A high-performance fluorescent and ratiometric colorimetric detection of Cu2+ in practice.
To monitor Cu2+ efficiently, a kind of D-π-A-π-D conjugated 3,5-di-(2-hydroxyl naphthaldehyde)-iminyl triazole (HNIT) was developed, using triazole as the electron acceptor, 2-hydroxyl naphthaline as the electron donor, and -CN- as the bridging group. The proposed HNIT possessed superior UV-vis and fluorescent spectral property with high molar absorption coefficient of 2.313 × 104 L mol-1 cm-1 and fluorescence quantum yield of 36.2%. Trace Cu2+ could exclusively alter its UV-vis and fluorescent property with clear color change. Under the optimized conditions, a high-performance fluorescent and ratiometric colorimetric detection of Cu2+ based on HNIT was efficient, with low detection limits of 3.3 × 10-8 mol L-1 (S/N = 3) and 9.6 × 10-8 mol L-1 (S/N = 3), respectively. It well satisfied with the safe value of 31.5 μM Cu2+ in drinking water recommended by World Health Organization (WHO). When applied for detection of Cu2+ in real environmental samples, the recovery was in the range of 97.5-105.2%. The recognition mechanism for HNIT to Cu2+ realized quite stable 6-membered rings between electron-deficient Cu2+ and electron-rich N and O atoms in HNIT with 1 : 2 chemical stoichiometry of HNIT to Cu2+.


Managing obstructive sleep apnea.
Obstructive sleep apnea, cessation of breathing during sleep, is potentially life threatening and requires prompt intervention. A prosthesis can reposition the mandible during sleep and minimize or prevent the tongue from collapsing against the pharynx. Two case reports discuss the effectiveness of prosthetic devices.


[Occipital dermal sinus associated to a cerebellar abscess. Case].
Congenital dermal sinuses are tubular tracts which communicate the skin with deeper structures. It is a manifestation of defective separation of the ectoderm and neuroderm. The incidence is 1/2500-3000 births alive. Almost 10 % of congenital dermal sinuses are localized in the occipitocervical region. They are usually asymptomatic, unless an infectious process is concurrent (meningitis, abscess). We are presenting the case of a 12 months girl with unnoticed cutaneous stigmata in the occipital region, who was admitted with a meningeal syndrome and secondary neurological impairment. She had a cerebellar abscess and was treated with decompression by puncture of the abscess and antibiotics. When infection was resolved, congenital dermal sinus was excised. Process solves without morbidity. We reviewed the clinical and therapeutic features in cases reported previously in the literature.


Examining Associations between Body Mass Index in 18⁻25 Year-Olds and Energy Intake from Alcohol: Findings from the Health Survey for England and the Scottish Health Survey.
Evidence on the relationship between alcohol consumption and body mass index (BMI) is mixed, particularly for young adults. This study explored the relationship between energy obtained from alcoholic beverages and BMI using data for 18⁻25 year-olds (n = 7691) from pooled cross-sections of the 2008⁻2014 Health Survey for England and the Scottish Health Survey. Energy obtained from alcoholic beverages (excluding mixers) on the heaviest drinking day in the past week was expressed as percentage of total recommended dietary allowance (RDA) of energy (% RDA Energy). Linear regressions were estimated of BMI on alcohol intake categories controlling for intake frequency, physical activity, longstanding illness and other covariates, with separate analyses for men and women, and by beverage type. Significant associations with BMI were observed with the 'Very High' category of alcohol intake (>75% RDA Energy) for men (p < 0.001, 1.74, 95% confidence interval (CI) 0.98, 2.49) and with the "High" (>50% to 75% RDA Energy) (p < 0.001, 1.67, 95% CI 0.26, 2.58) and above category for women, when compared with the Low (>0⁻25% RDA Energy) category. Young adults drinking the highest levels of alcohol on a single occasion were more likely to be obese than those with the lowest intake. Interventions to address internationally rising youth obesity rates should also consider reducing alcohol consumption by increasing alcohol prices, and reducing availability and marketing exposure.


Natural resistance against pre- and post-harvest pathogens in Sardinian pears germoplasm.
Natural resistance against Venturia pirina and Botrytis cinerea was investigated within the Sardinian pears germplasm. The natural occurrence of V. pirina was monitored at the orchard level for 5 years, while resistance against B. cinerea was evaluated by a bioassay using methanolic extracts of the fruit rind or by artificially inoculation. Methanolic extracts of the leaves were employed for the Cladosporium bioassay on TLC plates. Among the accessions, 8 resulted sensitive to V. pirina, vegetation and fruit are severely affected every year. Seven showed an intermediate behaviour and the sole vegetation was affected slightly in two out of the 5 years. Two inhibition spots, in the methanolic extract of the leaves, were clearly evidenced in 55 accessions and a positive correlation was found between the presence of these antifungal compounds in the leaves and the resistance to V. pirina in the field. The artificial inoculation of fruit with B. cinerea evidenced a great variability in resistance, with about 12 accessions that could be considered having a good resistance. The fruit rind methanolic extracts evidenced several inhibition spots in most accessions, but no correlation could be found with fruit resistance to B. cinerea. In addition, the activity of the polygalacturonase inhibiting protein (PGIP), determined with an agarose diffusion bioassay, indicate a positive correlation between the PGIP activity evidenced in the core tissue and the infection degree by B. cinerea.


Ascorbate preserves gastric mucosal metabolism and microcirculation after hemorrhagic shock and retransfusion in rats.
The gastric mucosal microcirculation and purine nucleotide metabolism were studied in rats after hemorrhagic shock and retransfusion. The mucosal surface density of perfused vessels (SDPV) and the mucosal levels of ATP, ADP, AMP, IMP, hypoxanthine and uric acid were measured following 15 min of hemorrhagic shock and 10 and 30 min after retransfusion, and the effects of pretreatment with allopurinol or ascorbate were studied. During shock there was a dephosphorylation of nucleotides and a decline in the SDPV. Retransfusion led to an additional reduction in the SDPV, but a complete restoration of preshock nucleotide levels 30 min after retransfusion. Allopurinol accelerated early rephosphorylation of nucleotides without effects upon SDPV while ascorbate completely preserved the mucosal level of energy-rich nucleotides 15 min after hemorrhagic shock and increased SDPV during early reperfusion. The results showed that there was a renewal of energy stores in gastric mucosa after hemorrhagic shock and retransfusion although parts of the vascular bed were not reperfused. The mucosal energy depletion after 15 min of hemorrhagic shock and part of the mucosal vessel injury after retransfusion were prevented by pretreatment with ascorbate.


Renal malformations in patients with Turner syndrome: imaging in 141 patients.
Turner syndrome occurs in 1/2,000 to 1/5,000 live female births. The presence of renal malformations was evaluated in 141 patients with Turner syndrome and abnormalities were found in 47 (33%). Prior to 1980, IVP was the radiologic method used for initial screening, and subsequently, ultrasonography has been used as the initial imaging technique. With both methods, major malformations can be detected. Ten patients had a horseshoe kidney, 11 had double collecting systems, four had complete absence of one kidney, three had crossed ectopia, and one had a pelvic kidney. Three patients had ureteropelvic junction obstruction; two of these were asymptomatic and the obstructions were detected only because of the routine imaging. Two patients had ureterovesicular junction obstruction, with one studied as part of a routine evaluation for short stature. Four of these five patients required surgery. Ultrasonography should be used as the initial renal imaging study for all patients at the time the diagnosis of Turner syndrome is made.


Improving adolescent knowledge of emergency contraception: challenges and solutions.
Globally, unintended adolescent pregnancies pose a significant burden. One of the most important tools that can help prevent unintended pregnancy is the timely use of emergency contraception (EC), which in turn will decrease the need for abortions and complications related to adolescent pregnancies. Indications for the use of EC include unprotected sexual intercourse, contraceptive failure, or sexual assault. Use of EC is recommended within 120 hours, though is most effective if used as soon as possible after unprotected sex. To use EC, adolescents need to be equipped with knowledge about the various EC methods, and how and where EC can be accessed. Great variability in the knowledge and use of EC around the world exists, which is a major barrier to its use. The aims of this paper were to 1) provide a brief overview of EC, 2) discuss key social determinants affecting knowledge and use of EC, and 3) explore best practices for overcoming the barriers of lack of knowledge, use, and access of EC.


[Sensitivity to clavulanic acid of Escherichia coli isolated at the Henri Mondor hospital in 1986 according to phenotypes of beta-lactam antibiotic resistance].
Susceptibility to Augmentin (AUG) was studied as a function of resistance phenotypes toward amoxicillin (AMX), carbenicillin (CAR), cephalothin (CFT) and cefotaxime (CTX) for 1817 strains of Escherichia coli isolated at Henri-Mondor hospital during 1986. For strains susceptible to the 4 beta-lactams (phenotype SSSS: 66%), the median zone diameter observed with AUG was 26.4 mm. It was slightly inferior (22.1) for acquired - penicillinase producing strains (phenotype RRSS: 21.5%), but zone diameters were greater than or equal to 21 mm for over than 75% of these strains. Strains of phenotype RRIS (6%), probably high penicillinase-producers, were generally intermediate to AUG (median zone diameter: 17.8), showing partial inhibition of enzyme by clavulanic acid. Cephalosporinase hyperproducers mutants (phenotype RSRS: 4%) and strains with a RRRS phenotype (2.5%), probably penicillinase and cephalosporinase producers, were resistant to AUG (median zone diameters: 15.6 and 12.6 mm). Among rarely observed phenotypes, some were readily integrated to major phenotypes: RSIS, ISRS and ISIS to phenotype RSRS; RIRS to phenotype RRRS; IISS to phenotype RRSS; apparently "aberrants" phenotypes (ISSS, RSSS, SSIS, SSRS) required interpretation of results as a function of observed zone diameters and at time a verification of tests. This study confirms the in vitro activity of AUG on penicillinase producing E. coli; in addition simultaneous reading of zone diameters observed with AMX, CAR, CFT and CTX, permitted to infer the probable mechanism of resistance to beta-lactams and therefore to correct possible discrepancies observed in antibiogram results.


Complete Genome Sequence of Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Myophage Miro.
Klebsiella pneumoniae is a Gram-negative pathogen frequently associated with antibiotic-resistant nosocomial infections. Bacteriophage therapy against K. pneumoniae may be possible to combat these infections. The following describes the complete genome sequence and key features of the pseudo-T-even K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae myophage Miro.


[Low-intensity ultrasound promotes uterine involution following cesarean section].
To observe the clinical effect of low-intensity ultrasound in promoting uterine involution following cesarean section. A total of 122 women undergoing cesarean section were randomly selected and divided into low-intensity ultrasound treatment group (67 cases) and control group (55 cases). The women in the treatment group received daily low-intensity ultrasound treatment for 30 min 24 h after the delivery for 3 consecutive days, and the control group had no particular treatments. The descent of the uterine fundus and cessation of lochia was observed in the two groups. The treatment group showed obviously greater descent of the uterine fundus with a higher rate of cessation of vaginal bleeding than the control group at 30 days postpartum. The ratio of incomplete uterine involution was significantly lower in the treatment group than in the control group. Low-intensity ultrasound is effective in promoting uterine contraction and uterine involution following cesarean section.


Maximal cardiac output in angina patients before abd after coronary artery surgery.
Ten patients with angina pectoris underwent multistage maximal treadmill exercise with hemodynamic measurements before, and again 6 months following coronary artery surgery. Subjectively, 9 patients experienced a total and one patient partial relief from angina, and all patients noted improved exercise tolerance following surgery. Objectively, significant improvement was found in duration of exercise, maximal oxygen intake in maximal cardiac output, maximal heart rate, and maximal pressure-rate product. Surgery did not significantly affect systemic or pulmonary arterial pressures during exercise. Despite these improvements, maximal cardiac output did not return to normal levels following surgery, due to an unexpected but significant reduction in stroke volume.


Prevalence and Treatment of Neuropathic Pain in Kidney and Liver Transplant Recipients.
Neurologic complications are common after kidney and liver transplant. Neurologic complications affect mortality and morbidity in transplant recipients, and neuropathic pain is an important symptom affecting a patient's quality of life. The aim of the present study was to provide readers with our experience regarding causes and treatment of neuropathic pain in patients undergoing kidney and liver transplant at our transplantation center. The medical data of 553 kidney transplant recipients and 258 liver transplant recipients who received transplant procedures at the Baskent University Transplantation Center between 2008 and May 2016 were retrospectively reviewed. Fifty-one patients who were examined by an expert neurologist and diagnosed with neuropathic pain on the basis of clinical, neurologic examination, and laboratory findings were included for analyses. Among 811 transplant recipients, 51 patients (6.2%) were diagnosed with neuropathic pain. Of these, 22 were female and 38 were male patients, and 42 were kidney transplant recipients and 9 were liver transplant recipients. Causes of neuropathic pain included uremia, diabetes mellitus, ischemic peripheral arterial disease, inflammatory neuropathy, vasculitis, discopathy, postherpetic neuralgia, carpal tunnel syndrome, and multiple myeloma. Patients with symptoms too mild to affect daily life activities were treated conservatively. Plasmapheresis, gabapentin, pregabalin, alpha-lipoic acid, and duloxetine were administered as treatment modalities and medications. Neuropathic pain was lower in our transplant recipients than in the general population. Treatment medications were effective for transplant recipients at lower doses for the management of neuropathic pain impairing quality of life than doses for the general population.


Data and knowledge standards for learning health: A population management example using chronic kidney disease.
The widespread creation of learning health care systems (LHSs) will depend upon the use of standards for data and knowledge representation. Standards can facilitate the reuse of approaches for the identification of patient cohorts and the implementation of interventions. Standards also support rapid evaluation and dissemination across organizations. Building upon widely-used models for process improvement, we identify specific LHS activities that will require data and knowledge standards. Using chronic kidney disease (CKD) as an example, we highlight the specific data and knowledge requirements for a disease-specific LHS cycle, and subsequently identify areas where standards specifications, clarification, and tools are needed. The current data standards for CKD population management recommendations were found to be partially ambiguous, leading to barriers in phenotyping, risk identification, patient-centered clinical decision support, patient education needs, and care planning. Robust tools are needed to effectively identify patient health care needs and preferences and to measure outcomes that accurately depict the multiple facets of CKD. This example presents an approach for defining the specific data and knowledge representation standards required to implement condition-specific population health management programs. These standards specifications can be promoted by disease advocacy and professional societies to enable the widespread design, implementation, and evaluation of evidence-based health interventions, and the subsequent dissemination of experience in different settings and populations.


Quantitative analysis of nuclear pore complex organization in Schizosaccharomyces pombe.
The number, distribution, and composition of nuclear pore complexes (NPCs) in the nuclear envelope varies between cell types and changes during cellular differentiation and in disease. To understand how NPC density and organization are controlled, we analyzed the NPC number and distribution in the fission yeast Schizosaccharomyces pombe using structured illumination microscopy. The small size of yeast nuclei, genetic features of fungi, and our robust image analysis pipeline allowed us to study NPCs in intact nuclei under multiple conditions. Our data revealed that NPC density is maintained across a wide range of nuclear sizes. Regions of reduced NPC density are observed over the nucleolus and surrounding the spindle pole body (SPB). Lem2-mediated tethering of the centromeres to the SPB is required to maintain NPC exclusion near SPBs. These findings provide a quantitative understanding of NPC number and distribution in S. pombe and show that interactions between the centromere and the nuclear envelope influences local NPC distribution.


Digest it all: the lysosomal turnover of cytoplasmic aggregates.
Aggrephagy describes the selective lysosomal transport and turnover of cytoplasmic protein aggregates by macro-autophagy. In this process, protein aggregates and conglomerates are polyubiquitinated and then sequestered by autophagosomes. Soluble selective autophagy receptors (SARs) are central to aggrephagy and physically bind to both ubiquitin and the autophagy machinery, thus linking the cargo to the forming autophagosomal membrane. Because the accumulation of protein aggregates is associated with cytotoxicity in several diseases, a better molecular understanding of aggrephagy might provide a conceptual framework to develop therapeutic strategies aimed at delaying the onset of these pathologies by preventing the buildup of potentially toxic aggregates. We review recent advances in our knowledge about the mechanism of aggrephagy.


Parotid gland oncocytoma in HCV-positive patient with non-Hodgkin's lymphoma. Case report.
We report a case of parotid gland oncocytoma in a patient with chronic infection from hepatitis C virus (HCV) and associated non-Hodgkin's lymphoma and xerophthalmia. Our case confirms the triple tropism of the HCV: hepatotropism, lymphotropism and sialotropism.


PATTERNS OF OXIDATIVE ASSIMILATION IN STRAINS OF ACETOBACTER AND AZOTOBACTER.
Tomlinson, Geraldine A. (The University of British Columbia, Vancouver, B.C., Canada), and J. J. R. Campbell. Patterns of oxidative assimilation in strains of Acetobacter and Azotobacter. J. Bacteriol. 86:1165-1172. 1963.-Oxidative assimilation of glucose-U-C(14) was studied with washed-cell suspensions of Acetobacter aceti, A. xylinum, Azotobacter vinelandii, and A. agilis. The suggestion that oxidative assimilation is largely the incorporation of endogenously produced ammonia is tenable. A. aceti did not exhibit oxidative assimilation and it did not incorporate ammonia in the presence of glucose, alpha-ketoglutarate, or pyruvate. A. xylinum, A. vinelandii, and A. agilis incorporated C(14) into the nitrogenous fractions of the cell. The level of assimilation into A. xylinum was low due to the accumulation of extracellular cellulose, and the level of assimilation into the Azotobacter was low presumably because of the requirement of energy for nitrogen fixation. The Azotobacter were characterized by the presence of a high level of radioactivity in the cold trichloroacetic acid-soluble pool. None of the organisms accumulated compounds in the supernatant fluid that might be considered pacemakers in glucose oxidation, and this could be a contributing factor in the low level of assimilation.


Preliminary screening of fluorine-stained osteoblastic apoptosis-related microRNA.
Endemic fluorosis is a chronic systemic disease that seriously endangers human health. In high fluoride areas, people consume excessive fluoride for a long time through drinking water or food, which leads to chronic cumulative fluorosis in the body. Fluorosis can cause changes in the expression of some miRNA in cells, and the miRNA can participate in fluoride-induced osteoblast activation through various signal pathways. To observe the differential expression of apoptosis-related microRNA (miRNA) in mouse osteoblasts under the action of excessive fluoride. Primary cultured mouse osteoblasts, identified by osteocalcin (OC) and alkaline phosphatase (ALP) staining, were treated with 20 mg/L sodium fluoride and 40 mg/L sodium fluoride for 12/24 hr, respectively, to establish the fluoride staining model for comparing and analyzing the sequence of miRNA among groups by bioinformatics methods; four miRNA chains were verified by fluorescence quantitative PCR. After treatment with 20 mg/L sodium fluoride for 12 hr and 24 hr, 128 miRNA expressions were up-regulated while 36 miRNA expressions were down-regulated. In Group 40 mg/L, 130 miRNA expressions were up-regulated while 29 miRNA expressions were down-regulated after 12 hr and 24 hr; 72 miRNA were up-regulated and 2 miRNA were down-regulated at the two time points. 10 up-regulated miRNA and 2 down-regulated miRNA with higher scores in Bioinformatics software were analyzed the target genes. Fluorescence quantitative PCR verified that the expressions of four miRNA were up-regulated. Target gene analysis of the 10 selected mouse osteoblastic apoptosis-related miRNA reveals their involvement of the functions of inhibiting or promoting apoptosis, which has certain theoretical significance for early identification of skeletal fluorosis. The involved signaling pathways include the Wnt signaling pathway, ubiquitin-regulated proteolysis, Toll signaling pathway, TNF signaling pathway, pluripotent stem cell signaling pathway, MAPK signaling pathway, phosphatidylinositide metabolism, FoxO signaling pathway, ErbB signaling pathway, autophagy, and so forth.


The potential role of antibodies against minor blood group antigens in renal transplantation.
Blood group antigens are red blood cell (RBC) surface markers comprising specific carbohydrate moieties attached to the glycolipids and glycoproteins within the membrane. In addition to the major ABO blood group antigens, at least 35 minor blood group antigens have been defined to date. These antigens have immunogenic potential and may cause a transfusion reaction. There is evidence for renal expression of antigens from the Kidd, MNS, Duffy and Lewis groups and therefore the potential for antibodies directed against these antigens to cross-react in a transplanted kidney. In individuals lacking a specific RBC antigen, antibodies may develop after de novo exposure to that antigen, in addition to the potential presence of pre-existing innate antibodies. Relatively little attention has been paid to non-ABO system antibodies, with most reports in the literature focusing on transfusion reactions rather than on any putative role in allograft rejection. Here, we review each of these antigens in the context of renal transplantation and what limited evidence there is on how such immunological risk may be assessed and managed.


Biocompatibility of PCL/PLGA-BCP porous scaffold for bone tissue engineering applications.
In this study, biomimic porous polycaprolactone/poly (lactide-co-glycolide) loading biphasic tricalcium phosphate (PCL/PLGA-BCP) scaffolds were fabricated successfully by solvent evaporation method. The distribution of biphasic tricalcium phosphate (BCP) in polycaprolactone/poly (lactide-co-glycolide) (PCL/PLGA) scaffold was confirmed by micro-computed tomography (micro-CT) scanning, scanning electron microscope (SEM) observation and Energy-dispersive X-ray Spectroscopy (EDS) analysis. The hydrophilicity of the scaffolds was confirmed by contact angle measurement. In in vitro experiments, proliferation of human bone marrow mesenchymal stem cell (hBMSCs) and its osteoblastic differentiation on scaffold were assessed for 1, 2 and 3 weeks using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, fluorescence observation, hematoxylin & eosin (H&E) staining and real-time polymerase chain reaction (RT-PCR). In in vivo experiments, ossification was observed using micro-CT analysis and histological staining.


A molecular mechanism for genetic warfarin resistance in the rat.
Warfarin targets vitamin K 2,3-epoxide reductase (VKOR), the enzyme that produces reduced vitamin K, a required cofactor for g-carboxylation of vitamin K-dependent proteins. To identify VKOR, we used 4'-azido-warfarin-3H-alcohol as an affinity label. When added to a partially purified preparation of VKOR, two proteins were identified by mass spectrometry as calumenin and cytochrome B5. Rat calumenin was cloned and sequenced and the recombinant protein was produced. When added to an in vitro test system, the 47 kDa recombinant protein was found to inhibit VKOR activity and to protect the enzyme from warfarin inhibition. Calumenin was also shown to inhibit the overall activity of the complete vitamin K-dependent g-carboxylation system. The results were repeated in COS-1 cells overexpressing recombinant calumenin. By comparing calumenin mRNA levels in various tissues from normal rats and warfarin-resistant rats, only the livers from resistant rats were different from normal rats by showing increased levels. Partially purified VKOR from resistant and normal rat livers showed no differences in Km-values, specific activity, and sensitivity to warfarin. A novel model for genetic warfarin resistance in the rat is proposed, whereby the concentration of calumenin in liver determines resistance.


Tissue renin-angiotensin systems aspects of molecular biology and pharmacology.
Advances in molecular biology over the last few years have made it possible to extend studies concerned with the role of renin in blood pressure regulation and fluid balance to the genetic level. Epidemiological data from cross-sectional population studies as well as experimental findings in spontaneously hypertensive rats suggest a greater disposition towards hypertension in males than in females. Testosterone (T) is known to raise blood pressure in female and castrated male SH-rats, while concomitantly increasing tissue renin activities. The availability of recombinant DNA technology and of a 32P labeled mouse submandibular gland renin cRNA as a hybridization probe enabled us to quantitatively assess whether this increase is paralleled by enhanced renin gene expression. In groups of female NMRI mice injected with DHT, we were able to show, that cardiac renin activity was significantly increased after 2 hours (1.6 fold) and 21 days (1.9 fold) of dihydrotestosterone (DHT) treatment compared to controls. DHT had no effect on renin mRNA concentration in the uterus, whereas in the ovary it resulted in a 50% decrease. We conclude that enhanced renin-activity and mRNA levels in peripheral organs and in the central nervous system are due to direct or indirect effects (cis, transacting) of T on renin gene expression. Thus, T may participate in the development of hypertension by stimulating the activity of tissue renin-angiotensin systems.


3-Hydroxymethyl-s-triazolo[3,4-a]phthalazine, a novel urinary hydralazine metabolite in man.
The elucidation of the structure of a new major metabolic product of hydralazine, 3-hydroxymethyl-s-triazolo[3,4-a]-phthalazine, is described. The structures of several other previously described metabolites of the drug, phthalazone, s-triazolo[3,4-a]phthalazine, and 3-methyl-s-triazolo[3,4-a]phthalazine, are confirmed. A metabolic pathway of hydralazine is also proposed.


Revealing the Thermodynamic Properties of Elementary Chemical Reactions at the Single-Molecule Level.
An understanding of the thermodynamic properties of elementary chemical steps of a reaction is important for the development of fundamental reaction theories and for effective industrial practice. In this work, temperature-variable single-molecule fluorescence microscopy was employed to study a reversible redox chemical process and reveal the thermodynamics of chemical elementary reactions at a single-molecule level. Activation energies of pure elementary steps were measured on the level of single molecules and found to be heterogeneously distributed across the population of individual molecules. The activation parameters measured across the population of individual molecules also exhibited a compensation effect and an isokinetic relationship. These results constitute a new single-molecule-level perspective into a chemical reaction.


Importance of hyperbilirubinemia in differentiation of primary and secondary hemophagocytic lymphohistiocytosis in pediatric cases.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory disease. It is difficult to differentiate between primary and secondary HLH based on clinical findings at the onset of disease. We aimed to find parameters that can help to differentiate primary and secondary HLH at initial diagnosis especially for physicians working in developing countries. We retrospectively analyzed data of 38 HLH patients who were admitted to the Pediatric Hematology Department of Gaziantep University between January 2009 and December 2013. Of 38 patients, 20 were defined as primary, and 18 were secondary HLH. The average age of primary and secondary HLH patients was 31±9 and 81±14 months, respectively (p=0.03). We found consanguinity rates significantly higher in primary HLH patients compared to secondary HLH patients (p=0.03). We found that total and direct bilirubin levels significantly increased in primary HLH patients compared to secondary HLH patients (p=0.006, p=0.044). Also, CRP levels were found markedly increased in secondary HLH patients compared to primary ones (p=0.017). We showed that cholestasis and hyperbilirubinemia findings of HLH patients at the initial diagnosis should be considered in favor of primary HLH, and an increased level of CRP should be considered in favor of secondary HLH.


Professional and educational needs of hospice and palliative care social workers.
In the past decade much growth has occurred in the numbers of patients and families served by hospices and palliative care services. Thus, not surprisingly, these services have also been subject to increasing regulation by governmental and accrediting entities. In order to stay up-to-date in this ever-changing environment and to continue to provide effective interventions, social workers must stay engaged in the professional community and continuing education. In this quantitative study, 1,169 practicing hospice and palliative care social workers provided information about their practice activities and agency characteristics, professional affiliations and certification, and ongoing educational needs. About one-half of respondents carried a caseload of 21-50 and were most engaged in communicating the psychosocial needs of the patient and family to other members of the team and assessing for grief and bereavement issues. The most important educational needs pertained to the psychological and social needs of patients and families and psychosocial interventions. Most were members of professional organizations and three-quarters were members of NASW. Although many were aware of the joint NASW-NHPCO social work hospice specialty certification, few held this certification yet. The results of this survey can be utilized in the design of continuing education programs and advocacy for programmatic and policy change within agencies and the industry.


Predicting synchronized gene coexpression patterns from fibration symmetries in gene regulatory networks in bacteria.
Gene regulatory networks coordinate the expression of genes across physiological states and ensure a synchronized expression of genes in cellular subsystems, critical for the coherent functioning of cells. Here we address the question whether it is possible to predict gene synchronization from network structure alone. We have recently shown that synchronized gene expression can be predicted from symmetries in the gene regulatory networks described by the concept of symmetry fibrations. We showed that symmetry fibrations partition the genes into groups called fibers based on the symmetries of their 'input trees', the set of paths in the network through which signals can reach a gene. In idealized dynamic gene expression models, all genes in a fiber are perfectly synchronized, while less idealized models-with gene input functions differencing between genes-predict symmetry breaking and desynchronization. To study the functional role of gene fibers and to test whether some of the fiber-induced coexpression remains in reality, we analyze gene fibrations for the gene regulatory networks of E. coli and B. subtilis and confront them with expression data. We find approximate gene coexpression patterns consistent with symmetry fibrations with idealized gene expression dynamics. This shows that network structure alone provides useful information about gene synchronization, and suggest that gene input functions within fibers may be further streamlined by evolutionary pressures to realize a coexpression of genes. Thus, gene fibrations provide a sound conceptual tool to describe tunable coexpression induced by network topology and shaped by mechanistic details of gene expression.


Higher Bifidobacterium spp. fecal abundance is associated with a lower prevalence of hyperglycemia and cardiovascular risk markers among schoolchildren from Bahia, Brazil.
The gut microbiome has recently been the subject of considerable scientific interest due to its essential bodily functions. Several factors can change the composition and function of the gut microbiome, and dietary habits are one of the most important contributors. Despite the recognition of the probiotic effects related to the genus Bifidobacterium spp. (BIF) studies aiming to assess its relationship with metabolic outcomes show conflicting results, particularly in the child population. This cross-sectional study aimed to evaluate the fecal abundance of BIF in a group of schoolchildren from public schools in Bahia, Brazil, and to investigate their relationship with food consumption and laboratory and anthropometric characteristics. A sample of 190 subjects aged 5 to 19y was randomly selected for dietary, laboratory, and anthropometric assessment. Fecal BIF abundance assessment was performed using the Real-Time Polymerase Chain Reaction assay. Fecal BIF abundance was higher among subjects who had lower intakes of meat. The abundance of BIF was also higher among subjects with lower Waist Circumference and Waist-to-Height Ratio (WHtR). Low BIF abundance was associated with a higher prevalence of hyperglycemia (PR 1.04, 95%CI 1.02-1.07, p = 0.001) and high WHtR (PR 1.04, 95%CI 1.01-1, 08, p = 0.015). These findings allow us to conclude that BIF fecal abundance is related to dietary and anthropometric parameters in schoolchildren, and its increase is associated with positive metabolic outcomes.


Chemerin as a marker of subclinical cardiac involvement in psoriatic patients.
Chemerin has been associated with psoriasis and inflammation, but there are no studies demonstrating an association between chemerin and subclinical cardiac involvement in psoriatic patients. Therefore, the present study aimed to evaluate whether psoriatic patients with increased epicardial fat tissue, impaired flow-mediated dilatation, and diastolic dysfunction have higher serum chemerin levels than a healthy control group. The study included 60 psoriatic patients and 32 healthy controls. Echocardiographic parameters, epicardial fat tissue, flow-mediated dilatation, and chemerin levels were recorded for both groups. The serum levels of chemerin in the psoriatic patients were significantly higher than in the control group. The diastolic function parameters, including isovolumic contraction and relaxation time, E'/A' (early diastolic mitral annular velocity/late diastolic mitral annular velocity), and E/E' (early diastolic peak velocity of mitral inflow/early diastolic mitral annular velocity) values, differed significantly between the groups. Epicardial fat tissue was significantly higher and flow-mediated dilatation was significantly lower in psoriatic patients than in the controls. Chemerin was significantly positively correlated with age, body mass index, systolic and diastolic blood pressures, waist circumference, E/E', and epicardial fat tissue. Serum chemerin was significantly negatively correlated with E', E'/A', and flow-mediated dilatation. A multiple linear regression analysis showed that chemerin was independently correlated with E/E'. Psoriatic patients exhibit early subclinical atherosclerosis and diastolic dysfunction. Chemerin can be used as a marker to screen for patients with subclinical cardiac involvement.


Serum levels of vitamin D metabolites in the elderly.
The serum concentrations of 25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, vitamin D-binding protein, PTH and calcitonin were measured in three groups of elderly Norwegian subjects (age 70-96 years): active elderly living at home, warded geriatric patients not supplemented with vitamin D, and warded geriatric patients supplemented with a daily dose of 400 IU vitamin D2. The results were compared with the concentrations of vitamin D metabolites found in a group of young and middle-aged adults (age 22-59 years). Decreased serum concentrations of 25-dihydroxyvitamin D3 were found in all groups of elderly compared with younger adults. Active elderly living at home had higher concentrations of 25-dihydroxyvitamin D3 than geriatric ward patients. Supplementation of geriatric ward patients with 400 IU vitamin D2 resulted in an increase in the median serum 25-dihydroxyvitamin D concentration by about 30 nmol/l. Decreased median concentration of 1,25-dihydroxyvitamin D was found in geriatric ward patients not supplemented with vitamin D, indicating that this group is at risk of vitamin D deficiency. The active elderly living at home and the warded geriatric patients receiving vitamin D supplementation had normal median concentrations of 1,25-dihydroxyvitamin D, indicating that nephrogenous synthesis of 1,25-dihydroxyvitamin D is not generally impaired in the elderly, and that a moderate vitamin D supplementation may correct low 1,25-dihydroxyvitamin D levels, owing to vitamin D deficiency. However, the serum concentrations of 1,25-dihydroxyvitamin D showed great individual variations. No significant differences were observed for vitamin D-binding protein, 'free-1,25-dihydroxyvitamin D, or PTH between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Clozapine and haloperidol reinstate latent inhibition following its disruption during amphetamine withdrawal.
Latent inhibition (LI) is a behavioral phenomenon whereby repeated exposure to a non-reinforced stimulus retards subsequent conditioning to that stimulus. Deficits in LI may reflect an inability to ignore irrelevant stimuli and are studied as a model of the cognitive/attentional abnormalities found in schizophrenia. We recently determined that pretreatment with escalating doses of the indirect dopamine agonist amphetamine (AMPH; 3 daily injections ip, 1-5 mg/kg, over 6 days) disrupts LI in rats tested in a 2-way active avoidance paradigm during withdrawal. In the present study, we evaluated the effects of the atypical neuroleptic clozapine and the typical neuroleptic haloperidol on the expression of LI on day 4 of AMPH withdrawal. Neuroleptic injections were given either 45 min prior to each of two tone preexposure sessions and a subsequent tone-shock avoidance test session, or only prior to the test session. As expected, saline-injected control groups showed LI during the test session, as reflected by significantly reduced avoidance in tone preexposed vs. non-preexposed rats. In contrast, animals pretreated with escalating doses of AMPH did not show LI, due to the improved avoidance of the preexposed animals. Both haloperidol (0.03 mg/kg) and clozapine (5 mg/kg) largely reversed the disruptive influence of AMPH on LI regardless of whether these drugs were administered prior to both preexposure and test sessions or only prior to the test session. These results provide pharmacological validation for an AMPH withdrawal model of schizophrenic symptoms.


The Presence and Duration of Overweight Are Associated with Low-Grade Inflammation in Prepubertal Chilean Children.
Overweight is associated with low-grade inflammation, but it is under debate whether the effect of fat mass accumulation is acute or chronic. We aimed to study the association of overweight duration with low-grade inflammation in children in whom overweight initiation can be established. Observational longitudinal study, including a subsample of 250 Chilean children from the Growth and Obesity Cohort Study followed-up yearly since preschool age (n = 1195). At 4 years, 324 children provided blood. From those, 272 participants were evaluated at 7 years. The current analysis includes 250 children with a blood sample at 4 and 7 years of age and C-reactive protein (CRP) <5 mg/L. Anthropometric data (0-4 years) were obtained from health records and measured thereafter; sex- and age-specific body mass index Z-scores (BAZ) were computed. Among overweight (BAZ ≥ 1) participants at 7 years, the duration of overweight (time since diagnosis) was computed and categorized according to tertiles: <36, 36-<72, or ≥72 months. The independent association between overweight (diagnosis and duration) and low-grade inflammation (CRP ≥ 1 mg/L) was studied (logistic regression models). Overweight was associated with CRP ≥ 1 mg/L at 7 years [odds ratio (OR) = 2.93 confidence interval (95% CI = 1.60-5.38)], but not at 4 years [OR = 1.26 (95% CI = 0.71-2.26)]. An overweight duration <36 m was independently associated with CRP ≥ 1 mg/L [OR = 3.53 (95% CI = 1.21-10.28)] (reference = normal weight), whereas longer overweight durations (36-<72 or ≥72 m) were not associated with CRP ≥ 1 mg/L [OR = 1.35 (95% CI = 0.41-4.40) and OR = 1.21 (95% CI = 0.35-4.18), respectively]. Overweight at 7 years of age was associated with low-grade inflammation only in the case of recent onset. Inflammatory disturbances may be associated with the early phases of excess weight.


Harnessing the preconditioning phenomenon: does remote organ ischaemia provide the answer?
Despite progress in defining the cellular mechanisms of the ischaemic preconditioning phenomenon, its conversion into convenient clinical practice has been slow. The possibility that an innate mechanism of tissue resistance to ischaemia could be harnessed as a clinical tool is an attractive and enticing prospect.


Mapping the SRY gene in Microtus cabrerae: a vole species with multiple SRY copies in males and females.
The SRY gene is a single-copy, male-specific gene, located on the Y chromosome in most mammals. However, recently we have described the presence of multiple polymorphic copies of this gene in both males and females of the vole species Microtus cabrerae. Here, we present the chromosomal localization of SRY gene copies in this species by fluorescent in situ hybridization (FISH). This technique localized these gene copies in the short arm, and hence in the euchromatic region, of the Y chromosome. Furthermore, several copies of the SRY gene are located on the X chromosome. These copies are spread along the entire heterochromatic region of the X chromosome, occupying the whole short arm, the centromeric region, and the pericentromeric region of the long arm.


Structure and Development of Flowers and Inflorescences in Burmannia (Burmanniaceae, Dioscoreales).
Species of the genus Burmannia possess distinctive and highly elaborated flowers with prominent floral tubes that often bear large longitudinal wings. Complicated floral structure of Burmannia hampers understanding its floral evolutionary morphology and biology of the genus. In addition, information on structural features believed to be taxonomically important is lacking for some species. Here we provide an investigation of flowers and inflorescences of Burmannia based on a comprehensive sampling that included eight species with various lifestyles (autotrophic, partially mycoheterotrophic and mycoheterotrophic). We describe the diversity of inflorescence architecture in the genus: a basic (most likely, ancestral) inflorescence type is a thyrsoid comprising two cincinni, which is transformed into a botryoid in some species via reduction of the lateral cymes to single flowers. Burmannia oblonga differs from all the other studied species in having an adaxial (vs. transversal) floral prophyll. For the first time, we describe in detail early floral development in Burmannia. We report presence of the inner tepal lobes in B. oblonga, a species with reportedly absent inner tepals; the growth of the inner tepal lobes is arrested after the middle stage of floral development of this species, and therefore they are undetectable in a mature flower. Floral vasculature in Burmannia varies to reflect the variation of the size of the inner tepal lobes; in B. oblonga with the most reduced inner tepals their vascular supply is completely lost. The gynoecium consists of synascidiate, symplicate, and asymplicate zones. The symplicate zone is secondarily trilocular (except for its distal portion in some of the species) without visible traces of postgenital fusion, which prevented earlier researchers to correctly identify the zones within a definitive ovary. The placentas occupy the entire symplicate zone and a short distal portion of the synascidiate zone. Finally, we revealed an unexpected diversity of stamen-style interactions in Burmannia. In all species studied, the stamens are tightly arranged around the common style to occlude the flower entrance. However, in some species the stamens are free from the common style, whereas in the others the stamen connectives are postgenitally fused with the common style, which results in formation of a gynostegium.


Embolisation of host kidneys for the control of hypertension after renal transplantation: radiological aspects.
In this study 12 patients with drug-resistant hypertension after renal transplantation had their own kidneys ablated by therapeutic embolisation. The technical aspects of the procedure are described in detail. An improvement in blood-pressure control was achieved in eight of the 12 patients. These results are similar to those which have been reported after bilateral nephrectomy. It is concluded that embolisation of the host kidneys is a simple, effective and less hazardous alternative to surgery in the treatment of severe hypertension after renal transplantation.


IR spectroscopy of water vapor confined in nanoporous silica aerogel.
The absorption spectrum of the water vapor, confined in the nanoporous silica aerogel, was measured within 5000-5600 cm(-1) with the IFS 125 HR Fourier spectrometer. It has been shown, that tight confinement of the molecules by the nanoporous size leads to the strong lines broadening and shift. For water vapor lines, the HWHM of confined molecules are on the average 23 times larger than those for free molecules. The shift values are in the range from -0.03 cm(-1) to 0.09 cm(-1). Some spectral lines have negative shift. The data on the half-widths and center shifts for some strongest H(2)O lines have been presented.


Comparing SNP panels and statistical methods for estimating genomic breed composition of individual animals in ten cattle breeds.
SNPs are informative to estimate genomic breed composition (GBC) of individual animals, but selected SNPs for this purpose were not made available in the commercial bovine SNP chips prior to the present study. The primary objective of the present study was to select five common SNP panels for estimating GBC of individual animals initially involving 10 cattle breeds (two dairy breeds and eight beef breeds). The performance of the five common SNP panels was evaluated based on admixture model and linear regression model, respectively. Finally, the downstream implication of GBC on genomic prediction accuracies was investigated and discussed in a Santa Gertrudis cattle population. There were 15,708 common SNPs across five currently-available commercial bovine SNP chips. From this set, four subsets (1,000, 3,000, 5,000, and 10,000 SNPs) were selected by maximizing average Euclidean distance (AED) of SNP allelic frequencies among the ten cattle breeds. For 198 animals presented as Akaushi, estimated GBC of the Akaushi breed (GBCA) based on the admixture model agreed very well among the five SNP panels, identifying 166 animals with GBCA = 1. Using the same SNP panels, the linear regression approach reported fewer animals with GBCA = 1. Nevertheless, estimated GBCA using both models were highly correlated (r = 0.953 to 0.992). In the genomic prediction of a Santa Gertrudis population (and crosses), the results showed that the predictability of molecular breeding values using SNP effects obtained from 1,225 animals with no less than 0.90 GBC of Santa Gertrudis (GBCSG) decreased on crossbred animals with lower GBCSG. Of the two statistical models used to compute GBC, the admixture model gave more consistent results among the five selected SNP panels than the linear regression model. The availability of these common SNP panels facilitates identification and estimation of breed compositions using currently-available bovine SNP chips. In view of utility, the 1 K panel is the most cost effective and it is convenient to be included as add-on content in future development of bovine SNP chips, whereas the 10 K and 16 K SNP panels can be more resourceful if used independently for imputation to intermediate or high-density genotypes.


Classification and reconstructive options in foot plantar skin avulsion injuries.
Between 1989 and 1994, 28 patients who had plantar avulsion injuries were treated. Patient ages averaged 30 years (range 7 to 62 years). Length of follow-up averaged 20 months. Five patients (18 percent) were classified as having suprafascial avulsions, where the shearing plane was limited to the superficial subcutaneous layer, leaving the deeper subcutaneous fat. Twenty-three patients (82 percent) were classified as having subfascial avulsions, where the stripping force extended deep into the plantar aponeurosis. For the suprafascial avulsions, defatting these flaps and replacing them with full-thickness skin grafts was the treatment of choice. For the subfascial group, the avulsions with proximally based flaps (4 patients) that were well nourished by mediolaterally orientated neurovascular bundles could be treated by sewing the avulsed flaps tension-free back to their former positions. For the subfascial group with distally based flaps (19 patients), the avulsed flaps were supplied by anteroposteriorly orientated vascular plexuses that were compromised. Primary revascularization of the soft tissue should be considered whenever possible. Among them, 10 patients attempted microvascular salvage. Only 3 patients succeeded with revascularization. In the remaining 16 patients, the avulsed flaps went on to partial or complete necrosis, and these required secondary reconstruction with free muscle flaps for heel defects.


Intracerebral penetration of a zygomatic dental implant and consequent therapeutic dilemmas: case report.
This case report describes a unique intracerebral penetration of a zygomatic implant inserted in the pterygoid region. A 47-year-old female patient developed severe persistent headaches immediately after two zygomatic and two standard implants were inserted under general anesthesia. However, no additional treatment or radiologic assessment was performed at that time by the treating surgeon. The maxilla was rehabilitated with an implant-supported fixed denture 3 months after the implants were placed. An episode of acute left maxillary sinusitis occurred shortly after insertion of the fixed denture. Treatment with antibiotics was insufficient, and the patient developed chronic left maxillary sinusitis. The patient presented herself to a neurologist with symptoms of chronic fatigue and severe headaches. Cerebral magnetic resonance imaging demonstrated the intracerebral penetration of a foreign body that resembled a dental implant. The authors sought to resolve the intracerebral penetration of the foreign body, along with the persistent maxillary chronic sinusitis with its concomitant risk of ascending cerebral infection. Computer-assisted preoperative planning associated with computer-assisted three-dimensional transfer should be used to avoid such a dangerous complication. Postoperative computed tomography assessment should be performed after zygomatic implant surgery. Finally, any neurologic impairment of the patient after pterygoid implantation should also be treated immediately.


Lightning safety guidelines.
On average, lightning causes more casualties annually in the United States than any other storm-related phenomenon except floods. Although 90% of those injured survive, they may have permanent sequelae and disability. Many of these people incur injuries or are killed by lightning because of misinformation and inappropriate behavior during thunderstorms. A few simple precautions can reduce lightning injury risk. To standardize recommended actions during thunderstorms, the Lightning Safety Group (LSG), composed of lightning experts from many lightning-related backgrounds, met at the American Meteorological Society meeting Phoenix, AZ, in January 1998 to collectively address personal lightning safety. This paper is a summary of the recommendations developed by the LSG.


Assessment of microbiological diagnostic procedures for respiratory specimens from cystic fibrosis patients in German laboratories by use of a questionnaire.
Respiratory specimens from cystic fibrosis (CF) patients challenge microbiological laboratories with their complexity of pathogens and atypical variants. We evaluated the diagnostic procedures in German laboratories by use of a questionnaire. Although most laboratories followed guidelines, some of them served only a small number of patients, while others did not use the recommended selective agars to culture the particular CF-relevant species.


Investigation of bias related to differences between case and control interview dates in five INTERPHONE countries.
Associations between cellular telephone use and glioma risk have been examined in several epidemiological studies including the 13-country INTERPHONE study. Although results showed no positive association between cellular telephone use and glioma risk overall, no increased risk for long-term users, and no exposure-response relationship, there was an elevated risk for those in the highest decile of cumulative call time. However, results may be biased as data were collected during a period of rapidly increasing cellular telephone use, and as controls were usually interviewed later in time than cases. Further analyses were conducted in a subset of five INTERPHONE study countries (Australia, Canada, France, Israel, New Zealand) using a post hoc matching strategy to optimize proximity of case-to-control interview dates and age. Although results were generally similar to the original INTERPHONE study, there was some attenuation of the reduced odds ratios and stronger positive associations among long-term users and those in the highest categories for cumulative call time and number of calls (eighth-ninth and 10th decile). Proximity and symmetry in timing of case-to-control interviews should be optimized when exposure patterns are changing rapidly with time.


Assessment of Grape, Plum and Orange Synthetic Food Flavourings Using in vivo Acute Toxicity Tests.
The present study evaluates the acute toxicity of synthetic grape, plum and orange flavourings in root meristem cells of Allium cepa at the doses of 3.5, 7.0 and 14.0 mL/kg and exposure times of 24 and 48 h, and in bone marrow erythrocytes of mice treated orally for seven days with 0.5, 1.0, 2.0, 5.0 and 10.0 mL/kg of flavouring. The results of the plant test showed that grape, plum and orange flavourings, at both exposure times, inhibited cell division and promoted the formation of a significant number of micronuclei and mitotic spindle changes. These alterations were observed in at least one exposure time analysed, demonstrating a significant cytotoxic, genotoxic and mutagenic activity. In mouse bioassay, animals treated with 2.0, 5.0 and 10.0 mL/kg of flavouring died before the seventh day of treatment. The amounts of 0.5 and 1.0 mL/kg of the three additives were cytotoxic to erythrocytes, and treatment with the grape flavouring significantly induced the formation of micronucleated cells in the bone marrow of animals. Therefore, under the study conditions, the grape, plum and orange flavouring additives promoted significant toxicity to cells of the test systems used.


Cytochrome aa3 Oxygen Reductase Utilizes the Tunnel Observed in the Crystal Structures To Deliver O2 for Catalysis.
Cytochrome aa3 is the terminal respiratory enzyme of all eukaryotes and many bacteria and archaea, reducing O2 to water and harnessing the free energy from the reaction to generate the transmembrane electrochemical potential. The diffusion of O2 to the heme-copper catalytic site, which is buried deep inside the enzyme, is the initiation step of the reaction chemistry. Our previous molecular dynamics (MD) study with cytochrome ba3, a homologous enzyme of cytochrome aa3 in Thermus thermophilus, demonstrated that O2 diffuses from the lipid bilayer to its reduction site through a 25 Å long tunnel inferred by Xe binding sites detected by X-ray crystallography [Mahinthichaichan, P., Gennis, R., and Tajkhorshid, E. (2016) Biochemistry 55, 1265-1278]. Although a similar tunnel is observed in cytochrome aa3, this putative pathway appears partially occluded between the entrances and the reduction site. Also, the experimentally determined second-order rate constant for O2 delivery in cytochrome aa3 (∼108 M-1 s-1) is 10 times slower than that in cytochrome ba3 (∼109 M-1 s-1). A question to be addressed is whether cytochrome aa3 utilizes this X-ray-inferred tunnel as the primary pathway for O2 delivery. Using complementary computational methods, including multiple independent flooding MD simulations and implicit ligand sampling calculations, we probe the O2 delivery pathways in cytochrome aa3 of Rhodobacter sphaeroides. All of the O2 molecules that arrived in the reduction site during the simulations were found to diffuse through the X-ray-observed tunnel, despite its apparent constriction, supporting its role as the main O2 delivery pathway in cytochrome aa3. The rate constant for O2 delivery in cytochrome aa3, approximated using the simulation results, is 10 times slower than in cytochrome ba3, in agreement with the experimentally determined rate constants.


Increase of cells expressing PD-1 and PD-L1 and enhancement of IFN-γ production via PD-1/PD-L1 blockade in bovine mycoplasmosis.
Bovine mycoplasma, chiefly Mycoplasma bovis, is a pathogen that causes pneumonia, mastitis, arthritis, and otitis media in cattle. This pathogen exerts immunosuppressive effects, such as the inhibition of interferon production. However, the mechanisms involved in bovine mycoplasmosis have not been fully elucidated. In this study, we investigated the role of the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in immunosuppression in bovine mycoplasmosis. In the initial experiments, we used enzyme-linked immunosorbent assay to measure interferon-γ (IFN-γ) from peripheral blood mononuclear cells (PBMCs) isolated from cattle with mycoplasmosis. Expectedly, IFN-γ production significantly decreased in cattle with mycoplasmosis compared with that in clinically healthy cattle. Concomitantly, flow cytometric analysis revealed that the proportions of PD-1+ CD4+ and PD-L1+ CD14+ cells significantly increased in peripheral blood of the infected cattle. Interestingly, the number of PD-1+ CD4+ and PD-1+ CD8+ T cells were negatively correlated with IFN-γ production from PBMCs in bovine mycoplasmosis. Additionally, blockade of the PD-1/PD-L1 pathway in vitro by anti-bovine PD-1- and anti-bovine PD-L1 antibodies significantly upregulated the production of IFN-γ from anti-mycoplasma-specific cells. These results suggest that the PD-1/PD-L1 pathway could be involved in immune exhaustion of bovine mycoplasma-specific T cells. In conclusion, our study opens up a new perspective in the therapeutic strategy for bovine mycoplasmosis by targeting the immunoinhibitory receptor pathways.


Fully relativistic form factor for Thomson scattering.
We derive a fully relativistic form factor for Thomson scattering in unmagnetized plasmas valid to all orders in the normalized electron velocity, beta[over ]=v[over ]/c. The form factor is compared to a previously derived expression where the lowest order electron velocity, beta[over], corrections are included [J. Sheffield, (Academic Press, New York, 1975)]. The beta[over ] expansion approach is sufficient for electrostatic waves with small phase velocities such as ion-acoustic waves, but for electron-plasma waves the phase velocities can be near luminal. At high phase velocities, the electron motion acquires relativistic corrections including effective electron mass, relative motion of the electrons and electromagnetic wave, and polarization rotation. These relativistic corrections alter the scattered emission of thermal plasma waves, which manifest as changes in both the peak power and width of the observed Thomson-scattered spectra.


Violent behavior by individuals with serious mental illness.
The perceived association between violent behavior and serious mental illness was explored to determine the validity of claims by mental health advocates that individuals with serious mental illness are no more dangerous than members of the general population. The author reviewed recent studies and media accounts of violent behavior by individuals with serious mental illness, with emphasis given to the most recent studies. Although the vast majority of individuals with serious mental illness are not more dangerous than members of the general population, recent findings suggest the existence of a subgroup that is more dangerous. A history of violent behavior, noncompliance with medications, and substance abuse are important predictors of violent behavior in this subgroup. The findings imply that the criteria for involuntary hospitalization, involuntary medication, outpatient commitment, the monitoring of medication compliance, and other mandated follow-up procedures may need to be revised. The existence of a subgroup of seriously mentally ill patients who exhibit violent behavior undermines efforts by mental health advocates to reduce the stigma of mental illness by denying an association with violence. Until the problem of violence by this subgroup is addressed, it will be difficult to substantially decrease the stigma associated with serious mental illness.


Biochemical, pathological, and clinical response to transplantation of normal bone marrow cells into acid sphingomyelinase-deficient mice.
Acid sphingomyelinase knock-out (ASMKO) mice are a model of types A and B Niemann-Pick disease. In the present study, we evaluated whether bone marrow transplantation (BMT) carried out on newborn ASMKO mice could prevent or alter the Niemann-Pick disease phenotype. Previous work from our laboratory had shown that ASMKO mice were highly susceptible to irradiation-induced death. Therefore, we preconditioned 1-day-old ASMKO (n=35) mice with a "sublethal" dose of 200 cGy of total body irradiation before BMT. The transplantation effects were then analyzed by biochemical, pathological, and clinical approaches. Engraftment ranging from 7% to 100% was achieved in 97% of the transplanted animals. Growth of the engrafted animals was improved, and their survival was increased (from a mean of 5 months to 9 months). The onset of ataxia also was delayed in most of the engrafted animals. In accordance with these observations, biochemical and pathological analysis revealed significant changes in the transplanted group as compared with nontransplanted animals. Lipid storage was reduced in several organs, and there was evidence of histologic improvement seen throughout the reticuloendothelial system, even in animals that were engrafted as low as 14%. In the central nervous system, lipid storage also was reduced, and the Purkinje cells, which are almost absent in ASMKO mice, were present in certain areas of the transplanted animals cerebella. These results demonstrated that BMT could alter the pathologic phenotype in ASMKO mice, but that this procedure alone was not sufficient to elicit a complete therapeutic effect.


Theoretical study of isomerization and dissociation of acetylene dication in the ground and excited electronic states.
Ab initio calculations employing the configuration interaction method including Davidson's corrections for quadruple excitations have been carried out to unravel the dissociation mechanism of acetylene dication in various electronic states and to elucidate ultrafast acetylene-vinylidene isomerization recently observed experimentally. Both in the ground triplet and the lowest singlet electronic states of C2H2(2+) the proton migration barrier is shown to remain high, in the range of 50 kcal/mol. On the other hand, the barrier in the excited 2 3A" and 1 3A' states decreases to about 15 and 34 kcal/mol, respectively, indicating that the ultrafast proton migration is possible in these states, especially, in 2 3A", even at relatively low available vibrational energies. Rice-Ramsperger-Kassel-Marcus calculations of individual reaction-rate constants and product branching ratios indicate that if C2H(2)2+ dissociates from the ground triplet state, the major reaction products should be CCH+(3Sigma-)+H+ followed by CH+(3Pi)+CH+(1Sigma+) and with a minor contribution (approximately 1%) of C2H+(2A1)+C+(2P). In the lowest singlet state, C2H+(2A1)+C+(2P) are the major dissociation products at low available energies when the other channels are closed, whereas at Eint>5 eV, the CCH+(1A')+H+ products have the largest branching ratio, up to 70% and higher, that of CH+(1Sigma+)+CH+(1Sigma+) is in the range of 25%-27%, and the yield of C2H++C+ is only 2%-3%. The calculated product branching ratios at Eint approximately 17 eV are in qualitative agreement with the available experimental data. The appearance thresholds calculated for the CCH++H+, CH++CH+, and C2H++C+ products are 34.25, 35.12, and 34.55 eV. The results of calculations in the presence of strong electric field show that the field can make the vinylidene isomer unstable and the proton elimination spontaneous, but is unlikely to significantly reduce the barrier for the acetylene-vinylidene isomerization and to render the acetylene configuration unstable or metastable with respect to proton migration.


Back focal plane imaging for light emission from a tunneling junction in a low-temperature ultrahigh-vacuum scanning tunneling microscope.
We report the design and realization of the back focal plane (BFP) imaging for the light emission from a tunnel junction in a low-temperature ultrahigh-vacuum (UHV) scanning tunneling microscope (STM). To achieve the BFP imaging in a UHV environment, a compact "all-in-one" sample holder is designed and fabricated, which allows us to integrate the sample substrate with the photon collection units that include a hemisphere solid immersion lens and an aspherical collecting lens. Such a specially designed holder enables the characterization of light emission both within and beyond the critical angle and also facilitates the optical alignment inside a UHV chamber. To test the performance of the BFP imaging system, we first measure the photoluminescence from dye-doped polystyrene beads on a thin Ag film. A double-ring pattern is observed in the BFP image, arising from two kinds of emission channels: strong surface plasmon coupled emissions around the surface plasmon resonance angle and weak transmitted fluorescence maximized at the critical angle, respectively. Such an observation also helps to determine the emission angle for each image pixel in the BFP image and, more importantly, proves the feasibility of our BFP imaging system. Furthermore, as a proof-of-principle experiment, electrically driven plasmon emissions are used to demonstrate the capability of the constructed BFP imaging system for STM induced electroluminescence measurements. A single-ring pattern is obtained in the BFP image, which reveals the generation and detection of the leakage radiation from the surface plasmon propagating on the Ag surface. Further analyses of the BFP image provide valuable information on the emission angle of the leakage radiation, the orientation of the radiating dipole, and the plasmon wavevector. The UHV-BFP imaging technique demonstrated here opens new routes for future studies on the angular distributed emission and dipole orientation of individual quantum emitters in UHV.


Mild hyperphenylalaninemia and heterozygosity of the phenylalanine hydroxylase gene.
Newborn screening for phenylketonuria (PKU) is now the standard of practice. Initial phenylalanine blood levels of 240 mumol/L result in referral of affected newborns to medical facilities experienced in caring for patients with metabolic disorders. This case report concerns a female infant born in 1976 with a presumptive positive PKU screening test on the third day of life of 240 mumol/L phenylalanine. Follow-up levels while the mother was breast feeding on the sixth day of life were 324 and, on the 27th day, 312 mumol/L. She was subsequently lost to follow-up at age 11 years, but returned at 19 years of age due to pregnancy, with a blood phenylalanine level of 132 mumol/L. Mutation studies then were performed documenting that she was a carrier for the phenylalanine hydroxylase gene and did not have hyperphenylalaninemia. The mother's parents and the infant were also genotyped confirming heterozygosity. The infant on follow-up is completely normal, following a normal pregnancy.


Density of medical and recreational cannabis outlets: racial/ethnic differences in the associations with young adult intentions to use cannabis, e-cigarettes, and cannabis mixed with tobacco/nicotine.
Differences in access to medical versus recreational cannabis outlets and their associations with intentions to use cannabis have not yet been examined among young adults. This study compares the associations between densities of medical versus recreational cannabis outlets and young adults' intentions to use cannabis, electronic cigarettes, and cannabis mixed with tobacco/nicotine products. Racial/ethnic differences in these associations were examined. Young adults ages 18-23 (mean age = 20.9) in Los Angeles County were surveyed online in 2018 after the legalization of recreational cannabis (n = 604). Multiple linear regressions were estimated for the entire sample and stratified by race/ethnicity. Outcomes were intentions to use cannabis, electronic cigarettes, and cannabis mixed with tobacco/nicotine in the next 6 months. Density was measured as the number of medical cannabis dispensaries (MCDs), recreational cannabis retailers (RCRs), and outlets of any type within 5 miles of respondents' homes. Living near more outlets of any type was not significantly associated with intentions to use in the full sample, adjusting for individual- and neighborhood-level characteristics. However, race/ethnicity-stratified models indicated that living near more outlets of any type and more RCRs were significantly associated with stronger co-use intentions among white young adults. Higher MCD density was marginally associated with stronger co-use intentions among Asian young adults. However, higher MCD density was significantly associated with lower intentions to use e-cigarettes among Hispanic young adults. The results suggest racial/ethnic differences in the impact of living near cannabis outlets on intentions to use. Prevention efforts targeting young adults who live near more cannabis outlets may be especially beneficial for white and Asian young adults.


Mineralized Biomaterials Mediated Repair of Bone Defects Through Endogenous Cells.
Synthetic biomaterials that create a dynamic calcium (Ca2+)-, phosphate (PO43-) ion-, and calcium phosphate (CaP)-rich microenvironment, similar to that found in native bone tissue, have been shown to promote osteogenic commitment of stem cells in vitro and in vivo. The intrinsic osteoconductivity and osteoinductivity of such biomaterials make them promising bone grafts for the treatment of bone defects. We thus aimed to evaluate the potential of mineralized biomaterials to induce bone repair of a critical-sized cranial defect in the absence of exogenous cells and growth factors. Our results demonstrate that the mineralized biomaterial alone can support complete bone formation within critical-sized bone defects through recruitment of endogenous cells and neo-bone tissue formation in mice. The newly formed bone tissue recapitulated many key characteristics of native bone such as formation of bone minerals reaching similar bone mineral density, presence of bone-forming osteoblasts and tartrate-resistant acid phosphatase-expressing osteoclasts, as well as vascular networks. Biomaterials that recruit endogenous cells and provide a tissue-specific microenvironment to modulate cellular behavior and support generation of functional tissues are a key step forward in moving bench-side tissue engineering approaches to the bedside. Such tissue engineering strategies could eventually pave the path toward readily available therapies that significantly reduce patient cost of care and improve overall clinical outcomes.


Tumor stroma Siglec15 expression is a poor prognosis predictor in colon adenocarcinoma.
Sialic acid binding Ig-like lectin 15 (Siglec15) is considered a novel immune checkpoint and an emerging target for next-generation cancer immunotherapy. However, the significance of Siglec15 and its relationship with programmed death-ligand 1 (PD-L1) in colon adenocarcinoma (COAD) remain unknown. In this study, we analyzed Siglec15 expression within stromal area (SA) and tumor area (TA), and its relationship with tumor-infiltrating lymphocytes (TILs) in COAD and mismatch repair-proficient (MMR-p) COAD. Siglec15 expression was significantly higher in COAD tissues than in normal tissues, and elevated Siglec15(SA) expression, rather than Siglec15(TA) and Siglec15 (whole) expression, was correlated with poor prognosis and inversely correlated with the density of CD8+ T cell, both in COAD and MMR-p COAD. Moreover, there were no correlations between Siglec15(SA) and PD-L1(SA), and between Siglec15(TA) and PD-L1(TA), whereas there was positive correlation between Siglec15(whole) and PD-L1(whole). A new immune classification based on the Siglec15(SA)/PD-L1(SA) expression, indicated that patients with Siglec15(SA)Low/PD-L1(SA)+ status had the longest survival times in COAD. Our study highlights that Siglec15(SA) is an independent predictor of poor prognosis and has an immunosuppressive role in COAD and MMR-p COAD tissues. These findings may provide insights into improving responses to immunotherapy-included comprehensive treatments for COAD in the future.


Physiology and endocrinology symposium: Anti-Müllerian hormone: a biomarker for the ovarian reserve, ovarian function, and fertility in dairy cows.
This review summarizes studies we conducted to test the hypothesis that size of the ovarian reserve (number of healthy follicles and oocytes in ovaries) positively impacts ovarian function and fertility in cattle. Key results, primarily in Bos taurus dairy cattle, show that antral follicle count (AFC) during follicular waves is highly variable between individuals, but very highly repeatable within individuals. Cycling heifers with low (≤15 follicles ≥3 mm, ~20% of a herd) vs. a high AFC (≥25, ~20% of a herd) have a smaller ovarian reserve, higher FSH but lower anti-Müllerian hormone (AMH), androstenedione, estradiol, and progesterone concentrations. Moreover, cattle with low AFC have a thinner endometrium, decreased response of granulosal, thecal, or luteal cells to FSH or LH and a poorer response to superovulation compared to cattle with high AFC. Interestingly, cows with a very high AFC as heifers have reduced fertility, fewer lactations, and shorter herd longevity, whereas cows with a low vs. intermediate AFC have reduced fertility, fewer lactations, and shorter herd longevity. Anti-Müllerian hormone concentrations are static within individuals but highly positively correlated with AFC, but fertility is not correlated with circulating AMH concentration in heifers and dairy cows with low vs. a higher AMH as heifers have reduced fertility and a shorter herd longevity. Anti-Müllerian hormone concentrations in dairy heifers are a moderately heritable trait (36%), and negatively impacted by inadequate maternal nutrition during early pregnancy or high maternal somatic cell count. We conclude that genetic or environmental manipulations of AMH could enhance size of the ovarian reserve and ovarian function, thereby improving fertility, response to superovulation, and longevity in dairy cows.


Exploring patients' perceptions and experiences of treatments for the prevention of variceal bleeding: a qualitative study.
The most common fatal complication of liver cirrhosis is haemorrhaging caused by variceal rupture. The prevention of the first variceal bleed is, therefore, an important clinical goal. Little is known about patients' experience of treatments geared towards this, or of their perceptions of treatments prior to being exposed to them. To explore the factors impacting patient preference for, and actual experience of carvedilol and variceal band ligation. Semistructured interviews were conducted with 30 patients from across the UK at baseline, prior to random allocation to either carvedilol or variceal band ligation. Twenty patients were interviewed a second time at 6-month follow-up. Five patients who declined the trial were also interviewed. Data were analysed using thematic analysis. There was no clear preference for either treatment pathway at baseline. Key factors reported by patients to influence their treatment preference included: negative experiences with key treatment processes; how long-term or short-term treatment was perceived to be; treatment misconceptions; concerns around polypharmacy and worries around treatment adherence. Patient treatment experience was influenced by their perceptions of treatment effectiveness; clinical surveillance; clinician interaction and communication, or lack thereof. Carvedilol-specific experience was also influenced by the manifestation of side effects and patient dosage routine. Variceal band ligation-specific experience was positively influenced by the use of sedation, and negatively influenced by the procedure recovery period. These data do not support a view that the patient experience of beta-blockade for prevention of variceal bleeds is likely to be superior to variceal band ligation.


Targeting quorum sensing and competence stimulation for antimicrobial chemotherapy.
Bacterial resistance to antibiotics is now a serious problem, with traditional classes of antibiotics having gradually become ineffective. New drugs are therefore needed to target and inhibit novel pathways that affect the growth of bacteria. An important feature in the survival of bacteria is that they coordinate their efforts together as a colony via secreted auto-inducing molecules. Competence stimulating peptides (CSPs) are among the quorum sensing pheromones involved in this coordination. These peptides activate a two-component system in gram-negative bacteria, binding to and activating a histidine kinase receptor called ComD, which phosphorylates a response regulator called ComE, leading to gene expression and induction of competence. Competent bacteria are able to take up exogenous DNA and incorporate it into their own genome. By this mechanism bacteria are able to acquire and share genes encoding antibiotic resistance. Despite having been studied for over 30 years, this pathway has only recently begun to be explored as a novel approach to modulating bacterial growth. Antagonists of ComD might block the signaling cascade that leads to competence, while overstimulation of ComD might also reduce bacterial growth. One possible approach to inhibiting ComD is to examine peptide sequences of CSPs that activate ComD and attempt to constrain them to bioactive conformations, likely to have higher affinity due to pre-organization for recognition by the receptor. Thus, small molecules that mimic an alpha helical epitope of CSPs, the putative ComD binding domain, have been shown here to inhibit growth of bacteria such as S. pneumoniae. Such alpha helix mimetics may be valuable clues to antibacterial chemotherapeutic agents that utilize a new mechanism to control bacterial growth.


[Dengue, arbovirus and migrations in the Indian Ocean].
An arbovirus requires a competent haematophagous arthropod for transmission from one vertebrate to another susceptible host. Air transportations allow quick transfers from place to place and the diffusion of potential vectors or infectious hosts. The merchandise transportation by containers allowed the diffusion of Ae. albopictus from Asia through Africa and America. Emerging arbovirusis may occur in zones where they do not exist. Dengue which originally was located in southeastern Asia, is the most important arbovirusis in the world. The occurrence of dengue haemorrhagic fever (DHF) in Asia and America, mostly in urban areas, increased the global concern about dengue. Likewise, cases of DHF are not reported in Africa and in the Indian Ocean southwestern islands. The principal vector of dengue, Aedes aegypti, was present during the dengue 1 outbreak in Comoros, in 1993. In the other islands, only few specimens of Ae. aegypti are observed, and described mostly as none anthropophilic forms. The role of Ae. albopictus as vector of dengue was suspected and reported during outbreaks in Seychelles and Réunion island in 1977-1978. Yellow fever, present in Africa mostly in restricted areas, is absent in Asia. Japanese encephalitis considered as an emerging disease in India could expand through the islands. Rift valley fever, with periodic epizootics in domestic ungulates in Africa, was described as a new disease in Madagascar in 1990-1991. Crimean-Congo haemorrhagic fever is also present in Madagascar. Humans can be infected by vector bite or by handling infectious animal products. The distribution of other viruses (West Nile, Sindbis, Wesselsbron or Chikungunya) is discussed.


Detection of bovine viral diarrhoea virus infected cattle--testing tissue samples derived from ear tagging using an Erns capture ELISA.
A new diagnostic approach testing tissue samples derived from cattle ear tagging for bovine viral diarrhoea virus (BVDV) antigen in a commercially available antigen capture enzyme-linked immunosorbent assay (ACE) was developed. To validate this method, 99 positive and 469 negative samples were tested. With those samples the assay yielded a sensitivity of 100% and specificity of >or=99.6%. Serum and ear tissue samples from 11 persistently infected (PI) BVDV calves were tested. While serum samples were negative after intake of colostrum, the ear tissue samples could be detected positive for BVDV all the time. Testing multiple samples derived from the same ear from PI cattle yielded positive results and low variation. Using cattle ear tags combining the ear tag application with sampling of a small ear tissue plug and testing those tissue samples with an ACE could be a reliable and economic way of BVDV testing.


Oral microbial communities in sickness and in health.
The relationship between humans and their oral microflora begins shortly after birth and lasts a lifetime. Up until fairly recently, the associations between the host and oral bacteria were considered in terms of a multiplicity of single species interactions. However, it is becoming more apparent that the oral microbes comprise a complex community, and that oral health or disease depends on the interface between the host and the microbial community as a whole. Although it is important to continue studies of the pathogenic properties of specific microbes, these are relevant only in the context of the properties of the community within which they reside. Understanding the microbial communities that drive sickness or health is a key to combating human oral diseases.


Ulnar nerve palsy caused by synovial protrusion in synovial chondromatosis of the elbow: a case report and literature review.
We describe an unusual case of ulnar nerve compression (cubital tunnel syndrome) caused by synovial protrusion in primary synovial chondromatosis of the elbow in a 59-year-old man. Magnetic resonance imaging is a useful tool for diagnosing this rare condition. Surgical excision of the intra-articular multiple loose bodies and ulnar nerve decompression were performed. The clinician should be aware of primary synovial chondromatosis as one of the causative factors of cubital tunnel syndrome.


Cardiovascular events on board commercial maritime vessels: a two-year review.
Cardiovascular diseases (CVDs) are an important concern in merchant maritime operations. They are responsible for the majority of deaths at sea that are not related to injury or violence. The objective was to better understand the epidemiology of CVD in merchant maritime operations. Retrospective review of medical events on board merchant maritime vessels over a period of two years, from a US-based telemedicine provider's database. A total of 1,394 cases were initially retrieved from the database. CVD was diagnosed in 29 cases and was the eleventh leading cause for accessing the telemedicine provider. Five deaths occurred in the study period, three of which related to CVDs. CVDs resulted in more diversions and the utilization of more urgent means of communication. CVDs present a challenge in maritime health. The current pre-employment system is not, in a reasonable cost/benefit balance, able to prevent on board events from occurring. The success of telemedicine depends heavily on the onsite resources, both human and material. Automated External Defibrillators (AEDs), along with other devices such as multi-parameter monitors, are tools generally available to address acute presentations of CVDs, but their applicability on board commercial ships is a matter of controversy. CVDs are an important concern in commercial maritime operations due to the need for subsequent evaluation and potential complications including the risk of sudden cardiac arrest. In this study, CVDs were probably responsible for three on board deaths. Additional research is warranted to provide more evidence about the best resources to have on board to handle CVDs more effectively.


Cerebellar contributions to the perception of temporal cues within the speech and nonspeech domain.
A previous study (Ackermann, Gräber, Hertrich, & Daum, 1997) reported impaired phoneme identification in cerebellar disorders, provided that categorization depended on temporal cues. In order to further clarify the underlying mechanism of the observed deficit, the present study performed a discrimination and identification task in cerebellar patients using two-tone sequences of variable pause length. Cerebellar dysfunctions were found to compromise the discrimination of time intervals extending in duration from 10 to 150 ms, a range covering the length of acoustic speech segments. In contrast, categorization of the same stimuli as a "short" or "long pause" turned out to be unimpaired. These findings, along with the data of the previous investigation, indicate, first, that the cerebellum participates in the perceptual processing of speech and nonspeech stimuli and, second, that this organ might act as a back-up mechanism, extending the storage capacities of the "auditory analyzer" extracting temporal cues from acoustic signals.


Dietary patterns and changes in body weight in women.
Our objective was to examine the association between adherence to dietary patterns and weight change in women. Women (51,670, 26 to 46 years old) in the Nurses' Health Study II were followed from 1991 to 1999. Dietary intake and body weight were ascertained in 1991, 1995, and 1999. A Western pattern, characterized by high intakes of red and processed meats, refined grains, sweets and desserts, and potatoes, and a prudent pattern, characterized by high intakes of fruits, vegetables, whole grains, fish, poultry, and salad dressing, were identified with principal component analysis, and associations between patterns and change in body weight were estimated. Women who increased their Western pattern score had greater weight gain (multivariate adjusted means, 4.55 kg for 1991 to 1995 and 2.86 kg for 1995 to 1999) than women who decreased their Western pattern score (2.70 and 1.37 kg for the two time periods), adjusting for baseline lifestyle and dietary confounders and changes in confounders over time (p < 0.001 for both time periods). Furthermore, among women who increased their prudent pattern score, weight gain was smaller (multivariate-adjusted means, 1.93 kg for 1991 to 1995 and 0.66 kg for 1995 to 1999) than among women who decreased their prudent pattern score (4.83 and 3.35 kg for the two time periods) (p < 0.001). The largest weight gain between 1991 and 1995 and between 1995 and 1999 was observed among women who decreased their prudent pattern score while increasing their Western pattern score (multivariate adjusted means, 6.80 and 4.99 kg), whereas it was smallest for the opposite change in patterns (0.87 and -0.64 kg) (p < 0.001). Adoption of a Western dietary pattern is associated with larger weight gain in women, whereas a prudent dietary pattern may facilitate weight maintenance.


Light-induced conformational changes of the chromophore and the protein in phytochromes: bacterial phytochromes as model systems.
Recombinant phytochromes Agp1 and Agp2 from Agrobacterium tumefaciens are used as model phytochromes for biochemical and biophysical studies. In biliverdin binding phytochromes the site for covalent attachment of the chromophore lies in the N-terminal region of the protein, different from plant phytochromes. The issue which stereochemistry the chromophore adopts in the so-called Pr and Pfr forms is addressed by using a series of locked chromophores which form spectrally characteristic adducts with Agp1 and Agp2. Studies on light-induced conformational changes of Agp1 give an insight into how the intrinsic histidine kinase is modulated by light. Comparison of the crystal structure of an Agp1 fragment with other phytochrome crystal structures supports the idea that a light induced rearrangement of subunits within the homodimer modulates the activity of the kinase.


The impact of liposomal linolenic acid on gastrointestinal microbiota in mice.
The prevalence of Helicobacter pylori has long been a global health issue. Triple therapy, being the first-line treatment, has caused dysbiosis of the gastrointestinal tract that led to various complications. A novel nanomedicine - liposomal linolenic acid (LipoLLA) - has been proven to have great potential in eradicating H. pylori. However, the possible side effects of LipoLLA due to alteration of the gastrointestinal microbiota remain unknown. This study focused on the impact of LipoLLA on gastrointestinal microbiota in mice in comparison with triple therapy in order to assess the safety profile. Mice were divided into five groups: blank control group; H. pylori control group; triple therapy group; low-dose LipoLLA group (25 mg/kg); and high-dose LipoLLA group (50 mg/kg). Fecal samples were collected before and after the intake of corresponding formulas. Gastric tissues were obtained after mice dissection. These samples were analyzed with high-throughput sequencing. The analysis revealed that LipoLLA resulted in minor gut microbiota alteration at different levels. The altered proportions in the high-dose group were higher than that of the low-dose group. On the other hand, the triple therapy group showed dramatic shifts in the major community composition. It displayed a notable boost in the relative abundance of Proteobacteria and Firmicutes along with a decrease in that of Verrucomicrobia and Bacteroidetes. All of them belonged to the major phyla in the microbiome. Triple therapy also led to the growth of the family Enterobacteriaceae, Enterococcaceae, and Clostridiaceae_1 that may be associated with clinical illnesses. Gastric microbiota analysis reached similar conclusions. Our findings indicated that LipoLLA causes minor gastrointestinal microbiota alterations while the triple therapy triggered dramatic changes. Thus, LipoLLA is not only promising but also a safe therapeutic medication to eradicate H. pylori infection.


Hypersensitivity to inhaled flour allergens. Comparison between cereals.
Radioallergosorbent testing (RAST) of sera from subjects sensitized to wheat and rye flour indicated that there is significant reaction with seed extracts of 12 cereals (wheat, durum wheat, triticale, cereal rye, barley, rye grass, oats, canary grass, rice, maize, sorghum and Johnson grass). Results were evaluated in terms of taxonomic relationships and of the electrophoretically determined protein composition of the cereal extracts. RAST uptakes were uniformly low in sera from four rhinitic bakers, yet were significantly above the levels for non-allergic and cord sera. Much higher RAST uptakes were obtained with sera from four asthmatic bakers when tested with wheat and its close relatives, but there was still reasonably high reactivity with more distantly related cereals. RAST inhibition experiments indicated in a more direct way the extent of cross-reactivity between grain extracts of wheat, rye, barley and oats. One baker had a history of more severe attacks of breathlessness following inhalation of rye flour compared with wheat flour. This was confirmed by bronchial challenge testing, but the comparison was not obviously consistent with the results of prick testing or estimation of histamine released from his leucocytes. The results as a whole suggested that the bran layers of cereal grains are at least as allergenic as flour.


Native valve, prosthetic valve, and cardiac device-related infective endocarditis: A review and update on current innovative diagnostic and therapeutic strategies.
Infective endocarditis (IE) is a life-threatening microbial infection of native and prosthetic heart valves, endocardial surface, and/or indwelling cardiac device. Prevalence of IE is increasing and mortality has not significantly improved despite technological advances. This review provides an updated overview using recent literature on the clinical presentation, diagnosis, imaging, causative pathogens, treatment, and outcomes in native valve, prosthetic valve, and cardiac device-related IE. In addition, the experimental approaches used in IE research to improve the understanding of disease mechanisms and the current diagnostic pipelines are discussed, as well as potential innovative diagnostic and therapeutic strategies. This will ultimately help towards deriving better diagnostic tools and treatments to improve IE patient outcomes.


Crystal structure of Zika virus NS5 RNA-dependent RNA polymerase.
The current Zika virus (ZIKV) outbreak became a global health threat of complex epidemiology and devastating neurological impacts, therefore requiring urgent efforts towards the development of novel efficacious and safe antiviral drugs. Due to its central role in RNA viral replication, the non-structural protein 5 (NS5) RNA-dependent RNA-polymerase (RdRp) is a prime target for drug discovery. Here we describe the crystal structure of the recombinant ZIKV NS5 RdRp domain at 1.9 Å resolution as a platform for structure-based drug design strategy. The overall structure is similar to other flaviviral homologues. However, the priming loop target site, which is suitable for non-nucleoside polymerase inhibitor design, shows significant differences in comparison with the dengue virus structures, including a tighter pocket and a modified local charge distribution.


Determining factors in children's screen time in early childhood.
The use of media by children in early childhood is increasingly common, and it is necessary to investigate the determinants of screen time, which is understood as the total child screen exposure time, including television and interactive media. This is a descriptive, exploratory, and cross-sectional study conducted with 180 children between 24 and 42 months of age, allocated in Group 1, less than two hours daily screen exposure time; Group 2, daily screen exposure time equal to or more than two hours. Bivariate and binary logistic regression analyses were performed. Screen time determining factors studied were family environment, evaluated with the Family Environment Resource Inventory; socioeconomic factors; nutritional status and child development status, evaluated with the Bayley III test. As a result, 63% of children had daily screen time exceeding two hours, and television still is the main culprit for children screen exposure. We observed that screen time exposure was positively associated with family resources, economic level, and language development. However, only the last two factors explained the longer screen time.