Effect of free ammonia shock on Chlorella sp. in wastewater: Concentration-dependent activity response and enhanced settleability.
The unstable microbial activity and unsatisfactory settling performance impede the development and implementation of microalgal wastewater treatment, especially in high-ammonium wastewater in the presence of free ammonia (FA). The shock of FA due to the nutrient fluctuation in wastewater was demonstrated as the primary stress factor suppressing microalgal activities. Recent study has clearly revealed the inhibition mechanism of FA at a specific high level (110.97 mg/L) by inhibiting the genetic information processing, photosynthesis, and nutrient metabolism. However, the effects of various FA shock concentrations on microalgal activities and settling performance remain unknown, limiting the wastewater bioremediation efficiencies improvement and the process development. Herein, a concentration-dependent shock FA (that was employed on microalgae during their exponential growth stages) effect on microalgal growth and photosynthesis was observed. Results showed that the studied five FA shock concentrations ranging from 25 to 125 mg/L significantly inhibited biomass production by 14.7-57.0%, but sharp reductions in photosynthesis with the 36.0-49.0% decreased Fv/Fm values were only observed when FA concentration was above 75.0 mg/L. On the other hand, FA shock enhanced microalgal settling efficiency by 12.8-fold, which was believed to be due to the stimulated intra- and extracellular protein contents and thereby the enhanced extracellular polymer substances (EPS) secretion. Specifically, FA shock induced 40.2 ± 2.3% higher cellular protein content at the cost of the decreased carbohydrates (22.6 ± 1.3%) and fatty acid (39.0 ± 0.8%) contents, further improving the protein secretion by 1.21-fold and the EPS production by 40.2 ± 2.3%. These FA shock-induced variations in intra- and extracellular biomolecules were supported by the up-regulated protein processing and export at the assistance of excessive energy generated from fatty acid degradation and carbohydrates consumption. In addition, FA shock significantly decreased the biomass nutritional value as indicated by the 1.86-fold lower essential amino acid score and nearly 50% reduced essential to non-essential amino acids ratio, while slightly decreased the biodiesel quality. This study is expected to enrich the knowledge of microalgal activities and settling performance in response to fluctuant ammonium concentrations in wastewater and to promote the development of microalgal wastewater treatment.


Gas chromatographic determination of noxyptyline in substance, tablets and in biological material.
Noxyptyline, i.e. 5-(2-dimethylaminoethyloxyimine)-5H-dibenzo[a,b] cyclohepta-1,4-diene hydrochloride, is an antidepressant. A new, direct method for its determination in substance and in tablets by means of gas chromatography has been developed. The results were compared with those of the spectrophotometric method, and the systematic errors(coefficient of variation) were 2.19% and 2.49%, respectively. Appropriate conditions were developed for the extraction of noxyptyline from plasma and urine, and the gas chromatographic method was applied for its determination. Within the concentration range 0.5-10 microgram/cm3, the systematic error after extraction from plasma was 4.61%, and after extraction from urine it was 2.08%. The recovery from plasma was 71.12 +/- 8%, and from urine it was 90.94 +/- 1.5%.


An unusual foreign body in an inguinal hernia sac: case report and literature review.
A 13-month-old boy accidentally ingested a 5 cm dressmaker's pin. On presentation, the pin was in the duodenum and there was a right inguinal hernia. After 17 days, the pin failed to progress. At surgery, the sac contained appendix perforated by the pin. This is the first case in the literature.


The impact of Water Ecological Civilization City Pilot on urban green innovation: the case of China.
As an essential part of ecological civilization, water ecological civilization has significant influence on the green and sustainable development of cities. Under the background of China's Water Ecological Civilization City Pilot (WECCP), based on data from 275 cities in China from 2007 to 2019 by using the difference-in-differences (DID) model, we empirically analyzed the influence of the WECCP establishment on urban green innovation and explored the impact mechanism in depth using a mediating effect model, which aimed to verify whether the "Porter hypothesis" holds true in China. The result indicated that the WECCP had made a remarkable contribution to enhancing urban green innovation in the pilot cities. Further research found that the input mechanism played an important mediating role. In addition, the heterogeneity test indicated that cities in the central region, at low administrative levels, and in the first batch of pilots gained more from the policy establishment. This paper has theoretical implications for understanding the derived innovation benefits of the environmental policy, practical implications for identifying new drivers of urban innovation, and provides related experience for the country to further promote and expand water ecological civilization construction and useful policy inspiration for other developing countries to formulate ecological and environmental policies.


Origin-specific epigenetic program correlates with vascular bed-specific differences in Rgs5 expression.
Cells from multiple origins contribute to vascular smooth muscle cell (VSMC) development. Phenotypic heterogeneity of VSMCs is associated with their point of developmental origin; however, the mechanisms driving such differences are unknown. We here examined the mechanisms controlling vascular bed-specific differences in Rgs5 expression during development. Rgs5 levels were similar across different regions of the vasculature in neonatal animals but were >15-fold higher in descending aortas compared with carotid arteries of adult mice. Thus, vessel bed-specific changes in regulation of Rgs5 expression occurred during vessel maturation. Examination of adult Rgs5-LacZ reporter mice revealed lower Rgs5 expression in VSMCs originating from the third (carotid artery) branchial arch compared with those originating in the fourth and sixth (aortic B segment, right subclavian, and ductus arteriosus) branchial arches. Indeed, a mosaic Rgs5 expression pattern, with discreet LacZ boundaries between VSMCs derived from different developmental origins, was observed. Furthermore, Rgs5-LacZ expression was correlated with the site of VSMC origin (splanchic mesoderm ≈ local mesenchyme > somites > proepicardium > mesothelium). Surprisingly, Rgs5 reporter activity in cultured carotid artery- and descending aorta-derived cells did not recapitulate the differences observed in vivo. Consistent with a developmental origin-specific epigenetic mechanism driving the observed expression differences in vivo, the Rgs5 promoter showed increased methylation on CpG dinucleotides in carotid arteries compared with that in descending aortas in adult but not in neonatal mice. In vitro methylation of the Rgs5 promoter confirmed that its activity is sensitive to transcriptional down-regulation by CpG methylation. These data suggest that an origin-dependent epigenetic program regulates vascular bed- and maturation state-dependent regulation of VSMC-specific gene transcription.


Evolving Surgical Techniques and Improving Outcomes for Aortic Arch Surgery in Canada.
To explore evolving surgical techniques and outcomes for aortic arch surgery. A total of 2435 consecutive patients underwent aortic arch repair with hypothermic circulatory arrest between 2008 and 2018 in 12 institutions across Canada. Trends in patient characteristics, surgical techniques, and in-hospital outcomes, including major morbidity or mortality, were examined. From 2008 to 2018, the age of patients (62.3 ± 13.2 years) and the proportion of women (30.2%) undergoing arch surgery did not change significantly. Aortic diameters at operation decreased (2008: 58 ± 13 mm; 2018: 53 ± 11 mm; P < 0.01). Surgeons performed more valve-sparing root replacements (2008: 0%; 2018: 15%; P < 0.001) and fewer Bentall procedures (2008: 27%; 2018: 20%; P < 0.01). Total arch replacement rates were similar (P = 0.18); however, elephant trunk (2008: 9.5%; 2018: 19%; P < 0.001) and frozen elephant trunk (2008: 3.1%; 2018: 15%; P < 0.001) repair rates have increased. Over time, higher nadir temperatures (2008: 18 [17-21]°C; 2018: 25 [23-28]°C; P < 0.001), and more frequent antegrade cerebral perfusion (2008: 61%; 2018: 83%; P < 0.001) were used. For elective cases, in-hospital mortality rates declined (2008: 6.8%; 2018: 1.2%; P = < 0.01), as did major morbidity or mortality (2008: 24%; 2018: 13%; P < 0.001) and transfusion rates (2008: 61%; 2018: 41%; P < 0.001), but stroke rates remained constant (2008: 6.8%; 2018: 5.3%; P = 0.12). Outcomes remained the same over time for urgent or emergent cases. Outcomes have improved over the past decade in Canada for elective aortic arch surgery, in the context of operating on smaller aortas, and more frequent use of moderate hypothermia and antegrade cerebral perfusion. Further research is needed to improve stroke rates and outcomes in the emergency setting.


The cholesteryl ester transfer protein (CETP) TaqIB polymorphism in the cholesterol and recurrent events study: no interaction with the response to pravastatin therapy and no effects on cardiovascular outcome: a prospective analysis of the CETP TaqIB polymorphism on cardiovascular outcome and interaction with cholesterol-lowering therapy.
On the basis of quantitative coronary angiography data, the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism has been postulated to predict the progression of coronary atherosclerosis and response to cholesterol-lowering therapy. Cholesteryl ester transfer protein mediates the exchange of lipids between anti-atherogenic high-density lipoprotein (HDL) and atherogenic apolipoprotein B containing lipoproteins and therefore plays a key role in human lipid metabolism. Hence, CETP gene polymorphisms may alter susceptibility to atherosclerosis. To investigate the significance of the CETP TaqIB gene polymorphism with respect to clinical end points, we used the Cholesterol And Recurrent Events (CARE) cohort. The CARE study was designed to investigate the effect of five years of pravastatin therapy on coronary events. We found that the odds ratios for the primary end point were not significantly different from unity for the three genetic subgroups after five years of placebo treatment. Furthermore, pravastatin induced similar changes in total cholesterol, low-density lipoprotein cholesterol, and HDL cholesterol among TaqIB genotypes, and both nonfatal myocardial infarction and deaths from coronary heart disease were reduced to the same extent in all three genotypes. In the CARE cohort, the CETP TaqIB polymorphism does not predict cardiovascular events or discriminate between those who will or will not benefit from pravastatin treatment.


Anatomy of the RNA and gene products of MC29 and MH2, two defective avian tumor viruses causing acute leukemia and carcinoma: evidence for a new class of transforming genes.
The RNA species of the defective avian acute leukemia virus MC29 and of the defective avian carcinoma virus MH2 and of their helper viruses were analyzed using gel electrophoresis, fingerprinting of RNase T1-resistant oligonucleotides, RNA-cDNA hybridization and in vitro translation. A28S RNA species, of 5700 nucleotides, was identified as MC29- or MH2-specific. MC29 RNA shared 4 out of about 17 and MH2 RNA at least 1 out of 16 T1-oligonucleotides with several other avain tumor virus RNAs. In addition MC29 and MH2 RNAs shared 2 oligonucleotides which were not found in any other viral RNA tested. 60% of each 28S RNA could be hybridized by DNA complementary to other avian tumor virus RNAs (group-specific) but 40% could only be hybridized by homologous cDNA (specific). Src gene-related sequences of Rous sarcoma virus were not found in MC29 or MH2 RNA. The specific and group-specific sequences of MC29, defined in terms of their T1-oligonucleotides, were located on a map of all T1-oligonucleotides of viral RNA. Specific sequences mapped between 0,4 and 0,7 map units from the 3'poly(A) end and group-specific sequences mapped between 0 and 0,4 and 0,7 and 1 map units. The MC29-specific RNA segment was represented by 6 oligonucleotides, two of which were those shared only by MC29 and MH2 RNAs. In vitro translation of MC29 RNA generated a major 120 000 dalton protein and minor 56 000 and 37 000 dalton proteins. The 120 000 dalton protein shared sequences with the proteins of the avian tumor viral gag gene, which maps at the 5' end of independently replicating viruses. Since a gag gene-related oligonucleotide was also found near the 5' end of MC29 RNA, we propose that the 120 000 MC29 protein was translated from the 5' 60% of MC29 RNA. It would then include sequences of the defective gag gene as well as MC29-specific sequences. Since both MC29 and MH2 lack the src (sarcoma) gene of Rous sarcoma virusk it is concluded that they contain a distinct class of transforming (onc) genes. We propose that the specific sequences of MC29 and MH2 represent all, or part of, their onc genes because the onc genes of MC29 and MH2 are specific and represent the only known genetic function of these viruses. If this proposal is correct, the onc genes of MC29 and MH2 would be related, because the specific RNA sequence of MC29 shares 2 of 6 oligonucleotides with MH2. It would also follow that the 120 000 dalton MC29 protein is a probable onc gene product, because it is translated from MC29-specific (and group-specific) sequences and because both MC29- and MH2-transformed cells contain specific 120 000 and 100 000 dalton proteins, respectively.


Cooled-radiofrequency neurotomy for the treatment of chronic lumbar facet (zygapophyseal) joint pain: A retrospective study.
Cooled-radiofrequency (CRFA) is a newer technique and may have some theoretical advantages over traditional radiofrequency ablation (TRFA). In this study, we aimed to investigate the efficacy and safety of CRFA for the treatment of lumbar facet joint-mediated pain. In this retrospective study, we evaluated 185 CRFA performed on 105 patients. All patients with axial lower back who received the preliminary diagnosis of lumbar facet joint-mediated pain and refractory to conservative therapy underwent diagnostic medial branch blocks. CRFA was recommended to those patients who responded favorably to two sets of diagnostic medial branch blocks. Pain scores in numeric rating scale (NRS) were recorded pre-treatment and post-treatment at different time-points. The primary outcome measure was to report descriptive NRS score and average % improvement from baseline at each time point. A significant pain relief was determined by a decrease of ≥50% of mean NRS. Secondary outcome measure was the time to repeat treatment with subsequent CRFA. Adverse events were also recorded.Primary outcome measure determined as the improvement in NRS, for at least 50% or more, was achieved in both 1st (4-8 weeks) and 2nd (>2-6 months) follow-up (FU) with 60.5% and 53.6% reduction in NRS respectively. Our subgroup analysis comparing the younger (<50) and older (≥50) age groups showed superior pain relief with CRFA in the older (≥50) age group, both in the 1st (4-8 weeks) and 2nd (>2-6 months) FU time points (63.4% and 58.4% reduction in NRS, respectively). Cooled-radiofrequency ablation is an effective and safe procedure for the treatment of chronic lumbar facet joint related pain. The duration of pain relief was comparable to traditional radiofrequency ablation as reported in the literature.


Toxic effects of triphenyltin on the silkworm Bombyx mori as a lepidopterous insect model.
Triphenyltin (TPT) is a widely used reagent in various industries and agriculture, but is also known to accumulate in natural ecosystems and animal tissues. Hence, the aim of this study was to comprehensively assess the toxicity of TPT in the silkworm Bombyx mori as a model insect. The results showed that TPT exposure for the entire 5th instar larval stage significantly reduced the weight of silkworm pupa and inhibited development of the silkworm midgut. Following exposure to 2 μg/kg of TPT for 4 days, differentially expressed genes in midgut were associated with enriched pathways involved in the metabolism of carbohydrates, lipids, and amino acids, as determined by RNA sequencing. Furthermore, the metabolic profiles of the intestinal content of silkworms exposed to 2 μg/kg of TPT for 4 days were markedly altered and differential metabolites produced by metabolism of carbohydrates, lipids, and amino acids were enriched as determined by non-targeted GC-MS/MS metabolomics. This study provides novel insights into the mechanisms underlying the toxicity of TPT and emphasizes the risks posed by such pollutants released into the environment.


Molecular identification of vivax malaria relapse patients in the Yunnan Province based on homology analysis of the Plasmodium vivax circumsporozoite protein gene.
More than 85% of the malaria burden in the Yunnan Province is caused by imported vivax malaria, and Yunnan is also where the majority of vivax malaria patients are diagnosed in China. Timely removal of the infection sources of Plasmodium vivax and its breeding environment remains the key to eliminating the secondary transmission of imported malaria. To that end, blood samples were collected from cases diagnosed and revalidated as single species infection with P. vivax in the Yunnan Province from 2013 to 2020. Specifically, samples from vivax malaria patients with suspected relapses episodes were subjected to PCR amplification, product sequencing, and analysis of the P. vivax circumsporozoite protein (pvcsp) gene. In total, 77 suspected relapse patients were identified out of 2484 cases infected with P. vivax, with a total of 81 recurrent episodes. A total of 156 CDS (coding DNA sequence) chains were obtained through PCR amplification and sequencing of the pvcsp gene from 159 blood samples, 121 of which can be matched to the paired sequences of 59 vivax malaria patients with both primary attack and recurrent experience. Of the 59 pairs of pvcsp gene sequences, every one of 31 pairs showed only one haplotype and no variant sites (VS), meaning every two paired sequence was completely homologous. Every one of the remaining 28 paired sequences had two haplotypes but no length polymorphism, indicating that the paired sequences was "weakly heterologous" with no fragment insertions (or deletions). All 59 vivax malaria patients with recurrences were caused by the activation of P. vivax hypnozoites originated from the same population as the primary infection. The paired analysis of the similarity between high variant genes allowed the identification of relapse episodes caused by P. vivax homologous hypnozoites and also demonstrated pvcsp gene as one of the candidate molecular markers for tracing infection origin.


Inequality trends in health and future health risk among English children and young people, 1999-2009.
To investigate trends in health inequality among children and young people between 1999 and 2009, using outcomes consistent with the current NHS reforms. Secondary analysis of participants aged 0-24 in the Health Surveys for England (HSE) undertaken in 1999, 2004, 2006 and 2009. Changes in the absolute and relative risks of four health outcomes by deprivation tertiles, based on occupation of the head of household: self/parent-reported general health; presence of a long-standing illness (LSI); obesity; smoking. No indicator showed a reduction in relative or absolute inequality between 1999 and 2009. For children (0-12 years), the relative risk comparing the most and least deprived tertiles increased significantly for poor general health (1999:1.6 (95% CI 1.2 to 2.2); 2009:3.9 (2.4 to 6.2), while the absolute difference in LSI prevalence(%) increased from 1.3 (-2.9 to 5.5) to 7.4 (3.6 to 11.4). Among young people (13-24 years), the absolute difference in LSI prevalence increased from -5.9 (-10.9 to -1.1) to 3.1 (-4.1 to 10.7). Absolute inequality in having tried smoking among children aged 8-15(%) increased significantly in the first half of the decade before decreasing in the second half (1999:3.3 (-1.1 to 7.7); 2004:14.1 (9.6 to 18.8); 2009:4.1 (0.1 to 8.8)). However, the increase in absolute inequality for smoking prevalence among young adults (16-24 years) was maintained throughout the decade (1999:-7.0 (-15.6 to 1.3); 2004:11.6 (3.7 to 20.0); 2009:8.2 (-0.3 to 16.9)). The national programme between 1999 and 2009 was not successful in reducing inequality in four key indicators of health status and future health risk among children and young people. Some inequality measures for general health, LSI prevalence and smoking increased over this time.


Trisomy 9p with an isochromosome of 9p.
An 18 1/2-year-old female is described with moderately severe mental retardation, the phenotype of the trisomy 9p syndromy, and an isochromosome for the short arm of a chromosome 9, contained in an unique karyotype, 46,XX,-9,t(7q9q),+ iso 9p.


Umami Ingredient: Flavor enhancer from shiitake (Lentinula edodes) byproducts.
An alternative use of shiitake stipes, usually treated as waste, was proposed for the production of a powder ingredient, rich in umami compounds, aiming its application in food. The extraction of umami compounds was optimized through the Response Surface Methodology (RSM), in order to obtain an extract with high umami taste intensity. From the optimized condition, a comparative analysis of shiitake stipes dehydration method was performed. Stipes were dehydrated by hot air drying (HD) and freeze drying (FD), submitted to extraction and the umami compounds in the extracts were compared. The comparative analysis showed that the 5' - nucleotides are more sensitive to prolonged heating, while the release of free amino acids (FAA) was favored by hot air drying. The HD samples extract showed higher Equivalent Umami Concentration (EUC). The spray drying of the HD samples extract allowed the production of a newly powder ingredient rich in umami compounds (Umami Ingredient) that can be applied in diverse food matrices. Due to the presence of umami compounds, Umami Ingredient can be a potential alternative to help in the process of sodium reduction by enhancing food flavor.


[Collagen synthesis and heart failure].
Little is known about collagen metabolism in heart failure, with or without left ventricular systolic dysfunction. We studied serum concentrations of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type-I synthesis, and of the carboxy-terminal telopeptide of collagen type I (ICTP), a marker of collagen type-I degradation, in 70 patients admitted for heart failure (35 with depressed left ventricular systolic function and 35 with preserved left ventricular systolic function) and in 30 control subjects. Patients with kidney failure, liver disease, metabolic bone disease, rheumatic disease, recent (within 3 months) major trauma or surgery, or serious wounds were excluded. The concentration of the collagen synthesis marker, PIP, was higher in heart failure patients than control subjects, at 140+/-56.38 mg/L vs 113.66+/-36.6 microg/L, respectively (P=.01). However, there was no difference in the concentration of the collagen degradation marker, ICTP, between heart failure patients and control subjects, at 2.89+/-2.37 mg/L vs 2.26+/-1.7 microg/l, respectively. In heart failure patients, left ventricular systolic function had nonsignificant effect on the PIP or ICTP concentration.


Biomass burning in the Amazon-fertilizer for the mountaineous rain forest in Ecuador.
Biomass burning is a source of carbon, sulfur and nitrogen compounds which, along with their photochemically generated reaction products, can be transported over very long distances, even traversing oceans. Chemical analyses of rain and fogwater samples collected in the mountaineous rain forest of south Ecuador show frequent episodes of high sulfate and nitrate concentration, from which annual deposition rates are derived comparable to those found in polluted central Europe. As significant anthropogenic sources are lacking at the research site it is suspected that biomass burning upwind in the Amazon basin is the major source of the enhanced sulfate and nitrate imput. Regular rain and fogwater sampling along an altitude profile between 1800 and 3185 m has been carried out in the Podocarpus National Park close to the Rio SanFrancisco (3 degrees 58'S, 79 degrees 5'W) in southern Ecuador. pH values, electrical conductivity and chemical ion composition were measured at the TUM-WZW using standard methods. Results reported cover over one year from March 2002 until May 2003. Annual deposition rates of sulfate were calculated ranging between 4 and 13 kg S/ha year, almost as high as in polluted central Europe. Nitrogen deposition via ammonia (1.5-4.4 kg N/ha year) and nitrate (0.5-0.8 kg N/ha year) was found to be lower but still much higher than to be expected in such pristine natural forest environment. By means of back trajectory analyses it can be shown that most of the enhanced sulfur and nitrogen deposition is most likely due to forest fires far upwind of the ecuadorian sampling site, showing a seasonal variation, with sources predominantly found in the East/North East during January-March (Colombia, Venezuala, Northern Brazil) and East/SouthEast during July-September (Peru, Brazil). Our results show that biomass burning in the Amazon basin is the predominant source of sulfur and nitrogen compounds that fertilize the mountaineous rain forest in south Ecuador. The mountaineous rain forest in south Ecuador has developed on poor and acid soils, with low nutrient availability. The additional ferilization resulting from anthropogenic biomass burning constitutes a significant disturbance of this ecosystem, its functioning and biodiversity. Thus it is planned to employ isotope analyses for quantifying the pathways. of nitrate and sulfate deposition in these natural forests.


Microsphere-based scaffolds encapsulating tricalcium phosphate and hydroxyapatite for bone regeneration.
Bioceramic mixtures of tricalcium phosphate (TCP) and hydroxyapatite (HAp) are widely used for bone regeneration because of their excellent cytocompatibility, osteoconduction, and osteoinduction. Therefore, we hypothesized that incorporation of a mixture of TCP and HAp in microsphere-based scaffolds would enhance osteogenesis of rat bone marrow stromal cells (rBMSCs) compared to a positive control of scaffolds with encapsulated bone-morphogenic protein-2 (BMP-2). Poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds encapsulating TCP and HAp mixtures in two different ratios (7:3 and 1:1) were fabricated with the same net ceramic content (30 wt%) to evaluate how incorporation of these ceramic mixtures would affect the osteogenesis in rBMSCs. Encapsulation of TCP/HAp mixtures impacted microsphere morphologies and the compressive moduli of the scaffolds. Additionally, TCP/HAp mixtures enhanced the end-point secretion of extracellular matrix components relevant to bone tissue compared to the "blank" (PLGA-only) microsphere-based scaffolds as evidenced by the biochemical, gene expression, histology, and immunohistochemical characterization. Moreover, the TCP/HAp mixture groups even surpassed the BMP-2 positive control group in some instances in terms of matrix synthesis and gene expression. Lastly, gene expression data suggested that the rBMSCs responded differently to different TCP/HAp ratios presented to them. Altogether, it can be concluded that TCP/HAp mixtures stimulated the differentiation of rBMSCs toward an osteoblastic phenotype, and therefore may be beneficial in gradient microsphere-based scaffolds for osteochondral regeneration.


[The clinical picture of "circumscribed granuloma diseases"].
Characteristic findings, differential diagnosis and clinical course of the so-called "circumscript granulomas" (Granuloma anulare, necrobiosis lipoidica, Miescher's granulomatosis, disciformis, necrobiosis maculosa, granuloma multiforme, actinic granuloma, granuloma faciale and lethal midline granuloma etc.) are represented in a condensed clinical survey.


18F-FDG PET for staging breast cancer in patients with inner-quadrant versus outer-quadrant tumors: comparison with long-term clinical outcome.
Extraaxillary metastases (i.e., in the absence of axillary involvement) are more likely to develop in patients with inner-quadrant (IQ) breast cancer than in patients with outer-quadrant (OQ) primary tumors. The relative difficulty of identifying extraaxillary metastases may lead to understaging of cancer in these patients. This study examined whether (18)F-FDG PET findings were differentially associated with the location of primary tumors, and with long-term prognosis, in IQ and OQ patients. Follow-up data were obtained for 141 patients whose breast cancer was staged by PET and who were documented to have IQ (n = 42) or OQ (n = 99) primaries. Results were stratified according to PET findings consistent with different metastatic patterns. Data were further analyzed with respect to disease outcome after a mean 3-y follow-up period. Among IQ patients, progressive disease was identified in 26.1%, compared with 13.1% of OQ patients, for a relative risk (RR) of 2.0. Of patients with PET findings of isolated extraaxillary metastases, 36.1% had progressive disease, compared with 10.7% of other patients (RR = 3.4), and 61.9% of IQ patients had isolated extraaxillary metastases identified on PET, compared with 10.1% of OQ patients (RR = 6.1). IQ patients demonstrated a 6-fold greater frequency of PET findings of isolated extraaxillary metastasis, and such findings were associated with triple the risk for disease progression. Patients with IQ tumors could be vulnerable to understaging with conventional staging approaches and may particularly benefit from PET during the staging process.


The subcellular localization of apomucin and nonreducing terminal N-acetylgalactosamine in porcine submaxillary glands.
Antibodies prepared against enzymatically deglycosylated porcine submaxillary gland mucin (apomucin), which were unreactive with native mucin and its partially deglycosylated derivatives, were used to immunolocalize apomucin in situ. Electron microscopy of sections of Lowicryl K4M-embedded tissue reacted successively with antibodies and protein A-gold complexes showed apomucin exclusively in mucous cells within the rough endoplasmic reticulum, transitional elements of the endoplasmic reticulum, and vesicles at the cis side of the Golgi apparatus. The Golgi apparatus, forming mucous droplets, and mucous droplets contained no apomucin. Although the rough endoplasmic reticulum contained most of the apomucin in mucous cells, some cisternae of the endoplasmic reticulum and the nuclear envelope were devoid of apomucin. Examination of tissue sections treated with the glycosidases used to prepare apomucin revealed immunolabel for apomucin throughout the secretory pathway. Colloidal gold coated with Helix pomatia lectin was used to detect nonreducing N-acetylgalactosamine residues. In mucin-producing cells lectin-gold was found in the mucous droplets, the forming mucous droplets, and throughout the Golgi apparatus but mostly in the cis portion of this organelle. In tissue sections reacted successively with lectin-gold and anti-apomucin/protein A-gold, both types of gold complex could be found in the cis side of the Golgi apparatus. These data indicate that the O-glycosylation of mucin is a posttranslational event that occurs in the Golgi apparatus and begins in the cis side of the Golgi apparatus.


Role of SulP, a nuclear-encoded chloroplast sulfate permease, in sulfate transport and H2 evolution in Chlamydomonas reinhardtii.
Antisense technology was applied to the green alga Chlamydomonas reinhardtiito probe the function of a novel nuclear gene encoding a chloroplast-envelope localized sulfate permease (SulP; GenBank Accession Numbers AF467891 and AF481828). Analysis showed that antiSulP transformants are impaired in sulfate uptake, a consequence of repression in the SulP gene expression. Antisense antiSulP transformants exhibited a sulfur-deprivation phenotype, strong induction of arylsulfatase activity, and global induction of sulfate assimilation gene expression. In sealed cultures, opposite to the wild-type control, antiSulP strains photo-evolved H2, underlining the notion of sulfate uptake limitation by the chloroplast, a slow-down in the rate of oxygen evolution, establishment of anaerobiosis due to internal respiration and spontaneous expression of the [Fe]-hydrogenase in these strains. It is concluded that antiSulP strains are promising as tools to limit the supply of sulfates to the chloroplast, leading to a down-regulation of H2O-oxidation and O2-evolution activity, to the constitutive expression of the [Fe]-hydrogenase and continuous H2-photoproduction in Chlamydomonas reinhardtii.Thus, antisulPstrains might permit a study of the biochemistry of H2 metabolism in this green alga under constitutive anaerobic oxygenic photosynthesis conditions.


Circulating and Tissue Expression Levels of YKL-40 in Renal Cell Cancer.
Blood levels of YKL-40 are elevated in various malignancies and other inflammatory diseases. Higher YKL-40 levels have consequently been shown to correlate with poor prognosis in several cancers. We investigated the prognostic value of circulating and tissue levels of YKL-40 in renal cell cancer. Preoperative YKL-40 serum/plasma levels were determined in 222 surgically treated patients with renal cell cancer and in 35 controls. Postoperative serum samples were analyzed in 19 of the 222 renal cell cancer cases. Gene expression levels were assessed in 101 renal cell cancer frozen tissue samples using quantitative real-time reverse transcriptase-polymerase chain reaction. Finally immunohistochemical analysis was done in 37 renal cell cancer cases to assess tissue localization of YKL-40. Results were correlated with clinicopathological and followup data. YKL-40 serum but not tissue gene expression levels were higher in patients with renal cell cancer compared to controls (p = 0.050). Serum YKL-40 levels significantly increased following nephrectomy (p <0.001). High circulating YKL-40 concentrations were independently associated with shorter survival in the serum and plasma cohorts. YKL-40 gene expression did not correlate with patient prognosis. Preoperatively elevated circulating levels of YKL-40 predict survival in patients treated with nephrectomy for renal cell cancer independently of levels determined in serum or plasma. Tumor cells do not seem to be the main source of increased serum/plasma YKL-40 levels in patients with renal cell cancer.


The effect of a fibre free and fibre supplemented polymeric enteral diet on normal human bowel function.
Although the effects of dietary fibre in a normal diet on intestinal function are well known, the effects of supplementing enteral diet with fibre on intestinal function are not so clear. The aims of the present study were two fold: firstly to compare intestinal function during ingestion of a self selected diet and fibre free polymeric enteral diet and secondly to investigate the effect of adding the fibre source, soy polysaccharide to the same polymeric diet, on bowel function. Six healthy subjects were randomly assigned to 3 treatment periods (7 days) of a self selected diet (SSD), 2 l polymeric enteral diet (ED), or 2 l of the same polymeric enteral diet supplemented with 20 g/l of soy polysaccharide fibre (SPED). Parameters measured were bowel frequency/day, mean daily wet stool weights and whole gut transit time. Highest stool wet weights (g/24 h +/- SEM) were obtained from subjects consuming a SSD (180.3 +/- 30.6). This was significantly higher (p < 0.02) than those consuming an ED (81.9 +/- 14.5) but not a SPED (123 +/- 22.3). Whole gut transit (h +/- SEM) on a SSD (47 +/- 5.9) was significantly (p < 0.05) quicker than on an ED (73 +/- 4.9), but not significantly different from those ingesting a SPED (54 +/- 5.5). Bowel frequency/day (+/- SEM) in subjects consuming a SPED (1.0 +/- 0.1) was significantly (p < 0.02) higher than in subjects ingesting an ED (0.8 +/- 0.1) but was not significantly different when compared to a SSD (1.0 +/- 0.2). We conclude that ingestion of an ED results in significantly longer whole gut transit time, significantly decreased daily stool wet weights and decreased bowel frequency when compared to a SSD. The ingestion of 30 g of soy polysaccharide in a polymeric enteral diet not only tends to normalise whole gut transit time and daily stool wet weights, but also significantly increases bowel frequency when compared with values seen during the consumption of a fibre free polymeric enteral diet.


Targeted delivery of proteins into the central nervous system mediated by rabies virus glycoprotein-derived peptide.
Delivery of therapeutic proteins across the blood-brain barrier (BBB) is severely limited by their size and biochemical properties. Here we showed that a 39-amino acid peptide derived from the rabies virus glycoprotein (RDP) was exploited as an efficient protein carrier for brain-targeting delivery. Three proteins with different molecular weight and pI, β-galactosidase (β-Gal), luciferase (Luc) and brain-derived neurotrophic factor (BDNF), were fused to RDP and intravenously injected into the mice respectively. The slices of different tissues with X-Gal staining were used to examine whether RDP could deliver β-Gal targeted into the CNS. The time-course relationship of RDP-Luc was studied to confirm the transport efficiency of RDP. The neuroprotective function of RDP-BDNF was examined in mouse experimental stroke to explore the pharmacological effect of RDP fusion protein. The results showed that the fusion proteins rapidly and specific entered the nerve cells in 15 min, and the t(1/2) was about 1 hr. Furthermore, RDP-BDNF fusion protein showed the neuroprotective properties in mouse experimental stroke including reduction of stroke volume and neural deficit. RDP provides an effective approach for the targeted delivery of biological active proteins into the central nervous system.


Health implications of war in Uganda and Sudan.
Civil war disrupted agriculture and trade in Uganda and Sudan. This reduced tax revenues and drained scarce resources away from health budgets to finance increased military expenditures. Hundreds and thousands of people were driven from their homes either as internally displaced people or as refugees. Normal health service delivery systems were broken down forcing doctors, nurses and other health professionals into towns, cities or neighbouring countries in search of peace and employment. Scores of hospitals, health centres and dispensaries were abandoned, destroyed or looted, rendering even the limited physical facilities useless. Preventive public health services such as immunization and provision of potable drinking water were discontinued leaving huge populations susceptible to controllable infectious diseases and epidemics.


Graft vascular disease after cardiac transplantation and its relationship to mean acute rejection score.
Graft vascular disease remains a significant source of morbidity and mortality in heart transplant patients. The influence of acute cellular rejection on the development of graft vascular disease is controversial. To determine the relationship between mean acute cellular rejection score and the presence of atherosclerosis or fibrointimal hyperplasia in cardiac allografts at autopsy. This retrospective, autopsy-based study examined 27 heart transplant patients to evaluate for graft vascular disease. A rejection score for each patient was calculated as the average of all the rejection scores determined by endomyocardial biopsy. Gross and histologic examination of the heart was used to divide patients into 3 groups: no coronary artery disease, atherosclerosis, and fibrointimal hyperplasia. Mean rejection scores were calculated for each of these groups for all patients and patients who survived longer than 3 months. Mean rejection scores were compared by an analysis of variance and pairwise t tests. Mean rejection scores demonstrated a trend of increasing value from no coronary disease (0.323) to atherosclerosis (0.569) to fibrointimal hyperplasia (0.835). Only fibrointimal hyperplasia had a significantly higher mean rejection score compared with patients with no coronary disease when examined in all patients (P = .01) and in patients who survived longer than 3 months (P = .049). This study showed that the development of coronary artery fibrointimal hyperplasia, but not atherosclerosis, was significantly related to mean acute rejection score.


Drug-induced liver disease.
Drug-induced liver injury (DILI), also known as hepatotoxicity, refers to liver injury caused by drugs or other chemical agents, and represents a special type of adverse drug reaction. It has been estimated that more than 600 drugs and chemicals have been associated with significant liver injury. Many previous reviews have focused on DILI pathogenesis or have outlined the clinical features of liver injury linked to different drugs. This article briefly touches on several areas that are potentially vexing for both the novice and cognoscenti, with the goal of guiding the consultant through one of the most challenging areas of hepatology.


Characteristics and outcomes of very low birth weight infants receiving epinephrine during delivery room resuscitation.
Delivery room resuscitation of very low birth weight infants can involve use of endotracheal or intravenous epinephrine. Data of the past 19 years were reviewed to identify the usage of epinephrine in delivery room and identify characteristics of these babies. Neonates with ≤1500g birthweight from January 1996 to August 2014 were reviewed. Infants born alive and admitted to NICU were eligible. Characteristics such as demographics, survival and outcomes were recorded. Variables significant at p≤0.1 among neonates receiving epinephrine were further analyzed via multiple logistic regressions. Out of 5868 eligible neonates, 416 (7%) received epinephrine in the delivery room. The infants who received epinephrine were of lower estimated gestational age (25 vs. 28wk) and lower birth weight (746 vs. 980g). Gender, race and mode of delivery were comparable between the two cohorts. Survival was higher in non-epinephrine group (89.4 vs. 61.1%). Bacterial infection (24.3 vs. 18.4%) and combined grade 3 and 4 intraventricular hemorrhage (18.4 vs. 8.4%) were higher in epinephrine group. Use of epinephrine in the delivery room was associated with decreased survival even after controlling for birth weight, gestational age and low Apgar scores [Odd ratio - 0.48 with 95% CI (0.37-0.62), p<0.001]. Neonates with lower birth weight and younger gestational age were more likely to receive epinephrine during resuscitation at birth. Use of epinephrine in delivery room was associated with lower survival and severe intraventricular hemorrhage among very low birth weight infants.


Readiness of ethics review systems for a changing public health landscape in the WHO African Region.
The increasing emphasis on research, development and innovation for health in providing solutions to the high burden of diseases in the African Region has warranted a proliferation of studies including clinical trials. This changing public health landscape requires that countries develop adequate ethics review capacities to protect and minimize risks to study participants. Therefore, this study assessed the readiness of national ethics committees to respond to challenges posed by a globalized biomedical research system which is constantly challenged by new public health threats, rapid scientific and technological advancements affecting biomedical research and development, delivery and manufacture of vaccines and therapies, and health technology transfer. This is a descriptive study, which used a questionnaire structured to elicit information on the existence of relevant national legal frameworks, mechanisms for ethical review; as well as capacity requirements for national ethics committees. The questionnaire was available in English and French and was sent to 41 of the then 46 Member States of the WHO African Region, excluding the five Lusophone Member States. Information was gathered from senior officials in ministries of health, who by virtue of their offices were considered to have expert knowledge of research ethics review systems in their respective countries. Thirty three of the 41 countries (80.5 %) responded. Thirty (90.9 %) of respondent countries had a national ethics review committee (NEC); 79 % of which were established by law. Twenty-five (83.3 %) NECs had secretarial and administrative support. Over 50 % of countries with NECs indicated a need for capacity strengthening through periodic training on international guidelines for health research (including clinical trials) ethics; and allocation of funds for administrative and secretariat support. Despite the existing training initiatives, the Region still experiences a shortage of professionals trained in health research ethics/ethicists. Committees continue to face various capacity needs especially for evaluating clinical trials, for monitoring ongoing research, database management and for accrediting institutional ethics committees. Given the growing number of clinical trials involving human participants in the African Region, there is urgent need for supporting countries without NECs to establish them; capacity strengthening where they exist; and creation of a regional network and joint ethical review mechanisms, whose membership would be open to all NECs of the Region.


Generating and evaluating evidence of the clinical utility of molecular diagnostic tests in oncology.
Enthusiasm for molecular diagnostic (MDx) testing in oncology is constrained by the gaps in required evidence regarding its impact on patient outcomes (clinical utility (CU)). This effectiveness guidance document proposes recommendations for the design and evaluation of studies intended to reflect the evidence expectations of payers, while also reflecting information needs of patients and clinicians. Our process included literature reviews and key informant interviews followed by iterative virtual and in-person consultation with an expert technical working group and an advisory group comprising life-sciences industry experts, public and private payers, patients, clinicians, regulators, researchers, and other stakeholders. Treatment decisions in oncology represent high-risk clinical decision making, and therefore the recommendations give preference to randomized controlled trials (RCTs) for demonstrating CU. The guidance also describes circumstances under which alternatives to RCTs could be considered, specifying conditions under which test developers could use prospective-retrospective studies with banked biospecimens, single-arm studies, prospective observational studies, or decision-analytic modeling techniques that make a reasonable case for CU. Using a process driven by multiple stakeholders, we developed a common framework for designing and evaluating studies of the clinical validity and CU of MDx tests, achieving a balance between internal validity of the studies and the relevance, feasibility, and timeliness of generating the desired evidence.Genet Med 18 8, 780-787.


Genitourinary and breast radiology.
This is the sixth in a series of short reviews of internet-based radiological learning resources and will focus on genitourinary (GU) and breast radiology. Below are details of a few of the higher quality resources currently available. Most of the sites cater for medical students and trainee or non-specialist radiologists, but may be also be of interest to specialists, especially for use in teaching. Hyperlinks are available in the electronic version of this article and were all active at the time of going to press (July 2006).


Doctors, lawyers evaluate each other in new study.
Asking doctors and lawyers what they like and dislike about each other brings strong, often negative results. Take a look at the level of trust between doctors and lawyers and learn how both sides view one another. And discover ways to patch up the rocky relationships.


A Case Report on Paget-Schroetter Syndrome Presenting as Acute Localized Rhabdomyolysis.
The life- or limb-threatening differential diagnosis for upper extremity swelling can include deep vein thrombosis (DVT), infectious processes, and compartment syndrome. Chronic anatomic abnormalities such as axillary vein stenosis are rarely a consideration in the emergency department. We present a 26-year-old female with history of Chiari type 1 malformation who presented with acute left arm swelling. Initial workup, including point-of-care ultrasound, revealed the presence of significant soft tissue swelling without evidence of DVT. Further workup revealed an early, localized rhabdomyolysis secondary to axillary vein stenosis or venous thoracic outlet syndrome, also known as Paget-Schroetter syndrome.


The laterally positioned flap.
The laterally positioned flap has shown itself to be the most predictable and esthetically successful procedure in the treatment of mucogingival defects such as gingival/periodontal recessions and root exposures. It is of utmost importance that the biologic principles of wound healing, which have been discussed in the literature and this article, should be adhered to prior to, during, and after the surgical procedure.


Risk factors for fatal and nonfatal reactions to subcutaneous immunotherapy: National surveillance study on allergen immunotherapy (2008-2013).
In 2008, an annual surveillance study of systemic reactions (SRs) from subcutaneous immunotherapy (SCIT) injections was initiated in North America. To define the incidence of SRs to SCIT. From 2008 to 2013, 27% to 51% of American Academy of Allergy, Asthma, and Immunology and American College of Asthma, Allergy, and Immunology members completed an annual survey of SCIT-related SRs of varying severity. From 2012 to 2013, data were collected regarding SRs with off-label sublingual immunotherapy (SLIT), selection of patients with asthma for SCIT, and strategies for dose adjustment during pollen seasons. From 2008 to 2013, data were gathered on 28.9 million injection visits, including 344,480 patients for 2012 to 2013. Since 2008, a total of 2 confirmed fatalities were directly reported that occurred under the care of allergists. Two additional fatalities occurred under the care of nonallergists. The rate of SRs from SCIT remained stable, occurring in 1.9% of patients, with 0.08% and 0.02% experiencing grade 3 and 4 SRs. SRs occurred in 1.4% of patients receiving off-label SLIT, including 0.03% with grade 3 SRs. There were no SLIT-related grade 4 SRs or fatalities. Practices that never administered SCIT in patients with uncontrolled asthma (Asthma Control Test score <20) had significantly fewer grade 3 and 4 SRs (odds ratio, 0.7; 95% confidence interval, 0.5-1.0, and odds ratio, 0.3; 95% confidence interval, 0.1-0.8, respectively). Lowering doses during pollen seasons for patients with highly positive skin tests reduced SRs of all severity grades (P < .05). SCIT-related fatality rates may be decreasing, but continued vigilance regarding modifiable risk factors, including careful patient selection, is needed. Dose adjustment during pollen seasons for highly sensitive patients may reduce risks. Potential risk for SRs from off-label SLIT exists.


Generation of internal image monoclonal anti-idiotypic antibodies against idiotypic antibodies to GP5 antigen of porcine reproductive and respiratory syndrome virus.
Syngeneic monoclonal anti-idiotypic antibodies (Mab2s) were generated against idiotypic antibodies to membrane glycoprotein GP5 of porcine reproductive and respiratory syndrome virus (PRRSV) using the sequential immunization method. Six of 12 Mab2s possessed potential internal image characteristics by recognizing a common idiotype on murine and swine anti-GP5 antibodies. Further serological characterization demonstrated that one of the Mab2 (Mab2-5G2) represents internal image anti-idiotope which mimicked the GP5 antigen that inhibited the interaction between idiotypic anti-GP5 antibodies and GP5 antigen, its reaction with the idiotypic anti-GP5 antibody was inhibited by GP5 antigen and detected the common Id on anti-PRRSV antibodies from pigs that were experimentally infected with PRRSV. In addition, Mab2-5G2 identified a soluble protein on MA-104 and porcine alveolar macrophages. These results indicate that Mab2-5G2 may be a useful candidate as an alternative PRRSV serodiagnostic reagent and a useful probe to study PRRSV-cell interaction.


The influence of FeCl3 on the photocatalytic degradation of dissolved azo dyes in aqueous TiO2 suspensions.
The study concerned decolouration of solutions of azo, anionic (Acid Orange 7, Reactive Red 45, Acid Yellow 23) and cationic (Basic Blue 41 and Basic Orange 66) dyes during illumination with UV (lambdamax 366 nm) irradiation in the presence of TiO2 and FeCl3. The process of decolouration during illumination of the solutions studied containing FeCl3 underwent significant intensification in the case of anionic dyes and unfavourable inhibition in case of cationic dyes. It was also observed that FeCl3 had a diverse influence on the adsorption of the dyes studied on TiO2. The adsorption of anionic dyes and decolouration of solutions before the illumination was observed only in the presence of FeCl3. In case of cationic dyes the addition of FeCl3 caused elimination of these phenomena. An additional cause of decolouration of anionic dyes solutions before illumination was the precipitation of their poorly soluble compounds from Fe3+. The processes of degradation and mineralization of the dye that accompanied decolouration of Acid Orange 7 solutions were also observed. It was stated that similarly to the case of Acid Orange 7, the decolouration of the studied anionic dyes' solutions can depend on the concentration of FeCl3, the amount of TiO2 and the initial concentration of the dye in its solution.


Isolation and identification of free-living amoeba from the hot springs and beaches of the Caspian Sea.
Free-living amoeba (FLA) such as Acanthamoeba, Naegleria, Balamuthia, and Vermamoeba have been identified from both natural and human-made environments such as Hot springs and spa. Naegleria fowleri causes Primary Amoebic Meningoencephalitis (PAM), while Acanthamoeba and Balamuthia cause chronic granulomatous encephalitis. Acanthamoeba also can cause cutaneous lesions and Amoebic Keratitis (AK) that is associated with contact lens use or corneal trauma. FLA are known to serve as host of and vehicles for diverse intracellular organisms. This study aimed was to identify the presence of FLA in the hot springs and beaches of the Caspian Sea in Ramsar tourist town located in the northern part of Iran. Water samples were collected in sterile bottles and were transferred to the laboratory. One litre of each sample passed through the nitrocellulose membrane filter. Each filter insert was then placed in non-nutrient agar plates already seeded with lawn culture of Escherichia coli. Positive samples were analyzed by morphological keys and Polymerase chain reaction (PCR) using 18S rDNA gene and ITS region to identify amoeba isolates. A total of 81 water sampled were tasted. After identified using the morphological key and PCR assay, 54 (66.6%) of the samples were positive for FLA. Ten of the samples were identified as Acanthamoeba (belong to T3, T4, and T5 genotypes), three as Vermamoeba vermiformis, four as Naegleria (3 N.australiensis and 1 N.grubery). Only one sample was positive Vahlkampfia. The presence of thermotolerant FLA in the Hot springs and beaches of the Caspian Sea as places for recreational purposes or wellness may be a potential health risk.


Molecular cloning of polyoma virus DNA in Escherichia coli: lambda phage vector system.
The biological activity of recombinant phage and recombinant phage DNA containing monomeric or dimeric polyoma DNA inserts was examined in mice and cultured mouse cells. Recombinant preparations containing a single copy of viral DNA were invariably noninfectious; molecules containing a dimeric polyoma DNA insert were at least seven orders of magnitude less infectious than polyoma virions after parenteral inoculation. No infection was detected with any recombinant preparation after oral administration.


Performance and mechanisms for tetrabromobisphenol A efficient degradation in a novel homogeneous advanced treatment based on S2O42- activated by Fe3.
Tetrabromobisphenol A (TBBPA), a representative brominated flame retardant (BFR), generally could be debrominated and degraded effectively in photolysis systems with the high energy consumption. In this study, the novel sulfate radical (SO4•-) generation resource of dithionite (S2O42-), activated by the common transition metal of Fe3+, has been applied for establishing an innovative homogeneous advance treatment system for BFR treatment in water. When coupling Fe3+ with S2O42-, TBBPA degradation efficiency could be remarkably improved from 38.7% to 93.8% with the debromination and mineralization efficiency of 83.9% and 18.5% in 60 min, respectively. The primary reactive species also have been identified as SO3•-, SO4•- and •OH responsible for TBBPA treatment and the contributions of SO4•- and •OH have been calculated as 43.8% and 28.4% for TBBPA degradation, respectively. In Fe3+/S2O42- system, TBBPA was effectively degraded in a wide initial pH range (3.0-9.0), whose activation energy was calculated as 32.01 kJ mol-1. Due to the only operation of reagents dosing, the energy consumption and cost could be decreasing significantly without any light energy input and reaction conditions (e.g., pH and dissolved oxygen) adjustment compared with the general photolysis process. Moreover, some possible degradation approaches of TBBPA also have been proposed via GC-MS including debromination, hydroxylation, methylation, and mineralization in Fe3+/S2O42- system. And these probable degradation pathways also have been confirmed with the decreased Gibbs free energy (ΔG) based on density functional theory (DFT). This study has revealed that it was promising of Fe3+/S2O42- system for BFRs degradation and detoxification efficiently through the simple operation and mild condtions.


Myelin plasticity during early literacy training in at-risk pre-readers.
A growing body of neuroimaging evidence shows that white matter can change as a result of experience and structured learning. Although the majority of previous work has used diffusion MRI to characterize such changes in white matter, diffusion metrics offer limited biological specificity about which microstructural features may be driving white matter plasticity. Recent advances in myelin-specific MRI techniques offer a promising opportunity to assess the specific contribution of myelin in learning-related plasticity. Here we describe the application of such an approach to examine structural plasticity during an early intervention in preliterate children at risk for dyslexia. To this end, myelin water imaging data were collected before and after a 12-week period in (1) at-risk children following early literacy training (n = 13-24), (2) at-risk children engaging with other non-literacy games (n = 10-17) and (3) children without a risk receiving no training (n = 11-22). Before the training, regional risk-related differences were identified, showing higher myelin water fraction (MWF) in right dorsal white matter in at-risk children compared to the typical control group. Concerning intervention-specific effects, our results revealed an increase across left-hemispheric and right ventral MWF over the course of training in the at-risk children receiving early literacy training, but not in the at-risk active control group or the no-risk typical control group. Overall, our results provide support for the use of myelin water imaging as a sensitive tool to investigate white matter and offer a first indication of myelin plasticity in young children at the onset of literacy acquisition.


Alterations in the thyroids of rats treated for long periods with di-(2-ethylhexyl) phthalate or with hypolipidaemic agents.
Treatment of rats for periods of 3 months or longer with the hypolipidaemic drugs clofibrate and fenofibrate or with the plasticiser di-(2-ethylhexyl) phthalate causes alterations in the thyroid. The colloid is shrunken and contains calcium-rich inclusions. Electron microscopy shows increases in the number and size of lysosomes, hypertrophy of the Golgi apparatus and dilation of the rough endoplasmic reticulum. These changes are consistent with persistent hyperactivity in the gland.


Influences of thoracic duct blockage on early enteral nutrition for patients who underwent esophageal cancer surgery.
We have previously reported the beneficial effects of immediate enteral nutrition (EN) after esophageal cancer surgery. This randomized control study was conducted to determine whether immediate EN is beneficial or not for patients whose thoracic ducts were ligated, as well as those whose thoracic ducts were preserved. Thirty-nine patients who underwent radical resection of the esophageal cancer entered this trial. After stratifying into two groups--patients whose thoracic ducts were preserved [D(+)] and those whose thoracic ducts were ligated [D(-)], they were randomly divided into two groups--the patients who received early EN and those who received parenteral nutrition (PN) followed by delayed enteral feeding. Thus, the number of patients in the D(+)-EN group, D(+)-PN group, D(-)-EN group and D(-)-PN group were 13, 12, 7 and 7, respectively. The mortality and morbidity rates, and several blood chemistries were compared between the EN groups and the PN groups. Total lymphocyte count showed a significant early increase and serum c-reactive protein (CRP) was significantly decreased in the D(+)-EN group compared to the D(+)-PN group. However those differences were not observed between the D(-) groups. Serum total bilirubin was significantly decreased in the both EN groups compared to the PN groups. The mortality and morbidity rates were not different between the EN group and the PN group in the D(+) patients and also in the D(-) patients. Patients whose thoracic ducts were ligated did not obtain any other benefit from early enteral feeding except for bilirubin metabolism. Early enteral feeding is not recommended for patients whose thoracic ducts are ligated during radical resection of a cancer in the thoracic esophagus.


Effect of ethanolic extract of Khaya senegalensis on some biochemical parameters of rat kidney.
The effect of administration of ethanolic extract of Khaya senegalensis (2mg/kg body weight) on some biochemical parameters of rat kidney were investigated. Experimental animals were randomly divided into the control, those administered with the extract for 6 days and those administered with extract for 18 days, respectively. The prolonged administration of the extract resulted in significant reduction in the alkaline phosphatase activities of the kidney and its body weight ratio (P<0.05). In contrast, the same prolonged administration of the extract resulted in significant increase in the serum sodium ion concentration (P<0.05) while there was no significant difference in serum potassium ion concentration when compared to control (P>0.05). Administration of the extract for 6 days produced no significant difference from the control values in all the parameters investigated except in serum urea concentration which produced a significant increase (P<0.05). The available evidence in this study suggest that the ethanolic extract of Khaya senegalensis exerted more deleterious effect on the kidney when administered continuously over a prolonged period than a short one and this will adversely affect the functioning of the kidney.


Fungal genes related to calcium homeostasis and signalling are upregulated in symbiotic arbuscular mycorrhiza interactions.
Fluctuations in intracellular calcium levels generate signalling events and regulate different cellular processes. Whilst the implication of Ca(2+) in plant responses during arbuscular mycorrhiza (AM) interactions is well documented, nothing is known about the regulation or role of this secondary messenger in the fungal symbiont. The spatio-temporal expression pattern of putatively Ca(2+)-related genes of Glomus intraradices BEG141 encoding five proteins involved in membrane transport and one nuclear protein kinase, was investigated during the AM symbiosis. Expression profiles related to successful colonization of host roots were observed in interactions of G. intraradices with roots of wild-type Medicago truncatula (line J5) compared to the mycorrhiza-defective mutant dmi3/Mtsym13. Symbiotic fungal activity was monitored using stearoyl-CoA desaturase and phosphate transporter genes. Laser microdissection based-mapping of fungal gene expression in mycorrhizal root tissues indicated that the Ca(2+)-related genes were differentially upregulated in arbuscules and/or in intercellular hyphae. The spatio-temporal variations in gene expression suggest that the encoded proteins may have different functions in fungal development or function during symbiosis development. Full-length cDNA obtained for two genes with interesting expression profiles confirmed a close similarity with an endoplasmic reticulum P-type ATPase and a Vcx1-like vacuolar Ca(2+) ion transporter functionally characterized in other fungi and involved in the regulation of cell calcium pools. Possible mechanisms are discussed in which Ca(2+)-related proteins G. intraradices BEG141 may play a role in mobilization and perception of the intracellular messenger by the AM fungus during symbiotic interactions with host roots.


Clinical features and prognosis of pregnancy-related renal damage and pregnancy after chronic kidney disease.
To explore the clinical features of renal damage related to pregnancy and pregnancy after chronic kidney disease (CKD), providing clinical evidence for the relationship between renal damage and pregnancy. A retrospective analysis was performed on patients admitted to our hospital between March 2013 and February 2021 who had both pregnancy and kidney damage. The study collected pathology results from renal biopsies, 24-hour urinary protein quantity, albumin (Alb), serum creatinine (Scr), blood lipids, coagulation function, blood routine, and other indicators during and after pregnancy. This study included 82 cases, with 48 cases in the pregnancy-related renal damage group. Thirty-four cases were in the post-CKD pregnancy group. Of the patients, 30 cases (88.24%) had CKD stage 1-2. Results showed better pregnancy and fetal outcomes in the post-CKD pregnancy group compared to the pregnancy-related renal damage group (Ρ was 0.029 and 0.036, respectively). Renal biopsy pathology revealed that 16 cases (33.33%) in the pregnancy-related renal damage group mainly had focal segmental glomerulosclerosis (FSGS), while the post-CKD pregnancy group was dominated by 14 cases (43.75%) of IgA nephropathy. The first blood test indicators revealed that the pregnancy-related renal damage group had lower estimated glomerular filtration (eGFR) and Alb levels compared to the post-CKD pregnancy group (Ρ was 0.003 and 0.000, respectively). Additionally, 24-hour urinary protein quantity, total cholesterol (Tch), triglyceride (TG), and platelet (PLT) counts were higher in the pregnancy-related renal damage group compared to the post-CKD pregnancy group (Ρ was 0.005, 0.001, 0.008, and 0.031, respectively). The abnormal rate of Scr during pregnancy was 41.67% (20/48) in the pregnancy-related renal damage group and 17.39% (4/23) in the post-CKD pregnancy group, with a statistically significant difference (Ρ was 0.043). The pregnancy-related renal damage group is mainly associated with FSGS, while the post-CKD pregnancy group is characterized by IgA nephropathy. Patients with CKD1-2 can have a successful pregnancy after achieving good control of eGFR, albumin, 24-hour urinary protein quantity and other indicators, resulting in better pregnancy and fetal outcomes. Abnormal Scr levels during pregnancy of pregnancy-related renal damage can be improved within 3 months after delivery.


Synchronizing systolic calcium release with azumolene in an experimental model.
Post-defibrillation myocardial contractile dysfunction adversely affects the survival of patients after cardiac arrest. Attenuation of diastolic calcium (Ca2+) overload by stabilization of the cardiac ryanodine receptor (RyR2) is found to reduce refibrillation after long-duration ventricular fibrillation (LDVF). In the present study, we explored the effects of RyR2 stabilization by azumolene on systolic Ca2+ release synchrony and myocardial contractility. After completion of baseline optical mapping, Langendorff-perfused rabbit hearts were subjected to global ischemia followed by reperfusion with azumolene or deionized distilled water (vehicle). Following reperfusion, LDVF was induced with burst pacing. In the first series of experiments (n = 16), epicardial Ca2+ transient was analyzed for Ca2+ transient amplitude alternans and dispersion of Ca2+ transient amplitude alternans index (CAAI). In the second series of experiments following the same protocol (n = 12), ventricular contractility was assessed by measuring the left ventricular pressure. Ischemic LDVF led to greater CAAI (0.06 ± 0.02 at baseline vs 0.12 ± 0.02 post-LDVF, P < .01) and magnitude of dispersion of CAAI (0.04 ± 0.01 vs 0.09 ± 0.01, P < .01) in control hearts. In azumolene-treated hearts, no significant changes in CAAI (0.05 ± 0.01 vs 0.05 ± 0.01, P = .84) and dispersion of CAAI (0.04 ± 0.01 vs 0.04 ± 0.01, P = .99) were noted following ischemic LDVF. Ischemic LDVF was associated with reduction in left ventricular developed pressure (100% vs 36.8% ± 6.1%, P = .002) and dP/dtmax (100% vs 45.3% ± 6.5%, P = .003) in control hearts, but these reductions were mitigated (left ventricular developed pressure: 100% vs 74.0% ± 8.1%, P = .052, dP/dtmax: 100% vs 80.8% ± 7.9%, P = .09) in azumolene-treated hearts. Treatment with azumolene is associated with improvement of systolic Ca2+ release synchrony and myocardial contractility following ischemic LDVF.


Drug-associated kidney injury in children: a disproportionality analysis of the FDA Adverse Event Reporting System.
Drug-associated kidney injury is related to longer hospitalization and increased risk of chronic kidney disease and mortality. However, there is currently a lack of large population studies on drug-associated kidney injury in children. This study aimed to study perform data mining to generate hypotheses on drugs, which may deserve to be assessed as per their potential risk of increasing kidney injury in children. We extracted and analyzed reports on drugs associated with kidney injury in children in the FDA Adverse Event Reporting System (FAERS). We conducted a disproportionality analysis using proportional reporting ratio (PRR) to evaluate the association between drugs and kidney injury in children. Meanwhile, comparisons were performed with drug labels to identify drugs that, despite not having kidney injury currently mentioned in their labels, may potentially be associated with risks of kidney injury in children. A total of 6347 children had drug-associated kidney injury in the FAERS database. The top five drugs with the highest PRR were gentamicin (PRR = 12.28, N = 157 cases, Chi-Squared = 1602.77), piperacillin-tazobactam (PRR = 9.77, N = 129 cases, Chi-Squared = 1003.24), amlodipine (PRR = 8.98, N = 271 cases, Chi-Squared = 1861.46), vancomycin (PRR = 8.91, N = 295 cases, Chi-Squared = 1998.64), and ceftriaxone (PRR = 8.00, N = 251 cases, Chi-Squared = 1494.02). According to drug labels, 9 drugs (9/30) were classified as potential nephrotoxins. Approximately one-third of drugs associated with kidney injury in children do not list kidney injury as a side effect in their drug labels. Future studies are therefore warranted to evaluate whether these drugs are associated with such a risk. • Nephrotoxic drugs are an increasingly common cause of acute kidney injury in hospitalized children. • Currently, no study has systematically combed drugs associated with kidney injury in children. • Approximately a third of drugs showing signals for potential kidney injury in children in data mining do not mention this side effect in their drug labels. • This study provides data on drugs needing further study to determine whether they might increase the risk of kidney injury in children.


Expression of the SOFaRP2 gene in the central nervous system of the adult cuttlefish Sepia officinalis.
FMRFamide-related Peptides (FaRPs) are involved in a variety of physiological processes, including reproduction, feeding, development, body patterning and osmoregulation in vertebrates and invertebrates. Here we investigate the expression pattern of cuttlefish Sepia officinalis FaRP2 gene in the brain by in situ hybridization. The SOFaRP2 gene was found to be expressed most intensively in the posterior chromatophore lobe, vasomotor lobe and subvertical lobe. In addition, positive staining was also found in the fin lobe, brachial lobe, anterior chromatophore lobe, anterior, dorsal and lateral basal lobes, inferior and superior frontal lobes, and optic lobe. The expression pattern of SOFaRP2 suggests its involvement in chromatophore regulation, feeding behavior, and learning and memory.


Serological analyses of different mink Aleutian disease virus strains.
Four different isolates of Aleutian disease virus have been compared electrophoretically and serologically. These were the DK and Utah 1 isolates, known as highly virulent strains, the Pullman isolate, known as a low virulent strain and the avirulent ADV-G isolate, which is the only strain grown in cell culture. ADV-G was shown to migrate in agarose electrophoresis 22 per cent slower than the other strains. Several murine monoclonal antibodies were prepared against each of the isolates. Each one reacted with all 4 of the isolates, but a few showed higher affinity for some of the isolates. Competitive RIA analyses were also performed, and these studies indicated some serological differences between the 4 strains. It is concluded that ADV-G polypeptides are chemically different but immunologically cross-reacting with the polypeptides present on the field ADV strains. It is suggested that the small serological differences seen between the field strains might be caused by slightly different in vivo proteolytic degradation of the viral capsid proteins and thus might not be taken as an indication of strain variation.


Endotoxin-Stimulated Hepatic Stellate Cells Augment Acetaminophen-Induced Hepatocyte Injury.
Acetaminophen (APAP)-induced liver injury is influenced by inflammatory Gram-negative bacterial endotoxin [lipopolysaccharide (LPS)], mechanisms of which are not completely understood. Because LPS-stimulated perisinusoidal hepatic stellate cells (HSCs) produce cytokines that affect survival of hepatocytes, this study investigated their role in APAP-induced liver injury. Fed (nonstarved) rats were administered 5 mg/kg LPS or phosphate-buffered saline (PBS) vehicle, followed by 200 mg/kg APAP or PBS an hour later, and euthanized at 6 hours. Control rats received PBS at both time points. Both LPS and APAP caused mild hepatocyte injury (apoptosis), as assessed by histopathology, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, and caspase-3 activation. The liver injury was augmented in rats administered LPS + APAP, in association with increased nuclear translocation of interferon-regulatory factor-1 (IRF1). In vitro, APAP augmented LPS/HSC-conditioned medium-induced inhibition of DNA and protein synthesis, apoptosis, and nuclear IRF1 in hepatocytes. LPS-stimulated HSCs produced interferon-β (IFN-β), and LPS/HSC + APAP-induced hepatocyte apoptosis was inhibited by anti-IFN-β antibody. Finally, HSC-depleted mice produced significantly lower IFN-β and tumor necrosis factor-α, exhibited less oxidative stress, and were protected from excessive injury due to high APAP dose (600 mg/kg), as well as LPS (5 mg/kg overnight) followed by APAP. In co-culture with or without LPS, HSCs increased expression of proinflammatory cytokines by Kupffer cells. These results suggest that HSCs play a critical role in APAP-induced liver injury without or with LPS preconditioning, and it involves INF-β-IRF1 signaling.


Mannan-Binding Lectin via Interaction With Cell Surface Calreticulin Promotes Senescence of Activated Hepatic Stellate Cells to Limit Liver Fibrosis Progression.
Liver fibrosis represents a hallmark of most chronic liver diseases (CLD) triggered by recurrent liver injury and subsequent myofibroblast transdifferentiations of resident hepatic stellate cells (HSCs). Mannan-binding lectin (MBL) is potentially involved in hepatic fibrosis in CLD through unclear mechanisms. Therefore, we investigated the crosstalk between MBL and HSCs, and the consequent effects on fibrosis progression. Samples from patients with liver cirrhosis were collected. MBL deficiency (MBL-/-) and wild-type (WT) C57BL/6J mice were used to construct a CCl4-induced liver fibrosis model. Administration of MBL-expressing, liver-specific, adeno-associated virus was performed to restore hepatic MBL expression in MBL-/- mice. The human HSC line LX-2 was used for in vitro experiments. MBL levels in patients with liver cirrhosis were correlated with disease severity. In the CCl4-induced liver fibrosis model, MBL-/- mice showed severer liver fibrosis accompanied by reduced senescent activated HSCs in liver tissue compared with WT mice, which could be inhibited by administering MBL-expressing, liver-specific, adeno-associated virus. Moreover, depleting senescent cells with senolytic treatment could abrogate these differences owing to MBL absence. Furthermore, MBL could interact directly with calreticulin associated with low-density lipoprotein receptor-related protein 1 on the cell surface of HSCs, which further promotes senescence in HSCs by up-regulating the mammalian target of rapamycin/p53/p21 signaling pathway. MBL as a newfound senescence-promoting modulator and its crosstalk with HSCs in the liver microenvironment is essential for the control of hepatic fibrosis progression, suggesting its potential therapeutic use in treating CLD associated with liver fibrosis.


Results of PAL feasibility test in primary health care facilities in four regions of Bolivia.
Primary health care (PHC) centres in four Bolivian regions. To test the feasibility and impact of training general practitioners (GPs) in standard case management of respiratory conditions in patients aged > or =5 years. Comparison of the results of two surveys: the baseline survey before training and the impact survey after training on standard guidelines on case management of respiratory conditions. A total of 78 GPs working in 65 health centres participated in both surveys. The baseline survey registered 1033 respiratory patients and the impact survey 1154. The patients were comparable in sex distribution, previous visits, duration of symptoms and clinical diagnoses. The differences were significant in age distribution, concomitant diseases and risk factors. As a result of training, referrals to a higher level decreased by 34.6% and the proportion of tuberculosis (TB) suspects identified increased by 30%. The number of drugs prescribed per patient decreased by 16.2%. The average cost of prescription of any drug per patient dropped by 32.3%. Training in the standard practical approach to lung health guidelines improved the quality and reduced the cost of treatment of respiratory diseases at PHC units. Training should be an integral part of a comprehensive managerial approach for the implementation of case management guidelines.


Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients with Acute Myocardial Infarction (IMPRESSION): study protocol for a randomized controlled trial.
Ticagrelor is an oral platelet P2Y12 receptor antagonist which is recommended for patients suffering from myocardial infarction, both with and without persistent ST segment elevation. Morphine is the first choice drug in pain alleviation in the same clinical subset. Recently a possible negative influence of morphine on the pharmacokinetics and antiplatelet effects of P2Y12 receptor blockers has been postulated. The IMPRESSION study is a phase IV, single center, randomized, double-blind, placebo-controlled clinical trial that is designed to assess the influence of morphine on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with myocardial infarction. The study is planned to include up to 100 patients with myocardial infarction who will be randomized into one of two arms in a 1:1 ratio. Subjects in the intervention arm prior to the loading dose of ticagrelor (180 mg) will receive morphine (5 mg) intravenously, whereas patients in the control arm will receive a placebo prior to the loading dose of ticagrelor (180 mg). The pharmacokinetics of ticagrelor and its active metabolite (AR-C124910XX) will be assessed by liquid chromatography mass spectrometry. Platelet function testing in each patient will be performed using up to four different methods (platelet vasodilator-stimulated phosphoprotein assay, multiple electrode aggregometry, VerifyNow, and light transmission aggregometry). This study is expected to provide essential evidence-based data on the impact of morphine on the absorption of ticagrelor in patients with myocardial infarction as well as to shed some light on the suspected connection between morphine use and antiplatelet activity of ticagrelor in the same group of patients. ClinicalTrials.gov identifier: NCT02217878 (14 August 2014).


Hemodynamics of concomitant tricuspid valve procedures at LVAD implantation.
Tricuspid regurgitation (TR) is common in patients receiving left ventricular assist device (LVAD) implantation. The current literature is conflicting regarding the effects of concomitant tricuspid valve repair (TVR) at LVAD implantation. We investigated the hemodynamic effects of concomitant TVR at LVAD implantation. Consecutive clinically stable LVAD outpatients who underwent hemodynamic ramp testings were enrolled in this study, and they were stratified by concomitant TVR. Results of hemodynamic ramp tests were compared between the TVR group and the non-TVR group. Among 65 LVAD patients undergoing ramp tests, 34 patients had received TVR, and 31 had not. There were no significant differences in baseline characteristics between two groups except for higher degree of TR and lower pulmonary artery pulsatility index in the TVR group (P < .05 for both). Following LVAD implantation, the degree of TR improved significantly in the TVR group down to the comparable level with the non-TVR group. During ramp tests, the TVR group had steeper cardiac index slope (0.14 ± 0.12 vs 0.07 ± 0.07 L/min/m2 /step, P = .002) and higher cardiac index at set LVAD speed (2.99 ± 0.84 vs 2.52 ± 0.42 L/min/m2 , P = .007). Concomitant TVR improves cardiac output and its response to LVAD speed change following LVAD implantation. Longitudinal clinical implications of such hemodynamic changes are unknown.


Preparation of solid water-equivalent radioactive standards.
The use of a superabsorbent polymer to prepare water-equivalent volume standards by solidification without the need of irradiation to effect the polymerization process, is described. Less than 40 g of the polymer is needed to solidify 1 litre of solution. Monte Carlo simulations of the gamma-ray escape probability indicate that the mixture is water-equivalent to better than 1.0%. During preparation, the solidified material can be mixed until homogeneity is achieved. Comparative measurements made before and after solidification confirmed the homogeneity and demonstrated water equivalence.


Urine metabolomic characteristics of female patients with occupational chronic cadmium poisoning after 15 years of treatment.
Occupational chronic cadmium poisoning (OCCP) can cause irreversible organ damage. Currently, no effective treatment is available for OCCP, and effective and sensitive biomarkers for treatment evaluation are still lacking. In this study, metabolomics techniques were used to analyze changes in endogenous metabolites in the urine of patients with OCCP after 15 years of treatment. Thirty urine samples from female patients with OCCP and healthy female controls (n = 15 per group) were assessed using gas chromatography-time-of-flight mass spectrometry and ultra-high-performance liquid chromatography-Q-Exactive mass spectrometry. The OCCP group had higher concentrations of blood urea nitrogen and urinary cadmium but near-normal urinary concentrations of β2 -microglobulin and retinol-binding protein. Compared with the control group, the OCCP group had 66 significantly different metabolites with a variable importance in projection score >1 and p < 0.05. These differential metabolites were involved in various metabolic pathways, such as creatine metabolism, nicotinate and nicotinamide metabolism, the pentose phosphate pathway, d-glutamine and d-glutamate metabolism, and amino acid metabolism. Compared with the control group, the OCCP group had significantly higher urinary concentrations of creatine, glutamic acid, quinolinic acid and nicotinic acid. In a receiver operator characteristic analysis, the area under the curve of creatine was higher than those for glutamic acid, quinolinic acid and nicotinic acid, indicating that urinary concentrations of creatine could be used as a sensitive biomarker for the diagnosis and prognosis of OCCP and for monitoring its treatment.


Chronic unexplained diarrhea: a logical and cost-effective approach to assessment.
The workup of chronic unexplained diarrhea can be equally frustrating for care providers and patients. It carries a physical, financial, and social toll. In this review we provide a sensible approach to evaluating and managing chronic diarrhea. Bile acid diarrhea is becoming increasingly recognized as a potential cause behind some cases of chronic diarrhea. A detailed history and physical examination can provide clues that guide a logical approach to the evaluation. We suggest a cost-effective approach to the workup and management of chronic diarrhea based on individual patient factors related to clinical history and physical exam. We find that this approach leads to initiation of treatment in a time-efficient fashion and avoids unnecessary testing.


Non-medical treatment of first epileptic seizures in adolescence and adulthood.
Preliminary results are presented of a prospective study of patients who after a first seizure were treated by avoidance of seizure-precipitating factors. Thirty patients have been enrolled of whom 13 (43.3%) already had had a relapse before study onset. Twenty-three patients have been followed for 12 to 102 months, and of these a total of 7 relapses were observed. The recurrence rate in the first year of follow-up was 17.4%, much below the rate expected from the previously observed relapses. Mostly, the relapses were caused by the same precipitating factors as before. The risk of relapse was not influenced by drug treatment, electroencephalogram findings, focal signs, and positive antecedents, but there was a non-significant trend of previous relapses to increase this risk. The observed seizure recurrences with antiepileptic drug treatment indicate that, if drugs are prescribed, a careful choice of medication is necessary even after a single seizure, and low-dose therapy may not be sufficient. However, careful evaluation of individual factors precipitating the first seizure(s), and careful subsequent avoidance of these factors seems to be a more efficient therapeutic strategy than pharmacotherapy.


Sphingosine Kinase Activates the Mitochondrial Unfolded Protein Response and Is Targeted to Mitochondria by Stress.
The mitochondrial unfolded protein response (UPRmt) is critical for maintaining mitochondrial protein homeostasis in response to mitochondrial stress, but early steps in UPRmt activation are not well understood. Here, we report a function for SPHK-1 sphingosine kinase in activating the UPRmt in C. elegans. Genetic deficiency of sphk-1 in the intestine inhibits UPRmt activation, whereas selective SPHK-1 intestinal overexpression is sufficient to activate the UPRmt. Acute mitochondrial stress leads to rapid, reversible localization of SPHK-1::GFP fusion proteins with mitochondrial membranes before UPRmt activation. SPHK-1 variants lacking kinase activity or mitochondrial targeting fail to rescue the stress-induced UPRmt activation defects of sphk-1 mutants. Activation of the UPRmt by the nervous system requires sphk-1 and elicits SPHK-1 mitochondrial association in the intestine. We propose that stress-regulated mitochondrial recruitment of SPHK-1 and subsequent S1P production are critical early events for both cell autonomous and cell non-autonomous UPRmt activation.


[The effect of inhibitors of ADP ribosylation on the restoration of the mitotic cycle and on DNA repair after the action of ionizing radiation in Chinese hamster cells].
Specific inhibitors of poly(ADP-ribose)polymerase-3-aminobenzamide and 3-metoxybenzamide (6, 12 mM) have been shown to: 1) reduce survival of X-irradiated CHO K1 cells to a slight degree; 2) increase S- and particularly G2-delays in X-irradiated cells, while progressing through the cell cycle as analysed by the DNA flow cytofluorimetry; 3) reduce effectiveness of DNA single-strand breaks repair. The above data suggest a definite role of ADP ribosylation in the cell repair activity.


Taxonomic relationships of Ansonia anotis Inger, Tan, and Yambun, 2001 and Pedostibes maculatus (Mocquard, 1890), with a description of a new genus (Amphibia, Bufonidae).
Examination of types and recently collected specimens revealed that Ansonia anotis Inger, Tan, and Yambun, 2001 and Pedostibes maculatus (Mocquard, 1890), both described from Kinabalu, Sabah, Malaysia, are hardly differentiated morphologically. Analyses of a total of 2,427 bp of the 12S rRNA, tRNA(val), and 16S mitochondrial rRNA genes revealed that the two species are very close genetically. Thus A. anotis is regarded as conspecific and is synonymized with P. maculatus. Genetically, this species proved to form a lineage distinct from other bufonids from Southeast Asia, including species of Ansonia and Pedostibes. Because the species has also some unique morphological traits different from known bufonid genera, we propose to establish a new genus for Nectophryne maculata Mocquard, 1890.


The subunit structure of Pseudomonas cytochrome oxidase.
Pseudomonas cytochrome oxidase (EC 126.96.36.199) is composed of two subunits. Each subunit has a molecular weight of approx. 63000 and, according to the iron determination, contains two hemes. Cytochrome oxidase was subjected to various dissociation procedures to determine the stability of the dimeric structure. Progressive succinylation of 14 to 68% of the lysine residues of the enzyme increases the amount of the protein appearing in the subunit form (S20,W approximately 4 S) from 18 to 92%. At a high degree of succinylation a component with a sedimentation coefficient of approx. 2 S appears. The subunits with sedimentation coefficients of approx. 4 S and 2 S are also formed when the pH is below 4 or above 11. The same molecular weight (63000) was found for these two components in sodium dodecylsulphate electrophoresis. No dissociation of cytochrome oxidase was observed in salt solutions like 3 M NaC1 and 1 M Na2SO4, or in 6 M urea. The slight decrease in the sedimentation coefficients in NaC1 solutions is partly explained by preferential hydratation of the protein.


Diagnosis of Cetacean morbillivirus: A sensitive one step real time RT fast-PCR method based on SYBR(®) Green.
Cetacean morbillivirus (CeMV) (family Paramyxoviridae, genus Morbillivirus) is considered the most pathogenic virus of cetaceans. It was first implicated in the bottlenose dolphin (Tursiops truncatus) mass stranding episode along the Northwestern Atlantic coast in the late 1980s, and in several more recent worldwide epizootics in different Odontoceti species. This study describes a new one step real-time reverse transcription fast polymerase chain reaction (real-time RT-fast PCR) method based on SYBR(®) Green to detect a fragment of the CeMV fusion protein gene. This primer set also works for conventional RT-PCR diagnosis. This method detected and identified all three well-characterized strains of CeMV: porpoise morbillivirus (PMV), dolphin morbillivirus (DMV) and pilot whale morbillivirus (PWMV). Relative sensitivity was measured by comparing the results obtained from 10-fold dilution series of PMV and DMV positive controls and a PWMV field sample, to those obtained by the previously described conventional phosphoprotein gene based RT-PCR method. Both the conventional and real-time RT-PCR methods involving the fusion protein gene were 100- to 1000-fold more sensitive than the previously described conventional RT-PCR method.


Focus on primary care: from nevus to neoplasm: myths of melanoma in pregnancy.
Malignant melanoma is one of the few malignancies that regularly affect women during their childbearing years. Additionally, the incidence of melanoma has been increasing over the last several decades. Early diagnosis of stage I disease may lead to curative therapy; thus it is important for physicians and midwives to do a full examination of the skin. However, the myth that nevi may naturally grow or change during pregnancy has been shown not to be true and should not delay a diagnostic evaluation of a suspicious nevus. Older studies had theorized a worse outcome for pregnant women with melanoma. However, multiple controlled series and investigations have found that stage for stage this cancer is not affected adversely by pregnancy. Prognosis, recurrence, and incidence of melanoma seemed to be unaffected. Estrogen-containing oral contraceptives, as well as hormone replacement therapy, have no adverse affect on the disease.


Balancing "on" and "off" response of hydroxyl groups to a nanozyme-catalyzing system for the construction of an ultra-sensitive and selective "signal-on" detection platform for dopamine.
Targeting the functional groups present in analytes by nanozyme-catalyzed systems is a promising strategy to construct sensitive and selective platforms for the sensing of specific analytes. Herein, various groups (-COOH, -CHO, -OH, and -NH2) on benzene were introduced in an Fe-based nanozyme system with MoS2-MIL-101(Fe) as the model peroxidase nanozyme, H2O2 as the oxidizing agent, and TMB as the chromogenic substrate, and the effects of these groups at both a low concentration and high concentration were further investigated. It was found that the hydroxyl group-based substance catechol showed an "on" effect at a low concentration to increase the catalytic rate and enhance the absorbance signal, whereas an "off" effect at a high concentration with a decreased absorbance signal. Based on these results, the "on" mode and "off" mode for the biological molecule dopamine, a type of catechol derivative, were proposed. In the control system, MoS2-MIL-101(Fe) catalyzed the decomposition of H2O2 to produce ROS, which further oxidized TMB. In the "on" mode, the hydroxyl groups of dopamine could combine with the Fe(iii) site of the nanozyme to lower its oxidation state, resulting in higher catalytic activity. In the "off" mode, the excess dopamine could consume ROS, which inhibited the catalytic process. Under the optimal conditions, by balancing the "on" and "off" modes, the "on" mode for the detection of dopamine was found to have better sensitivity and selectivity. The LOD was as low as 0.5 nM. This detection platform was successfully applied for the detection of dopamine in human serum with satisfactory recovery. Our results can pave the way for the design of nanozyme sensing systems with sensitivity and selectivity.


An atlas of the blood virome in healthy individuals.
Emerging evidence indicates that gut virome plays a role in human health and disease, however, much less is known about the viral communities in blood. Here we conducted a direct metatranscriptomic sequencing of virus-like-particles in blood from 1200 healthy individuals, without prior amplification to avoid potential amplification bias and with a strictly bioinformatic and manual check for candidate viral reads to reduce false-positive matches. We identified 55 different viruses from 36 viral families, including 24 human DNA, RNA and retroviruses in 70% of the studied pools. The study showed that anelloviruses are widely distributed and dominate the blood virome in healthy individuals. Human herpesviruses and pegivirus-1 are commonly prevalent in asymptomatic humans. We identified the prevalence of RNA viruses often causing acute infection, like HEV, HPIV, RSV and HCoV-HKU1, revealing of a transmissible risk of asymptomatic infection. Several viruses possible related to transfusion safety were identified, including human Merkel cell polyomavirus, papillomavirus, parvovirus B19 and herpesvirus 8 in addition to HBV. In addition, phages in Caudovirales and Microviridae, were commonly found in pools of samples with a very low abundance; a few sequences for invertebrate, plant and giant viruses were found in some of individuals; however, the remaining 31 viruses mostly reflect extensive contamination from commercial reagents and the work environments. In conclusion, this study is the first comprehensive investigation of blood virome in healthy individuals by metatranscriptomic sequencing of VLP in China. Further investigation of potential false positives representing a major challenge for the identification of novel viruses in mNGS, will offer a systemic idea and means to reveal true viral infections of human.