Socio-demographic correlates of early childhood caries prevalence and severity in a developing country--South Africa.
To describe Early Childhood Caries (ECC) severity in South Africa and examine the association between ECC and socio-demographic factors, area-based measures of sugar consumption and water fluoride levels. Children, aged 36-71 months, were examined during the 1999/2002 South African National Children's Oral Health Survey (n=5822). ECC severity was described using Wyne's ECC classification (adapted) and the Significant Caries Index (SIC). Socio-demographic factors, area-based fluoride levels in water supplies, and the area-based per capita sugar expenditure obtained from the 2000 Household Expenditure Survey were examined using bivariate and multivariate analyses. The mean population SiC was 7.6 and 32% presented with the severe forms of ECC. Increased per capita sugar expenditure and decreasing water fluoride levels, were significantly associated with an increased risk for any ECC, but was not significantly associated with the severe forms of ECC. Compared to blacks, being of mixed race and white were respectively associated with an increased and a decreased risk for ECC. Unemployment increased the risk for the severe forms of ECC. The study findings support the implementation of an integrated primary oral health care strategy in order to address the underlying socio-economic determinants of ECC in South Africa.


Chondrocyte-specific enhancer regions in the COMP gene.
The molecular events governing the differentiation of mesenchymal cells into chondrocytes and the expression of cartilage marker genes are poorly understood. Cartilage oligomeric matrix protein is a noncollagenous extracellular matrix protein with a relatively cartilage-specific spatial and temporal expression pattern. To understand the mechanisms controlling chondrocyte-specific expression of cartilage oligomeric matrix protein, we cloned 1.9 kb of the 5' flanking promoter sequence of the murine cartilage oligomeric matrix protein gene and identified two spatially distant cartilage-specific enhancer regions by deletion analysis. One element is situated proximally (proximal positive element: -125 to -75) and a second region is located distally (distal positive region: -1925 to -592) relative to the transcription start site. Interestingly, nucleotides within the proximal positive element are conserved between the mouse and human promoters and resemble consensus sites for the binding of members of the high mobility group class of transcription factors. Defining cartilage-specific regulatory elements in the cartilage oligomeric matrix protein promoter may provide useful molecular probes for identifying transcription factors that control acquisition of the chondrocytic phenotype.


Use of endotoxin retentive intravenous filters with paediatric total parenteral nutrition solutions.
We studied the retention of endotoxin released in a clinically relevant form by senescent bacteria during filtration of amino acid-based total parenteral nutrition (TPN) solutions by the PALL Intravenous Set Saver Filter (ELD96). The ELD96 was shown to be capable of providing an effluent free of detectable endotoxin (less than 0.125 endotoxin unit-equivalents/ml) when challenged with 10(6) total cells of Pseudomonas aeruginosa during simulated clinical TPN infusion. Parallel control experiments showed that endotoxin was released from the test organism and penetrated through conventional intravenous (i.v.) solution filters.


Serum zinc levels and goiter in Iranian school children.
Iodine deficiency has been shown to have high prevalence in Iran despite sufficient iodine supplementation. Zinc deficiency may also contribute to the pathogenesis of endemic goiter. The aim of this study was to compare serum zinc level in Iranian school children with and without goiter. A cross-sectional study was performed among urban children aged 8-12 years in city of Kerman, Iran. A multistage proportional to size cluster sampling method was used to screen 5500 subjects out of 29,787 students. After the screening phase, serum and urine specimens of randomly selected 165 students were evaluated for serum zinc levels and urinary iodine excretion and compared in goiterous and non-goiterous children. Serum zinc level was 149.5±29.4 μg/l in goiterous children and 141.2±52 μg/l in non-goiterous children but no significant difference was found between the groups (p=0.37). But urinary iodine excretion was significantly (p<0.001) lower in goiterous children (207.5 μg/l in goiterous children and 262.5 μg/l in non-goiterous children). This study showed that serum zinc level in goiterous and non-goiterus children is not different and zinc deficiency is not a risk factor for endemic goiter in this population.


Analysis of triple-label samples by liquid scintillation spectrometry.
The simultaneous analysis of three radionuclides present in a sample is demonstrated. The approach requires fitting a series of counting data acquired over a period of time to a triple exponential mathematical expression. The use and advantages of the method are illustrated for the case of the standardisation of 32P in the presence of 33P and 35S by 4pi-beta liquid scintillation spectrometry. The effects of sample preparation, chemical quenching and different activity ratios were studied.


The molecular mechanisms of virus-induced human cancers.
Cancer is a serious public health problem globally. Many human cancers are induced by viruses. Understanding of the mechanisms by which oncogenic (tumorigenic) viruses induce cancer is essential in the prevention and control of cancer. This review covers comprehensive characteristics and molecular mechanisms of the main virus-attributed cancers caused by human papillomavirus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, human herpesvirus type 8, human T-cell lymphotropic virus, human polyomaviruses, Merkel cell polyomavirus, and HIV. Oncogenic viruses employ biological processes to replicate and avoid detection by host cell immune systems. Tumorigenic infectious agents activate oncogenes in a variety of ways, allowing the pathogen to block host tumour suppressor proteins, inhibit apoptosis, enhance cell proliferation, and promote invasion of host cells. Furthermore, this review assesses many pathways of viruses linked to cancer, including host cellular communication perturbation, DNA damage mechanisms, immunity, and microRNA targets that promote the beginning and progression of cancer. The current cancer prevention is primarily focused on non-communicable diseases, but infection-attributable cancer also needs attention to significantly reduce the rising cancer burden and related deaths.


Fasciola hepatica: tegumental surface changes in adult and juvenile flukes following treatment in vitro with the sulphoxide metabolite of triclabendazole (Fasinex).
The effects of the novel benzimidazole, triclabendazole (Fasinex, Ciba-Geigy), in its active sulphoxide metabolite form (TCBZ-SX), on the tegumental surface of Fasciola hepatica has been examined in vitro. The tegument of adult flukes incubated in TCBZ-SX (50 micrograms/ml) appeared swollen and blebbed after only 6 h. In addition, progressive spine loss at the oral cone was evident following 12 h treatment. After 24 h, the tegumental syncytium and spines had completely sloughed away, leaving an exposed basal lamina and empty spine sockets. Juvenile flukes (3 weeks old) also demonstrated tegumental alterations after treatment with TCBZ-SX (20 micrograms/ml). The syncytium became extremely roughened and corrugated on both dorsal and ventral surfaces after only 3 h. Following 6- and 9-h incubations, there were many deep furrows, which were especially pronounced on the ventral surface, and by 18 h, the juvenile tegument was severely disrupted, especially on the ventral surface. In all cases, the effects were more marked than in the previous incubation periods. The results confirm the potent activity of triclabendazole against F. hepatica and suggest that the tegument of adult and juvenile flukes may be a target organ for this important fasciolicide.


The inhibition of 5-Lipoxygenase (5-LO) products leukotriene B4 (LTB4) and cysteinyl leukotrienes (cysLTs) modulates the inflammatory response and improves cutaneous wound healing.
To analyze the participation of the enzyme 5-lipoxygenase (5-LO) in skin repair, WT wounds were compared to those in 5-LO deficient mice (5-LO-/-), which presented faster closure and reduced inflammatory infiltrate in the skin, together with increased CD4 regulatory T cells markers in the draining lymph nodes. The 5-LO-/- wounds also had diminished TNF-α, CCL11, CCL7, CCL2, CXCL9, CCR1 and CXCR2 mRNA expression in the lesions, besides differential extracellular matrix remodeling. Furthermore, when cysteinyl leukotriene (cysLT) and leukotriene (LTB4) receptors were antagonized in WT mice, there was a remarkable reduction in TNF-α expression and faster skin healing, similarly to the findings in 5-LO-/- animals. Finally, our results suggested that 5-LO products, in special cysLT and LTB4, underline skin inflammation that follows skin injury and their neutralization may be an important strategy to improve cutaneous healing.


Canthal and cephalic indexes of children with homozygous sickle cell disease in Port-Harcourt.
This research was conducted in view of the importance of anthropometric indices of the head and face in forensic medicine, surgery, paediatrics and medical imaging. This study was put forward to determine some of the effects of chronic diseases on head and face of children with homozygous sickle cell disease. A comparative study on canthal and cephalic indexes were carried out on 100 patients, 54 males and 46 females who are homozygous for sickle cell anaemia, who attended the sickle cell clinic at the University of Port-HarcourtTeaching Hospital between the age ranges of 3-18 years. The same was also done for 500 normal growing children 291 males and 209 females between ages 3-18 years who are pupils of the University Kindergarten, Demonstration Primary and Secondary Schools as well as First International Academy Secondary School, Rumuokoro, Port Harcourt. The head length, head breadth, inner and outer canthal distances measured. The results showed a mean cephalic index value of 79.89 +/- 0.87 for the normal growing children while that of the sickle cell children was 79.54 +/- 2.14, which is not statistically significant (P>0.05). The mean canthal index for healthy children was 35.16 +/- 1.01 as against 37.28 +/- 1.65 for the sickle cell children, which is statistically significant. This research determined the possible effects of chronic diseases such as sickle cell anaemia on the diversity of head and face shapes in children.


Comparison of Temporary Epiphysiodesis With RigidTacks™ and Blount-Staples in a Porcine Animal Model Using Magnetic Resonance Imaging.
RigidTack™ is a newly developed implant for total temporary epiphyseodesis. The implant combines the technical advantages of the traditionally used rigid Blount-staples and the newer flexible eight-plates™. Thus, the implant is rigid like the Blount-staples, which may be a biomechanical advantage in temporary epiphyseodesis, and has an easy and guided implantation technique like the eight-plate™. As in eight-plates™, supposedly only two RigidTacks™ are sufficient for temporary epiphyseodesis compared to six Blount-staples in traditional treatment. The goal of this study was to compare Blount-staples and RigidTacks™ in regard to the total potential of growth arrest, the occurrence of postoperative implant-associated complications, secondary angular deformities, and central joint deformations. Twelve pigs were allocated in two groups (n = 6) for treatment of the proximal tibia. Total temporary epiphysiodesis was performed with either four Blount-staples or two RigidTacks™. Magnetic resonance imaging (MRI)-scans were performed before and 14 weeks after surgery, and the amount and distribution of growth arrest were evaluated by measuring the interphyseal distance in nine defined zones. Total temporary epiphysiodesis with two RigidTacks™ resulted in a similar amount of growth arrest as that of four Blount-staples. No significant coronal or sagittal angular deformities or joint deformities were observed in either group; however, one secondary loosening of a Blount-staple occurred. The study concluded that Blount-staples and RigidTacks™ are adequate implants for total temporary epiphysiodesis. Whether or not the precise implant-placement through the guided implantation technique of RigidTacks™ and a reduced number of implants indeed lead to a reduction of secondary angular deformities has to be investigated in further clinical trials. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:946-953, 2020.


Protein Microarray-Based IgE Immunoassay for Allergy Diagnosis.
Protein microarray is a miniaturized multi-analyte, solid-phased immunoassay where thousands of immobilized individual protein spots on a microscopic slide bind are bound to specific antibodies (immunoglobulins) from serum samples, which are then detected by fluorescent labeling. The image processing and pattern recognition are then quantitatively analyzed using advanced algorithms. Here, we describe the use of an in-house-produced complex protein microarray containing extracts and pure proteins that has been probed with antibodies present in the horse sera and detection by fluorophore-conjugated antibody and data analysis. The flexibility of the number and types of proteins that can be printed on the microarray allows different set of specific IgE immunoassay analysis to be carried out.


Lanostane Triterpenes Isolated from Antrodia heteromorpha and Their Inhibitory Effects on RANKL-Induced Osteoclastogenesis.
Two new spiro-lanostane triterpenoids, antrolactones A and B (1 and 2), along with polyporenic acid C (3), were isolated from an EtOAc-soluble extract of Antrodia heteromorpha culture medium, and the chemical structures of the new compounds were elucidated by application of NMR, MS, and ECD spectroscopic techniques. All isolated compounds exhibited inhibitory effects on receptor activator of nuclear factor-kappaB ligand-induced osteoclastogenesis.


In vitro and in vivo comparative colonization of Staphylococcus aureus and Staphylococcus epidermidis on orthopaedic implant materials.
Clinically, Staphylococcus aureus appears to be the dominant organism associated with infected metal implants, whereas coagulase-negative staphylococcal strains are more frequently isolated from infected polymer implants. We reproduced this trend experimentally in vitro and in vivo. Discs of a titanium alloy, poly(methyl methacrylate) and ultra-high molecular weight polyethylene were exposed to a clinical isolate of Staphylococcus aureus or either of two strains of Staphylococcus epidermidis. Within 1 h Staphylococcus aureus was always the most rapid colonizer regardless of biomaterial. However, after 8 to 24 h, Staphylococcus aureus was present in higher numbers on metal and Staphylococcus epidermidis on polymers. Moreover, the exopolysaccharide produced by Staphylococcus epidermidis appeared to offer an effective protection against host defences in vivo.


Coronary Microvascular Dysfunction: What Clinicians and Investigators Should Know.
Abnormal structure and function of the coronary microvasculature have been implicated in the pathophysiology of multiple cardiovascular disease processes. This article reviews recent research progress related to coronary microvascular dysfunction (CMD) and salient clinical takeaways. CMD is prevalent in patients with signs and symptoms of ischemia and no obstructive epicardial coronary artery disease (INOCA), particularly in women. CMD is associated with adverse outcomes, including most frequently the development of heart failure with preserved ejection fraction. It is also associated with adverse outcomes in patient populations including hypertrophic cardiomyopathy, dilated cardiomyopathy, and acute coronary syndromes. In patients with INOCA, stratified medical therapy guided by invasive coronary function testing to define the subtype of CMD leads to improved symptoms. There are invasive and non-invasive methodologies to diagnose CMD that provide prognostic information and mechanistic information to direct treatment. Available treatments improve symptoms and myocardial blood flow; ongoing investigations aim to develop therapy to improve adverse outcomes related to CMD.


Bone Turnover Markers After Sleep Restriction and Circadian Disruption: A Mechanism for Sleep-Related Bone Loss in Humans.
Sleep abnormalities are associated with low bone mineral density. Underlying mechanisms are unknown. Investigate the impact of sleep restriction with circadian disruption on bone biomarkers. Intervention study. Four bone biomarkers [C-terminal cross-linked telopeptide of type I collagen (CTX) = bone resorption, N-terminal propeptide of type I procollagen (P1NP) = bone formation, sclerostin and fibroblast growth factor 23 = osteocyte function] were measured in bihourly serum samples over 24 hours at baseline and after ∼3 weeks of sleep restriction (5.6 hours sleep/24 hours) with concurrent circadian disruption (recurring 28-hour "day" in dim light) in 10 men (age groups: 20 to 27 years, n = 6; 55 to 65 years, n = 4). The effects of sleep/circadian disruption and age on bone biomarker levels were evaluated using maximum likelihood estimation in a mixed model for repeated measures. P1NP levels were lower after intervention compared with baseline (P < 0.001); the decrease in P1NP was greater for younger compared with older men (28.0% vs 18.2%, P < 0.001). There was no change in CTX (Δ = 0.03 ± 0.02 ng/mL, P = 0.10). Sclerostin levels were higher postintervention in the younger men only (Δ = 22.9% or 5.64 ± 1.10 pmol/L, P < 0.001). These data suggest that 3 weeks of circadian disruption with concurrent sleep restriction can lead to an uncoupling of bone turnover wherein bone formation is decreased but bone resorption is unchanged. Circadian disruption and sleep restriction may be most detrimental to bone in early adulthood.


Spontaneous recovery in rabbit eyelid conditioning.
Spontaneous recovery of the classically conditioned rabbit eyelid response increased in a negatively accelerated function with an increase of postextinction rest from .17 to 24 hr. The data were obtained from six groups of male New Zealand rabbits which received an extinction session separated by rest intervals of varying duration from a spontaneous recovery test.


Comparison of the effect of nocturnal use of commercial versus custom-made wrist orthoses, in addition to gliding exercises, in the function and symptoms of carpal tunnel syndrome: A pilot randomized trial.
Conservative treatment for carpal tunnel syndrome (CTS) often includes wrist orthosis. However, there is no consensus on whether commercial or custom-made wrist orthosis is better for the treatment. To assess feasibility of a study comparing nocturnal use of commercial versus custom-made wrist orthosis in the treatment of mild/moderate CTS and estimate their potential effects on function and symptoms. Randomized clinical trial. Twenty-four individuals with mild/moderate CTS were randomized to wear either a commercial orthosis (n = 12) or a custom-made orthosis (n = 12). Participants used the assigned orthosis at night for 45 days and performed gliding exercises at home/work. We collected data on access to eligible population and feasibility of protocol. Data on use of orthosis, performance of exercises, and symptoms were collected through a dairy filled by the participant. Outcomes were pain (using Numeric Pain Rating Scale), symptom severity and functional status (using Boston Questionnaire), pinch strength (by dynamometry), and electromyographic activity of forearm muscles (sampled during a reach-to-grasp task). Outcomes were measured before and after the intervention. There were no loses to follow-up in either intervention group. After treatment, we found increased tripod pinch strength and better symptoms and function in both orthosis groups, with better outcomes for the custom-made orthosis, although the differences were not statistically significant. The preliminary results showed a potential for better outcomes from the custom-made orthosis. We established that a larger study would be feasible and could be designed and conducted based on the estimates provided by this study. Brazilian Registry of Clinical Trials (ReBEC) - registration number: RBR-74rqnz.


Phosphorylation of Syk activation loop tyrosines is essential for Syk function. An in vivo study using a specific anti-Syk activation loop phosphotyrosine antibody.
Syk is an important protein-tyrosine kinase in immunoreceptor signaling. FcepsilonRI aggregation in mast cells induces tyrosine phosphorylation and increased enzymatic activity of Syk. The two adjacent tyrosines in the Syk activation loop are thought to be important for the propagation of FcepsilonRI signaling. To evaluate the phosphorylation of these tyrosines in vivo and further understand the relationship of Syk tyrosine phosphorylation with its function, an antibody was developed specific for phosphorylated tyrosines in the activation loop of Syk. FcepsilonRI aggregation on mast cells induced the phosphorylation of both tyrosine residues of the activation loop. The kinase activity of Syk played the major role in phosphorylating its activation loop tyrosines both in vivo and in vitro. In FcepsilonRI-stimulated mast cells, the total Syk tyrosine phosphorylation paralleled the phosphorylation of its activation loop tyrosines and downstream propagation of signals for histamine release. In contrast, the cell surface binding of anti-ganglioside monoclonal antibody AA4 induced only strong general tyrosine phosphorylation of Syk and minimal histamine release and weak phosphorylation of activation loop tyrosines. These results demonstrate that phosphorylation of the activation loop tyrosines is important for mediating receptor signaling and is a better marker of Syk function than is total Syk tyrosine phosphorylation.


Pharmacological rescue of the 14CoS/14CoS mouse: hepatocyte apoptosis is likely caused by endogenous oxidative stress.
Whereas ch/ch wild-type mice and ch/14CoS heterozygotes are viable, 14CoS/14CoS mice homozygous for a 3800 kb deletion on chromosome 7 die during the first day postpartum. Death is caused by disruption of the fumarylacetoacetate hydrolase (Fah) gene; absence of FAH, final enzyme in the tyrosine catabolism pathway, leads to accumulation of reactive electrophilic intermediates. In this study, we kept 14CoS/14CoS mice alive for 60 d with oral 2-(2-nitro-4-trifluoromethyl-benzyol)-1,3-cyclohexanedione (NTBC), an inhibitor of p-hydroxyphenylpyruvate dioxygenase, second enzyme in the tyrosine catabolic pathway. The 70% of NTBC-treated 14CoS/14CoS mice that survived 60 d showed poor growth and developed corneal opacities, compared with ch/14CoS littermates; NTBC-rescued Fah(-/-) knockout mice did not show growth retardation or ocular toxicity. NTBC-rescued 14CoS/14CoS mice also exhibited a striking oxidative stress response in liver and kidney, as measured by lower GSH levels and mRNA induction of four genes: glutamate cysteine ligase catalytic (Gclc) and modifier (Gclm) subunits, NAD(P)H:quinone oxidoreductase (Nqo1), and heme oxygenase-1 (Hmox1). Withdrawal of NTBC for 24-48 h from rescued adult 14CoS/14CoS mice resulted in severe apoptosis of the liver, detected histologically and by cytochrome c release from the mitochondria, increased caspase 3-like activity, and further decreases in GSH content. In kidney, proximal tubular epithelial cells were abnormal. Human hereditary tyrosinemia type I (HT1), caused by mutations in the FAH gene, is an autosomal recessive disorder in which the patient usually dies of liver fibrosis and cirrhosis during early childhood; NTBC treatment is known to prolong HT1 children's lives-although liver fibrosis, cirrhosis, hepatocarcinoma, and corneal opacities sometimes occur. The mouse data in the present study are consistent with the possibility that endogenous oxidative stress-induced apoptosis may be the underlying cause of liver pathology seen in NTBC-treated HT1 patients.


Hydrothermal decomposition of yeast cells for production of proteins and amino acids.
This study examines hydrothermal decomposition of Baker's yeast cells, used as a model for spent Brewer's yeast waste, into protein and amino acids. The reaction was carried out in a closed batch reactor at various temperatures between 100 and 250 degrees C. The reaction products were separated into water-soluble and solid residue. The results demonstrated that the amount of yeast residue decreased with increasing hydrolysis temperature. After 20 min reaction in water at 250 degrees C, 78% of yeast was decomposed. The highest amount of protein produced was also obtained at this condition and was found to be 0.16 mg/mg dry yeast. The highest amount of amino acids (0.063 mg/mg dry yeast) was found at the lowest temperature tested after 15 min. The hydrolysis product obtained at 200 degrees C was tested as a nutrient source for yeast growth. The growth of yeast cells in the culture medium containing 2 w/v% of this product was comparable to that of the cells grown in the medium containing commercial yeast extract at the same concentration. These results demonstrated the feasibility of using subcritical water to potentially decompose proteinaceous waste such as spent Brewer's yeast while recovering more useful products.


Health impacts of the Southeast Asian haze problem - A time-stratified case crossover study of the relationship between ambient air pollution and sudden cardiac deaths in Singapore.
To investigate the association between air pollution and out-of-hospital cardiac arrest (OHCA) incidence in Singapore. A time-stratified case-crossover design study. OHCA incidences of all etiology in Singapore. 8589 OHCA incidences reported to Pan-Asian Resuscitation Outcomes Study (PAROS) registry in Singapore between 2010 and 2015. A conditional Poisson regression model was applied to daily OHCA incidence that included potential confounders such as daily temperature, rainfall, wind speed, Pollutant Standards Index (PSI) and age. All models were adjusted for over-dispersion, autocorrelation and population at risk. We assessed the relationship with OHCA incidence and PSI in the entire cohort and in predetermined subgroups of demographic and clinical characteristics. 334 out of 8589 (3.89%) cases survived. Moderate (Risk ratio/RR = 1.1, 95% CI = 1.07-1.15) and unhealthy (RR =1.37, 95% CI = 1.2-1.56) levels of PSI showed significant association with increased OHCA occurrence. Sub-group analysis based on individual demographic and clinical features showed generally significant association between OHCA incidence and moderate/unhealthy PSI, except in age < 65, Malay and other ethnicity, traumatic arrests and history of heart disease and diabetes. The association was most pronounced among cases age > 65, male, Indian and non-traumatic. Each increment of 30 unit in PSI on the same day and previous 1-5 days was significantly associated with 5.8-8.1% increased risk of OHCA (p < 0.001). We found a transient effect of short-term air pollution on OHCA incidence after adjusting for meteorological indicators and individual characteristics. These finding have public health implications for prevention of OHCA and emergency health services during haze.


Echocardiography in mitral stenosis.
Echocardiography plays a major role in diagnosis, etiology and severity of Mitral Stenosis (MS), analysis of valve anatomy and decision-making for intervention. This technique has also a crucial role to assess consequences of MS and follow up of patients after medical or surgical intervention. In this article we review the role of conventional echocardiography in assessment of mitral stenosis and future direction of this modality using 3D echocardiography.


Immunohistochemical study of central neurocytoma, subependymoma, and subependymal giant cell astrocytoma.
For investigation of histogenesis of central neurocytomas (CNs), subependymoma (SEs), subependymal giant cell astrocytomas (SEGAs), we studied expression of various neuronal and glial biomarkers by immunohistochemical (IHC) study and reverse transcriptase-polymerase chain reaction (RT-PCR). The materials for IHC were paraffin section of seven CNs, three SEs, and eight SEGAs and those for RT-PCR were frozen tissues of seven CNs, three SEs, and five SEGAs. Control group was five ependymomas (EPs) and four pilocytic astrocytomas (PAs). The neuronal biomarkers included nestin, chromogranin A (chrA), synaptophysin (SNP), neuronal cell adhesion molecule (NCAM), neuron specific enolase (NSE), neuronal nuclear antigen (NeuN), neurofilament (NF) and the glial marker was GFAP. CNs expressed all neuronal markers except NF (0%), SNP (100%), NCAM (100%), NSE (100%), NeuN (100%), nestin (29%) and chrA (43%), but GFAP expression was found only in one case (14%). SEGA coexpressed several neuronal markers and a glial marker; NeuN (100%), NSE (88%), NCAM (63%), nestin (100%), SNP (weakly and focally, 100%), and GFAP (100%), however, other neuronal markers including chrA, SNP and NF were all negative. SE expressed nonspecific neuronal markers (NCAM (100%) and NSE (100%)) which showed weak intensity and a GFAP (100%), but not nestin. Among control cases of EPs and PAs, no one case expressed neuronal markers except nonspecific neuronal marker of NCAM, but robustly expressed GFAP. RT-PCR product of nestin was expressed in 29% of CNs (2/7cases), 60% of SEGAs (3/5 cases), 100% of SEs (3/3 cases), 80% of EPs (4/5 cases), and 25% of PAs (1/4 cases). Conclusively, coexpression of neuronal and glial markers and expression of nestin in CNs, SEGAs and SEs suggested the origin of these tumor cells might be the stem cells being able to differentiate into both neuronal and glial phenotypes. But CNs might be originated from rather neuronally committed stem cells and SEs from rather glially committed stem cells.


Dietary antioxidants and beneficial effect on oxidatively damaged DNA.
Many biomonitoring studies have investigated the role of antioxidants in reducing oxidatively generated DNA damage in urine and white blood cells. A collective interpretation is difficult because many studies lack sufficient control and have unreasonably high baseline levels of oxidatively damaged DNA. In a survey of this antioxidant hypothesis, we identified 139 cross-sectional and intervention studies. Restricted selection criteria with exclusion of studies having suboptimal design or unreasonably high baseline damage level provided 85 eligible studies for analysis. Ten of the 27 cross-sectional studies reported negative correlations between antioxidants and oxidatively damaged DNA, albeit with correlation coefficients explaining less than 20% of the variance. Sixty-two intervention studies reported mixed results, which did not depend on sample size or duration of the intervention. Reduced levels of oxidatively damaged DNA in white blood cells and urine were reported in far more studies than expected by chance alone. Supplementation with antioxidant-rich foods was more effective than that with single antioxidants in lowering urinary excretion of oxidatively damage DNA. In conclusion, this survey indicates that ingestion of antioxidants may be associated with reduced level of DNA damage in white blood cells and urine of humans, albeit the effect is lower than previously expected.


Separation of the enantiomers of substituted dihydrofurocoumarins by HPLC using macrocyclic glycopeptide chiral stationary phases.
Enantiomer separations by HPLC using the macrocyclic glycopeptides teicoplanin (Chirobiotic T), teicoplanin aglycon (Chirobiotic TAG), and ristocetin A (Chirobiotic R) chiral stationary phases (CSP) have been achieved on a unique series of potentially biologically active racemic analogues of dihydrofurocoumarin. The macrocyclic glycopeptides have proven to be very selective for this class of compound. All of the 28 chiral analogues examined afforded baseline separation on at least one of the macrocyclic glycopeptide CSP. The teicoplanin CSP showed the broadest enantioselectivity with 24 of the compounds baseline separated. The TAG and the R CSP produced 23 and 14 baseline separations respectively. All three mobile phase modes, i.e. normal phase (NP), reversed phase (RP), and new polar organic modes (PO), have been evaluated. The NP mode proved to be most effective for the separation of chiral dihydrofurocoumarins on all CSP tested. In the reversed phase (RP) mode, all three CSP separated a similar number of compounds. It was observed that the structural characteristics of the analytes and steric effects are very important factors leading to chiral recognition. Hydrogen bonding was found to play a secondary role in chiral discrimination in the normal phase and polar organic modes. Hydrophobic interactions are important for chiral separation in the reversed-phase mode. Chromatographic retention data does not provide information on the absolute configuration of these chiral dihydrofurocoumarin derivatives. However, when coupled with circular dichroism using the exciton coupling chirality method, the enantiomer elution order and the absolute configuration of some chiral dihydrofurocoumarins were successfully determined.


Predicting patient satisfaction: a study of two emergency departments.
To identify perceptions that predict overall patient (dis)satisfaction with Emergency Department (ED) care, we studied responses to a survey mailed to all discharged patients over a 6-month period (Academic Hospital), and to a telephone interview of a random sample of discharged patients over a 1-year period (Community Hospital). The survey and interview both assessed overall satisfaction, as well as satisfaction with perceived waiting times, information delivery, and expressive quality of physicians, nurses, and staff. Data for 1176 patients (training sample) and 1101 patients (holdout sample) who rated overall satisfaction as either "very good" or "very poor" (Academic Hospital), and for 856 patients (training sample) and 431 patients (holdout sample) who rated overall satisfaction as either "excellent" or "poor" (Community Hospital), were retained for analysis. For both hospitals, nonlinear tree models efficiently achieved overall classification accuracy exceeding 98% in training analysis and 95% in holdout analysis (all p < .0001). The findings suggest that overall patient (dis)satisfaction with care received in the ED is nearly perfectly predictable on the basis of patient-rated expressive qualities of ED staff, particularly physicians and nurses. Interventions designed to reinforce positive (and extinguish negative) expressive health-care provider behaviors may cut the number of extremely dissatisfied patients in half.


Large scale isoelectric focusing analysis of the non-histone proteins of the nucleus: isolation of components with alkaline isoelectric points.
After large scale isoelectric focusing of rat liver non-histone protein in polyacrylamide gel, pH range 4--8.6, the only protein material found outside the gradient was present in the cathode solution (20 mM NaOH). This was low mol. wt protein material (approximately 10,000) with an acidic amino acid composition. It bound 5--6 times its own weight of basic ampholine carrier ampholytes to give a complex with a pI of 8.82. This could be dissociated by dialysis against 1 M NaCl.


Identification of the effects of aging-related gene-matrix metalloproteinase on allograft outcomes in kidney transplantation.
Aging plays a profound role in the ability of the kidney to function. Aging which varies among individuals, has been associated with the matrix metalloproteinase (MMP) 7 and 20 genes. This study was conducted to analyze correlations between polymorphisms of MMP genes [rs880197 in MMP7 (A>T) and rs1711437 in MMP20 (G>A)] and transplant outcomes in 235 recipients. Transplant outcomes were evaluated according to the sum of the A alleles in the recipients and the donors. The group with a high number of A alleles (≥3) was compared with the group with a low number (<3). The group with a high number of MMP7 A alleles showed a lower risk of chronic tubulointerstitial lesion than the group with a low number (P = .009). The group with a high number of MMP20 A alleles had showed better long-term kidney function at 10 years after transplantation than the group with a low number (P = .026). Furthermore, the group with a high number of MMP20 A alleles showed a trend toward better graft survival compared with the group with a low number, especially among recipients followed for >1 year (P = .022). Polymorphisms of MMP7 and MMP20 genes may be surrogate markers to predict long-term outcomes after kidney transplantation.


The Q-soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor (Q-SNARE) SNAP-47 Regulates Trafficking of Selected Vesicle-associated Membrane Proteins (VAMPs).
SNAREs constitute the core machinery of intracellular membrane fusion, but vesicular SNAREs localize to specific compartments via largely unknown mechanisms. Here, we identified an interaction between VAMP7 and SNAP-47 using a proteomics approach. We found that SNAP-47 mainly localized to cytoplasm, the endoplasmic reticulum (ER), and ERGIC and could also shuttle between the cytoplasm and the nucleus. SNAP-47 preferentially interacted with the trans-Golgi network VAMP4 and post-Golgi VAMP7 and -8. SNAP-47 also interacted with ER and Golgi syntaxin 5 and with syntaxin 1 in the absence of Munc18a, when syntaxin 1 is retained in the ER. A C-terminally truncated SNAP-47 was impaired in interaction with VAMPs and affected their subcellular distribution. SNAP-47 silencing further shifted the subcellular localization of VAMP4 from the Golgi apparatus to the ER. WT and mutant SNAP-47 overexpression impaired VAMP7 exocytic activity. We conclude that SNAP-47 plays a role in the proper localization and function of a subset of VAMPs likely via regulation of their transport through the early secretory pathway.


Reversible effect of calcium-binding protein regucalcin on the Ca(2+)-induced inhibition of deoxyuridine 5'-triphosphatase activity in rat liver cytosol.
The effect of regucalcin, a calcium-binding protein isolated from rat liver cytosol, on deoxyuridine 5'-triphosphatase (dUTPase) in the cytosol of rat liver was investigated. Addition of Ca2+ up to 5.0 microM to the enzyme reaction mixture caused a significant decrease of dUTPase activity, while Zn2+, Cd2+, Co2+, Al3+, Mn2+ and Ni2+ (10 microM) did not have an appreciable effect. The Ca(2+)-induced decrease of dUTPase activity was reversed by the presence of regucalcin; the effect was complete at 1.0 microM of the protein. Regucalcin had no effect on the basal activity of the enzyme. Meanwhile, the reversible effect of regucalcin on the Ca2+ (10 microM)-induced decrease of dUTPase activity was not altered by the coexistence of Cd2+ or Zn2+ (10 microM). The present data suggest that liver cytosolic dUTPase is uniquely regulated by Ca2+ of various metals, and that the Ca2+ effect is reversed by regucalcin.


Hiatal hernia is the key factor determining the lansoprazole dosage required for effective intra-oesophageal acid suppression.
Effective intra-oesophageal acid suppression can be achieved with lansoprazole. The daily dosage could be influenced by the presence of hiatal hernia. To assess the lansoprazole daily dosage required to normalize oesophageal acid exposure in patients with and without hiatal hernia. Fifty patients with complications or atypical manifestations of gastro-oesophageal reflux disease were given lansoprazole, 30 mg once daily. Three to four weeks after the start of treatment, patients underwent oesophageal pH monitoring while on therapy. If the results were still abnormal, the lansoprazole dosage was doubled and 24-h pH-metry was repeated 20-30 days thereafter. A 30-mg daily dosage of lansoprazole normalized oesophageal acid exposure in 70% of cases, whilst a 60-mg daily dosage was necessary in the remainder: the two groups differed only in the presence of hiatal hernia (28% vs. 100%, respectively; P=0.000). Effective intra-oesophageal acid suppression was obtained in all 25 patients without hiatal hernia with the 30-mg daily dosage of lansoprazole. Hiatal hernia is the key factor determining the lansoprazole dosage required for effective intra-oesophageal acid suppression in complicated and atypical gastro-oesophageal reflux disease. High efficacy of a 30-mg daily dosage of lansoprazole can be predicted in the absence of hiatal hernia.


An overview of stress urinary incontinence treatment in women.
Stress urinary incontinence (SUI) is common in women, but it is under-reported and under-treated. We review here the management of SUI in women. Pelvic floor muscle training treats SUI in the majority of female patients, whereas anti-SUI devices are not widely accepted. Duloxetine has been approved for treating SUI. Suburethral slings have revolutionized the surgical management of SUI with durable efficacy, in contrast with injectable bulking agents.


[1,2-Bis(diiso-propyl-phosphan-yl)ethane-κ2 P,P'](2-fluoro-N-{[(2-fluoro-phen-yl)aza-nid-yl]carbon-yl}anilinido-κ2 N,N')nickel(II).
The mol-ecular structure of the title complex, [Ni(C13H8F2N2O)(C14H32P2)] or Ni(oFPU)(dippe), where oFPU is the dianion of bis-(2-fluoro-phen-yl)urea and dippe is 1,2-bis-(di-iso-propyl-phosphino)ethane, comprises an NiII atom with a distorted square-planar coordination environment (geometry index τ4 = 0.195). One of the fluoro-phenyl rings of the oFPU ligand is disordered over two sets of sites in an 0.832 (7):0.168 (7) ratio. The crystal structure displays C-H⋯O and C-H⋯F hydrogen-bonding inter-actions, leading to chains with R 2 2(12) motifs extending parallel to [100]. The title compound might be of inter-est with respect to the production of urea and carbamate derivatives of nickel(II).


Massive pulmonary embolus without hypoxemia.
To describe a patient who had been taking ibuprofen for 3 days before the diagnosis of a massive pulmonary embolus without hypoxemia. Institutional review board-approved case report. Pediatric intensive care unit. A 16-yr-old male with a history of supraventricular tachycardia. The patient underwent an electrophysiology study and developed mild shortness of breath and then chest pain 2 and 4 days later, respectively. He took ibuprofen for 3 days. Evaluation 1 wk following the procedure revealed dyspnea and tachycardia. Arterial blood gas in room air was significant for hypocarbia without hypoxemia (Pao2, 108 mm Hg; Paco2, 28 mm Hg). Ventilation perfusion scan and computed axial tomography with intravenous contrast were consistent with a massive pulmonary embolus and left external iliac vein thrombus. He received anticoagulation, thrombolysis, a stent in the left iliac vein, and a filter in the inferior vena cava. Perfusion gradually improved and he was discharged home on oral anticoagulation. The absence of hypoxemia (including a normal alveolar-arterial oxygen difference) in our patient with a massive pulmonary embolus may have been related to cyclooxygenase inhibition due to ibuprofen, with improvement in ventilation-perfusion mismatch.


Symptomatic renal angiomyolipoma: report of 8 cases, 2 with spontaneous rupture.
Of the 97 patients with symptomatic renal angiomyolipoma not associated with tuberous sclerosis reported in the literature 13 have presented with a clinical picture of shock because of spontaneous rupture and massive retroperitoneal hemorrhage. Eight new patients with symptomatic renal angiomyolipomas are described, 2 of whom presented with an acute abdomen. Renal angiomyolipomas are essentially benign tumors. Several angiographic and pyelographic characteristics have been described but none appears to be unequivocally diagnostic. Because of the inability to make a precise preoperative diagnosis and the possibility of massive hemorrhage, nephrectomy is indicated in patients with such unilateral solid tumors in the absence of the tuberous sclerosis complex.


Attachment to God and coping with the diagnosis and treatment of breast cancer: a longitudinal study.
Religious/spiritual factors are important for some individuals in the context of life stress. To the authors' knowledge, the present study is the first to explore the role of women's attachment to God (anxious vs secure) in their adjustment to breast cancer. To explore the (1) pattern of change in women's attachment to God across time and (2) relationship between attachment to God and coping behaviors and depression. All English-speaking women who were scheduled to receive a core breast biopsy at a women's breast health center were eligible to participate in the study. Women were assessed on attachment to God, positive and negative coping, and depression at pre-diagnosis and 3, 6, and 12 months post-diagnosis. Women who received a benign diagnosis and those with a diagnosis of breast cancer participated in the study. Attachment to God remained stable across time for both diagnostic groups (cancer, benign). Women from both groups who had a more anxious attachment to God utilized more avoidance coping and reported more depression at different points across time. Breast cancer patients with a more anxious attachment to God reported engaging in less acceptance coping post-diagnosis. Finally, the association between attachment to God and depression was partially mediated by avoidance coping at pre-diagnosis. Findings indicate that a more anxious attachment to God may contribute to negative patterns of adjustment while a secure attachment may help women remain more directly engaged in their coping with the threat of breast cancer and related diagnostic procedures. It is suggested that clinicians remain sensitive to and assess the role of spiritual beliefs in women's adjustment to the threat of breast cancer from pre-diagnosis up to 1 year post-diagnosis. In particular, women's belief in and experience of a secure or an anxious attachment with God or higher power may function as a potential resource or as an exacerbating factor, respectively, in their adjustment to breast cancer.


Epizooic ciliates (Vorticella sp.) compete for food with their host Daphnia longispina in a small polyhumic lake.
Clearance rates of epizooic ciliates (Vorticella sp.) were measured together with their host, a planktonic cladoceran Daphnia longispina by using fluorescent latex beads as tracers of food. Vorticellans and their host graze on food of same size range (nanoplanktonic algae and bacteria). Individual clearance rates of Vorticella averaged 6.9 and 7.0 μl ind-1 h-1 and those of Daphnia 463 and 708 μl ind-1 h-1 for beads with diameter 2.00 and 3.92 μm. On the average, epizooic vorticellans together on the carapace of Daphnia cleared particles with rates representing 25-33% of that the host cleared, the maximum rates being 50-80%. In a steeply stratified polyhumic lake vorticellans take advantage of following Daphnia to food patches and they can severely compete for food with their host.


Tumoral environment triggers transcript anomalies in established tumors: induction of altered gene expression and of aberrant, truncated and B2 repeat-containing gene transcripts.
In addition to eugenetic changes, cancerous cells exhibit extensive modifications in the expression levels of a variety of genes. The phenotypic switch observed after inoculation of T lymphoma cells into syngenic mice illustrates the active participation of tumoral environment in the induction of an aberrant gene expression pattern. To further substantiate this contribution, we performed polymerase chain reaction (PCR)-based subtraction suppression hybridization (SSH) to identify genes that are differentially expressed in tumor-derived EL4/13.3 cells compared to the same cells isolated from cultures. Besides a number of unknown genes, the subtracted library contained several known genes that have been reported to be expressed at increased levels in tumors and/or to contribute to carcinogenesis. Apart from clones representing translated transcripts, the subtracted library also contained a high number of clones representing B2 repeat elements, viz. short interspersed repetitive elements that are transcribed by RNA polymerase III. Northern blotting confirmed the induction of B2 transcripts in tumor tissue and also revealed induction of chimeric, B2 repeat-containing mRNA. The appearance of chimeric transcripts was accompanied by aberrant, shorter-than-full-length transcripts, specifically from upregulated genes. Accordingly, in addition to altered gene expression, tumoral environmental triggers constitute a potent mechanism to create an epigenetic diversity in cancers by inducing extensive transcript anomalies.


Effect of methods of preparation on distribution of heavy metals in different size fractions of municipal solid waste composts.
The present study compares the distribution and nature of heavy metals in composts from 12 cities of India, prepared from different types of processed urban solid wastes, namely mixed wastes (MWC), partially segregated wastes (PSWC), and segregated bio-wastes (BWC). Compost samples were physically fractionated by wet sieving, followed by extraction of heavy metals by dilute HCl and NaOH. Bigger particles (>0.5 mm) constituted the major fraction in all three types of composts and had a relatively lower concentration of organic matter and heavy metals, the effect being more pronounced in MWC and PSWC in which a significant portion of the heavy metals was distributed in finer size fractions. Cd, Ni, Pb, and Zn were extracted to a greater extent by acid than by alkali, the difference being greater in MWC, which contained a higher amount of mineral matter. In contrast, Cu and Cr were extracted to a greater extent by dilute alkali, particularly from BWC containing a higher amount of organic matter. Water-soluble heavy metals were generally related to the water-soluble C or total C content as well as to pH, rather than to their total contents. This study concludes that wet sieving with dilute acid can effectively reduce heavy metal load in MWC and PSWC.


Purified protein kinase C phosphorylates a 47-kDa protein in control neutrophil cytoplasts but not in neutrophil cytoplasts from patients with the autosomal form of chronic granulomatous disease.
The neutrophil activators phorbol 12-myristate 13-acetate (PMA), formyl-methionyl-leucyl-phenylalanine, serum-treated zymosan, and IgG-coated latex cause an increase in protein phosphorylation in human neutrophil cytoplasts, concomitantly with an increase in oxygen consumption. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography, phosphorylation was apparent in many proteins, must abundantly in 42-, 47-, 50-, 60-, and 80-kDa proteins. In neutrophil cytoplasts from autosomal chronic granulomatous disease (CGD) patients that were stimulated with PMA, the phosphorylation of a 47-kDa protein is absent. The localization of this protein in PMA-activated control cytoplasts is mainly in the cytosol and, to a lower and more variable extent, in the membrane. After addition of purified protein kinase C to lysates of nonstimulated control cytoplasts, phosphorylation occurred at the 47-kDa level in both the cytosol and the membrane fraction. With lysates of autosomal CGD cytoplasts, in vitro phosphorylation of the 47-kDa protein was completely absent. After separation of cytoplast proteins on a sodium dodecyl sulfate-polyacrylamide gel and excision of the 47-kDa protein(s), phosphorylation of the isolated 47-kDa band was observed in the presence of purified protein kinase C. This reaction was again absent when autosomal CGD cytoplasts were used as starting material. Our studies have identified the 47-kDa protein in neutrophil cytoplasts as a true substrate for protein kinase C and indicate that the defect in phosphorylation at the 47-kDa level in autosomal CGD cytoplasts is due to a defective protein.


Implications for evolution of nuclear structures of animals, plants, fungi and protoctists.
The evolutionary variations of nuclear structure of animals, plants, fungi and protoctists were studied with electron microscopy by using techniques preferentially staining ribonucleoprotein (RNP) particles and chromatin. A remarkable similarity in the general morphological features of the RNP particles and chromatin arrangement is found in animals, plants and fungi. Important variations of these features were found in protoctists. These observations suggest that major evolutionary changes in the nuclear structure predate the acquisition of plastids by the ancestors of green plants. Once evolved, the nuclear structural pattern is conserved in plants and animals. Among protoctists studied, Kinetoplastida, Cryptomonadida and Volvocida have RNP particles and chromatin arrangement resembling those of plants and animals. These similarities may indicate a common ancestor. Important differences in the nuclear structure among Euglenida, Amebida, Cryptomonadida, Volvocida and Kinetoplastida support the view that Sarcomastigophora is a polyphyletic taxon. For the same reason Kinetoplastida and Euglenida must not be grouped in a monophyletic taxon. We propose that the variations of RNP particles may be related to the initial evolution of post-transcriptional processing.


Medial extrusion of the posterior segment of medial meniscus is a sensitive sign for posterior horn tears.
To evaluate medial extrusion of the posterior segment of the medial meniscus in posterior horn tears. This study enrolled 72 patients without medial meniscal tears (group N), 72 patients with medial meniscal tears without posterior horn tears (group PH-), 44 patients with posterior horn tears of the medial meniscus (group PH+). All meniscal tears were confirmed by arthroscopy. Medial extrusion of the middle segment and the posterior segment was measured on coronal MRIs. Extrusions of both middle and posterior segments in groups PH- and PH+ (middle segment; 2.94±1.51 mm for group PH- and 3.75±1.69 mm for group PH+, posterior segment; 1.85±1.82 mm for group PH- and 4.59±2.74 mm for group PH+) were significantly larger than those in group N (middle segment; 2.04±1.20, posterior segment; 1.21±1.86). Both indicators of extrusion in group PH+ were larger than those in group PH-. In the early OA category, neither middle nor posterior segment in group PH- extruded more than in group N. However, only the posterior segment in group PH+ extruded significantly more than in group N. Multiple lineal regression analyses revealed that posterior segment extrusion was strongly correlated with the posterior horn tears (p<0.001) among groups PH- and PH+. The newly presented indicator for extrusion of the posterior segment of the medial meniscus is associated with posterior horn tears in comparison with the extrusion of the middle segment, especially in the early stages of osteoarthritis. Level II--Diagnostic Study.


1977 National survey of support in space and dollars for departments of obstetrics and gynecology from their medical schools.
A questionnaire was sent to all chairpersons in obstetrics and gynecology departments in United States Medical Schools in the fall of 1977 seeking information on the school's support of that department for the year 1977 in terms of space and dollar commitments. A total of 113 schools were contacted; 106 responded (93.8%) and the data were tabulated. There were no significant differences between the private and state school resources. The average space commitment was 9,277 +/- SEM 709 square feet and the average school budget was 441,023 +/- SEM 24,265 dollars/year. These data were adjusted for class size and provide the first data base for assessing the adequacy of a medical school's commitment to a department of obstetrics and gynecology.


Evaluation of Etiology of Epistaxis and its Management in Dhulikhel Hospital.
Epistaxis is one of the most common and most difficult emergencies presenting in 7-14% of the general population each year. Although its lifetime incidence is about 60%, only 6% require formal medical intervention but they can be serious and even life threatening. The main objectives are to study different etiology, types, modality of treatment of epistaxis. Specific objective is also to find out if the modality of treatment is associated with age, site, amount of bleeding and etiology. It is a prospective, cross sectional, longitudinal, analytical study done in Department of ENT, Dhulikhel hospital, Kathmandu University School of Medical Sciences (KUSMS) from Aug. 2010 to Aug. 2013. Data was collected. This study was cleared through institutional review committee of hospital. Statistical analysis was done using SPSS 16.0. 487 patients were studied during the period. There was significant association between age group with type of treatment (p value 0.002); and with admission (p value < 0.001). Significance in the study was also shown in the correlation between site of bleeding and the type of treatment and also with alcohol intake with site of bleeding (p value < 0.001).However there was no significance between hypertension and the type of treatment methods chosen (p value > 0.01). Management of epistaxis is challenging. Most are managed by non surgical means whereas some by surgical treatment. Non surgical treatment is still useful, safe and cost effective. Type of treatment and need for hospital stay is related to age and site of bleeding.


[Echocardiographic diagnosis of thrombus on a Hancock bioprosthesis in mitral position following endocarditis (author's transl)].
Acute stenosis of a Hancock bioprosthesis in mitral position was found eight months after surgery and three months following septic periproctitic abscess in a 59 year old woman. Echocardiography revealed almost complete valve obstruction by thrombus formation: unusual dense and inhomogenous structures between the anterior and posterior stent echos of the prosthesis were seen in systole as well as in diastole. Echocardiography appears to be a useful non-invasive method for detection of the rare thrombotic complications in Hancock bioprostheses.


Ginsenoside Rg1, lights up the way for the potential prevention of Alzheimer's disease due to its therapeutic effects on the drug-controllable risk factors of Alzheimer's disease.
In traditional Chinese medicine, Shen Nong, BenCao Jing, and Compendium of Materia Medica (Bencao Gangmu), Panax ginseng, and its prescriptions have been used for the treatment of dementia, depression, weight loss, Xiaoke disease (similar to diabetes), and vertigo. All these diseases are associated with the drug-controllable risk factors for Alzheimer's disease (AD), including depression, obesity, diabetes, and hypertension. Ginsenoside Rg1, one of the main active ingredients of P. ginseng and its congener Panax notoginseng, possesses therapeutic potentials against AD and associated diseases. This suggests that ginsenoside Rg1 might have the potential for AD prevention and treatment. Although the anti-AD effects of ginsenoside Rg1 have received more attention, a systematic review of its effects on depression, obesity, diabetes, and hypertension is not available. This systematic literature review comprehensively summarized existing literature on the therapeutic potentials of ginsenoside Rg1 in AD prevention for the propose of providing a foundation of future research aimed at enabling the use of such drugs in clinical practice. Information on ginsenoside Rg1 was collected from relevant published articles identified through a literature search in electronic scientific databases (PubMed, Science Direct, and Google Scholar). The keywords used were "Ginsenoside Rg1," "Panax ginseng," "Source," "Alzheimer's disease," "Brain disorders," "Depression," "Obesity," "Diabetes," and "Hypertension." The monomer ginsenoside Rg1 can be relatively easily obtained and has therapeutic potentials against AD. In vitro and in vivo experiments have demonstrated the therapeutic potentials of ginsenoside Rg1 against the drug-controllable risk factors of AD including depression, obesity, diabetes, and hypertension. Thus, ginsenoside Rg1 alleviates diseases resulting from AD risk factors by regulating multiple targets and pathways. Ginsenoside Rg1 has the potentials to prevent AD by alleviating depression, obesity, diabetes, and hypertension.


Brain tumour segmentation based on an improved U-Net.
Automatic segmentation of brain tumours using deep learning algorithms is currently one of the research hotspots in the medical image segmentation field. An improved U-Net network is proposed to segment brain tumours to improve the segmentation effect of brain tumours. To solve the problems of other brain tumour segmentation models such as U-Net, including insufficient ability to segment edge details and reuse feature information, poor extraction of location information and the commonly used binary cross-entropy and Dice loss are often ineffective when used as loss functions for brain tumour segmentation models, we propose a serial encoding-decoding structure, which achieves improved segmentation performance by adding hybrid dilated convolution (HDC) modules and concatenation between each module of two serial networks. In addition, we propose a new loss function to focus the model more on samples that are difficult to segment and classify. We compared the results of our proposed model and the commonly used segmentation models under the IOU, PA, Dice, precision, Hausdorf95, and ASD metrics. The performance of the proposed method outperforms other segmentation models in each metric. In addition, the schematic diagram of the segmentation results shows that the segmentation results of our algorithm are closer to the ground truth, showing more brain tumour details, while the segmentation results of other algorithms are smoother. Our algorithm has better semantic segmentation performance than other commonly used segmentation algorithms. The technology we propose can be used in the brain tumour diagnosis to provide better protection for patients' later treatments.


Diisononyl 1,2-cyclohexanedicarboxylic acid (DINCH) and Di(2-ethylhexyl) terephthalate (DEHT) in indoor dust samples: concentration and analytical problems.
Possible human health effects of phthalate plasticizers have been intensely discussed during the last decade. Di(2-ethylhexyl) phthalate (DEHP), the phthalate acid ester with the largest production volume worldwide, has been substituted by new compounds like Diisononyl 1,2-cyclohexanedicarboxylic acid (DINCH) or Di(2-ethylhexyl) terephthalate (DEHT) in many applications. There are numerous reports about concentration levels of phthalates in indoor environments, but data on concentrations of these alternative plasticizers are not available yet. Also, the methods for the determination of phthalate substitutes are not yet established. This study presents the results achieved by quantification using different analytical methods. Data on the concentration of DEHT and DINCH in 953 dust samples from German households are presented. These samples were obtained in four different studies conducted from 1997 to 2009. Maximum concentrations of 110 mg DINCH/kg dust and 440 mg DEHT/kg dust were found. Especially the amount of DINCH has increased significantly after the market introduction of this plasticizer in 2002. Up to the beginning of 2006, DINCH was found in 44% of the dust samples. Dust samples collected in 2009 indicate an increased concentration for both softeners.


Generation of an Abcc8 homozygous mutation human embryonic stem cell line using CRISPR/Cas9.
The gene of ATP-binding cassette subfamily C member 8 (Abcc8) is cytogenetically located at 11p15.1 and encodes the sulfonylurea receptor (SUR1). SUR1 is a subunit of ATP-sensitive potassium channel (KAPT) in the β-cell regulating insulin secretion. Mutations of ABCC8 are responsible for congenital hyperinsulinism (CHI). Here we generated an Abcc8 homozygous mutant cell line by CRISPR/Cas9 technique with 22bp deletion resulting in abnormal splicing on human embryonic stem cell line H1. The phenotypic characteristics of this cell line reveal defective KATP channel and diazoxide-unresponsive that provides an ideal model for molecular pathology research and drug screening for CHI.


Amplification of nuclear aldolase A in mouse cell mutants resistant to Hoechst 33342.
5-Bromodeoxyuridine (BrdU) induces a phenomenon similar to cellular senescence in mammalian cells. AT-binding ligands such as Hoechst 33258 synergistically potentiate the effect of BrdU. We isolated mouse FM3A cell mutants resistant to Hoechst 33342 and characterized two highly resistant mutants. Two-dimensional gel electrophoresis followed by peptides sequence tags revealed that nuclear aldolase A was markedly increased in both mutants. Western blot analysis confirmed that nuclear aldolase A was increased leaving cytosolic aldolase A unaltered. Its mRNA levels were also increased in the mutants. Enforced expression of aldolase A conferred resistance to Hoechst 33342 on wild-type cells. Taken together, nuclear aldolase A was shown to somehow protect the cytotoxic effect of Hoechst 33342.


Reduced genetic diversity and restricted gene flow of broadcast-spawning coral Galaxea fascicularis in the South China Sea reveals potential degradation under environmental change.
Under the dual effects of climate change and anthropogenic activities, coral reefs in the South China Sea (SCS) are at serious risk of degradation. Galaxea fascicularis is a widely distributed species in the SCS, and the study of its genetics, survival, and adaptability is conducive to further understanding the future characteristics of coral reefs in the SCS. In this study, 146 G. fascicularis samples were selected from 9 survey stations across 12 latitudes in the SCS, and 8 pairs of microsatellite markers were used to characterize their genetic diversity and structure. The results showed moderate genetic diversity index values (Ar = 3.444-4.147, He = 0.634-0.782, Ho = 0.367-0.586). The AMOVA results and pairwise FST values showed a moderate level of genetic differentiation (ΦST = 0.119, P < 0.05) among G. fascicularis populations in the SCS, whereas its genetic structure showed high genetic differentiation (FST = 0.062-0.225) among relatively high-latitude populations (n = 3) and low genetic differentiation (FST = 0.012-0.064) in low-latitude populations (n = 6). The living environment of relatively high-latitude populations is disturbed by high-intensity human activities, leading to the specialization of local populations. Mantel test results showed a significant positive correlation between genetic differentiation among G. fascicularis populations and sea surface temperature (SST) variance (R2 = 0.4885; Mantel test, p = 0.010 < 0.05) in addition to geographical distance (R2 = 0.1134; Mantel, test p = 0.040 < 0.05), indicating that SST and geographical isolation were primary factors affecting the genetic structure of this species in the SCS. The lower genetic diversity and limited gene flow of G. fascicularis indicate limited genetic adaptation, and corresponding vulnerability may be more pronounced under future environmental changes. These findings provide a theoretical basis for the conservation and restoration of coral reefs in the SCS.


Action of serotonin (5-hydroxytryptamine) on cyclic nucleotides in glomeruli of rat renal cortex.
Serotonin (5-hydroxytryptamine) is known to influence glomerular function and may have an important role in the pathogenesis of glomerulopathies. Because serotonin acts in nonrenal tissues through mediation of cyclic nucleotides, we investigated in vitro its effect on cAMP and cyclic guanosine monophasphate (cGMP) in tissue slices and isolated glomeruli from rat kidney. Serotonin increased cAMP 161 +/- 35% but not cGMP in renal cortex; it had no effect on cyclic nucleotides in medulla and papilla. In isolated glomeruli, serotonin elicited a dose-dependent (in the range of 10-7 to 10-4 M) increase in cAMP; the maximum increase over basal values was 376 +/- 45%. Serotonin increased cAMP either in the presence or in the absence of a cAMP phosphodiesterase inhibitor. In tubular fraction, serotonin elevated cAMP to a much lesser degree (82 +/- 15%). Neither in glomeruli nor in tubules did cGMP concentrations change in response to serotonin, but carbamylcholine, a known cGMP agonist, significantly increased cGMP concentrations. The increase in cAMP in response to serotonin was blocked (greater than 85% inhibition) by equimolar concentrations of serotonin antagonists methysergide and cinanserine. Results of this study demonstrate that interaction of serotonin with receptors in the kidney, particularly in the glomeruli, cause a striking increase in cAMP concentrations without detectable changes in cGMP concentrations. These findings suggest that serotonin, either synthesized in the kidney or released locally from platelets aggregated in glomeruli (for example, in association with immunopathologic injury) may exert of modulate its physiologic or pathologic effects via mediation of cAMP.


Specific value of computed tomographic breast scanner (CT/M) in diagnosis of breast diseases.
CT/M study of the breast yields specific information about lesions and may provide the diagnosis when mammography fails to demonstrate the lesion or is unable to display the information necessary to make a definitive diagnosis. By using contrast medium to increase attenuation, very small carcinomas may be identified, even in dysplastic breasts.


The calibration of automated instruments for accuracy in hemoglobinometry.
The surveys of the College of American Pathologists indicate a consistent bias between the manual "reference" method for hemoglobin determinations and the Coulter S measurements. The Coulter S hemoglobin values are invariably lower; the difference averages 0.3 g/dl. The commonly used calibration methods for the Coulter appear to be subobtimal. The hemoglobin calibration and quality assurance method proposed by Bull and colleagues is advocated as the presently most acceptable method. Commercial hemoglobin control materials should not be used for hemoglobin calibration.


Investigation of the phenotype heterogeneity in severe hemophilia A using thromboelastography, thrombin generation, and thrombodynamics.
Hemophilia A (HA) patients with similar factor VIII levels can demonstrate varying bleeding tendencies. In particular, 10-15% of all severe HA patients (FVIII:C<1IUdL(-1)) do not require regular replacement therapy. Modern global coagulation assays can help to detect and study this "mild" bleeding phenotype. Here, we investigated the coagulation status of different bleeding phenotypes using various types of global coagulation assays. Ten HA patients with severe phenotype and eleven patients with mild phenotypes were included in the study. For each patient, thromboelastography (TE), thrombodynamics (TD), and kaolin- or tissue factor-induced thrombin generation (TG) were measured. TG in platelet-rich plasma (PRP) was investigated using our original modification when the thrombin generation curve showed two peaks, previously shown to depend on platelet activity. We also utilized TG and TD with the addition of thrombomodulin. The second peak amplitude and ETP of PRP TG were the only parameters that were significantly higher in mild bleeders (peak 41.6 ± 3.5 nM, ETP 1966 ± 169 nM*min) than in patients with severe bleeding (peak 28.3 ± 3.3 nM, ETP 1359 ± 130 nM*min). Our results suggest that severe and mild HA phenotypes could be distiguished by TG assay in PRP suggesting that difference in platelet activity can be involved in the phenotype formation. According to our previous results we can suppose that the mechanism of the phenotypic heterogeneity is linked with TG mediated by PS-expressing platelets.


Ultrasound induces contraction of the bladder smooth muscle.
To investigate whether the treatment of overt postpartum urinary retention (PUR) with low-intensity pulsed ultrasound (LIPUS) was clinically effective and whether LIPUS could accelerate bladder smooth muscle (BSM) contraction by opening the L-type calcium channels and activating the Ca(2+) signaling pathway. Records of 136 patients undergoing PUR were retrospectively reviewed in two different groups for LIPUS and neostigmine between from 2014 to July 2015. The rats BSM strips in vitro were irradiated by LIPUS. The contraction frequency and amplitude were recorded with BL-410F biological experimental system. The BSM cells were constructed and identified by α-actin-specific antibody staining, and the intracellular Ca(2+) concentration was analyzed by flow cytometry. The clinical trial indicated that LIPUS had potential therapeutic effect on PUR (80.6 vs. 64.1 %, p < 0.05), and the BSM strip contractility was increased by LIPUS (p < 0.001), and the concentration of Ca(2+) was markedly enhanced by about twofold than that without LIPUS exposure (p < 0.01). Besides, nimodipine could suppress the contraction of BSM and the concentration of intracellular Ca(2+) which was caused by ultrasound. The results suggested LIPUS had potential therapeutic effect on PUR and the Ca(2+) signaling pathway was involved in the mechanism. The ultrasound irradiation may provide a new method for PUR therapy.


Management of urethral stricture disease.
With the advent of modern tissue transfer techniques, most cases of urethral reconstruction can be approached with confidence that an excellent functional and cosmetic result is probable. The authors present a logical approach to urethral stricture disease predicated on the anatomy of the stricture disease. Only those procedures believed to offer a maximal chance of success are offered to the patients. Should a patient present with complex stricture disease, initially a flap procedure would be employed.


Rapid suppression of protein degradation in skeletal muscle after oral feeding of leucine in rats.
A diet containing adequate amounts of protein rapidly suppresses myofibrillar protein degradation in rats and mice. This study determined whether dietary amino acids inhibit postprandial protein degradation in rat skeletal muscle. When rats fed on a 20% casein diet for 1 h after 18 h starvation, the rate of myofibrillar protein degradation measured by N(tau)-methylhistidine release from the isolated extensor digitorum longus muscle was significantly (p < 0.05) decreased at 4 h after refeeding. A diet containing an amino acid mixture which is the same composition as casein also reduced myofibrillar protein degradation at 4 h after refeeding (p < 0.05). An essential amino acid mixture (15.1%, corresponding to casein composition) and a leucine (2.9%) diets reduced the rate of myofibrillar protein degradation after refeeding (p < 0.05), whereas a protein free diet did not. Administration of leucine alone (0.135 g/100 g body weight) by a feeding tube induced a decrease in the rate of myofibrillar protein degradation at 2 h after administration (p < 0.05), whereas the serum insulin concentration was constant after leucine administration. These results suggested that leucine is one of regulating factors of myofibrillar protein degradation after refeeding of a protein diet.


Bilayer STING goes head to head to stay put.
In this issue, Liu et al.1 provide structural insights into how STING remains inactive. Apo-STING adopts a bilayer conformation exhibiting head-to-head and side-to-side interactions in its autoinhibitory state on the ER. The apo-STING oligomer differs from the activated STING oligomer in its biochemical stability, protein domain contact, and membrane curvature.


Branched-chain amino acids enhance the cognitive recovery of patients with severe traumatic brain injury.
To investigate whether supplementation with branched-chain amino acids (BCAAs) in patients with severe traumatic brain injury (TBI) improves recovery of cognition and influences plasma concentrations of tyrosine and tryptophan, which are precursors of, respectively, catecholamine and serotonin neurotransmitters in the brain. Forty patients with TBI were randomly assigned to 15 days of intravenous BCAA supplementation (19.6g/d) (n=20) or an isonitrogenous placebo (n=20). Tertiary care rehabilitation setting in Italy. Forty men (mean age, 32+/-15 y) with TBI and 20 healthy subjects (controls) matched for age, sex, and sedentary lifestyle. Supplementation with BCAAs. Disability Rating Scale (DRS) and plasma concentrations of BCAAs, tyrosine, and tryptophan. Fifteen days after admission to the rehabilitation department, the DRS score had improved significantly in both the placebo group (P<.05 vs baseline) and in the BCAA-supplemented group (P<.01 vs baseline). The difference between the 2 groups was significant (P<.004). Plasma tyrosine concentration improved in the group given BCAA supplementation, and tryptophan concentration increased in patients receiving placebo. Supplemental BCAAs enhance the retrieval of DRS without causing negative effects on tyrosine and tryptophan concentration.


Detecting protein-phospholipid interactions. Epidermal growth factor-induced activation of phospholipase D1b in situ.
Phospholipase D (PLD) proteins have been identified in secretory and endocytic vesicles, consistent with their proposed role in regulating membrane traffic. However, their sites of catalytic action remain obscure. We have developed here a novel, analytical approach to monitor PLD activation in intact cells employing lifetime imaging microscopy to measure fluorescence resonance energy transfer between protein and membrane phospholipid. Verification and application of this technique demonstrates a dispersed endosomal, epidermal growth factor-induced activation of the PLD1b isoform. Application of this approach will facilitate the spatial resolution of many protein-phospholipid interactions that are key events in the regulation of cellular processes.


Polyamine sensing by nascent ornithine decarboxylase antizyme stimulates decoding of its mRNA.
Polyamines are essential organic polycations with multiple cellular functions relevant for cell division, cancer and ageing. Regulation of polyamine synthesis is mainly achieved by controlling the activity of ornithine decarboxylase (ODC) through an unusual mechanism involving ODC antizyme, the binding of which disrupts homodimeric ODC and targets it for ubiquitin-independent degradation by the 26S proteasome. Whereas mammals express several antizyme genes, we have identified a single orthologue, termed OAZ1, in Saccharomyces cerevisiae. Similar to its mammalian counterparts, OAZ1 synthesis is induced with rising intracellular polyamine concentrations, which also inhibit ubiquitin-dependent degradation of the OAZ1 protein. Together, these mechanisms contribute to a homeostatic feedback regulation of polyamines. Antizyme synthesis involves a conserved +1 ribosomal frameshifting (RFS) event at an internal STOP codon during decoding of its messenger RNA. Here we used S. cerevisiae OAZ1 to dissect the enigmatic mechanism underlying polyamine regulation of RFS. In contrast with previous assumptions, we report here that the nascent antizyme polypeptide is the relevant polyamine sensor that operates in cis to negatively regulate upstream RFS on the polysomes, where its own mRNA is being translated. At low polyamine levels, the emerging antizyme polypeptide inhibits completion of its synthesis causing a ribosome pile-up on antizyme mRNA, whereas polyamine binding to nascent antizyme promotes completion of its synthesis. Thus, our study reveals a novel autoregulatory mechanism, in which binding of a small metabolite to a nascent sensor protein stimulates the latter's synthesis co-translationally.


The effects of aging and disease duration on cognition in multiple sclerosis.
Multiple sclerosis (MS) is a disease of the central nervous system that can interfere with cognitive functions. The purpose of this study is to document the impact of MS, aging and disease duration on cognitive functioning as both life expectancy and incidence of the disease among persons with MS (PwMS) aged 50 years and over (late-onset MS) are increasing in the last two decades. Exhaustive neuropsychological evaluation was performed in 84 PwMS (30 young, 30 elderly adult-onset, 25 elderly late-onset) and 50 control participants (25 young, 24 elderly). ANCOVAs and hierarchical linear regressions were used to meet the objectives. Interaction effects were found between age and presence of MS on higher executive function and information processing speed/working memory. After controlling for confounding variables (fatigue, quality of life, depression, MS course, comorbidity), results demonstrated an important role of age on all cognitive functions but only a trend of disease duration on information processing speed/working memory. Decline in higher executive functions and information processing speed/working memory in aging is accentuated by the presence of MS, but the impact of age and MS on memory are independent. Age appears to be the variable having the most important role on cognition.


Transcriptional regulation of the human Runx2/Cbfa1 gene promoter by bone morphogenetic protein-7.
It is well established that core binding factor Runx2/Cbfa1 is required for osteoblast recruitment and differentiation from mesenchymal stem cells. Transcriptional regulation of the Runx2/Cbfa1 gene by osteogenic factors such as bone morphogenetic proteins (BMPs) plays an important role in the stimulation of bone formation by these cytokines. BMP7 (also termed OP-1) is a member of the transforming growth factor beta (TGF-beta) superfamily and induces osteoblast differentiation from mesenchymal precursor stem cells in vitro as well as bone formation in vivo. This study examines the effects of BMP7 on markers of osteoblast differentiation and specifically on human Runx2/Cbfa1 gene transcription in a mouse C2C12 myoblast cell line where it induces expression of both alkaline phosphatase (ALP) and endogenous Runx2/Cbfa1. To further understand the mechanisms of human Runx2/Cbfa1 transcriptional regulation by BMP7, we cloned 3.0 kb of the human Runx2/Cbfa1 gene 5'-upstream flanking region and created a series of promoter deletions cloned into luciferase-based reporter vectors (Runx2/Cbfa1/Luc). Sequence data revealed six copies of the osteoblastic cis-acting element (OSE2) in the proximal promoter region. In C2C12 cells transiently transfected with Runx2/Cbfa1/Luc deletion constructs, transcriptional activity of Runx2/Cbfa1 was upregulated up to 2-fold after 24 h of BMP7 treatment. Mutational analysis demonstrated that the minimal responsive promoter region for BMP7-regulated transcription maps to a proximal -74 OSE2 site. Electromobility shift assays with C2C12 cellular extracts indicate that BMP7 increases binding of OSE2 promoter sequences, and supershift assays with anti-Runx2/Cbfa1 antibodies demonstrate that Runx2/Cbfa1 is part of the nucleoprotein complex binding OSE2. Together, these data indicate BMP7 can upregulate Runx2/Cbfa1 gene expression in C2C12 myoblast cells, and suggest that Runx2/Cbfa1 may bind to OSE2 elements within its own promoter to autoregulate gene transcription in differentiating osteoblasts.


Gastric Bypass-Related Effects on Glucose Control, β Cell Function and Morphology in the Obese Zucker Rat.
Roux-en-Y gastric bypass (RYGB) may improve beta cell function by mechanisms other than caloric restriction and body weight loss. We aimed to assess the impact of anatomical and hormonal alterations specific to RYGB on glucose homeostasis, β cell function and morphology. Male Zucker(fa/fa) rats underwent either RYGB (n = 11) or sham surgeries (n = 10). Five of the shams were then food restricted and body weight matched (BWM) to the RYGB rats. Six male Zucker(fa/+) rats underwent sham surgery and served as additional lean controls. Twenty-seven days after surgery, an oral glucose tolerance test (OGTT) was performed and plasma levels of glucose, insulin and glucagon-like peptide-1 (GLP-1) were measured. Immunohistological analysis of pancreatic islets was performed, and GLP-1 receptor and PDX-1 mRNA content were quantified. Shams consumed more food and gained more weight compared to both RYGB and BWM (p < 0.001). Hyperglycaemia was evident in ad libitum-fed shams, whilst postprandial glucose levels were lower in RYGB compared to the BWM sham group (p < 0.05). During the OGTT, RYGB rats responded with >2.5-fold increase of GLP-1. Histology revealed signs of islet degeneration in ad libitum-fed shams, but not in RYGB and sham BWM controls (p < 0.001). GLP-1 receptor and PDX-1 mRNA content was similar between the RYGB and BWM shams but higher compared to ad libitum shams (p < 0.05). Combined molecular, cellular and histological analyses of pancreatic function suggest that weight loss alone, and not the enhancement of GLP-1 responses, is predominant for the short-term β cell protective effects of RYGB.


Targeted 16S rRNA amplicon analysis reveals the diversity of bacterial communities in carwash effluents.
This study aimed to analyze the bacterial diversity in carwash effluents and to determine their potential for use in microbial degradation of environmental contaminants. Nine carwash effluent samples were collected for physicochemical and bacterial community diversity analysis using multi-digital probes and 16S rRNA gene amplicon sequencing respectively. The pH of all effluent samples was neutral to slightly alkaline. Oil and grease concentrations ranged from 15.3 to 49.7 mg/L. 16S gene amplicon sequencing of the nine samples produced 45,934-sequence reads, which translated to 13 bacterial phyla, 26 classes, and 43 genera. The most dominant phyla were Proteobacteria, Bacteroidetes, Firmicutes, and Fusobacteria. Canonical correspondence analysis (CCA) showed that the distribution of the phyla Proteobacteria, Bacteroidetes, Acidobacteria, and Verrucomicrobia was influenced by the presence of oil and grease, total petroleum hydrocarbons-gasoline range organics (GRO-TPH), and metals species (Pb, Cu, and Zn). The dominant bacterial genera found in the present study were previously proven to biodegrade hydrocarbons, and their presence in carwash effluents could bode well for in situ natural bioremediation of these contaminated sites.


Genetically encoded sensors of protein hydrodynamics and molecular proximity.
The specialized light organ of the ponyfish supports the growth of the bioluminescent symbiont Photobacterium leiognathi. The bioluminescence of P. leiognathi is generated within a heteromeric protein complex composed of the bacterial luciferase and a 20-kDa lumazine binding protein (LUMP), which serves as a Förster resonance energy transfer (FRET) acceptor protein, emitting a cyan-colored fluorescence with an unusually long excited state lifetime of 13.6 ns. The long fluorescence lifetime and small mass of LUMP are exploited for the design of highly optimized encoded sensors for quantitative fluorescence anisotropy (FA) measurements of protein hydrodynamics. In particular, large differences in the FA values of the free and target-bound states of LUMP fusions appended with capture sequences of up to 20 kDa are used in quantitative FA imaging and analysis of target proteins. For example, a fusion protein composed of LUMP and a 5-kDa G protein binding domain is used as an FA sensor to quantify the binding of the GTP-bound cell division control protein 42 homolog (Cdc42) (21 kDa) in solution and within Escherichia coli. Additionally, the long fluorescence lifetime and the surface-bound fluorescent cofactor 6,7-dimethyl-8- (1'-dimethyl-ribityl) lumazine in LUMP are utilized in the design of highly optimized FRET probes that use Venus as an acceptor probe. The efficiency of FRET in a zero-length LUMP-Venus fusion is 62% compared to ∼ 31% in a related CFP-Venus fusion. The improved FRET efficiency obtained by using LUMP as a donor probe is used in the design of a FRET-optimized genetically encoded LUMP-Venus substrate for thrombin.


FO-SPR based dextrose sensor using Ag/ZnO nanorods/GOx for insulinoma detection.
In this piece of work, a fiber optic sensor has been fabricated and characterized using surface plasmon resonance for dextrose sensing. The concentration range used in this study is for diagnosing the cases of hypoglycaemia especially in suppression tests of insulinoma. Insulinoma is a medical case in which the person is recognized being hypoglycaemic with the blood dextrose level falling down to 2.2mM or less. Thus, the sensor has been characterized for the dextrose concentration range of 0 mM-10mM including the cases of normal blood dextrose range. Coatings of silver layer and zinc oxide nanorods have been carried out on the bare core fiber with a dual role of zinc oxide followed by immobilization of glucose oxidase. A three stage optimization procedure has been adopted for the best performance of the sensor. Absorbance spectra have been plotted and peak absorbance wavelengths have been extracted for each concentration chosen along with the sensitivities. The results have been made conclusive with control experiments. The probe has also been tested on sample having blood serum to check the reliability of the sensor. The sensor shows better selectivity and response time along with its real time applications, online monitoring, remote sensing and reusability.


Hypothalamic-pituitary-adrenal axis activity and vascular function in healthy adults.
The objective of this study is to assess the relationship between hypothalamic-pituitary-adrenal (HPA) axis activity, vascular function and insulin sensitivity in healthy adults. Open observational study. Thirty healthy adults were studied at the Endocrine Research Unit, Repatriation General Hospital, Adelaide, SA, Australia. HPA activity was assessed from the serum cortisol 30 min after 1 µg ACTH1-24 (Novartis Pharmaceuticals). Subjects with a cortisol below (n = 15) and above (n = 15) the median were categorized as low and high responders, respectively. Reactive hyperaemia index (RHI) was measured fasting to estimate endothelial function. Matsuda index was calculated from glucose and insulin concentrations collected fasting and 30 minutely for 2 h after a mixed meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat). The primary endpoint was the difference in RHI between low and high responders. There were no significant differences in age (61 ± 9 vs. 64 ± 7 years, p = .19), body mass index (BMI; 26 ± 3 vs. 24 ± 4 kg/m2 , p = .25) and sex (p = .71) between low and high responders. High responders had a lower RHI (2.1 ± 0.2 vs. 2.6 ± 0.2, p = .04) than low responders and there was a negative association between RHI and peak cortisol post ACTH1-24 (β = -.56, p < .01). There were no significant differences in Matsuda index (15.0 ± 2.4 vs. 22.7 ± 5.2, p = .19) between high and low responders. In healthy adults, endothelial dysfunction is likely to contribute to the association between HPA hyperactivity and increased cardiovascular risk. As insulin sensitivity was not different in high and low responders, endothelial dysfunction is not primarily secondary to insulin resistance.


Association of Drusen Phenotype in Age-Related Macular Degeneration from Human Eye-Bank Eyes to Disease Stage and Cause of Death.
To stage maculopathy, assess and quantify drusen, determine drusen subtype frequency, and compare subtypes with age-related macular degeneration (AMD) stage and cause of death using an eye-bank model of AMD. Cross-sectional study. Two thousand ninety-two human eyes from 1067 eye-bank donors, selected from a population at risk for AMD. We analyzed donor eye tissue images (2005-2020) using both the 4- and 9-step Minnesota Grading System (MGS), an AMD grading system for eye-bank eyes corresponding to the Age-Related Eye Disease Study classification. The 9-step MGS quantifies total drusen area, hyperpigmentation, and depigmentation. We analyzed reticular pseudodrusen (RPD), basal laminar drusen (BLD), and calcified drusen (CaD) frequency within this population and explored associations with AMD stage, donor age, gender, and cause of death. Statistical analyses were performed using Wilcoxon rank-sum and chi-square tests. Testing encompassed staging eye-bank eyes using MGS analysis. Drusen subtype frequency associations with AMD stage and cause of death. We detected RPD in 228 (13%), BLD in 131 (7%), and CaD in 84 (5%) of the examined eyes (n = 1777). All subtypes were associated with advanced AMD (RPD: odds ratio [OR], 3.4 [95% confidence interval (CI), 2.5-4.5; P < 0.0001]; BLD: OR, 2.2 [95% CI, 1.5-3.2; P < 0.0001]; and CaD: OR, 39.1 [95% CI, 16.8-91.0; P < 0.0001]). Only the RPD subtype was associated statistically with cardiovascular death when compared with those without cardiovascular death (48% vs. 32%; OR, 2.0 [95% CI, 1.4-2.9]; P = 0.0002). In a large group of eye-bank eyes selected from a population at risk for AMD and graded using the 4-step and 9-step MGS, RPD, BLD, and especially CaD were associated strongly with advanced AMD. The RPD subtype was associated with a cardiovascular cause of death and may represent an ophthalmologic biomarker for cardiovascular disease.


Molecular detection and phylogenetic analysis of Anaplasma bovis from Haemaphysalis longicornis feeding on grazing cattle in Korea.
Ticks are vectors of various pathogens that affect humans and animals throughout the world. Anaplasma bovis is one of the most important tick-borne pathogens that cause cattle diseases but there is still very little information available about this agent in Korea. In the present study, 535 Haemaphysalis longicornis tick pools were analyzed from grazing cattle in five Korean provinces. A. bovis was detected in 50 (9.3%) of 535 tick pools using 16S rRNA-based PCR. A. bovis infections were detected for the first time in ticks feeding on cattle in Chungbuk, Geongbuk, and Jeonbuk provinces in Korea. The 50 positive PCR products were sequenced successfully and compared with sequences in GenBank. Phylogenetic analysis of the Korean isolates classified them into four genotypes with nucleotide sequence identities of 99.4-100%. Two of the four genotypes had high similarity (99.8-100%) with known sequences. The other two genotypes have never been identified.


Yorkshire Enhanced Stop Smoking (YESS) study: a protocol for a randomised controlled trial to evaluate the effect of adding a personalised smoking cessation intervention to a lung cancer screening programme.
Integration of smoking cessation (SC) into lung cancer screening is essential to optimise clinical and cost effectiveness. The most effective way to use this 'teachable moment' is unclear. The Yorkshire Enhanced Stop Smoking study will measure the effectiveness of an SC service integrated within the Yorkshire Lung Screening Trial (YLST) and will test the efficacy of a personalised SC intervention, incorporating incidental findings detected on the low-dose CT scan performed as part of YLST. Unless explicitly declined, all smokers enrolled in YLST will see an SC practitioner at baseline and receive SC support over 4 weeks comprising behavioural support, pharmacotherapy and/or a commercially available e-cigarette. Eligible smokers will be randomised (1:1 in permuted blocks of random size up to size 6) to receive either an enhanced, personalised SC support package, including CT scan images, or continued standard best practice. Anticipated recruitment is 1040 smokers (January 2019-December 2020). The primary objective is to measure 7-day point prevalent carbon monoxide (CO) validated SC after 3 months. Secondary outcomes include CO validated cessation at 4 weeks and 12 months, self-reported continuous cessation at 4 weeks, 3 months and 12 months, attempts to quit smoking and changes in psychological variables, including perceived risk of lung cancer, motivation to quit smoking tobacco, confidence and efficacy beliefs (self and response) at all follow-up points. A process evaluation will explore under which circumstances and on which groups the intervention works best, test intervention fidelity and theory test the mechanisms of intervention impact. This study has been approved by the East Midlands-Derby Research Ethics Committee (18/EM/0199) and the Health Research Authority/Health and Care Research Wales. Results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and via the YLST website. ISRCTN63825779, NCT03750110.


Greater effects of mutual cooperation and defection on subsequent cooperation in direct reciprocity games than generalized reciprocity games: Behavioral experiments and analysis using multilevel models.
Reciprocity toward a partner's cooperation is a fundamental behavioral strategy underlying human cooperation not only in interactions with familiar persons but also with strangers. However, a strategy that takes into account not only one's partner's previous action but also one's own previous action-such as a win-stay lose-shift strategy or variants of reinforcement learning-has also been considered an advantageous strategy. This study investigated empirically how behavioral models can be used to explain the variances in cooperative behavior among people. To do this, we considered games involving either direct reciprocity (an iterated prisoner's dilemma) or generalized reciprocity (a gift-giving game). Multilevel models incorporating inter-individual behavioral differences were fitted to experimental data using Bayesian inference. The results indicate that for these two types of games, a model that considers both one's own and one's partner's previous actions fits the empirical data better than the other models. In the direct reciprocity game, mutual cooperation or defection-rather than relying solely on one's partner's previous actions-affected the increase or decrease, respectively, in subsequent cooperation. Whereas in the generalized reciprocity game, a weaker effect of mutual cooperation or defection on subsequent cooperation was observed.