Low-temperature co-fired ceramic microchannels with individually addressable screen-printed gold electrodes on four walls for self-contained electrochemical immunoassays.
Microchannel devices were constructed from low-temperature co-fired ceramic (LTCC) materials with screen-printed gold (SPG) electrodes in three dimensions--on all four walls--for self-contained enzyme-linked immunosorbant assays with electrochemical detection. The microchannel confines the solution to a small volume, allowing concentration of electroactive enzymatically generated product and nearby electrodes provide high-speed and high-sensitivity detection: it also facilitates future integration with microfluidics. LTCC materials allow easy construction of three-dimensional structures compared with more traditional materials such as glass and polymer materials. Parallel processing of LTCC layers is more amenable to mass production and fast prototyping, compared with sequential processing for integrating multiple features into a single device. LTCC and SPG have not been reported previously as the basis for microchannel immunoassays, nor with integrated, individually addressable electrodes in three dimensions. A demonstration assay for mouse IgG at 5.0 ng/mL (3.3 × 10(-11) M) with electrochemical detection was achieved within a 1.8 cm long × 290 μm high × 130 μm wide microchannel (approximately 680 nL). Two of four SPG electrodes span the top and bottom walls and serve as the auxiliary electrode and the assay site, respectively. The other two (0.7 cm long × 97 μm wide) are centered lengthwise on the sidewalls of the channel. One serves as the working and the other as the pseudoreference electrode. The immunoassay components were immobilized at the bottom SPG region. Enzymatically generated p-aminophenol was detected at the internal working electrode within 15 s of introducing the enzyme substrate p-aminophenyl phosphate. A series of buffer rinses avoided nonspecific adsorption and false-positive signals.


In vitro identification of four-element windkessel models based on iterated unscented Kalman filter.
Mock circulatory loops (MCLs) have been widely used to test left ventricular assist devices. The hydraulic properties of the mock systemic arterial system are usually described by two alternative four-element windkessel (W4) models. Compared with three-element windkessel model, their parameters, especially the inertial term, are much more difficult to estimate. In this paper, an estimator based on the iterated unscented Kalman filter (IUKF) algorithm is proposed to identify model parameters. Identifiability of these parameters for different measurements is described. Performance of the estimator for different model structures is first evaluated using numerical simulation data contaminated with artificial noise. An MCL is developed to test the proposed algorithm. Parameter estimates for different models are compared with the calculated values derived from the mechanical and hydraulic properties of the MCL to validate model structures. In conclusion, the W4 model with an inertance and an aortic characteristic resistance arranged in series is proposed to represent the mock systemic arterial system. Once model structure is appropriately selected, IUKF can provide reasonable estimation accuracy in a limited time and may be helpful for future clinical applications.


Effectiveness of Tai Chi for health promotion for adults with health conditions: a scoping review of Meta-analyses.
To complete a scoping review of meta-analyses summarizing evidence of the effectiveness of Tai Chi for adults with health conditions. Meta-analyses were retrieved from Medline, Embase, AMED, CINAHL, SPORTDiscus, PsychINFO, Web of Science, PubMed Health and the Cochrane Library from database inception to early September 2018. Multistage deduplication and screening processes identified full-length, unique, peer-reviewed meta-analyses. Two people independently appraised 42 meta-analyses based on the GRADE system and organized results into 3 appendices subsequently collated into heterogeneous, statistically significant, and statistically insignificant tables. "High" and "moderate" quality evidence indicates that Tai Chi can significantly benefit adults with health conditions including cancers, chronic obstructive pulmonary disease, coronary heart disease, depression, heart failure, hypertension, low back pain, osteoarthritis, osteoporosis, Parkinson's Disease and stroke. Outcomes included significant improvements in activities of daily living, balance, exercise capacity, gait, mastery, mental health, mobility, motor function, participation in daily life, physical function, quality of life, range of motion, and strength; with reductions in blood pressure, body mass index, depression, disability, dyspnea, falls, fatigue, pain, stiffness, and waist circumference. Healthcare providers now have information to advise clients with health conditions on the effectiveness of Tai Chi for overall health promotion. IMPLICATIONS FOR REHABILITATIONTai Chi is a form of safe, enjoyable, light-to-moderate aerobic physical activity for adults that is inexpensive to implement in diverse community settings.Adults with health conditions require physical activity for prevention of secondary impairments and over-all health promotion.This scoping review of meta-analyses elucidates "high" and "moderate" quality evidence of the effectiveness of Tai Chi in improving important outcomes for people with numerous health conditions.This information can be useful for healthcare providers who wish to recommend effective community-based physical activity to clients they are serving.


Description of Thalassotalea piscium gen. nov., sp. nov., isolated from flounder (Paralichthys olivaceus), reclassification of four species of the genus Thalassomonas as members of the genus Thalassotalea gen. nov. and emended description of the genus Thalassomonas.
A Gram-staining-negative, aerobic, rod-shaped bacterium, designated strain T202(T), was isolated from the gill of a cultured flounder (Paralichthys olivaceus). Based on 16S rRNA gene sequence similarity, strain T202(T) was a member of the family Colwelliaceae and shared 93.32-96.58 % similarity with type strains of all members of the most closely related genus Thalassomonas. Phylogenetically, the isolate shared a root with the type strains of four marine species, Thalassomonas agariperforans M-M1(T), Thalassomonas agarivorans TMA1(T), Thalassomonas loyana CBMAI 722(T) and Thalassomonas ganghwensis JC2041(T). Optimal growth occurred in the presence of 2-4 % (w/v) NaCl, at pH 7.0-8.0 and at 28 °C. Ubiquinone 8 (Q-8) was the predominant respiratory quinone. The major fatty acids were C16 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 1ω9c and C17 : 1ω8c. The major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. The DNA G+C content of strain T202(T) was 37 mol%. On the basis of polyphasic analysis, especially the phylogenetic relationships and the lower DNA G+C content, strain T202(T) is considered to represent a novel species in a new genus, for which the name Thalassotalea piscium gen. nov., sp. nov. is proposed. The type strain of Thalassotalea piscium is T202(T) ( = JCM 18590(T) = DSM 26287(T) = KCTC 32144(T)). Because Thalassomonas agariperforans M-M1(T), Thalassomonas agarivorans TMA1(T), Thalassomonas loyana CBMAI 722(T) and Thalassomonas ganghwensis JC2041(T) formed a phylogenetic group together with strain T202(T) that was clearly separated from other known strains of Thalassomonas, these four species are reclassified as members of the genus Thalassotalea as Thalassotalea agariperforans comb. nov. (type strain M-M1(T) = KCTC 23343(T) = CCUG 60020(T)), Thalassotalea agarivorans comb. nov. (type strain TMA1(T) = BCRC 17492(T) = JCM 13379(T) = DSM 19706(T)), Thalassotalea loyana comb. nov. (type strain CBMAI 722(T) = LMG 22536(T)) and Thalassotalea ganghwensis comb. nov. (type strain JC2041(T) = IMSNU 14005(T) = KCTC 12041(T) = DSM 15355(T)). The type species of the genus Thalassotalea is Thalassotalea ganghwensis gen. nov., comb. nov. An emended description of the genus Thalassomonas is also proposed.


Comparative study of transport processes of nitrogen, phosphorus, and herbicides to streams in five agricultural basins, USA.
Agricultural chemical transport to surface water and the linkage to other hydrological compartments, principally ground water, was investigated at five watersheds in semiarid to humid climatic settings. Chemical transport was affected by storm water runoff, soil drainage, irrigation, and how streams were linked to shallow ground water systems. Irrigation practices and timing of chemical use greatly affected nutrient and pesticide transport in the semiarid basins. Irrigation with imported water tended to increase ground water and chemical transport, whereas the use of locally pumped irrigation water may eliminate connections between streams and ground water, resulting in lower annual loads. Drainage pathways in humid environments are important because the loads may be transported in tile drains, or through varying combinations of ground water discharge, and overland flow. In most cases, overland flow contributed the greatest loads, but a significant portion of the annual load of nitrate and some pesticide degradates can be transported under base-flow conditions. The highest basin yields for nitrate were measured in a semiarid irrigated system that used imported water and in a stream dominated by tile drainage in a humid environment. Pesticide loads, as a percent of actual use (LAPU), showed the effects of climate and geohydrologic conditions. The LAPU values in the semiarid study basin in Washington were generally low because most of the load was transported in ground water discharge to the stream. When herbicides are applied during the rainy season in a semiarid setting, such as simazine in the California basin, LAPU values are similar to those in the Midwest basins.


A concussive-like brain injury model in mice (II): selective neuronal loss in the cortex and hippocampus.
A novel concussive-like brain injury (CLBI) model characterized by transient neurobehavioral depression, short duration of brain edema, and long-lasting memory deficits has been reported in our companion paper. This was achieved by dropping a 21-g weight from a height of 25 cm onto the head of a mouse. In the present study, we examined the histopathological changes in this model. Male ddY mice were subjected to either the trauma or sham injury. Gross pathological examination of the brain 1 h posttrauma did not demonstrate subdural, subarachnoid, intraventricular, periventricular, and intraparenchymatous hemorrhage, focal lesions or contusions. Microscopic examination 24 h posttrauma with Nissl staining (cresyl violet), however, revealed a selective bilateral neuronal cell loss in the cerebral cortex and hippocampus but not in the regions of the thalamus, cerebellum, and brain stem. The characteristics of neuronal cell loss in the cortex suggested that this pathology was related in part, to the head impact dynamics, since the cell loss was noted in the central portion of the supraventricular cerebral cortex (p < 0.001), the site of the weight impact, gradually decreasing peripheral to this site, and disappearing in the areas remote from this locus. In contrast, neuronal cell loss seen in the hippocampus did not suggest that this pathology was directly associated with the impact site. Neuronal cell loss was concentrated in the pyramidal cell layer of CA2 (p < 0.01) and CA3 (p < 0.01), and a lesser degree was noted in the subfields of CA3c (p < 0.05) and the hilar region (p < 0.05) but not in the subfields of CA1 and the dentate gyrus layers. The present study characterized the histopathological change seen in the CLBI model, demonstrating the selective neuronal cell loss following weight-drop concussion in mice.


Mortality among dust-exposed Chinese mine and pottery workers.
A cohort study of approximately 68,000 persons employed during 1972 to 1974 at metal mines and pottery factories in south central China was conducted to evaluate mortality from cancer and other diseases among workers exposed to different levels of silica and other dusts. A follow-up of subjects through December 31, 1989 revealed 6,192 deaths, a number close to that expected based on Chinese national mortality rates. There was, however, a nearly 6-fold increase in deaths from pulmonary heart disease (standard mortality ratio, 581; 95% confidence interval 538 to 626), and a 48% excess of mortality from nonmalignant respiratory diseases (standard mortality ratio, 148; 95% confidence interval, 139 to 158), primarily because of a more than 30-fold excess of pneumoconiosis. Pulmonary heart disease and noncancerous respiratory disease rates rose in proportion to dust exposure. Cancer mortality overall was not increased among the miners or pottery workers. There was no increased risk of lung cancer, except among tin miners, and trends in risk of this cancer with increasing level of dust exposure were not significant. Risks of lung cancer were 22% higher among workers with than without silicosis. The findings indicate that respiratory disease continues to be an occupational hazard among Chinese miners and pottery workers, but that cancer risks are not as yet strongly associated with work in these dusty trades.


Lead effects among secondary lead smelter workers with blood lead levels below 80 microgram/100 ml.
A subgroup of workers from a secondary lead smelter was defined to include those with blood lead levels not exceeding 80 microgram/100 ml and with no past history of elevated blood lead. Central nervous system symptoms (tiredness, sleeplessness, irritability, headache) were reported by 55% of the group and muscle and joint pain by 39%. Zinc protoporphyrin (ZPP) levels were elevated in 71% of cases. Low hemoglobin levels (less than 14 gm/100 ml) were found in more than a third of the workers. While BUN and creatinine were mostly in the normal range, there was nevertheless a correlation between ZPP and both BUN and creatinine. Reduced nerve-conduction velocities were present in 25% of the group; this was not significantly different from findings in a control group. The data indicate that a blood level of 80 microgram/100 ml is an inappropriate biological guide in the prevention of lead disease.


[Detection of trivalent chromium in the air].
The study was designed to develop an accelerated technique of air identification of trivalent chromium. The technique for alkali melting at 800-850 degrees, traditionally used for sample preparation, was replaced by acid treatment by a mixture of nitric, hydrochloric and chloric acids. Thus trivalent chromium was oxidized into hexavalent one, which was determined by means of the photocolorimetric technique by its reaction with diphenylcarbazite. The technique enabled one to lower the time for the analysis by 4 hours.


Trimethoprim/sulphamethoxazole resistance in Escherichia coli and Klebsiella spp. urinary isolates.
The susceptibility of 40 Escherichia coli and 35 Klebsiella spp. urinary isolates to trimethoprim/sulphamethoxazole (cotrimoxazole) was determined. The determination was based on the activity of the standard multodiscs-cotrimoxazole (25 micrograms), (Oxoid); sulphafurazole (500 micrograms), (Mastring-S); and the minimum inhibitory concentration of trimethoprim and sulphamethoxazole singly against the isolates. Thirty-two (80%) of 40 isolates of Escherichia coli, and 26 (74%) of 35 isolates of Klebsiella spp. were resistant to cotrimoxazole. All the isolates were resistant to more than 500 mg/l sulphamethoxazole. Twenty of the 32 (62%) cotrimoxazole-resistant E. coli strains and 18 of the 26 (69%) cotrimoxazole-resistant Klebsiella strains were resistant to more than 2000 mg/l trimethoprim. These high level trimethoprim-resistant strains invariably carried transferable resistance to at least the sulphonamides, ampicillin and tetracycline, which could be transferred en bloc to known sensitive recipients by the process of conjugation. The high incidence of the R-plasmid-mediated resistance to high levels of trimethoprim suggests the presence of a selective pressure from the increased, and probably the uncontrolled, use of trimethoprim/sulphonamide proprietary formulations in the society.


Regulation of acetyl coenzyme A synthetase in Escherichia coli.
Cells of Escherichia coli growing on sugars that result in catabolite repression or amino acids that feed into glycolysis undergo a metabolic switch associated with the production and utilization of acetate. As they divide exponentially, these cells excrete acetate via the phosphotransacetylase-acetate kinase pathway. As they begin the transition to stationary phase, they instead resorb acetate, activate it to acetyl coenzyme A (acetyl-CoA) by means of the enzyme acetyl-CoA synthetase (Acs) and utilize it to generate energy and biosynthetic components via the tricarboxylic acid cycle and the glyoxylate shunt, respectively. Here, we present evidence that this switch occurs primarily through the induction of acs and that the timing and magnitude of this induction depend, in part, on the direct action of the carbon regulator cyclic AMP receptor protein (CRP) and the oxygen regulator FNR. It also depends, probably indirectly, upon the glyoxylate shunt repressor IclR, its activator FadR, and many enzymes involved in acetate metabolism. On the basis of these results, we propose that cells induce acs, and thus their ability to assimilate acetate, in response to rising cyclic AMP levels, falling oxygen partial pressure, and the flux of carbon through acetate-associated pathways.


Performance of intensive care unit severity scoring systems across different ethnicities.
Despite wide utilisation of severity scoring systems for case-mix determination and benchmarking in the intensive care unit, the possibility of scoring bias across ethnicities has not been examined. Recent guidelines on the use of illness severity scores to inform triage decisions for allocation of scarce resources such as mechanical ventilation during the current COVID-19 pandemic warrant examination for possible bias in these models. We investigated the performance of three severity scoring systems (APACHE IVa, OASIS, SOFA) across ethnic groups in two large ICU databases in order to identify possible ethnicity-based bias. Data from the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care were analysed for score performance in Asians, African Americans, Hispanics and Whites after appropriate exclusions. Discrimination and calibration were determined for all three scoring systems in all four groups. While measurements of discrimination -area under the receiver operating characteristic curve (AUROC) -were significantly different among the groups, they did not display any discernible systematic patterns of bias. In contrast, measurements of calibration -standardised mortality ratio (SMR) -indicated persistent, and in some cases significant, patterns of difference between Hispanics and African Americans versus Asians and Whites. The differences between African Americans and Whites were consistently statistically significant. While calibrations were imperfect for all groups, the scores consistently demonstrated a pattern of over-predicting mortality for African Americans and Hispanics. The systematic differences in calibration across ethnic groups suggest that illness severity scores reflect bias in their predictions of mortality. LAC is funded by the National Institute of Health through NIBIB R01 EB017205. There was no specific funding for this study.


Nonablative neonatal bone marrow transplantation rapidly reverses severe murine osteopetrosis despite low-level engraftment and lack of selective expansion of the osteoclastic lineage.
Infantile malignant osteopetrosis (IMO) is caused by lack of functional osteoclasts leading to skeletal abnormalities, blindness owing to compression of the optic nerves, bone marrow (BM) failure, and early death. In most patients, TCIRG1, a proton pump subunit essential for bone resorption, is mutated. oc/oc mice represent a model for IMO owing to a deletion in Tcirg1 and die around 4 weeks of age. To determine if hematopoietic stem cell transplantation without prior conditioning can reverse osteopetrosis, neonatal mice were transplanted intravenously with lineage-depleted BM cells. More than 85% of oc/oc mice transplanted with 5 × 10(6) cells survived long term with an engraftment of 3% to 5% in peripheral blood (PB). At 3 weeks, engraftment in the BM was 1% to 2%, but the cellularity had increased 60-fold compared with untreated oc/oc mice, and RANKL and macrophage colony-stimulating factor (M-CSF) expression in the BM was normalized. Histopathology and micro-computed tomography revealed almost complete reversal of osteopetrosis after 4 weeks. In vitro studies showed that bone resorption by osteoclasts from transplanted oc/oc mice was 14% of transplanted controls, and immunofluorescence microscopy revealed that resorption was mainly associated with osteoclasts of donor origin. Lineage analysis of BM, PB, and spleen did not provide any evidence for selective recruitment of cells to the osteoclastic lineage. The vision also was preserved in transplanted oc/oc mice, as determined by a visual tracking drum test. In summary, nonablative neonatal transplantation leading to engraftment of only a small fraction of normal cells rapidly reverses severe osteopetrosis in the oc/oc mouse model.


Impaired cytosolic calcium mobilization and aggregation in response to collagen in platelets from Japanese black cattle with Chediak-Higashi syndrome.
To examine whether impaired aggregation of platelets from Japanese Black cattle with Chediak-Higashi syndrome (CHS) was attributable to mobilization of cytosolic Ca2+. 4 healthy Japanese Black cattle and 3 Japanese Black cattle with CHS. Aggregation and mobilization of cytosolic Ca2+ in response to various receptor agonists was measured in platelets from healthy cattle and cattle with CHS. Involvement of endogenous ADP and arachidonic acid in collagen-induced responses was examined. Cytosolic Ca2+ concentration was measured after platelets were loaded with the Ca2+ indicator fura-PE3. Platelet aggregation was measured with an aggregometer. Collagen (3 to 15 micrograms/ml)-induced increases in cytosolic Ca2+ concentration and aggregation were markedly impaired for platelets from cattle with CHS, compared with values for platelets from healthy cattle. Although aggregation and the sustained phase of the cytosolic Ca2+ response to ADP were also decreased in platelets from cattle with CHS, these decreases were small, compared with those in response to collagen. A cyclooxygenase inhibitor and a phospholipase A2 inhibitor did not have any effect on peak cytosolic Ca2+ concentration or collagen-induced aggregation of platelets from healthy cattle. Responses to a P2 tau-purinoceptor antagonist suggested that decreased release of endogenous ADP was only partially involved in the impaired response to collagen among platelets from cattle with CHS. Marked inhibition of collagen-induced Ca2+ mobilization, rather than decreased release of endogenous substances, appeared to be the major cause of impaired platelet response to collagen and the hemorrhagic tendency in cattle with CHS.


Incidence survey of Kawasaki disease in 1997 and 1998 in Japan.
To describe the results of a nationwide epidemiologic survey of Kawasaki disease for the 2-year period 1997 and 1998. We sent a questionnaire to all hospitals with 100 beds or more throughout Japan (2663 hospitals) requesting data on patients with Kawasaki disease. Study items included name, sex, date of birth, date of initial hospital visit, diagnosis, address, recurrence, sibling cases, gammaglobulin treatment, and cardiac lesion in the acute stage or 1 month after onset. Of the 2663 hospitals, 68.5% responded, reporting 12 966 patients-7489 males and 5477 females. Of the total patients reported, 6373 (incidence rate of 108.0 per 100 000 children <5 years old) occurred in 1997, and 6593 (111.7) in 1998. More than one half of the patients (54.9%) were <2 years old and 81.6% were <4 years old. In males, the incidence rates of cardiac lesions were 27.2 in the acute stage and 10.1 a month after onset. In females, the rates were 16.7 and 5.2, respectively. The incidence rates of cardiac lesions were highest in the youngest age group (<6 months old) both in the acute stage and 1 month after onset. The rates decreased with increasing ages. Although frequency of giant aneurysms was not high at the acute stage, it did not decrease 1 month after onset. The incidence rates have been steadily increasing for 11 years since 1987. The rate in 1998 was over 1.5 times higher than that in 1987. The age and sex distributions were identical in each survey. Although most of the cardiac lesions at the acute stage decreased to half or less 1 month after onset, giant aneurysms did not decrease and existed persistently after 1 month.


[Wide range of the use of natural lipases and esterases to inhibit Mycobacterium tuberculosis].
Lipases and/or esterases (hereinafter referred to as esterases) isolated from the wax moth (Galleria mellonella) were found to have a bacteriological action on Mycobacterium tuberculosis (MBT) H37Rv. Different types of raw esterase preparations (REP) were incubated with MBT at 37 degrees C for 18 hours, the incubate was seeded on the Finn-II solid medium or intraperitoneally injected into guinea pigs in a single dose of 100,000,000 bacteria. There was no growth of MBT in the medium within 8 weeks, some variants of REP causing a destruction of the medium for 3-7 days. This "toxic" effect on the lipid-containing Finn-II medium could be lowered by the simplest techniques for purifying esterases. In the experimental guinea pigs, a tuberculous process substantially regressed: autopsy of control animals at interval of 3-6 weeks after inoculation with native MBT showed the typical picture of progressive generalized tuberculosis; at the same time a visible pathology was not noted in the animals contaminated with MBT incubated with esterases. At week 7, control guinea pigs died; the onset of a tuberculous process was observed in experimental guinea pigs at week 8. An attempt to reveal the therapeutical effect of REP on guinea pigs with tuberculosis in a direct experiment failed. At the same time, there was a low toxicity of REP (in the used doses) for guinea pigs and B10.A(4R) mice. Based on their own findings and some data available in the literature, the authors have arrived at the following provisory conclusions: the studied REPs contain mammalian lysosomal lipase-type enzymes that determine the bacteriostatic and, perhaps, bacteriolytic effect of REP shown on MBT in vitro; there is evidence for promises of continued detailed studies of natural esterases for searching new antituberculous agents. A program of investigations of the studied and other natural esterases has been developed by taking into account the authors' developments and know-how. The study may be regarded as part of global unselected screening of biological and other materials for detecting new promising sources of drugs.


Guidelines and Considerations for Metabolic Tolerance Tests in Mice.
The epidemic of the century, Diabetes Mellitus (DM) is continuously rising. Intensive research is urgently needed whereby experimental models represent an essential tool to optimise the diagnostic strategy and to improve therapy. In this review, we describe the central principles of the metabolic tests available in order to study glucose and insulin homeostasis in mice, focusing on the most widely used - the glucose and insulin tolerance tests. We provide detailed experimental procedures as well as the practical implementation of these methods and discuss the main factors that should be taken into account when using this methodology.


Spatiotemporal patterns of paralytic shellfish toxins and their relationships with environmental variables in British Columbia, Canada from 2002 to 2012.
Harmful algal blooms produce paralytic shellfish toxins that accumulate in the tissues of filter feeding shellfish. Ingestion of these toxic shellfish can cause a serious and potentially fatal condition known as paralytic shellfish poisoning (PSP). The coast of British Columbia is routinely monitored for shellfish toxicity, and this study uses data from the monitoring program to identify spatiotemporal patterns in shellfish toxicity events and their relationships with environmental variables. The dinoflagellate genus Alexandrium produces the most potent paralytic shellfish toxin, saxitoxin (STX). Data on all STX measurements were obtained from 49 different shellfish monitoring sites along the coast of British Columbia for 2002-2012, and monthly toxicity events were identified. We performed hierarchical cluster analysis to group sites that had events in similar areas with similar timing. Machine learning techniques were used to model the complex relationships between toxicity events and environmental variables in each group. The Strait of Georgia and the west coast of Vancouver Island had unique toxicity regimes. Out of the seven environmental variables used, toxicity in each cluster could be described by multivariable models including monthly sea surface temperature, air temperature, sea surface salinity, freshwater discharge, upwelling, and photosynthetically active radiation. The sea surface salinity and freshwater discharge variables produced the strongest univariate models for both geographic areas. Applying these methods in coastal regions could allow for the prediction of shellfish toxicity events by environmental conditions. This has the potential to optimize biotoxin monitoring, improve public health surveillance, and engage the shellfish industry in helping to reduce the risk of PSP.


Hepatocellular carcinoma with foamy histiocyte-like appearance: a deceptively clear cell carcinoma appearing variant.
Hepatocellular carcinoma (HCC) shows many pathological features, and it varies architecturally and cytologically. There have been many reports and discussions of the morphological features of HCC. A 63-year-old man was found to have a solitary tumor in liver segment 7 that was diagnosed as HCC. A partial resection of liver segment 7 was performed. Microscopically, the tumor lesion showed a moderately differentiated HCC. There was also a lesion with foamy histiocyte-like cells corresponding to the white lesion in the face of the cut tumor. Immunohistochemical staining showed that they were negative for CD68, S-100, vimentin, and HMB-45. The cytoplasm itself was negative on periodic acid Schiff (PAS) and Sudan staining. Without immunohistological analysis, it is difficult to distinguish this HCC variant from clear cell carcinoma or metastases of renal cell carcinoma. It is important to recognize this type as a specific cytological variant of HCC that requires confirmation by immunohistochemistry. This report describes the case of a patient with a morphologically distinctive pattern of HCC with prominent cell cytoplasm that had a foamy histiocyte-like appearance. To the best of our knowledge, this is the first report of this HCC variant.


Weight training economy as a function of intensity of the squat and overhead press exercise.
The purpose of this investigation was to study the relationship between exercise intensity and weight training economy. Seven subjects performed squat and seated behind the neck press exercises at 60% and 80% of one repetition maximum (1 RM). Addition of net exercise oxygen uptake (VO2) to net recovery VO2 provided an estimate of metabolic cost for the exercise. Estimation of work performed was accomplished by calculation of vertical external work (VEW). Weight training economy was calculated (weight training economy = kcals consumed x VEW-1). The squat was significantly more economical than the overhead press (p = 0.002), and exercise at 60% 1 RM was more economical than exercise at 80% 1 RM (p less than 0.001). Correlations between VEW and kcals consumed at each intensity ranged between 0.85-0.98. It was determined that estimation of metabolic cost of weight training exercise must take into account not only the vertical external work accomplished, but also the intensity of the exercise (% 1 RM). Vertical external work performed on the bar appears to be as accurate as the total vertical external work value in prediction of metabolic cost of the squat and overhead press exercises. Use of the weight training economy values obtained in this study for prediction of metabolic cost will provide values with 4.2%-15.8% prediction error.


The provision of animal health care to smallholders in Africa: an analytical approach.
Many of the problems associated with the delivery of quality veterinary services to smallholders in Africa are attributed to the complexity of the provision of animal health care (AHC) in sub-Saharan Africa. In this region, a holistic and analytical approach is needed to determine area-specific requirements for sustainable, and thus quality, AHC. This study examines three components of the animal health care system in sub-Saharan Africa, namely, the structure, the process and the outcomes. It focuses particularly on the factors that contribute to the quality of the structure and the process. For this purpose, two measures of quality are used, i.e. availability (in relation to the structure) and acceptability (in relation to the process). The authors identify factors that affect the availability and acceptability of AHC and suggest ways in which they, and hence the quality of AHC provided to smallholders in Africa, can be improved.


Pelvic organ prolapse: does hormone therapy use matter?
To determine the effect of hormone therapy (HT) use on pelvic organ support. A retrospective observational study involving postmenopausal women with pelvic floor dysfunction attending a tertiary urogynecology center between January 2012 and March 2015. All underwent a clinical examination including International Continence Society Pelvic Organ Prolapse Quantification and 4D translabial ultrasound imaging. Information on current or former use of systemic HT and current local estrogen use was collected. Main outcome measure was pelvic organ support. One thousand four hundred forty-three women were seen during the study period. On univariate analysis, current HT was significantly associated with sonographically determined descent of the rectal ampulla (β [95% confidence interval] 3.4 mm [0.4-6.5], P = 0.03) and Gh + Pb (-0.45 mm [-0.8 to -0.1], P = 0.005). Past HT use, duration of HT use, or current vaginal estrogen use was not associated with pelvic organ support. On multivariate analysis controlling for age, parity, body mass index, history of forceps delivery, and avulsion, the association between current HT on the one hand and Gh + Pb as well as increased descent of the rectal ampulla on ultrasound, remained significant (P = 0.008 and P = 0.012, respectively). HT may have a minor negative effect on pelvic organ support; however, the effect is likely too small to be clinically relevant.


Total synthesis of the dictyodendrins as an arena to highlight emerging synthetic technologies.
Covering: 1993-2017This review discusses the isolation, biological activity, and syntheses of the dictyodendrin class of natural products, covering the years 1993-2017. The dictyodendrins are a family of alkaloids isolated from marine sponges, Dictyodendrilla verongiformis and Ianthella sp., which possess a highly substituted pyrrolo[2,3-c]carbazole core at the phenol or quinone oxidation states. Dictyodendrins exhibit a wide range of biological activities, such as telomerase inhibition, BACE1 enzyme inhibition, and cytotoxicity against several cancer cell lines. The unique structure and interesting biological activities of dictyodendrins provided a platform for the application of novel synthetic methods including C-H insertion, C-H arylation, and electrocyclization cascades.


Osteoporosis in men.
Osteoporosis is an important and often overlooked problem in men. Although the lifetime risk of hip fracture is lower in men than in women, men are twice as likely to die after a hip fracture. Bone mineral density measurement with a T-score of -2.5 or less indicates osteoporosis. The American College of Physicians recommends beginning periodic osteoporosis risk assessment in men before 65 years of age and performing dual-energy x-ray absorptiometry for men at increased risk of osteoporosis who are candidates for drug therapy. All men diagnosed with osteoporosis should be evaluated for secondary causes of bone loss. The decision regarding treatment of osteoporosis should be based on clinical evaluation, diagnostic workup, fracture risk assessments, and bone mineral density measurements. Pharmacotherapy is recommended for men with osteoporosis and for high-risk men with low bone mass (osteopenia) with a T-score of -1 to -2.5. Bisphosphonates are the first-line agents for treating osteoporosis in men. Teriparatide (i.e., recombinant human parathyroid hormone) is an option for men with severe osteoporosis. Testosterone therapy is beneficial for men with osteoporosis and hypogonadism. Adequate intake of calcium and vitamin D should be encouraged in all men to maintain bone mass. Men should be educated regarding lifestyle measures, which include weight-bearing exercise, limiting alcohol consumption, and smoking cessation. Fall prevention strategies should be implemented in older men at risk of falls.


Effect of maternal canine starvation on fetal and neonatal liver metabolism.
Heptic glycolytic and gluconeogenic intermediates from fasted newborns of five control and five 3-day starved canine mothers (MCS) were studied at 0, 3, 6, 9, and 24 h of age. MCS did not affect fetal hepatic glycogen concentration; however, a significant increase in uridine diphosphate glucose (UDPG) (0.186 vs. 0.106 mumol/g), fructose 6-phosphate (0.084 vs. 0.034), pyruvate (0.321 vs. 0.126), and citrate (0.190 vs. 0.140) concentrations occurred. At 3 h, the intrahepatic glucose concentration among the MCS newborns declined (3.09 vs. 6.34) and remained lower than the controls for up to 9 h. UDPG concentration, however, remained elevated throughout the 24 h. In addition intrahepatic pyruvate was significantly elevated in the MCS group. Elevated phosphoenolpyruvate concentrations were observed between 3 and 6 h. Malate levels were lower than controls between 6 and 9 h and alpha-ketoglutarate was significantly higher between 6 and 24 h. Calculated cytoplasmic NAD/NADH ratio was elevated throughout the 24 h. Hepatic triglycerides were higher than controls up to 9 h. A decline in hepatic triglycerides was observed between 9 and 24 h. The results suggest increased glycolysis and suppressed gluconeogenesis in the MCS puppies, probably because of increased triglyceride synthesis and decreased free fatty acid oxidation resulting in a lack of cytoplasmic NADH.


[The long term results and survival prognostic factors of surgical treatment ampulla Vateri cancer].
Results of radical operative treatment of 21 patients with ampulla Vateri cancer are presented. Within the first 30 days after pancreaticoduodenal resection 2 (9.5%) patients have died. The long-term results were studied at 19 (90.4%) patients. The one-year, the three-year and five-year survival percentage was 89.4, 57.8 and 36.8% accordingly. The median of life expectancy is equal to 44 months. Factors having prognostic value for survival rate are the stage of disease, metastatic regional spread, tumor invasion in a head of a pancreas, microscopic picture of a pancreatitis in a phase of acute condition. However, the only independent factor of the prognosis for a disease is the stage of neoplastic process.


Childhood Obesity: An Evidence-Based Approach to Family-Centered Advice and Support.
The prevalence of childhood obesity continues to rise despite decades of clinical and public health efforts. Early identification of children at risk of developing obesity is essential using newer electronic health systems, which move beyond traditional growth charts to provide a wealth of information about body mass index and other relevant parameters such as social determinants of health and comorbid conditions. For children who already have obesity, there are several evidence-based strategies health care providers can use as they work with patients and families to mitigate the effects. First and foremost, providers should address the issue; unfortunately, weight is often not discussed in clinical practice. In addressing the issue, providers should support families through effective, positive relationships. Providers must be aware of their biases; their language should be appropriate and nonstigmatizing. Helpful interventions should focus on behavior, not weight, health, or appearance. Motivational interviewing may be used to promote healthful behaviors: supportive parenting, regular exercise, healthful food choices, minimal screen time, and optimal sleep. There is limited evidence for the efficacy of specific weight loss diets. Both medication and bariatric surgery are indicated for select adolescents who have severe disease unresponsive to behavioral management.


Challenges of Using Text Classifiers for Causal Inference.
Causal understanding is essential for many kinds of decision-making, but causal inference from observational data has typically only been applied to structured, low-dimensional datasets. While text classifiers produce low-dimensional outputs, their use in causal inference has not previously been studied. To facilitate causal analyses based on language data, we consider the role that text classifiers can play in causal inference through established modeling mechanisms from the causality literature on missing data and measurement error. We demonstrate how to conduct causal analyses using text classifiers on simulated and Yelp data, and discuss the opportunities and challenges of future work that uses text data in causal inference.


Ganglion cardiacum or juxtaductal body of human fetuses.
The ganglion cardiacum or juxtaductal body is situated along the left recurrent laryngeal nerve in the aortic window and is an extremely large component of the cardiac nerve plexus. This study was performed to describe the morphologies of the ganglion cardiacum or juxtaductal body in human fetuses and to compare characteristics with intracardiac ganglion. Ganglia were immunostained in specimens from five fetuses of gestational age 12-16 weeks and seven fetuses of gestational age 28-34 weeks. Many ganglion cells in the ganglia were positive for tyrosine hydroxylase (TH; sympathetic nerve marker) and chromogranin A, while a few neurons were positive for neuronal nitric oxide synthase (NOS; parasympathetic nerve marker) or calretinin. Another ganglion at the base of the ascending aorta carried almost the same neuronal populations, whereas a ganglion along the left common cardinal vein contained neurons positive for chromogranin A and NOS but no or few TH-positive neurons, suggesting a site-dependent difference in composite neurons. Mixtures of sympathetic and parasympathetic neurons within a single ganglion are consistent with the morphology of the cranial base and pelvic ganglia. Most of the intracardiac neurons are likely to have a non-adrenergic non-cholinergic phenotype, whereas fewer neurons have a dual cholinergic/noradrenergic phenotype. However, there was no evidence showing that chromogranin A- and/or calretinin-positive cardiac neurons corresponded to these specific phenotypes. The present study suggested that the ganglion cardiacum was composed of a mixture of sympathetic and parasympathetic neurons, which were characterized the site-dependent differences in and near the heart.


Intraovarian markers of follicular and oocyte maturation.
The use of ovulation induction for multiple follicular growth in in vitro fertilization (IVF) has introduced the problem of follicular asynchrony. As a consequence of the asynchrony, the parameters most commonly used by IVF groups to assess follicular and oocyte quality within those follicles are not sufficiently sensitive or specific. Thus, each follicle must be considered separately, and specific markers of follicular and/or oocyte maturation must be sought from within the follicle. In this review we analyze previous reports of potential markers of follicular and oocyte maturation. In regards to the follicular fluid constituents, the level of estradiol in follicular fluid correlates with fertilization and pregnancy in stimulated cycles. Other steroids are only helpful when specific stimulation protocols are used. The level of some follicular proteins such as alpha-1-antitrypsin and fibrinogen also correlates with fertilization and pregnancy outcome. Cyclic AMP levels in follicular fluid are significantly reduced in follicles leading to conception. Regulators of oocyte maturation, such as the Oocyte Maturation Inhibitor (OMI) or the Meiosis Inducing Substance (MIS) have also been correlated with IVF outcome, but their exact structure remains still unknown. In addition, other sophisticated parameters, such as chemotactic activity of human leukocytes, or simple methods, such as the presence of intrafollicular echoes, have also been used as successful markers in predicting IVF outcome.


Classification and properties of acidic amino acid receptors in hippocampus. II. Biochemical studies using a sodium efflux assay.
The properties of excitatory amino acid receptors in hippocampal slices were analyzed using agonist-induced stimulation of 22Na efflux rate. Several amino acids (L- and D-glutamate, N-methylaspartate) produce progressively smaller responses upon successive applications, whereas D,L-homocysteate does not. Several lines of evidence suggest that depletion of an intracellular pool of 22Na is not responsible for the apparent desensitization. Addition of the amino acids in the presence of an antagonist does not affect the response of the slices to subsequent applications, indicating that desensitization is dependent upon the interaction of the agonist with its receptor. The antagonist D-alpha-aminoadipate discriminates between various excitatory amino acids, completely blocking the responses to N-methylaspartate, D-glutamate, and D,L-homocysteate; partially antagonizing those of quisqualate and kainate; and being without effect on L-glutamate. The order of potency of several excitatory amino acids on the stimulation of 22Na efflux rate in hippocampal slices is highly correlated with their relative effects measured with electrophysiological techniques, but does not correlate with their relative potencies to inhibit [3H]glutamate binding to hippocampal membranes. The similarities in the properties of excitatory amino acid receptors evidenced with the 22Na efflux assay or with the electrophysiological approach in the in vitro hippocampal slice preparation indicate that the same receptors are sampled by the two techniques. The results are discussed in terms of a classification of these receptors into four different groups: a synaptic receptor, activated by D,L-homocysteate (tentatively defined as a G1 receptor), an extrasynaptic glutamate receptor (defined as a G2 receptor), an N-methylaspartate receptor, and a kainate receptor.


Combination of extrinsic and intrinsic pathways significantly accelerates axial vascularization of bioartificial tissues.
In this study, the authors present a modification of the arteriovenous loop model that combines extrinsic and intrinsic vascularization modes to enhance vascularization of bioartificial matrices. An arteriovenous loop was created in the medial thighs of 24 rats. The loop was placed in a newly developed titanium chamber, which was fabricated with an electron beam melting facility, and was embedded in a hydroxyapatite/β-tricalcium phosphate/fibrin matrix. At the explantation time points (2, 4, 6, and 8 weeks), constructs were perfused by differently colored dyes to determine the amount of tissue vascularized by either the intrinsic or the extrinsic vascular pathway. Specimens were investigated by means of micro-computed tomography and histologic and morphometric analysis. Although there was an equal number of blood vessels originating from the center and the periphery, 83 percent of all vessels displayed a connection to the arteriovenous loop already at 2 weeks. There was a continuous increase of the relative proportion of vessels connected to the arteriovenous loop over time detectable. At 8 weeks, communications between the newly formed vessels and the arteriovenous loop were visible in 97 percent of all vessels. This study demonstrates for the first time the enhancement of angiogenesis in an axially vascularized tissue by an additional extrinsic vascular pathway. By 2 weeks, both pathways showed connections, allowing transplantation of the entire construct using the arteriovenous loop pedicle. This approach will allow for reduction of the time interval between arteriovenous loop implantation and transplantation into the defect site and limitation of operative interventions.


Life-style and drug use habits among secondary school students.
Four groups of respondents--non-users, users of psychoactive substances, users of legal substances and users of illegal substances--categorized on the basis of a survey of a representative sample of 3,690 secondary school students on the island of Mallorca, were correlated with 13 psycho-social variables, the results of which showed distinct characteristics for each of the four categories of respondents. Between two poles consisting of non-users and users of illegal substances, there is a category of users of legal substances, while all three categories form a continuum from one end to the other. This continuum supports the view that drug abuse is a sequential learning process that leads from simple drug use to drug addiction. The authors believe that it is essential to identify characteristics of specific groups among secondary school students in order to implement a realistic and effective drug abuse prevention programme in a given school. A prevention programme should meet the needs of the target group; this study identifies such needs and shows how they can be assessed. Many drug abuse prevention programmes in schools have been ineffective because they have failed to respond to the realistic requirement of specific school groups.


Reducing the risk, managing safety.
Fire safety in healthcare premises has always been a challenge to those that discharge this duty. Statutory compliance should be a matter of course, but in an ever increasingly challenged NHS, even this is not a given. While the NHS is driven by managing very complex risk to deliver cutting edge healthcare, providers cannot be risk averse. Which risk, however, takes priority? Here Peter Aldridge, fire and corporate services manager at Leeds Teaching Hospitals NHS Trust, and Secretary to the National Association of Healthcare Fire Officers (NAHFO)--which will this month and next jointly stage fire safety seminars with IHEEM; see page 8--considers the key issues, with input from a fire officer at a leading mental health and community Trust.


Calmodulin antagonists inhibit sea urchin sperm hyperpolarization necessary for directed movement toward the egg.
Speract, a decapeptide from Strongylocentrotus purpuratus sea urchin eggs, transiently stimulates a membrane guanylyl cyclase and activates a K(+)-selective channel that hyperpolarizes the sperm. Membrane potential recordings with fluorescent dyes in sperm flagellar vesicles were used to determine if calmodulin participates in the signal transduction induced by speract. The vesicle hyperpolarization induced by speract was inhibited by the calmodulin antagonists: trifluoperazine, mastoparan; N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide, (W-7); and N-(6-Aminohexyl)-1-naphthalenesulfonamide, (W-5). Since that inhibition occurred at concentrations at which calmodulin action is inhibited by these compounds, the overall findings suggested that calmodulin could be involved in the speract response. The speract response was Ca(2+)-independent however. Ten millimolar EGTA does not inhibit the hyperpolarization and 2 mM BAPTA only partially inhibited the response. High concentrations of calmodulin-dependent kinase II and phosphatase inhibitors did not alter the response of the flagella vesicles to speract. Taken as a whole, these results indicate that the speract-induced hyperpolarization involves the participation of calmodulin in a Ca2+ independent manner.


High conversion efficiency of an optical parametric amplifier pumped by 1 kHz Ti:Sapphire laser pulses for tunable high-harmonic generation.
We report that high-conversion efficiency of nearly 50% has been realized by combining a commercially available Ti:Sapphire femtosecond, 1 kHz laser system and an optical parametric amplifier (OPA). For an input energy of 2.2 mJ/pulse at 1 kHz and 35 fs duration, the total OPA output energy of the signal plus idler pulses is 1.09 mJ/pulse at a signal wavelength of 1310 nm. We found that the output beam profile is almost flat-top due to high gain saturation in the OPA. Using the signal pulse, we generate high-harmonics in gases and measure the velocity map images of photoelectrons ionized from argon gas as a function of the signal wavelength. We observe that in a particular range of the high-harmonic photon energy, a four-fold photoelectron angular structure is observed in the low kinetic energy region. Our results indicate that the output pulses with the high-conversion efficiency OPA and super Gaussian beam profile can be used for experiments requiring generation of tunable high-harmonics in the extreme ultra-violet region.


[Physico-chemical properties of specific protein kinases during intensification of lipogenesis and treatment with nicotinic acid].
Protein kinase strong-associated with acetyl-CoA-carboxylase is isolated from the liver of chicken and 300-fold purified with alimentary intensification of lipogenesis and under the effect of nicotinic acid against this background. The obtained enzymes are studied comparatively. It is found that their preparations are phosphorylated with different rate, have two pH optima and differ in the sensitivity to cAMP and to thermostable protein inhibitor. The hydrophobic chromatography was used to separate components of the acetyl-CoA-carboxylase-protein kinase complex and to reveal in the chicken liver cAMP-dependent and cAMP-independent protein kinases highly specific to acetyl-CoA-carboxylase and strongly bound with it.


The Burden of a Multiple Myeloma Diagnosis on Patients and Caregivers in the First Year: Western European Findings.
This research aimed to quantify the burden of illness (BoI) in transplant eligible (TE) and transplant non-eligible (TNE) newly diagnosed multiple myeloma (NDMM) patients and their caregivers, in the first year after diagnosis: at months 0, 3, and 12. Prospective, cross-sectional, observational NDMM study of TE and TNE patients and their caregivers from France, Germany, Italy, and Spain was conducted between May 2019 and January 2021. A structured, online questionnaire measuring disease burden, direct and costs, out-of-pocket expenses, and health-related quality of life (HRQoL) was used. Descriptive statistics were performed. A total of 164, 160, and 190 NDMM patients [>65 years; self-described healthy; not working; living with caregiver] answered at months 0, 3, and 12. Patients lost independence to perform daily activities; mean pain intensity rose and opioid utilization increased, more significantly among TNE patients. Overall health status and HRQoL remained stable. Median 3-month direct medical costs peaked at month 3. Specialist consultations and hospital admissions were the greatest cost amongst TE and TNE patients. Home adaptations increased out-of-pocket expenditures amongst TNE patients. Patients describing themselves as working spent a median 0 hours in the office at all time points. A total of 131, 122, and 124 caregivers answered at months 0, 3, and 12. Mean self-rated burden score rose. By month 12, half of caregivers developed stress, anxiety or depression. Most employed caregivers continued working. Productivity was low at month 0 with a trend of recovering at month 12. Caregivers of TNE compared to TE patients reported greater time burden. Caregivers' HRQoL was stable over time. NDMM is burdensome for patients and caregivers in the first year after diagnosis. TNE patients are more dependent on caregivers and incur higher care costs than TE patients. Despite the financial, physical, and emotional burden, HRQoL remains stable possibly indicating resilience and illness adjustment amongst patients and caregivers.


[Metal-on-metal hybrid hip resurfacing. Development and current state].
Worldwide the employment of surface replacements using metal-on-metal components as an option, particularly for the young and active patient, has gained broad acceptance. Part of the attraction for hip resurfacing is its conservative nature as a prosthetic solution for hip arthritis. It is anatomical, replicating the normal hip and limb length, preserving proximal femoral bone, and is a truly minimally bone invasive approach with excellent outcome of joint function. The purpose of this article is to show the data of 1,000 Conserve(c) Plus hybrid metal-on-metal prostheses in a consecutive study of 1,140 patients with a follow-up of 5.6 years. The current Kaplan and Meier survival estimates of the prosthesis, using any conversion to total hip replacement as the end point, were 98.1% at 3 years [95% confidence interval (CI): 96.8-98.9%], 96.7% at 4 years (95% CI: 94.8-97.8%), and 95.2% at 5 years (95% CI: 93.0-96.8%). The mean postoperative Harris hip score was 93.3. The current state of metal-on-metal surface replacement is positive. The new generation of hip resurfacing has a lot of improvements. The purpose of this review of the procedure is to point out the definite improvements from earlier designs using polyethylene as well as to highlight the overall results and durability achieved by one surgeon's extensive experience and to assess the results from other series and centers. We also want to point out the areas where further investigation is needed.


Standardized molecular typing.
Molecular typing methods are useful tools in molecular mycology. The results of these biotyping procedures may help to identify pathogenic strains in order to detect sources of nosocomial infection and for the investigation of epidemiological relationships. With respect to the facultative pathogen, Candida albicans, various methods such as pulse-field gel electrophoresis (PFGE), restriction fragment length polymorphism (RFLP), DNA fingerprinting methods and hybridization with repetitive DNA elements have been described as useful tools in molecular epidemiology. The previously described hybridization method with the Candida albicans specific CARE-2 probe and subsequent rehybridization with a molecular size marker is a standardized reproducible typing method for comparison of results obtained in different laboratories. In a larger epidemiological study conducted at the University Hospital of Würzburg analysing clinical C. albicans isolates, we were able to describe relationships between sequential patient isolates. These findings demonstrate that standardized molecular typing methods are a powerful tool in molecular mycology studies.


Antiedema effects of proanthocyanidin on experimental traumatic brain edema.
Brain edema developing due to central nervous system trauma is still a significant reason of mortality and morbidity. There is still no definite approach for the medical treatment of brain edema despite many clinical and laboratory studies in recent years. We therefore investigated the effect of proanthocyanidin, an antioxidant agent, on brain edema in this study. A total of 30 rats were used and divided into three as the control, trauma and treated trauma groups. Subjects were sacrificed after 72 hours. The brain tissue-water ratio was evaluated and biochemical analysis of brain tissue performed. The difference between the treated trauma and control groups was statistically significant while the trauma and control groups were relatively similar. Rats that had undergone trauma and received proanthocyanidin treatment were statistically significant and different from the trauma group rats regarding the biochemical analysis results, brain tissue water ratio, and the cold damage enzymatic antioxidant defense system of cortical neural tissue. We believe that proanthocyanidin, an antioxidant substance, can be an effective treatment for brain edema.


[Disorder of thyroid function in patients with cancer of the gastrointestinal tract].
A quantitative assessment of T3 pool was performed in patients with malignant tumors of the esophagus, stomach, pancreatic head, rectum and colon as well as in patients with chronic gastritis, peptic ulcer and benign stomach tumors. A high T3 pool deficiency was noted in patients with malignant GIT tumors. It was assumed that such a deficiency was indicative of profound disorder of hormone supply of tissues which could be regarded as an endogenous factor of predisposition to the development of malignant neoplasms.


Fine needle aspiration cytology of follicular dendritic cell sarcoma. Report of a case with cytologic detection in an extranodal site.
Follicular dendritic cell sarcoma (FDCS) is a rare malignancy of accessory immune cells that can present in both nodal and extranodal sites. Previous cytologic case reports of FDCS have focused on fine needle aspiration (FNA) findings in nodal sites with low grade morphology and indolent clinical courses. A 33-year-old female presented with a three-month history of abdominal distention, early satiety and nausea. Initial imaging studies showed a large abdominal mass, with subsequent studies showing lung, liver and lymph node metastases. Examination of primary and metastatic tumors by a combination of conventional histology, immunohistochemistry and FNA demonstrated an extranodal intraabdominal follicular dendritic cell sarcoma. FDCS demonstrates a characteristic cytologic picture on FNA, with important cytologic features, including both syncytial and discohesive large epithelioid to spindled malignant cells with intranuclear inclusions, nuclear grooves and a prominent, mature, lymphocytic inflammatory component. No evidence of morphologic tumor progression was noted in comparison of primary and metastatic tumors. To aid in the cytologic distinction of FDCS from other similar-appearing neoplasms, we recommend acquisition of material for immunohistochemical studies, recognition of diverse clinical presentations (including extranodal and aggressive) and acknowledgment of the range of tumor morphologic grades.


Serial multiple biomarkers in the assessment of suspected acute coronary syndrome: multiple infarct markers in chest pain (MIMIC) study.
To evaluate the accuracy of a 2-h serial multiple biomarker (SMB) protocol for exclusion of myocardial infarction (MI) in the Emergency Department. A prospective, multicentre, observational study enrolled patients undergoing evaluation for possible MI. Blood samples at presentation and 2 h later were analysed for myoglobin, creatinine kinase-MB, troponin-I and B-natriuretic peptide. Thrombolysis in Myocardial Infarction (TIMI) score and National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand (NHF/CSANZ) guideline for acute coronary syndrome were used to determine clinical risk. Primary outcome was MI diagnosed at index presentation. Secondary outcome was composite of all-cause mortality, MI and previously unplanned coronary revascularisation within 30 days. 1758 patients were recruited. 168 (11%) of 1501 with data sufficient for analysis had MI, and 223 (14%) of 1620 had a secondary outcome. SMB sensitivity and specificity were 0.90 (95% CI 0.84 to 0.94) and 0.41 (95% CI 0.39 to 0.44) for MI. For 30-day outcome, SMB sensitivity and specificity were 0.84 (95% CI 0.78 to 0.88) and 0.41 (95% CI 0.39 to 0.44), compared with standard 8-12 h troponin sensitivity and specificity of 0.79 (95% CI 0.73 to 0.84) and 0.96 (95% CI 0.95 to 0.97). Combined with risk scores, SMB had sensitivity and specificity for MI of 0.99 (0.96 to 1.00) and 0.11 (95% CI 0.09 to 0.12) for TIMI score 0, compared with 0.98 (95% CI 0.94 to 0.99) and 0.31 (95% CI 0.29 to 0.34) for NHF/CSANZ low/intermediate risk groups. SMB alone is not sufficiently sensitive to exclude MI. Combined with risk scoring, SMB appears to identify patients at lower risk. This requires prospective validation.


Urinary levels of phthalate esters and heavy metals in adolescents with thyroid colloid cysts.
We aimed to evaluate 14 urinary phthalate metabolites and 4 toxic metals in adolescents having thyroid colloid cyst (TCC) and compare with age and sex-matched others without TCC. Phthalate metabolites were analysed with UPLC-MS/MS and heavy metals with ICP-MS. TCC ratios in tertile subgroups of pollutants were compared with multiple logistic regression analysis after adjusting for age, sex, z-scores for body mass index and urinary creatinine values. Adolescents having the highest tertile of mono (2-ethylhexyl) phthalic acid and mercury had increased odds and those with the highest tertiles of monocarboxy-isononyl phthalate, mono (3-carboxypropyl) phthalate, monoisobutyl phthalate had lower odds for TCC than counterparts. The odds of TCC were lower for those in the second and the third tertiles. No differences in TCC ratios were detected with other pollutants. Given phthalate esters' and toxic metals' specific interactions on TCC, further studies were necessary to assess the influence of chemicals on TCC.


Lipid/protein interactions and the membrane/water interfacial region.
Despite the importance of lipid/protein interactions in the folding, assembly, stability, and function of membrane proteins, information at an atomic level on how such proteins interact with the lipids that surround them remains sparse. The dynamics and flexible nature of the protein/bilayer interaction make it difficult to study, for example, by crystallographic means. However, based on recent progress in molecular simulations of membranes it is possible to address this problem computationally. This communication reports one of the first attempts to use multiple ns molecular simulations to establish a qualitative picture of the intermolecular interactions between the lipids of a bilayer and two topologically different membrane proteins for which a high resolution (2 A or better) X-ray structure is available.


Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial.
At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.


Argininamide binding arrests global motions in HIV-1 TAR RNA: comparison with Mg2+-induced conformational stabilization.
The structure and dynamics of the stem-loop transactivation response element (TAR) RNA from the human immunodeficiency virus type-1 (HIV-1) bound to the ligand argininamide (ARG) has been characterized using a combination of a large number of residual dipolar couplings (RDCs) and trans-hydrogen bond NMR methodology. Binding of ARG to TAR changes the average inter-helical angle between the two stems from approximately 47 degrees in the free state to approximately 11 degrees in the bound state, and leads to the arrest of large amplitude (+/-46 degrees ) inter-helical motions observed previously in the free state. While the global structural dynamics of TAR-ARG is similar to that previously reported for TAR bound to Mg2+, there are substantial differences in the hydrogen bond alignment of bulge and neighboring residues. Based on a novel H5(C5)NN experiment for probing hydrogen-mediated 2hJ(N,N) scalar couplings as well as measured RDCs, the TAR-ARG complex is stabilized by a U38-A27.U23 base-triple involving an A27.U23 reverse Hoogsteen hydrogen bond alignment as well as by a A22-U40 Watson-Crick base-pair at the junction of stem I. These hydrogen bond alignments are not observed in either the free or Mg2+ bound forms of TAR. The combined conformational analysis of TAR under three states reveals that ligands and divalent ions can stabilize similar RNA global conformations through distinct interactions involving different hydrogen bond alignments in the RNA.


Reduction in mortality in pediatric patients with inhalation injury with aerosolized heparin/N-acetylcystine [correction of acetylcystine] therapy.
Smoke-inhalation injury causes a destruction of the ciliated epithelium that lines the tracheobronchial tree. Casts produced from these cells, polymorphonuclear leukocytes and mucus, can cause upper-airway obstruction, contributing to pulmonary failure. We have reported that a combination of aerosolized heparin and a mucolytic agent, N-acetylcystine [corrected], can ameliorate cast formation and reduce pulmonary failure secondary to smoke inhalation. In this study, 90 consecutive pediatric patients between 1985 and 1995 who had bronchoscopically diagnosed inhalation injury requiring ventilatory support were studied. Forty-three children admitted between 1985 and 1989 acted as controls. Forty-seven children admitted between 1990 and 1994 received 5000 units of heparin and 3 ml of a 20% solution of N-acetylcystine [corrected] aerosolized every 4 hours the first 7 days after the injury. All patients were extubated when they were able to maintain spontaneously a PaO2/FIO2 ratio of more than 400. The number of patients requiring reintubation for successive pulmonary failure was recorded, as was mortality. The results indicate a significant decrease in reintubation rates, in incidence of atelectasis, and in mortality for patients treated with the regimen of heparin and N-acetylcystine [corrected] when compared with controls. Heparin/N-acetylcystine [corrected] nebulization in children with massive burn injury and smoke-inhalation injury results in a significant decrease in incidence of reintubation for progressive pulmonary failure and a reduction in mortality.


Postpartum onset obsessive-compulsive disorder: diagnosis and management.
The postpartum period is associated with an increased risk of developing obsessive-compulsive disorder (OCD) in women. Postpartum onset OCD is often undiagnosed and untreated resulting in serious consequences for the patient, her family and the newborn. The symptoms of postpartum onset OCD may consist of obsessional intrusive thoughts about harming the newborn without compulsions or with both obsessions and compulsions. In this review, the phenomenology of postpartum onset OCD is described as well as strategies for screening and diagnosis. The review also characterizes the differences between postpartum onset OCD and postpartum depression and postpartum psychosis and explores strategies for managing postpartum onset OCD patients. Issues regarding pharmacologic treatment of OCD in breastfeeding mothers are also reviewed.


Comparative phenotypic characteristics of Staphylococcus aureus isolates from line and non-line associated septicaemia, CAPD peritonitis, bone/joint infections and healthy nasal carriers.
This study compared specific phenotypic and potential virulence characteristics of Staphylococcus aureus isolates from invasive infections and nasal carriers. Three hundred and sixty isolates were studied; 154 from septicaemia (69 line associated, 85 non-line), 79 from continuous ambulatory peritoneal dialysis (CAPD) peritonitis, 64 from bone/joint infections and 64 from healthy nasal carriers. The isolates were tested for production of enterotoxins (SE) A, B, C or E, toxic shock syndrome toxin-1 (TSST-1) protein A, and also for lipolytic, proteolytic, fibrinolytic and haemolytic activities. In addition phage typing, crystal violet reaction, urease and galactose breakdown were studied. Seventy-one percent of isolates were enterotoxigenic. Production of SEA was significantly lower amongst the bone/joint isolates. Production of SEB, was lower among the control group compared with CAPD, bone/joint, and non-line septicaemia isolates. SEE production was higher among the bone/joint isolates compared with the CAPD and non-line septicaemias and production of TSST-1 was significantly higher among nasal isolates compared with isolates causing infection. Almost all of the isolates were lipolytic, with highest activity amongst nasal and bone/joint isolates. Fibrinolytic activity was similar in the five groups of isolates. Proteolytic activity ranged from 35 to 62% of isolates with the lowest frequency among septicaemia isolates. In all, 80-90% of isolates were haemolytic, although CAPD isolates were less likely to be haemolytic. Isolates from the control and CAPD group more frequently belonged to phage group I. TSST-1 does not appear to be an important requirement for invasive infections, but SEB may be. Proteolysis and intensity of lipolysis appear to be less important in septicaemia, and haemolysis may not be important in CAPD peritonitis.


[Inhibitory effect of ginsenoside Rg3 on the tube-like structure formation in human nasopharyngeal carcinoma HNE-1 cell line in vitro].
To study the anti-angiogenic effect of ginsenoside Rg3 (Rg3 in abbreviation) in human nasopharyngeal carcinoma HNE-1 cells in vitro. The tube-like structure (TLS) formation of HNE-1 cells, cultured in medium with different concentrations of Rg3, was determined by in vitro anti-angiogenic test based on preliminary experiment observing the TLSs formed by HNE-1 cells on Matrigel and their structural characteristics. The VEGF expression level in HNE-1 cells was determined by immunohistochemistry (IHC) and Western-blot test after 48-hour cultured in medium with different concentrations of Rg3. HNE-1 cells could form TLSs and mosaic vessels when mix-cultured with CRL-2480 on Matrigel. Rg3 could inhibit the TLS formation of HNE-1 cells. After 24-hour culture in medium with Rg3 at concentrations of 0, 50, 100 and 200 µg/ml, the number of TLSs were 75.50 ± 6.86, 55.00 ± 11.92, 39.75 ± 7.93 and 24.50 ± 6.25, respectively, which were negatively correlated with the concentrations of Rg3 (r = -0.928; P < 0.01). After 48 hours of culture, the expressions of VEGF significantly declined by IHC test with results as 0.19 ± 0.03, 0.13 ± 0.02, 0.11 ± 0.01, and 0.08 ± 0.01, respectively, which were negatively correlated with the concentrations of Rg3 (r = -0.911; P < 0.01). The expressions of VEGF also gradually decreased as revealed by Western blot test, with corresponding results as 119.49, 111.51, 86.45, and 38.29. All of the tests showed significantly declined results in the group at the concentration of 200 µg/ml Rg3. Rg3 can inhibit the vasculogenic mimicry of HNE-1 cells, and the possible mechanism might be associated with the down-regulation of VEGF protein expression in HNE-1 cells.


Pain relief strategies used by older people with chronic pain: an exploratory survey for planning patient-centred intervention.
To explore pain relief interventions used by older people with chronic pain in Hong Kong. The frequency and perceived effectiveness of non-prescription measures were also explored. With increasing life expectancy, the incidence of chronic illness and chronic pain also increases. Chronic pain robs older people of their quality of life. This was a descriptive qualitative study. Forty-four older people (37 female and seven male) who were residents of a nursing home in Hong Kong took part in this study. Their ages ranged from 65 to 82 years, median age was 75 years. Almost 80% had experienced moderate to severe pain during the previous three months. The most common sites of pain were muscles and joints; 35% of subjects reported continuous pain, 27% reported pain associated with activities of daily living, and 38% reported pain during exercise but not at rest. Only a few of the study group had taken prescribed medication to relieve pain, and only two of the 44 subjects studied had used a combination of drug and non-prescription intervention for pain relief. The majority of participants used non-prescription intervention only and the most commonly used were topical analgesics with massage. The majority (58%) of the subjects perceived the used of non-prescription intervention to be very effective in pain relief. The prevalence of pain was found to be high among older people in this study. Yet, they were taking a pro-active and responsible role in treating their chronic pain by using non-pharmacological patient-initiated intervention; also older people perceive themselves to have control over their pain status. This active role of older people in their pain relief is likely to enhance the effect of education seminars and workshops aimed at novel, non-pharmacological pain relief strategies for older people with chronic pain.


[Cardiovascular disease prevention and health promotion in the French speaking community of Belgium].
Cardiovascular diseases remain the first cause of mortality in Belgium and are a priority for the Five-year program of health promotion in the French speaking Community. It is declined in operational programs by priority thematics, including the heart health. With this framework, it appeared necessary to operationalize cardiovascular priorities. A process of systemic and participative planning was set up in order to seek operational strategies and actions, and to cover the whole population and actors concerned with these health problems. The various cardiovascular risk factors, which potentiate one another, are approached together and in a global way. Upstream to the risk factors, social health determinants play an important role in cardiovascular diseases and others diseases like cancers. Tracking cardiovascular risk factors among people 30 to 75 years is also proposed. It makes it possible to identify people at risk and to put forward individual and adapted measures. The plan integrates actions of health promotion (acting on the health determinants and factors which influence them) as well as actions aiming at improving tracking and the accompaniment of the patients in secondary and tertiary prevention. Actions on health determinants and the factors influencing them present moreover the advantage of being often common to many chronic diseases.


Race and liver transplantation.
Little is known about the effect of race on the outcome of liver transplantation. We retrospectively reviewed a series of 358 recipients of orthotopic liver transplants to address this issue. Black recipients were underrepresented compared with the general population (6% of transplant recipients vs 12% of the population). Black recipients appeared sicker when presenting for transplantation, as evidenced by a higher priority score and a significantly greater incidence of acute and fulminant presentation. Despite this, black recipients had survival rates following transplantation that were not significantly different from those of white recipients; the 1-, 2-, and 3-year actuarial survival rates of blacks were 89.6%, 68.3%, and 68.3%, respectively, while the actuarial survival rates of whites at the same periods were 86%, 82.4%, and 78.6%, respectively. We conclude that blacks can have an outcome equal to whites following liver transplantation but they are underrepresented compared with the general population.


Coarse Surface Microcavities Permit Bone Ingrowth and Improve Implant Osseointegration.
To evaluate the effects of coarse microcavities added to micron and submicron rough implant surfaces in the implant-bone anchorage in rabbits. Confocal interferometry was used to quantify roughness. Electron microscopy and energy-dispersive x-rays characterized the surfaces prior to and after implantation. X-ray photoelectron spectroscopy and contact angle determined the surface chemistry and energy, respectively. Fifteen New Zealand White rabbits received, respectively, one cavity-less (C-) and one cavity-rich (C+) implant per femoral condyle and were allowed to integrate for 2 and 8 weeks. The bone-to-implant contact (BIC), bone volume density (BVD), and removal torque (RTQ) were then analyzed. The cavities produced on the surfaces were 48.4 ± 16.8 μm in diameter and 37.8 ± 36.5 μm deep (5.9% ± 1.1% surface coverage). C+ did not alter the surface chemistry or energy. In vivo, C+ implants produced more BIC and RTQ at 8 weeks (P = .002 and P = .059, respectively) and more BVD at 2 and 8 weeks postimplantation (P = .031 and P = .078, respectively). Bone tissue was observed inside the cavities of C+ both histologically and by scanning electron microscopy after implant removal. Unevenly distributed coarse cavities within a micron and submicron rough surface allow bone ingrowth and increase implant stability and bone-surface unions in rabbits. These results encourage the design of implants with multilevel surface topographies to improve implant-based regeneration.


Hormone contraception before the first birth and endometrial cancer risk.
There is a well-documented reduction in endometrial cancer risk with combined oral contraceptive (COC) use. COC use before the first full-term pregnancy may affect breast cancer risk for decades, but this relationship has not been investigated in endometrial cancer. We investigated the risk for endometrial cancer with COC use before the first full-term pregnancy. Cases (n = 524) from a population-based cancer registry and age-matched controls (n = 1,032) were recruited between 2002 and 2006 in Alberta, Canada. Participants completed an in-person interview and provided detailed information on exogenous hormone use and other risk factors. Risk reductions in endometrial cancer with COC use over the premenopausal years were consistent with the published literature. We also found evidence of a long-term, significant risk reduction in parous women with COC use before the first full-term pregnancy. Among parous women, ≥5 years of COC use before a first full-term pregnancy was associated with a significant reduction in risk [adjusted OR, 0.42; 95% confidence interval (CI), 0.25-0.72], even if this exposure was a woman's only use of COCs (adjusted OR, 0.35; 95% CI, 0.18-0.68). Further understanding of the long-term effects of COC use may help guide the timing of chemoprevention efforts via COCs.


Glucocorticoids and cardiovascular disease.
Chronic excessive activation of glucocorticoid receptors induces obesity, insulin resistance, glucose intolerance, dyslipidaemia and hypertension. Subtle abnormalities of the hypothalamic-pituitary-adrenal axis and/or of tissue sensitivity to glucocorticoids are also associated with these cardiovascular risk factors in patients with the metabolic syndrome. Furthermore, glucocorticoids have direct effects on the heart and blood vessels, mediated by both glucocorticoid and mineralocorticoid receptors and modified by local metabolism of glucocorticoids by the 11beta-hydroxysteroid dehydrogenase enzymes. These effects influence vascular function, atherogenesis and vascular remodelling following intra-vascular injury or ischaemia. This article reviews the systemic and cardiovascular effects of glucocorticoids, and the evidence that glucocorticoids not only promote the incidence and progression of atherogenesis but also modify the recovery from occlusive vascular events and intravascular injury. The conclusion is that manipulation of glucocorticoid action within metabolic and cardiovascular tissues may provide novel therapeutic avenues to combat cardiovascular disease.


Brain abscess in seven cats due to a bite wound: MRI findings, surgical management and outcome.
PRESENTATION AND LESION LOCALISATION: Seven adult domestic shorthair cats were presented with a 1- to 6-day history of progressive neurological signs. A focal skin puncture and subcutaneous swelling over the dorsal part of the head were detected on physical examination. Neurological examination indicated lesion(s) in the right forebrain in four cats, multifocal forebrain in one cat, left forebrain in one cat, and multifocal forebrain and brainstem in the remaining cat. In all cats, magnetic resonance imaging revealed a space-occupying forebrain lesion causing a severe mass effect on adjacent brain parenchyma. CLINICAL APPROACH AND OUTCOME: All cats were managed with a combination of medical and surgical treatment. At surgery a small penetrating calvarial fracture was detected in all cats, and a tooth fragment was found within the content of the abscess in two cats. The combination of surgical intervention, intensive care and intravenous antimicrobials led to a return to normal neurological function in five cats. As this series of cases indicates, successful resolution of a brain abscess due to a bite injury depends on early recognition and combined used of antimicrobials and surgical intervention. A particular aim of surgery is to remove any skull and foreign body (tooth) fragments that may represent a continuing focus of infection.


Effect of the herbicide glyphosate on glyphosate-tolerant maize rhizobacterial communities: a comparison with pre-emergency applied herbicide consisting of a combination of acetochlor and terbuthylazine.
A comparison was made of the effect of glyphosate (RoundupPlus), a post-emergency applied herbicide, and of HarnessGTZ, a pre-emergency applied herbicide, on the rhizobacterial communities of genetically modified NK603 glyphosate-tolerant maize. The potential effect was monitored by direct amplification, cloning and sequencing of soil DNA encoding 16S rRNA, rhizobacterial DNA hybridization to commercially available genome-wide microarrays from the soil bacterium Streptomyces coelicolor, and high-throughput DNA pyrosequencing of the bacterial DNA coding for 16S rRNA hypervariable V6 region. The results obtained strongly suggest that both herbicides do in fact affect the maize rhizobacterial communities, glyphosate being, to a great extent, the environmentally less aggressive herbicide.


Modulation of cortical acetylcholine and gamma-aminobutyric acid release in freely moving guinea pigs: effects of clonidine and other adrenergic drugs.
The effects of various doses of clonidine and norepinephrine (NE) on the release of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) from the brain surface of freely moving guinea pigs have been investigated in order to study the role of alpha adrenoceptors on the function of cortical cholinergic and GABAergic neurons. Clonidine administration at doses of 7.5 and 18.7 nmol/kg inhibits by 40% the release of ACh; larger doses (112 nmol/kg) are inactive. On the other hand, the largest dose of clonidine used in this study (112 nmol/kg) increases the release of GABA by 45%, whereas lower doses are inactive. Norepinephrine (0.9 mumol i.c.v.) decreases by 40% the release of ACh and increases by 80% that of GABA. The inhibitory effects of clonidine and of NE on cortical ACh output are completely antagonized by yohimbine (0.28 mumol/kg), a selective alpha-2 antagonist, thus suggesting an involvement of the alpha-2 adrenoceptors in the neurochemical action of the drug. However, yohimbine releases GABA and does not prevent the action of clonidine or of NE on the cortical GABA system. On the other hand, prazosin (35.8 nmol/kg), a selective alpha-1 antagonist, completely antagonizes the stimulating effects of clonidine and of NE on the release of GABA, suggesting that alpha-1 receptors modulate this release. The present experiments indicate that the neurochemical and neuropharmacological profile of activity of clonidine is strictly dependent upon the dose of the drug. In addition, they support the concept that cortical alpha adrenoceptors modulate the function of neurons releasing ACh or GABA.


Effects of lignin on nitrification in soil.
The effects of two lignins isolated from black liquor from pulping process on nitrification in soils after addition of urea, (NH4)2SO4 and (NH4)2HPO4 were investigated by incubation at 20 or 30 degrees C for 7 or 14 d. The effects of lignin on nitrous oxide emissions from soil were also determined. Results showed that both lignins were more effective for inhibiting nitrification of NH4(+)-N as (NH4)2SO4 or (NH4)2HPO4 as compared to urea-N. The effectiveness of lignin on nitrification was markedly affected by different soil type and temperature. Nitrous oxide emissions from soil declined when lignin was used. Urea plus 20 and 50 g/kg lignin reduced N2O emissions by about 83% and 96%. respectively, while (NH4)2HPO4 plus 20 and 50 g/kg lignin respectively reduced emissions by 83% and 93%. Because of its low cost and nonhazardous characteristics, lignin has potential value as a fertilizer amendment to improve N fertilizer efficiency.


The development of a real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay using TaqMan technology for the pan detection of bluetongue virus (BTV).
Bluetongue virus (BTV) is an infectious, non-contagious viral disease of domestic and wild ruminants that is transmitted by adult females of certain Culicoides species. Since 2006, several serotypes including BTV-1, 2, 4, 6, 8, 9 and 16, have spread from the Mediterranean basin into Northern Europe for the first time. BTV-8 in particular, caused a major epidemic in northern Europe. As a result, it is evident that most European countries are at risk of BTV infection. The objective of this study was to develop and validate a real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) assay based on TaqMan technology for the detection of representative strains of all BTV serotypes. Primers and probes were based on genome segment 10 of the virus, the NS3 gene. The assay was tested for sensitivity, and specificity. The analytical sensitivity of the rRT-PCR assay was 200 copies of RNA per reaction. The assay did not amplify the closely related orbivirus epizootic hemorrhagic disease virus (EHDV) but successfully detected all BTV reference strains including clinical samples from animals experimentally infected with BTV-8. This real time RT-PCR assay offers a sensitive, specific and rapid alternative assay for the pan detection of BTV that could be used as part of a panel of diagnostic assays for the detection of all serotypes of BTV.


Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency.
X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency characterized by increased vulnerability to Epstein-Barr virus infection. XLP type 1 is caused by mutations in SH2D1A, whereas X-linked inhibitor of apoptosis (XIAP) encoded by XIAP/BIRC4 is mutated in XLP type 2. In XIAP deficiency, hemophagocytic lymphohistiocytosis (HLH) occurs more frequently and recurrence is common. However, the underlying mechanisms remain mostly unknown. We describe the characteristics of the cytokine profiles of serum samples from 10 XIAP-deficient patients. The concentration of interleukin (IL)-18 was strikingly elevated in the patients presented with HLH, and remained high after the recovery from HLH although levels of other pro-inflammatory cytokines approached the normal range. Longitudinal examination of two patients demonstrated marked exacerbation of IL-18 levels during every occasion of HLH. These findings may suggest the association between HLH susceptibility and high serum IL-18 levels in XIAP deficiency.


Use of latent class analysis as a method of assessing the physical activity level, sedentary behavior and nutritional habit in the adolescents' lifestyle: A scoping review.
Currently, adolescents' lifestyle is commonly characterized by physical inactivity, sedentary behavior, and inappropriate eating habits in general. A person-oriented approach as Latent Class Analysis (LCA) can offer more insight than a variable-centered approach when investigating lifestyle practices, habits, and behaviors of adolescent population. The aim of the present study was to assess which variables are mostly used to represent the physical activity level, sedentary behavior SB) and nutritional habit in the adolescents' lifestyle in studies that used the LCA. Scoping review. The study was a performed in accordance with the proposed criteria for systematic reviews and meta-analyses-Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered in PROSPERO (CRD42018108444). The original articles were searched in MEDLINE/PubMed, Scopus, ScienceDirect, Web of Science, PsycINFO, and SPORTdiscus. The Quality Assessment Tool analyzed the risk of bias of the included studies. 30 original articles were selected. The physical activity level (28 studies), SB and nutritional habits (18 studies) were the most common variable used to evaluate the adolescent's lifestyle by LCA model. Specifically, physical inactivity and high SB were the manifest variables with higher frequency in the negative latent classes (LCs) in adolescent girls. On the other hand, physical exercises and sports were activities more commonly labeled as positive LCs. The LCA models of the most of selected studies showed that physical inactivity, high SB were the most common in the LCs with negative characteristics of the adolescents' lifestyle. Better understanding the results of analyzes of clusters of multivariate behaviors such as the LCA can help to create more effective strategies that can make the lifestyle of adolescents healthier.


Displaced cratonic mantle concentrates deep carbon during continental rifting.
Continental rifts are important sources of mantle carbon dioxide (CO2) emission into Earth's atmosphere1-3. Because deep carbon is stored for long periods in the lithospheric mantle4-6, rift CO2 flux depends on lithospheric processes that control melt and volatile transport1,3,7. The influence of compositional and thickness differences between Archaean and Proterozoic lithosphere on deep-carbon fluxes remains untested. Here we propose that displacement of carbon-enriched Tanzanian cratonic mantle concentrates deep carbon below parts of the East African Rift System. Sources and fluxes of CO2 and helium are examined over a 350-kilometre-long transect crossing the boundary between orogenic (Natron and Magadi basins) and cratonic (Balangida and Manyara basins) lithosphere from north to south. Areas of diffuse CO2 degassing exhibit increasing mantle CO2 flux and 3He/4He ratios as the rift transitions from Archaean (cratonic) to Proterozoic (orogenic) lithosphere. Active carbonatite magmatism also occurs near the craton edge. These data indicate that advection of the root of thick Archaean lithosphere laterally to the base of the much thinner adjacent Proterozoic lithosphere creates a zone of highly concentrated deep carbon. This mode of deep-carbon extraction may increase CO2 fluxes in some continental rifts, helping to control the production and location of carbonate-rich magmas.


Clips and scar as the guidelines for breast radiation boost after lumpectomy.
Breast-conserving therapy in early breast cancer is equally effective as mastectomy, with advantages of cosmesis and quality of life over mastectomy. Local control is improved when entire breast irradiation is combined with a radiation boost to the tumour bed. Localization of the tumour bed was compared in 45 consecutive patients using surgical scar and radiopaque clips placed intra-operatively in the lumpectomy cavity. The area (A) of the radiation boost field and volume (V) of the tumour bed, designed on the basis of scar (AS and VS), were 1.4 times larger than those designed on the basis of the clips (AC and VC). AS and VS missed about one-quarter of the tumour bed which had been delineated by clips intra-operatively, while about one-half of it encompassed tissues beyond the AC and VC. A boost planned by scar dimensions can miss a substantial portion of the tumour bed, compromising local control. On the other hand, a substantial amount of breast tissue beyond the tumour bed can be unnecessarily irradiated, compromising cosmetic treatment results. Thus, the scar provides an inadequate landmark for radiation boost planning in breast-conserving therapy.