DNA variability and parentage testing in captive Waldrapp ibises.
The Waldrapp ibis (Geronticus eremita) is one of the most endangered birds in the wild. The only real hope for its survival seems to rest with captive propagation, which has fortunately proved straightforward. Preservation of genetic diversity for maintaining viable populations is a major goal in any species conservation programme. Therefore sensitive tools have to be developed for the detection and regular monitoring of population variability. Individual identity has to be verified and each individual's pedigree defined in order to enable effective selective breeding. In this study, extensive DNA fingerprinting technology was applied to a group of 39 captive Waldrapp ibises. Five minisatellite probes were used. Despite the fact that the colony was founded by only six birds and that some of the founders were apparently related, highly polymorphic banding patterns were obtained. The human- and pig-derived probes MS1, MS31, p lambda g3 and pCMS12 each detected multiple distinct loci suitable for individual identification and resolution of parentage. Probe MS51 was locus-specific and revealed six different alleles. In addition, MS31 and p lambda g3 co-detected a band present in all females but none of the males and thus could be used for sex determination. For all but four individuals both parents could be identified unambiguously. The exceptions were offspring derived from a full sib mating in which DNA results allowed no distinction between the parents and the grandparents. Comparison of the parentage assigned by DNA analysis and by observation of breeding behaviour, respectively, showed agreement in all but five instances. Here, DNA data uncovered interchange of individuals in the stud book. Application of these minisatellite probes therefore offers an extremely sensitive means for individual identification and verification and completion of pedigree records.


Multiple Atlas construction from a heterogeneous brain MR image collection.
In this paper, we propose a novel framework for computing single or multiple atlases (templates) from a large population of images. Unlike many existing methods, our proposed approach is distinguished by its emphasis on the sharpness of the computed atlases and the requirement of rotational invariance. In particular, we argue that sharp atlas images that retain crucial and important anatomical features with high fidelity are more useful for many medical imaging applications when compared with the blurry and fuzzy atlas images computed by most existing methods. The geometric notion that underlies our approach is the idea of manifold learning in a quotient space, the quotient space of the image space by the rotations. We present an extension of the existing manifold learning approach to quotient spaces by using invariant metrics, and utilizing the manifold structure for partitioning the images into more homogeneous sub-collections, each of which can be represented by a single atlas image. Specifically, we propose a three-step algorithm. First, we partition the input images into subgroups using unsupervised or semi-supervised learning methods on manifolds. Then we formulate a convex optimization problem in each subgroup to locate the atlases and determine the crucial neighbors that are used in the realization step to form the template images. We have evaluated our algorithm using whole brain MR volumes from OASIS database. Experimental results demonstrate that the atlases computed using the proposed algorithm not only discover the brain structural changes in different age groups but also preserve important structural details and generally enjoy better image quality.


Amide bond-containing monodisperse polyethylene glycols beyond 10 000 Da.
Although monodisperse polyethylene glycols (M-PEGs) above 4000 Da are especially valuable in biomedical applications, their synthesis remains a long-standing challenge. To this end, a peptide-based strategy for such M-PEGs was developed. With macrocyclic sulfates as the key intermediates, a panel of oligoethylene glycol (OEG) containing ω-amino acids were prepared with high efficiency. Through solid phase peptide synthesis (SPPS), these amino acids were conveniently assembled into a series of amide bond-containing M-PEGs with high flexibility in molecular weight and amide density selection. With this strategy, an M-PEG of 10 262 Da was prepared on a gram scale and its biocompatibility was assessed in a mice model.


Esophageal cancer risk by ALDH2 and ADH2 polymorphisms and alcohol consumption: exploration of gene-environment and gene-gene interactions.
Alcohol drinking is a major risk factor for esophageal cancer in Japan and its impact may be modulated by levels of ALDH2, ADH2 and CYP2E1, three representative alcohol-metabolizing enzymes which display genetic polymorphisms altering individual alcohol-oxidizing capacity and drinking behavior. To assess the actual influence of ADH2 Arg47His, ALDH2 Glu487Lys and CYP2E1 variant c2 allele polymorphisms on esophageal cancer risk with conjunction with alcoholic consumption, the present 1:3 matched case-control study was conducted. The 165 histologically diagnosed Japanese esophageal cancer cases were here compared with 495 randomly selected controls, matched with respect to sex and age. Conditional logistic regression was used to calculated Odds Ratios (ORs) and 95% confidence intervals (95% CI). Significant gene-environment interactions between alcohol drinking and both ADH2 and ALDH2 were observed regarding esophageal cancer risk. The ADH2 Arg47His polymorphism showed moderately increased risk (OR for Arg/His and Arg/Arg relative to His/His: 2.01 (1.39-2.90)). In the ALDH2 case, comparing the Glu/Lys with the Glu/Glu genotype, ORs were markedly increased to 9.64 (3.23-28.8) and 95.4 (28.7-317) from 1.88 (0.42-8.37) and 4.62 (0.93-23.1) for moderate drinking and heavy drinking, respectively. No significant alteration in risk was observed with the CYP2E1 polymorphism. In conclusion, the present study revealed a significant gene-environment interaction between alcohol drinking and the ALDH2 polymorphism regarding esophageal cancer risk among a general population in Japan, providing concrete evidence of a role for acetaldehyde in neoplastic development. Interactions between ALDH2 and ADH2 need further clarification.


A model for the effect of constant photoperiods on the rate of sexual maturation in pullets.
1. This paper reviews evidence from 15 experiments, reported over a span of 44 years, in which pullets were reared from hatching to sexual maturity on 2 or more constant photoperiods. 2. The evidence strongly indicates that earliest age at first egg (AFE) was observed when pullets were held on constant 10 h days (though earlier maturity is easily induced by increasing the photoperiod during rearing). The pair of equations which best describe the relationship between AFE (y, d) and photoperiod (x, h) are for x < or = 10 h, y = 175.8-1.731x; for x > or = 10 h, y = 155.5 + 0.301x. 3. This 2-straight-line model, hinged at 10 h, should be used in preference to curvilinear models published earlier, which wrongly predict that pullets reared on long days (14 h to 17 h) mature faster than birds reared on constant 10 h.


Nona-coordinated chiral Eu(III) complexes with stereoselective ligand-ligand noncovalent interactions for enhanced circularly polarized luminescence.
Circularly polarized luminescence (CPL) of chiral Eu(III) complexes with nona- and octa-coordinated structures, [Eu(R/S-iPr-Pybox)(D-facam)(3)] (1-R/1-S; R/S-iPr-Pybox, 2,6-bis(4R/4S-isopropyl-2-oxazolin-2-yl)pyridine; D-facam, 3-trifluoroacetyl-d-camphor), [Eu(S,S-Me-Ph-Pybox)(D-facam)(3)] (2-SS; S,S-Me-Ph-Pybox, 2,6-bis(4S-methyl-5S-phenyl-2-oxazolin-2-yl)pyridine), and [Eu(Phen)(D-facam)(3)] (3; Phen, 1,10-phenanthroline) are reported, and their structural features are discussed on the basis of X-ray crystallographic analyses. These chiral Eu(III) complexes showed relatively intense photoluminescence due to their (5)D(0) → (7)F(1) (magnetic-dipole) and (5)D(0) → (7)F(2) (electric-dipole) transition. The dissymmetry factors of CPL (g(CPL)) at the former band of 1-R and 1-S were as large as -1.0 and -0.8, respectively, while the g(CPL) of 3 at the (5)D(0) → (7)F(1) transition was relatively small (g(CPL) = -0.46). X-ray crystallographic data indicated specific ligand-ligand hydrogen bonding in these compounds which was expected to stabilize their chiral structures even in solution phase. CPL properties of 1-R and 1-S were discussed in terms of transition nature of lanthanide luminescence.


Sulfasalazine metabolite pharmacokinetics in pediatric patients with inflammatory bowel disease: effects of disease activity, acetylator phenotype, and age.
The pharmacokinetics and protein binding of sulfapyridine (SP) and its major metabolite, acetylsulfapyridine (ACSP) were examined in 17 prepubertal children and 4 postpubertal adolescents receiving sulfasalazine (SASP) for treatment of inflammatory bowel disease (IBD). Five patients were studied in both active disease and remission. Comparisons were made with a group of 24 outpatients (9-62 years) with IBD controlled on SASP and in remission. Acetylator phenotype was calculated from plasma metabolite ratios. Slow acetylators had increased plasma concentrations of SP and ACSP + SP (P less than 0.05). Apparent SP clearance (clearance/availability) was increased in active disease (P less than 0.05) and AUCSP + ACSP and AUCSP were decreased (P less than 0.05). There were no age-related alterations in apparent SP clearance. Side effects were frequent but were unrelated to SASP dose, SP concentrations, or acetylator phenotype. Disease activity did not significantly alter the serum protein binding of SP or ACSP. The decreased SP and ACSP concentrations seen in active disease may be due to a combination of disease related alterations in either cleavage of SASP or absorption and clearance of SP.


Prevalence of vulvovaginal candidiasis among pregnant women in the Ho municipality, Ghana: species identification and antifungal susceptibility of Candida isolates.
Candida is the leading cause of vaginitis, and 75% of women have at least one episode of infection in their lives, with pregnancy being a predisposing factor. If left untreated, vulvovaginal candidiasis (VVC) can lead to chorioamnionitis with subsequent abortion, prematurity and congenital infection of the neonate. We aimed to determine the prevalence of VVC, identify the recent and most frequently occurring species of Candida in pregnant women, and determine the most effective antifungal drug of choice for treatment. A prospective cross-sectional study in which 176 high vaginal swab samples of consented pregnant women visiting the antenatal clinic from February 2018 to April 2018 were subjected to direct gram smear and culture for Candida isolation. Candida isolates were identified using a germ tube test and HiCrome Candida differential agar. Candida isolates were then subjected to a disk diffusion method using fluconazole (25 μg), nystatin (100 units), and voriconazole (1 μg) on Mueller-Hinton agar supplemented with 2% (w/v) glucose and 0.5 μg/ml methylene blue dye to determine the susceptibility pattern as per the guidelines of the Clinical Laboratory Standard Institute (CLSI). Chi-square analysis was used to ascertain the significant association of participants' sociodemographics and clinical presentations to VVC. A univariate logistic regression model was used to identify potential risk factors of VVC. The prevalence of VVC among our study participants was 30.7%. Non-albicans Candida (NAC) and Candida albicans had a prevalence of 74.1 and 25.9%, respectively. Candida glabrata was the most common species, followed by Candida albicans, Candida krusei, and Candida parapsilosis. 50.0, 18.5 and 3.7% of Candida species were susceptible to voriconazole, fluconazole and nystatin, respectively, whereas 37.0, 48.1 and 9.3% of Candida species were resistant to voriconazole, fluconazole and nystatin, respectively. The majority of isolates were susceptible dose dependent to all three antifungal agents, with voriconazole being the most efficacious antifungal agent. There was no significant association between participants' socio-demographic information and clinical presentations to VVC. The prevalence of VVC was high in the study area. C. glabrata was found to be the most common cause of VVC among the pregnant women attending antenatal clinics, in the Ho Municipality region of Ghana. The majority of the Candida isolates were susceptible and resistant to voriconazole and fluconazole, respectively.


CD3 limits the efficacy of TCR gene therapy in vivo.
The function of T-cell receptor (TCR) gene modified T cells is dependent on efficient surface expression of the introduced TCR α/β heterodimer. We tested whether endogenous CD3 chains are rate-limiting for TCR expression and antigen-specific T-cell function. We show that co-transfer of CD3 and TCR genes into primary murine T cells enhanced TCR expression and antigen-specific T-cell function in vitro. Peptide titration experiments showed that T cells expressing introduced CD3 and TCR genes recognized lower concentration of antigen than T cells expressing TCR only. In vivo imaging revealed that TCR+CD3 gene modified T cells infiltrated tumors faster and in larger numbers, which resulted in more rapid tumor elimination compared with T cells modified by TCR only. After tumor clearance, TCR+CD3 engineered T cells persisted in larger numbers than TCR-only T cells and mounted a more effective memory response when rechallenged with antigen. The data demonstrate that provision of additional CD3 molecules is an effective strategy to enhance the avidity, anti-tumor activity and functional memory formation of TCR gene modified T cells in vivo.


Metabolism of cinobufagin in rat liver microsomes. Identification of epimerized and deacetylated metabolites by liquid chromatography/mass spectrometry.
The metabolism of cinobufagin (CB) in rat liver microsomes was studied. By comparison of retention times and fragmentation patterns obtained by thermospray LC/MS with those of authentic standards, four metabolites of CB were also identified, in addition to deacetylCB (M1) and 3-epideacetylCB (M2), which have been reported previously. The additional four metabolites were identified to be 3-epiCB (M4), 3-ketoCB (M5), 3-keto-16 beta-OH-deacetylCB (M3), and 3-keto-16 alpha-OH-deacetylCB (M6). The primary metabolic products of CB were M1 and M2, with a small amount of M4 and trace amounts of M3, M5, and M6. These results indicate that major metabolic routes of CB were deacetylation at the 16-position and epimerization at the 3-position via the 3-keto intermediate.


[Acute chemical poisoning of humans as a medico-ecological problem].
Anthropogenic acute chemical exposures have become an important socioeconomic and environmental factor on the national, regional and global level. They present an actual or potential danger to vital activity and health of large population groups and normal operation of the Biosphere and natural components. Hence a problem of prevention and elimination of acute technogenic exposures hazardous for human health has expanded beyond the medical competence and grown to a major environmental issue.


An improved LC-MS/MS method for determination of cinacalcet in human plasma and its application to the evaluation of food intake effect on the pharmacokinetics of cinacalcet in healthy volunteers.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of cinacalcet in human plasma was developed and validated. This assay was based on liquid-liquid extraction and cinacalcet-d4 was used as an internal standard (IS). Separation was achieved on a C18 column by the mobile phase A of water (containing 0.1% formic acid) and the mobile phase B of acetonitrile-water (95:5, v/v) (containing 0.2% formic acid) with gradient elution. Quantification was done using multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 358.2 → m/z 155.2 for cinacalcet and m/z 362.3 → m/z 155.0 for IS at positive ionization mode. The calibration curve was established over the range 0.05-20.0 ng/mL and the correlation coefficient was >0.99. The intra- and inter-day relative standard deviations were <5.8%. Accuracy determined at four concentrations ranged between 96.0 and 106.0%. This method was successfully applied to a pharmacokinetic description of oral dose of cinacalcet and the significant effect of food intake on the pharmacokinetics of cinacalcet was first demonstrated in Chinese healthy volunteers.


High prevalence of antibiotic allergies in cladribine-treated patients with hairy cell leukemia - lessons for immunopathogenesis and prescribing.
The relationship between hematological malignancy and chemotherapy on the prevalence of antibiotic allergy label (AAL) is ill-defined. We performed a multicenter retrospective case-control study comparing AAL rates among cladribine-treated hairy cell leukemia (C-HCL) cases, non-HCL cladribine-treated controls (control-1), and fludarabine-treated controls (control-2). The prevalence of AALs in C-HCL patients was 60%, compared with control-1 (14%, p < .01) and control-2 patients (25%, p < .01). The predominant phenotype was maculopapular exanthem (92%). The drugs implicated in AAL causality in C-HCL patients included beta-lactams (81%), trimethoprim-sulfamethoxazole (58%), and allopurinol (69%). C-HCL patients demonstrate high rates of AAL, potentially due to immune dysregulation, impacting beta-lactam utilization.


Vascular Risk Factors and Findings on Brain MRI of Elderly Adult American Indians: The Strong Heart Study.
Clinical stroke is prevalent in American Indians, but the risk factors for cerebrovascular pathology have not been well-studied in this population. The purpose of this study was to correlate abnormalities on brain magnetic resonance imaging (MRI) with clinical risk factors in a cohort of elderly American Indians. Brain MRI scans from 789 participants of the Strong Heart Study were analyzed for infarcts, hemorrhage, white matter disease, and measures of cerebral atrophy including ventricular and sulcal grade and total brain volume. Clinical risk factors included measures of hypertension, diabetes, and high levels of low-density lipoprotein (LDL) cholesterol. Regression models adjusted for potential confounders were used to estimate associations between risk factors and brain MRI outcomes. -Hypertension was associated with the presence of infarcts (p = 0.001), ventricle enlargement (p = 0.01), and increased white matter hyperintensity volume (p = 0.01). Diabetes was associated with increased prevalence of cerebral atrophy (p < 0.001), ventricular enlargement (p = 0.001), and sulcal widening (p = 0.001). High LDL was not significantly associated with any of the measured cranial imaging outcomes. This study found risk factors for cerebrovascular disease in American Indians similar to those seen in other populations and provides additional evidence for the important roles of hypertension and diabetes in promoting cerebral infarcts and brain atrophy, respectively.


Beta-adrenergic receptors in cancer: therapeutic implications.
The beta-adrenergic receptors transduce catecholamine signals to the G protein, which through a cascade of chemical reactions in cells generates highly specific parallel signals. The beta2-adrenergic receptor (ADRB2) is the most involved in the carcinogenic processes. Previous studies have determined the relationship of ADRB2 with various aspects related to cancer. Basically, it seems to be related with cell proliferation and apoptosis, chemotaxis, development of metastasis and tumor growth, and angiogenesis. The purpose of this review is to update the implications of these receptors in the pathogenesis of cancer and study the possible application of agonist drugs and/or antagonists in antitumor therapy.


Multiple cranial nerve enhancement in mitochondrial neurogastrointestinal encephalomyopathy.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disease that often presents with nonspecific white matter abnormalities on magnetic resonance imaging. Ptosis and ophthalmoparesis are a part of its clinical features. We report multiple cranial nerve contrast enhancement on magnetic resonance imaging in a patient with MNGIE and postulate that demyelination may be the responsible substrate for this previously unreported finding. This finding may also explain the cranial neuropathies that patients with MNGIE have.


Ruptured abdominal aortic aneurysm: endovascular repair is feasible in 40% of patients.
Open repair of ruptured abdominal aortic aneurysm (rAAA) still has a high mortality. Endovascular aortic repair (EVAR) may be the way to improve survival rates. However, it is not clear how many patients with rAAA will be suitable for acute EVAR. Between October 2000 and April 2002 all patients with acute symptomatic or ruptured AAA were assessed for EVAR on an intention-to-treat basis with emergency computed tomographic angiography (CTA). Patient and logistic characteristics were analysed. We used two commercially available aorto uni-iliac devices with a maximum proximal diameter of 28 and 34 mm. Five out of 26 patients were excluded for CTA and EVAR because of severe and persistent hypotension (3 pts) or logistic reasons (2 pts, both eligible). Twelve patients were found not eligible for EVAR due to unsuitable infrarenal aortic neck length (3 pts), neck diameter (1 pt) or a combination of both (8 pts). The remaining six patients were treated with EVAR. After 6 months no graft failure or aneurysm related deaths were recorded in the EVAR group. A total of 28% of patients with symptomatic or ruptured AAA was treated with EVAR. A potential 42% of patients could have been suitable for EVAR, if the correct devices had been in stock and all patients had been properly assessed.


Effects of bias and random error in anthropometry and in age on estimation of malnutrition.
This paper describes a method of calculating theoretic bias in estimates of malnutrition due to errors in anthropometry and age. By this method, bias in estimates of malnutrition measured by weight for age, height for age, arm circumference for age, and weight for height is obtained and presented for different levels of bias and random error in anthropometry and age.


Effect of dietary vitamin E and selenium on DNA damage in fresh and frozen tissues.
To determine whether deficiencies of dietary vitamin E and Se can elevate background DNA damage, rats were fed diets deficient in or supplemented with vitamin E (30 and 200 mg/kg diet) and Se (0.2 mg/kg diet) for 8 weeks. DNA damage was measured using the Comet (single-cell electrophoresis) assay and 8-oxodeoxyguanosine (8-oxo-dG) in liver, kidneys, and lymphocytes. We found that a deficiency of vitamin E and/or Se for 8 weeks did not significantly increase DNA damage in freshly isolated liver, kidneys, or lymphocytes. However, deficiency of vitamin E and/or Se for 8 weeks markedly increased DNA strand breaks in frozen kidney (-80 degrees C for 72 hours) and in lymphocytes incubated overnight at 37 degrees C, both of which were effectively prevented by supplementation of Se and vitamin E. However, vitamin E at 200 mg/kg did not afford more protection than it did at 30 mg/kg). Little or no significant increase in DNA damage was found in frozen livers. These results indicate that freezing or freeze-thawing of tissues may cause oxidative damage to DNA when the tissues are deficient in a major antioxidant, and that normal levels of vitamin E (30 mg/kg diet) and Se (0.2 mg/kg diet) are sufficient to prevent the damage. Thus, our results caution against the interpretation of DNA data obtained from frozen rat tissues or cells in animal studies with dietary vitamin E or Se deficiencies.


Treatment of chronic myelogenous leukemia with 3,3'-iminodi-1-propanol, dimethanesulfonate (ester), p-toluenesulfonate (NSC-140117) given orally.
A methanesulfonic acid ester of the aminoglycols, 3,3'-iminodi-1-propanol, dimethanesulfonate (ester), p-toluenesulfonate (NSC-140117) has been found to be very effective in inducing and maintaining complete remissions in early cases of chronic myelogenous leukemia. The drug was given in daily doses of 1-2 mg/kg for remission induction and 0.5-1.0 mg/kg for remission maintenance, with dose adjustment according to blood cell counts. It induced complete remissions (normal white blood cell count and complete disappearance of splenomegaly) in all nine patients treated and has been maintaining these remissions (as well as a complete remission which was originally induced by NSC-84641 in an additional patient) for a period of 2 1/3 + to 15 1/3 + months. The only toxic effect observed occurred in two patients who had mild discomfort in the upper abdomen associated with soft stools. We need further observations, however, regarding the chronic toxic effects of this drug. The myelosuppressive effect of NSC-140117, within the dose range used, is granulocyte specific and appears less long lasting than that of busulfan.


Pharmacometabonomics Analysis Reveals Serum Formate and Acetate Potentially Associated with Varying Response to Gemcitabine-Carboplatin Chemotherapy in Metastatic Breast Cancer Patients.
Gemcitabine-carboplatin (GC) chemotherapy was efficacious in metastatic breast cancer (MBC) patients probably resistant to anthracyclines and taxanes, but showed significant interindividual variation in treatment responses. Early prediction of response to treatment is clinically relevant to identify patients who will achieve clinical benefit. In this study, nuclear magnetic resonance (NMR) based pharmacometabonomics was used to noninvasively predict the response to GC chemotherapy of 29 MBC patients with prior exposure to both anthracyclines and taxanes from a phase II study. Formate and acetate levels in the baseline serum collected prior to GC chemotherapy were identified as potential predictive markers to select patients who will achieve clinical benefit and to identify those who should not be treated with the therapy to avoid futile treatment. The significantly lower baseline levels of serum formate and acetate in patients with resistant disease may reflect the higher demand of them as alternate/additional nutritional sources to fuel the accelerated proliferation of breast cancer cells that are biologically more aggressive or resistant to therapy. The results suggest that pharmacometabonomics can be a potential useful tool for predicting chemotherapy response in the context of precision medicine. Prospective studies with larger patient cohorts are required for validation of the findings.


Angular dependence of the Wigner time delay upon tunnel ionization of H2.
When a very strong light field is applied to a molecule an electron can be ejected by tunneling. In order to quantify the time-resolved dynamics of this ionization process, the concept of the Wigner time delay can be used. The properties of this process can depend on the tunneling direction relative to the molecular axis. Here, we show experimental and theoretical data on the Wigner time delay for tunnel ionization of H2 molecules and demonstrate its dependence on the emission direction of the electron with respect to the molecular axis. We find, that the observed changes in the Wigner time delay can be quantitatively explained by elongated/shortened travel paths of the emitted electrons, which occur due to spatial shifts of the electrons' birth positions after tunneling. Our work provides therefore an intuitive perspective towards the Wigner time delay in strong-field ionization.


Bioactivities of natural product geodin congeners and their preliminary structure activity relationship.
A series of 6 novel ester derivatives 2-7 of natural product geodin 1 were designed and semi-synthesized through one mild step reaction with high yield. Compounds 2-7 showed strong inhibitory activities against Staphylococcus aureus in the range of 2.35-9.41 μM. Compounds 4 and 7 showed very strong inhibitory activities against antifouling bacteria Aeromonas salmonicida with MICs of 2.42 μM and 4.56 μM respectively. Most notably compounds 3-7 showed potent antifungal activities against Candida albicans in the range of 0.59-2.44 μM. Particularly, compound 3 showed the highest antifungal activity against C. albicans with a MIC value of 0.59 μM. The preliminary structure activity relationship of these derivatives showed that replacement of 4-OH group with benzoyl substituents could enhance the antibacterial and antifungal activities of geodin 1.


Gender differences in primary antiphospholipid syndrome with vascular manifestations in 433 patients from four European centres.
Gender can influence incidence and clinical course of autoimmune diseases (ADs). Antiphospholipid syndrome (APS) is a rare AD characterised by thromboses and/or pregnancy morbidities and antiphospholipid antibodies (aPL) positivity. Our aim is to conduct a gender-oriented analysis of primary thrombotic APS (t-APS). Consecutive patients diagnosed with primary t-APS, followed from 1967 to 2019 in four European Centres, were enrolled. The cohort included 296 women and 137 men. Median age at onset [31 (24-46) vs. 41 (29-53) years, p<0.001] was lower in females. In women, venous thromboses were more frequent while, among males, arterial events prevailed. During follow-up, 14% of patients suffered at least two relapses and this occurred especially among males (22% vs. 10%, p=0.001). No gender differences were found in the aPL profile (33% single, 24% double and 43% triple aPL positivity). Most patients had concomitant risk factors (RFs) for thrombosis: established cardiovascular RFs were represented especially among men while estrogenic exposure was the main RF in women. Women presented mostly with venous thromboses at a younger age, while men with arterial events, later in life and suffered more recurrent events. This different frequency of arterial and venous thromboses could be attributed mainly to the presence of additional RFs rather than to biological gender-specific issues. However, some RFs are exclusive or more represented in one gender rather than the other, so assessing the link of causality between gender and manifestations of t-APS remains difficult.


Mechanisms of the amplifying pathway of insulin secretion in the β cell.
Pancreatic islet β cells secrete insulin in response to nutrient secretagogues, like glucose, dependent on calcium influx and nutrient metabolism. One of the most intriguing qualities of β cells is their ability to use metabolism to amplify the amount of secreted insulin independent of further alterations in intracellular calcium. Many years studying this amplifying process have shaped our current understanding of β cell stimulus-secretion coupling; yet, the exact mechanisms of amplification have been elusive. Recent studies utilizing metabolomics, computational modeling, and animal models have progressed our understanding of the metabolic amplifying pathway of insulin secretion from the β cell. New approaches will be discussed which offer in-roads to a more complete model of β cell function. The development of β cell therapeutics may be aided by such a model, facilitating the targeting of aspects of the metabolic amplifying pathway which are unique to the β cell.


[ABO system polymorphism in the Tunisian population].
A survey carried out on 18820 Tunisian blood donors enabled us to evaluate the distribution of ABO blood group in Tunisia. The genic frequencies in ABO system were as follows: A(0,192), B(0,122), O(0,686).


Ectopic neurogenesis in the forebrain cholinergic system-related areas of a rat dementia model.
Lesions to the fimbria fornix (FiFx) plus cingulate bundle (CB), the principal routes of communication of forebrain cholinergic regions, produce lasting impairment of spatial learning and memory in mice. We report that extensive neurogenesis takes place in the FiFx, CB, and basalis magnocellularis following FiFx plus CB transection. Immunofluorescence revealed that nestin-expressing cells were present in all 3 areas following lesion; the majority of nestin-positive cells were also positive for 5-bromo-2-deoxy-uridine, a marker of DNA synthesis. Nestin-positive proliferative cells were almost entirely absent from unlesioned tissue. Neurospheres cultured in vitro from lesioned FiFx displayed the characteristics of neural stem cells--proliferation, expression of embryonic markers, and multipotential differentiation into neurons, astrocytes, and oligodendrocytes. At early stages after transection, a small number of immature and migrating doublecortin-immunopositive neurons were detected in lesioned FiFx, where neuronal cell bodies are normally absent. At later stages, postlesion immature neurons developed into β-tubulin III-positive mature neurons. Lentivirus labeling assay implied that the injury-induced neurogenesis in FiFx may be from local neurogenic astrocytes but not from dentate gyrus. These results demonstrate that insult to cholinergic tracts can stimulate neural stem cell proliferation and neuronal regeneration not only in innervated regions but also in the projection pathways themselves. Ectopic neurogenesis in cholinergic system-related areas provides an additional mechanism for repair of cholinergic innervation following damage.


Rapid progression of an aortic lesion in a patient with aortitis syndrome.
In a 28-year-old woman with aortitis syndrome, repeated aortography revealed the development of a coarctation of the abdominal aorta occurring over a period of 1 year. Clinical and surgical examinations showed evidence of inflammation and ruled out other diseases during that time. This suggests that in cases of aortitis syndrome arterial lesions may show rapid progression over short time periods and in the absence of untoward events.


[Interpretation of Detection and identification standard of hookworm-Hook-worm larvae coproculture techniques (WS/T 791-2021)].
Detection and identification standard of hookworm-Hookworm larvae coproculture techniques (WS/T 791-2021) is the first recommended technical standard for hookworm detection and species identification using the hookworm larvae coproculture technique in China. This standard was issued on November 23, 2021, and had been in effect since May 1, 2022. This article provides a detailed interpretation pertaining to the background, drafting process, main contents, and dos and don'ts for better understanding and application of this standard among professionals working in disease control and prevention institutions and medical institutions.


Radical anionic versus neutral 2,2'-bipyridyl coordination in uranium complexes supported by amide and ketimide ligands.
The synthesis and characterization of (bipy)(2)U(N[t-Bu]Ar)(2) (1-(bipy)(2), bipy = 2,2'-bipyridyl, Ar = 3,5-C(6)H(3)Me(2)), (bipy)U(N[(1)Ad]Ar)(3) (2-bipy), (bipy)(2)U(NC[t-Bu]Mes)(3) (3-(bipy)(2), Mes = 2,4,6-C(6)H(2)Me(3)), and IU(bipy)(NC[t-Bu]Mes)(3) (3-I-bipy) are reported. X-ray crystallography studies indicate that bipy coordinates as a radical anion in 1-(bipy)(2) and 2-bipy, and as a neutral ligand in 3-I-bipy. In 3-(bipy)(2), one of the bipy ligands is best viewed as a radical anion, the other as a neutral ligand. The electronic structure assignments are supported by NMR spectroscopy studies of exchange experiments with 4,4'-dimethyl-2,2'-bipyridyl and also by optical spectroscopy. In all complexes, uranium was assigned a +4 formal oxidation state.


Curative irradiation of limited endobronchial carcinomas with high-dose rate brachytherapy. Results of a pilot study.
Pilot study to assess high-dose rate (HDR) brachytherapy as sole treatment for limited endobronchial non-small cell lung carcinomas. Proximal non-small cell lung cancer in a not previously irradiated area, with a maximal diameter of 1 cm, no visible tumor on CT scan, lack of other treatment options in patients with severe, chronic respiratory failure, surgery, or external radiotherapy for a previous lung cancer. Treatment was based on an escalating dose protocol. Patients received three to five fractions of 7 Gy prescribed at 10 mm from the center of the applicator, once a week. Nineteen patients were included in this trial. The first two patients received three fractions of 7 Gy, the four next patients received four fractions, and the 13 remaining patients were treated with five fractions of 7 Gy. Two months after the end of the procedure, tumors in 15 of 18 evaluable patients (83%) were locally controlled with negative results of biopsies. At 1 year, local control was still obtained in 12 of 16 evaluable patients (75%). With a mean follow-up of 28-months, 1-year and 2-year actuarial survival rates were 78% and 58%, respectively, with a 28-month median survival. One patient with local control died from hemoptysis 12 months after treatment. Two patients suffered from severe necrosis of the bronchial wall; one of them died from hemoptysis. HDR brachytherapy is an effective treatment for small endobronchial tumors. Late toxicity on the bronchial wall is still too high and was attributed mainly to contact between the catheter and the bronchial mucosa. Exclusive HDR brachytherapy should be restricted to carefully selected patients for whom there is no alternative curative treatment. New bronchial applicators and a lower dose per fraction may reduce the incidence and attenuate the severity of late complications.


[COMPLETE REMISSION OF METASTATIC RENAL CELL CARCINOMA AFTER PARTIAL NEPHRECTOMY FOLLOWING PEMBROLIZUMAB PLUS AXITINIB THERAPY: A CASE REPORT].
This case is a 62-year-old man diagnosed with metastatic renal cell carcinoma. He was referred to our department due to the left renal mass pointed with ultra sound examination. Radiographical examination showed left-side 42 mm renal tumor with multiple lung tumors, suggesting renal cell carcinoma, cT1bN0M1 (pul). As an induction therapy, we selected Pembrolizumab plus Axitinib combination therapy. After 4 course of the therapy, the left kidney tumor shrank to 27 mm, and the lung metastasis disappeared with computed tomography imaging. For the next step, we performed laparoscopic partial nephrectomy. The pathological diagnosis was clear cell carcinoma, grade 2 with central necrosis. Since then, complete remission has been maintained without any treatment for 21 months.


Digital Images Authentication Technique Based on DWT, DCT and Local Binary Patterns.
In the last few years, the world has witnessed a ground-breaking growth in the use of digital images and their applications in the modern society. In addition, image editing applications have downplayed the modification of digital photos and this compromises the authenticity and veracity of a digital image. These applications allow for tampering the content of the image without leaving visible traces. In addition to this, the easiness of distributing information through the Internet has caused society to accept everything it sees as true without questioning its integrity. This paper proposes a digital image authentication technique that combines the analysis of local texture patterns with the discrete wavelet transform and the discrete cosine transform to extract features from each of the blocks of an image. Subsequently, it uses a vector support machine to create a model that allows verification of the authenticity of the image. Experiments were performed with falsified images from public databases widely used in the literature that demonstrate the efficiency of the proposed method.


Synthesis, cytostatic, antimicrobial, and anti-HCV activity of 6-substituted 7-(het)aryl-7-deazapurine ribonucleosides.
A series of 80 7-(het)aryl- and 7-ethynyl-7-deazapurine ribonucleosides bearing a methoxy, methylsulfanyl, methylamino, dimethylamino, methyl, or oxo group at position 6, or 2,6-disubstituted derivatives bearing a methyl or amino group at position 2, were prepared, and the biological activity of the compounds was studied and compared with that of the parent 7-(het)aryl-7-deazaadenosine series. Several of the compounds, in particular 6-substituted 7-deazapurine derivatives bearing a furyl or ethynyl group at position 7, were significantly cytotoxic at low nanomolar concentrations whereas most were much less potent or inactive. Promising activity was observed with some compounds against Mycobacterium bovis and also against hepatitis C virus in a replicon assay.


Imprinted Igf2r silencing depends on continuous Airn lncRNA expression and is not restricted to a developmental window.
The imprinted Airn macro long non-coding (lnc) RNA is an established example of a cis-silencing lncRNA. Airn expression is necessary to initiate paternal-specific silencing of the Igf2r gene, which is followed by gain of a somatic DNA methylation imprint on the silent Igf2r promoter. However, the developmental requirements for Airn initiation of Igf2r silencing and the role of Airn or DNA methylation in maintaining stable Igf2r repression have not been investigated. Here, we use inducible systems to control Airn expression during mouse embryonic stem cell (ESC) differentiation. By turning Airn expression off during ESC differentiation, we show that continuous Airn expression is needed to maintain Igf2r silencing, but only until the paternal Igf2r promoter is methylated. By conditionally turning Airn expression on, we show that Airn initiation of Igf2r silencing is not limited to one developmental 'window of opportunity' and can be maintained in the absence of DNA methylation. Together, this study shows that Airn expression is both necessary and sufficient to silence Igf2r throughout ESC differentiation and that the somatic methylation imprint, although not required to initiate or maintain silencing, adds a secondary layer of repressive epigenetic information.


Determinant factors for chronic kidney disease after partial nephrectomy.
The objective of this review is to evaluate the factors that determine the development or deterioration of Chronic Kidney Disease (CKD) after partial nephrectomy (PN). When current literature is reviewed, it is found that factors that influence renal function after partial nephrectomy, are multifactorial. Those are divided into pre-surgical factors, such as hypertension, diabetes mellitus, urolithiasis, obesity, metabolic syndrome among others; intra-surgical factors, like the surgical technique used, the remaining healthy tissue, the experience of the surgeon, the time and type of ischemia among others. Lastly, post-surgical factors, also impose some influence on the post-surgical renal performance. It was also found that minimally invasive surgery, in addition to its known advantages, seems to offer a greater field of action in the future that will allow more nephrons preservation in any future surgical scenario. Finally, the current trend is to perform PN on all patients, in whom surgery is technically feasible regardless of the approach used, without risking oncological outcomes, patient safety, and without being exposed to any additional complications.


Nutrition, dental caries and periodontal disease: a narrative review.
To provide a narrative review of the role of macro- and micronutrients in relation to dental caries, gingival bleeding and destructive periodontal disease. This review is based on systematic reviews (when available) and comparative human studies. Dental caries cannot develop without the presence of dietary fermentable carbohydrates, in particular sugar. The susceptibility to develop caries in the presence of carbohydrates may be influenced by genetics and micronutrients such as vitamin D. Gingival bleeding and destructive periodontal disease are sensitive markers to both abnormalities in macronutrient content (excessive carbohydrates or poly-unsaturated fat intake, deficient protein intake) and micronutrient intake (e.g. vitamin C and B12). Dental caries and periodontal diseases are a sensitive alarm bell for an unhealthy diet, which predicts the future onset of the diseases of civilizations.


Comprehensive review of the evidence regarding the effectiveness of community-based primary health care in improving maternal, neonatal and child health: 6. strategies used by effective projects.
As part of our review of the evidence of the effectiveness of community-based primary health care (CBPHC) in improving maternal, neonatal and child health (MNCH), we summarize here the common delivery strategies of projects, programs and field research studies (collectively referred to as projects) that have demonstrated effectiveness in improving child mortality. Other articles in this series address specifically the effects of CBPHC on improving MNCH, while this paper explores the specific strategies used. We screened 12 166 published reports in PubMed of community-based approaches to improving maternal, neonatal and child health in high-mortality, resource-constrained settings from 1950-2015. A total of 700 assessments, including 148 reports from other publicly available sources (mostly unpublished evaluation reports and books) met the criteria for inclusion and were reviewed using a data extraction form. Here we identify and categorize key strategies used in project implementation. Six categories of strategies for program implementation were identified, all of which required working in partnership with communities and health systems: (a) program design and evaluation, (b) community collaboration, (c) education for community-level staff, volunteers, beneficiaries and community members, (d) health systems strengthening, (e) use of community-level workers, and (f) intervention delivery. Four specific strategies for intervention delivery were identified: (a) recognition, referral, and (when possible) treatment of serious childhood illness by mothers and/or trained community agents, (b) routine systematic visitation of all homes, (c) facilitator-led participatory women's groups, and (d) health service provision at outreach sites by mobile health teams. The strategies identified here provide useful starting points for program design in strengthening the effectiveness of CBPHC for improving MNCH.


Effect of Nanoparticle Concentration on Physical and Heat-Transfer Properties and Evaporation Characteristics of Graphite/n-Decane Nanofluid Fuels.
n-Decane-based nanofluid fuels could be one of the most promising alternative fuels as aviation kerosene for aerospace application. However, the physical and heat-transfer properties of n-decane-based nanofuels have been rarely studied, and the influence of the concentration of nanoparticles on the evaporation characteristics of n-decane-based fuels has been sparsely investigated. This paper investigated physical and heat-transfer properties and evaporation characteristics of graphite/n-decane nanofluid fuels and emphasized the concentration effect of adding graphite nanoplatelets (GNPs) on these characteristics. It was found that there are a linear increase of density and thermal conductivity, a binomial increase of viscosity, and a binomial influence on surface tension as GNP concentration increases, while the boiling point almost remains constant, and the latent heat of vaporization largely decays. There exists a critical GNP concentration of 1.75 wt % for the evaporation performance. At 0∼1.75 wt %, the increase of GNP concentration benefits the evaporation. At 1.75∼4.0 wt %, the enhancement of GNP concentration deteriorates the evaporation performance. A detailed discussion of this evaporation behavior was made, which could be attributed to multiple factors, for example, the aggregation of nanoplatelets, the changes of physical and heat-transfer properties owing to the nanoparticle concentration effect, the surfactant concentration, and the ambient temperature. The concentration of surfactants has a binomial effect, and the ambient temperature has a linear effect on the evaporation rate. This study would promote in depth understanding of physical and heat-transfer properties and evaporation characteristics of nanofluid fuels and develop the application in turbine engines and ramjet engines.


Effect of Progesterone on Latent Phase Prolongation in Patients With Preterm Premature Rupture of Membranes.
Preterm premature rupture of membranes (PPROM) is a condition leading to an increased risk of maternal and neonatal morbidity and mortality in pregnant women. To prevent this complication, some studies have proposed using prophylactic progesterone. However, due to lack of sufficient relevant data, there is still need for further studies in this regard. This study was performed to determine the effect of rectal progesterone on the latent phase and maternal and neonatal outcome variables in females with PPROM. During the present randomized clinical trial study (IRCT201512077676N4), a total of 120 patients with PPROM at pregnancy ages between 26 and 32 weeks were randomly assigned to 2 equal intervention and control groups. In the intervention group, progesterone suppositories (400 mg per night) were administered until delivery or completion of the 34th gestational week and was compared with placebo effect in control group. The latent phase and maternal and neonatal outcome variables were compared between the two groups. The mean age of patients was 29.56±5.66 (19-42) and 29.88±5.57 (17-40) years in the intervention and control group, respectively. The two groups were almost identical in the confounding factors. The median latent phase was 8.5 days in the intervention group vs. 5 days in the control group in the 28th-30th weeks of gestation, which was significantly higher in the intervention group (P=0.001). Among maternal and neonatal outcome variables, only the mean birth-weight was significantly higher in the intervention group than that in the controls (1609.92±417.28 gr vs. 1452.03±342.35 gr, P=0.03). Administration of progesterone suppository in patients with PPROM at gestational ages of 28 to 30 weeks is effective in elongating the latent phase and increasing birth-weight with no significant complications.


[Cholesteatoma otitis media and supratubal recess].
To study the significance of supratubal recess and its aeration pathway to epitympanum in the pathogenesis of cholesteatoma otitis media. Fifty-two ears of cholesteatoma were selected as study group. Sixteen ears of traumatic facial palsy with pneumatic mastoid, which had no history of chronic otitis media were selected as control group. The status of supratubal recesses of all and their aeration pathways to epitympanum were observed in operations. Sixteen ears from control group clearly presented supratubal recesses. Membrane closure was founded in four of them. The aeration pathways of fifty-two ears (100%) from study group were all completely closed. Comparing with control group, the difference was obviously significant (chi2 = 41.7144, P = 0.000). Among these cases, bony closure was observed in thirty-four ears (65.4%), while membrane closure in eighteen ears (34.6%). Their epitympanum space was very narrow and mastoid was sclerotic or poorly developed. Blockage of the aeration pathway between supratubal recess and epitympanum was possible one of the origins of negative-pressure status of epitympanum and mastoid, which might lead to the formation of aural cholesteatoma. Anatomy variation of the aeration pathway from supratubal recess to epitympanum might be a pathogenesis factor of cholesteatoma otitis media. It suggested that opening the aeration pathway in tympanoplasty with intact canal wall up technique might be helpful to prevent recurrence of aural cholesteatoma.


Association of six susceptibility Loci with prostate cancer in northern chinese men.
Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide association study (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotide polymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimed to explore the loci associated with PCa risk in a Northern Chinese population. Blood samples and clinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPs were genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and gene sequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA], Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPs were analyzed using genetic statistics. Among the candidate SNPs, 11p15 (rs7127900, A) was associated with PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09-2.46). Genotypes showed differences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796, A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positively associated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02-4.55). Patients carrying TG on 17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44, 95% CI = 0.21-0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P = 0.002). Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associated with PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleason score, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G) could be negatively associated with an increased BMI in Chinese men with PCa.


A novel ABCD1 gene mutation in a Chinese patient with X-linked adrenoleukodystrophy.
X-linked adrenoleukodystrophy (X-ALD) (OMIM: 300100) is a recessive neurodegenerative disorder caused by defects in the ABCD1 gene on chromosome Xq28. Childhood cerebral ALD (CCALD) is the most frequent phenotype. We describe an affected boy who developed normally until he was 8 years old then suffered progressive neurological deficits that ultimately led to death. Diagnosis was based on clinical symptoms, an abnormal very long chain fatty acid profile in plasma, typical CCALD MRI pattern, and molecular analysis. Direct sequencing of the ABCD1 gene in this patient identified a novel splicing mutation (IVS1+1G>A) in intron 1, which is considered to be the pathogenic mutation. We have identified a novel ABCD1 mutation as the likely cause of CCALD in a Chinese patient.


Asymptotic aspect of derivations in Banach algebras.
We prove that every approximate linear left derivation on a semisimple Banach algebra is continuous. Also, we consider linear derivations on Banach algebras and we first study the conditions for a linear derivation on a Banach algebra. Then we examine the functional inequalities related to a linear derivation and their stability. We finally take central linear derivations with radical ranges on semiprime Banach algebras and a continuous linear generalized left derivation on a semisimple Banach algebra.


Spontaneous production of colony-stimulating activity by splenic Mac-1 antigen-positive cells from autoimmune motheaten mice.
Cultured splenocytes from 3-wk-old autoimmune motheaten mice (me/me) spontaneously produced colony-stimulating activity (CSA), which stimulated the formation of bone marrow myeloid colonies. The production of CSA was not dependent on the presence of serum; this activity was not produced by spleen cells from their phenotypically normal littermates (+/-) or from other normal mouse strains. The peak level of CSA occurred early during the culture period, and within 48 hr the activity was markedly diminished. Cell fractionation studies demonstrated that cells expressing Mac-1 antigen produce CSA and are most likely to be mononuclear phagocytes. The unusual proliferative capacity in vitro of splenic mononuclear phagocytes from motheaten mice probably results from the spontaneous production of CSA by Mac-1 antigen-positive cells. Defective regulation of the production of monokines may contribute to the severity of the immunologic disease of these mutant mice.


Non-surgical radiofrequency facelift.
There has been considerable interest in using non-ablative methods to rejuvenate the skin. The ThermaCool TC (Thermage Inc.) is a radiofrequency (RF) device that has been introduced to induce tightening of the address the problem of skin via a uniform volumetric heating into the deep dermis tightening, resulting in a 'non-surgical facelift'. Radiofrequency produces a uniform volumetric heating into the deep dermis. Twenty treatment areas in 17 patients were treated to evaluate the efficacy and safety of RF treatment to the brow and jowls. The technique was found to produce gradual tightening in most patients, and there were no adverse effects.


Regulating human genomic research in Africa: why a human rights approach is a more promising conceptual framework than genomic sovereignty.
This article revisits the debate on the regulation of human genomic research, with a focus on Africa. The article comprehensively examines the concept of genomic sovereignty, which was invoked mainly in the global South as a conceptual framework for state regulation of human genomic research. It demonstrates that genomic sovereignty has no utility value in human genomic research as it violates the rights of individuals and researchers. By analysing Mexico's regulatory approach based on genomic sovereignty and a divergent regulatory approach, viz Finland's human genomic research framework, we show that a human rights approach is more promising as it aligns with the state obligations under the right of everyone to participate in and benefit from scientific progress and its applications in international human rights law. We conclude by recommending that African states should anchor regulation of human genomic research on a human rights framework based on the right to science.


The Development of a Provincial Food and Nutrition Strategy through Cross-Sector Collaboration.
A whole-system perspective is critical in efforts to create a healthy population and a productive, equitable, and sustainable food system. In 2009, the Ontario Collaborative Group on Healthy Eating and Physical Activity undertook a bold initiative to develop a comprehensive provincial strategy encompassing the entire food system. The Ontario Food and Nutrition Strategy was shaped through extensive consultation with diverse stakeholders. This strategy identified strategic directions and priority actions for productive, equitable, and sustainable food systems intended to promote the health and well-being of all Ontarians. Paramount to the strategy is a collaborative governance mechanism allowing for a cross-government, multistakeholder coordinated approach to food policy development. Key actors participated in a collective impact process to develop a theory of change and potential governance model. Different models for collaborative work were examined and a governance model for a multistakeholder coordinated provincial mechanism was proposed. Lessons learned from this process will inform others involved in food systems work at the provincial, regional, or local level and may pave the way towards successful inter-sectoral action on priority recommendations geared towards improved nutrition-related and food systems outcomes.


Atypical reversible leucoencephalopathy syndrome after bevacizumab/folfox regimen for metastatic colon cancer.
We are reporting a case of multifocal reversible leucoencephalopathy syndrome induced by chemotherapy based on Folfox-Bevacizumab regimen. A 44-year-old female, with no history of hypertension, received a chemotherapy based on Folfox-Bevacizumab for her metastatic colon cancer (5 FU: 325 mg/m(2) d1 by intravenous infusion, Oxaliplatin 80 mg/m(2) d1, and Bevacizumab: 7.5 mg/Kg d1). During the fourth cure, she presented delirium, seizures, and visual disturbances. The computed tomography (CT) of the brain showed hypodense lesions of the white matter of frontal, parietal, and occipital lobes, which were bilateral and symmetrical. The clinical table was reversible under symptomatic treatment.


Rutaecarpine alleviates renal ischemia reperfusion injury in rats by suppressing the JNK/p38 MAPK signaling pathway and interfering with the oxidative stress response.
In the present study, the protective effect and the potential underlying mechanism of rutaecarpine (Ru) on renal ischemia reperfusion injury (IRI) in rats were investigated. A renal ischemia reperfusion mouse model was established. Ru at 30, 60 mg/kg administered intraperitoneally prior to reperfusion led to attenuated renal injury. The results demonstrated that Ru treatment significantly reduced the content of serum creatinine, urea nitrogen and neutrophil gelatinase‑associated lipocalin in rats with renal IRI. In addition, Ru treatment improved the degree of renal proximal tubular necrosis, decreased the content of inflammatory cytokines in reperfused renal tissue and increased serum superoxide dismutase levels to protect the kidney. The associated underlying mechanism may involve the inhibition of p38 kinase phosphorylation and c‑Jun N‑terminal kinase, anti‑lipid peroxidation, elimination of free radicals, and a reduction in the degree of apoptotic damage and oxidative stress injury induced by renal IRI. Therefore, Ru may be a suitable compound for the prevention and treatment of renal IRI.


High affinity binding of latent matrix metalloproteinase-9 to the alpha2(IV) chain of collagen IV.
Association of matrix metalloproteinases (MMPs) with the cell surface and with areas of cell-matrix contacts is critical for extracellular matrix degradation. Previously, we showed the surface association of pro-MMP-9 in human breast epithelial MCF10A cells. Here, we have characterized the binding parameters of pro-MMP-9 and show that the enzyme binds with high affinity (Kd approximately 22 nM) to MCF10A cells and other cell lines. Binding of pro-MMP-9 to MCF10A cells does not result in zymogen activation and is not followed by ligand internalization, even after complex formation with tissue inhibitor of metalloproteinase-1 (TIMP-1). A 190-kDa cell surface protein was identified by ligand blot analysis and affinity purification with immobilized pro-MMP-9. Microsequencing and immunoblot analysis revealed that the 190-kDa protein is the alpha2(IV) chain of collagen IV. Specific pro-MMP-9 surface binding was competed with purified alpha2(IV) and was significantly reduced after treatment of the cells with active MMP-9 before the binding assay since alpha2(IV) is hydrolyzed by MMP-9. A pro-MMP-9.TIMP-1 complex and MMP-9 bind to alpha2(IV), suggesting that neither the C-terminal nor the N-terminal domain of the enzyme is directly involved in alpha2(IV) binding. The closely related pro-MMP-2 exhibits a weaker affinity for alpha2(IV) compared with that of pro-MMP-9, suggesting that sites other than the gelatin-binding domain may be involved in the binding of alpha2(IV) to pro-MMP-9. Although pro-MMP-9 forms a complex with alpha2(IV), the proenzyme does not bind to triple-helical collagen IV. These studies suggest a unique interaction between pro-MMP-9 and alpha2(IV) that may play a role in targeting the zymogen to cell-matrix contacts and in the degradation of the collagen IV network.


Capillary electrophoresis of r-hirudin and a polyethylene glycol derivative of r-hirudin (PEG-hirudin).
Recombinant (r-) hirudins and PEG-hirudin are currently tested for anticoagulant therapy. For their concentration measurement, radioimmunoassay and HPLC methods are available. The separation of r- and PEG-hirudin is currently performed by HPLC. However, the sensitivity of the method is low. Capillary electrophoresis is a rapid, selective technique that requires low sample amounts. Our aim was the development of a capillary electrophoresis method to measure r- and PEG-hirudin. The results are as follows: In a borate solution (0.3% boric acid and 0.4% sodium tetraborate, pH 9.5) r-hirudin was separated from PEG-hirudin in a purified system using a fused silica capillary (50 cm long and 75-micron i.d. and reversed polarity). A neutral capillary with a 20 mM tricine buffer (pH 8.0, field strength 500 V/cm) was also effective in resolving r- from PEG-hirudin. A linear correlation was found between the peak area and the concentration between 20 micrograms/mL and 10 mg/mL for hirudin (r2 = 0.99) and between 1.25 and 10 mg/mL for PEG-hirudin (r2 = 0.99). In human plasma mixtures, r- and PEG-hirudin were completely separated. The linear correlation between the peak area and the concentration was r2 = 0.99. In a fused silica capillary, r- and PEG-hirudin are separated in a purified system. Capillary electrophoresis which is performed in a neutral capillary, resolves r- from PEG-hirudin in a purified system, in plasma and in urine. The sensitivities of the methods are comparable. Capillary electrophoresis separates r- from PEG-hirudin and may be applied to biologic systems to measure the concentration and purity of r- and PEG-hirudin.


[Neuroleptanesthesia for a patient with mitochondrial encephalomyopathy].
This report describes a patient with mitochondrial encephalomyopathy who underwent an ophthalmic surgery under original neuroleptanesthesia. This 28-year-old female patient had been suffering from bilateral external ophthalmoplegia and blepharoptosis. Her preoperative neurological examination revealed a mitochondrial encephalomyopathy. Biopsy and blepharo-elevation for her left eyelid were scheduled. Anesthesia was induced with thiopental 5 mg.kg-1 and vecuronium 0.07 mg.kg-1, and maintained with total doses of 10 mg of droperidol, 400 micrograms of fentanyl and 4 mg of vecuronium. The patient recovered from anesthesia smoothly and her postoperative course was uneventful. Anesthetic management of patients with this disease and possible complications were discussed.


Update on multikinase inhibitor therapy for differentiated thyroid cancer.
Curative therapies for radioiodine-refractory differentiated thyroid cancer remain lacking. However, oral multikinase inhibitors often allow for disease control and improved progression-free survival. Two agents, lenvatinib and sorafenib, have been approved for radioiodine-refractory differentiated thyroid cancer on the basis of phase III clinical trials showing marked response rates and improved progression-free survival over placebo. Several other multikinase inhibitors, including apatinib, axitinib, cabozantinib, pazopanib, sunitinib and vandetanib, have also been studied in phase II clinical trials, with varying response rates and comparable progression-free survival. Selective kinase inhibitors, including dabrafenib, vemurafenib, selumetinib and gefitinib, offer a more targeted approach and have also been studied in phase II clinical trials. While the emergence of these treatments has changed the landscape of management of advanced thyroid cancer, clinical challenges remain, and there are many areas of ongoing research.


In Silico Prediction of PAMPA Effective Permeability Using a Two-QSAR Approach.
Oral administration is the preferred and predominant route of choice for medication. As such, drug absorption is one of critical drug metabolism and pharmacokinetics (DM/PK) parameters that should be taken into consideration in the process of drug discovery and development. The cell-free in vitro parallel artificial membrane permeability assay (PAMPA) has been adopted as the primary screening to assess the passive diffusion of compounds in the practical applications. A classical quantitative structure-activity relationship (QSAR) model and a machine learning (ML)-based QSAR model were derived using the partial least square (PLS) scheme and hierarchical support vector regression (HSVR) scheme to elucidate the underlying passive diffusion mechanism and to predict the PAMPA effective permeability, respectively, in this study. It was observed that HSVR executed better than PLS as manifested by the predictions of the samples in the training set, test set, and outlier set as well as various statistical assessments. When applied to the mock test, which was designated to mimic real challenges, HSVR also showed better predictive performance. PLS, conversely, cannot cover some mechanistically interpretable relationships between descriptors and permeability. Accordingly, the synergy of predictive HSVR and interpretable PLS models can be greatly useful in facilitating drug discovery and development by predicting passive diffusion.


Burden and Causes of Hospital Admissions in Heart Failure During the Last Year of Life.
This study aimed to evaluate the incidence and causes of hospitalization in the year preceding death of patients with heart failure (HF). Hospitalizations in HF are common, especially in the last period of the lives of patients with HF, but little is known about hospitalization burden and causes during this phase of the disease. From Danish nationwide registries, we identified patients who died in the period 2001-2016 after having experienced HF for at least 1 year, and examined hospitalizations during the last year of life in age- and sex-stratified analyses. We included 32,157 patients. Median age at time of death was 81 years; 39% were women. A total of 26,561 (84%) patients were hospitalized at least once during the last year of life. The patients experienced a median of 2 (1 to 3) hospitalizations and spent 14 (3 to 31) days in the hospital. Of all hospitalizations (n = 80,362), 9,644 (12%) were due to HF, 14,738 (18%) due to other cardiovascular (CV) causes, and 51,696 (64%) due to non-CV causes (p < 0.001). The frequency of hospitalizations increased toward death, but the domination of non-CV causes remained consistent throughout the year, regardless of age and sex. If we included diagnoses covering renal insufficiency in the definition of HF hospitalizations, non-CV hospitalizations remained dominant (58%). During the last year alive, patients with HF were more often hospitalized due to non-CV causes rather than HF. These findings warrant more focus on a multidisciplinary approach toward end-of-life care in patients with HF.


Transcriptomic Analysis of Salivary Glands of Ornithodoros brasiliensis Aragão, 1923, the Agent of a Neotropical Tick-Toxicosis Syndrome in Humans.
Tick salivary glands produce and secrete a variety of compounds that modulate host responses and ensure a successful blood meal. Despite great progress made in the identification of ticks salivary compounds in recent years, there is still a paucity of information concerning salivary molecules of Neotropical argasid ticks. Among this group of ticks, considering the number of human cases of parasitism, including severe syndromes and hospitalization, Ornithodoros brasiliensis can be considered one of the major Neotropical argasid species with impact in public health. Here, we describe the transcriptome analysis of O. brasiliensis salivary glands (ObSG). The transcriptome yielded ~14,957 putative contigs. A total of 368 contigs were attributed to secreted proteins (SP), which represent approximately 2.5% of transcripts but ~53% expression coverage transcripts per million. Lipocalins are the major protein family among the most expressed SP, accounting for ~16% of the secretory transcripts and 51% of secretory protein abundance. The most expressed transcript is an ortholog of TSGP4 (tick salivary gland protein 4), a lipocalin first identified in Ornithodoros kalahariensis that functions as a leukotriene C4 scavenger. A total of 55 lipocalin transcripts were identified in ObSG. Other transcripts potentially involved in tick-host interaction included as: basic/acid tail secretory proteins (second most abundant expressed group), serine protease inhibitors (including Kunitz inhibitors), 5' nucleotidases (tick apyrases), phospholipase A2, 7 disulfide bond domain, cystatins, and tick antimicrobial peptides. Another abundant group of proteins in ObSG is metalloproteases. Analysis of these major protein groups suggests that several duplication events after speciation were responsible for the abundance of redundant compounds in tick salivary glands. A full mitochondrial genome could be assembled from the transcriptome data and confirmed the close genetic identity of the tick strain sampled in the current study, to a tick strain previously implicated in tick toxicoses. This study provides novel information on the molecular composition of ObSG, a Brazilian endemic tick associated with several human cases of parasitism. These results could be helpful in the understanding of clinical findings observed in bitten patients, and also, could provide more information on the evolution of Neotropical argasids.


Optimal place of treatment for young infants aged less than two months with any low-mortality-risk sign of possible serious bacterial infection: Study Protocol for a randomised controlled trial from low- and middle-income countries.
World Health Organization (WHO) recommends hospitalisation and injectable antibiotics for clinical sepsis / possible serious bacterial infection (PSBI) in young infants up to two months of age. However, some young infants with low-mortality risk signs of PSBI may not require hospitalisation, for which evidence needs to be generated. This is a protocol for a multicentre, individually randomised, open-label trial that will be conducted in seven sites in six countries Bangladesh, Ethiopia, India (two sites), Nigeria, Pakistan and Tanzania. All sites will use this common protocol with the same study design, inclusion of participants, intervention, comparison, and outcomes, as well as quality control and analysis procedures to contribute to the overall sample size. All young infants (age <60 days) presenting at study hospitals with any single low-mortality risk sign (high body temperature ≥38°C, severe chest indrawing, or fast breathing of ≥60 breaths per minute in <7 days old infants) will be randomised to either outpatient care with injectable gentamicin for two days and oral amoxicillin for seven days (intervention) or inpatient care with injection gentamicin plus injection ampicillin along with supportive treatment, where needed, for seven days (control). We plan to enrol 7000 eligible young infants, 3500 infants in each of the two study arms. A trained and standardised independent outcome assessor will visit all enrolled cases on days two, four, eight and 15 post-randomisation to assess the study outcomes in both intervention and control groups. The primary outcome of poor clinical outcome, defined as death within two weeks of initiation of treatment, deterioration during the 7-day treatment period, or persistence of the presenting sign at the end of the 7-day treatment period, will be compared to assess if the outpatient treatment leads to superior or at least non-inferior clinical outcome than inpatient treatment. The selected sites have extensive research experience. The methods and all study procedures will be harmonised through central training of research staff by WHO, standardisation exercises for clinical signs, central data coordination centre and internal and external monitoring. Continuous evaluation of the enrolment by the sites will be carried out through regular calls, databased monitoring, and site visits by WHO monitors. This trial has received ethical approvals from the WHO and local site institutional ethics committees. If the results show that young infants with any single low-mortality risk PSBI sign can be effectively and safely treated on an outpatient basis, it may substantially increase access to treatment for infants and families with poor access to health facilities. It may also reduce the human, financial and material costs to the health system and allow the currently overloaded health facilities to focus on more critically ill infants. This evidence will contribute toward making a case for reviewing the current WHO PSBI management guideline. International Standard Randomised Controlled Trial Number ISRCTN44033252.


Anti-apoptotic potential of gymnemic acid phospholipid complex pretreatment in Wistar rats with experimental cardiomyopathy.
Cardiomyocyte apoptosis in heart failure has been the topic of research in many recent studies. In the present investigation, the potential cardioprotective effect of gymnemic acid phospholipid complex (GPC) on myocardial apoptosis and cardiac function was studied in doxorubicin (DOX; 30 mg/kg/ip/single dose)-induced cardiomyopathy model in rats. Doxorubicin induced cardiomyopathy was evidenced by significant hemodynamic changes (increased systolic, diastolic, mean arterial pressure and heart rate), decreased heart weight to body weight ratio, increase in serum lactate dehydrogenase (LDH) and Ca2+ levels and decrease in myocardial Na+/K+ ATPase levels along with caspase-3 activation. A marked reduction in glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase and catalase levels along with increase in the levels of thiobarbituric acids (TBARS) were also observed in rat myocardium. In addition, DNA laddering observed on agarose gel electrophoresis and cardiac histopathology study further supplemented myocardial apoptosis. Pre-treatment with GPC significantly reduced DOX-induced cardiac toxicity, including improvement of hemodynamic variables and heart weight to body weight ratio, decreased serum Ca2+ level and LDH levels, myocardial caspase-3 levels, increased Na+/K+ ATPase levels and decreased myocardial TBARS levels and elevated antioxidant enzymes as compared to pathogenic control group. Further, the anti-apoptotic effect of GPC was verified by prevention of internucleosomal DNA laddering on agarose gel electrophoresis and attenuation of histopathological perturbations by doxorubicin. These observations demonstrate that GPC might serve as a cardioprotective formulation in DOX-induced cardiomyopathy in rats.


Separation and Enrichment of Antioxidant Peptides from Whey Protein Isolate Hydrolysate by Aqueous Two-Phase Extraction and Aqueous Two-Phase Flotation.
At present, peptides are separated by molecular exclusion chromatography and liquid chromatography. A separation method is needed in any case, which can be scaled up for industrial scale. In this study, aqueous two-phase extraction (ATPE) and aqueous two-phase flotation (ATPF) were applied to separate and enrich antioxidant peptides from trypsin hydrolysates of whey protein isolates (WPI). The best experimental conditions were investigated, and the results were evaluated using the 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) free radical scavenging activity of the peptides-per-unit concentration and the recovery rate (Y) of peptides in the top phase of both ATPE and ATPF. Under optimal conditions, the Y and ABTS free radical scavenging activity per unit concentration in top phase of ATPE could reach 38.75% and 12.94%, respectively, and in ATPF could reach 11.71% and 29.18%, respectively. The purified peptides were characterized by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and reversed-phase high-performance liquid chromatography (RP-HPLC). PeptideCutter and PeptideMass were applied to analyze and calculate the peptide sequencing. KILDKVGINYWLAHK, VGINYWLAHKALCSEK, and TPEVDDEALEKFDKALK sequences having antioxidant activity were detected in the top phase of ATPE, and VGINYWLAHKALCSEK, KILLDKVGINYWLAHK, ILLDKVGINYWLAHK, IIAEKTKIPAVFK, KIIAEKTKIPAVFK, and VYVEELKPTPEGDLEILLQK sequences having antioxidant activity were detected in the top phase of ATPF. In conclusion, antioxidant peptides were successfully separated from the WPI hydrolysate by ATPE and ATPF; compared with ATPE, ATPF has superior specificity in separating antioxidant peptides.


Estrus synchronization in sheep and goats using combinations of GnRH, progestagen and prostaglandin F2alpha.
The objective of this experiment was to evaluate the effect of GnRH, progestagen and prostaglandin F(2alpha) on estrus synchronization in sheep and goats. Sixty Awassi ewes and 53 Damascus does were used in the study. The experiment started at the beginning of the breeding season (June/July). The same treatments were applied to sheep and goats as follows: no treatment (CON), 14-day progestagen sponges and 600 IU equine chorionic gonadotropin (S), gonadotropin releasing hormone followed 5 days later by prostaglandin F(2alpha) (GP) and gonadotropin releasing hormone, progestagen sponges for 5 days and prostaglandin F(2alpha) on the day of sponge removal (GSP). None of the ewes in the S group lambed from mating during the induced cycle. A greater lambing rate (p < 0.05) was observed in the GSP group compared with the CON and S groups while the GP group was intermediate. The number of lambs born per lambed ewe was similar among the CON, GP and GSP groups. However, the number of lambs per exposed ewe was greater (p < 0.05) in the GSP than the remaining groups. The induced cycle kidding rate was 77% for all treatments combined. Similar kidding rate were observed among treatments. The numbers of kids born per kidded and exposed doe from mating during the induced estrus were also similar among treatments. Greater numbers of multiple births were observed in the GP and GSP than in the S group. In conclusion, a combination of GnRH, progestagen sponges and PGF(2alpha) can be effective in synchronizing estrus and improving fecundity in sheep and goats. Although the use of GnRH-PGF(2alpha) was effective, the addition of progestagen sponges at the time of GnRH administration appeared to improve reproductive parameters.


Identification of gene loci controlling pectate lyase production and soft-rot pathogenicity in Pseudomonas marginalis.
Pseudomonas marginalis is an important postharvest pathogen capable of causing soft rot in a wide variety of harvested fruits and vegetables. Following transposon mutagenesis, we isolated two groups of P. marginalis CY091 mutants deficient in production of pectate lyase (Pel) and soft-rot pathogenicity in plants. The first group, designated Pel-, was caused by the insertion of Tn5 into a pel structural gene, and the second group, designated LemA-, was caused by the insertion of Tn5 into a regulatory locus corresponding to the lemA gene previously identified in other Gram-negative bacteria. The LemA- mutants also exhibited alteration in colony morphology and showed deficiency in production of protease (Prt). A cosmid clone pCIC carrying the P. marginalis lemA gene was isolated and characterized. pCIC was capable of restoring Pel production and soft-rot pathogenicity in LemA- mutants of P. marginalis and Pseudomonas viridiflava, indicating that the function of lemA gene in these two pseudomonads was similar and interchangeable. Using MudI-mediated mutagenesis, we isolated a third group of P. marginalis mutants deficient in production of Pel, Prt, and soft-rot pathogenicity. Mutants in this group (designated GacA-1) contained an insertion of MudI in a locus corresponding to the gacA gene of P. viridiflava. Like LemA- mutants, GacA- mutants also exhibited alteration in colony morphology and showed deficiency in production of Pel and Prt. However, GacA- mutants produced much lower levels of levan and fluorescent pyoverdine siderophore than the wild type and LemA- mutants. These results provide the first genetic evidence that P. marginalis produces a single alkaline Pel for maceration of plant tissue and demonstrate that production of Pel, Prt, levan, and pyoverdin by this bacterium is mediated by the two-component lemA/gacA gene system.


Transition from pediatric to adult medical care - A survey in young persons with inflammatory bowel disease.
Transition to adult health services is a vulnerable phase in young persons with chronic disease. We describe how young persons with inflammatory bowel disease in Germany and Austria experience care during the transitional age, focusing on differences by type of provider (pediatric vs. adult specialist, no specialist). This was a follow up survey in patients previously registered with a pediatric IBD registry. Patients aged 15 to 25 received a postal questionnaire, including a measure of health care experience and satisfaction. Descriptive analyses were stratified by age. Sub-analyses in the 18-20 year age group compared health care experience by type of provider. Determinants of early or late transfer were examined using multinomial logistic regression. 619 patients responded to the survey; 605 questionnaires were available for analysis. Usual age of completing transition was 18. Earlier transfer was more common with low parental SES (OR 1.8, 95% CI 0.7 to 4.6), and less common with advanced schooling (OR 0.5, 95% CI 0.2 to 1.2). Structured transition was uncommon. 48% of the respondents had not received any preceding transition advice. Overall satisfaction with IBD care was high, especially with respect to interpersonal aspects, but less so in aspects of continuity of care. Despite high overall patient satisfaction, relevant deficiencies in transitional care were documented. Some of these were associated with lower parental social status. Differences in health care satisfaction by type of provider (adult vs. pediatric) were small.


Solvent- and thermoresponsive polyrotaxanes with beta-cyclodextrin dispersed/aggregated structures on a pluronic F127 backbone.
A series of polyrotaxane-based triblock copolymers comprising beta-cyclodextrins (beta-CDs) threaded onto a distal 2-bromopropionyl end-capped Pluronic F127 as a central block and poly(N-isopropylacrylamide) outer blocks as end-stoppers were prepared via ATRP of N-isopropylacrylamide in aqueous solution. The structure of the resulting copolymers was characterized in detail by (1)H NMR, (13)C NMR, GPC, and WXRD techniques. Unlike those CD-based polyrotaxanes exhibiting the characteristic tunnel-type crystal structure, these copolymers precipitated from DMF with anhydrous ether preserve a dispersed-state structure in which the beta-CDs are loosely distributed along the Pluronic F127 chain, while they present an aggregated structure in which the beta-CDs are densely stacked one by one along the polymer backbone, holding the typical tunnel-like crystal structure after incubation in water and freeze-drying. The beta-CD dispersed and aggregated states are convertible by the incubation or precipitation treatments. Furthermore, annealing at various temperatures manifests them having the thermoresponsibility in the solid state. These copolymers containing the beta-CD dispersed structure possess an imperfect crystal PEO domain, while those with the beta-CD aggregated structure hold both a microcrystal and an imperfect crystal PEO domain. Hence, the as-prepared polyrotaxane-based triblock copolymers are not only solvent-sensitive but also thermoresponsible supramolecular materials.


Comparative assessment of different percutaneous endoscopic interlaminar lumbar discectomy (PEID) techniques.
Percutaneous endoscopic lumbar discectomy is a common surgical treatment for lumbar disc herniation, and percutaneous endoscopic interlaminar lumbar discectomy (PEID) is commonly used for direct decompression of L5-S1. Like microdiscectomy, recurrence of herniation after endoscopic discectomy is an important problem. In this study, we aimed to decrease the recurrence after PEID using a new surgical technique. We propose a new surgical technique for reducing the recurrence after PEID for lumbar disc herniation. The new technique uses annular sealing after fragmentectomy. We compared clinical results and recurrent lumbar disc herniation (had radiculopathy and confirmed by MRI) between patients who underwent surgery with and without annular sealing during PEID. Retrospective cohort study of patients undergoing PEID. A total of 224 patients with radiculopathy due to L5-S1 disc herniation who were treated by PEID with (91 patients) or without annular sealing (133) were included in this study. We compared the demographic characteristics (age, sex, height, weight, BMI, smoking status, and occupation), clinical results, and recurrence rates between the 2 groups. We classified recurrence according to time period (early recurrence ≤ 6 months, late recurrence > 6 months). The study groups were demographically similar, and substantial improvement in clinical results was noted. There were 5 recurrences (5.5%) (2 early, 3 late recurrences) in the group with annular sealing, and 18 (13.5%) (13 early, 5 late recurrences) in the group without annular sealing. Early recurrence rates were significantly higher in the group without sealing (2 vs. 13, P = 0.029). Increasing age was associated with overall recurrence (P = 0.004) and late recurrence (P = 0.008), while operative technique correlated with early recurrence (P = 0.026). First, this study incorporates a retrospective design. Second, the operations were performed by 2 surgeons. Additionally, this is relatively a short-term follow-up study (mean 19.5 ± 5.0 months). Though a learning curve is needed in order to become familiar with PEID, recurrence after PEID was associated with advanced age, and PEID with annular sealing resulted in lower early recurrence rates than without annular sealing. Thus, PEID with annular sealing may be a useful technique for reducing early recurrence.


The present and the future of neuroimaging in amyotrophic lateral sclerosis.
In patients with ALS, conventional MR imaging is frequently noninformative, and its use has been restricted to excluding other conditions that can mimic ALS. Conversely, the extensive application of modern MR imaging-based techniques to the study of ALS has undoubtedly improved our understanding of disease pathophysiology and is likely to have a role in the identification of potential biomarkers of disease progression. This review summarizes how new MR imaging technology is changing dramatically our understanding of the factors associated with ALS evolution and highlights the reasons why it should be used more extensively in studies of disease progression, including clinical trials.


[Otologic determining factors on infra-red tympanic thermometry in children].
To evaluate the influence of different otoscopic findings on body thermometry in children using an infra-red tympanic thermometer. Body temperature was measured on healthy right and left ear canals with Thermoscan systems. Moreover, it was determined on children with altered otoscopy, companng to normal contralateral ear. To assess its diagnostic fiability, accuracy ratios were calculated in different temperatures. Temperature measured bilaterally did not offer differences, and intra/interassay variation ratios were always less than 0.34%. Acute otitis externa increased tympanic thermometry a mean of 0.36 degrees C (p < 0.001), and cerumen and previously radical surgery decreased a mean of 0.62 and 0.53 degrees C, respectively (p < 0.001). The conditions mentioned before modify body thermometry if measured by infra-red tympanic thermometer. So, this system must be avoided in these circumstances. Otitis media, fluid in middle ear, tympanic perforation and ventilation tubes did not modify thermometric results.


Escherichia coli K-12 has two distinguishable PriA-PriB replication restart pathways.
In Escherichia coli, PriA, PriB, PriC, and DnaT proteins mediate three pathways for Replication Restart called PriA-PriB, PriA-PriC, and PriC. PriA is crucial for two of the three pathways. Its absence leads to slow growth, high basal levels of SOS expression, poorly partitioning nucleoids, UV sensitivity, and recombination deficiency. PriA has ATPase and helicase activities and interacts with PriB, DnaT, and single-stranded DNA-binding protein (SSB). priA300 (K230R) and priA301 (C479Y) have no phenotype as single mutants, but each phenocopy a priA-null mutant combined with ∆priB. This suggested that the two priA mutations affected the helicase activity that is required for the PriA-PriC pathway. To further test this, the biochemical activities of purified PriA300 and PriA301 were examined. As expected, PriA300 lacks ATPase and helicase activities but retains the ability to interact with PriB. PriA301, however, retains significant PriB-stimulated helicase activity even though PriA301 interactions with PriB and DNA are weakened. A PriA300,301 variant retains only the ability to interact with DNA in vitro and phenocopies the priA-null phenotype in vivo. This suggests that there are two biochemically and genetically distinct PriA-PriB pathways. One uses PriB-stimulated helicase activity to free a region of ssDNA and the other uses helicase-independent remodeling activity.


Resonance-thrombography indices of the haemostatic process in relation to risk of incident coronary heart disease: 9 years follow-up in the Caerphilly Prospective Heart Disease Study.
Global assays, such as resonance-thrombography (RTG), which measure the interaction between platelets, coagulation and fibrinolysis have been used as summary measures of risk for over two decades but have not been evaluated in epidemiological studies. We examined whether RTG indices are risk indicators for incident coronary heart disease (CHD). RTG indices, related haematological variables and other risk factors were measured between 1984 and 1988 in a cohort of 2398 British men. Reaction time (r) and amplitude of fibrin leg (AF) were associated with lifestyle risk factors. During 9 years of follow-up, 282 (12%) men developed a major new CHD event, as classified by World Health Organization criteria. On adjustment for age, only r and AF measured at baseline were related to risk of incident CHD. On multivariate adjustment in a multiple logistic regression model that included age, diastolic blood pressure, body mass index, total and high-density lipoprotein cholesterol, lifestyle risk factors and use of prescribed medicine, these associations weakened but remained significant. Additional adjustment for fibrinogen, viscosity, white cell count and fibrin d-dimer either reduced these associations to non-significance (AF) or to borderline significance (r).


A ZONE OF OVERLAP AND HYBRIDIZATION BETWEEN TWO GROUND CRICKET SPECIES.
In this paper I describe a zone of overlap and hybridization between the ground crickets, Allonemobius fasciatus and A. socius (Orthoptera: Gryllidae). The former occurs in the northeastern United States, the latter is found in the southeastern United States. They meet in a contact zone of variable width that extends from the East Coast to at least Ohio. In the Allegheny Mountains, where appropriate habitats for a species adapted to a northern climate and a species adapted to a southern climate are patchily distributed and widely intermingled, the zone is broad-at least 200 km. Along the coastal plain of New Jersey, where appropriate habitats are not as widely intermingled, the zone is comparatively narrow (5-100 km). Levels of hybridization were assessed by analyzing electrophoretic data, using population genetic models and a character index approach. Both methods of data analysis agreed-where the zone is broader, levels of hybridization appear reduced.


An atypical case of atypical lipomatous tumor.
A 56-year-old woman was referred to us with an asymptomatic nodule on the thigh. The nodule was about 11x7 cm in diameter with a well-demarcated, smooth, surface. Magnetic resonance imaging showed the intensity of the nodule to be entirely monotonous or partially heterogeneous. Histological examination revealed a proliferation of adipocytes varying considerably in size and including many mono- or multivacuolated lipoblasts. Immunohistochemically, some of the tumor cells were positive for p53 and MDM2. Histologically, the atypical lipomatous tumor, lipoblastoma, spindle cell lipoma, pleomorphic liposarcoma, and hibernoma comprised the list of possible, differential diagnoses. We considered our case to be a variant of atypical lipomatous tumor, although it did not correspond to any of the 4 atypical lipomatous tumor subgroups. There has been no recurrence to date.


Distribution of ion contents and microorganisms during the electro-bioremediation of petroleum-contaminated saline soil.
This study investigated the distribution of ion contents and microorganisms during the electro-bioremediation (EK-Bio) of petroleum-contaminated saline soil. The results showed that soil ions tend to accumulate around the electrodes, and the concentration was correlated with the distance from the electrodes. The average soil ion content was 7.92 g/kg around the electrodes (site A) and 0.55 g/kg at the furthest distance from the electrodes (site B) after 112 days of treatment, while the initial average content was 3.92 g/kg. Smooth linear (R2 = 0.98) loss of soil ions was observed at site C, which was closer to the electrodes than site B, and had a final average soil ion content of 1.96 g/kg. The dehydrogenase activity was much higher in EK-Bio test soil than in the Bio test soil after 28 days of treatment, and followed the order: site C > site B > site A. However, the soil dehydrogenase activity dropped continuously when the soil ion reached very high and low concentrations at sites A and B. The soil microbial community varied in sample sites that had different ion contents, and the soil microbial diversity followed the order: site C > site B > site A. The applied electric field clearly enhanced the biodegradation efficiency for soil petroleum contaminants. However, the biodegradation promotion effects were weakening in soils where the ion contents were extremely high and low (sites A and B). These results can provide useful information for EK-Bioremediation of organic-contaminated saline soil.


Sleep in Parkinson's Disease with Impulse Control Disorder.
This paper aims to explore the relationship between impulse-control disorders (ICDs) and sleep problems in patients with Parkinson's disease (PD) among scientific literature. Previously published results are controversial and sometimes inconclusive. ICDs and sleep disruption represent important non-motor features of Parkinson's disease, responsible for reducing quality of life and increasing burden of disease. The relationship between sleep problems and ICDs is complex and bidirectional. Indeed, sleep disturbances and fragmentation may play a crucial role in increasing susceptibility to impulsive behavior and may represent a risk factor for developing ICDs in PD patients. Moreover, REM sleep behavior disorder (RBD) and restless legs syndrome (RLS) have been indicated as independent risk factors for ICDs in PD patients. On the other hand, also ICDs may lead to sleep restriction and fragmentation, suggesting a bidirectional relationship. The association between sleep problems and ICDs in PD is far from being completely understood. Further studies are needed to confirm the nature of this relationship and its pathophysiology.