From the Centers for Fatigue Control (CFC) Weekly Report : Epidemiologic Notes and Reports.
From 1985 to 1990, the CFC has monitored the growing national epidemic of Lime disease, which appears to parallel increased public awareness and knowledge of Lyme disease. Cases have now been reported from all 50 states, but the national surveillance program has been hampered by persistent confusion between the two diseases, with clinicians frequently reporting a case of Lime disease as Lyme disease. Analysis of surveillance reports of cases fulfilling the case-definition of Lime disease indicates that Lime disease is distributed uniformly throughout the United States (in contrast to the focal geographic occurrence of Lyme disease); the...


Use of plastic adhesive drapes during surgery for preventing surgical site infection.
Surgical site infection has been estimated to occur in about 15% of clean surgery and 30% of contaminated surgery cases. Using plastic adhesive drapes to protect the wound from organisms that may be present on the surrounding skin during surgery is one strategy used to prevent surgical site infection. Results from non-randomised studies have produced conflicting results about the efficacy of this approach, but no systematic review has been conducted to date to guide clinical practice. To assess the effect of adhesive drapes used during surgery on surgical site infection, cost, mortality and morbidity. For this third update we searched the Cochrane Wounds Group Specialised Register (searched 19 July 2012); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7); Ovid MEDLINE (1946 to July Week 2, 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, July 18, 2012); Ovid EMBASE (1974 to Week 28, 2012); and EBSCO CINAHL (1982 to July 6, 2012). Randomised controlled trials comparing any plastic adhesive drape with no plastic adhesive drape, used alone or in combination with woven (material) drapes or disposable (paper) drapes, in patients undergoing any type of surgery. Two review authors independently selected and assessed studies for trial quality and both independently extracted data. We contacted study authors for additional information. We identified no new studies for this third update. The review includes five studies involving 3082 participants comparing plastic adhesive drapes with no drapes and two studies involving 1113 participants comparing iodine-impregnated adhesive drapes with no drapes. A significantly higher proportion of patients in the adhesive drape group developed a surgical site infection when compared with no drapes (risk ratio (RR) 1.23, 95% confidence interval (CI) 1.02 to 1.48, P = 0.03). Iodine-impregnated adhesive drapes had no effect on the surgical site infection rate (RR 1.03, 95% CI 0.06 to 1.66, P = 0.89). Length of hospital stay was similar in the adhesive drape and non-adhesive drape groups. There was no evidence from the seven trials that plastic adhesive drapes reduce surgical site infection rates, and some evidence that they increase infection rates. Further trials may be justified, using blinded outcome assessment to examine the effect of adhesive drapes on surgical site infection, based on different wound classifications.


Establishment of a free-mating colony of Anopheles albitarsis from Brazil.
The establishment of a free-mating colony of Anopheles albitarsis sensu siricto, a member of the Anopheles albitarsis complex, is described. Groups of females from the F5, F6, and F11 generations were examined, and the percent inseminated, mean number of eggs oviposited, and percent hatch discussed. The colony has been continued through 18 generations, with larval development averaging 10 days, and larval mortality ranging between 20 and 30%.


beta-very low density lipoprotein enhances inducible nitric oxide synthase expression in cytokine-stimulated vascular smooth muscle cells.
beta-very low-density lipoprotein (beta-VLDL), a collective term for VLDL and chylomicron remnants, has recently shown to potently promote the development of atherosclerosis. However, the effects of beta-VLDL on the accumulation of nitric oxide (NO) and the expression of inducible NO synthase (iNOS) in vascular smooth muscle cells (VSMC) have not been determined. In this study, we measured the accumulation of nitrite, stable metabolite of NO and examined the expression of iNOS protein and mRNA using Western blotting and RT-PCR, respectively, in VSMC. NF-kappaB activation in VSMC was examined by gel retardation assay. Incubation of cell cultures with interleukin-1beta (IL-1beta) for 24 h caused a significant increase in nitrite accumulation. Although beta-VLDL alone did not increase nitrite accumulation in unstimulated VSMC, beta-VLDL significantly enhanced nitrite accumulation in IL-1beta-stimulated VSMC in a time- and dose-dependent manner. beta-VLDL-induced nitrite accumulation in IL-1beta-stimulated VSMC was accompanied by an increase in iNOS protein and mRNA expression. In addition, IL-1beta induced NF-kappaB activation in VSMC, an effect that was increased by the addition of beta-VLDL. Use of specific tyrosine kinase inhibitor herbimycin A, genistein, or PP2 (Src family kinase inhibitor) indicated that tyrosine kinases are required for IL-1beta-stimulated and beta-VLDL-enhanced nitrite accumulation, while specific inhibition of ERK1/2 or p38-MAP kinase had no effects. Our results suggest that beta-VLDL enhances iNOS expression and nitrite accumulation in IL-1beta-stimulated VSMC through tyrosine kinase(s)-dependent mechanisms.


[Monoclonal antibodies ICO-20 against human thymocyte antigen T10].
Monoclonal antibodies (Mab) Ig G2a isotypes reacting in indirect immunofluorescence assay with 68.7 +/- 4.1% of thymocytes, 7% of T-cells and not determining the antigen on other blood cells were obtained. Mab ICO-20 reacted in complement-dependent cytotoxic test. The antigen was expressed on colony-forming cells of granulocyte-macrophage row. Mab ICO-20 reaction with 100% of thymocytes was defined by flow cytometry. Antigen molecular mass is 45000 Dalton. The antigen was expressed on blast cells of patients with ALL and AML. Mab ICO-20 reaction was more more often with T-cell ALL.


Network organization of co-opetitive genetic influences on morphologies of the human cerebral cortex.
The brain can be represented as a network, where anatomical regions are nodes and relations between regions are edges. Within a network, the co-existence of co-operative and competitive relationships between different nodes is called co-opetition. Inter-regional genetic influences on morphological phenotypes (thickness, surface area) of the cerebral cortex display such co-opetitive relationships. However, whether these co-operative and competitive genetic influences are organized similarly has remained elusive. How the collective organization of the co-operative and competitive genetic influences is related to the inter-individual variations of cortical morphological phenotypes has also remained unexplored. We constructed inter-regional genetic influence networks underlying the morphologies (thickness, surface area) of the human cerebral cortex combining the T1 weighted MRI of genetically confirmed 593 siblings and twin-study design. Graph theory was used to characterize the genetic influence networks and the collective organizations of genetic influences were characterized using the theory of structural balance. Principal component (PC) analysis was used to estimate the principal modes of morphological phenotype variations. The inter-regional co-operative genetic influences are assortative, while competitive influences are disassortative. Co-operative genetic influences are more cohesive and less diverse than the competitive influences. The collective organization of co-opetitive genetic influences partially explains the fifth principal modes of inter-individual variation of cortical morphological phenotypes. Other principal modes were not significantly associated with collective genetic influences. Our study furnishes fundamental insight regarding the organization of co-opetitive genetic influences underlying the morphologies of the human cerebral cortex. In future studies, investigation of the alterations of co-opetitive genetic network properties in brain disorders may furnish disorder-specific insight that may be associated with the disease state or lead to vulnerability to those conditions.


[Development of Markov models for economics evaluation of strategies on hepatitis B vaccination and population-based antiviral treatment in China].
Objective: To construct the Markov models to reflect the reality of prevention and treatment interventions against hepatitis B virus (HBV) infection, simulate the natural history of HBV infection in different age groups and provide evidence for the economics evaluations of hepatitis B vaccination and population-based antiviral treatment in China. Methods: According to the theory and techniques of Markov chain, the Markov models of Chinese HBV epidemic were developed based on the national data and related literature both at home and abroad, including the settings of Markov model states, allowable transitions and initial and transition probabilities. The model construction, operation and verification were conducted by using software TreeAge Pro 2015. Results: Several types of Markov models were constructed to describe the disease progression of HBV infection in neonatal period, perinatal period or adulthood, the progression of chronic hepatitis B after antiviral therapy, hepatitis B prevention and control in adults, chronic hepatitis B antiviral treatment and the natural progression of chronic hepatitis B in general population. The model for the newborn was fundamental which included ten states, i.e. susceptiblity to HBV, HBsAg clearance, immune tolerance, immune clearance, low replication, HBeAg negative CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC) and death. The susceptible state to HBV was excluded in the perinatal period model, and the immune tolerance state was excluded in the adulthood model. The model for general population only included two states, survive and death. Among the 5 types of models, there were 9 initial states assigned with initial probabilities, and 27 states for transition probabilities. The results of model verifications showed that the probability curves were basically consistent with the situation of HBV epidemic in China. Conclusion: The Markov models developed can be used in economics evaluation of hepatitis B vaccination and treatment for the elimination of HBV infection in China though the structures and parameters in the model have uncertainty with dynamic natures.


Anti-peptide antibodies detect a lupus-related interspecies idiotype that maps to H chain CDR2.
Antibodies to the small nucleoprotein Sm occur spontaneously in human and murine systemic lupus erythematosus. Human and mouse monoclonal anti-Sm autoantibodies designated 4B4 and Y2 share an idiotype (Id) determinant located on the Ig H chain. To understand the molecular basis of this cross-reactivity, the VH regions of both antibodies were sequenced and analyzed for homology. The antibodies showed only 49.6% homology. The second complementary determining region (CDR2) was the most likely candidate for the Id site. To investigate this possibility, rabbit antiserum was made against a peptide corresponding to the CDR2 of 4B4. This antiserum was specific for the immunizing peptide and reacted weakly to a peptide corresponding to the CDR2 of Y2. Anti-CDR2 antibody bound to 4B4 and Y2 but not to other human and mouse mAb. Binding was directed at the H chain when analyzed by Western blots. Anti-CDR2 antibody blocked anti-Id antibody binding to 4B4 and Y2 by 58% and 24%, respectively. These studies suggest that this interspecies Id maps to the H chain CDR2 and that a conserved Id can occur within molecules that are otherwise radically different.


Updates on smart polymeric carrier systems for protein delivery.
Smart materials are those materials that are responsive to chemical (organic molecules, chemical agents or specific agents), biochemical (protein, enzymes, growth factors, substrates or ligands), physical (electric field, magnetic field, temperature, pH, ionic strength or radiation) or mechanical (pressure or mechanical stress) signals. These responsive materials interact with the stimuli by changing their properties or conformational structures in a predictable manner. Recently, smart polymers have been utilized in various biomedical applications. Particularly, they have been used as a platform to synthesize stimuli-responsive systems that could deliver therapeutics to a specific site for a specific period with minimal adverse effects. For instance, stimuli-responsive polymers-based systems have been recently reported to deliver different bioactive molecules such as carbohydrates (heparin), chemotherapeutic agents (doxorubicin), small organic molecules (anti-coagulants), nucleic acids (siRNA), and proteins (growth factors and hormones). Protein therapeutics played a fundamental role in treatment of various chronic and some autoimmune diseases. For instance insulin has been used in treatment of diabetes. However, being a protein in nature, insulin delivery is limited by its instability, short half-life, and easy denaturation when administered orally. To overcome these challenges, and as highlighted in this review article, much research efforts have been recently devoted to design and develop convenient smart controlled nanosystems for protein therapeutics delivery.


Molecular docking and spectroscopic study of bovine serum albumin interaction with new anticancer Pt complex with isopentyl dithiocarbamate ligand.
Although cisplatin is useful in the treatment of cancer, it has a series of side effects that limit its use. Dithiocarbamates reduce the toxicity of platinum due to their structure and the presence of S, and N donating groups. In this article, the interaction of [Pt(bpy)(isopentyl.dtc)]NO3, where bpy is bipyridine and isopentyl.dtc is isopentyl-dithiocarbamate, with BSA, bovine serum albumin has been studied. The molecular binding method, including UV-Vis and fluorescence titration, was carried out in conditions including pH = 7.4 and temperatures of 27 and 37 °C. The negative values of enthalpy (ΔH°b) and entropy (ΔS°b) show that the driving forces of this interaction are hydrogen and van der Waals, and the negative value of the Gibbs free energy, ΔG°b indicates that the interaction proceeds spontaneously. The fluorescence results showed that the quenching mechanism is the static type and the Stern Volmer constant, KSV, was also obtained. The fluorescence titration method data displayed that the quenching mechanism is static. Binding constant (Kb), binding point (n), Hill coefficients, nH, Hill constant, KH, number of binding sites, g, BSA melting temperature, Tm, were also obtained. Finally, the molecular docking method result shows the binding constant, Ki and binding free energy for the platinum complex are -6.53 and 16.39 kcal mol-1, respectively, and also the proper position of binding on BSA can be considered the site I in the subdomain IIA.


Direct observation of the oxidative addition of the aryl carbon-oxygen bond to a ruthenium complex and consideration of the relative reactivity between aryl carbon-oxygen and aryl carbon-hydrogen bonds.
When RuH2(CO)(PPh3)3 was reacted with 2,2-dimethyl-1-(2-p-tolylphenyl)propan-1-one (2), the ruthenium-aryloxy complex 3 was obtained in 76% yield. The structure of this complex was determined from 1H and 31P NMR and X-ray data. Complex 3 showed the catalytic activity for the coupling of 2 with the phenylboronate 4. The 1H and 31P NMR studies of the reaction of Ru(CO)(PPh3)3 with o-aryloxy pivalophenone revealed that the C-H bond cleavage is a kinetically favorable process but the C-O bond cleavage is a thermodynamic one. The reaction of 2'-methoxyacetophenone with vinylsilane and organoboronate resulted in chemoselective C-C bond formation.


Clinical significance of hypertriglyceridemia.
Available data suggest that elevated triglyceride levels in plasma, associated with increased VLDL or chylomicron remnants, are associated with premature coronary artery atherosclerosis. Whether this is a direct effect or as a result of the association of hypertriglyceridemia with decreased HDL as well as decreased LDL particle size remains to be determined. Many families with premature coronary disease have a genetic form of hypertriglyceridemia associated with decreased HDL, or with both decreased HDL and increased LDL cholesterol concentrations. In addition, subjects with severe hypertriglyceridemia in excess of 1000 mg/dl associated with elevation of plasma chylomicrons are at increased risk of developing recurrent pancreatitis. Therefore, triglycerides have been implicated in the pathogenesis of both atherosclerosis and pancreatitis.


The testate amoebae of New Zealand: A checklist, identification key and assessment of biogeographic patterns.
New Zealand (NZ) is a well-known hotspot of biodiversity and endemism for macroscopic organisms, but its microbial diversity is comparatively poorly documented. We assembled all records on NZ testate amoebae published since the early 20th century and present a comprehensive taxonomic checklist for NZ. Testate amoebae are reported from six major habitat types across both the North and South Islands of NZ, but the sampling effort is ecologically and geographically biased in favour of wetlands and the South Island. As a result, 93% of all 128 morphotypes recorded in NZ occur in wetlands, 28% are restricted to the South Island, and diversity is greater at higher latitudes. Around 50% of morphotypes have a broad latitudinal distribution across the NZ mainland, whereas 15% have narrow latitudinal ranges. Future research should aim to broaden the geographical and ecological ranges. We predict that our list of NZ testate amoebae will expand substantially with future work, and that the latitudinal diversity gradient will be inverted. We also introduce an interactive, fully illustrated, online Lucid key for the rapid identification of NZ testate amoebae. As many morphospecies are cosmopolitan, this key provides a useful tool for testate amoebae identification in other parts of the world.


Rare case report of idiopathic gingival fibromatosis in childhood and its management.
Idiopathic gingival fibromatosis (GF), also known as gingivomatosis, is a rare condition in childhood, with an unknown aetiology. The oral manifestations of the condition are varied and depend on the severity and age of involvement. This paper describe the case of a 5-year-old male child with extensive gingival enlargement covering almost all the maxillary and mandibular teeth resulted in difficulty with speech, mastication and poor aesthetics. Clinical and radiographic examination along with haematological investigations ruled out any systemic association. The case was managed with conventional scalpel blade surgery along with electrocautery under general anaesthesia yielding good results without any recurrence after a 12-month follow-up. The results revealed that the oral manifestations of GF depend on its severity and the age of onset. Timely intervention can help to prevent associated complications in a growing child.


ProgPerm: Progressive permutation for a dynamic representation of the robustness of microbiome discoveries.
Identification of features is a critical task in microbiome studies that is complicated by the fact that microbial data are high dimensional and heterogeneous. Masked by the complexity of the data, the problem of separating signals (differential features between groups) from noise (features that are not differential between groups) becomes challenging and troublesome. For instance, when performing differential abundance tests, multiple testing adjustments tend to be overconservative, as the probability of a type I error (false positive) increases dramatically with the large numbers of hypotheses. Moreover, the grouping effect of interest can be obscured by heterogeneity. These factors can incorrectly lead to the conclusion that there are no differences in the microbiome compositions. We translate and represent the problem of identifying differential features, which are differential in two-group comparisons (e.g., treatment versus control), as a dynamic layout of separating the signal from its random background. More specifically, we progressively permute the grouping factor labels of the microbiome samples and perform multiple differential abundance tests in each scenario. We then compare the signal strength of the most differential features from the original data with their performance in permutations, and will observe a visually apparent decreasing trend if these features are true positives identified from the data. Simulations and applications on real data show that the proposed method creates a U-curve when plotting the number of significant features versus the proportion of mixing. The shape of the U-Curve can convey the strength of the overall association between the microbiome and the grouping factor. We also define a fragility index to measure the robustness of the discoveries. Finally, we recommend the identified features by comparing p-values in the observed data with p-values in the fully mixed data. We have developed this into a user-friendly and efficient R-shiny tool with visualizations. By default, we use the Wilcoxon rank sum test to compute the p-values, since it is a robust nonparametric test. Our proposed method can also utilize p-values obtained from other testing methods, such as DESeq. This demonstrates the potential of the progressive permutation method to be extended to new settings.


Regulation of the autophagy plays an important role in acute kidney injury induced acute lung injury.
This study aimed to investigate the regulatory role of autophagy in acute kidney injury (AKI) induced acute lung injury (ALI). The male Sprague-Dawley rats were divided into four groups: normal saline-treated sham rats (sham group), normal saline-treated ischemia-reperfusion injury rats (IRI group), 3-methyladenine-treated IRI rats (3-MA group), and rapamycin-treated IRI rats (RA group). The rats in the IRI rat model received the nephrectomy of the right kidney and was subjected to 60 mins of left renal pedicle occlusion, followed by 12, 24, 48, and 72 h of reperfusion. The levels of Scr, BUN, wet-to-dry ratio of lung, inflammatory cytokines, and oxidative stress were determined. The damage to tissues was detected by histological examinations. The western blot and immunohistochemistry methods were conducted to determine the expression of indicated proteins. Renal IRI could induce the pulmonary injury after AKI, which caused significant increases in the function index of pulmonary and renal, the levels of inflammatory cytokines, and biomarkers of oxidative stress. In comparison to the IRI group, the RA group showed significantly decreased P62 and Caspase-3 expression and increased LC-II/LC3-I, Beclin-1, Bcl-2, and unc-51-like autophagy activating kinase 1 expression. Meanwhile, by suppressing the inflammation and oxidative stress, as well as inhibiting the pathological lesions in kidney and lung tissues, the autophagy could effectively ameliorate IRI-induced AKI and ALI. Autophagy plays an important role in AKI-induced ALI, which could be used as a new target for AKI therapy and reduce the mortality caused by the complication.


A highly repetitive and transcribable sequence in the tortoise genome is probably a retroposon.
On in vitro transcription of total genomic DNA of the tortoise (Geoclemys reevessi), a discrete-sized RNA of 6.5S was obtained that represented a highly repetitive and transcribable sequence in the tortoise genome. Three sequences of the 6.5S RNA gene were sequenced, and a consensus sequence was deduced from these three sequences and one reported previously [Endoh, H & Okada, N. (1986) Proc. Natl Acad. Sci. USA 83, 251-255]. The 5' part of the gene showed close similaries to lysine (rabbit) and threonine (mouse) tRNAs (overall similarity 68-70%), so this tortoise sequence may have evolved from one of these tRNAs. The consensus sequence retained the expected CCA triplet at the 3' end of tRNA, but not at the 3' end of tDNA, supporting the idea that the tRNA-related region of the gene was generated via an RNA intermediate. The 5' and 3' flanking sequences of the four genes were found to be completely different from each other. Fingerprint analysis and S1 nuclease mapping analysis also showed that sequence boundaries of tortoise repetitive units exactly corresponded to RNA species. These results, together with data obtained by Southern blot hybridization, indicated that the 6.5S RNA genes are dispersed in the tortoise genome. Therefore, generation of the tRNA-related region of the gene and amplification of the whole unit of the gene are both RNA-mediated events. The existence of this tortoise sequence suggests that short interspersed sequences are more common in eukaryotic genomes than had previously been thought.


Systematic Analysis of the Pharmacological Effects of Alcoholic Components in Maotai.
Maotai liquor is one of the most famous traditional Chinese distilled liquor enjoyed by many people all over the world for its unique production method, impressive liquor quality, and soy sauce-like and roasted aroma style. It is known that aroma characteristics of liquor mainly depend on the aroma compounds. Alcohols as one of the most important categories of aroma components have been determined in Maotai liquor. However, the systemic analysis of alcoholic compounds in liquor is limited, especially the active alcoholic components and their pharmacological effects. Therefore, in this study, a systemic analysis method was proposed by combining in silico absorption, distribution, metabolism, and excretion (ADME) evaluation, target fishing, network pharmacology technology, pathway analysis, and experimental verification to interpret the pharmacological mechanism of alcoholic compounds in Maotai liquor. Finally, 15 compounds with favorable pharmacokinetic profiles were screened through in silico ADME models. Thirty-eight related targets of these active compounds were identified by target prediction method. The network pharmacology and pathway analysis were developed to clarify the pharmacological effect of alcoholic compounds in Maotai liquor at the system and pathway level. Moreover, the key active compounds were validated by in vitro experiments that verified the effectiveness of our methods. Our study provides a novel approach to systematically analyze the pharmacological effect of alcoholic compounds in Maotai liquor, which would be beneficial for promoting the in-depth study of various liquors. PRACTICAL APPLICATION: Maotai liquor is popularly enjoyed in the world for a very long time. However, the systemic analysis of compounds in liquor is limited. Our systematic analysis approach was developed to explore the bioactive ingredients and their related target proteins as well as the pharmacological effects of Maotai liquor. This will provide a new method to understand the pharmacological mechanisms of compounds in various liquors at the systems level, so as to promote the development of liquors and to increase the public awareness of science about alcohol consumption.


Cerebral aneurysms of traumatic origin.
This report reviews 41 cases of traumatic cerebral aneurysms, including four cases of our own which are presented in detail. They may follow penetrating or closed head injury, and are usually associated with significant additional intracranial damage. Almost half of the patients presented with a delayed subarachnoid hemorrhage within three weeks of the initial head injury, defining an important neurological syndrome. Those patients whose post-traumatic aneurysms have been surgically obliterated have an associated mortality which is half that of patients treated by nonsurgical methods.


The English lexicon of interpersonal affect: Love, etc.
Three studies were conducted to determine some aspects of the semantic structure of words referring to positive interpersonal affect. Two studies determined dimensions of difference and families of related words on the basis of the target persons associated with each. These results were compared with those from sorting on the basis of overall similarity of meaning. There was close agreement among the three studies, using different samples of words, indices of similarity, and judges. The relation of the similarity structure of the words to the dimensions of affective experience and to discrete, basic, emotion is discussed.


Examination of Dosing of Antipsychotic Drugs for Relapse Prevention in Patients With Stable Schizophrenia: A Meta-analysis.
The doses of antipsychotic drugs needed for relapse prevention in schizophrenia is a debated issue. To examine dose-response findings in a meta-analysis of randomized clinical trials. Studies were identified through the Cochrane Schizophrenia Group's Study-Based Register of Trials (March 9, 2020), PubMed (January 1, 2021), and previous reviews. First authors and/or pharmaceutical companies were contacted for additional information. Two reviewers independently selected randomized clinical trials that compared fixed doses of a second-generation antipsychotic, haloperidol, or fluphenazine for relapse prevention in patients with stable schizophrenia. Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline, all parameters in duplicate were extracted and frequentist dose-response random-effects meta-analyses were conducted. Study-defined relapse (primary outcome), rehospitalization, Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale total score reduction from baseline, all-cause discontinuation, and dropouts due to adverse events. Evidence from 72 dose arms from 26 studies with 4776 participants was analyzed. The efficacy-related dose-response curves had a hyperbolic shape meaning that the probability to relapse decreased rapidly with doses of up to 5-mg/d risperidone equivalent (relative relapse risk, 0.43; 95% CI, 0.31-0.57; standardized mean difference for Positive and Negative Syndrome Scale total score reduction, -0.55; 95% CI, -0.68 to -0.41), but flattened thereafter. In contrast, dropouts due to adverse events continued to increase beyond this dose (relative risk at 5 mg/d, 1.38; 95% CI, 0.87-2.55; relative risk at 15 mg/d, 2.68; 95% CI, 1.49-4.62). In a subgroup analysis of patients in remission, a plateau was reached earlier, at approximately 2.5-mg/d risperidone equivalent. The findings of this meta-analysis suggest that doses higher than approximately 5-mg/d risperidone equivalent may provide limited additional benefit for relapse prevention but more adverse events. For patients in remission or who are receiving high-potency first-generation antipsychotics, doses as low as 2.5-mg/d risperidone equivalent may be sufficient. However, caution is needed at this low dose end when further decreases of dose may be accompanied by a disproportionally higher relapse risk. Moreover, the observations are averages, and factors such as slow or rapid metabolism, age, illness stage, comorbidities, and drug-drug interactions suggest that individual patients will often need higher or lower doses.


Identification and characterization of a gene required for alpha1,2-mannose extension in the O-linked glycan synthesis pathway in Schizosaccharomyces pombe.
The KTRalpha1,2-mannosyltransferase gene family of Saccharomyces cerevisiae is responsible not only for outer-chain modifications of N-linked oligosaccharides but also for elongation of O-linked mannose residues. To identify genes involved in the elongation step of O-linked oligosaccharide chains in Schizosaccharomyces pombe, we characterized six genes, omh1(+)-omh6(+), that share significant sequence similarity to the S. cerevisiae KTR family. Six deletion strains were constructed, each carrying a single disrupted omh allele. All strains were viable, indicating that none of the omh genes was essential. Heterologous expression of a chitinase from S. cerevisiae in the omh mutants revealed that O-glycosylation of chitinase had decreased in omh1Delta cells, but not in the other mutants, indicating that the other omh genes do not appear to be required for O-glycan synthesis. Addition of the second alpha1,2-linked mannose residue was blocked in omh1Delta cells. An Omh1-GFP fusion protein was found to be localized in the Golgi apparatus. These results indicate that Omh1p plays a major role in extending alpha1,2-linked mannose in the O-glycan pathway in S. pombe.


[Sensory neuropeptide SP modulating expression of EGF, FGF-2 and their receptors in fibroblasts of granulation in vivo and in vitro].
To study the modulating effect of sensory neuropeptide substance P (SP) on gene expression of epidermal growth factor (EGF), fibroblast growth factor-2 (FGF-2) and EGF receptor (EGFR), FGF receptor-1 (FGFR-1) in granulation fibroblast. The study consisted of two parts, in vivo and in vitro. In vivo, fifty wistar rats were randomly arranged into capsaicin group and control group. The rats in capsaicin group were subcutaneously injected with neurotoxin dose of capsaicin (50 mg/kg) on the back of the rats to chemically destroy sensory nerves to prevent the release of SP. After one week, full-thickness skin wounds were created on the rats' back. SP content and EGF, EGFR, FGF-2, FGFR-1 gene expression in the granulation tissue were observed using immunohistochemistry and in situ hybridization combined with image analysis on 3rd, 6th, 9th 12th after skin injury, respectively. The experimental procedure in control group were similar with that in capsaicin group except injection with capsaicin. In vitro, SP (10(-9)-10(-5) mol/L) was added into culture medium for cultured fibroblasts from granulation and mRNA expressions of EGF, FGF-2 and their receptors were assayed with RT-PCR. In the present study, immunoreactive stain for SP in granulation tissue were correlated with gene expression of EGF, FGF-2 and their receptors using in situ hybridization in vivo. Once sensory nerves were destroyed and SP release was inhibited in capsaicin group, the gene expression of above growth factors and their receptors were attenuated. SP concentrations in culture medium for upregulation of mRNA expressions of EGF and EGFR in cultured fibroblasts were from 10(-8) mol/L to 10(-6) mol/L and from 10(-6) mol/L to 10(-5) mol/L, respectively. SP concentration was from 10(-9) mol/L to 10(-5) mol/L for upregulation of FGF-2 mRNA expression in cultured fibroblasts and from 10(-6) mol/L to 10(-5) mol/L for upregulation of FGFR-1. Sensory neuropeptide SP released from sensory nerve participates in upregulation of gene expressions of EGF, EGF-2 and their receptors in granulation fibroblasts during wound healing.


Compliance, adverse events and antibiotic resistance in Helicobacter pylori treatment.
The highest H. pylori eradication rates have been reported with triple therapy, using metronidazole with amoxycillin or tetracycline, and colloidal bismuth subcitrate or bismuth subsalicylate. The use of such therapies, however, may be impeded by a number of major disadvantages, including reduced patient compliance, the incidence of adverse events and primary or acquired antibiotic resistance. Patient compliance is a particular problem with triple therapy owing to the quantity of drugs taken, treatment duration and regimen complexity; the eradication rate is reduced from 96% to 69% when only 60% of the medication is taken. The risk of adverse events resulting from the inclusion of antibiotics in the regimen is increased in triple therapy, and this generates reluctance in many practitioners to prescribe such therapy despite its well-documented efficacy. An important cause of antibiotic failure lies in the development of H. pylori resistance; between 6% and 27% of H. pylori strains are primarily resistant to the 5-nitroimidazoles--metronidazole and tinidazole--both of which are used in triple therapy. In contrast, no resistance of H. pylori to amoxycillin has been reported. The combination of an acid pump inhibitor with a single antibiotic represents a promising novel therapy for H. pylori-associated peptic ulcer disease. Treatment with omeprazole and amoxycillin could provide both rapid healing of ulcers and eradication of H. pylori, coupled with few adverse events, good drug compliance and low ulcer relapse rates, and may replace triple therapy as first-line medication.


CRP measurement: does the assay matter in hemodialysis patients?
The serum level of C-reactive protein, an acute-phase marker of systemic inflammation, has been shown to predict cardiovascular events in the general population and cardiovascular and total mortality in hemodialysis patients. High-sensitivity CRP assays (hs-CRP) have been used in numerous studies. We hypothesized that the level of CRP as measured by the conventional assay (c-CRP) would predict mortality in hemodialysis patients with an accuracy similar to that of high-sensitivity assays. In April 2001 CRP serum level was measured with both a conventional and a high-sensitivity assay in 102 prevalent hemodialysis patients. Mortality was prospectively monitored over 6 years. 49 patients (48%) died during follow-up. With both assays, almost 2/3 of patients had high CRP levels (> 1 mg/dl). Survival at 6 years was significantly lower in patients with high CRP levels, no matter which assay was used (31.5% for patients with high hs-CRP and 27.3% for patients with high c-CRP vs 48.4% for patients with low hs-CRP and 47.1% for patients with low c-CRP). Cardiovascular mortality was also higher in patients with high CRP levels, whatever the type of assay (conventional or high sensitivity) used. The correlation between the two tests was excellent. CRP level, measured by a conventional inexpensive assay, is predictive of mortality in hemodialysis patients.


A Simple and Versatile Amide Directing Group for C-H Functionalizations.
Achieving selective C-H activation at a single and strategic site in the presence of multiple C-H bonds can provide a powerful and generally useful retrosynthetic disconnection. In this context, a directing group serves as a compass to guide the transition metal to C-H bonds by using distance and geometry as powerful recognition parameters to distinguish between proximal and distal C-H bonds. However, the installation and removal of directing groups is a practical drawback. To improve the utility of this approach, one can seek solutions in three directions: 1) Simplifying the directing group, 2) using common functional groups or protecting groups as directing groups, and 3) attaching the directing group to substrates via a transient covalent bond to render the directing group catalytic. This Review describes the rational development of an extremely simple and yet broadly applicable directing group for Pd(II) , Rh(III) , and Ru(II) catalysts, namely the N-methoxy amide (CONHOMe) moiety. Through collective efforts in the community, a wide range of C-H activation transformations using this type of simple directing group have been developed.


FuzzyGap: Sequential Pattern Mining for Predicting Chronic Heart Failure in Clinical Pathways.
The rapid growth of electronic health records (EHRs) facilitates the use of clinical pathways, an actionable plan for patients which is represented as sequences of diagnostic records ordered by visit dates. We propose to extract discriminative and representative clinical pathways from EHRs using sequential pattern mining. However, existing sequential patterns cannot efficiently extract patterns due to patient variations in length and time period between visits. To resolve this problem, we propose FuzzyGap, a sequential pattern mining-based framework that extracts a discriminative subsequent pattern from the proper representation of the sequence of encounters which also emphasizes the last visit that is more significant than others. We demonstrate FuzzyGap using a case study of heart failure and show the effectiveness of sequential pattern mining.


Computational and biological analysis of 680 kb of DNA sequence from the human 5q31 cytokine gene cluster region.
With the human genome project advancing into what will be a 7- to 10-year DNA sequencing phase, we are presented with the challenge of developing strategies to convert genomic sequence data, as they become available, into biologically meaningful information. We have analyzed 680 kb of noncontiguous DNA sequence from a 1-Mb region of human chromosome 5q31, coupling computational analysis with gene expression studies of tissues isolated from humans as well as from mice containing human YAC transgenes. This genomic interval has been noted previously for containing the cytokine gene cluster and a quantitative trait locus associated with inflammatory diseases. Our analysis identified and verified expression of 16 new genes, as well as 7 previously known genes. Of the total of 23 genes in this region, 78% had similarity matches to sequences in protein databases and 83% had exact expressed sequence tag (EST) database matches. Comparative mapping studies of eight of the new human genes discovered in the 5q31 region revealed that all are located in the syntenic region of mouse chromosome 11q. Our analysis demonstrates an approach for examining human sequence as it is made available from large sequencing programs and has resulted in the discovery of several biomedically important genes, including a cyclin, a transcription factor that is homologous to an oncogene, a protein involved in DNA repair, and several new members of a family of transporter proteins.


Examining the most relevant conceptualization of the socioeconomic status construct for cancer research.
Although previous research has established a link between socioeconomic status (SES) and cancer outcomes, there is still little understanding of the processes that contribute to these outcome disparities. This study aimed to describe the ways a family's SES influences their healthcare behavior after a child is diagnosed with cancer. The sample included 5 case study families and in-depth interviews with 21 parents. Case study families were interviewed and observed once a month for 6 months. Parents' finances influenced their ability to maintain household expenses and to pay for healthcare expenses and household help. Wealth and help from friends and family are important aspects of families' financial statuses. Parents' educational attainment affected their ability to understand diagnosis and treatment options, their confidence and communication with healthcare professionals, and the utility of their social networks. Parents' occupation influenced their work schedule flexibility, fringe benefits, and their access to and quality of employer-sponsored health insurance. Findings suggest that 3 overarching domains of SES (eg, financial, education, and occupation) have important implications for parents' healthcare navigation. This study underscores the need to use a nuanced set of SES measures (beyond income and education) in future research to enhance our understanding of how SES affects healthcare navigation and refine intervention initiatives designed to help reduce health disparities. Cancer education initiatives should focus on enhancing patient-provider interactions, health communication, accessing health information, and resolving work and financial barriers to cancer care.


Knockdown of the lncRNA MALAT1 alleviates lipopolysaccharide‑induced A549 cell injury by targeting the miR‑17‑5p/FOXA1 axis.
Long‑noncoding RNAs (lncRNAs) are crucial for the pathophysiology of acute lung injury (ALI). Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) suppresses inflammatory responses via microRNA (miR)‑146a in lipopolysaccharide (LPS)‑induced ALI. However, the molecular mechanisms underlying the MALAT1‑mediated regulation of cell proliferation and apoptosis in LPS‑induced ALI remain unclear. In the present study, it was found that LPS treatment upregulated MALAT1 expression and suppressed the proliferation of A549 cells. MALAT1 knockdown significantly promoted the proliferation and G1/S phase transition and inhibited apoptosis in LPS‑treated A549 cells. In addition, miR‑17‑5p was a direct target of MALAT1. miR‑17‑5p expression was downregulated and FOXA1 expression was upregulated in LPS‑treated A549 cells. Further, MALAT1 knockdown promoted miR‑17‑5p expression and inhibited FOXA1 expression, whereas the combined suppression of MALAT1 and miR‑17‑5p induced FOXA1 expression. Moreover, miR‑17‑5p knockdown reversed the effects of MALAT1 suppression on LPS‑induced A549 cell proliferation. These results indicated that MALAT1 serves as a competing endogenous lncRNA that, by sequestering miR‑17‑5p, stimulates FOXA1 expression and mediates LPS‑induced A549 cell injury. In conclusion, the present study demonstrated that MALAT1 knockdown alleviates LPS‑induced A549 cell injury by targeting the miR‑17‑5p/FOXA1 axis.


Risk factors for cardiovascular disease in pediatric renal transplant recipients.
About 1,000 children develop end-stage renal disease (ESRD) each year in the United States and about 5,000 children are currently receiving dialysis. Children who develop ESRD are eligible to receive renal replacement therapy, including renal transplantation. There are inherent risks associated with transplantation, including renal insufficiency, infections, post-transplant lymphoproliferative disorder, and cardiovascular disease (CVD). Potential risk factors for CVD in pediatric renal transplant recipients include renal insufficiency, hyperlipidemia, hyperhomocysteinemia, inflammation, malnutrition, anemia, and hyperglycemia/insulin resistance. Despite evidence that many children may possess various risk factors for CVD post-renal transplantation, there are very few studies that have attempted to assess the link between these risk factors and CVD in pediatric renal transplant recipients.


A Highly Versatile Expression System for the Production of Multiply Phosphorylated Proteins.
Genetic Code Expansion (GCE) can use TAG stop codons to guide site-specific incorporation of phosphoserine (pSer) into proteins. To eliminate prematurely truncated peptides, improve yields, and enhance the production of multiphosphorylated proteins, Release Factor 1 (RF1)-deficient expression hosts were developed, yet these grew slowly and their use was associated with extensive misincorporation of natural amino acids instead of pSer. Here, we merge a healthy RF1-deficient E. coli cell line with a high-efficiency pSer GCE translation system to produce a versatile pSer GCE platform in which only trace misincorporation of natural amino acids is detected even when five phosphoserines were introduced into one protein. Approximately 400 and 200 mg of singly and doubly phosphorylated GFP per liter of culture were obtained. Importantly, the lack of truncated protein permits expression of oligomeric proteins and the use of N-terminal solubility-enhancing proteins to aid phospho-protein expression and purification. To illustrate the enhanced utility of this system, we produce doubly phosphorylated STING (Stimulator of Interferon Genes), as well as triply phosphorylated BAD (Bcl2-associated agonist of cell death) complexed with 14-3-3, in quantity, purity, and homogeneity sufficient for structural biology applications. We anticipate that the facile access to phosphoproteins enabled by this system, which we call pSer-3.1G, will expand studies of the phospho-proteome.


Polyfluorides and Neat Fluorine as Host Material in Matrix-Isolation Experiments.
The use of neat fluorine in matrix isolation is reported, as well as the formation of polyfluoride monoanions under cryogenic conditions. Purification procedures and spectroscopic data of fluorine are described, and matrix shifts of selected molecules and impurities in solid fluorine are compared to those of common matrix gases (Ar, Kr, N2 , Ne). The reaction of neat fluorine and IR-laser ablated metal atoms to yield fluorides of chromium (CrF5 ), palladium (PdF2 ), gold (AuF5 ), and praseodymium (PrF4 ) has been investigated. The fluorides have been characterized in solid fluorine by IR spectroscopy at 5 K. Also the fluorination of Kr and the photo-dismutation of XeO4 have been studied by using IR spectroscopy in neat fluorine. Formation of the [F5 ](-) ion was obtained by IR-laser ablation of platinum in the presence of fluorine and proven in a Ne matrix at 5 K by two characteristic vibrational bands of [F5 ](-) at $\tilde \nu $=850.7 and 1805.0 cm(-1) and its photo-behavior.


Sensitization of sarcoma cells to doxorubicin treatment by concomitant wild-type adeno-associated virus type 2 (AAV-2) infection.
Doxorubicin-based chemotherapy is used in the treatment of sarcomas. Toxic side effects and poor response rates underline the demand for an improvement in current chemotherapeutic protocols. Recently, it has been reported that parvoviruses confer various antineoplastic properties to infected cells, and that adeno-associated virus type 2 (AAV-2) infection sensitizes malignant epithelial cells to radiation- or chemotherapy-based genotoxic treatment. Thus, we analyzed whether AAV-2 infection leads to an improved efficacy of doxorubicin chemotherapy in malignant mesenchymal cells, using 13 human sarcoma cell lines. Therapeutic effects were analyzed by measuring cell viability and proliferation (WST-1, colony forming, and propidium iodide assays). Additionally, permissivity for AAV-2 infection was determined by Southern dot blot analysis. AAV-2 infection strongly increased the efficacy of doxorubicin treatment in rhabdomyo-, fibro-, osteo- and chondrosarcoma cells in a dose-dependent manner. This effect was not observed in liposarcoma and synovial sarcoma cells, although a susceptability to AAV-2 infection was documented. Our results indicate that the sensitization effects towards genotoxic treatment exerted by non-pathogenic AAV-2 infection are not restricted to epithelial malignancies but may also be exploited for the improvement of chemotherapy in patients suffering from rhabdomyo-, fibro-, osteo-, or chondrosarcomas.


[Evaluation of vascular function in patients with Fabry disease].
To evaluate the endothelial functions and autoregulation capacity of cerebral blood flow in patients with Fabry disease. Brachial artery vasodilation was assessed in 8 patients with Fabry disease and 14 healthy controls by means of flow-mediated dilation (FMD) and Nitroglycerin-mediated dilation (NMD). Cerebrovascular reactivity was calculated in terms of breath-holding index (BHI) and vascular motor reactivity (VMR) by TCD-CO2 test in 4 patients and 14 healthy controls. Compared with the controls, brachial artery vasodilation experiment showed no difference (the patients: FMD 15.94%±5.03% and NMD 23.92%±7.23%, the controls: FMD 14.57%±5.84% and NMD 22.64%±6.96%), there was no relationship between FMD or NMD and the age, course of disease, MSSI or enzyme activity. In respect of cerebrovascular autoregulation capacity, there was no difference in anterior circulation, while cerebrovascular reactivity tended to be impaired in posterior circulation. Endothelial function showed no decline in patients with Fabry disease, but cerebrovascular autoregulation capacity tended to be impaired in posterior circulation.


A simple diagnostic index comprising epithelial membrane antigen and fibronectin for hepatocellular carcinoma.
Background and rationale for the study. Continuing search for suitable tumor-markers is of clinical value in managing patients with various malignancies. These markers may be presented as intracellular substances in tissues or may be released into the circulation and appear in serum. Therefore, this work is concerned with identification and quantitative determination of epithelial membrane antigen (EMA) and fibronectin and estimating their performances as surrogate markers for identifying hepatocellular carcinoma (HCC). A total of 627 individuals constituted this study [fibrosis (F1-F3) = 217; cirrhosis = 191; HCC = 219]. Western-blot was used for identifying EMA and fibronectin in sera. As a result, a single immunoreactive band was shown at 130-kDa and 90-kDa corresponding to EMA and fibronectin, respectively. They were quantified using ELISA providing values in HCC higher than fibrosis or cirrhosis with a significant difference (P < 0.0001). For identifying HCC, EMA showed 0.82 area under receiver-operating characteristic curve (AUC) with sensitivity = 70% and specificity = 78% while fibronectin yielded AUC = 0.70 with sensitivity = 67% and specificity = 82%. FEBA-Test comprising fibronectin and EMA together with total-bilirubin and AFP was constructed yielding AUC = 0.92 for identifying HCC from cirrhosis with sensitivity = 89% and specificity = 85%. FEBA-Test was then tested for differentiating HCC from fibrosis showing AUC = 0.97 with sensitivity = 90% and specificity = 89%. FEBA-Test enabled the correct identification of HCC patients with CLIP 0-1 and size ≤ 3 cm with AUC = 0.80 and AUC = 0.84, respectively, indicating its ability in identifying early HCC. A four-marker index may improve the early detection of HCC with a high degree of accuracy.


Ischemic electrocardiographic abnormalities and prognosis in decompensated heart failure.
Identification of coronary ischemia may enable targeted diagnostic and therapeutic strategies for acute heart failure. We determined the risk of 30-day mortality associated with ischemic ECG abnormalities in patients with acute heart failure. Among 8772 patients (53.4% women, median 78 years [Q1, Q3: 68,84]) presenting with acute heart failure to 86 hospital emergency departments in Ontario, Canada, Q-waves, T-wave inversion, or ST-depression were present in 51.8% of subjects. However, presence of ST-depression was the only finding associated with 30-day mortality with adjusted odds ratio 1.24 (95% confidence interval [CI], 1.02-1.50). Using continuous net reclassification improvement, addition of ST-depression to the Emergency Heart failure Mortality Risk Grade model reclassified 16.9% of patients overall, and 29.3% of those with a history of ischemic heart disease (both P<0.001). By adding ST-depression to the model, the Emergency Heart failure Mortality Risk Grade was extended to predict 30-day death with high discrimination (c-statistic 0.801), with 0.57% mortality rate in the lowest risk decile. Adjusted odds ratios for 30-day mortality were 2.81 (95% CI, 1.48-5.31; P=0.002) in quintile 2, 7.41 (95% CI, 4.13-13.30; P<0.001) in quintile 3, and 14.47 (95% CI, 8.20-25.54; P<0.001) in quintile 4 compared with the lowest risk quintile. When the highest risk quintile was subdivided into 2 equally sized risk strata (deciles 9 and 10), the adjusted odds ratios for 30-day mortality were 27.20 (95% CI, 15.33-48.27; P<0.001) in decile 9 and 58.96 (95% CI, 33.54-103.65; P<0.001) in highest risk decile 10. Presence of ST-depression on the ECG reclassified risk of 30-day mortality in patients with acute heart failure, identifying both high- and low-risk subsets.


BB0562 is a nutritional virulence determinant with lipase activity important for Borrelia burgdorferi infection and survival in fatty acid deficient environments.
The Lyme disease spirochete Borrelia burgdorferi relies on uptake of essential nutrients from its host environments for survival and infection. Therefore, nutrient acquisition mechanisms constitute key virulence properties of the pathogen, yet these mechanisms remain largely unknown. In vivo expression technology applied to B. burgdorferi (BbIVET) during mammalian infection identified gene bb0562, which encodes a hypothetical protein comprised of a conserved domain of unknown function, DUF3996. DUF3996 is also found across adjacent encoded hypothetical proteins BB0563 and BB0564, suggesting the possibility that the three proteins could be functionally related. Deletion of bb0562, bb0563 and bb0564 individually and together demonstrated that bb0562 alone was important for optimal disseminated infection in immunocompetent and immunocompromised mice by needle inoculation and tick bite transmission. Moreover, bb0562 promoted spirochete survival during the blood dissemination phase of infection. Gene bb0562 was also found to be important for spirochete growth in low serum media and the growth defect of Δbb0562 B. burgdorferi was rescued with the addition of various long chain fatty acids, particularly oleic acid. In mammals, fatty acids are primarily stored in fat droplets in the form of triglycerides. Strikingly, addition of glyceryl trioleate, the triglyceride form of oleic acid, to the low serum media did not rescue the growth defect of the mutant, suggesting bb0562 may be important for the release of fatty acids from triglycerides. Therefore, we searched for and identified two canonical GXSXG lipase motifs within BB0562, despite the lack of homology to known bacterial lipases. Purified BB0562 demonstrated lipolytic activity dependent on the catalytic serine residues within the two motifs. In sum, we have established that bb0562 is a novel nutritional virulence determinant, encoding a lipase that contributes to fatty acid scavenge for spirochete survival in environments deficient in free fatty acids including the mammalian host.


Patterning Superconductivity in a Topological Insulator.
Topologically protected states in combination with superconductivity hold great promise for quantum computing applications, but the progress on electrical transport measurements in such systems has been impeded by the difficulty of fabricating devices with reliable electrical contacts. We find that superconductivity can be patterned directly into Bi2Se3 nanostructures by local doping with palladium. Superconducting regions are defined by depositing palladium on top of the nanostructures using electron beam lithography followed by in situ annealing. Electrical transport measurements at low temperatures show either partial or full superconducting transition, depending on the doping conditions. Structural characterization techniques indicate that palladium remains localized in the targeted areas, making it possible to pattern superconducting circuits of arbitrary shapes in this topological material.


The Effect of Jacobson's Progressive Relaxation Technique on Postoperative Pain, Activity Tolerance, and Sleeping Quality in Patients Undergoing Gynecological Surgery.
Inadequate pain management and sleep disturbances of patients undergoing gynecological surgery are associated with delayed recovery time. This study aimed to assess the effect of Jacobson's Progressive Relaxation Technique (JPRT) on postoperative pain, activity tolerance, and sleeping quality in patients undergoing gynecological surgery. A randomized controlled clinical trial conducted at Obstetrics and Gynecology Department/Damanhour educational institute, Elbehira, Egypt. The study sample involved 116 patients undergoing gynecological surgery who were equally distributed between intervention and control groups. Data collected from April to September 2019. Four tools were used for data collection: Demographic data interview schedule, pain analog scale, activity tolerance questionnaire, and the Groningen sleeping quality scale. For the intervention group, the women were asked to perform JPRT for 30 min on the second and third postoperative day, three times a day. SPSS 23.0 is used to analyze data using Chi-square, Fisher's exact, independent t-test, and Analysis of Covariance (ANCOVA). A significance level considered at p < 0.05. The study results showed that JPRT significantly improves pain, sleep quality, and activity tolerance mean scores among the intervention group compared to the control group (F1 = 119.13, p < 0.001), (F1 = 361.49, p < 0.001), and (F1 = 157.49, p < 0.001), respectively. ANCOVA results showed that 33% of the decreased pain score, 12% of decreased sleeping quality score, and 26% of improved activity tolerance score are due to JPRT. JPRT should be offered as a part of standard postoperative nursing care for patients undergoing gynecological surgery to control pain and improve sleeping quality and activity tolerance.


Trastuzumab-induced myocardiotoxicity mimicking acute coronary syndrome.
Trastuzumab is an important biological agent in the treatment of HER2-positive breast cancer, with effects on response rates, progression-free survival, overall survival and quality of life. Although this drug is well tolerated in terms of adverse effects, trastuzumab-associated myocardiotoxicity has been described to have an incidence of 0.6-4.5% and in rare cases, the drug can trigger severe congestive heart failure with progression to death or even mimic acute coronary syndrome with complete left bundle branch blockade. In this paper is reported a case of trastuzumab-associated myocardiotoxicity manifesting as acute coronary syndrome in a 69-year-old female. The patient is currently undergoing a conservative clinical treatment that restricts overexertion.The majority of clinical studies report trastuzumab-induced cardiotoxicity as a rare event, and, when present, characterized by mild to moderate clinical signs, the ease of reversibility with pharmacological measures and the temporary discontinuation of the medication. Conversely, it is vital for the oncologist/cardiologist to consider the possibility that trastuzumab-induced cardiotoxicity may manifest itself as a severe clinical case, mimicking acute coronary syndrome, justifying careful risk stratification and adequate cardiac monitoring, especially in high-risk patients.


Online spike-based recognition of digits with ultrafast microlaser neurons.
Classification and recognition tasks performed on photonic hardware-based neural networks often require at least one offline computational step, such as in the increasingly popular reservoir computing paradigm. Removing this offline step can significantly improve the response time and energy efficiency of such systems. We present numerical simulations of different algorithms that utilize ultrafast photonic spiking neurons as receptive fields to allow for image recognition without an offline computing step. In particular, we discuss the merits of event, spike-time and rank-order based algorithms adapted to this system. These techniques have the potential to significantly improve the efficiency and effectiveness of optical classification systems, minimizing the number of spiking nodes required for a given task and leveraging the parallelism offered by photonic hardware.


SARS-CoV-2 Infection of Airway Epithelial Cells.
Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide since its outbreak in December 2019, and World Health Organization declared it as a pandemic on March 11, 2020. SARS-CoV-2 is highly contagious and is transmitted through airway epithelial cells as the first gateway. SARS-CoV-2 is detected by nasopharyngeal or oropharyngeal swab samples, and the viral load is significantly high in the upper respiratory tract. The host cellular receptors in airway epithelial cells, including angiotensin-converting enzyme 2 and transmembrane serine protease 2, have been identified by single-cell RNA sequencing or immunostaining. The expression levels of these molecules vary by type, function, and location of airway epithelial cells, such as ciliated cells, secretory cells, olfactory epithelial cells, and alveolar epithelial cells, as well as differ from host to host depending on age, sex, or comorbid diseases. Infected airway epithelial cells by SARS-CoV-2 in ex vivo experiments produce chemokines and cytokines to recruit inflammatory cells to target organs. Same as other viral infections, IFN signaling is a critical pathway for host defense. Various studies are underway to confirm the pathophysiological mechanisms of SARS-CoV-2 infection. Herein, we review cellular entry, host-viral interactions, immune responses to SARS-CoV-2 in airway epithelial cells. We also discuss therapeutic options related to epithelial immune reactions to SARS-CoV-2.


Cut-off values of visceral fat area and waist circumference: diagnostic criteria for abdominal obesity in a Korean population.
The aim of this study was to determine the appropriate cut-off values for visceral fat area and waist circumference (WC) associated with an increase in risk for obesity-related disorder, and to validate diagnostic criteria for abdominal obesity and the metabolic syndrome in a Korean adult population. We included 413 subjects (174 men and 239 women) for this study. Subjects were selected among Korean adults who visited the obesity clinic at St. Mary's Hospital and Kangnam St. Mary's Hospital from January 1999 to August 2005. All patients had computed tomography performed. The cut-off value, of visceral fat area associated with an increase risk of obesity-related disorder, according to the receiver operating characteristics curve, was 103.8 cm2 (sensitivity 74.5%, specificity 64.7%, p<0.001). The cut-off value for the WC was 89.8 cm in men (sensitivity 84.7%, specificity 91.7%, p<0.005) and 86.1 cm in women (sensitivity 83.9%, specificity 62.9%, p<0.001). Based on the results of this study, the visceral fat area associated with an increased risk of obesity-related disorder in Korea was 103.8 cm2 and the WC was 89.8 cm in men and 86.1 cm in women.


Inhibition of fast anterograde axoplasmic transport by a pressure barrier. The effect of pressure gradient and maximal pressure.
Fast anterograde axoplasmic transport was studied in the motor fibres of the vagus nerve of rabbits in vitro at 22 degrees C with a pressure barrier applied to a small section of the nerve. The barrier was characterized by the maximal pressure and the gradients on each side of the maximum. The range tested was 16 to 45 mmHg maximal pressure and 30 to 140 mmHg/mm length of nerve for the pressure gradients. It was found that in the ranges tested the maximal pressure was of major importance for the inhibition of transport, the pressure gradient being of little significance. The results indicate that at least one part of fast anterograde axoplasmic transport occurs within collapsible canalicular structures.


Anion effects on kinetics and thermodynamics of CO2 absorption in ionic liquids.
A thermogravimetric technique based on a magnetic suspension balance operating in dynamic mode was used to study the thermodynamics (in terms of solubility and Henry's law constants) and kinetics (i.e., diffusion coefficients) of CO2 in the ionic liquids [bmim][PF6], [bmim][NTf2], and [bmim][FAP] at temperatures of 298.15, 308.15, and 323.15 K and pressures up to 20 bar. The experimental technique employed was shown to be a fast, accurate, and low-solvent-consuming method to evaluate the suitability of the ionic liquids (ILs) to be used as CO2 absorbents. Thermodynamic results confirmed that the solubility of CO2 in the ILs followed the order [bmim][FAP] > [bmim][NTf2] > [bmim][PF6], increasing with decreasing temperatures and increasing pressures. Kinetic data showed that the diffusion coefficients of CO2 in the ILs followed a different order, [bmim][NTf2] > [bmim][FAP] > [bmim][PF6], increasing with increasing temperatures and pressures. These results evidenced the different influence of the IL structure and operating conditions on the solubility and absorption rate of CO2, illustrating the importance of considering both thermodynamic and kinetic aspects to select adequate ILs for CO2 absorption. On the other hand, the empirical Wilke-Chang correlation was successfully applied to estimate the diffusion coefficients of the systems, with results indicating the suitability of this approach to foresee the kinetic performance of ILs to absorb CO2. The research methodology proposed herein might be helpful in the selection of efficient absorption solvents based on ILs for postcombustion CO2 capture.


[New targets of antiphospholipid antibodies].
"Antiphospholipid" antibodies (aPL) are a heterogenous group of autoantibodies with clinical importance because of their association with thrombotic events, both venous and arterial. Traditionally, aPL have been assayed using phospholipid-dependent tests and are classified as lupus anticoagulants and anticardiolipin antibodies (ACA), based on the method of detection. Most antibodies associated with the aPL syndrome and detected in standard assays are actually directed against two phospholipid-binding plasma proteins, beta 2 glycoprotein I and prothrombin. These antibodies can also be detected in immunoassays (ELISA) utilizing purified protein antigens, in the absence of phospholipids. The main advantage of beta 2 GPI-ELISA compared with conventional cardiolipin-ELISA appearing from initial clinical studies is greater specificity for the aPL syndrome, due to (i) ignorance of "authentic" ACA that interact directly with cardiolipin; (ii) detection of species specific anti-beta 2 GPI antibodies poorly reactive with bovine beta 2 GPI in the cardiolipin-ELISA. Other proteins proposed as target antigens of aPL are protein C, protein S, annexin V, high- and low-molecular weight kininogens, the latter being involved in the binding of antibodies to phosphatidylethanolamine. The possibility that particular autoantibodies (or combinations of autoantibodies) explain the observed clinical spectrum of the aPL syndrome is attractive, but much remains to be learned about their pathogenicity and origin in order to improve diagnosis and therapy.


[Polymorphic loci and polymorphism analysis of short tandem repeats within XNP gene].
To select polymorphic short tandem repeat markers within X-linked nuclear protein (XNP) gene, genomic clones which contain XNP gene were recognized by homologous analysis with XNP cDNA. By comparing the cDNA with genomic DNA, non-exonic sequences were identified, and short tandem repeats were selected from non-exonic sequences by using BCM search Launcher. Polymorphisms of the short tandem repeats in Chinese population were evaluated by PCR amplification and PAGE. Five short tandem repeats were identified from XNP gene, two of which were polymorphic. Four and 11 alleles were observed in Chinese population for XNPSTR1 and XNPSTR4, respectively. Heterozygosities were 47% for XNPSTR1 and 70% for XNPSTR4. XNPSTR1 and XNPSTR4 localized within 3' end and intron 10, respectively. Two polymorphic short tandem repeats have been identified within XNP gene and will be useful for linkage analysis and gene diagnosis of XNP gene.


(2'-5')oligo(A) synthetase as a monitor of interferon action in juvenile laryngeal papillomatosis.
Four children with juvenile laryngeal papillomatosis were treated with human leukocyte interferon (IFN-alpha) by intravenous infusions. In three cases the clinical course of the disease was effected favorably. Serum IFN titers and (2'-5')oligo(A) synthetase (OAS) levels in lymphocytes of the patients were measured once a week during therapy. Levels of serum IFN determined 15 min after the end of 1 h infusions corresponded to only 15%-40% of the amount infused. Comparable OAS activities in the four children were measured before infusion, i.e., one, two, or three days, respectively, after the preceding infusion, though mean IFN titers of the patients differed from each other (200-400 and 400-600 u/ml). This suggests a saturation of the lymphocytes' antiviral system by these IFN levels. A discontinuation for two weeks in the early phase of IFN treatment, accompanied by a decrease of the OAS activity in the lymphocytes to the basal level, resulted in a deterioration of the patient's condition. A change in treatment schedule causing a decrease of OAS activity to a lower, though still elevated level, for six weeks until the present did not influence the course of therapy. Therefore, we suppose that the maintenance of elevated levels of OAS activity in lymphocytes for some months may be a necessary, even though not always a sufficient, criterion for a successful therapy schedule in IFN treatment of juvenile laryngeal papillomatosis. In addition, our results suggest OAS activity to be suitable in monitoring effects of an IFN therapy.


Developments in clinical neuropsychology: implications for school psychological services.
According to the 2000 Report of the Surgeon General's Conference on Children's Mental Health, a significant percentage of children and adolescents have emotional or behavioral problems serious enough to merit a mental health diagnosis. The No Child Left Behind Act of 2001 and the Individuals With Disabilities Education Improvement Act of 2004 reemphasized the schools' importance in supporting cognitive and behavioral development in students, particularly those identified with learning problems. In this article, we examine the growing specialty of clinical neuropsychology and provide suggestions for integrating this field into school-based psychological services. This article provides a review of the neuropsychological bases for many childhood learning disorders and addresses how school psychologists can work with clinical neuropsychologists to better address the needs of exceptional children through neuropsychological testing. There is substantial neurological evidence for attention-deficit hyperactivity disorder as well as disorders of reading, language, and mathematics. Close collaborative partnerships between clinical neuropsychologists and school psychologists will help develop assessment protocols that are likely to result in more effective intervention services for students with neuropsychological conditions. Schools are being asked to support the physical, cognitive, and emotional development in students, particularly those identified with chronic physical and mental health challenges. Dissatisfaction with minimal screenings, the growing awareness of the neurology of learning disorders, and the passage of the Individuals With Disabilities Education Improvement Act of 2004 obliges all school-based mental health providers to consider how to fully integrate the tools of clinical neuropsychology into school-based psychological services.


Enhanced Internal Quantum Efficiency in Dye-Sensitized Solar Cells: Effect of Long-Lived Charge-Separated State of Sensitizers.
Effective charge separation is one of the key determinants for the photovoltaic performance of the dye-sensitized solar cells (DSSCs). Herein, two charge-separated (CS) sensitizers, MTPA-Pyc and YD-Pyc, have been synthesized and applied in DSSCs to investigate the effect of the CS states of the sensitizers on the device's efficiency. The CS states with lifetimes of 64 and 177 ns for MTPA-Pyc and YD-Pyc, respectively, are formed via the photoinduced electron transfer (PET) from the 4-styryltriphenylamine (MTPA) or 4-styrylindoline (YD) donor to the pyrimidine cyanoacrylic acid (Pyc) acceptor. DSSCs based on MTPA-Pyc and YD-Pyc exhibit high internal quantum efficiency (IQE) values of over 80% from 400 to 600 nm. In comparison, the IQEs of the charge transfer (CT) sensitizer cells are 10-30% lower in the same wavelength range. The enhanced IQE values in the devices based on the CS sensitizers are ascribed to the higher electron injection efficiencies and slower charge recombination. The results demonstrate that taking advantage of the CS states in the sensitizers can be a promising strategy to improve the IQEs and further enhance the overall efficiencies of the DSSCs.


Biphenylene and Phagraphene as Lithium Ion Battery Anode Materials.
We present results of density functional theory calculations on the lithium (Li) ion storage capacity of biphenylene (BP) membrane and phagraphene (PhG) which are two-dimensional defected-graphene-like membranes. Both membranes show a larger capacity than graphene, Li2C6 and Li1.5C6 compared to LiC6. We find that Li is very mobile on these materials and does not interact as strongly with the membranes. In the case of BP we also investigated the possible volume expansion on Li insertion. We find a 11% expansion, which is very similar to the one found in graphite. Our findings show that both membranes are suitable materials for lithium ion battery anodes.


[Bacteriologic characteristics of 25 strains of Vibrio cholerae, biotype eltor isolated in Mali].
This work studies bacteriological characters of 25 strains of V. cholerae isolated in Mali during the outbreak of 1984-1987. These strains were precisely identified by biochemistry characters, toxin secretion, presence of a structure considered as attachment factor. Antibiotic susceptibility study confirmed the great sensibility of V. cholerae to this products, and allowed to classify them according to their Cl90. This contribution of the laboratory is very interesting for the control of the disease and the choice of standardized scheme of treatment.


Nitrite conversion to nitric oxide in red cells and its stabilization as a nitrosylated valency hybrid of hemoglobin.
The authors describe a method for the preparation, isolation and purification from human red blood cells of a stable form of hemoglobin containing both oxidized and reduced subunits. After isoelectric focusing across a pH gradient, it occupies the same position as the synthetically reconstituted or chemically generated species, (alpha 2+ beta 3+)2 (I). Unlike its synthetic or chemically generated counterpart, however, it (HbX) does not bind oxygen. A different method for the preparation in situ of the (alpha 3+ beta 2+)2 valency hybrid results in a pigment with chemical and spectral properties identical with those ascribed to its synthetically reconstituted counterpart, and both bind oxygen. HbX is generated in highest yield when red cells are incubated under N2 in the presence of glucose, methylene blue and nitrite for several hours. Its visible absorption spectrum differs from that reported for I, and it reacted very slowly with ferricyanide. Exposure to CO did not result in spectral shifts over that for HbX in air, but spectral shifts were produced with CO exposure of (alpha 3+ beta 2+)2. HbX had an inositol hexaphosphate difference-binding spectrum quite unlike that described for I. HbX also had a distinctive electron paramagnetic resonance spectrum that shifted after inositol hexaphosphate addition with a new three-line hyperfine pattern. Both spectra were characteristic for an unpaired electron in an iron-centered orbital with a hyperfine coupling to the nitrogen nuclear spin of a nitrosyl ligand on heme iron. The authors conclude that HbX is a form of I, but it has NO bound to its reduced subunits.


Airway symptoms and biological markers in nasal lavage fluid in subjects exposed to metalworking fluids.
Occurrence of airway irritation among industrial metal workers was investigated. The aims were to study the association between exposures from water-based metal working fluids (MWF) and the health outcome among the personnel, to assess potential effects on the proteome in nasal mucous membranes, and evaluate preventive actions. The prevalence of airway symptoms related to work were examined among 271 metalworkers exposed to MWF and 24 metal workers not exposed to MWF at the same factory. At the same time, air levels of potentially harmful substances (oil mist, morpholine, monoethanolamine, formaldehyde) generated from MWF was measured. Nasal lavage fluid was collected from 13 workers and 15 controls and protein profiles were determined by a proteomic approach. Airway symptoms were reported in 39% of the workers exposed to MWF although the measured levels of MWF substances in the work place air were low. Highest prevalence was found among workers handling the MWF machines but also those working in the same hall were affected. Improvement of the ventilation to reduce MWF exposure lowered the prevalence of airway problems. Protein profiling showed significantly higher levels of S100-A9 and lower levels of SPLUNC1, cystatin SN, Ig J and β2-microglobulin among workers with airway symptoms. This study confirms that upper airway symptoms among metal workers are a common problem and despite low levels of MWF-generated substances, effects on airway immune proteins are found. Further studies to clarify the role of specific MWF components in connection to airway inflammation and the identified biological markers are warranted.


Influence of beta-adrenoceptor agonists and antagonists on baclofen-induced memory impairment in mice.
Post-training administration of different doses of baclofen (a GABAB agonist) has been shown to impair memory retention, in a step-down passive avoidance test in mice. We have studied the effects of beta-adrenergic agonists and antagonists on baclofen-induced memory impairment in mice. Dobutamine (a beta 1-agonist) or salbutamol (a beta 2-agonist) reversed the memory impairment induced by baclofen without exhibiting intrinsic actions on memory when administered alone. The administration of atenolol (a beta 1-antagonist) or propranolol (a beta-antagonist) produced a memory impairment. When co-administered with baclofen, both atenolol and propranolol exacerbated the memory impairment induced by the GABAB agonist. It is concluded that beta-adrenergic mechanisms may be involved in the modulation of memory via GABAB receptors.


Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy.
Bacterial infections are a major cause of morbidity and mortality in neutropenic patients following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in decreasing the incidence of bacterial infections, but not in reducing mortality rates. This review aimed to evaluate whether antibiotic prophylaxis in afebrile neutropenic patients reduced mortality when compared to placebo or no intervention. Electronic searches on The Cochrane Cancer Network Register of Trials (2004), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to 2004) and EMBASE (1980 to 2004) and abstracts of conference proceedings; references of identified studies; the first author of each included trial was contacted. RCTs or quasi-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic to prevent bacterial infections in afebrile neutropenic patients. Two authors independently appraised the quality of each trial and extracted data from the included trials. Relative risks (RR) or average differences, with their 95% confidence intervals (CI) were estimated. One hundred trials (10,274 patients) performed between the years 1973 to 2004 met inclusion criteria. Antibiotic prophylaxis significantly decreased the risk for death when compared with placebo or no intervention (RR, 0.66 [95% CI 0.54 to 0.81]). The authors estimated the number needed to treat (NNT) in order to prevent 1 death from all causes as 60 (95% CI 34 to 268). Prophylaxis resulted in a significant decrease in the risk of infection-related death, RR 0.58 (95% CI 0.45 to 0.74) and in the occurrence of fever, RR 0.78 (95% CI 0.75 to 0.82). A reduction in mortality was also evident when the more recently conducted quinolone trials were analysed separately. Quinolone prophylaxis reduced the risk for all-cause mortality, RR 0.52 (95% CI, 0.37 to 0.84). Our review demonstrated that prophylaxis significantly reduced all-cause mortality. The most significant reduction in mortality was observed in trials assessing prophylaxis with quinolones. The benefit demonstrated in our review outweighs harm, such as adverse effects, and development of resistance, since all-cause mortality is reduced. Since most trials in our review were of patients with haematologic cancer, prophylaxis, preferably with a quinolone, should be considered for these patients.


[The ideal image and sex role norms in the Giessen Test].
This study was intended to test the assumption whether the ideal-image measure within the Giessen-Test reflects the specific personality as hypothesized by psychoanalytic theory or a general norm-orientation. To test this assumptions the items of the Giessen-Test were transformed an submitted to random samples of in- and out-patients. The results clearly indicate that the ideal-image as measured by the Giessen-Test is a general norm-orientation and consists of the dimensions "social-acknowledgement" and "capability of binding". Within the second dimension there seems to be a gender difference. Additional analysis of variance and Cronbachs alpha indicate that differences between in- and out-patients are the result of a possible "curative effect".


The interaction of temporal generalization gradients predicts the context effect.
In a temporal double bisection task, animals learn two discriminations. In the presence of Red and Green keys, responses to Red are reinforced after 1-s samples and responses to Green are reinforced after 4-s samples; in the presence of Blue and Yellow keys, responses to Blue are reinforced after 4-s samples and responses to Yellow are reinforced after 16-s samples. Subsequently, given a choice between Green and Blue, the probability of choosing Green increases with the sample duration-the context effect. In the present study we asked whether this effect could be predicted from the stimulus generalization gradients induced by the two basic discriminations. Six pigeons learned to peck Green following 4-s samples (S(+)) but not following 1-s samples (S(-)) and to peck Red following 4-s samples (S(+)) but not following 16-s samples (S(-)). Temporal generalization gradients for Green and Red were then obtained. Finally, the pigeons were given a choice between Green and Red following sample durations ranging from 1 to 16 s. Results showed that a) the two generalization gradients had the minimum at the S(-) duration, an intermediate value between the S(-) and the S(+) durations, and the maximum at the S(+) as well as more extreme durations; b) on choice trials, preference for Green over Red increased with sample duration, the context effect; and c) the two generalization gradients predicted the average context effect well. The Learning-to-Time model accounts for the major trends in the data.


Variants of human papillomavirus types 16 and 18: histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in cervical smear.
Human papillomavirus (HPV) genotypes cannot fully explain the histological diagnosis of women with glandular abnormalities detected by cervical smear. Thus, this study was designed to analyze the distribution of HPV-16 and HPV-18 variants in women referred because of atypical glandular cells and adenocarcinoma in situ in their cervical smears and its association with histological results. Twenty-four women with HPV-16 and 6 with HPV-18, selected from 160 women with cervical smears suggestive of glandular abnormalities, were included. Histological results showed cervicitis (1 case), squamous neoplasia (18 cases), glandular neoplasia (7 cases), and glandular neoplasia associated with a squamous component (4 cases). Among the 24 cases presenting HPV-16, the European variant was detected in 15 (62%) and the Asian American in 9 (38%). Among the 15 cases associated with the European variant, 14 (93%) presented squamous neoplasia and 1 (7%) invasive adenocarcinoma. Asian-American HPV-16 variants were significantly associated with histological diagnosis of glandular neoplasia alone (odds ratio, 9.3 [1.4-60.2]) or associated with squamous neoplasia (odds ratio, 18.7 [1.5-232.3]). Adenocarcinomas were detected in 4 of 6 HPV-18-positive cases, being 2 cases had the European variant, 1 had the Asian Amerindian variant, and 1 had the African variant. The association of HPV-16 with squamous or glandular neoplasia is explained by its variants. In this study, squamous neoplasia was related to the European variant of HPV-16, whereas glandular neoplasia was related to the Asian-American variant. Glandular neoplasia is associated with HPV-18, but the results of our analysis of its variants were inconclusive.


Bellilinea caldifistulae gen. nov., sp. nov. and Longilinea arvoryzae gen. nov., sp. nov., strictly anaerobic, filamentous bacteria of the phylum Chloroflexi isolated from methanogenic propionate-degrading consortia.
Thermophilic (strain GOMI-1(T)) and mesophilic (strain KOME-1(T)) strains were isolated from two different cultures of propionate-degrading consortia obtained from thermophilic digester sludge and rice paddy soil, respectively. The two strains were non-spore-forming, non-motile and Gram-negative. Both strains were obligately anaerobic micro-organisms, showing multicellular filamentous morphotypes more than 100 mum in length. The cell width for strain GOMI-1(T) was 0.2-0.4 mum and that of strain KOME-1(T) was 0.4-0.6 mum. Strain GOMI-1(T) could grow at 45-65 degrees C with a pH range of 6.0-7.5 (optimum growth at 55 degrees C, pH 7.0). The temperature range for growth of strain KOME-1(T) was 30-40 degrees C and the pH range was pH 5.0-8.5 (optimum growth around 37 degrees C, pH 7.0). Yeast extract was required for growth of both strains. Strain GOMI-1(T) was able to grow with a number of carbohydrates in the presence of yeast extract. In yeast extract-containing medium, strain KOME-1(T) could utilize proteins and a limited range of sugars for growth. The G+C contents of the DNA of strains GOMI-1(T) and KOME-1(T) were respectively 54.7 and 57.6 mol%. Major fatty acids of strain GOMI-1(T) were C(16 : 0), C(14 : 0) and iso-C(15 : 0), whereas those of strain KOME-1(T) were iso-C(15 : 0), anteiso-C(15 : 0) and C(14 : 0). Based on comparative analysis of 16S rRNA gene sequences of strains GOMI-1(T) and KOME-1(T), the strains were placed in different phylogenetic positions in the class Anaerolineae of the bacterial phylum Chloroflexi. Their phenotypic and genetic traits strongly supported the conclusion that the strains should be described as two independent taxa in the class Anaerolineae. Hence, we propose the names Bellilinea caldifistulae gen. nov., sp. nov., and Longilinea arvoryzae gen. nov., sp. nov., for strains GOMI-1(T) and KOME-1(T). The type strains of Bellilinea caldifistulae and Longilinea arvoryzae are respectively GOMI-1(T) (=JCM 13669(T) =DSM 17877(T)) and KOME-1(T) (=JCM 13670(T) =KTCC 5380(T)).


[Quality evaluation of artificial musk based on its inhibitory effect on cyclooxygenase-2].
The inhibitory ratio (1%) of artificial musk on cyclooxygenase-2 (COX-2) was determined by enzyme immunoassay (EIA). The dose-effect relationship between concentrations of artificial musk and 1% was established. It was found that artificial musk had obvious inhibitory action on COX-2. The concentration for 50% of maximum inhibitory effect (IC50) was about 2.26 mg x mL(-1). There was a good relationship between the logarithm concentrations of artificial musk and 1% when the concentrations of artificial musk ranged from 0.31-20.0 mg x mL(-1). The results indicated that this EIA method could be applied to evaluate the anti-inflammatory activity of artificial musk quickly, conveniently, sensitively and exactly. This paper provided a novel method and foundational research for the bioassay of artificial musk.


The role of NdgR in glycerol metabolism in Streptomyces coelicolor.
Streptomyces, which produces many pharmaceutical antibiotics and anticancer agents, is a genus of soil-dwelling bacteria with numerous regulators that control both primary and secondary metabolism. NdgR is highly conserved in Streptomyces spp. and is known to be involved in antibiotic production, tolerance against shock and physical stress, nitrogen metabolism, leucine metabolism, and N-acetylglucosamine metabolism. As another function of NdgR, we report the involvement of NdgR in glycerol metabolism in S. coelicolor. Initially, a glycerol utilization operon containing gylCABX was found to be up-regulated in an ndgR deletion mutant (BG11) grown in N-acetylglucosamine solid minimal media compared with wild-type strain (M145). BG11 produced more antibiotics with a small amount of glycerol and increased glycerol utilization, yielding higher concentrations of lactate and acetate per cell. Moreover, fatty acid production was also changed in BG11 to produce longer chain fatty acids, phenolic compounds, alkanes, and fatty alcohols. Using a gel retardation assay, NdgR was found to bind the upstream region of gylC, working as a repressor. NdgR is a second regulator of a glycerol utilization operon, for which only one regulator, GylR was previously known.


Focused lung ultrasound to predict respiratory failure in patients with symptoms of COVID-19: a multicentre prospective cohort study.
In this study we aimed to assess if a focused lung ultrasound examination predicts the need for mechanical ventilation, admission to an intensive care unit, high-flow oxygen treatment, death from COVID-19 within 30 days and 30-day all-cause mortality in patients with clinical suspicion of COVID-19 or PCR-verified SARS-CoV-2 infection. A multicentre prospective cohort trial was performed. Film clips from focused lung ultrasound examinations were recorded and rated by blinded observers using different scoring systems. A prediction model was built and used to test relationship between lung ultrasound scores and clinical outcomes. Diagnostic performance of scoring systems was analysed. A total of 3889 film clips of 398 patients were analysed. Patients who had any of the outcomes of interest had a significantly higher ultrasound score than those who did not. Multivariable logistic regression analyses showed that lung ultrasound predicts mechanical ventilation (relative risk 2.44, 95% CI 1.32-5.52), admission to intensive care (relative risk 2.55, 95% CI 1.41-54.59) and high-flow oxygen treatment (relative risk 1.95, 95% CI 1.5-2.53) but not survival when adjusting for sex, age and relevant comorbidity. There was no diagnostic difference in area under the receiver operating characteristic curve between a scoring system using only anterolateral thorax zones and a scoring system that also included dorsal zones. Focused lung ultrasound in patients with clinical suspicion of COVID-19 predicts respiratory failure requiring mechanical ventilation, admission to intensive care units and the need for high-flow oxygen treatment. Thus, focused lung ultrasound may be used to risk stratify patients with COVID-19 symptoms.


Large-Scale in Vitro Transcription, RNA Purification and Chemical Probing Analysis.
RNA elements such as catalytic RNA, riboswitch, microRNA, and long non coding RNA (lncRNA) play central roles in many cellular processes. Studying diverse RNA functions require large quantities of RNA for precise structure analysis. Current RNA structure and function studies can benefit from improved RNA quantity and quality, simpler separation procedure and enhanced accuracy of structural analysis. Here we present an optimized protocol for analyzing the structure of any RNA, including in vitro transcription, size-exclusion chromatography (SEC) based denaturing purification and improved secondary structure analysis by chemical probing. We observed that higher Mg2+, nucleoside triphosphate (NTP) concentrations and longer reaction duration can improve the RNA yield from in vitro transcription, specifically for longer and more complicated constructs. Our improved SEC-based denaturing RNA purification effectively halved the experiment duration and labor without introducing any contaminant. Finally, this study increased the accuracy and signal-to-noise ratio (SNR) of selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemical probing for analyzing RNA structure. Part or all of our modified method can improve almost any RNA-related study from protein-RNA interaction analysis to crystallography.


Effects of mTOR on Neurological Deficits after Transient Global Ischemia.
Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR and its downstream products to brain injuries and neurological deficiencies after cardiac arrest (CA) induced-transient global ischemia. CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats. Our results showed that expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in CA rats compared to their controls. Blocking mTOR using rapamycin attenuated upregulation of pro-inflammatory cytokines (namely IL-1β, IL-6 and TNF-α), and Caspase-3, indicating cell apoptosis and also promoting the levels of vascular endothelial growth factor (VEGF) and its subtype receptor VEGFR-2 in the hippocampus. Moreover, the effects of rapamycin were linked to improvement of neurological deficits and increased brain water content observed in CA rats. In conclusion, activation of mTOR signal is engaged in pathophysiological process during CA-induced transient global ischemia and blocking mTOR pathway plays a beneficial role in regulating injured neuronal tissues and neurological deficits via PIC, apoptotic Caspase-3 and VEGF mechanisms. Targeting one or more of these specific mTOR pathways and its downstream signaling molecules may present new opportunities for neural dysfunction and vulnerability related to transient global ischemia.


Nephrotic syndrome resulting from focal segmental glomerulosclerosis in a peripheral blood stem cell transplant patient.
We describe the case of a male patient who was diagnosed with acute monoblastic leukemia and received a peripheral stem cell transplantation (PSCT) with peripheral blood hematopoietic progenitors. Because he was in clinical remission with no evidence of chronic graft-versus-host disease (GVHD), immunosuppression was withdrawn, and he developed nephrotic syndrome (NS) months later. A kidney biopsy showed focal segmental glomerulosclerosis (FSGS) as part of the GVHD. Soon after the reintroduction of previous immunosuppressive therapy, we observed a complete remission of the NS.