressed separately. These three proteins were used in an immunoprecipitation assay to detect the presence of antiviral antibodies in sera of patients infected with the same isolate of HCV (HCV-AD78). Sera were obtained 4-8 months postinfection from patients who later resolved an acute infection or developed chronic liver disease. A high prevalence of antibodies (up to 85.7%) against pE1 and pE2 delta could be detected in both groups of patients, suggesting that these forms of the HCV envelope proteins contain B-cell epitopes. The antibody responses against proteins pE1 and pE2 delta did not differ significantly between patients with resolving or chronic infection, whereas antibodies against protein pG.HVR1 were associated with resolution of infection. Rabbit antisera raised against pE1 and pE2 delta were tested for their ability to neutralize the binding of HCV to susceptible cells in tissue cultures. The results suggested that although a few B-cell epitopes outside of HVR1 can induce virus neutralizing antibodies, these antibodies are probably not associated with the resolution of infection.