Spectroscopic and Structural Characterization of Water-Shared Ion-Pairs in Aqueous Sodium and Lithium Hydroxide.
The structures of the ion-pairs formed in aqueous NaOH and LiOH solutions are elucidated by combining Raman multivariate curve resolution (Raman-MCR) experiments and ab initio molecular dynamics (AIMD) simulations. The results extend prior findings to reveal that the initially formed ion-pairs are predominantly water-shared, with the hydroxide ion retaining its full first hydration-shell, while direct contact ion-pairing only becomes significant at higher concentrations. Our results confirm previous experiments and simulations indicating greater ion-pairing in aqueous LiOH than NaOH as well as at high temperatures. Our results further imply that NaOH and LiOH ion-pairing free energies have an approximately linear (rather than square-root) dependence on ion concentration (in the molar range), with positive enthalpies and entropies that increase with concentration, thus implying that water-mediated interactions enthalpically disfavor and entropically favor ion-pair formation.


[POSSIBILITIES FOR COMPREHENSIVE LABORATORY EXAMINATION OF WOMEN WITH OSTEOPOROSIS ON AN OUTPATIENT BASIS].
The current possibilities for comprehensive laboratory examination of women with osteoporosis on an outpatient basis are discussed with reference to the use of different specific biomarkers of bone metabolism are discussed. The use of biochemical markers of bone metabolism and osteoporosis together with the determination of bone mineral tissue density as an additional factor for the prediction of bone density reduction and risk of fractures is considered. Such approach is believed to be instrumental for the correct choice and improvement of antiresorption therapy.


Modification of human U4 RNA requires U6 RNA and multiple pseudouridine synthases.
Small nuclear RNAs (snRNA), cofactors in the splicing of pre-mRNA, are highly modified. In this report the modification of human U4 RNA was studied using cell extracts and in vitro synthesized, and therefore unmodified, U4 RNA. The formation of pseudouridine (Psi) at positions 4, 72 and 79 in U4 RNA was dependent on an RNA-containing cofactor, since the activities in the extracts were micrococcal nuclease (MN) sensitive. Extracts were fractionated on glycerol gradients and there was a broad peak of reconstitution activity centered at 14 S. Reconstitution was not due to additional enzymatic activity, since the peak fraction was MN sensitive. Oligodeoxynucleotide-mediated RNase H digestion of U6 RNA in the extracts inhibited formation of Psi in U4 RNA. From glycerol gradient analysis we determined that exogenously added U4 RNA that is associated with U6 RNA (sedimentation velocity 16 S) was significantly higher in Psi content than U4 RNA not associated with U6 RNA (8 S). Competitive inhibitors of Psi synthases, 5-fluorouridine-containing (5-FU) wild-type and mutant U4 RNAs, were used to investigate formation of Psi in U4 RNA. Deletions and point mutations in these 5-FU-containing U4 RNAs affected their ability to inhibit Psi synthase in vitro. With the aid of these potent inhibitors it was determined that at least two separate activities modify the uridines at these positions.


Adverse effects of growth hormone replacement therapy in children.
Human growth hormone (hGH) replacement therapy has been widely available for clinical purposes for more than fifty years. Starting in 1958, hGH was obtained from cadaveric pituitaries, but in 1985 the association between hGH therapy and Creutzfeldt-Jakob disease was reported. In the same year, the use of recombinant hGH (rhGH) was approved. Side effects of rhGH replacement therapy in children and adolescents include rash and pain at injection site, transient fever, prepubertal gynecomastia, arthralgia, edema, benign intracranial hypertension, insulin resistance, progression of scoliosis, and slipped capital femoral epiphysis. Since GH stimulates cell multiplication, development of neoplasms is a concern. We will review the side effects reported in all rhGH indications.


[New treatment possibilities for skin changes with the CO2 laser in head and neck surgery].
Laser treatment of various skin changes has become common clinical practice in recent years. Due to its physical properties, the CO2 laser is particularly well suited for cutting and ablating tissue. The high absorption of its wavelength in water (lambda = 10600 nm) is responsible for its low penetration depth in biological tissue. Shortening the exposure time minimizes thermal side effects, such as carbonization and coagulation. This effect can be lessened with the Silk Touch scanner, since the focussed laser beam is moved over a defined area by rapidly rotating mirrors. This enables a controlled and reliable removal of various dermal lesions. Particularly well-suited for treatment hypertrophic scars, post-acne scarring, perioral and periorbital wrinkles, rhinophymas and benign neoplasms including verruca vulgaris. Cosmetically favorable reepithelialization of the treated skin surfaces occurs within a very short time after treatment. Periorbital resurfacing and correction of a rhinophyma are used as examples of dermal treatment with the CO2 laser and the Silk Touch scanner.


[The induction of labor by using extra-amniotic intrauterine estrogens. Our experience].
Induction of labour using extra-amniotic intrauterine estrogens. Personal experience. The study was carried out in a series of 20 primagravidae in whom it was necessary to induce labour. The method used entailed the introduction, via an extra-amniotic transcervical route, of approximately 16 mg of estrogen paste. There is a full discussion of the technical details and results obtained which appear to be encouraging for the routine use of this method.


Far-Infrared Rotational Spectrum of ArD+
Rotational transition frequencies of ArD+ were measured with an accuracy of a few hundred kilohertz in the 0.95-4.7 THz region, using a tunable far-infrared radiation source. Effective rotational parameters B, D, and H were determined for the ground vibrational state. The observed frequencies were combined with the previous data on all isotopic species of protonated argon ion to improve the mass-independent Dunham parameters Ukl, DeltaArkl, and DeltaHkl. Copyright 1999 Academic Press.


Trehalose 6,6'-dimycolate (Cord factor) enhances neovascularization through vascular endothelial growth factor production by neutrophils and macrophages.
Trehalose 6,6'-dimycolate (TDM) plays important roles in the development of granulomatous inflammation during infection with Mycobacterium spp., Rhodococcus spp., etc. To reveal the augmenting effect of TDM on vascular endothelial growth factor (VEGF) production and neovascularization, we investigated murine granulomatous tissue air pouches induced by Rhodococcus sp. strain 4306 TDM dissolved in Freund's incomplete adjuvant (FIA), comparing them to pouches treated with FIA alone. Histologically, granulomatous tissue and new vessel formation, which reached a maximum at day 7, was greatly enhanced by treatment with TDM. At day 1, VEGF-positive neutrophils accumulated in the pouch wall with frequency of 95% of total infiltrating cells, adhering to TDM-containing micelles. By day 3, granulomatous tissue and new vessels started to develop, and VEGF-positive macrophages appeared in a small number and gradually increased in number thereafter. The pouch contents of VEGF, interleukin-1beta, tumor necrosis factor alpha, and transforming growth factor beta were significantly elevated in TDM-treated pouches, with peaks at days 1, 0.5, 1, and 3, respectively, compared to those of control pouches, while that of basic fibroblast growth factor showed no significant increase. Treatment with anti-VEGF antibody inhibited TDM-induced granulomatous tissue formation and neovascularization, and administration of recombinant VEGF into pouches treated with FIA alone induced neovascularization comparable to that in the TDM-treated pouches. Incubation of neutrophils and macrophages on TDM-coated plastic dishes increased the VEGF release. The present results indicate that TDM augments VEGF production by neutrophils and macrophages and induces neovascularization in the granulomatous tissue.


A Comprehensive Analysis of Human Endogenous Retroviruses HERV-K (HML.2) from Teratocarcinoma Cell Lines and Detection of Viral Cargo in Microvesicles.
About 8% of our genome is composed of sequences from Human Endogenous Retroviruses (HERVs). The HERV-K (HML.2) family, here abbreviated HML.2, is able to produce virus particles that were detected in cell lines, malignant tumors and in autoimmune diseases. Parameters and properties of HML.2 released from teratocarcinoma cell lines GH and Tera-1 were investigated in detail. In most experiments, analyzed viruses were purified by density gradient centrifugation. HML.2 structural proteins, reverse transcriptase (RT) activity, viral RNA (vRNA) and particle morphology were analyzed. The HML.2 markers were predominantly detected in fractions with a buoyant density of 1.16 g/cm3. Deglycosylation of TM revealed truncated forms of transmembrane (TM) protein. Free virions and extracellular vesicles (presumably microvesicles-MVs) with HML.2 elements, including budding intermediates, were detected by electron microscopy. Viral elements and assembled virions captured and exported by MVs can boost specific immune responses and trigger immunomodulation in recipient cells. Sequencing of cDNA clones demonstrated exclusive presence of HERV-K108 env in HML.2 from Tera-1 cells. Not counting two recombinant variants, four known env sequences were found in HML.2 from GH cells. Obtained results shed light on parameters and morphology of HML.2. A possible mechanism of HML.2-induced diseases is discussed.


High-yield expression of periplasmic single-chain variable fragments by solid Escherichia coli cultures.
High-yield expression of quality antibody fragments is indispensable for research and diagnosis. Most recombinant antibody fragments are expressed in Escherichia coli using liquid cultures; however, their yields and quality are often poor. Here the authors expressed a single-chain variable fragment in E. coli cultivated on the wet surface of a solid support. Compared with a liquid culture, the authors obtained 2.5-times more single-chain variable fragments with membrane-cultivated E. coli. This method has two important advantages: it enables high yields of periplasmic single-chain variable fragments compared with liquid culture and offers simple and rapid expression and extraction.


Soluble Complement Component 1q Receptor 1 (sCD93) Is Associated with Graft Function in Kidney Transplant Recipients.
Cluster of differentiation 93 (CD93), also known as complement component 1q receptor 1 is a transmembrane glycoprotein expressed in endothelial and hematopoietic cells and associated with phagocytosis, cell adhesion, angiogenesis and inflammation. The extracellular part, soluble CD93 (sCD93), is released to body fluids in inflammation. Data on sCD93 in kidney diseases are limited. Our aim was to evaluate serum sCD93 in long-term kidney transplant recipients as a marker of inflammation and endothelial dysfunction that may be potentially useful in early recognition of graft dysfunction. Seventy-eight adult patients with functioning kidney graft and stable clinical state were examined at least one year after kidney transplantation. Serum sCD93 was measured by enzyme immunosorbent assay. Estimated glomerular filtration rate (eGFR) and albuminuria or proteinuria were assessed at baseline and over one-year follow-up. Increased sCD93 was associated with lower baseline eGFR independently of the confounders. Moreover, sCD93 was negatively associated with eGFR during one-year follow-up in simple analysis; however, this was not confirmed after adjustment for confounders. Baseline sCD93 was positively associated with baseline albuminuria and with increased proteinuria during the follow-up. Serum sCD93 was not correlated with other studied inflammatory markers (interleukin 6, C-reactive protein, procalcitonin and C3 and C4 complement components). To the best of our knowledge, this is the first report regarding the concentrations of sCD93 in kidney transplant recipients and one of the first reports showing the inverse association between sCD93 and renal function. Serum sCD93 should be further evaluated as a diagnostic and prognostic marker in renal transplantation.


Proline-rich tyrosine kinase 2 and Src kinase signaling transduce monosodium urate crystal-induced nitric oxide production and matrix metalloproteinase 3 expression in chondrocytes.
Articular deposition of monosodium urate monohydrate (MSU) crystals may promote cartilage and bone erosion. Therefore, the aim of this study was to determine how MSU crystals stimulate chondrocytes. Nitric oxide (NO) release, and expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase 3 (MMP-3) were assessed in cultured chondrocytes treated with MSU. MSU-induced functional signaling by specific protein kinases (p38, Src, and the focal adhesion kinase [FAK] family members proline-rich tyrosine kinase 2 [Pyk-2] and FAK) was also examined using selective pharmacologic inhibitors and transfection of kinase mutants. MSU induced MMP-3 and iNOS expression and NO release in chondrocytes in a p38-dependent manner that did not require interleukin-1 (IL-1), as demonstrated by using IL-1 receptor antagonist. MSU induced rapid tyrosine phosphorylation of Pyk-2 and FAK, their adaptor protein paxillin, and interacting kinase c-Src. Pyk-2 and c-Src signaling both mediated p38 MAPK activation in response to MSU. Pyk-2 and c-Src signaling played a major role in transducing MSU-induced NO production and MMP-3 expression. But, despite the observed FAK phosphorylation, a selective pharmacologic FAK inhibitor and a FAK dominant-negative mutant both failed to block MSU-induced NO release or MMP-3 expression in parallel experiments. In chondrocytes, MSU crystals activate a signaling kinase cascade typically employed by adhesion receptors that involves upstream Src and FAK family activation and downstream p38 activation. In this cascade, Pyk-2, Src, and p38 kinases transduce MSU-induced NO production and MMP-3 expression. Our results identify Pyk-2 and c-Src as novel sites for potential therapeutic intervention in cartilage degradation in chronic gout.


When legal worlds collide: from research to treatment in hereditary cancer prevention.
This paper critically examines the legal and ethical dilemma in the institutionalization of a prevention and treatment technology on hereditary non-polyposis colorectal cancer (HNPCC) in Finland. Current medical practice and legislation support the notion of non-directiveness in genetic counselling, patient autonomy and personal privacy. Clinical doctors in Finland, however, proposed that a research register of HNPCC carriers should be nationalized through a legal mandate, which would require all carriers to be identified on the basis of the mutation, but also provide a national healthcare and counselling infrastructure for preventive treatment. This paper argues that although such a register would undermine personal autonomy and privacy, there should be a strong incentive by the state to intervene from a preventive health perspective. Such a position would be contrary to current medical ethics and legal practice, but it would ensure that all patients receive equal access to information, screening and treatment, as well as help to reduce mortality rates.


Magnetic resonance arthrography of the cubital joint in dogs affected with fragmented medial coronoid processes.
To evaluate efficacy of intra-articular injection of gadolinium tetra- azacyclododecane tetraacetic acid (gadolinium-DOTA) for delineating fragmented medial coronoid processes (FMCP) and lesions on the medial aspect of the humeral condyle (MAHC). 14 cubital joints in 9 dogs. Magnetic resonance imaging (MRI) was performed with and without intra-articular injection of a solution of 2 mmol of gadolinium-DOTA/L. Arthrographic images obtained after injection of contrast medium were compared with those obtained without contrast medium. Evidence of contrast medium around or in the medial coronoid process and infiltration of contrast medium in subchondral bone lesions was recorded. Twenty-four hours after imaging, arthroscopy was performed, and lesions detected were correlated with results of MRI. An abnormal coronoid process was diagnosed in 13 of 14 joints. A fragmented process (free) was seen in 7 of 14 joints; nondisplaced mineralized medial (in situ) coronoid processes were evident in 4 joints; and nondisplaced unmineralized medial coronoid processes were evident in 2 joints. Lesions on the MAHC were diagnosed in 4 of 12 joints. In 5 joints, a hyperintense signal resulted from contrast medium that infiltrated between the fragmented process and ulna. In 2 joints, contrast medium did not infiltrate completely around the process and was stopped by an isointense structure (ie, abnormal cartilage). Subchondral bone lesions were enhanced by use of contrast medium. Use of arthrography enabled us to identify FMCP easily, but did not provide important additional information about changes on the medial coronoid process, compared with MRI performed without contrast medium.


Ocular fundus images with confocal scanning laser ophthalmoscopy in the dog, monkey and minipig.
Confocal scanning laser ophthalmoscopy (CSLO) is a new technique that enables ocular fundus image recording and retinal dynamic angiography to be performed. The ocular fundus image is acquired sequentially, point by point, and is reconstructed on a video monitor at the rate of 25 images per second. The feasibility of performing both ocular fundus image recordings and retinal angiography image recordings were tested on two dogs, two monkeys and two minipigs using a 40 degrees field I + Tech CSLO. Fundus area of each dog, monkey and minipig were examined without any additional optical devices. The ocular fundus and angiography images were recorded, stabilized and analyzed under the same conditions. For each species, all images were easily recorded without any additional optical device in a lighted room and the morphology of the retinal images generated was similar to those obtained with a camera or angiography of higher resolution. Capillary phase or venous times are presented. Image recording at 25 frames/second enabled more retinal dynamics to be demonstrated than with use of regular angiography. This technique is noninvasive and easy to perform if the eye is fixed and eyelids maintained open. It also allows exploration of retinal microvascularization and could be utilized for clinical, pharmacologic and toxicologic investigations as well.


Effect of maternal age on birth outcomes among young adolescents.
This study examined the effect of maternal age on birth outcomes among young adolescents, ages 10 through 15. All records representing single births of primipara, Black or White adolescents, were selected for analysis from the 1983-1986 National Center for Health Statistics' Public Use Linked Live Birth-Infant Death Data File (n = 127,668). Logistic regression analyses controlled for effects of maternal race, marital status, prenatal care, gravidity, education, and metropolitan/nonmetropolitan residency. Univariate analyses indicated that the youngest adolescents were at greatest risk for negative birth outcomes including very preterm and preterm delivery, low birth weight, small for gestational age (SGA), and neonatal mortality. Logistic analyses showed similar results, with the exception that differences in SGA were insignificant. This study indicates the importance of examining age-specific birth outcomes among a population that has traditionally been studied in aggregate and underscores the need for increased prevention efforts.


Paradigm shifts in the management of poor-risk chronic lymphocytic leukemia.
With the growing complexity of treatment options for chronic lymphocytic leukemia (CLL) and variables that influence the underlying biology of this disease, providing allogeneic stem cell transplant (alloSCT) to appropriate candidates poses a challenge for transplant physicians. Novel small molecule inhibitors hold unprecedented promise for poor-risk subgroups, which will likely alter decision-making and referral patterns for transplant. In this review, we analyze what is known and may still remain true about indications for transplant based on outcomes reported in the literature recently and over the last decade.


accuMUlate: a mutation caller designed for mutation accumulation experiments.
Mutation accumulation (MA) is the most widely used method for directly studying the effects of mutation. By sequencing whole genomes from MA lines, researchers can directly study the rate and molecular spectra of spontaneous mutations and use these results to understand how mutation contributes to biological processes. At present there is no software designed specifically for identifying mutations from MA lines. Here we describe accuMUlate, a probabilistic mutation caller that reflects the design of a typical MA experiment while being flexible enough to accommodate properties unique to any particular experiment. Availability and implementation accuMUlate is available from https://github.com/dwinter/accuMUlate. Supplementary data are available at Bioinformatics online.


Defective K-Ras oncoproteins overcome impaired effector activation to initiate leukemia in vivo.
Reversing the aberrant biochemical output of oncogenic Ras proteins is one of the great challenges in cancer therapeutics; however, it is uncertain which Ras effectors are required for tumor initiation and maintenance. To address this question, we expressed oncogenic K-Ras(D12) proteins with "second site" amino acid substitutions that impair PI3 kinase/Akt or Raf/MEK/ERK activation in bone marrow cells and transplanted them into recipient mice. In spite of attenuated signaling properties, defective K-Ras oncoproteins initiated aggressive clonal T-lineage acute lymphoblastic leukemia (T-ALL). Murine T-ALLs expressing second site mutant proteins restored full oncogenic Ras activity through diverse mechanisms, which included acquiring novel somatic third site Kras(D12) mutations and silencing PTEN. T-ALL cell lines lacking PTEN had elevated levels of phosphorylated Akt, a gene expression pattern similar to human early T-cell precursor ALL, and were resistant to the potent and selective MEK inhibitor PD0325901. Our data, which demonstrate strong selective pressure to overcome the defective activation of PI3 kinase/Akt and Raf/MEK/ERK, implicate both Ras effector pathways as drivers of aberrant growth in T-ALL and further suggest that leukemia cells will deploy multiple mechanisms to develop resistance to targeted inhibitors in vivo.


Validation of real-time PCR for laboratory diagnosis of Acanthamoeba keratitis.
Confirmation of Acanthamoeba keratitis by laboratory diagnosis is the first step in the treatment of this vision-threatening disease. Two real-time PCR TaqMan protocols (the Rivière and Qvarnstrom assays) were developed for the detection of genus-specific Acanthamoeba DNA but lacked clinical validation. We have adapted these assays for the Cepheid SmartCycler II system (i) by determining their real-time PCR limits of detection and amplification efficiencies, (ii) by determining their ability to detect trophozoites and cysts, and (iii) by testing a battery of positive and negative samples. We also examined the inhibitory effects of a number of commonly used topical ophthalmic drugs on real-time PCR. The results of the real-time PCR limit of detection and amplification efficiency of the Rivière and Qvarnstrom assays were 11.3 DNA copies/10 microl and 94% and 43.8 DNA copies/10 microl and 92%, respectively. Our extraction protocol enabled us to detect 0.7 Acanthamoeba cysts/10 microl and 2.3 Acanthamoeba trophozoites/10 microl by both real-time PCR assays. The overall agreement between the assays was 97.0%. The clinical sensitivity and specificity of both real-time PCR assays based on culture were 100% (7 of 7) and 100% (37 of 37), respectively. Polyhexamethylene biguanide was the only topical drug that demonstrated PCR inhibition, with a minimal inhibitory dilution of 1/640 and an amplification efficiency of 72.7%. Four clinical samples were Acanthamoeba culture negative and real-time PCR positive. Our results indicate that both real-time PCR assays could be used to diagnose Acanthamoeba keratitis. Polyhexamethylene biguanide can inhibit PCR, and we suggest that specimen collection occur prior to topical treatment to avoid possible false-negative results.


Changes in the Sodium Content of Foods Sold in Four Latin American Countries: 2015 to 2018.
In 2015, the Pan American Health Organization (PAHO) published sodium targets for packaged foods, which included two distinct levels: one "regional" and one "lower" target. Changes to the sodium content of the food supply in Latin American Countries (LAC) has not been evaluated. A repeated cross-sectional study used food label data from 2015 (n = 3859) and 2018 (n = 5312) to determine changes in the proportion of packaged foods meeting the PAHO sodium targets and the distribution in the sodium content of foods in four LAC (Argentina, Costa Rica, Paraguay, Peru). Foods were classified into the 18 food categories in the PAHO targets. The proportion of foods meeting the regional targets increased from 82.9% to 89.3% between 2015 and 2018 (p < 0.001). Overall, 44.4% of categories had significant decreases in mean sodium content. Categories with a higher proportion of foods meeting the regional and lower targets in 2018 compared to 2015 (p < 0.05) were breaded meat and poultry, wet and dry soups, snacks, cakes, bread products, flavored cookies and crackers, and dry pasta and noodles. While positive progress has been made in reducing the sodium content of foods in LAC, sodium intakes in the region remain high. More stringent targets are required to support sodium reduction in LAC.


Treatment of COPD: the sooner the better?
Classical belief is that only smoking cessation, and not pharmacotherapy, beneficially affect disease progression in chronic obstructive pulmonary disease (COPD). In recent years, new data on pharmacotherapy of COPD became available that shed new light on this question. The present paper reviews these data critically in an attempt to put them in a proper perspective. The most impressive new data are subgroup analyses of two large-scale long-term trials. With these new data it is now clear that patients in GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease) stage II benefit as much from pharmacotherapy as patients in the later stages of the disease. Effects on prebronchodilator and postbronchodilator forced expiratory volume in 1 s (FEV(1)), health-related quality of life, exacerbations and hospitalisations appear at least as pronounced in GOLD stage II as in the other GOLD stages. In addition, evidence suggestive of an effect on disease progression is available in the sense of an effect on rate of decline of FEV(1), and trends for reductions in mortality. Finally, good evidence is available that, in contrast to conventional thinking, decline of FEV(1) occurs at a considerably faster rate in the early stages of the disease. These data together with the high prevalence of co-morbidities from early in the disease onwards provide us with strong suggestive evidence for early intensive intervention in COPD. New trials, particularly demonstrating the detrimental effects of delaying treatment until later in the course of the disease, are required to render the evidence for early intensive intervention irrefutable.


Tpr homologs in Treponema paraluiscuniculi Cuniculi A strain.
Treponema paraluiscuniculi, the etiologic agent of rabbit venereal syphilis, is morphologically indistinguishable from Treponema pallidum subsp. pallidum (T. pallidum), the human syphilis treponeme, and induces similar immune responses and histopathologic changes in the infected host. Because of their high degree of relatedness, comparative studies are likely to identify genetic determinants that contribute to pathogenesis or virulence in human syphilis. The tpr (Treponema pallidum repeat) genes are believed to code for potential virulence factors. In this study, we identified 10 tpr homologs in Treponema paraluiscuniculi Cuniculi A strain and determined their sequence architecture. Half of this group of paralogous genes were predicted to be nonfunctional due to the presence of frameshifts and premature stop codons. Furthermore, the immune response against the T. paraluiscuniculi Tpr homologs in long-term-infected rabbits was studied by enzyme-linked immunosorbent assay and lymphocyte proliferation assay, showing that TprK is the only target of the antibody and T-cell responses during experimental infection and emphasizing the importance of this putative virulence factor in venereal treponematosis.


Development of bladder outlet obstruction after a single treatment of prostate cancer with high-intensity focused ultrasound: experience with 226 patients.
To investigate the occurrence of bladder outlet obstruction (BOO) after high-intensity focused ultrasound (HIFU) therapy of prostate cancer, the need for secondary transurethral interventions for BOO, and the benefit of transurethral resection of the prostate (TURP) before HIFU. After a single HIFU treatment between 2002 and 2007, 226 consecutive patients were examined and followed at least 2 years. The Ablatherm Maxis and the Integrated Imaging devices were used. The sites of BOO were recorded. Median follow-up after HIFU was 52 months (range 24-80 mos). BOO developed in 58 (25.66%) patients. Repeated BOO episodes were observed in 27 (11.94%), three to seven episodes in 13 (5.75%) patients. Patients with repeated BOO were older than patients with singular BOO (71.75 ± 4.97 vs 68.18 ± 5.03; P = 0.024). In primary BOO, multiple sites of obstruction were more often involved than in repeated BOO (25/58 vs 8/27). Conversely, isolated bladder neck stenosis was predominantly found in patients with ≥two episodes of BOO. The rate of primary BOO was significantly different between patients who had undergone TURP the same day as HIFU or within 2 days of HIFU (33/96; 34.38%) and patients with TURP more than 1 month (16/89; 17.98%) before HIFU (P = 0.032). BOO occurred in 21.95% (9/41) of the patients who were treated with HIFU only. BOO after HIFU is common, particularly affecting the bladder neck. The risk of repeated BOO is associated with age. A longer interval between TURP and HIFU (>1 month) might reduce the risk for the development of BOO.


In vitro hematopoietic and endothelial potential of flk-1(-/-) embryonic stem cells and embryos.
Mice deficient in the Flk-1 receptor tyrosine kinase are known to die in utero because of defective vascular and hematopoietic development. Here, we show that flk-1(-/-) embryonic stem cells are nevertheless able to differentiate into hematopoietic and endothelial cells in vitro, although they give rise to a greatly reduced number of blast colonies, a measure of hemangioblast potential. Furthermore, normal numbers of hematopoietic progenitors are found in 7.5-day postcoitum flk-1(-/-) embryos, even though 8. 5-day postcoitum flk-1(-/-) embryos are known to be deficient in such cells. Our results suggest that hematopoietic/endothelial progenitors arise independently of Flk-1, but that their subsequent migration and expansion require a Flk-1-mediated signal.


Modulation of murine macrophage function by methamphetamine.
The abuse of methamphetamine (MA) is an increasingly growing problem globally and produces serious side effects. In the present study, the immunomodulating effects of MA were examined on murine peritoneal macrophages after MA (5 mg/kg body weight) was administered daily orally for 2 wk. When purified macrophages were stimulated with lipopolysaccharide (LPS), the tumoricidal activity induced by LPS was significantly suppressed by MA. MA also inhibited poly I:C-induced antiviral activity in macrophages and decreased the number of peritoneal macrophages. FACS analysis showed that the expression of CD14 was markedly decreased by MA in LPS-stimulated macrophages. The production of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha: which are known to be major effector molecules in macrophage-mediated cytotoxicity, was decreased by MA. MA produced a significant effect on phagocytosis and interleukin-1 (IL-1) and IL-6 at 14 d. In addition, the level of hydrogen peroxide (H2O2) was not altered by MA. Taken together, these data indicate that MA has a differential immunomodulating effect on macrophage secretory and cellular activities.


Muscarinic receptors on rat ileal villus and crypt cells.
Ileal villus and crypt cells exhibit morphological and biochemical differences which may be responsible for functional differences in relation to ion transport. Cholinergic agonists act directly on epithelial cell muscarinic receptors, but it is not known if these receptors exist on both villus and crypt cells. Using the potent muscarinic antagonist [3H](-)-quinuclidinyl benzilate (QNB) we have determined the distribution of muscarinic receptors in rat ileal villus and crypt cells. Plasma membrane preparations from ileal villus and crypt cells possessed a specific, saturable, and high affinity QNB binding site with apparent dissociation constants of 0.23 +/- 0.05 and 0.21 +/- 0.04 nM (mean +/- s.e., n = 6) and densities of 92.2 +/- 2.8 and 90.1 +/- 16.2 fmol (mg protein)-1, respectively. Both types of cells showed similar potencies for agonist and antagonist competition of QNB binding. The muscarinic receptors in membrane fractions from villus cells were found primarily on the basolateral membrane rather than on the brush border membrane. Secretion induced by cholinergic stimulation of the small intestine might, therefore, be due to an effect on both villus and crypt cells as both types contain muscarinic receptors. Furthermore, such stimulation also may result in mucin secretion, as goblet cells were present in the preparation we studied, and receptors on these cells may have contributed to the amount of binding of [3H]QNB.


The prevalence and severity of dental caries in Chad: a pilot study.
This study was undertaken to determine the prevalence and severity of dental caries among a cross section of a sample from different locations in Chad as part of a general assessment of their oral health status. A cross-sectional descriptive survey of a nationwide sample included volunteers, 10 years or older, for a total of 1,011 participants. The survey consisted of a brief interview followed by a 1-2 minute oral examination of each subject. The mean age of the participants was 29.61 ±12.59 years and the total mean value for Decayed/Missing/Filled Teeth (DMFT)=1.96 ±1.78. Females had a higher mean DMFT (2.72 ±1.88); decayed (2.82 ±1.07); missing teeth (1.81 ±1.14) than males (1.61 ±1.60): decayed (2.11 ±1.09); missing (1.45 ±0.89, respectively; all p<0.001). The older group (>30 years) had higher DMFT (2.79 ±1.93) than the younger group (d"30 years; p<0.001). Urban area showed lower DMFT (1.81 ±1.68) than rural areas (2.31 ±1.95). In this study, the prevalence of dental caries is very low which is similar to the most of the African Saharan and sub-Saharan countries. However, there is need to establish caries control programs to prevent tooth decay in the future and help people maintain lifelong dental health.


[A case of metastatic vaginal tumor of rectal cancer].
The majority of vaginal metastases from extra-genital tumors are from colorectal cancer. A case of metastases to the vagina from a huge rectal carcinoma is described. A 55-year-old woman was admitted to the hospital because of a barium ileus after upper GI. Further examination revealed that she had a huge rectal carcinoma. Hartmann's operation combined with resection of the right ureter, posterior wall of the uterus and left ovary was performed. Postoperative chemoradiotherapy was performed with 60 Gy of irradiation to the small pelvis with 500 mg/day continuous infusion of 5-FU. After 18 months, she had genital bleeding. Digital examination revealed a vaginal tumor and metastasis of the rectal carcinoma to the vagina was confirmed histologically. Abdominoperineal resection of the rectum and vagina combined with simple total hysterectomy and bilateral salpingo-oophorectomy was performed. Thirty-three months after operation, there is no sign of recurrence.


Asian labour mobility: new dimensions and implications for development.
The author "argues that the rise of organized labour migration has introduced a new structural feature in the international labour market.... This new factor....contributes to making labour supply highly elastic during upswings in demand for expatriate labour....[and] makes for inelasticity during periods of weakening demand because of its 'stockpiling effect' on labour supply." The impacts on migrants' wages and on the labor forces of labor-exporting countries are considered. The focus is on Asian labor migration to the Middle East. Separate comments by M. Irfan and Nadeem A. Burney are included (pp. 378-81).


Donor-based single electron pumps with tunable donor binding energy.
We report on single electron pumping via a tunable number of individual donors. We use a device that essentially consists of a silicon nanowire with local arsenic implantation between a set of fine gates. A temperature-dependent characterization of the pumped current allows us to extract the ionization energy of a single arsenic donor. We observe the ionization energy to be tunable by the gate electric field over a large range of energies.


Acetylation of putative arylamine and alkylaniline carcinogens in immortalized human fibroblasts transfected with rapid and slow acetylator N-acetyltransferase 2 haplotypes.
Exposure to alkylanilines found in tobacco smoke and indoor air is associated with risk of bladder cancer. Genetic factors significantly influence the metabolism of arylamine carcinogens and the toxicological outcomes that result from exposure. We utilized nucleotide excision repair (NER)-deficient immortalized human fibroblasts to examine the effects of human N-acetyltransferase 1 (NAT1), CYP1A2, and common rapid (NAT2*4) and slow (NAT2*5B or NAT2*7B) acetylator human N-acetyltransferase 2 (NAT2) haplotypes on environmental arylamine and alkylaniline metabolism. We constructed SV40-transformed human fibroblast cells that stably express human NAT2 alleles (NAT2*4, NAT2*5B, or NAT2*7B) and human CYP1A2. Human NAT1 and NAT2 apparent kinetic constants were determined following recombinant expression of human NAT1 and NAT2 in yeast for the arylamines benzidine, 4-aminobiphenyl (ABP), and 2-aminofluorene (2-AF), and the alkylanilines 2,5-dimethylaniline (DMA), 3,4-DMA, 3,5-DMA, 2-6-DMA, and 3-ethylaniline (EA) compared with those of the prototype NAT1-selective substrate p-aminobenzoic acid and NAT2-selective substrate sulfamethazine. Benzidine, 3,4-DMA, and 2-AF were preferential human NAT1 substrates, while 3,5-DMA, 2,5-DMA, 3-EA, and ABP were preferential human NAT2 substrates. Neither recombinant human NAT1 or NAT2 catalyzed the N-acetylation of 2,6-DMA. Among the alkylanilines, N-acetylation of 3,5-DMA was substantially higher in human fibroblasts stably expressing NAT2*4 versus NAT2*5B and NAT2*7B. The results provide important insight into the role of the NAT2 acetylator polymorphism (in the presence of competing NAT1 and CYP1A2-catalyzed N-acetylation and N-hydroxylation) on the metabolism of putative alkyaniline carcinogens. The N-acetylation of two alkylanilines associated with urinary bladder cancer (3-EA and 3,5-DMA) was modified by NAT2 acetylator polymorphism.


NeuroRegen Scaffolds Combined with Autologous Bone Marrow Mononuclear Cells for the Repair of Acute Complete Spinal Cord Injury: A 3-Year Clinical Study.
Spinal cord injury (SCI) remains among the most challenging pathologies worldwide and has limited therapeutic possibilities and a very bleak prognosis. Biomaterials and stem cell transplantation are promising treatments for functional recovery in SCI. Seven patients with acute complete SCI diagnosed by a combination of methods were included in the study, and different lengths (2.0-6.0 cm) of necrotic spinal cord tissue were surgically cleaned under intraoperative neurophysiological monitoring. Subsequently, NeuroRegen scaffolds loaded with autologous bone marrow mononuclear cells (BMMCs) were implanted into the cleaned site. All patients participated in 6 months of rehabilitation and at least 3 years of clinical follow-up. No adverse symptoms associated with stem cell or functional scaffold implantation were observed during the 3-year follow-up period. Additionally, partial shallow sensory and autonomic nervous functional improvements were observed in some patients, but no motor function recovery was observed. Magnetic resonance imaging suggested that NeuroRegen scaffold implantation supported injured spinal cord continuity after treatment. These findings indicate that implantation of NeuroRegen scaffolds combined with stem cells may serve as a safe and promising clinical treatment for patients with acute complete SCI. However, determining the therapeutic effects and exact application methods still requires further study.


Xenin-25 induces anion secretion by activating noncholinergic secretomotor neurons in the rat ileum.
Xenin-25 is a neurotensin-like peptide that is secreted by enteroendocrine cells in the small intestine. Xenin-8 is reported to augment duodenal anion secretion by activating afferent neural pathways. The intrinsic neuronal circuits mediating the xenin-25-induced anion secretion were characterized using the Ussing-chambered, mucosa-submucosa preparation from the rat ileum. Serosal application of xenin-25 increased the short-circuit current in a concentration-dependent manner. The responses were abolished by the combination of Cl--free and HCO3- -free solutions. The responses were almost completely blocked by TTX (10-6 M) but not by atropine (10-5 M) or hexamethonium (10-4 M). The selective antagonists for neurotensin receptor 1 (NTSR1), neurokinin 1 (NK1), vasoactive intestinal polypeptide (VIP) receptors 1 and 2 (VPAC1 and VPAC2, respectively), and capsaicin, but not 5-hydroxyltryptamine receptors 3 and 4 (5-HT3 and 5-HT4), NTSR2, and A803467, inhibited the responses to xenin-25. The expression of VIP receptors (Vipr) in rat ileum was examined using RT-PCR. The Vipr1 PCR products were detected in the submucosal plexus and mucosa. Immunohistochemical staining showed the colocalization of NTSR1 and NK1 with substance P (SP)- and calbindin-immunoreactive neurons in the submucosal plexus, respectively. In addition, NK1 was colocalized with noncholinergic VIP secretomotor neurons. Based on the results from the present study, xenin-25-induced Cl-/ HCO3- secretion is involved in NTSR1 activation on intrinsic and extrinsic afferent neurons, followed by the release of SP and subsequent activation of NK1 expressed on noncholinergic VIP secretomotor neurons. Finally, the secreted VIP may activate VPAC1 on epithelial cells to induce Cl-/ HCO3- secretion in the rat ileum. Activation of noncholinergic VIP secretomotor neurons by intrinsic primary afferent neurons and extrinsic afferent neurons by postprandially released xenin-25 may account for most of the neurogenic secretory response induced by xenin-25. NEW & NOTEWORTHY This study is the first to investigate the intrinsic neuronal circuit responsible for xenin-25-induced anion secretion in the rat small intestine. We have found that nutrient-stimulated xenin-25 release may activate noncholinergic vasoactive intestinal polypeptide (VIP) secretomotor neurons to promote Cl-/ HCO3- secretion through the activation of VIP receptor 1 on epithelial cells. Moreover, the xenin-25-induced secretory responses are mainly linked with intrinsic primary afferent neurons, which are involved in the activation of neurotensin receptor 1 and neurokinin 1 receptor.


Perception of silent-center syllables by native and non-native English speakers.
The amount of acoustic information that native and non-native listeners need for syllable identification was investigated by comparing the performance of monolingual English speakers and native Spanish speakers with either an earlier or a later age of immersion in an English-speaking environment. Duration-preserved silent-center syllables retaining 10, 20, 30, or 40 ms of the consonant-vowel and vowel-consonant transitions were created for the target vowels /i, I, eI, epsilon, ae/ and /a/, spoken by two males in /bVb/ context. Duration-neutral syllables were created by editing the silent portion to equate the duration of all vowels. Listeners identified the syllables in a six-alternative forced-choice task. The earlier learners identified the whole-word and 40 ms duration-preserved syllables as accurately as the monolingual listeners, but identified the silent-center syllables significantly less accurately overall. Only the monolingual listener group identified syllables significantly more accurately in the duration-preserved than in the duration-neutral condition, suggesting that the non-native listeners were unable to recover from the syllable disruption sufficiently to access the duration cues in the silent-center syllables. This effect was most pronounced for the later learners, who also showed the most vowel confusions and the greatest decrease in performance from the whole word to the 40 ms transition condition.


A completed audit to reduce hospital outpatients non-attendance rates.
An audit loop for patients failing to attend a paediatric outpatient department was completed by repeating the analysis three years after interventions were put into place. The 1995 study had shown non-attendance for clinic visits was 34%, varying from 32.5% for Europeans and 50% for Asian patients. A follow up study in 1998 showed a fall to 12.04% and 13.5%, respectively, with an overall rate of 12.3%. The Manor Hospital NHS Trust had the lowest non-attendance rate of the 30 hospitals in the West Midlands region for the year 1996-7.


Effect of trichloroethylene on spatiotemporal pattern of LTP in mouse hippocampal slices.
The effect of trichloroethylene (TCE) on long-term potentiation (LTP) was studied using both electrical and optical recording. The hippocampi from mice injected with 300 mg/kg or 1000 mg/kg TCE were sliced 24 h after administration. The field potential from the CAI was recorded. After the application of tetanus, population spikes (PS) were potentiated in all groups, but the post-per-pre ratio of PS was smaller in TCE groups than in the control. Optical recording was also carried out in 1000 mg/kg TCE-injected mice and a new analytical method using a high speed camera was employed. After the induction of tetanus, the optical signal was potentiated in both TCE and control groups. However, the post-per-pre ratio of the optical signals and response area were smaller in the TCE groups than in the control. It was suggested that the impairment of LTP is one of the mechanisms of the impairment of immediate memory after acute exposure to TCE in humans.


Two-Layer Palatal Reconstruction Reduces Postoperative Intraoral Complications in Head and Neck Surgery.
Although microvascular free flaps are commonly performed and have high success rates, postoperative oronasal fistulas or infections do occur. The authors hypothesized that a two-layer closure is effective for prevention of intraoral complications. Patients who underwent palatal reconstruction with a microvascular free flap were evaluated retrospectively. The cases were divided into two groups (palatal reconstruction with or without a two-layer closure). A two-layer closure involves unilateral reconstruction with a free flap, then reconstruction of the nasal lining with a local flap or folding free flap. The postoperative complication rates between these two groups were compared. One hundred fifty-five cases were evaluated. A two-layer closure was performed in 65 cases (41.9 percent). The incidence of infections, dehiscence of the recipient site, and oronasal fistula were significantly higher in the single-layer closure group than in the two-layer closure group [10.0 percent versus 0 percent (p = 0.011); 15.6 percent versus 4.6 percent (p = 0.036); and 17.8 percent versus 4.6 percent (p = 0.013), respectively]. A two-layer closure in palatal reconstruction was shown to reduce the rate of infection, intraoral wound dehiscence, and oronasal fistula in the current study. A two-layer closure provides greater support and stability and reduces the risk of failure in reconstruction of the palate with a microvascular free flap. Therapeutic, III.


[The effect of self-foot reflexology on the relief of premenstrual syndrome and dysmenorrhea in high school girls].
This study was aimed to identify the effect of self-foot reflexology on the relief of premenstrual syndrome and dysmenorrhea in high school girls. Study subjects was 236 women residing in the community, teachers and nurses who were older than 45 were recruited. Data was collected with self administered questionnaires from July 1st to August 31st, 2003 and analysed using SPSS/WIN 10.0 with Xtest, t-test, and stepwise multiple logistic regression at a significant level of =.05. The breast cancer screening rate was 57.2%, and repeat screening rate was 15.3%. With the multiple logistic regression analysis, factors associated with mammography screening were age and perceived barriers of action, and factors related to the repeat mammography screening were education level and other cancer screening experience. Based on the results, we recommend the development of an intervention program to decrease the perceived barrier of action, to regard mammography as an essential test in regular check-up, and to give active advertisement and education to the public to improve the rates of breast cancer screening and repeat screening.


Comparison of water potentials measured by in situ psychrometry and pressure chamber in morphologically different species.
Leaf water potentials measured by in situ psychrometry were compared with leaf water potentials measured by the pressure chamber technique at various values of water potential in Helianthus annuus, Helianthus nuttallii, Vigna unguiculata, Nerium oleander, Pistacia vera, and Corylus avellana. In V. unguiculata, the leaf water potentials measured by the in situ psychrometer oscillated at the same periodicity as, and proportional to, the leaf conductance. In all species, potentials measured by in situ psychrometers operating in the psychrometric mode were linearly correlated with potentials measured with the pressure chamber. However, the in situ psychrometers underestimated the leaf water potential in the two Helianthus species at low water potentials and overestimated the water potential in P. vera, N. oleander, and C. avellana. The underestimation in the two Helianthus species at low water potentials resulted from differences in water potential across the leaf. The overestimation in P. vera, N. oleander, and C. avellana was considered to arise from low epidermal conductances in these species even after abrasion of the cuticle. Pressure-volume studies with Lycopersicon esculentum showed that less water was expressed from distal than proximal leaflets when the whole leaf was slowly pressurized. The implication of this for water relations characteristics obtained by pressure-volume techniques is discussed. We conclude that in situ psychrometers are suitable for following dynamic changes in leaf water potential, but should be used with caution on leaves with low epidermal conductances.


[Quality standard of tanre kesou granules].
A TLC method was used in the identification of the following chemical consitituents of medicinal herbs in Tanre Kesou Granules: Radix Scutellariae, Bulbus Fritillariae Thunbergii, Pericarpium Citri Reticulatae and Fructus Aurantii Immaturus. The sample was purified through acidification with hydrochloric acid and extraction with ethyl acetatethe. The contents of baicalin in the preparation and Radix Scutellariae were determined by means of HPLC and TLC-densitometry. These methods fit for quality control of the preparation containing baicalin.


[A case of sarcomatoid carcinoma of the urinary bladder].
We reported a case of sarcomatoid carcinoma of the bladder in a 62-year-old man admitted to our hospital because of intermittent macroscopic hematuria. Under the diagnosis of invasive bladder tumor, the patient underwent radical cystectomy and construction of an ileal conduit. Microscopic examination showed a tumor composed of spindle cells that are arranged in a storiform pattern reminiscent of that seen in malignant fibrous histiocytoma without any component of obvious epithelial tumors. Immunohistochemical examination showed that the spindle cells were positive for cytokeratin and we diagnosed the tumor as sarcomatoid carcinoma. The patient has remained well without any evidence of recurrence for 30 months after radical cystectomy. The distinction between sarcomatoid carcinoma that lacks conventional epithelial component and MFH is very difficult and important.


Nuclear receptors and their coregulators in kidney.
Nuclear receptors are transcription factors that are essential in embryonic development, maintenance of differentiated cellular phenotypes, metabolism, and apoptosis. Dysfunction of nuclear receptor signaling leads to a wide spectra of proliferative, reproductive, and metabolic diseases, including cancers, infertility, obesity, and diabetes. In addition, many proteins have been identified as coregulators which can be recruited by DNA-binding nuclear receptors to affect transcriptional regulation. The cellular level of coregulators is crucial for nuclear receptor-mediated transcription and many coregulators have been shown to be targets for diverse intracellular signaling pathways and posttranslational modifications. This review provides a general overview of the roles and mechanism of action of nuclear receptors and their coregulators. Since progression of renal diseases is almost always associated with inflammatory processes and/or involve metabolic disorders of lipid and glucose, cell proliferation, hypertrophy, apoptosis, and hypertension, the importance of nuclear receptors and their coregulators in these contexts will be addressed.


Cytochrome P450. The Dioxygen-Activating Heme Thiolate.
Cytochromes P450 (CYPs) are heme b-binding enzymes and belong to Nature's most versatile catalysts. They participate in countless essential life processes, and exist in all domains of life, Bacteria, Archaea, and Eukarya, and in viruses. CYPs attract the interest of researchers active in fields as diverse as biochemistry, chemistry, biophysics, molecular biology, pharmacology, and toxicology. CYPs fight chemicals such as drugs, poisonous compounds in plants, carcinogens formed during cooking, and environmental pollutants. They represent the first line of defense to detoxify and solubilize poisonous substances by modifying them with dioxygen. The heme iron is proximally coordinated by a thiolate residue, and this ligation state represents the active form of the enzyme. The Fe(III) center displays characteristic UV/Vis and EPR spectra (Soret maximum at 418 nm; g-values at 2.41, 2.26, 1.91). The Fe(II) state binds the inhibitor carbon monoxide (CO) to produce a Fe(II)-CO complex, with the major absorption maximum at 450 nm, hence, its name P450. CYPs are flexible proteins in order to allow a vast range of substrates to enter and products to leave. Two extreme forms exist: substrate-bound (closed) and substrate-free (open). CYPs share a sophisticated catalytic cycle that involves a series of consecutive transformations of the heme thiolate active site, with the strong oxidants compound I and II as key intermediates. Each of these high-valent Fe(IV) species has its characteristic features and chemical properties, crucial for the activation of dioxygen and cleavage of strong C-H bonds.


PGD2 induces pulmonary hyperresponsiveness to acetylcholine in vivo in the guinea-pig.
1 A threshold dose of Prostaglandin D2 (PGD2) (0.5 microgram/kg i.v.), which did not modify the basal values of airway resistance, potentiated the acetylcholine induced bronchospasm in anaesthetized guinea-pigs. 2 beta-adrenoreceptors blockade induced by propranolol enhanced the positive interaction between PGD2 and acetylcholine in the pulmonary dynamics. 3 Active sensitization of guinea-pigs by ovalbumin increased the pulmonary PGD2-acetylcholine interaction and the phenomenon was sustained during the time. 4 The inability of PGD2 to potentiate histamine-induced bronchoconstriction suggests a specificity for the interaction.


[Application of V-Y advanced flap pedicled with posterior perforator from medial malleolus for small skin defect at achilles tendon region].
To investigate the therapeutic effect of V-Y advanced flap pedicled with posterior perforator from medial malleolus for small skin defect at achilles tendon region. From Mar. 2011 to Sep. 2012, 7 cases with small skin defect at achilles tendon region were treated by V-Y advanced flap pedicled with posterior perforator from medial malleolus. The flaps was 6.0 cm x 3.0 cm-9.0 cm x 4.5 cm in size. The defects at the donor sites were closed directly. All flaps survived completely. 7 cases were followed up for 6-8 months after operation. The flaps had good texture and color match. The function of ankle was normal. All patients were satisfied with postoperative function and shape. It is an ideal reconstruction method for skin defect at achilles tendon region with V-Y advanced flap pedicled with posterior perforator from medial malleolus. It is easily performed with low risk and short recovery time.


Clinical implications of proteolytic activity imbalance in breast cancer diagnosis.
Matrix metalloproteinase-9 and its tissue inhibitor TIMP-1 have been documented as putative tumor markers because of their involvement in cancer invasion and metastasis. The aim of our study was to elucidate the diagnostic efficacy of proteolytic activity markers among traditional tumor markers (CEA and CA15.3) and clinicopathological variables. Serum samples were withdrawn from 160 individuals (80 patients with primary breast cancer, 40 patients with benign breast lesions and 40 individuals serve as healthy controls). MMP-9 and TIMP-1 were measured by ELISA and gelatin zymography. The best cutoff points for MMP-9 and TIMP-1 were depicted by receiver operating characteristic (ROC) curve. The positivity rates and the median levels for MMP-9 and TIMP-1 showed significant difference among the three investigated groups (P< 0.0001). MMP-9 and MMP-9/TIMP-1 were inversely related to clinical stage and lymph node involvement (P< 0.0001). TIMP-1 was significantly correlated with hormonal receptor status (ER, and PgR). MMP zymography results were comparable to those from ELISA. The sensitivity and the specificity of MMP-9, TIMP-1 and MMP-9/TIMP-1 were superior to traditional tumor markers (CEA and CA15.3) especially for early stages (T1) and low grade breast cancer patients. These findings indicate that investigated biomarkers are constructive for early diagnosis of breast cancer and MMP-9/TIMP-1 ratio might be a new significant marker in predicting breast cancer development.


Determination of toe-off event time during treadmill locomotion using kinematic data.
Researchers collecting gait kinematic data during treadmill locomotion are often interested in determining the times of toe off and heel strike for each stride. In the absence of additional hardware, only position data collected with motion-capture equipment may be available. Others have published methods for using kinematic data for detecting overground gait events. However, during treadmill locomotion, especially running, overground methods may not possess sufficient accuracy. The purpose of this paper is to describe a method for using kinematic data to determine the time of toe off during treadmill locomotion. Ten subjects walked and ran on a treadmill while a motion-capture system collected positional data from heel and toe markers. The treadmill was equipped with force platforms that allowed an accurate determination of foot-ground contact. The time of toe off was determined using the vertical component of the toe marker, and this method was found to have greater accuracy for event detection than other published methods. Researchers can use the described method to determine times of heel strike and toe off during treadmill locomotion using only kinematic data.


Perinatal and infant mortality in a north Swedish population, 1875-1975.
Trends in infant and perinatal mortality in Sweden over the period 1875 to 1975 are analyzed. The study is based on data from three parish registers in northern Sweden. The data are presented for four 25-year periods for five categories of survival: less than 1 day, 2-7 days, 8-28 days, 1-6 months, and 7-12 months. "The main question was whether and to what extent the specific general characteristics of this population influenced the general infant mortality statistics in the area."


[Skin layer thickness at the ear of the domesticated pig , with special reference to the use of the ear integument for human dermatological research].
Based on a shrinkage-free methodical approach (special plastic resin embedding, frozen section technique) and histological routine staining, the thickness of the different skin layers was measured from 15 regions of the outer and the inner side of the porcine auricle. Mean thickness values were for the str. corneum: 19 microns outside/20 microns inside, vital epidermis without ridges: 52 microns outside/56 microns inside, dermis: 1175 microns outside/1112 microns inside, hypodermis: 1024 microns outside/741 microns inside, perichondrium: 295 microns outside/220 microns inside. When both sides of the auricle were compared, it became obvious that the outer side generally had a thicker dermis (1140-1290 microns) and hypodermis (780-1150 microns), whereas the inner side had a thicker vital epidermis (50-60 microns) and deeper epidermal ridges (145-165 microns). The results are discussed with regard to corresponding findings from the human skin, and one region of the outer side of the porcine auricle is recommended as suitable for human dermatological research.


Open mastoidectomy and temporalis flap in the control of chronic otorrhoea.
Open mastoid surgery still remains a principal operative treatment for chronic discharging ear. The indications for this procedure still abound in the tropics although it is rarely done in the developed countries nowadays. This series re-emphasize the control of chronic otorrhoea and operative wound infection as benefiting from a combined open mastoidectomy and reconstruction with deep temporalis fascia flap in children. The operative technique is further discussed. It is our hope that repopularising this procedure will help in the control of highly prevalent chronic ear in the tropical environment.


Optimizing information flow in small genetic networks. IV. Spatial coupling.
We typically think of cells as responding to external signals independently by regulating their gene expression levels, yet they often locally exchange information and coordinate. Can such spatial coupling be of benefit for conveying signals subject to gene regulatory noise? Here we extend our information-theoretic framework for gene regulation to spatially extended systems. As an example, we consider a lattice of nuclei responding to a concentration field of a transcriptional regulator (the input) by expressing a single diffusible target gene. When input concentrations are low, diffusive coupling markedly improves information transmission; optimal gene activation functions also systematically change. A qualitatively different regulatory strategy emerges where individual cells respond to the input in a nearly steplike fashion that is subsequently averaged out by strong diffusion. While motivated by early patterning events in the Drosophila embryo, our framework is generically applicable to spatially coupled stochastic gene expression models.


Prostate cancer in African Americans: relationship of patient and partner self-efficacy to quality of life.
This study examined the relationship between patient and partner ratings of self-efficacy for symptom control and quality of life (QOL) among 40 African American prostate cancer survivors and their intimate partners. Data analyses revealed that cancer survivors who had rated their self-efficacy for symptom control higher reported better QOL related to urinary, bowel, and hormonal symptoms and better general health QOL (i.e., better physical functioning and better mental health). Data analyses also revealed that partners who rated their self-efficacy for helping the patient manage symptoms as higher reported better QOL (i.e., less negative mood and less caregiver strain). Finally, exploratory analyses indicated that higher self-efficacy in patients was associated with less anxiety and caregiver strain in partners, and higher self-efficacy in partners was associated with better adjustment to bowel and hormonal symptoms and better mental health in patients. The clinical implications of these findings are discussed and future directions for research on self-efficacy in African American prostate cancer survivors are identified.


Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 8. Central (Zn(II), Cu(II), Mg(II)(H2O), Cd(II)) and exocyclic (Pd(II)) metal ion binding in heteropentametallic complexes from tetrakis-2,3-[5,6-di(2-pyridyl)pyrazino]porphyrazine.
A series of heteropentametallic porphyrazine macrocycles, represented as [(PdCl(2))(4)LM], where L = dianion of tetrakis-2,3-[5,6-di(2-pyridyl)pyrazino]porphyrazine and M = Zn(II), Cu(II) Mg(II)(H(2)O) or Cd(II), were prepared by reaction of the corresponding mononuclear [LM] species, and their behavior was examined by UV-visible and NMR spectroscopy, electrochemistry, and thin layer spectroelectrochemistry in nonaqueous media. The PdCl(2) units in [(PdCl(2))(4)LM] are coordinated at the pyridine N atoms of the external dipyridinopyrazine fragments ("py-py" coordination) and are displaced out of the plane of the central pyrazinoporphyrazine macrocycle as verified by (1)H and (13)C NMR data on [(PdCl(2))(4)LZn]. The same arrangement is also strongly suggested by similar NMR data on the Mg(II) and Cd(II) analogues. The predominant component in the synthesized materials among the four predictable macrocyclic isomers has the four exocyclic N(2(py))PdCl(2) square planar coordination sites on the same side of the central macrocyclic framework (4:0 isomer, C(4v) symmetry), and this is accompanied by a minor isomeric component (2:2 cis or trans), in line with previous findings on the pentapalladated species [(PdCl(2))(4)LPd]. IR, UV-visible, and NMR spectral data also provide evidence for transmetalation reactions of the type [(PdCl(2))(4)LMg(H(2)O)] --> [(PdCl(2))(4)LPd] and [(PdCl(2))(4)LCd] --> [(PdCl(2))(4)LPd], with the amount of [(PdCl(2))(4)LPd] formed varying from batch to batch. Dissociation of the four exocyclic PdCl(2) units from [(PdCl(2))(4)LM] occurs in pyridine, but the compounds are stable in N,N-dimethylformamide (DMF) or dimethylsulfoxide (DMSO) and can be stepwise reduced via two one-electron reversible or quasi-reversible processes, prior to an irreversible electroreduction of the bound PdCl(2) group at more negative potentials. This metal-centered reduction leads to a [LM](2-) product which is then further reduced to [LM](3-) and [LM](4-) at the electrode surface. The first two reductions of the heteropentametallic compounds are easier than those of the monometallic [LM] species but generally more difficult than reduction of the related octacationic [L'M](8+) derivatives (L' = the octamethylated free-base dianion) whose redox properties were previously reported. The Cd(II) octacation [L'Cd](8+), isolated as an iodide salt, was also synthesized for the first time in the current study, and its spectroscopic and electrochemical properties are compared to that of the previously examined analogues.


[Methods and technics of electrostimulation].
The author presents a series of techniques and methods for electrostimulation that are widely used in various medical specialties, such as anesthesiology and intensive care, neurology and psychiatry, obstetrics and gynecology, internal medicine, otorhinolaryngology, urology, orthopaedics, stomatology, etc. Methods, devices and indications are described for electrostimulation, and the formation is proposed of a "group for electrostimulation" in the frame of the Society for Anesthesiology and Intensive Care from our country.


Physical Activity in Crisis: The Impact of COVID-19 on Danes' Physical Activity Behavior.
Objectives: Because of the COVID-19 pandemic, societies have been shut down, changing the lives of citizens worldwide, including their physical activity (PA) behavior. This cross-sectional study aimed to investigate the impact of the shutdown on Danish citizens' leisure PA throughout different stages of life: 15-18, 19-29, 30-59, and 60+ years. Methods: Between April 3 and 15, 2020, while Denmark was shut down, a survey was distributed through online platforms. Danish citizens (>15 years) could participate in the study, answering questions about their PA behavior before, and during the shutdown. Results: The number of total participants was 1,802; 7.9% teens, 21.5% younger adults, 58.7% adults, and 11.9% older adults. Mean minutes of PA decreased 16.1% from before to during the shutdown. Teens had the largest decrease in PA (36.6%) followed by older (24.9%) and younger adults (21.3%). Low educated (31.5%) and those living in rural areas (30.9%) experienced the largest decrease in PA. Main factors for not doing PA during the shutdown were that they missed what they used to do, lacked social support, and did not have access to the right facilities. Conclusions: During the shutdown, the Danish population struggled even more to comply with national PA guidelines compared with before the shutdown. Although social distancing and shutting down sports facilities are important for preventing the spread of the virus, it can have negative consequences for teens' and younger and older adults' opportunities and motivation for PA, leading to an alarming decrease in PA, and, consequently, will have major public health consequences.


The Use of Media as a Sleep Aid in Adults.
A sample of 844 adults, aged 18-94 years old, was queried about media habits and sleep behavior in face-to-face interviews with standardized questionnaires. A substantial proportion of this sample reported using books (39.8%), television (31.2%), music (26.0%), Internet (23.2%), and videogames (10.3%) as a sleep aid. The use of media as sleep aids was associated with increased fatigue and higher scores on the Pittsburgh Sleep Quality Index (PSQI), indicating poorer sleep quality. There was no relationship with sleep duration. Finally, results suggest that media use coincides with later bedtimes, but also later rise times, a process called time shifting.


A Comprehensive Analysis of Cerebellar Volumes in the 22q11.2 Deletion Syndrome.
The presence of a 22q11.2 microdeletion (22q11.2 deletion syndrome [22q11DS]) ranks among the greatest known genetic risk factors for the development of psychotic disorders. There is emerging evidence that the cerebellum is important in the pathophysiology of psychosis. However, there is currently limited information on cerebellar neuroanatomy in 22q11DS specifically. High-resolution 3T magnetic resonance imaging was acquired in 79 individuals with 22q11DS and 70 typically developing control subjects (N = 149). Lobar and lobule-level cerebellar volumes were estimated using validated automated segmentation algorithms, and subsequently group differences were compared. Hierarchical clustering, principal component analysis, and graph theoretical models were used to explore intercerebellar relationships. Cerebrocerebellar structural connectivity with cortical thickness was examined via linear regression models. Individuals with 22q11DS had, on average, 17.3% smaller total cerebellar volumes relative to typically developing subjects (p < .0001). The lobules of the superior posterior cerebellum (e.g., VII and VIII) were particularly affected in 22q11DS. However, all cerebellar lobules were significantly smaller, even after adjusting for total brain volumes (all cerebellar lobules p < .0002). The superior posterior lobule was disproportionately associated with cortical thickness in the frontal lobes and cingulate cortex, brain regions known be affected in 22q11DS. Exploratory analyses suggested that the superior posterior lobule, particularly Crus I, may be associated with psychotic symptoms in 22q11DS. The cerebellum is a critical but understudied component of the 22q11DS neuroendophenotype.


A PLCdelta1-binding protein, p122RhoGAP, is localized in focal adhesions.
We have investigated the cellular distribution of p122RhoGAP, a GTPase-activating protein of Rho small GTPase and an activator of phospholipase C-delta(1). Immunofluorescence studies demonstrated that endogenous p122 is localized at the tips of actin stress fibres and co-localizes with vinculin in normal rat kidney cells. In immunoprecipitation studies, p122 co-precipitated with vinculin, indicating that p122 is localized at the sites of focal adhesion. We have also shown that the N-terminal half of p122 is responsible for this localization. It is conceivable, therefore, that p122 is involved in the reorganization of the actin cytoskeleton and focal adhesions that regulate cell-substratum adhesion and cell migration.


Emerging roles of circular RNAs in retinal diseases.
Retinal disorders are a group of ocular diseases whose onset is associated with a number of aberrant molecular and cellular processes or physical damages that affect retinal structure and function resulting in neural and vascular degeneration in the retina. Current research has primarily focused on delaying retinal disease with minimal success in preventing or reversing neuronal degeneration. In this review, we explore a relatively new field of research involving circular RNAs, whose potential roles as biomarkers and mediators of retinal disease pathogenesis have only just emerged. While knowledge of circular RNAs function is limited given its novelty, current evidence has highlighted their roles as modulators of microRNAs, regulators of gene transcription, and biomarkers of disease development and progression. Here, we summarize how circular RNAs may be implicated in the pathogenesis of common retinal diseases including diabetic retinopathy, glaucoma, proliferative vitreoretinopathy, and age-related macular degeneration. Further, we explore the potential of circular RNAs as novel biomarkers and therapeutic targets for the diagnosis and treatment of retinal diseases.


Theoretical studies of CH4 inside an open-cage fullerene: translation-rotation coupling and thermodynamic effects.
Molecules trapped inside fullerenes exhibit interesting quantum behavior, including quantization of their translational degrees of freedom. In this study, a theoretical framework for predicting quantum properties of nonlinear small molecules in nonsymmetric open-cage fullerenes (OCFs) has been described along the lines of similar theories which treat small molecules inside C(60) and clathrate cages. As an example, the coupled translational-rotational energy structure has been calculated for the case of CH(4) inside a known OCF. The calculated energy levels have been used to calculate the equilibrium fraction of incorporated CH(4) as well as the translational heat capacity for the encapsulated molecule. The heat capacity shows an anomalous maximum at 239 K for CH(4) and 215 K for CD(4) which are not present in free methane.


Isoindolone-Containing Meroperpenoids from the Endophytic Fungus Emericella nidulans HDN12-249.
Six isoindolone containing meroterpenoids, emericellolides A-C (1-3) and emeriphenolicins E-G (4-6), were isolated from a plant endophytic fungus Emericella nidulans HDN12-249. Emericellolides A-C (1-3) feature the unprecedented macrolide skeleton composed of an unusual l-glutamate fragment, an isoindolone unit, and a sesquiterpene moiety, while structures of emeriphenolicins E-G (4-6) with two farnesyl groups attached to one isoindolone unit are rare in isoindolone-derived meroterpenoids. These structures including the absolute configurations were established on the basis of MS, NMR, Mo2(AcO)4-induced ECD, Marfey's method, and chemical conversion. Compound 4 exhibited cytotoxicity against HeLa cells with IC50 value of 4.77 μM.


Developmental expression of Xenopus myosin 1d and identification of a myo1d tail homology that overlaps TH1.
Xenopus laevis myosin 1d (XlMyo1d) is a member of the myosin I class, subclass 4. Members of this class are single headed, bind calmodulin light chains and have lipid binding domains in their tails. The rat myo1d homologue has been implicated in endosome vesicle recycling in epithelial cells. Mutations in the Drosophila myosin 1d homologue cause situs inversus in the abdomen. The XlMyo1d cDNA has been cloned and the derived amino acid sequence is 80% identical to the rat and human homologues. Sequence comparison revealed a novel isoform-specific tail homology embedded in the Tail Homology 1 (TH1) domain characteristic of myosin I isoforms. Western blot analysis using a polyclonal antibody raised against an isoform-specific peptide showed that the protein is present in eggs and levels increase at early neurula through tadpole stages. Whole mount in situ hybridization using a probe containing the 5'UTR (untranslated region) showed that XlMyo1d mRNA is expressed in neural tube, pre-somitic mesoderm, somites and all three segments of cranial neural crest cells during their migration. Sections of the in situ hybridizations revealed that during somitogenesis, XlMyo1d mRNA was localized to a stripe overlapping the nuclear region of somites during early tadpole stages.


Landscape risk factors for attacks of vampire bats on cattle in Sao Paulo, Brazil.
Vampire-bat (Desmodus rotundus) attacks on cattle are a major concern for cattle-raising area. Blood loss and paralytic rabies due to bat bites can impose severe losses on the livestock. We took four municipalities inside the Sao Joao da Boa Vista veterinary district (Sao Paulo, Brazil) as a study area and tested a set of landscape features for spatial correlation with distance to areas in which vampire-bat attacks on cattle were documented. Bat- and cattle-related data from the Sao Paulo State Rabies Control Program were used. Landscape data (first-order rivers and their tributaries, main roads, railways and urban areas) were obtained from official cartographic agencies; forest, sugarcane and pasture data were acquired from remote-sensing mappings. The study area was taken as a grid split into 178 cells. Each 4kmx4km cell was filled with bat, cattle and landscape data. Our analysis detected that grid cells that were closer to areas of bat attacks on cattle had higher cattle density and a greater percentage of the land committed to sugarcane cropping, and were close to forest fragments. These results shed light on the need for rethink the Rabies Control Program strategies for defining the surveillance of vampire-bat populations and rabies control in the state of Sao Paulo, Brazil.


Metabolic Disorders After Liver Transplantation.
Early after surgery, liver transplant (LT) recipients often develop weight gain due to an increase of caloric intake and fat mass (without recovery of muscle frame). This modification of body composition together with a negative metabolic impact of immunosuppressive drugs leads to a high prevalence of all the main metabolic disorders. Indeed, as expected, transplanted patients show a higher cardiovascular risk in comparison with general population. Notably, seeing the increase of mean age of transplanted population, metabolic disorders represent the true challenge for the transplant community. Considering the lack of evidences or clear indications about prevention, early diagnosis and treatment of metabolic disorders after LT, it would be mandatory to develop targeted further studies on this matter.


The importance of lipid spectrum changes in women with polycystic ovary syndrome(PCOS).
of the study was to compare levels of blood lipids, anthropometric characteristics and their relationship in women with PCOS with a group of healthy women. We determined anthropometric indicators (BMI - body mass index, waist measurement, waist/hip ratio), blood lipid levels (total cholesterol TCH, high density cholesterol HDL, low density cholesterol LDL and triglycerides TAG) in a group of women with PCOS and a healthy control group. Levels of evaluated blood lipids in women with PCOS and the healthy control group were within the normal range. Women with PCOS differed statistically significantly from the control group in a higher concentration of triglycerides (control 1.01 ± 0.7 mmol.l-1, PCOS 1.17 ± 0.58). In women with PCOS we proved a positive correlation between BMI, total cholesterol, LDL cholesterol and levels of triglycerides. In women with PCOS waist measurement showed a statistically significant relationship to values of LDL cholesterol, HDL cholesterol and level of triglycerides. All women with PCOS in our study had very good levels of blood lipoproteins (total cholesterol, LDL and HDL cholesterol, triglycerides) so we are not sure if there is any importance of changes in blood lipid metabolism in these patients (Tab. 1, Fig. 2, Ref. 16).


Function-related changes in energy metabolism in the nervous system: localization and mechanisms.
Previous neuroanatomical and electrophysiological methods to localize functional activity in the nervous system focus on perikarya as the sites of the activity. Metabolic mapping of local functional activity in the nervous system provides a new dimension, the activity in the neuropil. Studies of local glucose utilization have shown that energy metabolism is increased by functional activation, but the effects are mainly in the terminal projection zones of the activated pathway. Electrical stimulation of a pathway raises glucose utilization in the projection zones of the pathway in almost direct proportion to the spike frequency. For example, electrical stimulation of the sciatic nerve produces frequency-dependent metabolic activation in the dorsal horn of the lumbar cord, where the axonal terminals of the afferent pathway reside, but no apparent metabolic effects in the cell bodies of the pathway in the dorsal root ganglia. Functional activation of the hypothalamo-hypophysial pathway by salt-loading increases glucose utilization in the pituitary neural lobe, where the terminal axons of the pathway reside, but not in the paraventricular and supraoptic nuclei, the sites of the cell bodies of origin of the pathway. Reflex activation by hypotension of pathways to these nuclei from brain stem structures involved in baroreceptor reflexes, however, increases glucose utilization in these nuclei. Depolarization induced by electrical stimulation, extracellular K+, or opening of Na+ channels with veratridine, stimulates glucose utilization in neural tissues, and this increase is blocked by ouabain, a specific inhibitor of Na+, K(+)-ATPase. Activation of this enzyme to restore ionic gradients across cellular membranes appears to trigger the functional activation of energy metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)


#metoo? The association between sexual violence history and parturients' gynecological health and mental well-being.
Sexual violence is a global health problem. We aimed to evaluate the association between self-reported history of sexual violence and parturients' health behaviors, focusing on routine gynecological care, and mental well-being. This was a retrospective questionnaire-based study, including mothers of newborns delivered at the "Soroka" University Medical Center (SUMC). Participants were asked to complete three validated questionnaires, including: screening for sexual violence history (SES), post-traumatic stress disorder (PDS) and post-partum depression (EPDS). Additionally, a demographic, pregnancy and gynecological history data questionnaire was completed, and medical record summarized. Multiple analyses were performed, comparing background and outcome variables across the different SES severity levels. Multivariable regression models were constructed, while adjusting for confounding variables. The study included 210 women. Of them, 26.3% (n = 57) reported unwanted sexual encounter, 23% (n = 50) reported coercion, 1.8% (n = 4) assault and attempted rape, and 1.4% (n = 3) reported rape. A significant association was found between sexual violence history and neglected gynecological care, positive EPDS screening, and reporting experiencing sexual trauma. Several multivariable regression models were constructed, to assess independent associations between sexual violence history and gynecological health-care characteristics, as well as EPDS score. Sexual violence history was found to be independently and significantly associated with a negative relationship with the gynecologist, avoidance of gynecological care, sub-optimal routine gynecological follow-up, and seeking a gynecologist for acute symptoms (adjusted OR = 0.356; 95% CI 0.169-0.749, adjusted OR = 0.369; 95% CI 0.170-0.804, adjusted OR = 2.255; 95% CI 1.187-4.283, and adjusted OR = 2.113; 95% CI 1.085-4.111, respectively), as well as with the risk of post-partum depression (adjusted OR = 4.46; 95% CI 2.03-9.81). All models adjusted for maternal age and ethnicity. Sexual violence history is extremely common among post-partum women. It is independently associated with post-partum depression, neglected gynecological care, a negative relationship with the gynecologist, and with reporting of experiencing sexual trauma. Identifying populations at risk and taking active measures, may reduce distress and improve emotional well-being and family function.


In vitro reconstruction of an autologous, watertight, and resistant vesical equivalent.
Currently, bladder repair is performed using gastrointestinal segments; however, this technique has a high morbidity rate, and new alternatives are thus needed. The lack of native or synthetic tissue with similar properties of the bladder led us to develop autologous vesical substitutes entirely made by tissue engineering and without exogenous matrices. Watertight function and mechanical resistance are fundamental for the model. The aim of this study was to determine the structural and functional characteristics of our vesical equivalent (VE). Porcine VEs are produced in 55 days. The cellular types that make up the vesical wall are extracted and purified simultaneously from a small porcine bladder biopsy. Dermal fibroblasts are extracted and cultured in vitro to form cellular sheets. Endothelial cells were seeded on the fibroblast sheets before their superimposition. Urothelial cells are then seeded onto this cellular construction. VEs are characterized by histology, immunostaining, electron microscopy, and cell viability. Mechanical properties of the reconstructed substitutes are evaluated by uniaxial tensile tests, and tissue absorption is verified with (14)C-urea, which quantifies the degree of impermeability. This process allowed us to obtain a highly structured tissue with a total fusion of the fibroblast layers. As expected, histological observations showed a pseudostratification of the urothelium developing on an organized self-secreted extracellular matrix. Positive markers for cytokeratin 8/18 in immunostaining confirmed the presence of a urinary epithelium. Electron microscopy confirmed the normal aspect of urothelial cells. Our VE's permeability to (14)C-urea was significantly similar to porcine bladder, and characterization of the mechanical properties indicated that our tissue could be suitable for grafting since its ultimate tensile strength compares favorably with a native porcine bladder. The construction of a VE using this method seems very promising in meeting the needs in the urological field. Our substitute has proven its efficiency as a barrier to urea and has a sufficient mechanical resistance to support suturing. Additionally, this model is completely autologous, and its possible endothelialization could promote the early vascularization process after grafting and thus significantly reducing inflammation and possible rejection.


A comparative study of ultrasonic pretreatment and an internal recycle for the enhancement of mesophilic anaerobic digestion.
The objective of this study was to investigate the use of ultrasonic energy in an internal recycle and pretreatment mode of operation relative to a conventional mode of mesophilic anaerobic digestion. The primary focus was to determine if using ultrasonics in a pretreatment mode and in an internal recycle line produced changes in performance relative to each other and the control. Using a relatively low-energy sonication system, the data showed that the addition of ultrasonic energy, in either a recycle line or as a pretreatment technology, improved anaerobic digestion efficiency for waste-activated sludge. There was a 13 to 21% increase in biogas yield and an increase in total and volatile solids destruction of 3 to 10.3 additional percentage points, depending on the ultrasonic dose and location. Dewatering of the biosolids following ultrasonic treatment was poorer, as measured by an increase in the optimum polymer conditioning dose. The addition of ultrasonics to the digestion systems generated a more stable biosolids product, with a 2 to 58% reduction in organo-sulfur gas production from dewatered biosolids cakes.


Designing "high-affinity, high-specificity" glycosaminoglycan sequences through computerized modeling.
The prediction of high-affinity and/or high-specificity protein-glycosaminoglycan (GAG) interactions is an inherently difficult task, due to several factors including the shallow nature of the typical GAG-binding site and the inherent size, flexibility, diversity, and polydisperse nature of the GAG molecules. Here, we present a generally applicable methodology termed Combinatorial Library Virtual Screening (CVLS) that can identify potential high-affinity, high-specificity protein-GAG interactions from very large GAG combinatorial libraries and a suitable GAG-binding protein. We describe the CVLS approach along with the rationale behind it and provide validation for the method using the well-known antithrombin-thrombin-heparin system.


Extensor tendon rupture associated with osteoarthritis of the distal radioulnar joint.
Non-rheumatoid osteoarthritis of the distal radioulnar joint can cause extensor tendon rupture. We analysed the radiographic morphology of the distal radioulnar joint to identify the risk factors for this complication. Forty-one wrist X-rays of 37 patients with extensor tendon rupture caused by distal radioulnar joint osteoarthritis were evaluated retrospectively for the severity of osteoarthritis by the Kellgren/Lawrence scoring system. Measurements were obtained from posteroanterior views. All but one wrist had severe osteoarthritic changes exceeding grade 3. The radiographic features that were different from those of the contralateral wrists included deepening and widening of the sigmoid notch, radial shift of the ulnar head and dorsal inclination of the sigmoid notch. There was no significant association between tendon rupture and the morphology of the ulnar head or ulnar variance. The scallop sign, dorsal inclination of the sigmoid notch and radial shift of the ulnar head are radiological risk factors for extensor tendon ruptures.


[Effect of Film Mulching, Straw Retention, and Nitrogen Fertilization on the N2O and N2 Emission in a Winter Wheat Field].
In order to explore the characteristics of N2O emissions from winter wheat fields in the Loess Plateau under different farming methods and nitrogen levels, the dynamic changes in N2O emissions from rain-fed winter wheat fields were quantified using static box-gas chromatography. Winter wheat 'Xiaoyan22' was used as the material, and a two-factor split area design was adopted. The conventional tillage (CT), straw incorporated into soil (SM), and flat film mulching (FM) were assigned as the main plot, and three nitrogen fertilizer rates (no nitrogen fertilization, 20% nitrogen reduction (144 kg·hm-2), and conventional nitrogen application (180 kg·hm-2)) were assigned as a split plot. Taking CT as a control, the effects of FM and SM on soil N2O emissions under different nitrogen rates were assessed. Furthermore, the correlation between relevant environmental factors and N2O emission flux were analyzed, and N2 emissions were estimated using empirical formulas. The results showed the following:the N2O emissions from the soil of each nitrogen treatment occurred within 20 days, and N2O emission flux peaked within two weeks post-fertilization. The average N2O flux, the total N2O emissions, and the global warming potential of N2O were 1.92-22.75 μg·(m2·h)-1, 0.10-0.46 kg·hm-2, and 26.72-122.15 kg·hm-2, respectively. The N2O emission coefficient of fertilizer nitrogen was 0.05%-0.28%. The total N2 emissions ranged from 0.70-1.82 kg·hm-2. The N fertilization and film mulching significantly increased the N2O emission flux (P<0.05) and the cumulative N2O emissions (P<0.05); however, SM marginally reduced the total N2O emissions. The N2O emission coefficient and global warming potential of fertilizer nitrogen under FM were significantly higher than those under CT and SM (P<0.05). The N2O emissions without nitrogen treatment were only significantly positively correlated with soil water-filled pore spaces (WFPS) (P<0.05); the N2O emissions in the N fertilization condition were significantly positively correlated with WFPS, ω(NO3--N), ω(NH4+-N), and 0-5 cm soil layer temperature (P<0.05). Overall, under the condition of no fertilization, water was the main factor to control the nitrogen transformation and soil N2O emission; nevertheless, under the N fertilization condition, both nitrification and denitrification contributed to the N2O emissions in the rain-fed winter wheat fields. Film mulching practice and nitrogen application markedly increased the N2O emissions, fertilizer nitrogen emission coefficient, and global warming potential in the rain-fed winter wheat fields. Nonetheless, straw incorporated into the soil resulted in a marginal reduction in N2O emissions.


Generalized joint hypermobility among school-aged children in Majmaah region, Saudi Arabia.
Generalized joint hypermobility (GJH) is common among schoolchildren and usually benign. However, it may progressively lead to joint pain and developmental delay. Identifying GJH in school-aged children would facilitate the monitoring of early changes and planning for early rehabilitative intervention. Epidemiological studies addressing the prevalence of GJH among children in the Gulf region and Arab ethnicity are lacking. Hence, we aimed to determine the prevalence, pattern, and factors associated with GJH among school-aged children in the Majmaah region, Saudi Arabia. Male and female school-aged children 8-14 years of age from the Majmaah region of Saudi Arabia participated in this cross-sectional study. Beighton score was used to assess GJH. Personal characteristics such as age, height, weight, body mass index, and handedness were also collected. Descriptive statistics were obtained for personal characteristics, the point prevalence of hypermobility, frequency of Beighton score distribution, and prevalence of GJH. The associations between specific factors and the presence of GJH were analyzed using chi-square and Mann-whitney tests. Using the Beighton score cutoff ≥ 4 and ≥ 6, 15.2% and 7.6% of the school children in our study were diagnosed with GJH respectively. The prevalence of GJH was higher among females (16.8%) than among males (13.4%), but the difference was not statistically significant. The elbow joints (17.2%) were the most common hypermobile joints and the trunk (0.7%) was the least involved. The children with GJH were younger and had lesser BMI compared to children without GJH (P < 0.05). The prevalence reported in this study among school-aged children was comparable with those reported worldwide.