Cellular autophagocytosis induced by deprivation of serum and amino acids in HeLa cells.
Morphologic alterations in HeLa cells deprived of serum and amino acids were studied by light and electron microscopy. After complete deprivation for 1, 3, or 6 hours, many cells contained autophagic vacuoles enclosing clearly recognizable cell organelles. The proportion of cells showing autophagy rose from 4 to 37% in the first 3 hours of deprivation. Acid phosphatase reaction product was localized within many of the autophagic vacuoles by a modified Gomori method. After 12 to 24 hours of deprivation, many membranous residual bodies were noted within the starved HeLa cells. These electron microscopic studies indicate that complete deprivation of serum and amino acids provides a useful model for the further study of cellular autophagocytosis.


Women's relative earnings and depressive symptoms in dual-earner households in South Korea: Traditional gender role attitudes as moderators.
This study investigated the association between relative earnings and depressive symptoms among 578 married women from dual-earning households. We also examined the moderating role of both spouses' traditional gender role attitudes. Women's relative earnings in their households did not directly predict their depressive symptoms. However, there was a significant three-way interaction effect of women's relative earnings and both spouses' traditional gender role attitudes on women's depressive symptoms. Particularly, women with considerably stronger-than-average traditional gender role attitudes reported more depressive symptoms when their relative earnings were greater and when their husbands showed strong traditional gender role attitudes. However, women holding even slightly weaker-than-average traditional gender role attitudes reported significantly fewer depressive symptoms as their relative earnings increased, even when their husbands showed strong traditional gender role attitudes. These results indicate that traditional wives with high relative earnings may feel threatened by the discrepancy between their values (traditional gender role attitudes) and behaviors (high relative earnings), especially when their husbands hold strong traditional gender role attitudes.


Psychiatric findings related to neurological complications in Behcet's disease: A short review and a case presentation.
Behcet's disease affects the skin, mucosa, joints, vascular system, eyes, the central nervous system (CNS) and gastrointestinal system. In Behcet's disease, the obvious illness mechanism in all organ systems is occlusive vasculitis of unknown etiology. CNS involvement in Behcet's disease sometimes causes psychiatric disorders. In this paper we discuss a case with neurobehcet disease who was admitted with psychotic symptoms. This 29-year-old male patient had symptoms of Behcet's disease and concomitant psychiatric symptoms. An advanced evaluation of the CNS was performed following unresponsiveness to antipsychotic treatment. It was concluded that the psychotic picture was a result of CNS involvement related to Behcet's disease. Colchicine was added to the treatment and upon discharge the case was in remission. Differences in treatment and prognosis between psychiatric disorder due to Behcet's disease and psychiatric disorders comorbid to Behcet's disease are discussed.


Optimal production of 7,10-dihydroxy-8(E)-hexadecenoic acid from palmitoleic acid by Pseudomonas aeruginosa PR3.
The hydroxylation of unsaturated fatty acids by bacterial strains is one type of value-adding bioconversion processes. This process generates new hydroxy fatty acids (HFA) carrying special properties such as higher viscosity and reactivity compared with normal fatty acids. Among microbial strains tested for HFA production, Pseudomonas aeruginosa PR3 is well known to utilize various unsaturated fatty acids to produce mono-, di- and tri-hydroxy fatty acids. Previously we reported that strain PR3 could produce a novel value-added hydroxy fatty acid 7,10-dihydroxy-8(E)-hexadecenoic acid (DHD) from palmitoleic acid (Bae et al. (2007) Appl. Microbiol. Biotechnol. 75, 435-440). In this study, we focused on the development of the optimal nutritional and environmental conditions for DHD production from palmitoleic acid by PR3. Optimal carbon and nitrogen sources for DHD production were fructose and yeast extract, respectively. Optimal initial medium pH and incubation temperature were pH 8.0 and 30 degrees C and magnesium ion was essentially required for DHD production. Substrate concentration and time of substrate addition were also optimized. Under optimized conditions, maximal DHD production was 1600mg/l representing 26.7% conversion yield.


Population-based food consumption survey as an additional tool for foodborne outbreak investigations, Germany, 2017.
We conducted a food consumption survey in the general adult population of 18 years and older in Germany to obtain data on the frequency of consumption of food items that caused foodborne disease outbreaks in the past. A total of 1010 telephone interviews were completed that queried the consumption of 95 food items in the 7-day period before the interview. Survey results were weighted to be representative. Six exemplary 'high risk' food items were consumed by 6% to 16% of the general population. These were raw ground pork: 6.5%; 'Teewurst' (=spreadable sausage-containing raw pork): 15.7%; unpasteurised milk consumed without prior heating: 9.0%; food items prepared with raw eggs: 9.8%; unheated sprouts or seedlings: 8.8% and frozen berries consumed without prior heating: 6.2%. Data from our food consumption survey were comparable to data obtained from control persons in case-control studies conducted during past foodborne disease outbreak investigations. We consider our survey an additional helpful tool that will allow comparison with food consumption data from case-patients obtained in exploratory, hypothesis-generating interviews early on in outbreak investigations, and which may assist in forming hypotheses regarding associations of illnesses with suspected food vehicles. This may facilitate and accelerate investigations of future foodborne disease outbreaks.


Measurements of immature platelets with haematology analysers are of limited value to separate immune thrombocytopenia from bone marrow failure.
Detection of immature platelets in the circulation may help to dissect thrombocytopenia due to platelet destruction from bone marrow failure (BMF). We prospectively tested the predictive value of immature platelets, measured as immature platelet fraction (IPF) on the XE-5000 (Sysmex, Kobe, Japan) or percentage of reticulated platelets (rPT) on the CD Sapphire (Abbott Diagnostics, Santa Clara, CA, USA) to separate immune thrombocytopenia (ITP) from BMF (leukaemia, myelodysplastic syndrome, aplastic anaemia). We analysed 58 samples of patients with BMF, 47 samples of patients with ITP and 97 controls. Median rPT (CD Sapphire) was increased to 9·0% in ITP and to 10·9% in BMF, compared to 1·9% in controls. Median IPF (XE-5000) was 16·2% in ITP, 10·2% in BMF and 2·5% in controls. We found an inverse correlation between high fractions of immature platelets and low platelet counts in thrombocytopenic samples regardless of the diagnosis. In conclusion, we observed a broad overlap of immature platelets between ITP and BMF, which may be caused by an accelerated release of immature platelets in any thrombocytopenic state and decreased production in many patients with ITP. Despite this, IPF (XE-5000) had some power to discriminate ITP from BMF, whereas rPT (CD Sapphire) was of no predictive value.


Application of a sensitive collection heuristic for very large protein families: evolutionary relationship between adipose triglyceride lipase (ATGL) and classic mammalian lipases.
Manually finding subtle yet statistically significant links to distantly related homologues becomes practically impossible for very populated protein families due to the sheer number of similarity searches to be invoked and analyzed. The unclear evolutionary relationship between classical mammalian lipases and the recently discovered human adipose triglyceride lipase (ATGL; a patatin family member) is an exemplary case for such a problem. We describe an unsupervised, sensitive sequence segment collection heuristic suitable for assembling very large protein families. It is based on fan-like expanding, iterative database searches. To prevent inclusion of unrelated hits, additional criteria are introduced: minimal alignment length and overlap with starting sequence segments, finding starting sequences in reciprocal searches, automated filtering for compositional bias and repetitive patterns. This heuristic was implemented as FAMILYSEARCHER in the ANNIE sequence analysis environment and applied to search for protein links between the classical lipase family and the patatin-like group. The FAMILYSEARCHER is an efficient tool for tracing distant evolutionary relationships involving large protein families. Although classical lipases and ATGL have no obvious sequence similarity and differ with regard to fold and catalytic mechanism, homology links detected with FAMILYSEARCHER show that they are evolutionarily related. The conserved sequence parts can be narrowed down to an ancestral core module consisting of three beta-strands, one alpha-helix and a turn containing the typical nucleophilic serine. Moreover, this ancestral module also appears in numerous enzymes with various substrate specificities, but that critically rely on nucleophilic attack mechanisms.


[Utility of urease rapid test for detection of Helicobacter pylori in patients with upper gastrointestinal bleeding from peptic ulcer].
Peptic ulcer disease is the main cause of upper gastrointestinal bleeding and Helicobacter pylori is its principal etiology. The sensitivity of the diagnostics tests is low for the detection of H. pylori en the setting of bleeding peptic ulcer. In addition there are different results among them. To validate the rapid urease test (RUT) in patients with bleeding peptic ulcer. We prospectively included patients older than 14 years old who presented with bleeding peptic ulcer and performed diagnostic studies of RUT and histology for the detection of H. pylori. Two biopsies were taken (one from the antrum and another one from the corpus) for RUT and four biopsies (two from both antrum and corpus) for histology. RESULTS Ninety-three patients were included, gastric ulcer was the most frequent site of the bleeding. 48 patients were positive for H. pylori by histology studies and 55 patients were positive to H. pylori by RUT. The sensitivity and specificity of the RUT were 89.6% (IC 77.3-96.5) y 73.3% (IC 58.0-85.4) respectively. The RUT has a high sensitivity for the detection of H. pylori en the setting of bleeding peptic ulcer.


Sex, puberty, and the timing of sleep EEG measured adolescent brain maturation.
The steep adolescent decline in the slow wave (delta, 1-4 Hz) electroencephalogram (EEG) of nonrapid eye movement (NREM) sleep is a dramatic maturational change in brain electrophysiology thought to be driven by cortical synaptic pruning. A perennial question is whether this change in brain electrophysiology is related to sexual maturation. Applying Gompertz growth models to longitudinal data spanning ages 9-18 y, we found that the timing of the delta decline was significantly (P < 0.0001) linked to timing of pubertal maturation. This timing relation remained significant when sex differences in the timing of the delta decline were statistically controlled. Sex differences and the relation to the timing of puberty jointly explained 67% of the between-subject variance in the timing of the delta decline. These data provide a demonstration of a temporal relation between puberty and an electrophysiological marker of adolescent brain development. They can guide research into whether the neuroendocrine events of puberty are mechanistically linked to cortical maturation or whether, instead, the two maturational processes are parallel but independent programs of human ontogenesis.


Identification of a retroelement from the resurrection plant Boea hygrometrica that confers osmotic and alkaline tolerance in Arabidopsis thaliana.
Functional genomic elements, including transposable elements, small RNAs and non-coding RNAs, are involved in regulation of gene expression in response to plant stress. To identify genomic elements that regulate dehydration and alkaline tolerance in Boea hygrometrica, a resurrection plant that inhabits drought and alkaline Karst areas, a genomic DNA library from B. hygrometrica was constructed and subsequently transformed into Arabidopsis using binary bacterial artificial chromosome (BIBAC) vectors. Transgenic lines were screened under osmotic and alkaline conditions, leading to the identification of Clone L1-4 that conferred osmotic and alkaline tolerance. Sequence analyses revealed that L1-4 contained a 49-kb retroelement fragment from B. hygrometrica, of which only a truncated sequence was present in L1-4 transgenic Arabidopsis plants. Additional subcloning revealed that activity resided in a 2-kb sequence, designated Osmotic and Alkaline Resistance 1 (OAR1). In addition, transgenic Arabidopsis lines carrying an OAR1-homologue also showed similar stress tolerance phenotypes. Physiological and molecular analyses demonstrated that OAR1-transgenic plants exhibited improved photochemical efficiency and membrane integrity and biomarker gene expression under both osmotic and alkaline stresses. Short transcripts that originated from OAR1 were increased under stress conditions in both B. hygrometrica and Arabidopsis carrying OAR1. The relative copy number of OAR1 was stable in transgenic Arabidopsis under stress but increased in B. hygrometrica. Taken together, our results indicated a potential role of OAR1 element in plant tolerance to osmotic and alkaline stresses, and verified the feasibility of the BIBAC transformation technique to identify functional genomic elements from physiological model species.


[Spice in France: mixed herbs containing synthetic cannabinoids].
Smokable herbal mixtures under the brand name Spice were first sold on the Internet and in various specialised shops in 2006 or earlier. When smoked, the Spice products have effects similar to those of cannabis. Forensic investigations were undertaken by German and Austrian authorities in order to identify the psychoactive ingredients of Spice. A new psychoactive substance JWH-018 has been identified in Spice products. JWH-018 was first synthesized in 1995 and produces effects similar to those THC. Subsequently, the synthetic cannabinoid CP 47,497 was also identified. Outside of Europe, the United States Drug Enforcement Administration reported that another potent synthetic cannabinoid, HU-210, had been found. Since 2009, other synthetic cannabinoids were identified in Europe. None of the above-mentioned synthetic cannabinoids is internationally controlled as a drug and there is no information on any of them having been authorised as a medicinal product in the European Union. There are no officially published safety data and little is known about their effects in humans. Some of the characteristics of these compounds, e.g. volatility and activity in small doses, are likely to present further analytical and toxicological challenges. Responding to potential health concerns, Europe has taken legal actions to ban or otherwise control Spice products and related compounds.


Identification and Modification of Porphyromonas gingivalis Cysteine Protease, Gingipain, Ideal for Screening Periodontitis.
Chronic periodontitis is an inflammatory disease caused by the formation of oral microbial biofilms. Periodontitis is associated with general health and not only oral diseases. Porphyromonas gingivalis is a well-known keystone pathogen for periodontitis and is associated with several systemic diseases, such as diabetes mellitus and Alzheimer's disease. We previously developed a system for screening periodontitis using P. gingivalis-specific serum immunoglobulin G (IgG) in an enzyme-linked immunosorbent assay with a sensitivity of 0.774 and a specificity of 0.586 and an area under the receiver operating characteristic curve of 0.708. However, the antigens elicited non-specific responses, since they were obtained from whole extracts of sonicated cultured bacteria. The purpose of this study was to identify antigens ideal for a sensitive and specific serum test. We identified the specific antigens using immunoaffinity columns immobilized with IgG antibodies from periodontitis patients. Liquid chromatography-tandem mass spectrometry identified 29 antigens from the elutes. Recombinant proteins for these candidates were synthesized using the wheat germ cell-free translation system and screened by dot blot analysis with serum from the columns. Three of the 16 candidates that reacted showed strongest affinities upon dot blot analysis; they included outer membrane protein 28, cysteine proteases, lysine gingipain Kgp, and arginine gingipain RgpA. Outer membrane protein 28 was not suitable for screening P. gingivalis infection because of its high false-negative rates. Kgp and RgpA were unstable antigens since they underwent self-digestion. They were made stable by substituting the active cysteine residues in Kgp and RgpA with alanine using site-directed mutagenesis. Using the modified antigens, we demonstrated that the patient serum IgG level against RgpA was the highest among all the antigens expressed in P. gingivalis. Moreover, the N-terminus of recombinant RgpA was excellent in differentiating between diseased and non-diseased states (with sensitivity of 0.85, specificity of 0.9, and area under the curve of 0.915). Although dot blot analysis was the only experiment used, the N-terminus of RgpA is an excellent antigen to immunologically test for P. gingivalis infection, especially for estimating the risks for periodontitis-associated systemic diseases. In conclusion, we have developed a P. gingivalis antigen for screening periodontitis.


Anaemia of acute malaria infections in non-immune patients primarily results from destruction of uninfected erythrocytes.
While anaemia has long been recognized as a consequence of acute infections with malaria, the relative contributions of direct erythrocyte destruction by parasites, destruction of uninfected erythrocytes and changes in erythropoiesis have been unclear. Fitting of parasitaemia and anaemia data from neurosyphilis patients undergoing malaria therapy to a mathematical model shows that in these patients, an average of 8.5 erythrocytes were destroyed in addition to each erythrocyte observed to become parasitized. The model also showed that dyserythropoiesis plays an insignificant role in the resulting anaemia. The anaemia occurs before a substantial antibody response to parasites or erythrocytes could be generated. We postulate that uninfected erythrocyte destruction occurs through phagocytosis of erythrocytes bound to merozoites killed as a result of the accompanying malaria paroxysms.


Effects of long-term consumer manipulations on invasion in oak savanna communities.
Consumer-plant interactions can alter the outcome of biological invasions when native and exotic plants differ systematically in their resistance to and/or tolerance of consumer impacts. Given evidence for indirect interactions and shifts in plant communities from the few existing long-term studies, it is clear that long-term studies are a critical component for understanding the role of consumers in plant invasions. Moreover, studies of the role of consumers in mediating invasions have focused on the effects of exotic consumers, while the effects of native consumers on invasion have received little attention. Here we examine the long-term impact of a largely native vertebrate consumer community on native and exotic understory plants and recruitment of native oaks in a California oak savanna. We sampled plant community composition, oak recruitment, and soils inside and outside of 10 exclosures (mean area = 1000 m2) that had been in place for an average of 32 years. Plots with consumers present had 41% more exotic species, 31% higher cover of exotic species, and 33% lower richness of native herbaceous perennials, suggesting that native consumers may play an important role in mediating invasion in this system. The presence of oak canopies had a strong impact on the plant community independent of consumer effects, with greater recruitment of oaks, higher cover of native shrubs, and lower cover of exotic species cover under oak canopies. The concordant variation of native tree canopy and native woody plants suggests that adult oaks provide a refuge for their seedlings and other native woody plants. Thus, the widespread loss of native oaks has likely increased exotic invasion into an important refuge for native species in the California oak savanna ecosystem.


Dyspoietic changes associated with hepatosplenic T-cell lymphoma are not a manifestation of a myelodysplastic syndrome: analysis of 25 patients.
Hepatosplenic T-cell lymphoma (HSTCL) is a rare T-cell lymphoma commonly associated with cytopenias. The pathogenesis of cytopenias in patients with HSTCL is not well defined, although the presence of dyspoietic hematopoietic cells and the common association with trisomy 8 raise the possibility of an associated myelodysplastic syndrome (MDS). In 25 bone marrow specimens involved by HSTCL, we systematically assessed for morphologic features of dyspoiesis and correlated the findings with peripheral cytopenia(s), cytogenetic findings, and detection of chromosome 8 by fluorescence in situ hybridization. The median patient age was 33 years. One patient had a history of MDS diagnosed 1 year prior to the diagnosis of HSTCL. Thirteen (54%) patients had anemia less than 100 g/L, 10 (53%) of 19 had neutropenia less than 1.8 × 10(9)/L, and 15 (60%) had thrombocytopenia less than 100 × 10(9)/L. Dyspoietic features were identified in 1 to 3 hematopoietic cell lineages in 20 (80%) of 25 patients. Cytogenetic analysis identified trisomy 8 in 7 cases. Patients with trisomy 8 had a lower platelet count, but trisomy 8 was not associated with cytopenias, dyspoietic features, or cytogenetic abnormalities. Combined morphologic and fluorescence in situ hybridization analysis showed that trisomy 8 was restricted to the lymphoma cells, except in the 1 patient with a history of MDS. In conclusion, dyspoietic changes are common in the bone marrow of patients with HSTCL. These changes are not associated with cytopenias or chromosomal abnormalities, suggesting that dyspoiesis in patients with HSTCL is not a manifestation of a MDS.


High archaeal diversity in Antarctic circumpolar deep waters.
Archaea are abundant in polar oceans but important ecological aspects of this group remain enigmatic, such as patterns of diversity and biogeography. Here, we provide the first high-throughput sequencing population study of Antarctic archaea based on 198 bp fragments of the 16S rRNA gene, targeting different water masses across the Amundsen and Ross Seas. Our results suggest that archaeal community composition is strongly shaped by hydrography and significantly influenced by environmental parameters. Archaeal communities from cold continental shelf waters (SW) of the Ross Sea were similar over depth with a single thaumarchaeal phylotype dominating Antarctic surface waters (AASW) and deeper SW (contributing up to 80% of reads). However, this phylotype contributed less than 8% of reads in circumpolar deep waters (CDW). A related thaumarchaeon (98% identity) was almost absent in AASW, but contributed up to 30% of reads in CDW, suggesting ecological differentiation of closely related phylotypes. Significantly higher archaeal richness and evenness were observed in CDW, with Shannon indices (c. 2.5) twice as high as for AASW, and high contributions of Group II Euryarchaeota. Based on these results, we suggest that CDW is a hotspot of archaeal diversity and may play an important role in the dispersal of archaeal phylotypes to other oceanic water masses.


Spatially adaptive subsampling of image sequences.
In a spatially adaptive subsampling scheme, the subsampling lattice is adapted to the local spatial frequency content of an image sequence. In this paper, we use rate-distortion theory to show that spatially adaptive subsampling gives a better performance than subsampling with a fixed sampling lattice. A new algorithm that optimally assigns sampling lattices to different parts of the image is presented. The proposed spatially adaptive subsampling method can be applied within a motion-compensated coding scheme as well. Experiments show an increased performance over fixed lattice subsampling.


NGF rescues substance P expression but not neurofilament or tubulin gene expression in axotomized sensory neurons.
A reduction in the supply of retrogradely transported NGF has been proposed as a possible signal for the axotomy response in dorsal root ganglion (DRG) neurons. Components of the axotomy response that have previously been well characterized in axotomized DRG cells include changes in cytoskeletal gene expression and changes in the expression of neurotransmitters/neuromodulators such as substance P. In this study, we examined the role of NGF in the axotomy response by examining protein synthesis and mRNA levels of the low-MW neurofilament protein (NF-L) and beta-tubulin in DRG cells at 1, 7, and 12 d after axotomy with and without continuous administration of exogenous NGF. We also examined substance P levels in the DRG by immunocytochemistry under the same experimental conditions. Sciatic nerves of adult male rats were unilaterally transected at the midthigh level, and the proximal nerve stumps were placed into Silastic tubes connected to osmotic minipumps that were filled with biologically active NGF. NGF (0.5 mg/ml in saline) was continuously infused (0.5 microliter/hr) onto the proximal stumps of transected sciatic nerves for 1-12 d. Control animals were prepared in an identical fashion except that the nerves were treated with saline alone. At death, DRGs were removed from the animals; the L4 experimental DRGs (axotomized) and contralateral L4 DRGs (uninjured) were used immediately for protein synthesis experiments, while the experimental and contralateral L5 DRGs were fixed in 4% paraformaldehyde and subsequently used for in situ hybridization and immunocytochemistry. From another set of experimental animals, the L4 and L5 DRGs were harvested and used for total RNA isolation and RNA blotting experiments. Immunocytochemical studies using a polyclonal antibody to substance P showed that the immunodetectable levels of this peptide decreased to undetectable levels in DRG neurons after axotomy and saline administration. However, in axotomized neurons treated with NGF, the level of immunodetectable substance P did not decrease, but instead, increased over even that present in normal DRG neurons. Pulse labeling of DRGs with 35S-methionine:cysteine followed by 2-dimensional (2D) gel electrophoresis and fluorography revealed that the synthesis of neurofilament (NF) proteins was decreased, while that of tubulin was increased, 12 d after sciatic nerve transection. NGF administration to axotomized neurons did not alter this pattern. Quantitative analysis of in situ hybridizations of DRG neurons and RNA blot analysis with cDNA probes specific for NF-L and beta-tubulin mRNAs showed that NGF treatment of axotomized DRGs did not significantly affect cytoskeletal gene expression at the mRNA level.(ABSTRACT TRUNCATED AT 400 WORDS)


Predictors of race time in male Ironman triathletes: physical characteristics, training, or prerace experience?
The aim of the present study was to assess whether physical characteristics, training, or prerace experience were related to performance in recreational male Ironman triathletes using bi- and multivariate analysis. 83 male recreational triathletes who volunteered to participate in the study (M age 41.5 yr., SD = 8.9) had a mean body height of 1.80 m (SD = 0.06), mean body mass of 77.3 kg (SD = 8.9), and mean Body Mass Index of 23.7 kg/m2 (SD = 2.1) at the 2009 IRONMAN SWITZERLAND competition. Speed in running during training, personal best marathon time, and personal best time in an Olympic distance triathlon were related to the Ironman race time. These three variables explained 64% of the variance in Ironman race time. Personal best marathon time was significantly and positively related to the run split time in the Ironman race. Faster running while training and both a fast personal best time in a marathon and in an Olympic distance triathlon were associated with a fast Ironman race time.


Predictive Antibiotic Susceptibility Testing by Next-Generation Sequencing for Periprosthetic Joint Infections: Potential and Limitations.
Joint replacement surgeries are one of the most frequent medical interventions globally. Infections of prosthetic joints are a major health challenge and typically require prolonged or even indefinite antibiotic treatment. As multidrug-resistant pathogens continue to rise globally, novel diagnostics are critical to ensure appropriate treatment and help with prosthetic joint infections (PJI) management. To this end, recent studies have shown the potential of molecular methods such as next-generation sequencing to complement established phenotypic, culture-based methods. Together with advanced bioinformatics approaches, next-generation sequencing can provide comprehensive information on pathogen identity as well as antimicrobial susceptibility, potentially enabling rapid diagnosis and targeted therapy of PJIs. In this review, we summarize current developments in next generation sequencing based predictive antibiotic susceptibility testing and discuss potential and limitations for common PJI pathogens.


Lonicera caerulea Berry Polyphenols Activate SIRT1, Enhancing Inhibition of Raw264.7 Macrophage Foam Cell Formation and Promoting Cholesterol Efflux.
Lonicera caerulea berry polyphenols (LCBP) are known to reduce cholesterol accumulation. Currently, it is unknown whether LCBP can activate Sirtuin 1 (SIRT1) to regulate the formation of RAW264.7 macrophage foam cells. In this study, the effect of LCBP on lipid accumulation in macrophages was evaluated. Fluorescently labeled ox-LDL and 25-NBD cholesterol were used to detect the ox-LDL uptake and cholesterol outflow rate from macrophages. Gene silencing was performed using siRNA to detect changes in the expression of the ATP-binding cassette transporter A1 (ABCA1), sterol regulatory element-binding protein 2 (SREBP2), and SIRT1 proteins using Western blotting, and changes in the expression of miR-33 were detected by real-time polymerase chain reaction. The results showed that treatment with 80 μg/mL LCBP significantly inhibited the accumulation of lipids in RAW264.7 macrophages induced by ox-LDL and reduced intracellular cholesterol levels by activating SIRT1 to enhance the expression of ABCA1, a cholesterol efflux gene, but not independent effect. Of the three key LCBP components investigated, chlorogenic acid was found to activate SIRT1 and regulate the expression of the cholesterol-related factors ABCA1, SREBP2, and miR-33; cyanidin-3-glucoside and catechins were effective to a lesser extent. Our results suggest a novel hypolipidemic mechanism of LCBP.


[The beneficial effects of iron supplementation other than improvement of anemia].
Previous randomized controlled trials (RCTs) have shown beneficial effects of iron supplementation other than anemia improvement including treatment of restless leg syndrome and general fatigue, even in non-anemic subjects with iron deficiency. Recently, some RCTs in congestive heart failure (CHF) demonstrated that intravenous administration of ferric carboxymaltose improves patient symptoms and reduces incidence of hospitalization for worsening heart failure. Consequently, the European Society of Cardiology recommends that iron deficient patients with CHF are administered ferric carboxymaltose (evidence level A). Moreover, the PIVOTAL study for hemodialysis patients proved that proactive administration of iron sucrose decreases the dose of erythropoiesis-stimulating agents and frequency of transfusion compared with its sole administration in reaction to iron deficiency. Notably, this proactive treatment is superior to a low-dose regimen in preventing the primary composite endpoints of nonfatal myocardial infarction, stroke, hospitalization for CHF, and death. These clinical findings are supported by basic research on cardiomyocyte-specific transferrin receptor knock-out mice showing heart failure with impaired mitochondrial respiratory function. In this model, cardiac iron deficiency impairs the mitochondrial electron transport chain, thus leading to low adenosine triphosphate production, and it subsequently prevents mitophagy resulting in damaged mitochondrial accumulation in the heart.


[Novel CD19-KIRS2/Dap12-BB CAR-T Treatment for 3 Patients with Relapsed and Refractory B-Cell Tumors].
To investigate the safety and efficacy of novel CD19-KIRS2/Dap12-BB chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory B-cell malignancy (R/R BCM). Three patients with R/R BCM treated with novel CD19-KIRS2/Dap12-BB CAR-T cells from June 2020 to November 2020 were enrolled, including 1 case of B-cell acute lymphoblastic leukaemia (B-ALL) and 2 cases of non-Hodgkin's lymphoma (NHL), and the efficacy and adverse reactions were observed. After CAR-T cells infusion, patient with B-ALL achieved complete remission (CR) and minimal residual disease (MRD) turned negative, and 2 patients with NHL achieved partial remission (PR). Grade 2 cytokine release syndrome (CRS) occurred in B-ALL patient, grade 1 CRS occurred in 2 NHL patients, and grade II to IV hematologic adverse reactions occurred in 3 patients, all of which were controllable and reversible. The progression-free survival (PFS) of the 3 patients was 143, 199, and 91 days, and overall survival (OS) was 282, 430, and 338 days, respectively. The novel CD19-KIRS2/Dap12-BB CAR-T cells in treatment of 3 patients with R/R BCM have significant short-term efficacy and controllable adverse reactions, but the long-term efficacy needs to be further improved.


Probing functional sites on complement protein B with monoclonal antibodies. Evidence for C3b-binding sites on Ba.
We used four mouse monoclonal antibodies (Mab) as probes of functional sites of human complement protein B. Two Mab, HA4-1B (gamma 2a kappa) and HA4-15 (gamma 2a kappa), reacted with the same or adjacent epitopes on the Bb fragment of B, while the other two, HA4-1A (gamma 1 kappa) and FD3-20 (gamma 1 kappa), reacted with distinct epitopes on Ba. All reactive epitopes were expressed on native B and only one, recognized by the anti-Ba Mab HA4-1A was more reactive on isolated Ba than on B. These binding specificities were determined by direct binding radioassays and confirmed by inhibition studies. Immunoelectron microscopy of B and Bb in complex with anti-Ba and anti-Bb revealed that the recognized epitopes are on opposite sides of the molecule and are on discrete domains. All four Mab inhibited the hemolytic activity of B, although with different efficiencies and through different mechanisms. The main effect of the two anti-Bb Mab was an increased rate of loss of hemolytic sites from preformed EC3bBb C3 convertase presumably through accelerated dissociation of Bb. On the other hand, the main effect of the two anti-Ba Mab was inhibition of binding of B to C3b. HA4-1A was more efficient, inhibiting by 50% the binding of [125I]B to EC3b at 10 micrograms/ml as IgG and at 13 micrograms/ml as Fab. The data suggest that a binding site for C3b on intact B is located on the Ba portion of the molecule.


Pharmacokinetic Profiles of Metamizole Metabolites after Intramuscular and Intravenous Administration in Healthy Arabian Horses.
Metamizole sodium (MT) is an analgesic and antipyretic drug molecule used in humans, horses, cattle, swine, and dogs. Metamizole rapidly hydrolyzes and turns into methylamino antipyrine (MAA), an active primary metabolite of MT. The present study aims to determine the pharmacokinetic (PK) profiles of MT metabolites after intravenous (IV) and intramuscular (IM) administration into sex of Arabian horses (Equus ferus caballus) using a cross-over study design. The plasma samples were extracted by solid-phase extraction (SPE) method, and plasma concentrations of MT metabolites were analyzed by high-performance liquid chromatography (HPLC). After administrations of MT, plasma concentrations of methylamino antipyrine (MAA), amino antipyrone (AA), and acetylamino antipyrone (AAA) were determined within range of 15 min-12 h. Plasma concentrations of AA and AAA were lower than the plasma concentrations of major metabolite MAA at each sampling point. The PK parameters were statistically evaluated for MT's metabolites between male and female horses and also between IM and IV administrations of PK parameters such as Cmax , tmax , t1/2λz , AUC0-t , AUC0-∞ , λz, Cl and Vss (p < .05). The AUCIM /AUCIV ratio in female and male horses for MAA was 1.19 and 1.13, respectively. The AUCIM /AUCIV ratio for AA was lower than those found for MAA. AUCIM /AUCIV ratio was statistically significantly different between male and female horses for AA (p < .05). According to these results, some PK parameters such as Cmax, AUC, and MRT, MAA and AA concentrations have shown statistically significant differences by MT administrations.


Current Challenges in Neonatal Resuscitation: What is the Role of Adrenaline?
Adrenaline, also known as epinephrine, is a hormone, neurotransmitter, and medication. It is the best established drug in neonatal resuscitation, but only weak evidence supports current recommendations for its use. Furthermore, the available evidence is partly based on extrapolations from adult studies, and this introduces further uncertainty, especially when considering the unique physiological characteristics of newly born infants. The timing, dose, and route of administration of adrenaline are still debated, even though this medication has been used in neonatal resuscitation for a long time. According to the most recent Neonatal Resuscitation Guidelines from the American Heart Association, adrenaline use is indicated when the heart rate remains < 60 beats per minute despite the establishment of adequate ventilation with 100% oxygen and chest compressions. The aforementioned guidelines recommend intravenous administration (via an umbilical venous catheter) of adrenaline at a dose of 0.01-0.03 mg/kg (1:10,000 concentration). Endotracheal administration of a higher dose (0.05-0.1 mg/kg) may be considered while venous access is being obtained, even if supportive data for endotracheal adrenaline are lacking. The safety and efficacy of intraosseous administration of adrenaline remain to be investigated. This article reviews the evidence on the circulatory effects and tolerability of adrenaline in the newborn, discusses literature data on adrenaline use in neonatal cardiopulmonary resuscitation, and describes international recommendations and outcome data regarding the use of this medication during neonatal resuscitation.


The reliability and validity of the Biering-Sorensen test in asymptomatic subjects and subjects reporting current or previous nonspecific low back pain.
A reliability study and case-control study were conducted. To determine the reliability and discriminative validity of the Biering-Sorensen test. A low Biering-Sorensen score has been found to predict who will have nonspecific low back pain. However, the reliability of the test remains controversial, implying that some studies may have produced results that underestimated the magnitude of the predictive validity of this test. Two raters measured the time holding a specific position (holding time) of 63 subjects (23 currently experiencing nonspecific low back pain, 20 who had had an episode, and 20 who were asymptomatic) while they performed the Biering-Sorensen test twice, 15 minutes apart. A standardized protocol was followed. Test-retest reliability was evaluated by calculating intra-class correlation coefficients (ICC 1,1), 95% confidence intervals (CI), and standard errors of the measurement (SEM) for the total group and for the subgroups. A three-way analysis of variance was used to determine whether test order, subject gender, or symptom status affected holding time. High reliability indices were obtained for the Biering-Sorensen test in subjects with current nonspecific low back pain (ICC [1,1], 0.88; 95% CI, 0.73-0.95; SEM, 11.6 seconds), in subjects who had had nonspecific low back pain (ICC [1,1], 0.77; 95% CI, 0.52-0.90; SEM, 17.5 seconds), and in asymptomatic subjects (ICC [1,1], 0.83; 95% CI, 0.62-0.93; SEM, 17.4 seconds). Results of an analysis of variance showed that subjects asymptomatic for low back pain had a significantly longer holding time than the other two groups (P < 0.05). The Biering-Sorensen test provides reliable measures of position-holding time and can discriminate between subjects with and without nonspecific low back pain.


[High-dose intravenous penicillin therapy in neurosyphilis: study of 62 cases. II. Evaluation of cerebrospinal fluid].
Sixty-two patients with symptomatic neurosyphilis were treated with 20 or 24 megaunits of intravenous penicillin G daily for 15 to 30 days. The mean follow-up time after the treatment was 30 months. Forty-one patients had pleocytosis in the CSF before treatment. Six months and twelve or more months later, abnormal cell count was observed in 4 (9.8%) and in 3 patients (7.3%), respectively. The CSF protein level and the titers of Wassermann reaction in the CSF decreased slowly after treatment. The gammaglobulin concentration of the CSF and the immunoglobulin production inside the blood-brain barrier were still increased beyond the first year after treatment. The results of the treatment of these patients with high doses of intravenous penicillin G were not different from the results verified with lesser doses of intramuscular penicillin that were reported in the literature.


Spanish study of anticoagulation in haemodialysis.
This study's objectives were to determine which anticoagulation methods are commonly used in patients who are undergoing haemodialysis (HD) in Spain, on what criteria do they depend, and the consequences arising from their use. Ours was a cross-sectional study based on two types of surveys: a "HD Centre Survey" and a "Patient Survey". The first survey was answered by 87 adult HD units serving a total of 6093 patients, as well as 2 paediatric units. Among these units, 48.3% were part of the public health system and the remaining 51.7% units were part of the private health system. The patient survey analysed 758 patients who were chosen at random from among the aforementioned 78 HD units. A) HD Centre Survey: The majority of adult HD units (n=61, 70.2%) used both kinds of heparin, 19 of them (21.8%) only used LMWH and 7 of them (8%) only used UFH. The most frequently applied criteria for the use of LMWH were medical indications (83.3% of HD units) and ease of administration (29.5%). The most frequently used methods for adjusting the dosage were clotting of the circuit (88.2% of units), bleeding of the vascular access after disconnection (75.3%), and patient weight (57.6%). B) Patient Survey: The distribution of the types of heparin used was: UFH: 44.1%, LMWH: 51.5%, and dialysis without heparin in 4.4% of patients. LMWH was more frequently used in public medical centres (64.2% of patients) than in private medical centres (46.1%) (P<.001). LMWH was more frequently used in on-line haemodiafiltration (HF) than in high-flux HD (P<.001). Antiplatelet agents were given to 45.5% of patients, oral anticoagulants to 18.4% of patients, and both to 5% of patients. Additionally, 4.4% of patients had suffered bleeding complications during the previous week, and 1.9% of patients suffered thrombotic complications. Bleeding complications were more frequent in patients with oral anticoagulants (P=.001), although there was no association between the type of heparin and the occurrence of bleeding or thrombotic complications. We are able to conclude that there is a great amount of disparity in the criteria used for the medical prescription of anticoagulation in HD. It is advisable that each HD unit revise their own results as well as those from other centres, and possibly to create an Anticoagulation Guide in Haemodialysis.


Atomically dispersed dual-atom catalysts: A new rising star in environmental remediation.
Single-atom catalysts, characterized by individual metal atoms as active centers, have emerged as promising candidates owing to their remarkable catalytic efficiency, maximum atomic utilization efficiency, and robust stability. However, the limitation of single-atom catalysts lies in their inability to cater to multistep reactions using a solitary active site. Introducing an additional metal atom can amplify the number of active sites, modulate the electronic structure, bolster adsorption ability, and enable a gamut of core reactions, thus augmenting their catalytic prowess. As such, dual-atom catalysts have risen to prominence. However, a comprehensive review elucidating the realm of dual-atom catalysts in environmental remediation is currently lacking. This review endeavors to bridge this gap, starting with a discourse on immobilization techniques for dual-atom catalysts, which includes configurations such as adjacent atoms, bridged atoms, and co-facially separated atoms. The review then delves into the intrinsic activity mechanisms of these catalysts, elucidating aspects like adsorption dynamics, electronic regulation, and synergistic effects. Following this, a comprehensive summarization of dual-atom catalysts for environmental applications is provided, spanning electrocatalysis, photocatalysis, and Fenton-like reactions. Finally, the existing challenges and opportunities in the field of dual-atom catalysts are extensively discussed. This work aims to be a beacon, illuminating the path towards the evolution and adoption of dual-atom catalysts in environmental remediation.


Electrostatic properties of bovine beta-lactoglobulin.
Bovine beta-Lactoglobulin (BLG) has been studied for many decades, but only recently structural data have been obtained, making it possible to simulate its molecular properties. In the present study, electrostatic properties of BLG are investigated theoretically using Poisson-Boltzmann calculations and experimentally following pH titration via NMR. Electrostatic properties are determined for several structural models, including an ensemble of NMR structures obtained at low pH. The changes in electrostatic forces upon changes in ionic strength, solvent dielectric constant, and pH are calculated and compared with experiments. pK(a)s are computed for all titratable sites and compared with NMR titration data. The analysis of theoretical and experimental results suggests that (1) there may be more than one binding sites for negatively charged ligands; (2) at low pH the core of the molecule is more compact than observed in the structures obtained via restrained molecular dynamics from NMR data, but loop and terminal regions must be disordered.


[Analysis of electroencephalogram formation in terms of the XX "EEG-quantum" concept].
Mechanism of EEG formation was studied in terms of "EEG quantum". The "quantum" approach gives the same results as that based on the cell dipole concept. EEG is created by partially correlated activity of vertically oriented pyramide neurons of the cortex; the value of correlation coefficient between EEG of two points of the cortex and its dependence on interelectrode distance are determined by an increased level of intercellular correlation in the cortex microvolumes by the value of intercellular correlation drop on the borders of these microvolumes and by the dimensions of these microvolumes. The advantage of the "quantum" approach lies in the fact that final expressions include the mean values of correlation coefficients between impulse currents generated by the cortical cells, i. e. the parameters which can be measured experimentally.


Modeling the Effects of Helminth Infection on the Transmission Dynamics of Mycobacterium tuberculosis under Optimal Control Strategies.
A deterministic mathematical model for the transmission and control of cointeraction of helminths and tuberculosis is presented, to examine the impact of helminth on tuberculosis and the effect of control strategies. The equilibrium point is established, and the effective reproduction number is computed. The disease-free equilibrium point is confirmed to be asymptotically stable whenever the effective reproduction number is less than the unit. The analysis of the effective reproduction number indicates that an increase in the helminth cases increases the tuberculosis cases, suggesting that the control of helminth infection has a positive impact on controlling the dynamics of tuberculosis. The possibility of bifurcation is investigated using the Center Manifold Theorem. Sensitivity analysis is performed to determine the effect of every parameter on the spread of the two diseases. The model is extended to incorporate control measures, and Pontryagin's Maximum Principle is applied to derive the necessary conditions for optimal control. The optimal control problem is solved numerically by the iterative scheme by considering vaccination of infants for Mtb, treatment of individuals with active tuberculosis, mass drug administration with regular antihelminthic drugs, and sanitation control strategies. The results show that a combination of educational campaign, treatment of individuals with active tuberculosis, mass drug administration, and sanitation is the most effective strategy to control helminth-Mtb coinfection. Thus, to effectively control the helminth-Mtb coinfection, we suggest to public health stakeholders to apply intervention strategies that are aimed at controlling helminth infection and the combination of vaccination of infants and treatment of individuals with active tuberculosis.


Periodic hexagonal mesostructured chalcogenides based on platinum and [SnSe4]4- and [SnTe4]4- precursors. Solvent dependence of nanopore and wall organization.
Mesostructured chalcogenide-based materials with long-range order and semiconducting properties can be prepared using suitable molecular building blocks, linkage metal ions and surfactant molecules. In this paper we present surfactant templated, open framework platinum tin selenide and telluride materials assembled using K4SnQ4 (Q = Se, Te) salts and K2PtCl4 as precursors and a study of pore and wall organization. We find that materials prepared in water exhibit disordered pore organization, whereas those prepared in formamide are long-range ordered with hexagonal symmetry. In formamide the [SnQ4]4- anions undergo condensation-oligomerization reactions that produce different chalcogenido molecular species, whereas in water the anions remain intact. In addition to solvent, the pore organization and overall quality of the mesostructured materials strongly depend on the surfactant molecules, i.e., chain length and headgroup size. For example, highly ordered mesostructured platinum tin selenides with hexagonal symmetry were obtained using the hydroxyl-functionalized surfactants CnH2n+1N(CH3)(CH2CH2OH)2Br (n = 16, 18, and 20), but when the headgroup was triethylammonium, hexagonal pore order was achieved only for n = 20 and not for n = 16 and 18. The experimental results imply that in order to achieve highly ordered chalcogenide frameworks a single building anionic block might be insufficient. Finally, we also report the first examples of hexagonal mesostructured Pt/Sn/Te materials based on K4SnTe4 as the precursor. The tellurides behave differently for their selenium analogues and have very low energy band gaps, in the range 0.5-0.7 eV.


Effect of gamma-thio-ATP on dog stomach smooth muscle membranes.
The effect of gamma-Thio-ATP on high affinity ATPase and on the ATP-dependent Ca-uptake of a plasma membrane fraction prepared from the dog stomach smooth muscle was examined. gamma-Thio-ATP did not act as a substrate for the ATP-dependent Ca-uptake and was only a poor substrate for the high affinity Ca-ATPase reaction. The compound, however, reversibly inhibited the uptake and the ATPase.


A multistage, one-pot procedure mediated by a single catalyst: a new approach to the catalytic asymmetric synthesis of beta-amino acids.
A catalytic asymmetric procedure for the preparation of beta-amino acids (specifically beta-substituted aspartic acid derivatives) is reported. The cinchona alkaloid catalyst benzoylquinine (BQ) mediates up to five distinct steps of a reaction pathway, all in one reaction vessel. The products of this reaction, highly optically enriched beta-substituted aspartic acid derivatives, were prepared from N-acyl-alpha-chloroglycine esters and acid chlorides in the presence of the catalyst. This approach was also amenable to the synthesis of small polypeptides containing beta-substituted aspartic acid units, including a non-natural fragment of the antibiotic lysobactin. The addition of Lewis acids to this system was found to accelerate the rate of specific steps in the reaction pathway. Mechanistic aspects of this reaction, such as imine formation and Lewis acid chelation to the beta-lactam intermediate, were investigated through comparison of IR, NMR, and other physical data.


Response of uremic patients to nandrolone decanoate.
The effect of anabolic steroid therapy on anemia in 13 women with and without kidneys undergoing chronic hemodialysis for renal failure was investigated. All but one of the six patients with kidneys demonstrated a noticeable increase in hematocrit level (6.4% to 14.6%). Of the anephric women, four of the seven also showed hematocrit level elevations, but these were less remarkable (3.1% to 6.4%). A majority of patients demonstrated increments in weight and serum creatinine measurements but no definitive alteration in serum blood urea nitrogen levels. The androgenic effects of nandrolone decanoate were minimal and well tolerated. We conclude that anabolic steroid therapy is effective in ameliorating the anemia of women undergoing hemodialysis, if given in a dose that produces minimal and tolerable untoward effects.


[John Flamsteed's horoscope for laying the groundwork of Greenwich astronomy and astrology].
The paper deals with the astronomical and astrological contents of a horoscope cast by John Flamsteed in 1675 for the foundation of Greenwich Observatory. So far no analysis of its astronomical contents has been made. It can be shown that the chart has been drawn correctly, as is to be expected from a competent astronomer. For calculating the planetary positions he most likely used tables issued by Johann Hecker, a pupil of Hevelius, based on Kepler's "Tabulae Rudolphinae" in 1627. The cusps of the twelve astrological houses Flamsteed calculated trigonometrically; so he used no table of houses. Flamsteed employed a method of house division (domification) which was commonly used in the 16th and 17th century and connected with the name of Johannes Regiomontanus. Positional circles joining in the north and south points of the observer's horizon are laid through distances of 30 degrees on the celestial equator, thus giving unequal sections of the ecliptic. By consulting contemporary sources for the interpretation of the chart (Ramesey's Astrologia Restaurata, 1653) it appears that the time for laying the foundation stone was well chosen from the astrological point of view. There were precursors in this practice, e.g. the Italian astrologer Luca Gaurico, who was commissioned to submit an astrological report for the foundation for the Franse Wing in the Vatican in 1543, and Tycho Brahe, who performed a solemn ceremony on the island of Hven in 1576 at the laying of the foundation stone of his observatory in an astrologically propitious moment. This leads to the question whether Flamsteed believed in astrology. Michael Hunter has already given evidence that Flamsteed was indeed well-versed with astrological techniques and supplied astrologers with data. But at the same time he expressed hostility towards astrological interpretations issued frequently by different parties during Civil War in England. In an unpublished preface for Hecker's Tables (edited by Hunter) Flamsteed tried to show the "Vanity of Astrology, & the Practice of Astrologers". Therefore he cannot be taken as an ardent astrologer, although he was well acquainted with the art.


Infliximab and etanercept have distinct actions but similar effects on cytokine profiles in rheumatoid arthritis.
Pro-inflammatory cytokines, especially TNFα, play a central role in the pathogenesis of rheumatoid arthritis (RA). The available TNF inhibitors are only slightly different from one another in terms of clinical efficacy, at least at the group level, but their structures and modes of action are not identical. Infliximab (IFX) and etanercept (ETN) differ in their ability to induce antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, and in their ability to bind TNFβ. The purpose of our study was to elucidate the different cytokine pathways through which these two drugs enact their clinical efficacy. Serum from 44 RA patients treated with IFX and 24 patients treated with ETN was studied. All patients had been given these biologics at identical dosages and intervals for one year. The concentrations of 11 inflammatory cytokines and their receptors (IL-1β, IL-2, IL-6, IL-6R, IL-8, IL-10, IL-12, TNFα, TNFβ, IFNγ, and GM-CSF) were measured at weeks 0, 22, and 54 using a high-sensitivity electro-chemiluminescence assay. Cytokine profiles were analyzed along with clinical efficacy. IL-6 was significantly decreased in the ETN+MTX and IFX+MTX groups, although not in the ETN-only group; this change was consistent with changes in disease activity. IFNγ was gradually increased only in the non-remission subgroup of the IFX group, and not at all in the ETN group. TNFβ increased after starting IFX regardless of clinical efficacy. IL-6 inhibition is a pathway affected by both IFX and ETN. In addition, IFNγ increase is a distinctive feature of the inefficacy of IFX.


Comparative effectiveness of fluphenazine decanoate injections every 2 weeks versus every 6 weeks.
Dose reduction strategies for the maintenance treatment of schizophrenia are designed to maintain the benefits of antipsychotic drug therapy while reducing risks. Previous strategies with decanoate preparations have been based on the use of lower doses per injection to achieve dose reduction; these strategies have achieved dose reduction but have resulted in some increase in symptoms. The authors tested a new dose reduction approach: increasing the interval between injections during intramuscular decanoate antipsychotic treatment. Fifty outpatients with schizophrenia or schizoaffective disorder were randomly assigned to receive 25 mg of fluphenazine decanoate intramuscularly either every 2 weeks or every 6 weeks for 54 weeks in a double-blind design. The two dose regimens did not differ significantly in relapse, symptom, or side effect measures. The every-6-weeks regimen was associated with a significant reduction in total antipsychotic exposure. The use of injections every 6 weeks instead of every 2 weeks may increase compliance and improve patients' comfort as well as decrease cumulative antipsychotic exposure, without increasing relapse rates or symptoms.


Method to obtain endoscopic esophageal samples for primary cell culture: focus on infectious contamination.
Cell culture techniques hold great importance for the development of molecular biology. However, when used to study oncology, most of the samples come from surgical specimens. Endoscopy is a interesting alternative to get samples for culture. We studied a protocol to allow the control of infectious contamination potentially related to endoscopy, which could preclude it as a method to obtain cells for culture. Esophageal biopsies from 30 patients were taken through upper gastrointestinal endoscopy, using a previously flamed forceps, and were cultivated with and without amphotericin. Our results showed contamination in 3.3% of the wells without the antifungal and in 0.8% of those with it. Regarding the 30 cases studied, the described protocol was able to provide samples free of contamination in all of them.


Safety and effectiveness of medication and aspiration abortion before or during the sixth week of pregnancy: A retrospective multicenter study.
To compare adverse outcomes of medication and aspiration abortion among those with intrauterine pregnancy <43 days gestation versus abortions performed at 43-48 days. We conducted a multicenter retrospective chart review study to review all medication and aspiration abortion of visualized pregnancy <49 days gestation at Planned Parenthood Columbia Willamette (Oregon) and Planned Parenthood of Orange and San Bernardino Counties (California) in 2014-2015. We identified incident cases by billing codes and performed chart review for adverse outcomes (ED visits, incomplete abortion), need for further interventions, or complications (hemorrhage, infection, and uterine perforation), captured up to 90 days post-abortion. The 3930 abortions during the study period at the two sites included 2914 medication abortions and 1016 aspiration abortions, with 1470 medication abortions and 469 aspiration abortions at <43 days gestation. Composite adverse outcomes did not vary by gestation, for either medication abortion (75/1470; 5.1% for <43 days versus 94/1444; 6.5% at 43-48 days, p = 0.10) or aspiration (12/469; 2.6% for <43 days versus 16/547; 2.9% at 43-48 days, p = 0.72). Fewer incomplete abortions (ongoing pregnancy, symptomatic retained tissue, or retained gestational sac) occurred in the earlier gestational group (3.1% for <43 days versus 4.3% at 43-48 days, p = 0.04). Composite adverse outcomes were higher after medication versus aspiration abortion (169/2914; 5.8% versus 28/1016; 2.7%, p < 0.01). Medication and aspiration abortion performed either before or during the sixth week of ultrasound-confirmed intrauterine pregnancy have low rates of composite adverse outcomes, including complications or incomplete abortion. However, unplanned interventions are more common after medication compared to aspiration abortions. Very early medication and aspiration abortion are similarly safe and effective before or during the sixth week of ultrasound-confirmed pregnancy, though subsequent interventions are more likely after medication abortion. Patients with early pregnancy can safely initiate abortion with follow-up to ensure complete abortion.


SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines.
Small-conductance Ca(2+)-activated K(+) channels (SK channels) influence the induction of synaptic plasticity at hippocampal CA3-CA1 synapses. We find that in mice, SK channels are localized to dendritic spines, and their activity reduces the amplitude of evoked synaptic potentials in an NMDA receptor (NMDAR)-dependent manner. Using combined two-photon laser scanning microscopy and two-photon laser uncaging of glutamate, we show that SK channels regulate NMDAR-dependent Ca(2+) influx within individual spines. SK channels are tightly coupled to synaptically activated Ca(2+) sources, and their activity reduces the amplitude of NMDAR-dependent Ca(2+) transients. These effects are mediated by a feedback loop within the spine head; during an excitatory postsynaptic potential (EPSP), Ca(2+) influx opens SK channels that provide a local shunting current to reduce the EPSP and promote rapid Mg(2+) block of the NMDAR. Thus, blocking SK channels facilitates the induction of long-term potentiation by enhancing NMDAR-dependent Ca(2+) signals within dendritic spines.


Real-time photonic blind interference cancellation.
mmWave devices can broadcast multiple spatially-separated data streams simultaneously in order to increase data transfer rates. Data transfer can, however, be compromised by interference. Photonic blind interference cancellation systems offer a power-efficient means of mitigating interference, but previous demonstrations of such systems have been limited by high latencies and the need for regular calibration. Here, we demonstrate real-time photonic blind interference cancellation using an FPGA-photonic system executing a zero-calibration control algorithm. Our system offers a greater than 200-fold reduction in latency compared to previous work, enabling sub-second cancellation weight identification. We further investigate key trade-offs between system latency, power consumption, and success rate, and we validate sub-Nyquist sampling for blind interference cancellation. We estimate that photonic interference cancellation can reduce the power required for digitization and signal recovery by greater than 74 times compared to the digital electronic alternative.


Ipilimumab: its potential in non-small cell lung cancer.
Ipilimumab is a fully human monoclonal antibody that enhances antitumor immunity by way of cytotoxic T-lymphocyte antigen 4 blockade. It has already been approved by the US Food and Drug Administration for the treatment of metastatic melanoma and is being investigated for treating other solid tumors such as renal cell, prostate and lung cancers. This review details the potential of ipilimumab in the management of non-small cell lung cancer (NSCLC). In particular, ipilimumab showed promising results in a first-line NSCLC phase II study combining carboplatin/paclitaxel chemotherapy with concurrent or phased ipilimumab. The median immune-related progression-free survival was 5.68 months for the phased ipilimumab arm versus 4.63 months for chemotherapy alone (hazard ratio [HR] = 0.68, p = 0.026) and 5.52 months for the concurrent ipilimumab arm versus 4.63 months for chemotherapy alone (HR = 0.77, p = 0.094). The main adverse events were immune related, such as hypophysitis, enterocolitis, and hyperthyroidism. These adverse events may be improved with high-dose glucocorticoids and may be correlated with tumor response. Phase III studies are ongoing. Future studies may investigate ipilimumab in the management of early stage lung cancer. Strategies for potential translational research studies are also discussed to identify prognostic and predictive biomarkers for the use of ipilimumab in the treatment of patients with NSCLC.


Systematic decomposition of sequence determinants governing CRISPR/Cas9 specificity.
The specificity of CRISPR/Cas9 genome editing is largely determined by the sequences of guide RNA (gRNA) and the targeted DNA, yet the sequence-dependent rules underlying off-target effects are not fully understood. To systematically explore the sequence determinants governing CRISPR/Cas9 specificity, here we describe a dual-target system to measure the relative cleavage rate between off- and on-target sequences (off-on ratios) of 1902 gRNAs on 13,314 synthetic target sequences, and reveal a set of sequence rules involving 2 factors in off-targeting: 1) a guide-intrinsic mismatch tolerance (GMT) independent of the mismatch context; 2) an "epistasis-like" combinatorial effect of multiple mismatches, which are associated with the free-energy landscape in R-loop formation and are explainable by a multi-state kinetic model. These sequence rules lead to the development of MOFF, a model-based predictor of Cas9-mediated off-target effects. Moreover, the "epistasis-like" combinatorial effect suggests a strategy of allele-specific genome editing using mismatched guides. With the aid of MOFF prediction, this strategy significantly improves the selectivity and expands the application domain of Cas9-based allele-specific editing, as tested in a high-throughput allele-editing screen on 18 cancer hotspot mutations.


An uncommon ocular manifestation of Sweet syndrome: peripheral ulcerative keratitis and nodular scleritis.
Sweet syndrome (acute febrile neutrophilic dermatosis) is characterized by fever, neutrophilic leukocytosis, and abrupt appearance of painful erythematous nodules and plaques, particularly on the face, neck, and limbs. In this study, we report a very rare case of Sweet syndrome in which the patient presented nodular scleritis and peripheral ulcerative keratitis during the dermatologically inactive period of the disease.


Low dose methotrexate induces apoptosis with reactive oxygen species involvement in T lymphocytic cell lines to a greater extent than in monocytic lines.
The mechanism by which low dose methotrexate (MTX) exerts its anti-inflammatory and immunosuppressive effect in rheumatoid arthritis (RA) patients is still debated. Recently it has been related to the induction of apoptosis. We investigated the degree of apoptotic induction by MTX in lymphocytic (Jurkat T, EL4 T, and Raji B) and monocytic cell lines (U937 and THP1) and its relation to reactive oxygen species (ROS) generation, as a possible mechanism underlying the apoptotic events. All cell types were incubated with a range of MTX concentrations (0.001, 0.01, 0.1, 1, and 10 muM) for up to 24 h. Cytotoxicity was assessed by Trypan Blue exclusion and MTT test; cell size and granularity by forward and side scatters (FSC, SSC). Apoptosis was measured by Annexin V test and FDA polarization; and mitochondrial ROS generation by DHR123 probe and by NAC inhibition. MTX significantly reduced cell viability and proliferation in all cell lines, being most effective in the Jurkat T lymphocytic line. The MTX cytotoxicity (at the optimal concentrations corresponding to low dose MTX therapy) was attributed to apoptosis, as suggested by morphological changes (shrinkage, increased granularity) and confirmed by Annexin V binding and FDA hyperpolarization. The apoptotic induction and the ROS generation (statistically correlated to apoptosis) were most pronounced in the Jurkat and EL4 T cell lines, and were partially inhibited by the antioxidant N-acetyl L-cysteine (NAC). According to the present observations, MTX may most likely induce apoptosis through oxidative stress. The high susceptibility of T cell lines to MTX induced apoptosis may account for the beneficial effect of MTX treatment in rheumatoid arthritis, which is characterized by hyperproliferation of T cells.


Clinal patterns of human Y chromosomal diversity in continental Italy and Greece are dominated by drift and founder effects.
We explored the spatial distribution of human Y chromosomal diversity on a microgeographic scale, by typing 30 population samples from closely spaced locations in Italy and Greece for 9 haplogroups and their internal microsatellite variation. We confirm a significant difference in the composition of the Y chromosomal gene pools of the two countries. However, within each country, heterogeneity is not organized along the lines of clinal variation deduced from studies on larger spatial scales. Microsatellite data indicate that local increases of haplogroup frequencies can be often explained by a limited number of founders. We conclude that local founder or drift effects are the main determinants in shaping the microgeographic Y chromosomal diversity.


[Not Available].
C. Khosrovaninéjad, Ph. Marchal, S. Daligaux, M. Blaustein, G. Martane, Ch. Bodiou Hemorrhoidectomy is the treatment of choice for Stage 3 and 4 hemorrhoids; the most popular technique is that described by Milligan et al. Longo has recently introduced stapled anopexy as an alternative to the Milligan hemorrhoidectomy, however long-term results do not yet demonstrate a convincing superiority. The Parks technique of hemorrhoidectomy is another alternative to Milligan's procedure; it is an established and widely known procedure. The present prospective trial reports the immediate and medium-term results of Parks hemorrhoidectomy performed on 327 consecutive patients between 1997 and 2001. All patients were interviewed using a standard questionnaire before surgery and at 1 and 3 weeks after surgery. An anal incontinence score was recorded before and after surgery in the first 198 patients. No serious operative complications were seen. The daily mean postoperative pain score was less than 3. Mean hospital stay was 2.2 days and work incapacity was 11 days. The anal incontinence score was unchanged or improved in 179 patients (90.4%) and was worsened in 19 patients (9.6%). This trial confirms that Parks hemorrhoidectomy is safe and leads to satisfactory outcome. Postoperative pain is reduced and anal functional sequelae are few.


Chromatic and spatial properties of parvocellular cells in the lateral geniculate nucleus of the marmoset (Callithrix jacchus).
The parvocellular (PC) division of the afferent visual pathway is considered to carry neuronal signals which underlie the red-green dimension of colour vision as well as high-resolution spatial vision. In order to understand the origin of these signals, and the way in which they are combined, the responses of PC cells in dichromatic ('red-green colour-blind') and trichromatic marmosets were compared. Visual stimuli included coloured and achromatic gratings, and spatially uniform red and green lights presented at varying temporal phases and frequencies.The sensitivity of PC cells to red-green chromatic modulation was found to depend primarily on the spectral separation between the medium- and long-wavelength-sensitive cone pigments (20 or 7 nm) in the two trichromatic marmoset phenotypes studied. The temporal frequency dependence of chromatic sensitivity was consistent with centre-surround interactions. Some evidence for chromatic selectivity was seen in peripheral PC cells. The receptive field dimensions of parvocellular cells were similar in dichromatic and trichromatic animals, but the achromatic contrast sensitivity of cells was slightly higher (by about 30%) in dichromats than in trichromats. These data support the hypothesis that the primary role of the PC is to transmit high-acuity spatial signals, with red-green opponent signals appearing as an additional response dimension in trichromatic animals.


Fibromyalgia and depression.
Fibromyalgia and depression might represent two manifestations of affective spectrum disorder. They share similar pathophysiology and are largely targeted by the same drugs with dual action on serotoninergic and noradrenergic systems. Here, we review evidence for genetic and environmental factors that predispose, precipitate, and perpetuate fibromyalgia and depression and include laboratory findings on the role of depression in fibromyalgia. Further, we comment on several aspects of fibromyalgia which support the development of reactive depression, substantially more so than in other chronic pain syndromes. However, while sharing many features with depression, fibromyalgia is associated with somatic comorbidities and absolutely defined by fluctuating spontaneous widespread pain. Fibromyalgia may, therefore, be more appropriately grouped together with other functional pain disorders, while psychologically distressed subgroups grouped additionally or solely with affective spectrum disorders.


Relationship between zolpidem use and stroke risk: a Taiwanese population-based case-control study.
To evaluate the relationship between the use of zolpidem and risk of subsequent stroke in Taiwanese patients. This case-control study used data obtained from the National Health Insurance Research Database to determine whether the use of zolpidem is associated with an increased risk of stroke. The case group comprised 12,747 patients who were newly diagnosed with stroke between January 1, 2005, and December 31, 2009. We also randomly selected a 4-fold greater number of patients without stroke as a control group. Patients with ischemic and hemorrhagic stroke were frequency-matched with controls on sex, age, and year of index date. We measured the effect of zolpidem and determined the adjusted odds ratios (ORs) with 95% confidence intervals (CIs). We found that exposure to zolpidem was associated with increased risk of ischemic stroke (OR = 1.37; 95% CI, 1.30-1.44). The risk of ischemic stroke increased significantly with increasing exposure to zolpidem; for average exposures of ≤ 70, 71-470, and > 470 mg per year, the ORs were 1.20, 1.41, and 1.50, respectively; the P value for the trend was < .0001. Regardless of whether people presented with a sleep disorder, the risk of stroke was still greatly increased with zolpidem exposure; the adjusted OR was 1.37 without sleep disorder and 1.41 with sleep disorder. This population-based study positively associated the use of zolpidem with increased risk of ischemic stroke. Our findings warrant further large-scale and in-depth investigations in this area.


Factors Influencing Parental Satisfaction of Mothers with Preschool Children.
The purpose of the study was to identify degrees of parenting stress, parenting efficacy, parenting behavior and parental satisfaction, and to identify factors influencing parenting satisfaction of mothers who had preschool children. The research participants were 176 mothers. All of mothers had preschool children, aged 2 to 6 years old, and attended one of 3 day care centers or 2 Kindergartens located in J city. Data were collected by convenience sampling using self-report questionnaires which contained items on general characteristics, parenting stress, parenting efficacy, parenting behavior, and parenting satisfaction. Data were analyzed using descriptive statistics, t-test, ANOVA, correlation, and multiple regression. The average level of parenting satisfaction of mothers with preschool children was 5.38±0.79. Positive parenting behavior and affective parenting efficacy were verified factors influencing parental satisfaction. These factors accounted for 41.4% of parental satisfaction. The results indicate that positive parenting behavior and affective parenting efficacy have the biggest impact on parental satisfaction. The results of this study provide the basic data for the development of parental education program aimed at improving parental satisfaction of mothers who have preschool children.


Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast.
Mass spectrometry is a powerful technology for the analysis of large numbers of endogenous proteins. However, the analytical challenges associated with comprehensive identification and relative quantification of cellular proteomes have so far appeared to be insurmountable. Here, using advances in computational proteomics, instrument performance and sample preparation strategies, we compare protein levels of essentially all endogenous proteins in haploid yeast cells to their diploid counterparts. Our analysis spans more than four orders of magnitude in protein abundance with no discrimination against membrane or low level regulatory proteins. Stable-isotope labelling by amino acids in cell culture (SILAC) quantification was very accurate across the proteome, as demonstrated by one-to-one ratios of most yeast proteins. Key members of the pheromone pathway were specific to haploid yeast but others were unaltered, suggesting an efficient control mechanism of the mating response. Several retrotransposon-associated proteins were specific to haploid yeast. Gene ontology analysis pinpointed a significant change for cell wall components in agreement with geometrical considerations: diploid cells have twice the volume but not twice the surface area of haploid cells. Transcriptome levels agreed poorly with proteome changes overall. However, after filtering out low confidence microarray measurements, messenger RNA changes and SILAC ratios correlated very well for pheromone pathway components. Systems-wide, precise quantification directly at the protein level opens up new perspectives in post-genomics and systems biology.


Effect of glucagon on hepatic lactate metabolism in the conscious dog.
The present experiments were undertaken to assess hepatic lactate metabolism in the overnight-fasted, conscious dog after a physiological elevation in glucagon. Animals were given somatostatin plus intraportal insulin (243 microU . kg-1 . min-1) and glucagon (0.65 ng . kg-1 . min-1) to initially fix the pancreatic hormone levels at basal values. After a 40-min control period the glucagon level was increased to 527 +/- 27 pg/ml, while the insulin level was left unchanged (10 microU/ml). Fifteen minutes later blood lactate had increased by 215 +/- 24 mumol/l because of a marked increase in lactate output by the liver [2.4 +/- 2.0 to 10.0 +/- 3.8 mumol . kg . min (P less than 0.05)]. Subsequently, hepatic lactate output decreased, and after 3 h the liver was taking up lactate at a rate of 3.1 +/- 1.6 mumol . kg-1 . min-1 (P less than 0.05). Gut and renal lactate production were not significantly affected by glucagon. The rate of conversion of lactate and alanine to glucose had tripled after 3 h of hyperglucagonemia, while the efficiency with which the liver converted the incoming gluconeogenic precursors to glucose had doubled. The fractional extraction of alanine by the liver had more than doubled by 3 h, and net hepatic alanine uptake had increased by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)


Voluntary medical male circumcision for HIV prevention and early resumption of sexual activity: a literature review.
A number of programs have focused on scale-up and implementation research regarding voluntary medical male circumcision; however, there is limited research with regard to factors and strategies related to abstinence compliance and the effects of resuming sex during the wound healing period (42-day post-circumcision). We searched the literature for peer-reviewed articles examining early resumption of sex during this period. This review identifies factors that may predispose a client to engage in sex during the 42-day postoperative period, examines how early resumption of sex can inhibit wound healing and increase seroconversion, and reviews strategies that may increase adherence to abstinence during the wound healing period. We found that the most common factor that may predispose a client to engage in sex before the end of the postoperative period is marriage or cohabitation with a sexual partner. With regard to the effect of sex during the postoperative period on wound healing and seroconversion, we found that adverse events incurred were mild, and there was an increased risk of seroconversion. The only strategy studied to increase compliance to abstinence during the postoperative period utilized text messaging, and the trial results indicate that text messaging did not increase abstinence compliance.


Acute Pyelonephritis - Correlation of Clinical Parameter with Radiological Imaging Abnormalities.
Pyelonephritis (PN) is a suppurative infection of the kidney, most commonly due to bacterial infection and may be either acute or chronic. Acute PN (APN) subdivided into uncomplicated and complicated. Severity of PN cannot be assessed by clinical or laboratorial parameters alone, radiological imaging such as Ultrasound (USG) abdomen, Computed Tomography (CT) is required to know the nature, extent and severity of disease and for planning interventions. The aim of this study was to compare clinical and biochemical parameters with radiological findings (USG/CT) among patients diagnosed to have PN. The medical records of all patients admitted with PN at the Institute of Nephrourology, Bangalore from January 2016 to December 2016 were reviewed. Their clinical and biochemical parameter were compared with radiological findings. Statistical analysis was performed with Statistical Package for the Social Sciences (SPSS) Version 15.0. There were 100 patients diagnosed with PN in the study period. Mean age of patient was 48.7 years and PN was common among females (62%). Classical triad of PN was present in 87% of patients. Acute kidney injury was present in 47% of patients. Diabetes (69%) was the most common comorbid condition. Positive urine culture was found in 24% of patients. USG abdomen was performed in all patients and it was suggestive of APN in 66% cases. CT abdomen was available for 74% and it revealed PN in 70%, of patients. Among these Emphysematous PN (EPN) was found in 4% and renal abscess in 3% of patients. In this study, USG findings of PN were correlated with triad of PN symptoms and those who had PN for the first time. In this study, majority of the patients presented with clinical triad of PN-fever, flank pain and dysuria. Urine culture was positive only in few cases. USG was able to diagnose large number of PN cases except emphysematous change and renal abscess which was detected by CT. The detection of PN was better with CT when compared to USG.


The effect of copper on intact cattle erythrocytes.
The effect of copper on intact cattle erythrocytes was investigated in vitro. When treated with copper, a decrease in the GSH content, accumulation of copper in the cell, loss of potassium and gain of sodium, cross-linking of membrane proteins, and echinocytic transformation were observed. All of these phenomena seem to be caused by a potent oxidant action of copper. These cytotoxic effects of copper were markedly inhibited by the addition of bovine serum albumin in the incubation medium. These results may help to understand the mechanism of hemolysis associated with copper poisoning in vivo.


Evaluation of the turbine pocket spirometer.
A compact electronic spirometer, the turbine pocket spirometer, which measures the FEV1, forced vital capacity (FVC), and peak expiratory flow (PEF) in a single expiration, was compared with the Vitalograph and the Wright peak flow meter in 99 subjects (FEV1 range 0.40-5.50 litres; FVC 0.58-6.48 l; PEF 40-650 l min-1). The mean differences between the machines were small--0.05 l for FEV1, 0.05 l for FVC, and 11.6 l min-1 for PEF, with the limits of agreement at +/- 0.25 l, +/- 0.48 l, and +/- 52.2 l min-1 respectively. The wide limits of agreement for the PEF comparison were probably because of the difference in the technique of blowing: a fast, long blow was used for the pocket spirometer and a short, sharp one for the Wright peak flow meter. The FEV1 and FVC showed a proportional bias of around 4-5% in favour of the Vitalograph. The repeatability coefficient for the pocket spirometer FEV1 was 0.18 l, for FVC 0.22 l, and for PEF 31 l min-1. These compared well with the repeatability coefficients of the Vitalograph and the Wright peak flow meter, which gave values of 0.18 l, 0.28 l, and 27 l min-1 respectively. At flow rates of over 600 l min-1 the resistance of the pocket spirometer marginally exceeded the American Thoracic Society recommendations. The machine is easy to operate and portable, and less expensive than the Vitalograph and Wright peak flow meter combined. It can be recommended for general use.


Treating adults raised by alcoholic parents.
The concept of adult children of alcoholics (ACOAs) is a recent one, yet ACOAs have had a formidable influence on the chemical dependence and mental health treatment field. Through their sponsorship of workshops and conferences, development of specialized inpatient and outpatient treatment programs, and generation of publications dedicated to understanding themselves with common interpersonal and intrapersonal problems, ACOAs have organized themselves into an influential social movement. Most ACOA treatment philosophies and programs are derived from the ACOA social movement using the concept of the "inner child" to guide the treatment. Unfortunately, few studies of treatment efficacy are available in the scientific literature. In this chapter, our discussion concentrates on the central treatment theme of the ACOA movement as it influences the treatment ideologies that currently guide ACOA treatment programs. We conclude by addressing the obvious need for research and the necessity for maintaining our ethical responsibility both in scientific inquiry and in the treatment of needy individuals.


Outcomes of pregnancies with fetal gastroschisis.
To describe pregnancy outcomes with fetal gastroschisis, including the associations of prenatal ultrasound findings with neonatal surgical complications and other morbidities. This was a review of pregnancies complicated by fetal gastroschisis and delivered from January 1998 through June 2006. The last ultrasonogram before delivery was reviewed to determine stomach dilatation, bowel dilatation, or abnormalities of amniotic fluid volume. Neonatal records were reviewed to determine type of closure and any bowel complications. There were 66 pregnancies with gastroschisis, 1 per 2,000 deliveries. There were three stillbirths and three neonatal deaths. Delayed closure was necessary in 49% who underwent surgery. Birth weight below the third percentile, which occurred in 38%, was associated with need for delayed closure, 64% compared with 25% without growth restriction, P<.001, but was not associated with longer hospital stay or neonatal death. Fetal gastroschisis was diagnosed by prenatal ultrasonography in 58 cases. Bowel complications requiring surgery were more frequent when ultrasonography had demonstrated stomach dilatation (five cases), 60% compared with 10%, P=.002. Fetuses with defects so large that no normal ventral wall could be visualized ultrasonographically (three cases) were at increased risk for neonatal death, 100% compared with 0%, P<.001. Ultrasound findings associated with adverse outcome in fetal gastroschisis included stomach dilatation and a defect so large that no normal ventral wall could be visualized. Fetal growth restriction was common, and such infants were more likely to require delayed gastroschisis closure. Despite more than 90% survival, morbidity with gastroschisis remains high. II.


Preanalytical Processing and Biobanking Procedures of Biological Samples for Metabolomics Research: A White Paper, Community Perspective (for "Precision Medicine and Pharmacometabolomics Task Group"-The Metabolomics Society Initiative).
The metabolome of any given biological system contains a diverse range of low molecular weight molecules (metabolites), whose abundances can be affected by the timing and method of sample collection, storage, and handling. Thus, it is necessary to consider the requirements for preanalytical processes and biobanking in metabolomics research. Poor practice can create bias and have deleterious effects on the robustness and reproducibility of acquired data. This review presents both current practice and latest evidence on preanalytical processes and biobanking of samples intended for metabolomics measurement of common biofluids and tissues. It highlights areas requiring more validation and research and provides some evidence-based guidelines on best practices. Although many researchers and biobanking personnel are familiar with the necessity of standardizing sample collection procedures at the axiomatic level (e.g., fasting status, time of day, "time to freezer," sample volume), other less obvious factors can also negatively affect the validity of a study, such as vial size, material and batch, centrifuge speeds, storage temperature, time and conditions, and even environmental changes in the collection room. Any biobank or research study should establish and follow a well-defined and validated protocol for the collection of samples for metabolomics research. This protocol should be fully documented in any resulting study and should involve all stakeholders in its design. The use of samples that have been collected using standardized and validated protocols is a prerequisite to enable robust biological interpretation unhindered by unnecessary preanalytical factors that may complicate data analysis and interpretation.


Control of food-borne viruses.
There are two main food-borne virus infections. These are viral gastroenteritis caused by small round structured viruses (SRSV) of the Norwalk group and hepatitis A. Both infections are normally transmitted directly from person-to-person, but on occasions they may also be food-borne or water-borne. Viruses do not multiply or produce toxins in foods, and foods merely act as vehicles for their passive transfer. Foods may be contaminated by infected food-handlers, and outbreaks frequently involve cold foods that require much handling during preparation. Foods may also be contaminated in their growing and harvesting areas by sewage polluted water, and molluscan shellfish have been particularly implicated. PCR and ELISA based methods are being developed for detection and typing of viruses in patients and also in food samples. Sensitive detection methods should facilitate the design of improved food processing methods to ensure virus-free food.


BK channels control cerebellar Purkinje and Golgi cell rhythmicity in vivo.
Calcium signaling plays a central role in normal CNS functioning and dysfunction. As cerebellar Purkinje cells express the major regulatory elements of calcium control and represent the sole integrative output of the cerebellar cortex, changes in neural activity- and calcium-mediated membrane properties of these cells are expected to provide important insights into both intrinsic and network physiology of the cerebellum. We studied the electrophysiological behavior of Purkinje cells in genetically engineered alert mice that do not express BK calcium-activated potassium channels and in wild-type mice with pharmacological BK inactivation. We confirmed BK expression in Purkinje cells and also demonstrated it in Golgi cells. We demonstrated that either genetic or pharmacological BK inactivation leads to ataxia and to the emergence of a beta oscillatory field potential in the cerebellar cortex. This oscillation is correlated with enhanced rhythmicity and synchronicity of both Purkinje and Golgi cells. We hypothesize that the temporal coding modification of the spike firing of both Purkinje and Golgi cells leads to the pharmacologically or genetically induced ataxia.


Transcription repression by Xenopus ET and its human ortholog TBX3, a gene involved in ulnar-mammary syndrome.
T box (Tbx) genes are a family of developmental regulators with more than 20 members recently identified in invertebrates and vertebrates. Mutations in Tbx genes have been found to cause several human diseases. Our understanding of functional mechanisms of Tbx products has come mainly from the prototypical T/Brachyury, which is a transcription activator. We previously discovered ET, a Tbx gene expressed in Xenopus embryos. We report here that ET is an ortholog of the human Tbx3 and that ET is a repressor of basal and activated transcription. Functional dissection of the ET protein reveals a novel transcription-repression domain highly conserved among ET, human TBX3, and TBX2. These results reveal a new transcription repressor domain, show the existence of a subfamily of transcription repressors in the Tbx superfamily, and provide a basis for understanding etiology of diseases caused by Tbx3 mutations.


Rab32 connects ER stress to mitochondrial defects in multiple sclerosis.
Endoplasmic reticulum (ER) stress is a hallmark of neurodegenerative diseases such as multiple sclerosis (MS). However, this physiological mechanism has multiple manifestations that range from impaired clearance of unfolded proteins to altered mitochondrial dynamics and apoptosis. While connections between the triggering of the unfolded protein response (UPR) and downstream mitochondrial dysfunction are poorly understood, the membranous contacts between the ER and mitochondria, called the mitochondria-associated membrane (MAM), could provide a functional link between these two mechanisms. Therefore, we investigated whether the guanosine triphosphatase (GTPase) Rab32, a known regulator of the MAM, mitochondrial dynamics, and apoptosis, could be associated with ER stress as well as mitochondrial dysfunction. We assessed Rab32 expression in MS patient and experimental autoimmune encephalomyelitis (EAE) tissue, via observation of mitochondria in primary neurons and via monitoring of survival of neuronal cells upon increased Rab32 expression. We found that the induction of Rab32 and other MAM proteins correlates with ER stress proteins in MS brain, as well as in EAE, and occurs in multiple central nervous system (CNS) cell types. We identify Rab32, known to increase in response to acute brain inflammation, as a novel unfolded protein response (UPR) target. High Rab32 expression shortens neurite length, alters mitochondria morphology, and accelerates apoptosis/necroptosis of human primary neurons and cell lines. ER stress is strongly associated with Rab32 upregulation in the progression of MS, leading to mitochondrial dysfunction and neuronal death.