Retinal fluid changes and therapeutic effects in symptomatic circumscribed choroidal hemangioma patients: a long-term follow up study.
Changes in retinal fluid patterns associated with circumscribed choroidal hemangioma (CCH) have not been investigated yet. A long-term follow-up study was performed to evaluate the changes of retinal fluid patterns and treatment responses. We retrospectively reviewed medical records of all CCH patients diagnosed between November 2005 and March 2017. Enrolled patients had visual symptoms, were treatment-naïve, and had been followed-up for more than 2 years. Best corrected visual acuities (BCVA) and the presence, severity, and pattern change of the subretinal fluid (SRF) and intraretinal fluid (IRF) in the macula on optical coherence tomography (OCT) were analyzed at initial presentation and follow-up visits. Twenty-six patients were enrolled. All patients received one or more of the following treatments: PDT, TTT, and intravitreal bevacizumab (Avastin) injection (IVB). Primary therapy consisted of PDT in 9 patients (34.6%), TTT in 7 patients (26.9%) and IVB in 10 patients (38.5%). At initial presentation, the SRF-only pattern was mostly observed. Despite treatment, IRF occurred over time; eventually, advanced cystoid macular oedema (CME) developed. In terms of retinal fluid reduction, PDT was most efficacious (9/9, 100%), and TTT and IVB showed moderate efficacy (TTT: 4/7, 57.1%; IVB: 5/10, 50%) as a primary therapy. After advanced CME developed, IVB and TTT showed no or minimal effect (TTT: 0/1, 0%; IVB: 0/19, 0%), and PDT was the only effective therapy (6/10, 60%). The pattern of retinal fluid accompanied by CCH evolved from an SRF-only pattern initially to an advanced CME pattern. The effectiveness of treatments decreased over time, and advanced CME generally showed resistance to treatments. PDT would be the most recommended treatment.


Measuring and monitoring lean body mass in critical illness.
To help guide metabolic support in critical care, an understanding of patients' nutritional status and risk is important. Several methods to monitor lean body mass are increasingly used in the ICU and knowledge about their advantages and limitations is essential. Computed tomography scan analysis, musculoskeletal ultrasound, and bioelectrical impedance analysis are emerging as powerful clinical tools to monitor lean body mass during ICU stay. Accuracy, expertise, ease of use at the bedside, and costs are important factors which play a role in determining which method is most suitable. Exciting new research provides an insight into not only quantitative measurements, but also qualitative measurements of lean body mass, such as infiltration of adipose tissue and intramuscular glycogen storage. Methods to monitor lean body mass in the ICU are under constant development, improving upon bedside usability and offering new modalities to measure. This provides clinicians with valuable markers with which to identify patients at high nutritional risk and to evaluate metabolic support during critical illness.


Effects of competitive red blood cell binding and reduced hematocrit on the blood and plasma levels of [14C]Indapamide in the rat.
The effects of chlorthalidone and acetazolamide on the red blood cell binding of indapamide were investigated. Both drugs caused a substantial decrease in the amount of indapamide bound to the erythrocytes in vitro. This effect was demonstrated by a change in the indapamide blood/plasma ratio from approximately 6 in control samples, to a value of 1 when either of the displacing agents was added. Coadministration of acetazolamide with 14C-labeled indapamide to rats, resulted in a 5-fold drop in the blood levels of total radioactivity, relative to rats dosed with [14C]indapamide alone. Concomitantly, there was a 2-fold increase in the plasma levels of total radioactivity after acetazolamide coadministration. In rats whose hematocrits had been reduced by extensive bleeding, there were only minor alterations in the blood/plasma partitioning of [14C]indapamide. Thus, chlorthalidone and acetazolamide were able to displace indapamide from erythrocytes in vitro and in vivo, possibly by competition at a carbonic anhydrase binding site. The pharmacokinetics of drugs which are extensively bound to erythrocytes may be significantly altered by the presence of other agents capable of competitive binding.


Comparison of diffusivity data derived from electrochemical and NMR investigations of the SeCN¯/(SeCN)2/(SeCN)3¯ system in ionic liquids.
Electrochemical studies in room temperature ionic liquids are often hampered by their relatively high viscosity. However, in some circumstances, fast exchange between participating electroactive species has provided beneficial enhancement of charge transport. The iodide (I¯)/iodine (I(2))/triiodide (I(3)¯) redox system that introduces exchange via the I¯ + I(2) ⇌ I(3)¯ process is a well documented example because it is used as a redox mediator in dye-sensitized solar cells. To provide enhanced understanding of ion movement in RTIL media, a combined electrochemical and NMR study of diffusion in the {SeCN¯-(SeCN)(2)-(SeCN)(3)¯} system has been undertaken in a selection of commonly used RTILs. In this system, each of the Se, C and N nuclei is NMR active. The electrochemical behavior of the pure ionic liquid, [C(4)mim][SeCN], which is synthesized and characterized here for the first time, also has been investigated. Voltammetric studies, which yield readily interpreted diffusion-limited responses under steady-state conditions by means of a Random Assembly of Microdisks (RAM) microelectrode array, have been used to measure electrochemically based diffusion coefficients, while self-diffusion coefficients were measured by pulsed field gradient NMR methods. The diffusivity data, derived from concentration and field gradients respectively, are in good agreement. The NMR data reveal that exchange processes occur between selenocyanate species, but the voltammetric data show the rates of exchange are too slow to enhance charge transfer. Thus, a comparison of the iodide and selenocyanate systems is somewhat paradoxical in that while the latter give RTILs of low viscosity, sluggish exchange kinetics prevent any significant enhancement of charge transfer through direct electron exchange. In contrast, faster exchange between iodide and its oxidation products leads to substantial electron exchange but this effect does not compensate sufficiently for mass transport limitations imposed by the higher viscosity of iodide RTILs.


Mitochondria-Targeting Selenophene-Modified BODIPY-Based Photosensitizers for the Treatment of Hypoxic Cancer Cells.
Two red-absorbing, water-soluble and mitochondria (MT)-targeting selenophene-substituted BODIPY-based photosensitizers (PSs) were realized (BOD-Se, BOD-Se-I), and their potential as photodynamic therapy (PDT) agents were evaluated. BOD-Se-I showed higher 1 O2 generation yield thanks to the enhanced heavy-atom effect, and this derivative was further tested in detail in cell culture studies under both normoxic and hypoxic conditions. BOD-Se-I not only effectively functioned under hypoxic conditions, but also showed highly selective photocytotoxicity towards cancer cells. The selectivity is believed to arise from differences in mitochondrial membrane potentials of healthy and cancerous cells. To the best of our knowledge, this marks the first example of a MT-targeted BODIPY PS that functions under hypoxic conditions. Remarkably, thanks to the design strategy, all these properties where realized by a compound that was synthesized in only five steps with 32 % overall yield. Hence, this material holds great promise for the realization of next-generation PDT drugs for the treatment of hypoxic solid tumors.


Life history evolution, species differences, and phenotypic plasticity in hemiparasitic eyebrights (Euphrasia).
Species delimitation in parasitic organisms is challenging because traits used to identify species are often plastic and vary depending on the host. Here, we use species from a recent radiation of generalist hemiparasitic Euphrasia to investigate trait variation and trait plasticity. We tested whether Euphrasia species show reliable trait differences, investigated whether these differences correspond to life history trade-offs between growth and reproduction, and quantified plasticity in response to host species. Common garden experiments were used to evaluate trait differences between 11 Euphrasia taxa grown on a common host, document phenotypic plasticity when a single Euphrasia species is grown on eight different hosts, and relate observations to trait differences recorded in the wild. Euphrasia exhibited variation in life history strategies; some individuals transitioned rapidly to flowering at the expense of early season growth, while others invested in vegetative growth and delayed flowering. Life history differences were present between some species, though many related taxa lacked clear trait differences. Species differences were further blurred by phenotypic plasticity-many traits were plastic and changed with host type or between environments. Phenotypic plasticity in response to host and environment confounds species delimitation in Euphrasia. When grown in a common garden environment, some morphologically distinct taxa can be identified, though others represent morphologically similar shallow segregates. Trait differences present between some species and populations demonstrate the rapid evolution of distinct life history strategies in response to local ecological conditions.


Statin use and risk of community acquired pneumonia in older people: population based case-control study.
To test the hypothesis that hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) may decrease the risk of community acquired pneumonia. Population based case-control study. Group Health, a large integrated healthcare delivery system. Population Immunocompetent, community dwelling Group Health members aged 65 to 94; two matched controls for each case with pneumonia. Information on comorbid illnesses and functional and cognitive status, potential confounders of the association between statin use and risk of pneumonia, came from medical record review and computerised pharmacy data. Adjusted estimates of risk of pneumonia in relation to current statin use. 1125 validated cases of pneumonia and 2235 matched controls were identified. Compared with controls, cases were more likely to have chronic lung and heart disease, especially severe disease, and functional or cognitive impairment. Current statin use was present in 16.1% (181/1125) of cases and 14.6% (327/2235) of controls (adjusted odds ratio 1.26, 95% confidence interval 1.01 to 1.56). Among cases admitted to hospital and matched controls, current statin use was present in 17.2% (68/395) of cases and 14.2% (112/788) of controls (adjusted odds ratio 1.61, 1.08 to 2.39, compared with non-use). In people in whom statins were indicated for secondary prevention, the adjusted odds ratio for risk of pneumonia in relation to current statin use was 1.25 (0.94 to 1.67); in those with no such indication, it was 0.81 (0.46 to 1.42). Statin use was not associated with decreased risk of pneumonia among immunocompetent, community dwelling older people. Findings of previous studies may reflect "healthy user" bias.


Nonmydriatic ultra-wide-field scanning laser ophthalmoscopy (Optomap) versus two-field fundus photography in diabetic retinopathy.
The purpose of this study was to investigate the diagnostic properties of a 2-laser wavelength nonmydriatic 200° ultra-wide-field scanning laser ophthalmoscope (SLO) versus mydriatic 2-field 45° color fundus photography (EURODIAB standard) for assessing diabetic retinopathy (DR). A total of 143 consecutive eyes of patients with different levels of DR were graded regarding DR level and macular edema based on 2-field color photographs or 1 Optomap Panoramic 200 SLO image. All SLO images were nonmydriatic and all photographs mydriatic. Grading was performed masked to patient and clinical data. Based on photography, 20 eyes had no DR, 44 had mild, 18 moderate and 42 severe nonproliferative DR, and 19 eyes had proliferative DR. Overall correlation for grading DR level compared to Optomap SLO was moderate with kappa 0.54 (p < 0.001), fair-to-moderate in macular edema grading with kappa 0.39 (p < 0.001), and substantial for grading clinically significant macular edema (kappa 0.77). The wide-field SLO offers a wider field of view and can potentially better differentiate lesions by applying the 2 laser wavelengths. However, these advantages over 2-field fundus photography need to be confirmed in further studies.


A Semi-Automated Usability Evaluation Framework for Interactive Image Segmentation Systems.
For complex segmentation tasks, the achievable accuracy of fully automated systems is inherently limited. Specifically, when a precise segmentation result is desired for a small amount of given data sets, semi-automatic methods exhibit a clear benefit for the user. The optimization of human computer interaction (HCI) is an essential part of interactive image segmentation. Nevertheless, publications introducing novel interactive segmentation systems (ISS) often lack an objective comparison of HCI aspects. It is demonstrated that even when the underlying segmentation algorithm is the same throughout interactive prototypes, their user experience may vary substantially. As a result, users prefer simple interfaces as well as a considerable degree of freedom to control each iterative step of the segmentation. In this article, an objective method for the comparison of ISS is proposed, based on extensive user studies. A summative qualitative content analysis is conducted via abstraction of visual and verbal feedback given by the participants. A direct assessment of the segmentation system is executed by the users via the system usability scale (SUS) and AttrakDiff-2 questionnaires. Furthermore, an approximation of the findings regarding usability aspects in those studies is introduced, conducted solely from the system-measurable user actions during their usage of interactive segmentation prototypes. The prediction of all questionnaire results has an average relative error of 8.9%, which is close to the expected precision of the questionnaire results themselves. This automated evaluation scheme may significantly reduce the resources necessary to investigate each variation of a prototype's user interface (UI) features and segmentation methodologies.


Identification of major allergens of two species of local snappers: Lutjanus argentimaculatus (merah/ red snapper) and Lutjanus johnii (jenahak/ golden snapper).
Fish has been recognized as a source of potent allergens both in food and occupational allergy. Lutjanus argentimaculatus (red snapper) and Lutjanus johnii (golden snapper) locally known as merah and jenahak, respectively, are among the most commonly consumed fish in Malaysia. The objective of this study is to identify the IgE-binding proteins and major allergens of these species of fishes. Extracts of both fish species were prepared and fractionated by sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE). IgE binding patterns were then demonstrated by immunoblotting using sera from patients allergic to the fishes. The raw extracts of both fish produced 26 protein bands. Both species of fishes had similar protein profiles. In cooked extracts, several protein bands in the range of about 40 to 90 kD which were present in the uncooked extracts appeared to be denatured and formed high molecular weight complexes. The immunoblotting of golden snapper and red snapper revealed 16 and 15 various IgE-binding bands, in the range of 151 to 12-11 kD, respectively. A 51 kD protein was identified as a major allergen for both fishes. A 46 kD protein was also demonstrated as a major allergen in golden snapper and a 42 kD protein was also seen as a major allergen in red snapper. A heat-resistant protein of ~12 kD which is equivalent in size with fish parvalbumin was demonstrated only as minor allergen for both fishes.


[Medico-biological evaluation of sodium salt of nitrofurylacrylic acid as a food additive].
Nitrofurylacrylic acid sodium salt is a substance of moderate toxicity. Its LD50 for male rats after oral administration comprises 1220 mg/kg, for female rats--1400 mg/kg. The minimal toxic dose, in case of long-term administration comprises 14 mg/kg. At the level of doses from 0.04 to 4.0 mg/kg no mutagenic effect was detected. Oral and subcutaneous administration of minimal tolerance doses of the agent induced formation of malignant neoplasms developing, predominantly, from the epithelial tissue, with localization depending on the route of the agent administration. A conclusion has been made on impossibility of using this substance as a food additive.


Suppression of Vps13 adaptor protein mutants reveals a central role for PI4P in regulating prospore membrane extension.
Vps13 family proteins are proposed to function in bulk lipid transfer between membranes, but little is known about their regulation. During sporulation of Saccharomyces cerevisiae, Vps13 localizes to the prospore membrane (PSM) via the Spo71-Spo73 adaptor complex. We previously reported that loss of any of these proteins causes PSM extension and subsequent sporulation defects, yet their precise function remains unclear. Here, we performed a genetic screen and identified genes coding for a fragment of phosphatidylinositol (PI) 4-kinase catalytic subunit and PI 4-kinase noncatalytic subunit as multicopy suppressors of spo73Δ. Further genetic and cytological analyses revealed that lowering PI4P levels in the PSM rescues the spo73Δ defects. Furthermore, overexpression of VPS13 and lowering PI4P levels synergistically rescued the defect of a spo71Δ spo73Δ double mutant, suggesting that PI4P might regulate Vps13 function. In addition, we show that an N-terminal fragment of Vps13 has affinity for the endoplasmic reticulum (ER), and ER-plasma membrane (PM) tethers localize along the PSM in a manner dependent on Vps13 and the adaptor complex. These observations suggest that Vps13 and the adaptor complex recruit ER-PM tethers to ER-PSM contact sites. Our analysis revealed that involvement of a phosphoinositide, PI4P, in regulation of Vps13, and also suggest that distinct contact site proteins function cooperatively to promote de novo membrane formation.


Structure-based comparison of four eukaryotic genomes.
The field of comparative genomics allows us to elucidate the molecular mechanisms necessary for the machinery of an organism by contrasting its genome against those of other organisms. In this paper, we contrast the genome of homo sapiens against C. Elegans, Drosophila melanogaster, and S. cerevisiae to gain insights on what structural domains are present in each organism. Previous work has assessed this using sequence-based homology recognition systems such as Pfam [1] and Interpro [2]. Here, we pursue a structure-based assessment, analyzing genomes according to domains in the SCOP structural domain dictionary. Compared to other eukaryotic genomes, we observe additional domains in the human genome relating to signal transduction, immune response, transport, and certain enzymes. Compared to the metazoan genomes, the yeast genome shows an absence of domains relating to immune response, cell-cell interactions, and cell signaling.


Risk of recurrent childhood arterial ischemic stroke in a population-based cohort: the importance of cerebrovascular imaging.
Few data exist regarding rates and predictors of recurrence after childhood arterial ischemic stroke. We sought to establish such rates within a large, multiethnic population and determine whether clinical vascular imaging predicts recurrence. In a population-based cohort study, we collected data on all documented cases of arterial ischemic stroke among 2.3 million children (<20 years old) enrolled in a northern Californian managed care plan from January 1993 to December 2004. Perinatal strokes were those that occurred by 28 days of life. Data on cerebrovascular imaging (conventional or magnetic resonance angiography), including presence of vascular abnormalities, were abstracted from official radiology reports. We used Kaplan-Meier survival-analysis techniques to determine rates and predictors of recurrent stroke. Among 181 incident childhood stroke cases (84 perinatal; 97 later childhood), there were 16 recurrent strokes (1 after a perinatal stroke) at a median of 2.7 months. The 5-year cumulative recurrence rates were 1.2% after perinatal stroke and 19% after later childhood stroke. Of the 97 children with later childhood strokes, 52 received cerebrovascular imaging, predominantly magnetic resonance angiography (n = 36) and conventional angiography (n = 26). Although there were no recurrences among children with normal vascular imaging, children with a vascular abnormality had a 5-year cumulative recurrence rate of 66%. Strokes recur in one fifth of cases of later childhood arterial ischemic stroke but are rare after perinatal stroke. Among the later childhood cases, cerebrovascular imaging identifies those at highest risk for recurrence.


Pedobacter pituitosus sp. nov., isolated from a waterfall.
A taxonomic study was carried out on a novel bacterial strain, designated MIC2002(T), which was isolated from Wibong falls in Korea. Cells were Gram-stain-negative, aerobic, non-motile and rods, 0.3-0.5 µm wide and 4.0-5.0 µm long. The optimum temperature and pH range for growth were 25 °C and pH 6.5-7.0, respectively. Catalase and oxidase activities were positive. Flexirubin pigments were not produced. Comparison of the 16S rRNA gene sequences indicated that the isolate belonged to the genus Pedobacter, with Pedobacter daechungensis as its closest relative, with a similarity of 94.4%. It contained iso-C(15:0), anteiso-C(15:0), C(16:0), summed feature 3 (C(16:1)ω6c and/or C(16:1)ω7c) and iso-C(17:0) 3-OH as the major fatty acids and menaquinone MK-7 as isoprenoid quinone. The polar lipid profile of strain MIC2002(T) revealed the presence of phosphatidylethanolamine and an unknown lipid. The DNA G+C content of the strain was 34.7 mol%. On the basis of the evidences presented, it was concluded that strain MIC2002(T) represents a novel species of the genus Pedobacter within the family Sphingobacteriaceae, for which the name Pedobacter pituitosus sp. nov. is proposed. The type strain is MIC2002(T) ( =KACC 17064(T) =JCM 18729(T)).


Activation of Insulin-Like Growth Factor-2 Ameliorates Retinal Cell Damage and Exerts Protection in in vitro Model of Diabetic Retinopathy.
The major event in the development of diabetes-related blindness and vision impairment is the onset of retinal cell damage. Overall awareness of insulin-like growth factor-2 (IGF2) mechanisms emphasizes its protective behavior in retinal cells that help to provide new information about the development of treatment for retinal complications. This study analyzes the effect of in vitro changes associated with the cell survival and rescue mechanism in IGF2 inhibition and activation using chromeceptin and IGF2 peptides in ARPE-19 cells cultured in high glucose conditions. Cell death was induced using high glucose (15 mmol/L), IGF2 inhibition was done using chromeceptin (1 µM) (Sigma Aldrich, Saint Louis, MO, USA), and IGF2 activation was done using IGF2 peptide (10 ng/mL). The cells were analyzed for changes in cell proliferation, apoptosis markers, antioxidant molecules, and alteration of cytokines. The study demonstrated that cells lacking IGF2 exhibited a significant increase in reactive oxygen levels with apoptosis patterns. Also, gene expression analysis by qRT-PCR demonstrated a significant increase in Yes-associated protein 1, CDK2, TNF-α, and BIRC5 genes in cells under high glucose stress and IGF inhibition compared to control. Further, the cytokine analysis also revealed that cells devoid of IGF2 activated an increase in cytokines such as IL-8, CX43, ICAM-1, IL-17, CCL3, and MCP-1 and decreased paraoxonase compared to normal control cells. On the other hand, ARPE-19 cells grown in high glucose shows that IGF2 increases the survival genes with reduced levels of inflammatory cytokines. The finding of the investigation, therefore, shows that the use of IGF2 activators may prevent the progression of ocular dysfunction in the control of diabetes-related complications.


Utilization of medical and health-related services among school-age children and adolescents with special health care needs (1994 National Health Interview Survey on Disability [NHIS-D] Baseline Data).
To determine how sociodemographic factors and type of insurance influence use of medical and health-related services by children with special health care needs (CSHCN), after controlling for need. A cross-sectional analysis of 1994 National Health Interview Disability Survey was conducted. Children between 5 and 17 years were identified as chronically ill according to the Questionnaire for Identifying Children with Chronic Conditions (n = 3061). Independent variables included child and family characteristics categorized as predisposing, enabling, and need. Dependent variables included use of 4 medical or 7 health-related services. Most children (88.7%) had seen a physician; 23.9% had an emergency department visit, 11.4% had a mental health outpatient visit, and 6.4% were hospitalized. Health-related service use ranged from <5.0% (transportation and social work) to 65.1% (medical care coordination); 20% to 30% of children used the remaining services (therapeutic, assistive devices, nonmedical care coordination, housing modifications). In fully adjusted logistic models, children with public insurance were significantly more likely than privately insured children to use 2 of the 4 medical services and 5 of the 7 health-related services. Non-Hispanic black children and children from less educated families were significantly less likely to use many of the services examined. In 1994, factors in addition to need influenced medical and health-related service use by CSHCN. Differences in the scope of benefits covered by public insurance compared with private insurance may influence utilization of medical and especially health-related services. Attention is needed to ensure that CSHCN who are racial/ethnic minorities or are from less educated families have access to needed services. Future studies should determine whether these patterns have changed over time.


Response gene to complement 32 expression is induced by the luteinizing hormone (LH) surge and regulated by LH-induced mediators in the rodent ovary.
Response gene to complement 32 (Rgc32) has recently been suggested to be expressed in the ovary and regulated by RUNX1, a transcription factor in periovulatory follicles. In the present study, we determined the expression profile of the Rgc32 gene in the rodent ovary throughout the reproductive cycle and the regulatory mechanism(s) involved in Rgc32 expression during the periovulatory period. Northern blot and in situ hybridization analyses revealed the up-regulation of Rgc32 expression in periovulatory follicles. Rgc32 mRNA was also localized to newly forming corpora lutea (CL) and CL from previous estrous cycles. Further studies using hormonally induced luteal and luteolysis models revealed a transient increase in levels of Rgc32 mRNA at the time of functional regression of the CL. Next, the regulation of Rgc32 expression was investigated in vitro using rat preovulatory granulosa cells. The effect of human chorionic gonadotropin on Rgc32 expression was mimicked by forskolin, but not phorbol 12-myristate 13-acetate, and was mediated by the activation of progesterone receptors and the epidermal growth factor-signaling pathway. The mechanism by which RUNX1 regulates Rgc32 expression was investigated using chromatin immunoprecipitation and Rgc32 promoter-luciferase reporter assays. Data from these assays revealed direct binding of RUNX1 in the Rgc32 promoter region in vivo as well as the involvement of RUNX binding sites in the transactivation of the Rgc32 promoter in vitro. In summary, the present study demonstrated the spatial/temporal-specific expression of Rgc32 in the ovary, and provided evidence of LH-initiated and RUNX1-mediated expression of Rgc32 gene in luteinizing granulosa cells.


Do oral biofilms influence the wear and corrosion behavior of titanium?
The main aim of this work was to study the simultaneous wear-corrosion of titanium (Ti) in the presence of biofilms composed of Streptococcus mutans and Candida albicans. Both organisms were separately grown in specific growth media, and then mixed in a medium supplemented with a high sucrose concentration. Corrosion and tribocorrosion tests were performed after 48 h and 216 h of biofilm growth. Electrochemical corrosion tests indicated a decrease in the corrosion resistance of Ti in the presence of the biofilms although the TiO(2) film presented the characteristics of a compact oxide film. While the open circuit potential of Ti indicated a tendency to corrosion in the presence of the biofilms, tribocorrosion tests revealed a low friction on biofilm covered Ti. The properties of the biofilms were similar to those of the lubricant agents used to decrease the wear rate of materials. However, the pH-lowering promoted by microbial species, can lead to corrosion of Ti-based oral rehabilitation systems.


Friends Helping Friends: a nonrandomized control trial of a peer-based response to dating violence.
Dating violence is a significant problem for older adolescents with implications for the survivor's health. Survivors disclose the violence to friends who are often ill equipped to help them manage the consequences. The purpose of this pilot study was to evaluate the effectiveness and feasibility of Friends Helping Friends, a community-level education program to teach older adolescents to recognize and intervene in dating violence. A convenience sample of 101 students aged 18 to 22 years were nonrandomly allocated to a treatment or control group and completed pre- and post-test measures. Compared with the control group, treatment group participants reported increased perceived responsibility to help, skills to act as a bystander, and intention to help and decreased rape myth acceptance. Friends Helping Friends shows promise as an effective strategy for older adolescent females in the prevention and response to dating violence.


Chondrogenic and fibrotic process in the ligamentum flavum of patients with lumbar spinal canal stenosis.
A histological, biological, and immunohisto-chemical study of human lumbar ligamentum flavum. To analyze changes in the hypertrophied ligamentum flavum and clarify their etiology. Hypertrophy of the ligamentum flavum has been considered a major contributor to the development of lumbar spinal canal stenosis (LSCS). Although previous studies have reported some factors related to ligamentum flavum hypertrophy, its etiology is still unclear. Ligamentum flavum samples were collected from 20 patients with LSCS (LSCS group) and 10 patients with lumbar disc herniation (LDH group) as a control. The thickness of the ligamentum flavum was measured histologically. The amounts of elastic fibers and proteoglycans were assessed by Elastica-Masson staining and alcian blue staining, respectively. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. The total genes of the 2 groups were compared by DNA microarray analysis. The ligamentum flavum was significantly thicker in the LSCS group, which had a smaller amount of elastic fibers and a larger amount of proteoglycans. The gene expression related to fibrosis was significantly higher in the LSCS group; however, the immunoreactivities of collagen types I and III were weaker on the dorsal side of the ligamentum flavum in the LSCS group. The gene expression related to chondrogenesis and proteoglycan synthesis was significantly higher in the LSCS group. There was no significant difference in the gene expression related to inflammation between the 2 groups. Synthesis of the collagenous fibers and degradation of the elastic and collagenous fibers are both accelerated in the ligamentum flavum of patient with LSCS, which may be the reason for hypertrophy of the tissue. In addition, chondrogenesis and proteoglycan synthesis may have critical roles in the pathogenesis of the ligamentum flavum hypertrophy. 5.


Neural control of circulation in Aplysia. III. Neurotransmitters.
In the abdominal ganglion of Aplysia californica, seven motoneurons have been described which modulate the myogenic heart beat and vasomotor tone (28). These neurons mediate their motor effects by chemical transmission. In this paper we have attempted to specify the transmitters of six of these motoneurons. We have 1) studied the effects of several common transmitters on the innervated structures and compared these effects with the effects of firing the motoneurons, 2) examined whether blocking agents influence similarly the effect of a putative transmitter applied to the innervated structure and the effect of firing a motoneuron, and 3) tested the capability of the motoneurons to synthesize the putative transmitters from precursors. The positive inotropic and chronotropic effects of firing the excitor motoneuron RB(HE) were mimicked by perfusion of the heart with serotonin at a low concentration. Cinanserin blocked both the effects of motoneuron excitation and serotonin perfusion. RB(HE) was also shown to synthesize [3H]serotonin from L-[3H]tryptophan injected directly into the cell body. The effects of firing the two LD(HI) heart-inhibitory motoneurons were mimicked by perfusion of the heart with acetylcholine. Benzoquinonium blocked the effects of the inhibitory motoneuron and acetylcholine perfusion. Perfusion with arecoline also inhibited the heart beat. Acetylcholine applied to the arteries mimicked the vasoconstriction caused by the LB(VC) motoneurons. Aortic constriction in response to activity in LB(VC) cells or to acetylcholine was blocked by hexamethonium and curare. The heart inhibitor and vasoconstrictor motoneurons synthesized [3H] acetylcholine from [3H] choline injected into their cell bodies. Thus, as in vertebrates, acetylcholine mediates inhibition to the heart. Unlike vertebrates, however, serotonin mediates excitation to the heart and acetylcholine mediates peripheral vasoconstriction.


An industrial developmental toxicologist's view of behavioral teratology and possible guidelines.
Many events or studies, such as the Minimata episode, during the past three decades have shown that prenatal insults can have lasting effects on the postnatal functioning of the offspring. These have been duplicated in animal models, and animal studies have been extended to other compounds with the eventual goal of being able to establish the risk in humans of neurological damage a priori from prenatal exposures. However, behavioral tests are not standardized with many of them lacking sensitivity, and are so vulnerable to environmental factors, that little confidence can be placed in their ability to predict risk to the human at this time. More research is needed to develop better tests and an understanding of their significance to humans before they are useful in regulatory toxicology.


Latest advances in cannabinoid receptor agonists.
Since the discovery of cannabinoid receptors and their endogenous ligands in early 1990s, the endocannabinoid system has been shown to play a vital role in several pathophysiological processes. It has been targeted for the treatment of several diseases including neurodegenerative diseases (Parkinson's disease, Alzheimer's disease, Huntington's disease and MS), cancer, obesity, inflammatory bowel disease, neuropathic and inflammatory pain. The last decade has witnessed remarkable advances in the development of cannabinergic ligands displaying high selectivity and potency towards two subtypes of cannabinoid receptors, namely CB1 and CB2. In this review, we highlight the latest advances made in the development of cannabinoid agonists and summarize recently disclosed, novel chemical scaffolds as CB-selective agonists in patents that appeared during January 2008 - June 2009. Data presented here are obtained through the search of PubMed for research articles and reviews, and the website of European patents (http://ep.espacenet.com), SciFinder Scholar and US patents (www.uspto.gov). Our analysis reveals prolific patenting activity mainly in the CB2 selective agonist area. Limiting the BBB penetrability, thereby, leading to peripherally restricted CB1/CB2 agonists and enhancing CB2-selectivity emerge as likely prerequisites for avoidance of adverse central CB1 mediated side effects.


Transphyletic conservation of developmental regulatory state in animal evolution.
Specific regulatory states, i.e., sets of expressed transcription factors, define the gene expression capabilities of cells in animal development. Here we explore the functional significance of an unprecedented example of regulatory state conservation from the cnidarian Nematostella to Drosophila, sea urchin, fish, and mammals. Our probe is a deeply conserved cis-regulatory DNA module of the SRY-box B2 (soxB2), recognizable at the sequence level across many phyla. Transphyletic cis-regulatory DNA transfer experiments reveal that the plesiomorphic control function of this module may have been to respond to a regulatory state associated with neuronal differentiation. By introducing expression constructs driven by this module from any phyletic source into the genomes of diverse developing animals, we discover that the regulatory state to which it responds is used at different levels of the neurogenic developmental process, including patterning and development of the vertebrate forebrain and neurogenesis in the Drosophila optic lobe and brain. The regulatory state recognized by the conserved DNA sequence may have been redeployed to different levels of the developmental regulatory program during evolution of complex central nervous systems.


Microbacterium populi sp. nov., isolated from Populus×euramericana bark.
Five non-spore-forming, aerobic and Gram-stain-positive bacterial strains, 10-107-8(T), 1C-4, NHI3_6, 4107_1_2, and 3D-3, were isolated from Populus × euramericana bark collected in Puyang City, Henan Province, PR China. The isolates grew at 15-40 °C and pH 5-10. The optimum temperature and pH for growth were 30 °C and pH 8.0, respectively. Chemotaxonomic features included MK-10 and MK-11 as major menaquinones (type strain); predominating iso- and anteiso-branched cellular fatty acids; diphosphatidylglycerol and phosphatidylglycerol as major polar lipids (type strain); ornithine as the principal diamino acid of the cell-wall peptidoglycan (type strain); glycolyl type as cell-wall acyl type; and DNA G+C content of 66.8-67.6 mol%. These features were consistent with classification in the genus Microbacterium . Analysis of 16S rRNA gene sequence data indicated that the five isolates belonged to the genus Microbacterium and were closely related to Microbacterium halotolerans . A high 16S rRNA gene sequence similarity of 96.97% to M. halotolerans YIM 70130(T) was observed. The five isolates showed less than 96.20% 16S rRNA gene sequence similarity to the other species of the genus Microbacterium with validly published names. DNA-DNA relatedness of the five isolates with M. halotolerans JCM 13013(T) ranged from 35.62% to 44.36%. Considering the results of 16S rRNA gene sequence analysis and the physiological and biochemical characteristics, we propose that the five strains should be assigned to a novel species of the genus Microbacterium . The name proposed for the five strains is Microbacterium populi sp. nov., and the type strain is 10-107-8(T) ( =CFCC 11275(T) =KCTC 29152(T)).


Auxin biology revealed by small molecules.
The plant hormone auxin regulates virtually every aspect of plant growth and development and unraveling its molecular and cellular modes of action is fundamental for plant biology research. Chemical genomics is the use of small molecules to modify protein functions. This approach currently rises as a powerful technology for basic research. Small compounds with auxin-like activities or affecting auxin-mediated biological processes have been widely used in auxin research. They can serve as a tool complementary to genetic and genomic methods, facilitating the identification of an array of components modulating auxin metabolism, transport and signaling. The employment of high-throughput screening technologies combined with informatics-based chemical design and organic chemical synthesis has since yielded many novel small molecules with more instantaneous, precise and specific functionalities. By applying those small molecules, novel molecular targets can be isolated to further understand and dissect auxin-related pathways and networks that otherwise are too complex to be elucidated only by gene-based methods. Here, we will review examples of recently characterized molecules used in auxin research, highlight the strategies of unraveling the mechanisms of these small molecules and discuss future perspectives of small molecule applications in auxin biology.


Functional haplotypes of the RET proto-oncogene promoter are associated with Hirschsprung disease (HSCR).
The activation of the RET signaling pathway during embryogenesis is a crucial prerequisite for a directional migration of enteric nervous system progenitor cells. Loss-of-function germline mutations of the RET proto-oncogene are reported in familial and sporadic cases of Hirschsprung disease (HSCR) with a variable frequency. Furthermore, variants of several RET polymorphisms are over- or under-represented in HSCR populations. Specifically, the c.135A RET variant has been previously shown to be strongly associated with the HSCR phenotype. We have reported an HSCR-phenotype modifying effect of the RET c.135G>A polymorphism due to a within-gene interaction in patients harboring RET germline mutations, yet the function of the c.135G>A variant is unknown. The basic RET promoter region was investigated by DNA sequencing approach in 80 HSCR patients. Identified polymorphisms were genotyped in the HSCR and in a control population and haplotypes were reconstructed. The dual-luciferase assay was used to evaluate the activity of different RET promoter haplotypes. We demonstrate that variants of two RET promoter polymorphisms -5G>A and -1C>A from the transcription start site are associated with HSCR. Furthermore, the -5G>A polymorphism is in strong linkage disequilibrium with the c.135G>A polymorphism. The promoter haplotype -5/-1AC associated with HSCR has a significantly lower activity in an in vitro dual-luciferase expression assay compared with those haplotypes identified in the majority of normal controls. These data suggest a role for RET haplotypes containing the -5A promoter variant in the etiology of HSCR.


Synthesis and antibacterial properties of 7-[2-(3-substituted-5-isoxazolyl)-2-methoxyiminoacetamido]cep halospora nic acid derivatives.
The synthesis of new 2-(3-substituted-5-isoxazolyl)-2-methoxyiminoacetic acids and their condensation derivatives with a suitable cephalosporanic nucleus, is reported. Their antibacterial properties were tested in vivo and in vitro also against beta-lactamase producer microorganisms; particularly the oral bioavailability of some of these new derivatives was studied.


The effect of community-level unemployment on preventive oral health care utilization.
To test the hypothesis that high community-level unemployment is associated with reduced use of preventive dental care services by a dentally insured population. The study uses monthly data on population dental visits and unemployment in the Seattle and Spokane areas from 1995 to 2004. Utilization data come from Washington Dental Services. Unemployment data were obtained from the Bureau of Labor Statistics and Washington's Employment Security Department. The study uses a Box-Jenkins Autoregressive Integrated Moving Average (ARIMA) method to measure the association between the variables over time. The approach controls for the effects of autocorrelation, seasonality, and confounding variables. In the Seattle area, an unexpected 10,000 unit increase in the number of unemployed individuals is associated with a 1.24 percent decrease in preventive visits during the month ( p=.0043). In the Spokane area, a similar increase in unemployment is associated with a 5.95 percent decrease in preventive visits ( p=.0326). The findings persist when the independent variable is the number of initial unemployment insurance claims. The analysis suggests that utilization of preventive dental care declines during periods of high community-level unemployment. Community-level unemployment may impede or distract populations from utilizing preventive dental services. The study's findings have implications for insurers, dentists, policy makers, and researchers.


Factors associated with outcome of cognitive-behavioural therapy for complicated grief: a preliminary study.
Complicated grief (CG), also called prolonged grief disorder, is a debilitating condition that can develop following a loss. There is growing evidence that cognitive-behavioural interventions are efficacious in the treatment of CG. The present preliminary study used data from 43 patients with CG who were randomly assigned to cognitive-behavioural therapy in an earlier treatment trial to explore (a) predictors of outcome of cognitive-behavioural therapy for CG and (b) the relationship between symptom improvement and changes in loss-related negative cognitions and avoidance behaviours. Analyses showed that worse treatment outcome was associated with lower education attainment, loss of a partner/child (instead of some other relative), early treatment discontinuation, less patient motivation and more severe CG symptoms at pre-treatment. As predicted, stronger reduction in CG severity was significantly associated with stronger reductions in negative cognitions and avoidance. Implications of these findings are discussed.


Arthroscopic assessment for lateral collateral ligament complex deficiency of the elbow: a cadaveric study.
To evaluate whether elbow instability due to lateral collateral ligament complex injury can be assessed reliably through arthroscopy. Eight fresh human cadaveric elbows were placed in a simulated lateral decubitus position. The radiocapitellar joint (RCJ) gap and ulnohumeral joint (UHJ) gap (mm) were measured with different sizes of probes from the posterolateral viewing portal. The elbow was 90 degrees flexed with neutral forearm rotation for RCJ gap measurement and 30 degrees flexed with full supination for UHJ gap measurement. Sequential testing was performed from Stage 0 to Stage 3 (Stage 0: intact; Stage 1: the release of the anterior 1/3 LCL complex; Stage 2: the release of the anterior two thirds of the LCL complex; and Stage 3: the release of the entire LCL complex) on each specimen. The mean gap of RCJ and lateral UHJ was used for the comparison between stages with the intact elbow. The mean RCJ gap distance in Stage 2 and Stage 3 was significantly increased compared to that in Stage 0 (Stage 0 vs. Stage 2: P = .008; Stage 0 vs. Stage 3: P = .010). The mean UHJ gap distance of Stage 1, Stage 2, and Stage 3 was significantly increased compared to that in Stage 0 (Stage 0 vs. Stage 1: P = 0.025; Stage 0 vs. Stage 2: P = .010; Stage 0 vs. Stage 3: P = .011). In contrast, the release of the anterior 1/3 of the LCL complex (Stage 1) was not significantly increased compared to the mean joint gap distance of RCJ (P = .157). Arthroscopic measurement of joint gap widening in RCJ and UHJ is a reliable assessment method to detect LCL complex deficiency that involves the anterior two thirds or more.


CYP2D6 polymorphisms and the risk of tardive dyskinesia in schizophrenia: a meta-analysis.
The present study aimed to evaluate whether there is any association between CYP2D6 alleles and susceptibility to tardive dyskinesia in patients with schizophrenia under treatment. A meta-analysis considered case-control studies determining the distribution of genotypes for any CYP2D6 polymorphism in unrelated tardive dyskinesia cases and controls without tardive dyskinesia among patients with schizophrenia who were treated with antipsychotic agents. Loss of function alleles were grouped together in a single comparison, whereas other alleles (2 and 10) were examined separately. Data were available for eight (n=569 patients), three (n=325 patients) and four (n=556) studies evaluating the effect of the loss of function alleles, the 2 allele and the 10 allele, respectively. Summary odds ratios (ORs) suggested that loss of function alleles increased the risk of tardive dyskinesia significantly [OR=1.43, 95% confidence interval (CI) 1.06-1.93, P=0.021], whereas there was no effect for 2 and inconclusive evidence for 10 (OR=0.82, 95% CI 0.50-1.32, P=0.41 and OR=1.19, 95% CI, 0.89-1.60, P=0.24, respectively). Patients who were homozygotes for loss of function alleles (poor metabolizers) had 1.64-fold greater odds of suffering tardive dyskinesia compared to other patients with schizophrenia, but the effect was not formally significant (95% CI 0.79-3.43). For the risk conferred by loss of function alleles, large studies provided more conservative estimates of a genetic effect than smaller studies (P=0.003). CYP2D6 loss of function alleles may predispose to tardive dyskinesia in patients with schizophrenia under treatment, but bias cannot be excluded.


Detecting noise with shot noise using on-chip photon detector.
The high-frequency radiation emitted by a quantum conductor presents a rising interest in quantum physics and condensed matter. However, its detection with microwave circuits is challenging. Here, we propose to use the photon-assisted shot noise for on-chip radiation detection. It is based on the low-frequency current noise generated by the partitioning of photon-excited electrons and holes, which are scattered inside the conductor. For a given electromagnetic coupling to the radiation, the photon-assisted shot noise response is shown to be independent on the nature and geometry of the quantum conductor used for the detection, up to a Fano factor, characterizing the type of scattering mechanism. Ordered in temperature or frequency range, from few tens of mK or GHz to several hundred of K or THz respectively, a wide variety of conductors can be used like Quantum Point Contacts (this work), diffusive metallic or semi-conducting films, graphene, carbon nanotubes and even molecule, opening new experimental opportunities in quantum physics.


Detection of four human polyomaviruses (MCPyV, HPyV6, HPyV7 and TSPyV) in cervical specimens from HIV-infected and HIV-uninfected women.
To investigate the presence of recently discovered human polyomaviruses in cervical specimens collected from African and French women, in relation to HIV serostatus, high-risk human papillomavirus infection (HR-HPV) and cervical disease. Cervical specimens were collected from 140 HIV-1-seropositive African women and 50 HIV-seronegative French women. Presence of Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), human polyomavirus 7 (HPyV7) and trichodysplasia spinulosa-associated polyomavirus (TSPyV) was detected by real-time PCR, and presence of HR-HPV DNA by Hybrid Capture 2 assay with subsequent HPV genotyping using the INNO-LiPA HPV Genotyping Extra assay. Cervical biopsies were analysed by histopathology. The detection rates were 55.3%, 3.2%, 2.1% and 0% for MCPyV, HPyV6, HPyV7 and TSPyV, respectively, with no significant difference by population. The MCPyV viral load ranged from 14 to 210 DNA copies/106 cells (median, 80 DNA copies/106 cells), with no difference between women with and without cervical precancerous lesions. There was no association between detection of human polyomaviruses in cervical specimens and geographical origin/HIV serostatus, HR-HPV coinfection or precancerous cervical lesions. These observations argue against a possible role of MCPyV as a cofactor in HPV-induced carcinogenesis. MCPyV and, to a lesser extent, HPyV6 and HPyV7 might belong to the female genital tract microbiota.


Fusion Molecules of Heat Shock Protein HSPX with Other Antigens of Mycobacterium tuberculosis Show High Potential in Serodiagnosis of Tuberculosis.
Variable individual response against the antigens of Mycobacterium tuberculosis necessitates detection of multiple antibodies for enhancing reliability of serodiagnosis of tuberculosis. Fusion molecules consisting of two or more antigens showing high sensitivity would be helpful in achieving this objective. Antigens of M. tuberculosis HSPX and PE35 were expressed in a soluble form whereas tnPstS1 and FbpC1 were expressed as inclusion bodies at 37°C. Heat shock protein HSPX when attached to the N-termini of the antigens PE35, tnPstS1 and FbpC1, all the fusion molecules were expressed at high levels in E. coli in a soluble form. ELISA analysis of the plasma samples of TB patients against HSPX-tnPstS1 showed 57.7% sensitivity which is nearly the same as the expected combined value obtained after deducting the number of plasma samples (32) containing the antibodies against both the individual antigens. Likewise, the 54.4% sensitivity of HSPX-PE35 was nearly the same as that expected from the combined values of the contributing antigens. Structural analysis of all the fusion molecules by CD spectroscopy showed that α-helical and β-sheet contents were found close to those obtained through molecular modeling. Molecular modeling studies of HSPX-tnPstS1 and HSPX-PE35 support the analytical results as most of the epitopes of the contributing antigens were found to be available for binding to the corresponding antibodies. Using these fusion molecules in combination with other antigenic molecules should reduce the number of antigenic proteins required for a more reliable and economical serodiagnosis of tuberculosis. Also, HSPX seems to have potential application in soluble expression of heterologous proteins in E. coli.


Expectation pooling: an effective and interpretable pooling method for predicting DNA-protein binding.
Convolutional neural networks (CNNs) have outperformed conventional methods in modeling the sequence specificity of DNA-protein binding. While previous studies have built a connection between CNNs and probabilistic models, simple models of CNNs cannot achieve sufficient accuracy on this problem. Recently, some methods of neural networks have increased performance using complex neural networks whose results cannot be directly interpreted. However, it is difficult to combine probabilistic models and CNNs effectively to improve DNA-protein binding predictions. In this article, we present a novel global pooling method: expectation pooling for predicting DNA-protein binding. Our pooling method stems naturally from the expectation maximization algorithm, and its benefits can be interpreted both statistically and via deep learning theory. Through experiments, we demonstrate that our pooling method improves the prediction performance DNA-protein binding. Our interpretable pooling method combines probabilistic ideas with global pooling by taking the expectations of inputs without increasing the number of parameters. We also analyze the hyperparameters in our method and propose optional structures to help fit different datasets. We explore how to effectively utilize these novel pooling methods and show that combining statistical methods with deep learning is highly beneficial, which is promising and meaningful for future studies in this field. All code is public in https://github.com/gao-lab/ePooling. Supplementary data are available at Bioinformatics online.


Genes that affect both cell growth and polarity mediate stem cell quiescence.
Stem cells possess the capacity to expand and self-renew and do so by dividing in either a symmetrical or an asymmetrical manner. Under particular circumstances, some stem cell populations can undergo prolonged cell cycle arrest or quiescence, until they are triggered to divide by a given stimulus. In cancer treatment, these populations represent a significant roadblock to efficient therapies as their non-dividing state renders them refractory to most commonly used cytotoxic interventions. In certain organisms, germline stem cells undergo quiescence if animals experience inappropriate growth conditions, and recent studies have determined that the level of insulin signaling is key in the regulation of their proliferation rate, and that it functions through at least two tumor suppressor genes, PTEN and LKB1. These gene products regulate both growth and polarity in diverse cellular contexts, while it remains unclear how they can modulate cell division and prevent tumorigenesis through each of these functions, and whether indeed these functions are separable. We hope that understanding how these tumor suppressor genes impinge on quiescent stem cell populations could provide us with a means of designing more effective therapies to reduce the frequency of stem cell-derived tumor growth that occurs following treatment.


Development of a tool to assess psychosocial indicators of fruit and vegetable intake for 2 federal programs.
Development of an evaluation tool of psychosocial constructs for use by participants in 2 federal programs, Food Stamp Nutrition Education and the Expanded Food and Nutrition Education Program. Cross-sectional data from a longitudinal study. Limited-resource women (n = 111) living in low-income communities. Test-retest reliability, internal consistency, ethnic differences, convergent validity. Spearman rank order correlation, analysis of variance, principal components analysis. Reliability coefficients ranged from a low of r = .18 (not significant) to r = .74 (P < .0001). Two items were deleted for not meeting criteria for reliability and 2 for redundancy. Ethnic differences at baseline were significant for 1 item. Domain constructs loaded on 4 to 5 factors for the biopsychosocial framework. Estimates of convergent validity of 9 constructs led to the deletion of 3 (ie, perceived barriers, social support, and perceived norms), with retention of perceived benefits, perceived control, self-efficacy, readiness to eat more fruit, readiness to eat more vegetables, and perceived diet quality. As an estimate of convergent validity, the final version of the tool with 6 constructs remaining showed significant correlations with indicators of diet quality: serum carotenoid values (r = .38, P < .001); hypothesized nutrients calculated from the mean of 3 24-hour dietary recalls (vitamin C, r = .47, P < .0001; vitamin A, r = .39, P < .0001; folate, r = .37, P < .0001; beta-carotene, r =.31, P < .001; and fiber, r = .46, P < .0001); fruit and vegetable servings (r = 0.55, P < .0001); Healthy Eating Index (r = .27, P < .05); and a fruit and vegetable behavioral scale (r = .60, P < .0001). This systematic process yielded a fruit and vegetable evaluation tool useful for practitioners and researchers. This is the first validation study of this type to estimate convergent validity with 5 indicators of diet quality, including a biomarker.


Genetic conjugation of components in two pneumococcal fusion protein vaccines enhances paediatric mucosal immune responses.
Streptococcus pneumoniae colonises the upper respiratory tract and can cause pneumonia, meningitis and otitis media. Existing pneumococcal conjugate vaccines are expensive to produce and only protect against 13 of the 90+ pneumococcal serotypes; hence there is an urgent need for the development of new vaccines. We have shown previously in mice that pneumolysin (Ply) and a non-toxic variant (Δ6Ply) enhance antibody responses when genetically fused to pneumococcal surface adhesin A (PsaA), a potentially valuable effect for future vaccines. We investigated this adjuvanticity in human paediatric mucosal primary immune cell cultures. Adenoidal mononuclear cells (AMNC) from children aged 0-15 years (n=46) were stimulated with conjugated, admixed or individual proteins, cell viability and CD4+ T-cell proliferative responses were assessed using flow cytometry and cytokine secretion was measured using multiplex technology. Proliferation of CD4+ T-cells in response to PsaAPly, was significantly higher than responses to individual or admixed proteins (p=0.002). In contrast, an enhanced response to PsaAΔ6Ply compared to individual or admixed proteins only occurred at higher concentrations (p<0.01). Evaluation of cytotoxicity suggested that responses occurred when Ply-induced cytolysis was inhibited, either by fusion or mutation, but importantly an additional toxicity independent immune enhancing effect was also apparent as a result of fusion. Responses were MHC class II dependent and had a Th1/Th17 profile. Genetic fusion of Δ6Ply to PsaA significantly modulates and enhances pro-inflammatory CD4+ T-cell responses without the cytolytic effects of some other pneumolysoids. Membrane binding activity of such proteins may confer valuable adjuvant properties as fusion may assist Δ6Ply to deliver PsaA to the APC surface effectively, contributing to the initiation of anti-pneumococcal CD4+ T-cell immunity.


Treatment of extraprostatic cancer in clinically organ-confined prostate cancer by permanent interstitial brachytherapy: is extraprostatic seed placement necessary?
Successful treatment with ultrasound-guided transperineal interstitial permanent prostate brachytherapy (TIPPB) relies on effective radiation coverage of intraprostatic and clinically occult extraprostatic cancer. This study examines prostatectomy findings as they relate to treatment of extraprostatic extension (EPE) of cancer and TIPPB techniques and dosimetry. A total of 313 prostatectomy specimens from patients with clinical tumor classification T1-T2b adenocarcinomas, serum prostate-specific antigen <20 ng/mL, and Gleason score <8 were whole mounted and evaluated for intraprostatic cancer volume and extraprostatic radial distance, area of perforation, and cancer density. From these data, extraprostatic cancer volume is calculated and used to estimate extraprostatic tumor control probabilities using the linear quadratic radiobiological model and Poisson statistics. TIPPB dose-gradient characteristics at the prostate periphery are examined. Intraprostatic cancer volume ranges from 0 to 38 cc, whereas extraprostatic cancer volume ranges from 0 to 4.6 cc (mean 0.06 cc). The radial distance of EPE ranges from 0 to 4.4 mm (mean 0.18 mm). The ratio of extraprostatic to intraprostatic cancer volume ranges from 0% to 18% (mean 0.4%). Only small amounts of clinically occult extraprostatic cancer were identified in the majority of specimens with EPE. Tumor control probability calculations suggest that this volume of cancer may be treated effectively with TIPPB. Treatment of this cancer possibly is achieved with an intraprostatic implant, but treatment of all cancers identified in this study suggests that some extraprostatic seed placement is desirable.


Acceleration patterns of the head and pelvis when walking on level and irregular surfaces.
The aim of this study was to evaluate acceleration patterns at the head and pelvis while subjects walked on a level and an irregular walking surface, to develop an understanding of how the postural control system responds to challenging walking conditions. Thirty young, healthy subjects walked on a level corridor and on artificial grass underlain with foam and wooden blocks placed in an arbitrary manner. Temporo-spatial gait parameters and acceleration patterns at the head and pelvis were measured. The results revealed that when walking on the irregular surface, subjects were able to maintain their velocity, but adopted a slower and more variable cadence and a significantly longer stride length. The magnitude of pelvis accelerations increased, however head accelerations were not affected by the walking surface. When considered as an overall pattern of movement, these findings suggest that one of the primary objectives of the postural control system when walking on irregular surfaces is head control, and that subjects adapt their stepping pattern on irregular surfaces to ensure that the head remains stable.


The intracellular triacylglycerol/fatty acid cycle: a comparison of its activity in hepatocytes which secrete exclusively apolipoprotein (apo) B100 very-low-density lipoprotein (VLDL) and in those which secrete predominantly apoB48 VLDL.
Hamster hepatocytes, like human hepatocytes, secrete triacylglycerol (TAG) as very-low-density lipoprotein (VLDL) in association with apolipoprotein (apo) B100, whereas in the rat, TAG is secreted predominantly in association with apoB48. Nevertheless, in hepatocytes from both species, a minimum of between 60% and 70% [69. 1+/-1.4% (hamster), 60.6+/-2.5% (rat)] of the VLDL TAG was secreted following lipolysis and re-esterification of intracellular TAG. The fractional rates of hepatocellular TAG turnover (lipolysis and re-esterification) were similar in both species [1.83+/-0.28 pools/24 h (hamster), 1.39+/-0.23 pools/24 h (rat)]. Comparison of the relative changes in the 3H and 14C specific radioactivities of the VLDL and cellular TAG, pre-labelled with [3H]glycerol and [4C]oleate, suggested that fatty acids released by lipolysis either were recruited directly into a VLDL assembly pool or were recycled to the cellular pool following re-esterification. Recycling in the hamster was somewhat greater than in the rat (66.1+/-5.7% versus 53. 7+/-4.8% of TAG lipolysed respectively). Similarly, a larger proportion of newly synthesized TAG was retained within the cell, rather than secreted as VLDL, in the hamster compared with the rat (37.9+/-2.8% versus 20+/-3.8%, P<0.01). These factors may have contributed to the somewhat lower rate of VLDL TAG secretion in the hamster hepatocytes compared with those from the rat (43.3+/-4.2 versus 96.4+/-3.4 microg/24 h per mg of cell protein). Rat hepatocytes were more sensitive to inhibition of VLDL secretion by insulin than were those from hamster. In neither case did insulin affect total or fractional TAG turnover. The results suggest that assembly of both apoB100 VLDL and apoB48 VLDL is associated with efficient intracellular TAG lipolysis.


Bionomics of Anopheles culicifacies giles in riverine tract rural areas of district Shahjahanpur, Uttar Pradesh.
Studies on seasonal prevalence, resting behaviour, gonotropic conditions and breeding habits of Anopheles culicifacies were carried out from January 1987 to December 1989 in riverine villages of Dadraul PHC in Shahjahanpur district, Uttar Pradesh. Man hour densities of An. culicifacies varied from 11.3 to 125.1 during the study period. The species showed two peaks of high prevalence: one during March to June and the other during October to December. The first peak was higher than the second. The collection revealed a higher proportion of freshly fed to semi-gravid females thus indicating the outdoor resting behaviour of the species. From the immatures collected from riverbed pools, 7 anopheline species were identified. Of the 955 specimens identified, An. culicifacies constituted the highest number (62.1%). The study indicates that low rainfall and drought did not affect An. culicifacies densities or malaria transmission in riverine areas.


Infantile Cytomegalovirus-Associated Severe Warm Autoimmune Hemolytic Anemia: A Case Report.
Autoimmune hemolytic anemia is a rare hematologic entity in children. Etiologies are mainly viruses or bacteria. We describe here a case of severe warm autoimmune hemolytic anemia (IgG- and C3d-positive direct antiglobulin test) in an immunocompetent 6-month-old infant with acute Cytomegalovirus infection that responded well to corticotherapy and intraveneous immunoglobulins without using blood component transfusion. This case demonstrates the importance of recognizing CMV in infantile Autoimmune Hemolytic Anemia, especially because hemolysis can be severe and lethal.


FRACTALS WITH POINT IMPACT IN FUNCTIONAL LINEAR REGRESSION.
This paper develops a point impact linear regression model in which the trajectory of a continuous stochastic process, when evaluated at a "sensitive time point", is associated with a scalar response. The proposed model complements and is more interpretable than the functional linear regression approach that has become popular in recent years. The trajectories are assumed to have fractal (self-similar) properties in common with a fractional Brownian motion with an unknown Hurst exponent. Bootstrap confidence intervals based on the least-squares estimator of the sensitive time point are developed. Misspecification of the point impact model by a functional linear model is also investigated. Non-Gaussian limit distributions and rates of convergence determined by the Hurst exponent play an important role.


THE CANONICAL WNT PATHWAY IN GASTRIC CARCINOMA.
It is believed that the Wnt pathway is one of the most important signaling involved in gastric carcinogenesis. To analyze the protein expression of canonical and non-canonical Wnt pathways in gastric carcinoma. The immunohistochemistry was performed in 72 specimens of gastric carcinomas for evaluating the expression of Wnt-5a, FZD5, GSK3β, axin, CK1, ubiquitin, cyclin D1 and c-myc. There were significant differences for cytoplasm and nucleus ubiquitin for moderately and well differentiated tumors (p=0.03) and for those of the intestinal type of the Lauren classification (p=0.03). The absence of c-myc was related to Lauren's intestinal tumors (p=0.03). Expression of CK1 in the cytoplasm was related to compromised margin (p=0.03). Expression of cyclin D1 protein was more intense in male patients (p=0.03) There was no relation of the positive or negative expression of the Wnt-5a, FZD5, GSK3 and Axin with any clinicopathological variables. The canonical WNT pathway is involved in gastric carcinoma.


Blood Pressure Variability and Prediction of Target Organ Damage in Patients With Uncomplicated Hypertension.
The average of multiple blood pressure (BP) readings (mean BP) independently predicts target organ damage (TOD). Observational studies have also shown an independent relationship between BP variability (BPV) and TOD, but there is limited longitudinal data. This study aimed to determine the effects of changes in mean BP levels compared with BPV on left ventricular mass index (LVMI) and aortic pulse wave velocity (aPWV). Mean BP levels (research-protocol clinic BP (clinic BP), 24-hour ambulatory BP, and 7-day home BP) and BPV were assessed in 286 patients with uncomplicated hypertension (mean age 64±8 SD years, 53% women) over 12 months. Reading-to-reading BPV (from 24-hour ambulatory BP) and day-to-day BPV (from 7-day home BP) were assessed at baseline and 12 months, and visit-to-visit BPV (clinic BP) was assessed from 5 visits over 12 months. LVMI was measured by 3D echocardiography and aPWV with applanation tonometry. The strongest predictors of the changes in LVMI (ΔLVMI) were the changes in mean 24-hour systolic BPs (SBPs) (P < 0.02). Similarly, the strongest predictors of the changes in aPWV (ΔaPWV) were the changes in mean 24-hour ambulatory SBPs (P < 0.01) and the changes in mean clinic SBP (P < 0.001). However, none of the changes in BPV were independently associated with ΔLVMI or ΔaPWV (P > 0.05 for all). Changes in mean BP levels, but not BPV, were most relevant to changes in TOD in patients with uncomplicated hypertension. Thus, from this point of view, BPV appears to have limited clinical utility in this patient population.


Intestinal infection due to enteroaggregative Escherichia coli among human immunodeficiency virus-infected persons.
To investigate the pathogenic role of enteroaggregative Escherichia coli (EAggEC) among human immunodeficiency virus-infected persons, 111 outpatients with and 68 without diarrhea were evaluated. Examination of stool samples included the HeLa cell adherence assay and an EAggEC polymerase chain reaction (PCR) assay using primers complementary for the plasmid locus CVD432. The pCVD432 genotype, adherence phenotype, and patient characteristics were correlated with occurrence of diarrhea by multivariate analyses. EAggEC PCR and adherence assays were positive in 7 (6%) and 24 (22%) patients with diarrhea and in 1 (1%) and 21 (31%) asymptomatic control patients, respectively. Clinical manifestations associated with EAggEC PCR-positive isolates were nonspecific; EAggEC infections were independent of CD4 lymphocyte counts. Of the pCVD432 genotype, 5 (71%) of 7 were resistant to cotrimoxazole and ampicillin, and 1 strain was resistant to ciprofloxacin. Overall, pCVD432 PCR-positive E. coli was the most prevalent intestinal organism associated with diarrhea. The adherence assay results did not correlate with diarrhea.


Women's status and violence against young married women in rural Nepal.
Studies conducted around the world consistently show the existence of violence against women. Despite the increasing number of studies being conducted on violence against young married women elsewhere, this subject has received little attention from researchers and policy makers in Nepal. This paper assesses the prevalence of violence among young married women in rural Nepal. Specifically, it examines [factors related to] women's status in order to better understand the risk of violence. A cross-sectional study was conducted in 2009 among 1,296 young married women aged 15-24 years in four major ethnic groups. Bivariate analysis and multivariate logistic regression were used to examine the association between selected risk factors and violence. More than half the women (51.9%) reported having experienced some form of violence in their lifetime. One-fourth (25.3%) reported physical violence and nearly half (46.2%) reported sexual violence. Likewise, one-third (35.8%) of women reported experiencing some form of violence in the past 12 months. No or little inter-spousal communication and low autonomy of women significantly increases the odds of experiencing violence among married women. The violence against women is quite common among young married women in rural Nepal. Although the Domestic Violence and Punishment Act 2066 has been enacted, equal attention needs to be given to increasing women's autonomy and activities that encourage inter-spousal communication. Furthermore, more research is required in Nepal that examines dynamics of violence perpetrated by husbands.


The role of the chemokines MCP-1, GRO-alpha, IL-8 and their receptors in the adhesion of monocytic cells to human atherosclerotic plaques.
Monocyte adhesion to the arterial endothelium and subsequent migration into the intima are central events in the pathogenesis of atherosclerosis. Previous experimental models have shown that chemokines can enhance monocyte-endothelial adhesion by activating monocyte integrins. Our study assesses the role of chemokines IL-8, MCP-1 and GRO-alpha, together with their monocyte receptors CCR2 and CXCR2 in monocyte adhesion to human atherosclerotic plaques. In an adhesion assay, a suspension of monocytic U937 cells was incubated with human atherosclerotic artery sections and the levels of endothelial adhesion were quantified. Adhesion performed in the presence of a monoclonal antibody to a chemokine, chemokine receptor or of an isotype matched control immunoglobulin, shows that antibodies to all chemokines tested, as well as their receptors, inhibit adhesion compared to the control immunoglobulins. Immunohistochemistry demonstrated the expression of MCP-1, GRO-alpha and their receptors in the endothelial cells and intima of all atherosclerotic lesions. These results suggest that all these chemokines and their receptors can play a role in the adhesion of monocytes to human atherosclerotic plaques. Furthermore, they suggest that these chemokine interactions provide potential targets for the therapy of atherosclerosis.


Healthy Properties of a New Formulation of Pomegranate-Peel Extract in Mice Suffering from Experimental Autoimmune Encephalomyelitis.
A new formulation of a pomegranate-peel extract (PEm) obtained by PUAE (Pulsed Ultrasound-Assisted Extraction) and titrated in both ellagic acid (EA) and punicalagin is proposed, characterized and then analyzed for potential health properties in mice suffering from the experimental autoimmune encephalomyelitis (EAE). PEm effects were compared to those elicited by a formulation containing EA (EAm). Control and EAE mice were chronically administered EAm and Pem dissolved in the drinking water, starting from the day 10 post-immunization (d.p.i.), with a "therapeutic" protocol to deliver daily 50 mg/kg of EA. Treated EAE mice did not limit their daily access to the beverage, nor did they show changes in body weight, but they displayed a significant amelioration of "in vivo" clinical symptoms. "Ex vivo" histochemical analysis showed that spinal-cord demyelination and inflammation in PEm and EAm-treated EAE mice at 23 ± 1 d.p.i. were comparable to those in the untreated EAE animals, while microglia activation (measured as Ionized Calcium Binding Adaptor 1, Iba1 staining) and astrocytosis (quantified as glial fibrillar acid protein, GFAP immunopositivity) significantly recovered, particularly in the gray matter. EAm and PEm displayed comparable efficiencies in controlling the spinal pathological cellular hallmarks in EAE mice, and this would support their delivery as dietary supplementation in patients suffering from multiple sclerosis (MS).


Expression in Escherichia coli and function of Pseudomonas aeruginosa outer membrane porin protein F.
The gene encoding porin protein F of Pseudomonas aeruginosa was cloned onto a cosmid vector into Escherichia coli. Protein F was expressed as the predominant outer membrane protein in a porin-deficient E. coli background and was clearly visible on one-dimensional sodium dodecyl sulfate-polyacrylamide gels in a porin-sufficient background. The identity of the protein F from the E. coli clone and native P. aeruginosa protein F was demonstrated by their identical mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoretograms, 2-mercaptoethanol modifiabilities, and reactivities with monoclonal antibodies specific of two separate epitopes of protein F. In the course of gene subcloning, a 2-kilobase DNA fragment was isolated, with an apparent truncation of the part of the gene encoding the carboxy terminus of protein F. This subclone produced a 24,000-molecular-weight, outer membrane-associated, truncated protein F derivative which was not 2-mercaptoethanol modifiable and which reacted with only one of the two classes of protein F-specific monoclonal antibodies. The 2-kilobase fragment was used in Southern blot hybridizations to construct a restriction map of the cloned and subcloned fragments and to demonstrate with restriction digests of whole P. aeruginosa DNA that only one copy of the protein F gene was present in the P. aeruginosa chromosome. The protein F produced by the original cosmid clone in a porin-deficient E. coli background was purified. To demonstrate retention of porin function after cloning, the protein F from the E. coli clone was incorporated into black lipid bilayer membranes. Two major classes of channels were revealed. The predominant class of channels had an average conductance of 0.36 nS in 1 M KCl, whereas larger channels (4 to 7 nS) were seen at a lower frequency. Similar channel sizes were observed for porin protein F purified by the same method from P. aeruginosa outer membranes.


DCEBIO-mediated dilations are attenuated in the female rat middle cerebral artery.
Unlike in peripheral vessels, the endothelium-derived hyperpolarizing factor (EDHF)-mediated component to P2Y(2) receptor-mediated dilations is significantly attenuated in the middle cerebral artery (MCA) of female rats compared to male rats. One aspect to the EDHF phenomenon is activation of the intermediate calcium-sensitive potassium (IK(Ca)) channels located on the endothelium. In an attempt to pinpoint the site along the EDHF pathway that is compromised in females, we tested the hypothesis that direct activation of IK(Ca) channels with DCEBIO would elicit attenuated hyperpolarization in the endothelium and smooth muscle of females compared to males. Inhibitors of nitric oxide synthase and cyclooxygenase were present throughout all experiments. Vessel diameter changes were assessed in pressurized and luminally perfused MCAs. Membrane potential changes in the endothelium and smooth muscle were measured using the perforated patch clamp method and sharp electrodes, respectively. The maximum vasodilation to 3 x 10(-4)M DCEBIO was significantly reduced in females (37 +/- 9%) compared to intact males (70 +/- 4%). Endothelial cell hyperpolarization to DCEBIO was similar in both males and females. Smooth muscle cell hyperpolarization was attenuated in females (2 +/- 1 mV) compared to males (15 +/- 3 mV). Taken together, our data suggest that the transfer of hyperpolarization from the endothelium to the smooth muscle is impeded in the female rat MCA.


The feasibility of screening preschool children for urinary tract infection using dipslides.
Preschool children were screened for urinary tract infection (UTI) using Oxoid dipslides. A colony count of greater than 10(5) per ml was obtained from 64 out of 566 boys, and 58 out of 446 girls. A diagnosis of UTI was established in 3 boys, all aged 6 months or less, and 5 girls. No child was found to have either vesico-ureteric reflux (VUR) or renal scarring. False positive results were obtained in 15-17% of male and female infants and were attributable to the obligatory use of bag urine collection. These high rates preclude the use of this method in identifying UTI in preschool children on a wide scale.


Repetitive and Self-injurious Behaviors in Children with Cornelia de Lange Syndrome.
Cornelia de Lange syndrome (CdLS) is associated with repetitive and self-injurious behaviors (RBs, SIB). Evaluating children with CdLS, this study: (1) characterizes the spectrum of RBs; (2) characterizes the impact and severity of RBs including SIB; (3) describes how age and adaptive functioning relate to RBs including SIB. Fifty children (5-17 years) with CdLS were assessed with Children's Yale-Brown Obsessive Compulsive Scale Modified for PDD; Aberrant Behavior Checklist (ABC); Vineland Adaptive Behaviors Scales (VABS). All children had ≥ 1 type of RB; 44% had some form of SIB. 64% spent > 1 h/day displaying RBs. Lower VABS adaptive functioning was associated with higher stereotypy and SIB scores (ABC). In children with CdLS, RBs including SIB are common, impactful, and associated with lower adaptive functioning.


Tanshinone IIA induces autophagic cell death via activation of AMPK and ERK and inhibition of mTOR and p70 S6K in KBM-5 leukemia cells.
Although tanshinone IIA (Tan IIA) from Salviae miltiorrhizae was known to induce apoptosis in various cancers, its underlying mechanism of autophagic cell death was not reported yet. Thus, in the present study, the molecular mechanism of autophagic cell death by Tan IIA was investigated in KBM-5 leukemia cells. Tan IIA significantly increased the expression of microtubule-associated protein light chain 3 (LC3) II as a hallmark of autophagy in western blotting and immunofluorescence staining. Tan IIA augmented the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and attenuated the phosphorylation of mammalian target of rapamycin (mTOR) and p70 S6K in a dose-dependent manner. Conversely, autophagy inhibitor 3-methyladenine partly reversed the cytotoxicity and the phosphorylation of AMPK, mTOR and p70 S6K induced by Tan IIA in KBM-5 leukemia cells. In addition, Tan IIA dramatically activated the extracellular signal regulated kinase (ERK) signaling pathway including Raf, ERK and p90 RSK in a dose-dependent and time-dependent manner. Consistently, ERK inhibitor PD184352 suppressed LC3-II activation induced by Tan IIA, whereas PD184352 and PD98059 did not affect poly (ADP-ribose) polymerase cleavage and sub-G1 accumulation induced by Tan IIA in KBM-5 leukemia cells. Furthermore, Tan IIA could induce autophagy via LC3-II activation in various cancer cells such as prostate (PC-3), multiple myeloma (U266), lung (NCI-H460), and breast (MDA-MB-231) cells. Overall, these findings suggest that Tan IIA induces autophagic cell death via activation of AMPK and ERK and inhibition of mTOR and p70 S6K in KBM-5 cells as a potent natural compound for leukemia treatment.


Colonoscopy in Acute Lower Gastrointestinal Bleeding: Diagnosis, Timing, and Bowel Preparation.
Lower gastrointestinal bleeding is bleeding from a colonic source. Rapid colon purge using 4 to 6 L of polyethylene glycol followed by early colonoscopy, within 24 hours of presentation, is recommended to optimize the detection and management of bleeding sources. Although the data are mixed, early colonoscopy seems to be associated with higher detection of bleeding lesions and therapeutic interventions. There is no clear benefit for early colonoscopy in terms of reduced duration of stay, rebleeding, transfusion requirement, or surgery compared with patients undergoing elective colonoscopy. Further studies are needed to determine the effect of early colonoscopy on clinically important outcomes.


Involvement of extracytoplasmic function sigma factors in virulence regulation in Porphyromonas gingivalis W83.
Extracytoplasmic function (ECF) sigma factors are known to play an important role in the bacterial response to various environmental stresses and can significantly modulate their pathogenic potential. In the genome of Porphyromonas gingivalis W83, six putative ECF sigma factors were identified. To further evaluate their role in this organism, a PCR-based linear transformation method was used to inactivate five ECF sigma factor genes (PG0162, PG0214, PG0985, PG1660, and PG1827) by allelic exchange mutagenesis. All five isogenic mutants formed black-pigmented colonies on blood agar. Mutants defective in PG0985, PG1660, and PG1827 genes were more sensitive to 0.25 mM of hydrogen peroxide compared with the wild-type strain. Isogenic mutants of PG0162 and PG1660 showed a 50% decrease in gingipain activity. Reverse transcription-PCR analysis showed that there was no alteration in the expression of rgpA, rgpB, and kgp gingipain genes in these mutants. Hemolytic and hemagglutination activities were decreased by more than 50% in the PG0162 mutant compared with the wild type. Taken together, these findings suggest that ECF sigma factors can modulate important virulence factors in P. gingivalis. ECF sigma factors encoded by the PG0162 and PG1660 genes might also be involved in the post-transcriptional regulation of the gingipains.


Peritoneal carcinomatosis: limits of diagnosis and the case for liquid biopsy.
Peritoneal Carcinomatosis (PC) is a late stage manifestation of several gastrointestinal malignancies including appendiceal, colorectal, and gastric cancer. In PC, tumors metastasize to and deposit on the peritoneal surface and often leave patients with only palliative treatment options. For colorectal PC, median survival is approximately five months, and palliative systemic therapy is able to extend this to approximately 12 months. However, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with a curative intent is possible in some patients with limited tumor burden. In well-selected patients undergoing complete cytoreduction, median survival has been reported as high as 63 month. Identifying patients earlier who are either at risk for, or who have recently developed PC may provide them with additional treatment options such as CRS/HIPEC. PC is diagnosed late by imaging findings or often times during an invasive procedures such as laparoscopy or laparotomy. In order to improve the outcomes of PC patients, a minimally invasive, accurate, and specific PC screening method needs to be developed. By utilizing circulating PC biomarkers in the serum of patients, a "liquid biopsy," may be able to be generated to allow a tailored treatment plan and early intervention. Exosomes, stable patient-derived nanovesicles present in blood, urine, and many other bodily fluids, show promise as a tool for the evaluation of labile biomarkers. If liquid biopsies can be perfected in PC, manifestations of this cancer may be more effectively treated, thus offering improved survival.


The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae.
Epidemiological investigations have linked Chlamydia pneumoniae infection to atherosclerosis. It is not clear, however, whether C. pneumoniae infection plays a causal role in the development of atherosclerosis. Mice with low-density lipoprotein receptor deficiency were induced to develop atherosclerotic lesions in aorta with a cholesterol-enriched diet that increased serum cholesterol by two- to threefold. Using this mouse model, we found that the chlamydial infection alone with either the C. pneumoniae AR39 or the C. trachomatis MoPn strain failed to induce any significant atherosclerotic lesions in aorta over a period of nine months. However, in the presence of a high-cholesterol diet, infection with the C. pneumoniae AR39 strain significantly exacerbated the hypercholesterolemia-induced atherosclerosis, demonstrating that a hypercholesterolemic condition is required for the C. pneumoniae to aggravate the development of atherosclerosis. Although both AR39 and MoPn antigens were detected in aorta of mice infected with the corresponding strains, only mice infected with the C. pneumoniae strain AR39 displayed enhanced atherosclerotic lesions, suggesting that the C. pneumoniae species may possess a unique atherogenic property. This study may provide a model for further understanding the mechanisms of C. pneumoniae atherogenesis and evaluating chlamydial intervention strategies for preventing the advancement of atherosclerotic lesions enhanced by C. pneumoniae infection.


Attitudes of Bavarian bovine veterinarians towards pain and pain management in cattle.
Pain recognition in cattle is difficult, but the control and treatment of pain are essential for animal welfare. Pain evaluation depends on the observer's experience and opinion, resulting in different approaches towards pain and the use of analgesics. A questionnaire to assess the attitudes of veterinarians towards pain and pain management in cattle was sent to 1097 bovine practitioners in Bavaria. Out of 287 returned questionnaires, 274 could be analysed. Claw amputation, extirpation of the eye bulb and caesarean section were considered to be the most painful procedures in adult cattle, and castration, umbilical surgery and laparotomy in calves. Orthopaedic diseases like bone fractures or arthritis were estimated to be the most painful conditions in both cattle and calves, and ileus and meningitis in calves. Female veterinarians scored pain higher than their male colleagues. Even though 75.5 per cent of veterinarians stated that they used analgesics adequately, pain management during surgery was low, especially for castration and dehorning in calves. Bavarian bovine veterinarians differ in their opinions about pain in cattle and the results of this study indicate that there a mismatch between their use of analgesics and the pain scores they awarded.


Current and emerging targeted therapies for spinal muscular atrophy.
Spinal muscular atrophy (SMA) is a progressive neurodegenerative disorder caused by insufficiency or total absence of the survival motor neuron protein due to a mutation in the SMN1 gene. The copy number of its paralog, SMN2, influences disease onset and phenotype severity. Current therapeutic approaches include viral and non-viral modalities affecting gene expression. Regulatory-approved drugs Spinraza (Nusinersen), Zolgensma (Onasemnogene abeparvovec), and Evrysdi (Risdiplam) are still being investigated during clinical trials and show benefits in the long-term for symptomatic and pre-symptomatic patients. However, some ongoing interventions require repeated drug administration. In this review, the authors describe the existing therapy based on point of application, focusing on recent clinical trials of antisense oligonucleotides, viral gene therapy, and splice modulators and thepotential routes for correcting the mutation to provide therapeutic levels of SMN protein. In the opinion of the authors, multiple treatment options for patients with SMA shifted the treatment paradigm from palliative supportive care to improvedmotor function, increased survival, and greater quality of life for such patients. They further believe that the future in SMA treatment development lies incombining existing treatment options, targeting aspects of the disease refractory to these treatments, and using gene editing technologies.


A Review of Public Health Training Needs Assessment Approaches: Opportunities to Move Forward.
Assessing training needs of the public health workforce is crucial for creating professional development opportunities to improve knowledge, competence, and effectiveness of this workforce. Regional Public Health Training Centers (RPHTCs) assess workforce training needs and deliver training based on identified needs. To determine training priorities, several needs assessment surveys have been administered by RPHTCs and national public health member organizations. This study identified the types of training questions being asked to public health practitioners in the various assessment surveys implemented by RPHTCs and national membership organizations. Although the surveys measured similar overarching constructs, multiple approaches with limited consistency were used to measure training needs. Although successful in responding to the needs of their targeted constituents, the limited consistency among survey types makes generalization of findings difficult. Disseminating common metrics and aggregate survey findings would increase efficiency in determining workforce training needs and developing targeted training.


Calcium transport in the pars recta and thin descending limb of Henle of the rabbit, perfused in vitro.
Unidirectional calcium flux (JCa) in the superficial pars recta and thin descending limb of Henle (DLH) was examined by the isolated tubule microperfusion technic using 45Ca as the isotopic tracer. In the pars recta sequential measurements of lumen-to-bath flux (JlbCa) and bath-to-lumen flux (JblCa) revealed: JlbCa 22.4 +/- 4.18, JblCa 7.97 +/- 1.95, and calculated net efflux of calcium (JnetCa 13.0 +/- 1.74 peq min-1 mm-u. To measure JnetCa directly, 45Ca of identical specific activity was used to bathe and perfuse the tubule. These studies revealed: JlbCa 14.1 +/- 1.33, JnetCa 11.2 +/- 1.15, and calculated JblCa 2.91 +/- 0.49 peq min-1 mm-1. The addition of ouabain (10 microM) resulted in a rise in potential difference and a fall in water absorption, but not a statistically significant change in JnetCa. Tubules studies at 25 degrees C bath temperature, showed no significant JnetCa, and upon heating the bath to 37 degrees C, showed JnetCa of 3.75--5.00 peg min-1 mm-1. Unidirectional and net efflux studies in six DLH showed no significant transport of calcium. These studies demonstrate substantial active absorption of calcium by the superficial pars recta, which is not inhibitable by ouabain but is inhibited by lowering bath temperature to 25 degrees C. No significant calcium transport was found in the DLH using identical technics.


Determining plant-leaf miner-parasitoid interactions: a DNA barcoding approach.
A major challenge in network ecology is to describe the full-range of species interactions in a community to create highly-resolved food-webs. We developed a molecular approach based on DNA full barcoding and mini-barcoding to describe difficult to observe plant-leaf miner-parasitoid interactions, consisting of animals commonly regarded as agricultural pests and their natural enemies. We tested the ability of universal primers to amplify the remaining DNA inside leaf miner mines after the emergence of the insect. We compared the results of a) morphological identification of adult specimens; b) identification based on the shape of the mines; c) the COI Mini-barcode (130 bp) and d) the COI full barcode (658 bp) fragments to accurately identify the leaf-miner species. We used the molecular approach to build and analyse a tri-partite ecological network of plant-leaf miner-parasitoid interactions. We were able to detect the DNA of leaf-mining insects within their feeding mines on a range of host plants using mini-barcoding primers: 6% for the leaves collected empty and 33% success after we observed the emergence of the leaf miner. We suggest that the low amplification success of leaf mines collected empty was mainly due to the time since the adult emerged and discuss methodological improvements. Nevertheless our approach provided new species-interaction data for the ecological network. We found that the 130 bp fragment is variable enough to identify all the species included in this study. Both COI fragments reveal that some leaf miner species could be composed of cryptic species. The network built using the molecular approach was more accurate in describing tri-partite interactions compared with traditional approaches based on morphological criteria.


The Appropriate Use of Testing for COVID-19.
Many public officials are calling for increased testing for the 2019 novel coronavirus disease (COVID-19), and some governments have taken extraordinary measures to increase the availability of testing. However, little has been published about the sensitivity and specificity of the reverse transcriptase-polymerase chain reaction (RT-PCR) nasopharyngeal swabs that are commonly used for testing. This narrative review evaluates the literature regarding the accuracy of these tests, and makes recommendations based on this literature. In brief, a negative RT-PCR nasopharyngeal swab test is insufficient to rule out COVID-19. Thus, over-reliance on the results of the test may be dangerous, and the push for widespread testing may be overstated.