Quenching the thirst in dialysis patients.
In a double-blind cross-over trial, 22 stable end-stage renal failure patients on maintenance haemodialysis were subjected to conventional dialysis with dialysate containing 137 mEq/l sodium and constant ultrafiltration (UF) and to a different dialysis therapy, in which, by linear sodium modelling, the dialysate sodium was reduced from 137 to 128 mEq/l. A computerized UF program was used to gradually reduce the UF to a minimum towards the end of the session. Severity of thirst, interdialytic weight gain and intradialytic complications were less with low sodium dialysate. It allowed adequate UF with absolute hemodynamic stability. The reduced incidence of complication with low sodium dialysate therapy was probably because they required less UF.


Maintenance of stem cell populations in plants.
Flowering plants have the unique ability to produce new organs continuously, for hundreds of years in some species, from stem cell populations maintained at their actively growing tips. The shoot tip is called the shoot apical meristem, and it acts as a self-renewing source of undifferentiated, pluripotent stem cells whose descendents become incorporated into organ and tissue primordia and acquire different fates. Stem cell maintenance is an active process, requiring constant communication between different regions of the shoot apical meristem to coordinate loss of stem cells from the meristem through differentiation with their replacement through cell division. Stem cell research in model plant systems is facilitated by the fact that mutants with altered meristem cell identity or accumulation are viable, allowing dissection of stem cell behavior by using genetic, molecular, and biochemical methods. Such studies have determined that in the model plant Arabidopsis thaliana stem cell maintenance information flows via a signal transduction pathway that is established during embryogenesis and maintained throughout the life cycle. Signaling through this pathway results in the generation of a spatial feedback loop, involving both positive and negative interactions, that maintains stem cell homeostasis. Stem cell activity during reproductive development is terminated by a temporal feedback loop involving both stem cell maintenance genes and a phase-specific flower patterning gene. Our current investigations provide additional insights into the molecular mechanisms that regulate stem cell activity in higher plants.


Estimated risk of cardiovascular events and long-term complications: The projected future of diabetes patients in Delhi from the DEDICOM-II survey.
Despite high prevalence and ethnic susceptibility, limited published estimates are available on long term complication risks among known diabetes patients in India. Hence, we undertook evaluation of the cardiovascular risk of known diabetes patients from Delhi. The community-survey was conducted using a probability-proportionate-to-size(systematic) 2-stage cluster design. Thirty areas were selected for a house-to-house survey to recruit 25 to 30 subjects (known diabetes ≥1 year; 35-65 years of age) per area. Scores from the UKPDS 2.1, UKPDS 2.0, Framingham, ASCVD, WHO, NHS and SCORE studies were used for 10-year risk calculation. We enrolled 843 subjects of which 800 consented for blood sampling. The mean age of the subjects was 53.0(52.1-54.0) years, the mean duration since diagnosis was 7.1(6.7-7.5) years, with 49.8 % women. 61.8 % were hypertensive, 81.5 % were dyslipidaemic and 53.3 % had poor glycaemic control. Although variable, risk engines estimates were consensual in projecting a high ten-year Coronary-Heart-Disease risk of 10-16 %, a stroke risk of 3.7-5.0 %, and a 5.0-5.7% risk of cardiovascular fatality. These risks were 1.5-3 times the 'risk at target levels' suggesting mitigability. Only 9.3 %, 16.0 %, and 30.0 % were taking aspirin, lipid lowering drugs and antihypertensives respectively. The study highlights the impending impact of, and the scope for improvement in the cardiovascular risk profile of diabetes patients in Delhi, including the use of cardioprotective medications. It strengthens the case for developing and testing potential interventions for improvement.


A comparative diuretic and tissue distribution study of bumetanide and furosemide in the dog.
Intravenous dose-response data obtained from renal clearance studies in anesthetized dogs indicated that bumetanide was approximately 30-fold more potent than furosemide in enhancing sodium excretion. After the administration of 0.01 mg/kg of bumetanide or 1.0 mg/kg of furosemide, the relationship between i.v. diuretic activity and tissue distribution was evaluated. In dog renal clearance experiments, bumetanide and furosemide significantly enhanced urine flow, sodium and potassium excretion. Inulin clearance as an estimate of glomerular filtration rate was not altered by either drug, but sodium reabsorption was decreased with bumetanide (13%) and furosemide (12%). At these diuretic doses, both compounds were bound to dog plasma protein to about the same extent (86-91%), although total plasma levels were 100-fold higher for furosemide. Within 1/2 hour after the i.v. administration of 14C-bumetanide or 14C-furosemide, 86 to 99% of the 14C in urine, plasma, kidney, and liver appeared as unchanged drug. One minute after maximal diuresis bumetanide was found to have a higher affinity (3-fold) for kidney compared to furosemide. These data offer a possible explanation for the i.v. diuretic potency difference between these two compounds. Furthermore, the lack of significant difference in plasma protein binding and the absence of urinary metabolites of either drug suggest that other factors may also contribute to the marked differences in diuretic activity between bumetanide and furosemide.


Cytotoxicity and antineoplastic activities of alkylamines and their borane derivatives.
The alkylamines and their related boron derivatives demonstrated potent cytotoxicity against the growth of murine and human tissue cultured cells. These agents did not necessarily require the boron atom to possess potent cytotoxic action in certain tumor lines. Their ability to suppress tumor cell growth was based on their inhibition of DNA and protein syntheses. DNA synthesis was reduced because purine synthesis was blocked at the enzyme site of IMP dehydrogenase by the agents. In addition ribonucleotide reductase and nucleoside kinase activities were reduced by the agents which would account for the reduced d[NTP] pools. The DNA template or molecule may be a target of the drugs with regard to binding of the drug to nucleoside bases or intercalaction of the drug between DNA base pairs. Only some Of the agents caused DNA fragmentation with reduced DNA viscosity. These effects would contribute to overall cell death afforded by the agents.


Posterior fossa lesion volume and slowed information processing in multiple sclerosis.
The relationship between performance on information processing efficiency measures and MRI-derived lesion volume including global and regional T2 and T1 lesion volumes was investigated in 20 patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). Processing speed, as measured by the Sternberg Memory Scanning Test, was significantly correlated with posterior fossa lesion volume and slowed reaction time in seven out of eight patients (six out of seven with SPMS) with any lesion volume in the posterior fossa suggesting a 'threshold effect'. Processing capacity as measured by the Salthouse Keeping Track Test was not significantly correlated with the MRI measures. Cognitive performance did not correlate with Expanded Disability Status Scale score, depression or fatigue, and patients performed within normal limits on tests of attention/concentration ability. The significant relationship between posterior fossa lesion volume and memory scanning speed in this study suggests that pathological damage in the posterior fossa may contribute to slowed cognitive processing and may be an important direction for future studies of cognitive function in multiple sclerosis. Lack of correlation of cognitive measures with the other MRI measures may be due to low lesion volume relative to other studies, sample composition, and limited pathological specificity of the MRI measures.


Stable transformation of an episomal protein-tagging shuttle vector in the piscine diplomonad Spironucleus vortens.
Diplomonads are common free-living inhabitants of anoxic aquatic environments and are also found as intestinal commensals or parasites of a wide variety of animals. Spironucleus vortens is a putatively commensal diplomonad of angelfish that grows to high cell densities in axenic culture. Genomic sequencing of S. vortens is in progress, yet little information is available regarding molecular and cellular aspects of S. vortens biology beyond descriptive ultrastructural studies. To facilitate the development of S. vortens as an additional diplomonad experimental model, we have constructed and stably transformed an episomal plasmid containing an enhanced green fluorescent protein (GFP) tag, an AU1 epitope tag, and a tandem affinity purification (TAP) tag. This construct also contains selectable antibiotic resistance markers for both S. vortens and E. coli. Stable transformants of S. vortens grew relatively rapidly (within 7 days) after electroporation and were maintained under puromycin selection for over 6 months. We expressed the enhanced GFP variant, eGFP, under transcriptional control of the S. vortens histone H3 promoter, and visually confirmed diffuse GFP expression in over 50% of transformants. Next, we generated a histone H3::GFP fusion using the S. vortens conventional histone H3 gene and its native promoter. This construct was also highly expressed in the majority of S. vortens transformants, in which the H3::GFP fusion localized to the chromatin in both nuclei. Finally, we used fluorescence in situ hybridization (FISH) of the episomal plasmid to show that the transformed plasmid localized to only one nucleus/cell and was present at roughly 10-20 copies per nucleus. Because S. vortens grows to high densities in laboratory culture, it is a feasible diplomonad from which to purify native protein complexes. Thus, we also included a TAP tag in the plasmid constructs to permit future tagging and subsequent purification of protein complexes by affinity chromatography via a two-step purification procedure. Currently, progress in protistan functional and comparative genomics is hampered by the lack of free-living or commensal protists in axenic culture, as well as a lack of molecular genetic tools with which to study protein function in these organisms. This stable transformation protocol combined with the forthcoming genome sequence allows Spironucleus vortens to serve as a new experimental model for cell biological studies and for comparatively assessing protein functions in related diplomonads such as the human intestinal parasite, Giardia intestinalis.


Translation and cultural adaptation of the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale into Arabic for use with patients with diabetes in Libya.
In Libya neuropathic pain is rarely assessed in patients with diabetes. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale is used worldwide to screen for neuropathic pain. There is no Arabic version of LANSS for use in Libya. The aim of this study was to develop an Arabic version of LANSS and to assess its validity and reliability in diabetic patients in Benghazi, Libya. LANSS was translated into Arabic by four bilingual translators and back translated to English by a university academic. Validity and reliability of the Arabic LANSS was assessed on 110 patients attending a Diabetes Centre in Benghazi. Concurrent validity was tested and compared with the Self-completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS). Test-retest reliability was conducted 1-2 weeks later. Internal consistency and inter-class correlation (ICC) between LANSS and S-LANSS was also tested. Internal consistency within first completion of the Arabic LANSS was acceptable (Cronbach's alpha = 0.793) and similar to the Arabic S-LANSS (0.796) and the second completion of the Arabic LANSS (0.795). ICC between the Arabic LANSS and the Arabic S-LANSS was 0.999 (p < 0.001). Test-retest reliability (ICC) between first and second completions of the Arabic LANSS was 0.999 (p < 0.001). Kappa measurement of agreement between the two Arabic LANSS completions and S-LANSS was high on all seven items (Kappa >0.95, p < 0.0001). We concluded that the Arabic version of LANSS pain scale was valid and reliable for use on Libyan diabetic patients. This study provided results suggesting that the S-LANSS could also be used on diabetic patients.


Effects of food factors on signal transduction pathways.
Consumption of plant-derived foods, especially fruits and vegetables, has been linked to decreased risk of cancer. Laboratory studies with animals and cells in culture have shown cancer preventive activity of chemicals isolated from soy, tea, rice and many green, yellow and orange fruits and vegetables. Using cell culture, transgenic mice and knockout mice models to examine the anti-cancer effects of these dietary factors at the molecular level, we found that (11) (-)-epigallocatechin gallate (EGCG), the major active polyphenol in green tea, and theaflavins, the major active components in black tea, inhibit epidermal growth factor (EGF)- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced JB6 cell transformation. At the same dose range that inhibited cell transformation, EGCG and theaflavins inhibited activator protein-1 (AP-1) activation. These compounds also inhibited ultraviolet B (UVB)-induced AP-1 and nuclear factor kappa B (NFkappaB)-dependent transcriptional activation; (2) resveratrol, found at high levels in grapes, inhibited cell transformation through the induction of apoptosis, mediated through JNK and p53-dependent pathways; (3) inositol hexaphosphate (InsP6), an active compound from rice and other grains, inhibited TPA- or EGF-induced transformation and signal transduction through its effects on phosphatidylinositol-3 kinase (PI-3) kinase; (4) phenethyl isothiocyanate (PEITC), which occurs as a conjugate in certain cruciferous vegetables, inhibited cell transformation corresponding with the induction of apoptosis. An elevation of p53 is required for PEITC-induced apoptosis. Our studies indicated that the chemopreventive effect of these food factors may be mediated by their effects on different signal transduction pathways; (5) retinoids (vitamin A and its metabolites) inhibited tumor promoter-induced cell transformation and tumor promotion in transgenic mice through the inhibition of AP-1 action but not through the activation of retinoic acid response element (RARE).


Tualang honey has higher phenolic content and greater radical scavenging activity compared with other honey sources.
Many chronic diseases are associated with increased oxidative stress caused by an imbalance between free-radical production and the antioxidant level. Antioxidants, which are abundant in natural honey, are free-radical scavengers that either reduce the formation of or neutralize free radicals. The composition and source of honey greatly dictates its biochemical properties. We performed a comparative analysis of the total phenolic content and antioxidant potential of common commercially available honeys along with Malaysian tualang honey. In vitro biochemical analysis of the phenolic content by the Folin-Ciocalteau method revealed a significantly elevated phenolic content (83.96 ± 4.53 mg gallic acid equivalents per 100 g) in tualang honey. In addition, the antioxidant capacity (53.06 ± 0.41 mg ascorbic acid equivalents per gram) of tualang honey was greater, as assessed by the phosphomolybdenum method, 2,2-diphenyl-1-picryl-hydrazyl assay, and ferric reducing/antioxidant power assay. Peroxynitrite and superoxide radical scavenging activity was determined by spectrophotometric analysis in different honey types. Our data suggest that the elevated free-radical scavenging and antioxidant activity observed in tualang honey is due to the increased level of phenolic compounds. In addition to its antibacterial, anticarcinogenic, and anti-inflammatory properties, our study highlights the favorable antioxidant properties of tualang honey, which may be important to human nutrition and health.


Cigarette smoke induces pulmonary arterial dysfunction through an imbalance in the redox status of the soluble guanylyl cyclase.
Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking (CS), is one of the most common diseases globally. Some COPD patients also develop pulmonary hypertension (PH), a severe complication that leads to premature death. Evidence suggests reactive oxygen species (ROS) involvement in COPD and PH, especially regarding pulmonary artery smooth muscle cells (PASMC) dysfunction. However, the effects of CS-driven oxidative stress on the pulmonary vasculature are not completely understood. Herein we provide evidence on the effects of CS extract (CSE) exposure on PASMC regarding ROS production, antioxidant response and its consequences on vascular tone dysregulation. Our results indicate that CSE exposure promotes mitochondrial fission, mitochondrial membrane depolarization and increased mitochondrial superoxide levels. However, this superoxide increase did not parallel a counterbalancing antioxidant response in human pulmonary artery (PA) cells. Interestingly, the mitochondrial superoxide scavenger mitoTEMPO reduced mitochondrial fission and membrane potential depolarization caused by CSE. As we have previously shown, CSE reduces PA vasoconstriction and vasodilation. In this respect, mitoTEMPO prevented the impaired nitric oxide-mediated vasodilation, while vasoconstriction remained reduced. Finally, we observed a CSE-driven downregulation of the Cyb5R3 enzyme, which prevents soluble guanylyl cyclase oxidation in PASMC. This might explain the CSE-mediated decrease in PA vasodilation. These results provide evidence that there might be a connection between mitochondrial ROS and altered vasodilation responses in PH secondary to COPD, and strongly support the potential of antioxidant strategies specifically targeting mitochondria as a new therapy for these diseases.


Competition between two Usutu virus isolates in cell culture and in the common house mosquito Culex pipiens.
Usutu virus (USUV) is a mosquito-borne flavivirus of African origin. Over the past decades, USUV has spread through Europe causing mass die-offs among multiple bird species. The natural transmission cycle of USUV involves Culex spp. mosquitoes as vectors and birds as amplifying hosts. Next to birds and mosquitoes, USUV has also been isolated from multiple mammalian species, including humans, which are considered dead-end hosts. USUV isolates are phylogenetically classified into an African and European branch, subdivided into eight genetic lineages (Africa 1, 2, and 3 and Europe 1, 2, 3, 4, and 5 lineages). Currently, multiple African and European lineages are co-circulating in Europe. Despite increased knowledge of the epidemiology and pathogenicity of the different lineages, the effects of co-infection and transmission efficacy of the co-circulating USUV strains remain unclear. In this study, we report a comparative study between two USUV isolates as follows: a Dutch isolate (USUV-NL, Africa lineage 3) and an Italian isolate (USUV-IT, Europe lineage 2). Upon co-infection, USUV-NL was consistently outcompeted by USUV-IT in mosquito, mammalian, and avian cell lines. In mosquito cells, the fitness advantage of USUV-IT was most prominently observed in comparison to the mammalian or avian cell lines. When Culex pipiens mosquitoes were orally infected with the different isolates, no overall differences in vector competence for USUV-IT and USUV-NL were observed. However, during the in vivo co-infection assay, it was observed that USUV-NL infectivity and transmission were negatively affected by USUV-IT but not vice versa.


[Electron microscopic research in non-A, non-B viral hepatitis with a fecal-oral mechanism of infection transmission].
Fecal specimens collected in the early stage of the disease from hepatitis patients classified by serological, clinical, and epidemiological data as non-A-non-B hepatitis were examined by means of cross immune electron microscopy. Extracts of feces from such patients were found to contain full, semi-empty, and empty virus particles without envelopes, 27-30 nm in size, forming immune complexes only in the presence of acute and convalescent sera from patients with this type of hepatitis. The lack of serological crosses with hepatitis A and non-A-non-B viruses isolated in other regions suggests that this virus is antigenically distinct. The final solution requires further studies in which methods of molecular biology of viruses should be used.


A new approach to identifying patients with elevated risk for Fabry disease using a machine learning algorithm.
Fabry disease (FD) is a rare genetic disorder characterized by glycosphingolipid accumulation and progressive damage across multiple organ systems. Due to its heterogeneous presentation, the condition is likely significantly underdiagnosed. Several approaches, including provider education efforts and newborn screening, have attempted to address underdiagnosis of FD across the age spectrum, with limited success. Artificial intelligence (AI) methods present another option for improving diagnosis. These methods isolate common health history patterns among patients using longitudinal real-world data, and can be particularly useful when patients experience nonspecific, heterogeneous symptoms over time. In this study, the performance of an AI tool in identifying patients with FD was analyzed. The tool was calibrated using de-identified health record data from a large cohort of nearly 5000 FD patients, and extracted phenotypic patterns from these records. The tool then used this FD pattern information to make individual-level estimates of FD in a testing dataset. Patterns were reviewed and confirmed with medical experts. The AI tool demonstrated strong analytic performance in identifying FD patients. In out-of-sample testing, it achieved an area under the receiver operating characteristic curve (AUROC) of 0.82. Strong performance was maintained when testing on male-only and female-only cohorts, with AUROCs of 0.83 and 0.82 respectively. The tool identified small segments of the population with greatly increased prevalence of FD: in the 1% of the population identified by the tool as at highest risk, FD was 23.9 times more prevalent than in the population overall. The AI algorithm used hundreds of phenotypic signals to make predictions and included both familiar symptoms associated with FD (e.g. renal manifestations) as well as less well-studied characteristics. The AI tool analyzed in this study performed very well in identifying Fabry disease patients using structured medical history data. Performance was maintained in all-male and all-female cohorts, and the phenotypic manifestations of FD highlighted by the tool were reviewed and confirmed by clinical experts in the condition. The platform's analytic performance, transparency, and ability to generate predictions based on existing real-world health data may allow it to contribute to reducing persistent underdiagnosis of Fabry disease.


Is there a place for liver grafting for malignancy?
In 94 patients liver transplantations for malignant tumors of the liver have been performed in this institution from 1972 to 1987. The long-term overall results in hepatic transplantation for irresectable tumors are disappointing in spite of good short-term palliation in most of the patients. Tumor recurrence is the rule. But individual long-living patients demonstrate the potentials of this treatment. Thus the crucial question will be a proper selection of patients. The relative suitability (in descending order of favorableness) of the kinds of tumors may range from HCC without cirrhosis, to central bile duct tumors, to HCC in cirrhosis, to CCC, and finally to secondaries. But this range can only give some probability for the success rate. More important is the tumor stage. Survival in lymph node-positive stages is by far worse than in lymph node-negative stages. The 6-month, 1-year, and 2-year actuarial survival data in our experience for lymph node-negative (lymph node-positive) HCC without cirrhosis are 83%, 75%, 75% (33%, 11%, 11%); in bile duct carcinomas in lymph node-negative stages (lymph node-positive) they are 6 months, 100% (40%); 1 year, 100% (13%); and 2 years, 83% (0%). Hepatic transplantation for selected tumor patients furthermore seems justified and is essential for a detailed analysis of the chance of different tumor types for success with this method of treatment.


Different Secondary Metabolite Profiles of Phylogenetically almost Identical Streptomyces griseus Strains Originating from Geographically Remote Locations.
As Streptomyces have shown an outstanding capacity for drug production, different campaigns in geographically distant locations currently aim to isolate new antibiotic producers. However, many of these newly isolated Streptomyces strains are classified as identical to already described species. Nevertheless, as discrepancies in terms of secondary metabolites and morphology are possible, we compared two Streptomyces strains with identical 16S rRNA gene sequences but geographically distant origins. Chosen were an Easter Island Streptomyces isolate (Streptomyces sp. SN25_8.1) and the next related type strain, which is Streptomyces griseus subsp. griseus DSM 40236T isolated from Russian garden soil. Compared traits included phylogenetic relatedness based on 16S rRNA gene sequences, macro and microscopic morphology, antibiotic activity and secondary metabolite profiles. Both Streptomyces strains shared several common features, such as morphology and core secondary metabolite production. They revealed differences in pigmentation and in the production of accessory secondary metabolites which appear to be strain-specific. In conclusion, despite identical 16S rRNA classification Streptomyces strains can present different secondary metabolite profiles and may well be valuable for consideration in processes for drug discovery.


An ontology for Xenopus anatomy and development.
The frogs Xenopus laevis and Xenopus (Silurana) tropicalis are model systems that have produced a wealth of genetic, genomic, and developmental information. Xenbase is a model organism database that provides centralized access to this information, including gene function data from high-throughput screens and the scientific literature. A controlled, structured vocabulary for Xenopus anatomy and development is essential for organizing these data. We have constructed a Xenopus anatomical ontology that represents the lineage of tissues and the timing of their development. We have classified many anatomical features in a common framework that has been adopted by several model organism database communities. The ontology is available for download at the Open Biomedical Ontologies Foundry http://obofoundry.org. The Xenopus Anatomical Ontology will be used to annotate Xenopus gene expression patterns and mutant and morphant phenotypes. Its robust developmental map will enable powerful database searches and data analyses. We encourage community recommendations for updates and improvements to the ontology.


Self- and informant perceptions of psychopathic traits in relation to the triarchic model.
The validity of self-report psychopathy measures may be undermined by characteristics thought to be defining features of the construct, including poor self-awareness, pathological lying, and impression management. The current study examined agreement between self- and informant perceptions of psychopathic traits captured by the triarchic model (Patrick, Fowler, & Krueger, 2009) and the extent to which psychopathic traits are associated with socially desirable responding. Participants were undergraduate roommate dyads (N = 174; Mage = 18.9 years; 64.4% female; 59.8% Caucasian) who completed self- and informant reports of boldness, meanness, and disinhibition. Self-reports of psychopathic traits reasonably aligned with the perceptions of informants (rs = .36-.60), and both predicted various types of antisocial behaviors, although some associations were only significant for monomethod correlations. Participants viewed by informants as more globally psychopathic did not engage in greater positive impression management. However, this response style significantly correlated with self- and informant-reported boldness, suppressing associations with antisocial behavior. These findings suggest that participants are willing and able to disclose psychopathic personality traits in research settings under conditions of confidentiality. Nonetheless, accounting for response style is potentially useful when using self-report measures to examine the nature and correlates of psychopathic traits.


Genotypic variation in whole-plant transpiration efficiency in sorghum only partly aligns with variation in stomatal conductance.
Water scarcity can limit sorghum (Sorghum bicolor (L.) Moench) production in dryland agriculture, but increased whole-plant transpiration efficiency (TEwp, biomass production per unit of water transpired) can enhance grain yield in such conditions. The objectives of this study were to quantify variation in TEwp for 27 sorghum genotypes and explore the linkages of this variation to responses of the underpinning leaf-level processes to environmental conditions. Individual plants were grown in large lysimeters in two well-watered experiments. Whole-plant transpiration per unit of green leaf area (TGLA) was monitored continuously and stomatal conductance and maximum photosynthetic capacity were measured during sunny conditions on recently expanded leaves. Leaf chlorophyll measurements of the upper five leaves of the main shoot were conducted during early grain filling. TEwp was determined at harvest. The results showed that diurnal patterns in TGLA were determined by vapour pressure deficit (VPD) and by the response of whole-plant conductance to radiation and VPD. Significant genotypic variation in the response of TGLA to VPD occurred and was related to genotypic differences in stomatal conductance. However, variation in TGLA explained only part of the variation in TEwp, with some of the residual variation explained by leaf chlorophyll readings, which were a reflection of photosynthetic capacity. Genotypes with different genetic background often differed in TEwp, TGLA and leaf chlorophyll, indicating potential differences in photosynthetic capacity among these groups. Observed differences in TEwp and its component traits can affect adaptation to drought stress.


An audit of obstetricians' management of women potentially infected with blood-borne viruses.
To assess obstetricians' current antenatal screening practices for blood-borne viruses (hepatitis B, hepatitis C and HIV) and how they manage pregnant women infected with a blood-borne virus. National cross-sectional survey conducted between September 2002 and January 2003. All obstetricians (n = 767) registered with the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) were mailed a questionnaire assessing their antenatal screening practices and knowledge of management of women potentially infected with a blood-borne virus. Concordance of clinical practice with RANZCOG recommendations and current evidence-based guidelines. 523 obstetricians (68% response rate) completed the questionnaire. Fifty-one per cent of respondents said they would always offer HIV screening and 60% would always offer HCV screening. For HIV-infected women, 36% of obstetricians would always recommend elective caesarean section and 33% would always avoid rupture of membranes. Despite a lack of evidence, 34% of obstetricians advise patients that the risk of HBV transmission is increased with breastfeeding, and 47% give the same advice about HCV transmission. There is some discordance between the RANZCOG antenatal screening recommendations for HCV and HIV and current practice. Knowledge about the management of HIV-infected women could be improved, and more obstetricians need to be aware that current evidence suggests there is no increased risk of transmission of HBV or HCV with breastfeeding.


Heterologous Expression of Two Brassica campestris CCCH Zinc-Finger Proteins in Arabidopsis Induces Cytoplasmic Foci and Causes Pollen Abortion.
The membrane-less organelles in cytoplasm that are presented as cytoplasmic foci were successively identified. Although multiple CCCH zinc-finger proteins have been found to be localized in cytoplasmic foci, the relationship between their specific localization and functions still needs further clarification. Here, we report that the heterologous expression of two Brassica campestris CCCH zinc-finger protein genes (BcMF30a and BcMF30c) in Arabidopsis thaliana can affect microgametogenesis by involving the formation of cytoplasmic foci. By monitoring the distribution of proteins and observing pollen phenotypes, we found that, when these two proteins were moderately expressed in pollen, they were mainly dispersed in the cytoplasm, and the pollen developed normally. However, high expression induced the assembly of cytoplasmic foci, leading to pollen abortion. These findings suggested that the continuous formation of BcMF30a/BcMF30c-associated cytoplasmic foci due to high expression was the inducement of male sterility. A co-localization analysis further showed that these two proteins can be recruited into two well-studied cytoplasmic foci, processing bodies (PBs), and stress granules (SGs), which were confirmed to function in mRNA metabolism. Together, our data suggested that BcMF30a and BcMF30c play component roles in the assembly of pollen cytoplasmic foci. Combined with our previous study on the homologous gene of BcMF30a/c in Arabidopsis, we concluded that the function of these homologous genes is conserved and that cytoplasmic foci containing BcMF30a/c may participate in the regulation of gene expression in pollen by regulating mRNA metabolism.


A homologues prediction strategy for comprehensive screening and characterization of C21 steroids from Xiao-ai-ping injection by using ultra high performance liquid chromatography coupled with high resolution hybrid quadrupole-orbitrap mass spectrometry.
Because of the complicated chemical composition of Traditional Chinese Medicines, their chemical profile study has been a great challenge. In the present work, a homologues prediction strategy for rapid screening and identification of C21 steroids in Xiao-ai-ping injection was developed by using an ultra high performance liquid chromatography coupled with high resolution hybrid quadrupole-orbitrap mass spectrometry. This strategy was characterized by the design of C21 steroidal skeleton, substituent group and glycan chain in an orderly way, which could quickly and efficiently screen the interested precursor ions. As a result, a total of 95C21 steroids including 47 potential new ones were identified or tentatively identified, which greatly expanded our knowledge of C21 steroids in Xiao-ai-ping injection. The results indicated that the homologues prediction strategy not only provided an efficient technique to screen and identify target constituents, but also offered a new perspective for discovery new components in Traditional Chinese Medicines.


Potential effectiveness of integrating human milk banking and lactation support on neonatal outcomes at Pumwani Maternity Hospital, Kenya.
We assessed the potential effectiveness of human milk banking and lactation support on provision of human milk to neonates admitted in the newborn unit (NBU) at Pumwani Maternity Hospital, Kenya. This pre-post intervention study collected data from mothers/caregivers and their vulnerable neonates or term babies who lacked sufficient mother's milk for several reasons admitted in the NBU. The intervention included establishing a human milk bank and strengthening lactation support. Preintervention data were collected between 5 October 2018 and 11 November 2018, whereas postintervention data were collected between 4 September 2019 and 6 October 2019. Propensity score-matched analysis was performed to assess the effect of the intervention on exclusive use of human milk, use of human milk as the first feed, feeding intolerance and duration of NBU stay. The surveys included 123 and 116 newborns at preintervention and postintervention, respectively, with 160 newborns (80 in each group) being included in propensity score matched analysis. The proportion of neonates who exclusively used human milk during NBU stay increased from 41.3% preintervention to 63.8% postintervention (adjusted odds ratio [OR]: 2.68; 95% confidence interval [CI]: 1.31, 5.53) and those whose first feed was human milk increased from 55.0% preintervention to 83.3% postintervention (adjusted OR: 5.09; 95% CI: 2.18, 11.88). The mean duration of NBU stay was 27% (95% CI: 5.8%, 44.0%) lower in the postintervention group than in the preintervention group. The intervention did not affect feeding intolerance. Integrating human milk banking and lactation support may improve exclusive use of human milk among vulnerable neonates in a resource limited setting.


Antibiotics in the aquatic environment--a review--part I.
Although antibiotics have been used in large quantities for some decades, until recently the existence of these substances in the environment has received little notice. It is only in recent years that a more complex investigation of antibiotic substances has been undertaken in order to permit an assessment of the environmental risks they may pose. Within the last decade an increasing number of studies covering antibiotic input, occurrence, fate and effects have been published, but there is still a lack of understanding and knowledge about antibiotics in the aquatic environment despite the numerous studies performed. This review addresses the present state of knowledge concerning the input, occurrence, fate and effects of antibiotics in the environment. It brings up important questions that are still open, and addresses some significant issues which must be tackled in the future for a better understanding of the behavior of antibiotics in the environment, as well as the risks associated with their occurrence. Questions related to resistance in the environment that may be caused by antibiotics will be addressed in the second part.


Computational Evaluation of Al-Decorated g-CN Nanostructures as High-Performance Hydrogen-Storage Media.
Density functional theory (DFT) calculations were employed to solve the electronic structure of aluminum (Al)-doped g-CN and further to evaluate its performance in hydrogen storage. Within our configurations, each 2 × 2 supercell of this two-dimensional material can accommodate four Al atoms, and there exist chemical bonding and partial charge transfer between pyridinic nitrogen (N) and Al atoms. The doped Al atom loses electrons and tends to be electronically positive; moreover, a local electronic field can be formed around itself, inducing the adsorbed H2 molecules to be polarized. The polarized H2 molecules were found to be adsorbed by both the N and Al atoms, giving rise to the electrostatic attractions between the H2 molecules and the Al-doped g-CN surface. We found that each 2 × 2 supercell can adsorb at most, 24 H2 molecules, and the corresponding adsorption energies ranged from -0.11 to -0.31 eV. The highest hydrogen-storage capacity of the Al-doped g-CN can reach up to 6.15 wt%, surpassing the goal of 5.50 wt% proposed by the U.S. Department of Energy. Additionally, effective adsorption sites can be easily differentiated by the electronic potential distribution map of the optimized configurations. Such a composite material has been proven to possess a high potential for hydrogen storage, and we have good reasons to expect that in the future, more advanced materials can be developed based on this unit.


Gouty tophi in the penis: a case report and review of the literature.
Gout is a metabolic disease characterized by hyperuricemia and the deposition of monosodium urate crystals in different anatomical locations. We report the case of a 61-year-old man who received consultation for gouty tophi in the penis, which is an unusual location for this type of pathology, that was resolved with the surgical removal of the tophi. We provide a review on gout and its treatment as well as other locations where atypical gouty tophi have been described.


Hierarchical classification with a competitive evolutionary neural tree.
A new, dynamic, tree structured network, the Competitive Evolutionary Neural Tree (CENT) is introduced. The network is able to provide a hierarchical classification of unlabelled data sets. The main advantage that the CENT offers over other hierarchical competitive networks is its ability to self determine the number, and structure, of the competitive nodes in the network, without the need for externally set parameters. The network produces stable classificatory structures by halting its growth using locally calculated heuristics. The results of network simulations are presented over a range of data sets, including Anderson's IRIS data set. The CENT network demonstrates its ability to produce a representative hierarchical structure to classify a broad range of data sets.


[Hemostasis in hemorrhage from varicose veins of the esophagus and stomach].
The results of treatment of 15 patients with bleeding from varicose veins of the esophagus and stomach are discussed. Blakemore's tube and endoscopic sclerosing of the veins with 3% Thrombovar solution were applied for hemostasis. It is concluded that nonoperative measures are preferable. The most effective method of hemostasis in intensive bleeding is the use of Blakemore's tube for temporary arrest of bleeding followed by endoscopic sclerosing for preventing recurrent hemorrhage.


The effectiveness of continuous quality improvement for developing professional practice and improving health care outcomes: a systematic review.
Efforts to improve the quality, safety, and efficiency of health care provision have often focused on changing approaches to the way services are organized and delivered. Continuous quality improvement (CQI), an approach used extensively in industrial and manufacturing sectors, has been used in the health sector. Despite the attention given to CQI, uncertainties remain as to its effectiveness given the complex and diverse nature of health systems. This review assesses the effectiveness of CQI across different health care settings, investigating the importance of different components of the approach. We searched 11 electronic databases: MEDLINE, CINAHL, EMBASE, AMED, Academic Search Complete, HMIC, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, LISTA, and NHS EED to February 2019. Also, we searched reference lists of included studies and systematic reviews, as well as checking published protocols for linked papers. We selected randomized controlled trials (RCTs) within health care settings involving teams of health professionals, evaluating the effectiveness of CQI. Comparators included current usual practice or different strategies to manage organizational change. Outcomes were health care professional performance or patient outcomes. Studies were published in English. Twenty-eight RCTs assessed the effectiveness of different approaches to CQI with a non-CQI comparator in various settings, with interventions differing in terms of the approaches used, their duration, meetings held, people involved, and training provided. All RCTs were considered at risk of bias, undermining their results. Findings suggested that the benefits of CQI compared to a non-CQI comparator on clinical process, patient, and other outcomes were limited, with less than half of RCTs showing any effect. Where benefits were evident, it was usually on clinical process measures, with the model used (i.e., Plan-Do-Study-Act, Model of Improvement), the meeting type (i.e., involving leaders discussing implementation) and their frequency (i.e., weekly) having an effect. None considered socio-economic health inequalities. Current evidence suggests the benefits of CQI in improving health care are uncertain, reflecting both the poor quality of evaluations and the complexities of health services themselves. Further mixed-methods evaluations are needed to understand how the health service can use this proven approach. Protocol registered on PROSPERO (CRD42018088309).


Characterizing cancer cells with cancer stem cell-like features in 293T human embryonic kidney cells.
Since the first suggestion of prospectively identifiable cancer stem cells in solid tumors, efforts have been made to characterize reported cancer stem cell surrogates in existing cancer cell lines, and cell lines rich with these surrogates have been used to screen for cancer stem cell targeted agents. Although 293T cells were derived from human embryonic kidney, transplantation of these cells into the mammary fat pad yields aggressive tumors that self-renew as evidenced by serial xenograft passages through transplantation. Herein we fully characterize cancer stem cell-like features in 293T human embryonic kidney cells. 293T cells can be readily cultured and passaged as spheres in serum-free stem cell promoting culture conditions. Cells cultured in vitro as three-dimensional spheres (3D) were shown to contain higher ALDH1 and CD44+/CD24- population compared to monolayer cells. These cells were also resistant to radiation and upregulate stem cell survival signaling including beta-catenin, Notch1 and Survivin in response to radiation. Moreover, 3D spheres generated from the 293T cells have increased expression of mesenchymal genes including vimentin, n-cadherin, zeb1, snail and slug as well as pro-metastatic genes RhoC, Tenascin C and MTA1. In addition, microRNAs implicated in self-renewal and metastases were markedly reduced in 3D spheres. 293T cells exhibit a cancer stem cell-like phenotype when cultured as 3D spheres and represent an important research tool for studying the molecular and biological mechanisms of cancer stem cells and for testing and developing novel targets for cancer therapy.


Cell death and lumen formation in spheroids of MCF-7 cells.
3D (three-dimensional) cell culture permits a more integrated analysis of the relationship between cells, inserting them into a structure more closely resembling the cellular microenvironment in vivo. The development of in vitro parameters to approximate in vivo 3D cellular environments makes a less reductionist interpretation of cell biology possible. For breast cells, in vitro 3D culture has proven to be an important tool for the analysis of luminal morphogenesis. A greater understanding of this process is necessary because alterations in the lumen arrangement are associated with carcinogenesis. Following lumen formation in 3D cell culture using laser scanning confocal microscopy, we observed alterations in the arrangement of cytoskeletal components (F-actin and microtubules) and increasing levels of cell death associated with lumen formation. The formation of a polarized monolayer facing the lumen was characterized through 3D reconstructions and the use of TEM (transmission electron microscopy), and this process was found to occur through the gradual clearing of cells from the medullary region of the spheroids. This process was associated with different types of cell death, such as apoptosis, autophagy and entosis. The present study showed that changes in the extracellular matrix associated with long periods of time in 3D cell culture lead to the formation of a lumen in MCF-7 cell spheroids and that features of differentiation such as lumen and budding formation occur after long periods in 3D culture, even in the absence of exogenous extracellular compounds.


The association between panic disorder and coronary artery disease among primary care patients presenting with chest pain: an updated literature review.
Although panic disorder is linked to hypertension and smoking, the relationship between panic disorder and coronary artery disease (CAD) is unclear. To extend our understanding about the strength of the association between panic disorder and coronary artery disease and known cardiovascular risk factors. Potential studies were identified via a computerized search of MEDLINE and PsycINFO databases and review of bibliographies. MeSH headings used included panic disorder with chest pain, panic disorder with coronary disease or cardiovascular disorders or heart disorders, and panic disorder with cholesterol or essential hypertension or tobacco smoking. The diagnosis of panic disorder in eligible studies was based on DSM-IV criteria, and studies must have used objective criteria for CAD and risk factors. Only case-control and cohort studies were included. Concerning the relationship between panic disorder and CAD, studies conducted in emergency departments found a relative risk [RR] of 1.25 (95% CI = 0.87 to 1.80), while those conducted in cardiology settings found an inverse relationship (RR = 0.19, 95% CI = 0.10 to 0.37). However, there is an inverse relationship between the prevalence of CAD in the study and the RR (r = -.554, p = .097), suggesting that, in primary care settings in which the prevalence of CAD is low, there may be a significant association between panic disorder and CAD. The association between panic disorder and CAD has several implications for primary care physicians managing patients with chest pain. When comorbid, the panic attacks may cause the patient with coronary disease to seek care but could also provoke a cardiac event. If one condition is recognized, a search for the other may be warranted because of the potential consequences if left undetected. The treatment approach to the panic disorder should be adjusted in the presence of comorbid CAD.


Emergency management of children with acute severe asthma requiring transfer to intensive care.
Children presenting to emergency departments (ED) with acute severe asthma unresponsive to initial medical therapy may require endotracheal intubation and mechanical ventilation. There is little data on complications during the acute management of children with life-threatening asthma, particularly at hospitals where specialist paediatric staff are lacking. It was hypothesised that a better understanding of complications, particularly associated with intubation and mechanical ventilation, would improve acute management in ED, aid quality improvement initiatives at district general hospitals (DGH) and form the basis for educational interventions from regional paediatric critical care units. A retrospective case note review was performed for all children referred to a regional intensive care retrieval service with status asthmaticus over a 2-year period. Initial treatment, patient-related factors, indication for endotracheal intubation and the type and occurrence of adverse events during acute management at the DGH were studied. Bivariate and multivariate analyses were undertaken to identify factors associated with the occurrence of complications. 51 (85%) of the 60 children transferred to a paediatric intensive care unit for acute severe asthma required intubation. 36 (70.5%) experienced one or more complications during intubation and in the early phase of mechanical ventilation. The most common complications were hypotension (requiring fluid resuscitation and/or inotropic support) and severe bronchospasm with acute hypercarbia. The indication for intubation significantly affected the chances of a complication occurring during stabilisation. There is considerable morbidity in asthmatic children who are referred to paediatric intensive care. The majority of complications may be anticipated and prevented resulting in improved management at DGH.


Comparison of cyanide-degrading nitrilases.
Recombinant forms of three cyanide-degrading nitrilases, CynD from Bacillus pumilus C1, CynD from Pseudomonas stutzeri, and CHT from Gloeocercospora sorghi, were prepared after their genes were cloned with C-terminal hexahistidine purification tags and expressed in Escherichia coli, and the enzymes purified using nickel-chelate affinity chromatography. The enzymes were compared with respect to their pH stability, thermostability, metal tolerance, and kinetic constants. The two bacterial genes, both cyanide dihydratases, were similar with respect to pH range, retaining greater than 50% activity between pH 5.2 and pH 8 and kinetic properties, having similar K(m) (6-7 mM) and V(max) (0.1 mmol min(-1) mg(-1)). They also exhibited similar metal tolerances. However, the fungal CHT enzyme had notably higher K(m) (90 mM) and V(max) (4 mmol min(-1) mg(-1)) values. Its pH range was slightly more alkaline (retaining nearly full activity above 8.5), but exhibited a lower thermal tolerance. CHT was less sensitive to Hg(2+) and more sensitive to Pb(2+) than the CynD enzymes. These data describe, in part, the current limits that exist for using nitrilases as agents in the bioremediation of cyanide-containing waste effluent, and may help serve to determine where and under what conditions these nitrilases may be applied.


Comparative study of tomato and tomato paste supplementation on the level of serum lipids and lipoproteins levels in rats fed with high cholesterol.
Hypercholesterolemia is one of the risk factors of cardiovascular diseases. Increased blood cholesterol affects general health and increases mortality due to cardiovascular disease. Poor nutrition increases LDL cholesterol and decreases LDL receptor activities in the liver. Scientists have shown that consumption of antioxidants can reduce hypercholesterolemia and proved benefits of fruit and vegetables. Tomato reduces oxidative stress by increasing serum total antioxidant level. This study compared the tomato and tomato paste supplementation on the level of serum lipids and lipoproteins in rats fed with high cholesterol. In this study, four male rat groups (10 rats per group) were used. Control group received basal diet, second group received basal diet and 2% cholesterol (Chol), third and fourth groups received basal diet, 2% cholesterol tomato and tomato paste respectively (20 percent of the diet) for a month. Then serum TC, LDL, HDL and TG were measured. Results showed that in Chol group, all lipids increased significantly (P < 0.05) except HDL compared to the control group. Tomato and tomato paste supplementation decreased TC, LDL and TG concentration significantly (P < 0.05) compared to Chol group. Tomato paste had the higher effect on lipids decreasing than tomato. Decreases of TC, LDL and TG may be related to tomato antioxidant effect. This course in human required more investigations.


[Effects of pulmonary surfactant in treatment of acute lung injury after cardiac surgery in infants].
Acute lung injury is a severe complication after cardiac surgery performed with cardiopulmonary bypass in infant patients. Pulmonary surfactant has been successfully used in treating neonatal respiratory distress syndrome for many years. This study focused on exploring the clinical efficacy of exogenous pulmonary surfactant in treating infant patients with acute lung injury after cardiac surgery with the use of extracorporeal circulation. Twenty-three infants with ventricular septal defect (VSD) were enrolled in the study. None of the patients needed oxygen treatment nor ventilation before heart surgery. VSD repair operation was done under cardiopulmonary bypass, and acute lung injury was found postoperatively. Ten infant patients in the treatment group were given pulmonary surfactant by tracheal instillation during mechanical ventilating postoperatively. Thirteen patients in control group were randomly selected in the same period in hospital, and acute lung injury was diagnosed without pulmonary surfactant treatment after cardiopulmonary bypass. Blood samples were obtained from all the patients, and blood gas analysis was performed every 6 hours. Demographics (body weigh, age, gender, VSD diameter) and clinical characteristics (CPB time, oxygenation index, mean airway pressure, pH and PCO2) of all the patients were collected, and statistical analysis was done to compare the data between treatment and control group. In the first 24 hours after heart surgery, compared with the control group, a more increased oxygenation index (from 89.36 ± 12.69 to 285 ± 16.51) was observed in treatment group, and it was from 93.71 ± 11.82 to 133 ± 19.62 in the control group. There was a significant difference in oxygenation index between the two groups (P < 0.05). At the same time, the MAP (from 17.5 ± 3.18 to 10.4 ± 3.37) of the patients in comparison with the control group (from 18.2 ± 2.63 to 13.8 ± 2.55), a more significantly decreased MAP was observed in the treatment group (P < 0.05). There was no significant difference in pH and PCO2 between the two groups. The ventilation time in cardiac care unit was shorter in treatment group (17.43 ± 9.12) h compared with the control group [(30.97 ± 14.85) h, P < 0.05]. ICU stay time of treatment group (3.90 ± 1.34) d was shorter than that of control group [(6.18 ± 1.90) d, P < 0.05].Two infants of the control group died, but none in treatment group died. In this study, a satisfactory curative effect was observed for the treatment of acute lung injury with PS intratracheal instillation after heart surgery under cardiopulmonary bypass in infant patients. It can reduce the duration of mechanical ventilation and cardiac care unit stay and improve prognosis. In addition, this study was a pilot study and the limited sample size was probably the cause of insufficient statistical power. Further study of larger scale is needed.


Immunological probes reveal spatial and developmental diversity in insect neuroglia.
A set of monoclonal antibodies (MAbs) has been generated that recognizes distinct classes of neuroglia in the adult nervous system of the cricket Acheta domesticus corresponding to glial types distinguished by morphological criteria. These include antibodies that bind to the neuroglia of the ganglionic cortex, perineurium, neuropil, and glia associated with the glial lacunar system (interface) and fiber tracts. Another MAb specifically labels components of the neural lamella, a complex extracellular matrix secreted by underlying perineurial cells. Selected adult glial-specific MAbs recognize particular glial antigens expressed during embryonic development of Acheta. Immunohistochemical staining of frozen sections of late- (90-95%) and intermediate- (50-55%) stage whole embryos reveals that the spatial distribution, degree of tissue restriction, or level of expression of some glial determinants changes as development proceeds. Labeling of certain neuroblasts in the embryonic CNS at 50-55% development by an antibody (MAb 3G6) that binds to neuropil glia in the adult CNS implies that at least 1 class of insect glia may be generated by these cells.


A Retrospective Analysis of the Contribution of Reported Factors in Cochlear Implantation on Hearing Preservation Outcomes.
Preservation of residual hearing is essential to perceive acoustic stimulation from hybrid cochlear implants (CI). Preservation is a good marker of atraumatic surgery and residual hearing may be exploited further or enhanced in future therapies, making complete hearing preservation a desirable goal for all current CI surgeries. There is large variability in the amount of hearing preserved and the timeframe over which it is lost after CI. The increase in numbers of patients with high levels of residual hearing at implantation means that understanding the variables affecting its preservation is more important than ever. An English search term with generic and specific items concerning hearing preservation and cochlear implantation was searched on the Web of Science service. The search timeframe was limited to 2000 to 2014, with no language limitations on results. Hearing preservation, retrospective CI outcome studies which reported pre- and post-surgical pure-tone audiometry (PTA) were identified and selected. PTA thresholds were extracted from audiograms or tables and converted into a low-frequency hearing preservation (LFHP) score. Data for 21 factors associated with hearing preservation were collected from studies. Factors were included in a hearing preservation model if they had both a significant bivariate correlation with LFHP and a significant Kruskal-Wallis H test result (for ordinal data) or a significant multiple regression analysis result (for scale data). Seven factors were found to have a significant effect on hearing preservation: insertion site, progressive versus stable hearing loss, insertion angle of electrode, use of intraoperative topical steroids, use of steroids (via any route/timing), hearing etiology, and electrode array type. The best hearing preservation options are given.


Vertical distribution of antibiotic resistance genes in an urban green facade.
The phyllosphere is considered a key site for the transfer of both naturally and anthropogenically selected antimicrobial resistance genes (ARGs) to humans. Consequently, the development of green building systems may pose an, as yet, unexplored pathway for ARGs and pathogens to transfer from the environment to outdoor plants. We collected leaves from plants climbing up buildings at 1, 2, 4 and 15 m above ground level and collected associated dust samples from adjacent windowsills to determine the diversity and relative abundance of microbiota and ARGs. Overall, a total of 143 ARGs from 11 major classes and 18 mobile genetic elements (MGEs) were detected. The relative abundance of ARGs within the phyllosphere decreased with increasing height above ground level. Fast expectation-maximization microbial source tracking (FEAST) suggested that the contribution of soil and aerosols to the phyllosphere microbiome was limited. A culture-dependent method to isolate bacteria from plant tissues identified a total of 91 genera from root, stem, and leaf samples as well as endophytes isolated from leaves. Of those bacteria, 20 isolates representing 9 genera were known human pathogenic members to humans. Shared bacterial from culture-dependent and culture-independent methods suggest microorganisms may move from soil to plant, potentially through an endophytic mechanism and thus, there is a clear potential for movement of ARGs and human pathogens from the outdoor environment.


Microcircuitry of beta ganglion cells in cat retina.
We reconstructed from electron micrographs of 189 serial ultrathin sections a major portion of the dendritic tree of an on-beta ganglion cell through its sixth order of branching. One hundred three contacts from three cone bipolar cells were identified. Forty-seven contacts were from a single CBb1 cone bipolar. These were distributed widely over the dendritic tree but were frequently found on the slender "basal tuft" dendrites. Twenty-two additional contacts from a second CBb1 cell were found but not studied in detail. Thirty-four contacts were from a single CBb2 cone bipolar; these also were distributed widely but were primarily on the branches of the main dendritic arborization. A major portion of the dendritic tree of an off-beta cell was also reconstructed through its seventh order of branching. Thirty-five contacts from two cone bipolar cells were identified. Twenty-three contacts were from a single CBa1 cone bipolar and 12 widely distributed over the off-beta cell dendritic tree. We propose that the photopic receptive field center of a beta cell corresponds to the envelope of the receptive fields of the bipolar cells that connect it to the cones. The center response of a beta cell may be generated by a "push-pull" mechanism. For the on-beta cell there would be excitation at light on from CBb1 and disinhibition from CBb2 and the reverse at light off. For the off-beta cell there would be inhibition at light on from CBa2 and withdrawal of excitation from CBa1. Should the bipolars have antagonistic surrounds (so far reported only for CBb1), the beta cell surrounds as well as their centers might be generated by this push-pull mechanism.


Time-of-day and days-on-shift predict increased fatigue over two-week offshore day-shifts.
The purpose of this study was to investigate the accumulation of fatigue over a two-week offshore period. In particular, the effects of (1) time-of-day and days-on-shift as well as (2) acute and chronic sleep loss on the rate at which fatigue accumulates were investigated. 42 day-shift offshore workers were examined. Fatigue was measured using pre- and post-shift scores on the Karolinska Sleepiness Scale (KSS). Total sleep time was measured using actigraphy (Motionwatch8, Camntech). Data was analyzed using a linear mixed model analyses. Average sleep loss per night was 92 min (95%CI: 89.6-94.0; p < .001). Mean cumulative sleep loss across the study was 21:20hrs (SD = 08:10hrs) over the 14 days. Chronic sleep loss was significantly related to a modest increase in sleepiness (KSS) across the shift (95%CI: 0.01-0.17; p = .020) and in post-shift scores (95%CI:.07-0.19; p < .001). Time-of-day (95%CI: 0.63 to -0.01; p = .042) and days-on-shift (95%CI: 0.03-0.08; p < .001) as well as their interaction (95%CI: 0.08 to -0.00; p = .027) influenced the rate at which fatigue accumulated over a two-week offshore period. Pre- and post-shift fatigue accumulate in different ways over the two-week offshore period. The accumulation of post-shift fatigue scores was positively related to successive days-on-shift and chronic sleep loss. Our results suggest that prolonging offshore periods will likely result in elevated fatigue risk. Accumulating fatigue and sleep loss over two-week offshore periods should be considered in fatigue risk management plans and systems.


Manual interception of moving targets. II. On-line control of overlapping submovements.
We studied the kinematic characteristics of arm movements and their relation to a stimulus moving with a wide range of velocity and acceleration. The target traveled at constant acceleration, constant deceleration, or constant velocity for 0.5-2.0 s, until it arrived at a location where it was required to be intercepted. For fast moving targets, subjects produced single movements with symmetrical, bell-shaped velocity profiles. In contrast, for slowly moving targets, hand velocity profiles displayed multiple peaks, which suggests a control mechanism that produces a series of discrete submovements according to characteristics of target motion. To analyze how temporal and spatial aspects of these submovements are influenced by target motion, we decomposed the vertical hand velocity profiles into bell-shaped velocity pulses according to the minimum-jerk model. The number of submovements was roughly proportional to the movement time, resulting in a relatively constant submovement frequency (approximately 2.5 Hz). On the other hand, the submovement onset asynchrony showed significantly more variability than the intersubmovement interval, indicating that the submovement onset was delayed more following a submovement with a longer duration. Examination of submovement amplitude and its relation to target motion revealed that the subjects achieved interception mainly by producing a series of submovements that would keep the displacement of the hand proportional to the first-order estimate of target position at the end of each submovement along the axis of hand movement. Finally, we did not find any evidence that information regarding target acceleration is properly utilized in the production of submovements.


π-Delocalization and the vibrational spectroscopy of conjugated materials: computational insights on Raman frequency dispersion in thiophene, furan, and pyrrole oligomers.
The symmetric C═C stretching frequency (ν(Я)) of conjugated polymers and oligomers is a sensitive spectroscopic reporter of molecular structure and material morphologies; however, thorough understanding of how structure affects this frequency is lacking because computational investigations of this relationship have been undertaken with limited approaches. We present a comprehensive computational investigation of the structure-dependent Raman spectroscopy of oligothiophenes, oligofurans, and oligopyrroles in their ground electronic states using density functional theory. We assessed how various functionals (BLYP, B3LYP, BHLYP, and CAM-B3LYP) impact predictions of length-dependent trends in ν(Я). The amount of Hartree-Fock exchange in a functional is critical for accurately treating π-delocalization and polarizability and hence the structure-dependent Raman behavior. BLYP and B3LYP fail to accurately predict trends in ν(Я) with oligomer length because they over-represent delocalization; in contrast, the range-corrected CAM-B3LYP functional produces the same trends observed experimentally for oligomers in solution and in the solid phase. Through comparisons with a simple mechanical model, we demonstrate that the length- and conformation-dependent spectroscopy of oligothiophenes results from a delicate balance between delocalization-induced softening of ν(Я) and the coupling of oscillators that increase ν(Я). These findings are used to address how variations in inter- and intramolecular order impact the Raman spectroscopy of polythiophenes.


Control of Tumors by Antigen-Specific CD8+ T Cells through PDL1-Targeted Delivery of Antigenic Peptide.
Tumor antigen-specific T cell function is limited by immune tolerance in the tumor microenvironment. In the tumor microenvironment, tumor cells upregulate PD-L1 expression to promote T cell exhaustion by PD-1/PD-L1 interactions and undergo mutations to avoid being targeted by tumor antigen-specific T cells. Thus, tumor cells escape the immune surveillance by causing immune tolerance. We reason that a chimeric molecule made of a PD-L1-specific antibody linked to a cleavable antigenic peptide can target the antigenic peptide to the tumor microenvironment, resulting in the blockade of the PD-1/PD-L1 pathway and killing tumor cells through the coating of antigenic peptide. Here, we have generated a therapeutic chimeric protein containing the PD-L1 single-chain variable fragment (scFv) linked to a cleavable model cytotoxic T lymphocyte (CTL) epitope: E7 CTL peptide. Our study demonstrated that our chimeric protein (named PDL1-scFv-Fc-RE7) can target PD-L1-expressing tumor cells and enable E7 presentation by releasing cleavable E7 CTL peptide to coat tumor cells, resulting in tumor clearance by E7-specific CD8+ T cells. The presentation of the E7 peptide by cancer cells can then render tumor cells susceptible to the killing of preexisting E7-specific CD8+ T cells and contribute to tumor clearance. Our finding suggests a synergistic approach to not only enhance antigen-specific tumor clearance but also bypass immune tolerance.


Variability in Azithromycin Susceptibility Results for Neisseria gonorrhoeae Obtained Using Gradient MIC Strip and Agar Dilution Techniques.
Azithromycin is a component of empirical treatment regimens for Neisseria gonorrhoeae infections, but antimicrobial susceptibility testing for this agent is technically challenging. We compared the intertest variability, MIC values, and CLSI/EUCAST categorization of clinical and reference isolates of N. gonorrhoeae treated with azithromycin by testing 107 clinical isolates and nine reference isolates by agar dilution and in duplicates using MIC test strips (Liofilchem, Italy) and Etests (bioMérieux, France). Replicate isolate agreement within 1 log2 between duplicate tests was 87% for MIC test strips and 100% for Etests (P < 0.001). Essential agreement with the agar dilution method was higher for Etests (91%) than for MIC test strips (44%, P < 0.001). The geometric mean MIC was highest for MIC test strips (0.8 mg/liter) and significantly higher than both Etest (0.47 mg/liter, P < 0.001) and agar dilution (0.26 mg/liter, P < 0.001) methods. Etest MICs were higher than those obtained with agar dilution (P < 0.001). Agar dilution, MIC test strip, and Etest methods categorized 96%, 85%, and 95% (P = 0.003) of clinical isolates, respectively, as susceptible/wild type according to CLSI/EUCAST criteria. Our results illustrate the difficulties underlying azithromycin susceptibility testing for N. gonorrhoeae and demonstrate that results can vary using different methods. This variability could influence antimicrobial resistance reporting between laboratories involved in N. gonorrhoeae surveillance programs.


Efficacy of Immunohistochemical Staining in Differentiating a Squamous Cell Carcinoma in Poorly Differentiated Rectal Cancer: Two Case Reports.
A rectal carcinoma, including primary an adenosquamous and a squamous cell carcinoma (SCC), is a very rare disease, accounting for 0.025% to 0.20% of all large-bowel malignant tumors. Because SCCs have a higher mortality than adenosquamous carcinomas, determining whether the primary rectal cancer exhibits an adenomatous component or a squamous component is important. While differentiating between these 2 components, especially in poorly differentiated rectal cancer, is difficult, specific immunohistochemical stains enable accurate diagnoses. Here, we report the use of immunohistochemical stains to distinguish between the adenomatous and the squamous components in 2 patients with low rectal cancer, a 58-year-old man and a 73-year-old woman, who were initially diagnosed using the histopathologic results for a poorly differentiated carcinoma. These data suggest that using these immunohistochemical stains will help to accurately diagnose the type of rectal cancer, especially for poorly differentiated carcinomas, and will provide important information to determine the proper treatment for the patient.


The 'other' telomerase inhibitors: non-G-quadruplex interactive agent, non-antisense, non-reverse transcriptase telomerase inhibitors.
Human telomeres are several kilobases of repeated (TTAGGG)(n) sequences at the ends of chromosomes, a short fragment of which is lost with each cell division. This shortening serves as a "mitotic clock" which limits the number of divisions that a normal somatic cell can undergo. Cells undergoing continuous division need some method of bypassing this clock. One such method is the expression of telomerase. This ribonucleoprotein is an enzyme that rebuilds the lost portion of the telomeres. Between 80-95% of tumors are telomerase-positive, including ovarian carcinoma, hepatocellular carcinoma, neuroblastoma, leukemia/lymphoma, and cancers of the breast, prostate, lung, kidneys and bladder, as well as many immortalized cell lines. While absent in most normal tissues, this enzyme is expressed at higher levels in germline tissues, bone marrow, and lymphocytes. Due to the expression of telomerase in most tumor cells and its absence in most normal tissues, telomerase inhibitors are being investigated as possible anticancer agents. This review focuses on non-reverse transcriptase inhibitor, non-oligonucleotide and non-G-quartet interactive agent telomerase inhibitors. These agents include: differentiating agents, kinases and phosphatases, cell cycle and apoptosis regulating agents, immunotherapeutic agents, antibiotics, steroids, bisindole derivatives, and a variety of other compounds. These agents hold much promise for the future treatment of malignancies.


Important biological information uncovered in previously unaligned reads from chromatin immunoprecipitation experiments (ChIP-Seq).
Establishing the architecture of gene regulatory networks (GRNs) relies on chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) methods that provide genome-wide transcription factor binding sites (TFBSs). ChIP-Seq furnishes millions of short reads that, after alignment, describe the genome-wide binding sites of a particular TF. However, in all organisms investigated an average of 40% of reads fail to align to the corresponding genome, with some datasets having as much as 80% of reads failing to align. We describe here the provenance of previously unaligned reads in ChIP-Seq experiments from animals and plants. We show that a substantial portion corresponds to sequences of bacterial and metazoan origin, irrespective of the ChIP-Seq chromatin source. Unforeseen was the finding that 30%-40% of unaligned reads were actually alignable. To validate these observations, we investigated the characteristics of the previously unaligned reads corresponding to TAL1, a human TF involved in lineage specification of hemopoietic cells. We show that, while unmapped ChIP-Seq read datasets contain foreign DNA sequences, additional TFBSs can be identified from the previously unaligned ChIP-Seq reads. Our results indicate that the re-evaluation of previously unaligned reads from ChIP-Seq experiments will significantly contribute to TF target identification and determination of emerging properties of GRNs.


Age-related changes in pineal "synaptic" ribbon populations in rats exposed to continuous light or darkness.
"Synaptic" ribbon (SR) populations in the rat pineal gland were analyzed morphometrically at various ages from birth to early adulthood. The rats were born and raised in continuous light or continuous darkness. SR numbers were high irrespective of the presence or absence of light during the early neonatal period. However, SR numbers decreased substantially during the second neonatal week of continuous light, remaining low at subsequent ages, including early adulthood. In contrast, SR numbers apparently remained elevated during continuous darkness at various ages from the early neonatal period to early adulthood. Stimulation of pineal adrenergic receptors with L-isoproterenol during continuous light resulted in an acute, reversible increase in SR numbers; blockade of these receptors with L-propranolol during continuous darkness resulted in an acute decrease in SR numbers. These results indicate that light-mediated changes in SR populations were 1) age related and 2) related to some component of the pineal beta-adrenergic receptor mechanism. A hypothesis that SR formation may be related to beta-adrenergic receptor-associated membrane turnover is presented.


Acceptability of medical male circumcision among uncircumcised men in Kenya one year after the launch of the national male circumcision program.
Numerous studies have demonstrated that male circumcision (MC) reduces the incidence of the Type-1 human immunodeficiency virus (HIV) among heterosexual men by at least half. One year after the launch of a national Voluntary Medical Male Circumcision program in Kenya, this study conducted 12 focus group discussions among uncircumcised men in Nyanza Province to assess the revealed, non-hypothetical, facilitators and barriers to the uptake of MC. The primary barriers to MC uptake included time away from work; culture and religion; possible adverse events; and the post-surgical abstinence period. The primary facilitators of MC uptake included hygiene; social pressure; protection against HIV and other sexually transmitted infections; and improved sexual performance and satisfaction. Some activities which might increase MC uptake include dispelling MC misconceptions; increasing involvement of religious leaders, women's groups, and peer mobilizers for MC promotion; and increasing the relevance of MC among men who are already practicing an HIV prevention method.


Control of lead and trail limbs during obstacle crossing following stroke.
Obstacle crossing is compromised following stroke. The purpose of this study was to quantify modifications during obstacle clearance following stroke. Twelve subjects with stroke and 12 subjects without stroke participated in the study. Kinematic variables were measured while participants crossed a 4-cm-high obstacle. Subjects with stroke walked at a self-selected speed; subjects without stroke walked at a comparable speed and at a self-selected speed. Several modifications were observed following stroke with both groups walking at self-selected speeds. The affected lead limb was positioned closer to the obstacle before crossing. Affected trail-limb clearance over the obstacle was reduced. Both affected and unaffected lead and trail limbs landed closer to the obstacle after clearance. Swing time was increased in the affected lead limb after obstacle clearance. Fewer modifications were detected at matched walking speed; the trail limb still landed closer to the obstacle. Modifications during obstacle crossing following stroke may be partly related to walking speed. The findings raise issues of safety because people with stroke demonstrated reduced clearance of a 4-cm obstacle and limb placement closer to the obstacle after clearance.


[Penicillin for acute throat infections. Are there arguments for modifying the guidelines of the Dutch College of General Practitioners?].
A recent study concludes that a 7-day penicillin treatment for a sore throat is superior to a 3-day treatment or a placebo, because the symptoms are resolved two days earlier. Prior to this study, the difference--based on the conclusions of a Cochrane review--was thought to be just 8 hours. The total number of patients included was too small to conclude that penicillin could reduce the number of short-term and long-term complications. In the guidelines of the Dutch College of General Practitioners, a 7-day penicillin treatment for a sore throat is only recommended in severe cases. It is still quite acceptable for Dutch GPs to discuss the treatment options for a sore throat with their patients. A change to the current guidelines is not necessary.


Epstein-Barr virus membrane antigens: characterization, distribution, and strain differences.
The Epstein-Barr virus (EBV)-associated membrane antigen polypeptides (350,000, 220,000, 140,000, and 85,000 daltons) are recognized by a rabbit anti-EBV serum and are present on the plasma membranes of producer cell lines, as we demonstrated previously. In this report, we show that these polypeptides are present on intact virus particles. Subcellular fractionation revealed that these antigens are distributed throughout the cell, except for the 85,000-dalton protein, which was poorly represented in the nuclear fraction. In addition, an EBV-associated protein of 160,000 daltons, which comigrates with a major component of the viral capsid, was detected in the cytoplasmic and nuclear fractions. The immunoprecipitation patterns of 13 different EBV isolates were similar, with two exceptions. First, the 350,000- and 220,000-dalton polypeptides from marmoset cell lines had slightly larger molecular sizes than the corresponding polypeptides from human cell lines. Second, B95-8 virus and B95-8-derived human and marmoset cell lines contained little of the 220,000-dalton protein; however, 883L, the human parent line of B95-8, has a normal amount of the 220,000-dalton protein. Thus, the B95-8 strain of EBV appears to be a structurally defective variant. We have not observed any variation in protein patterns associated with different EBV disease states. The 350,000-, 220,000-, and 85,000-dalton polypeptides were shown to be glycoproteins by incorporation of [3H]mannose and [3H]glucosamine and to contain N-asparagine-linked glycosyl groups by their sensitivity to tunicamycin. To simplify future work, the following nomenclature for these EBV-associated polypeptides is suggested: 350,000 (gp350), 220,000 (gp220), 160,000 (p160), 140,000 (p140), and 85,000 (gp85).


Increased circulating Th22 cells in patients with acute gouty arthritis: A CONSORT-compliant article.
T-helper 22 (Th22) cells are involved in host immunity against pathogen invasion and have been implicated in the pathogenesis of inflammatory diseases. However, the roles of Th22 cells in acute gouty arthritis remain unclear. A case-control study was employed to illustrate the clinical significance of Th22 cells in acute gouty arthritis. In this study, 27 patients with acute gouty arthritis, 22 patients with intercritical gout (IG), and 20 healthy controls were recruited, and peripheral blood cells and plasma were collected for the detection of Th22, Th17, and Th1 cells, and plasma interleukin (IL)-22. The relative and absolute numbers of Th22 and Th17 cells were significantly higher in patients with acute gouty arthritis than in patients with IG and healthy controls. Plasma IL-22 levels were consistently higher in patients with acute gouty arthritis than in patients with IG and healthy controls (P < .05). Th22 cell numbers were positively correlated with Th1 (r = 0.648, P < .05) and Th17 (r = 0.379, P < .05) cell numbers in patients with gout. Moreover, Th22 cell numbers and plasma IL-22 levels were positively correlated with C-reactive protein levels (Th22: r = 0.444, P < .05; IL-22: r = 0.282, P < .05). Our results indicate that peripheral blood levels of Th22 cells increase during acute gouty arthritis suggesting a role for these cells in the pathophysiology of the disease.


Ethyl pyruvate ameliorates inflammatory arthritis in mice.
Ethyl pyruvate (EP) is the ethyl ester of pyruvate and has antioxidative and anti-inflammatory effects. This study aimed to evaluate the therapeutic effect of EP in inflammatory arthritis and to identify the underlying mechanisms. Mice with collagen-induced arthritis (CIA) were treated with the vehicle control or EP at 20mg/kg, and clinical and histological analyses were performed on the animals. The differentiation of murine CD4+ T cells into T helper 17 (Th17) cells in the presence of EP was investigated in vitro. The effects of EP on osteoclastogenesis were determined by staining for tartrate-resistant acid phosphatase, and measuring the mRNA levels of osteoclastogenesis-related genes. The expression of high-mobility group box 1 (HMGB1) was evaluated after EP therapy using immunohistochemical staining and Western blotting. EP significantly improved the clinical and histological features of arthritis in CIA mice. EP suppressed the differentiation of CD4+ T cells into Th17 cells, and inhibited the expression of RORγt. The generation of osteoclasts and osteoclastogenic markers from murine and human monocytes was significantly reduced in the presence of EP. The expression of HMGB1 in the synovium was significantly lower in CIA mice treated with EP, compared to control CIA mice. During osteoclastogenesis, HMGB1 release from monocytes was inhibited in the presence of EP. EP attenuated synovial inflammation and bone destruction in the experimental arthritis model through suppression of IL-17 and HMGB-1. The data suggests that EP could be a novel therapeutic agent for the treatment of inflammatory arthritis, such as rheumatoid arthritis.


Is the sensory innervation disturbed in the lower urinary tract of children with bed-wetting?
The sensation of bladder filling during cystometry and the sensory thresholds towards electrical stimulation in the bladder and urethra were determined in a group of 35 children and young adults with enuresis nocturna and in 28 similar patients with other urodynamic dysfunctions. The variables of the filling sensation were not different between the groups. The sensory threshold of the urethra in girls was significantly higher in the bed-wetting group indicating a diminished electrosensation in this structure. In 2 patients with absent electrosensation, an unsuspected neuropathy was discovered. A search for an eventual deficient sensation in the lower urinary tract in children with persistent enuresis nocturna would seem worthwhile.


The Bacillus cereus GerN and GerT protein homologs have distinct roles in spore germination and outgrowth, respectively.
The GerT protein of Bacillus cereus shares 74% amino acid identity with its homolog GerN. The latter is a Na(+)/H(+)-K(+) antiporter that is required for normal spore germination in inosine. The germination properties of single and double mutants of B. cereus ATCC 10876 reveal that unlike GerN, which is required for all germination responses that involve the GerI germinant receptor, the GerT protein does not have a significant role in germination, although it is required for the residual GerI-mediated inosine germination response of a gerN mutant. In contrast, GerT has a significant role in outgrowth; gerT mutant spores do not outgrow efficiently under alkaline conditions and outgrow more slowly than the wild type in the presence of high NaCl concentrations. The GerT protein in B. cereus therefore contributes to the success of spore outgrowth from the germinated state during alkaline or Na(+) stress.


Residence times of branching diffusion processes.
The residence time of a branching Brownian process is the amount of time that the mother particle and all its descendants spend inside a domain. Using the Feynman-Kac formalism, we derive the residence-time equation as well as the equations for its moments for a branching diffusion process with an arbitrary number of descendants. This general approach is illustrated with simple examples in free space and in confined geometries where explicit formulas for the moments are obtained within the long time limit. In particular, we study in detail the influence of the branching mechanism on those moments. The present approach can also be applied to investigate other additive functionals of branching Brownian process.


Phthalate and Bisphenol Urinary Concentrations, Body Fat Measures, and Cardiovascular Risk Factors in Dutch School-Age Children.
The purpose of this study was to investigate the associations of urinary phthalates and bisphenols at age 6 years old with body fat and cardiovascular risk factors at 6 and 10 years and with the change from 6 to 10 years. Among 471 Dutch children, the phthalates and bisphenols urinary concentrations at 6 years and BMI, fat mass index, android fat mass, blood pressure, glucose, insulin, and lipids blood concentrations at 6 and 10 years were measured. An interquartile range increase in di-n-octyl phthalate (DNOP) metabolites concentrations at 6 years was associated with an increased risk of overweight at 6 and 10 years (odds ratio: 1.44; 95% CI: 1.11-1.87, and 1.43; 95% CI: 1.09-1.86, respectively). Also, higher DNOP metabolites concentrations were associated with higher fat mass index at 6 years, higher systolic blood pressure at 10 years, a decrease in high-density lipoprotein cholesterol, and an increase in triglycerides concentrations from 6 to 10 years (P < 0.05). Higher total bisphenols and bisphenol A concentrations were associated with a decrease in BMI from 6 to 10 years (P < 0.01). DNOP metabolites are associated with overweight and an adverse cardiovascular profile in childhood. Total bisphenols and bisphenol A are associated with a decrease in BMI from 6 to 10 years.


Carbon-14 radiolabeling and tissue distribution evaluation of MMV390048.
The antimalarial compound MMV390048 ([14 C]-11) was labeled with carbon-14 isotope via a 3-step synthesis. It was obtained in a 15.5% radiochemical overall yield from carbon-14 labeled methyl iodide with a radiochemical purity of >99%. After single oral administration of [14 C]-11 to albino and pigmented rats its tissue distribution profile was studied. Tissue distribution results showed high local exposure in the GI tract and excretory organs but low exposure of all other tissues. The radioactivity uptake was higher in the eyes of the pigmented rats than in the eyes of the albino rats at all-time points. The highest accumulation reached in the eyes of the pigmented rats was 0.46% at 6 hours. However, these levels are still very low as compared to the other organs studied. There was very little radioactivity from MMV390048 ([14 C]-11) present in the skin of both the albino and pigmented rats. The results obtained are supportive of further development of MMV390048 as a potential antimalarial compound.


Topological solitons in helical strings.
The low-energy physics of (quasi)degenerate one-dimensional systems is typically understood as the particle-like dynamics of kinks between stable, ordered structures. Such dynamics, we show, becomes highly nontrivial when the ground states are topologically constrained: a dynamics of the domains rather than on the domains which the kinks separate. Motivated by recently reported observations of charged polymers physio-adsorbed on nanotubes, we study kinks between helical structures of a string wrapping around a cylinder. While their motion cannot be disentangled from domain dynamics, and energy and momentum is not concentrated in the solitons, the dynamics of the domains can be folded back into a particle-like description of the local excitations.


Pretraining Exposure to Physiologically Patterned Electromagnetic Stimulation Attenuates Fear-Conditioned Analgesia.
The effect of weak electromagnetic stimulation on the emergence of conditioned analgesia was examined in the adult rat. Subjects were conditioned to associate a continuous 20 kHz ultrasonic tone (CS) with 0.2 mA footshock (UCS(-) ) over five successive days. For 30 min either before or after conditioning sessions, rats were exposed to sham or pulsed (primed burst potentiation) magnetic fields (500 nT). At the end of the conditioning phase, all animals were evaluated for anticipatory analgesia following CS presentation using a hotplate analgesiometer. Data analysis suggested a statistically significant attenuation of fear-conditioned analgesia in rats exposed to electromagnetic stimulation prior to conditioning, whereas post-conditioning exposure potentiated the reduction in pain sensitivity compared to baseline measures. The present results suggest that the emergence of fear-conditioned responses is sensitive to whole body exposure to a magnetic field pattern that has been shown to induce long-term potentiation in hippocampal slices.


Genetic characterization of HIV type 1 among patients with suspected immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy in Kenya.
Antiretroviral therapy (ART) has improved the survival of HIV patients but is also associated with unique manifestations of disease in some subjects during the initial months of therapy. Immune reconstitution inflammatory syndrome (IRIS) is a disorder among individuals starting ART, with no evidence-based treatment and management guidelines. We characterized HIV-1 and determined drug resistance among 14 Kenyan patients with suspected IRIS after ART initiation in 2005. Polymerase chain reaction, sequencing, and phylogenetic analysis of viral pol and env showed the following HIV-1 subtypes: A1/A1/A1 (pol-RT/gp41/C2V3), 5; A1/C/A1, 1; A1/D/A1, 2; D/A1/A1, 1; D/C/A1, 1; D/D/A1, 2; D/D/D, 1; and D/A1/A2, 1. Three patients had viruses with major drug resistance-associated mutations. These included nucleoside reverse transcriptase inhibitor (RTI) mutations: M41L, K65R, D67N, K70R, M184V, and K219Q, and nonnucleoside RTI mutations: K101P, L100I, K103N, and Y181C. Twelve patients harbored viruses that are predicted to use chemokine coreceptor 5 (CCR5) whereas two had variant viruses predicted to use the CXCR4 coreceptor. Drug resistance may not be the only cause of ART adverse events. HIV-1 characterization would be important before and during HIV therapy to avoid treatment failure.


Review of ceftaroline fosamil microbiology: integrated FOCUS studies.
Ceftaroline fosamil, the prodrug form of ceftaroline, is a novel broad-spectrum parenteral cephalosporin that exhibits antibacterial activity against typical respiratory pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and common Gram-negative pathogens. In particular, ceftaroline has activity against resistant Gram-positive cocci, including penicillin- and multidrug-resistant S. pneumoniae, as well as methicillin-resistant S. aureus. The activity of ceftaroline against these phenotypes is attributed to its ability to bind to modified penicillin-binding proteins with high affinity when compared with other β-lactams. The activity of ceftaroline is not compromised by the ability of H. influenzae to produce β-lactamase. Ceftaroline fosamil was compared with ceftriaxone for safety and efficacy in two randomized, double-blinded, controlled Phase III clinical trials for the treatment of community-acquired pneumonia (CAP). Microbiological assessments at baseline included respiratory specimen cultures, blood cultures, urinary antigen testing and atypical pathogen serology testing. By-subject and by-pathogen microbiological outcomes were assessed in the microbiologically evaluable population at the test-of-cure visit. The favourable microbiological response rates by subject for ceftaroline were 87.0% compared with 81.0% for ceftriaxone. The by-pathogen microbiological response rates of ceftaroline and ceftriaxone were 87.3% and 72.9% for S. pneumoniae, 83.3% and 85.0% for H. influenzae and 76.0% and 70.4% for S. aureus, respectively. Key baseline pathogens such as S. pneumoniae, H. influenzae and methicillin-susceptible S. aureus were susceptible to ceftaroline, with MIC(90)s of 0.03, 0.03 and 0.25 mg/L, respectively, supporting its utility as a promising new agent for treatment of CAP.