Relationship of arterial stiffness and early mild diastolic heart failure in general middle and aged population.
The brachial-ankle pulse wave velocity (baPWV) has been recognized as a marker that reflects arterial stiffness. We conducted an investigation to evaluate whether baPWV is independently associated with early mild diastolic heart failure (DHF) in a general middle and aged population. From 1 July 2009 until 31 August 2009, we investigated 2095 subjects for the relevant factors of heart failure in the Lujiazui Community, Shanghai. The baPWV, echocardiography, and blood sampling were performed in the morning after a 12 h overnight fast. A total of 1929 subjects had the complete data, including questionnaire, age, gender, baPWV, brain natriuretic peptide, and E/A ratio. Early mild DHF was defined as a left ventricular ejection fraction >50%, E/A ratio <0.8, and E/E' ≤ 8; finally, 482 subjects with early mild DHF and 1282 subjects with non-DHF entered into analysis. Among 1764 subjects, 31.6% of the subjects were male (average age was 58.0 ± 12.3), 35.8% of the subjects had hypertension, the average body mass index (BMI) was 24.2 ± 3.3 kg/m(2), baPWV was 1513.0 (1329.1, 1763.5) cm/s, and the baPWV was significantly correlated with the E/A ratio (r = -0.39, P < 0.01). There was a difference of the baPWV [1456.0 (1295.3, 1698.3) vs. 1670.5 (1465.6, 1910.8) cm/s] between the non-DHF group and the early mild DHF group (P < 0.01). Multiple logistic-regression analyses demonstrated that age, male gender, BMI, baPWV, posterior left ventricular wall thickness (PVWT), interventricular septal thickness (IVST), E/E' ratio, left ventricular mass index (LVMI), systolic blood pressure (≥140 mmHg), and diastolic blood pressure (≥90 mmHg) were independently correlated with early mild DHF. The increased arterial stiffness is associated with early mild DHF in a general middle and aged population independently of age, male gender, BMI, PVWT, IVST, E/E' ratio, LVMI, and high blood pressure. The non-invasive techniques described may allow serial measurements to be made over time to monitor baPWV changes in arteries provided the introduction of anti-arteriosclerosis therapy.


Biochemical and developmental characterization of the murine cluster of differentiation 1 antigen.
The cluster of differentiation-1 (CD1) antigens are major histocompatibility complex (MHC) class I-like glycoproteins belonging to the immunoglobulin supergene family. Initially described in humans, more recently putative CD1 encoding genes have been identified in several other species, including the mouse where it has been clearly demonstrated that CD1 mRNA is expressed. However, in the mouse both its unusually wide tissue distribution and the prevalence of incompletely spliced RNA have raised the possibility that the mRNA did not encode a functional protein. We have utilized a rabbit polyclonal antiserum raised against an Escherichia coli-expressed recombinant murine CD1 fusion protein to characterize the murine CD1 protein. Here we demonstrate that the antiserum binds specifically to a set of glycoproteins (49,000-55,000 MW) which contain a common core protein with both a size (36,000 MW) and tissue distribution in accordance with those predicted. During thymic ontogeny, this protein is highly expressed by Day 14 of embryonic development and persists into adulthood, while its pattern of expression in other organs changes significantly during development. Thus, the mouse provides an amenable model system for the study of CD1 function.


Transcription of foreign DNA in Escherichia coli.
Propagation of heterologous DNA in E. coli host cells is central to molecular biology. DNA constructs are often engineered for expression of recombinant protein in E. coli, but the extent of incidental transcription arising from natural regulatory sequences in cloned DNA remains underexplored. Here, we have used programmable microarrays and RT-PCR to measure, comprehensively, the transcription of H. influenzae, P. aeruginosa, and human DNA propagating in E. coli as bacterial artificial chromosomes. We find evidence that at least half of all H. influenzae genes are transcribed in E. coli. Highly transcribed genes are principally involved in energy metabolism, and their proximal promoter regions are significantly enriched with E. coli sigma(70) (also known as RpoD) binding sites. H. influenzae genes acquired from an ancient bacteriophage Mu insertion are also highly transcribed. Compared with H. influenzae, a smaller proportion of P. aeruginosa genes are transcribed in E. coli, and in E. coli there is punctuated transcription of human DNA. The presence of foreign DNA in E. coli disturbs the host transcriptional profile, with expression of the E. coli phage shock protein operon and the flagellar gene cluster being particularly strongly up-regulated. While cross-species transcriptional activation is expected to be enabling for horizontal gene transfer in bacteria, incidental expression of toxic genes can be problematic for DNA cloning. Ongoing characterization of cross-expression will help inform the design of biosynthetic gene clusters and synthetic microbial genomes.


Point-of-Care Assays Could Be Useful for Therapeutic Drug Monitoring of IBD Patients in a Proactive Strategy with Adalimumab.
The objective of the study was to evaluate whether Point-of-Care (POC) assays are equivalent to ELISAs for measuring residual trough levels of adalimumab (ADA) in a cohort of Inflammatory Bowel Disease (IBD) patients. ADA trough levels obtained by POC assays were used to optimize patients in daily clinical practice. Different assays (three ELISAs (Enzyme-Linked ImmunoSorbent Assay) from two different suppliers and two POC assays) were compared to measure ADA trough levels in a first cohort of 31 IBD patients. All assays revealed a high correlation within the assays, ranging from 0.86 to 0.99. Cut-off values were always higher with ELISAs than with POC assays. Then, a small prospective clinical study with a second cohort of 37 IBD patients was performed to compare POC assays and ELISAs for their ability to optimize patients on the basis of the measured ADA trough levels. The use of a POC assay to monitor ADA trough levels did not improve the follow-up of patients with loss of response, as they were always optimized whatever their ADA residual rate. For patients in clinical remission, a POC assay can be useful in some clinical situations to maintain or de-escalate ADA doses according to the measured trough levels. In conclusion, different assays for ADA monitoring are quite equivalent. A POC assay could be only useful for a proactive strategy for asymptomatic patients with a sub-therapeutic dose of ADA, but new therapeutic thresholds need to be identified.


Grafted tendon healing in tibial tunnel is inferior to healing in femoral tunnel after anterior cruciate ligament reconstruction: a histomorphometric study in rabbits.
This study aimed to test whether graft healing in the tibial tunnel was inferior to that in the femoral tunnel after anterior cruciate ligament (ACL) reconstruction in rabbits. Surgical reconstruction by use of the digital extensor tendon in the bone tunnel was performed in 18 rabbits. The rabbits were killed at weeks 2, 6, and 12 postoperatively, with 6 at each time point, for histologic examination. The transiently formed cartilaginous interface was gradually mineralized during re-establishment of direct tendon-to-bone integration, which was observed significantly less in the tibial tunnel than in the femoral tunnel (P < .05). The cell density of the graft was significantly lower in the tibial tunnel than that in the femoral tunnel at weeks 2 and 6 postoperatively (P < .05 for both). An increase in the immature type III collagen content was accompanied by a decrease in graft collagen fiber organization, with healing over time in both the femoral and tibial tunnels. The collagen fiber organization of the graft was significantly poorer in the tibial tunnel than that in the femoral tunnel at week 12 after surgery (P < .05). Grafted tendon healing in the tibial tunnel was inferior to that in the femoral tunnel at the tendon-to-bone interface and with regard to the grafted tendon within the bone tunnel after ACL reconstruction in rabbits. Future biopsy study is desirable to test whether this observation was valid clinically, which might provide a scientific basis for therapeutic targets to improve the outcome of ACL surgery.


New insights into osteoarthritis: early developmental features of an ageing-related disease.
This review addresses possible common mechanisms of how recently identified consistent osteoarthritis susceptibility genes influence both the onset of osteoarthritis and its progression towards clinical outcomes. Genetic association studies have identified a few consistent osteoarthritis susceptibility genes (FRZB, GDF5, and DIO2) that replicate across different populations. Remarkably, each of these genes appears to be primarily involved in the endochondral ossification processes. We hypothesize that these osteoarthritis susceptibility genes may play a dual negative role. In early developmental processes, they may involve aberrant skeletal morphogenesis leading to either malformation of joints or aberrant bone composition or both, thereby increasing the biomechanical burden on the articular cartilage surface. Later in life in articular cartilage, these genes may affect the propensity of articular chondrocytes to become hypertrophic. As hypertrophic chondrocytes are not able to maintain cartilage homeostasis, these genes may, in part, be responsible for both the onset of osteoarthritis and the progression towards clinical outcomes. Major therapeutic advances may come from a focus on factors that enhance phenotypic stability of the articular chondrocyte during life, promoting the healthy articular cartilage.


Effects of Pinus massoniana bark extract on the adhesion and migration capabilities of HeLa cells.
Pinus massoniana Lamb is a Chinese red pine species used in traditional medicine for the treatment of a variety of human health disorders. Recent studies have shown that P. massoniana bark extract (PMBE) has an anti-proliferation effect on cancer cells. However, it is not clear if PMBE affects cancer cell migration and/or invasion. We tested the effect of PMBE, which has B-type procyanidin as its main constituent, on the adhesion and migration capabilities of HeLa cells, a human cervical cancer cell line, cultured in vitro. Our results showed that PMBE has no significant effect on the adhesion capability of HeLa cells, but strongly inhibits their migration. This finding suggests that PMBE could be a potential therapeutic agent for metastatic cancer.


Unilateral blindness following septoplasty.
Visual loss following routine nasal surgery is an extremely rare and devastating complication. We report a case of unilateral blindness due to orbital apex syndrome following septoplasty. We also review the literature and discuss probable causes. To the best of our knowledge, this is only the second published report of this complication.


Peripheral neuropathy in Parkinson's disease: prevalence and functional impact on gait and balance.
Peripheral neuropathy is a common problem in patients with Parkinson's disease. Peripheral neuropathy's prevalence in Parkinson's disease varies between 4.8-55%, compared with 9% in the general population. It remains unclear whether peripheral neuropathy leads to decreased motor performance in Parkinson's disease, resulting in impaired mobility and increased balance deficits. We aimed to determine the prevalence and type of peripheral neuropathy in Parkinson's disease patients and evaluate its functional impact on gait and balance. A cohort of consecutive Parkinson's disease patients assessed by movement disorders specialists based on the UK Brain Bank criteria underwent clinical, neurophysiological (nerve conduction studies and quantitative sensory testing) and neuropathological (intraepidermal nerve fibre density in skin biopsy punches) evaluation to characterize the peripheral neuropathy type and aetiology using a cross-sectional design. Gait and balance were characterized using wearable health-technology in OFF and ON medication states, and the main parameters were extracted using validated algorithms. A total of 99 Parkinson's disease participants with a mean age of 67.2 (±10) years and mean disease duration of 6.5 (±5) years were assessed. Based on a comprehensive clinical, neurophysiological and neuropathological evaluation, we found that 40.4% of Parkinson's disease patients presented peripheral neuropathy, with a predominance of small fibre neuropathy (70% of the group). In the OFF state, the presence of peripheral neuropathy was significantly associated with shorter stride length (P = 0.029), slower gait speed (P = 0.005) and smaller toe-off angles (P = 0.002) during straight walking; significantly slower speed (P = 0.019) and smaller toe-off angles (P = 0.007) were also observed during circular walking. In the ON state, the above effects remained, albeit moderately reduced. With regard to balance, significant differences between Parkinson's disease patients with and without peripheral neuropathy were observed in the OFF medication state during stance with closed eyes on a foam surface. In the ON states, these differences were no longer observable. We showed that peripheral neuropathy is common in Parkinson's disease and influences gait and balance parameters, as measured with mobile health-technology. Our study supports that peripheral neuropathy recognition and directed treatment should be pursued in order to improve gait in Parkinson's disease patients and minimize balance-related disability, targeting individualized medical care.


Tubulovascular nitric oxide crosstalk: buffering of angiotensin II-induced medullary vasoconstriction.
Studies were designed to determine the source of NO responsible for buffering of the angiotensin II (Ang II)-mediated decrease of blood flow in the renal medulla. Intracellular Ca2+ concentration ([Ca2+]i) and NO production ([NO]i) of pericytes and endothelium of the vasa recta were independently measured with the use of fura 2-AM and 4,5-diaminofluorescein diacetate (DAF-2DA), respectively, in microtissue strips of the vascular bundles of the outer medullary vasa recta. Disruption of the endothelium of the vasa recta by perfusion with latex microspheres enabled imaging of the pericytes. Ang II (1 micromol/L) produced an increase of [NO]i of 19+/-6 U in pericytes of the vasa recta when the vessels were adjacent to medullary thick ascending limbs (mTALs). Pericytes of isolated vasa recta without surrounding mTALs showed a rapid peak increase in [Ca2+]i of 248+/-107 nmol/L, with a sustained elevation of 107+/-75 nmol/L, but did not show an increase in [NO]i to either Ang II (1 micromol/L) or the Ca2+ ionophore 4-bromo-A23187 (5 micromol/L). These observations indicated the lack of Ang II and Ca2+-sensitive NO production in pericytes of the vasa recta. In isolated vasa recta with intact endothelium, Ang II reduced [Ca2+]i from 128+/-28 to 62+/-13 nmol/L and failed to increase [NO]i. However, the Ca2+ ionophore did increase [NO]i in the endothelium (47+/-8 U), indicating the presence of Ca2+-sensitive NO production. Significant increases of [NO]i were observed in single isolated mTALs in response to both Ang II (33+/-6 U) and the Ca2+ ionophore (51+/-18 U). We conclude that Ang II increases [Ca2+]i in pericytes of the descending vasa recta as part of its constrictor action and that this vasoconstriction is buffered by the NO from the surrounding tubular elements, such as mTALs.


Primary Squamous Cell Carcinoma of the Cecum Presenting as Spontaneous Perforation.
Squamous cell carcinoma (SCC) of the colon is an extremely rare condition, and its pathogenesis is not fully understood. Bowel perforation is a very infrequent manifestation of colonic SCC, and only a few cases have been reported in the literature involving sigmoid and splenic flexure perforation. To the best of our knowledge, no cases of ileocecal perforation have been documented in the literature. Here we present a case of cecal SCC that presented with bowel perforation, necessitating emergent surgical intervention. Histopathological examination showed SCC with lymph node metastasis. This case reviews current knowledge and highlights the rare manifestation that these rare tumors can present.


Mapping the papillary renal cell carcinoma gene between loci D17S787 and D17S1799 on chromosome 17q21.32.
Trisomy of chromosome 17 is associated with the development of papillary renal cell tumors (RCT). We have analyzed 37 papillary RCT by applying 25 polymorphic microsatellite markers and found an overlapping duplication including loci D17S1795 and D17S1306 on chromosome 17q21. This region was then analyzed in additional 118 sporadic and hereditary papillary RCT. Overlapping partial duplications at the chromosome 17q21.32 region localized the papillary RCT gene to an approximately 300 kb genomic sequences flanked by loci D17S787 and D17S1799. Altogether, 92% of the 100 papillary RCT showed allelic duplication at this region. We did not find mutation in coding sequences or altered expression of the hepatic leukemia factor gene, which is mapped the smallest duplicated interval, in any type of RCT. Therefore, another gene within the 300 kb region might be responsible for the development of papillary RCT.


Delinquent-Victim Youth-Adapting a Trauma-Informed Approach for the Juvenile Justice System.
The connection between victimization and later delinquency is well established and most youth involved with the juvenile justice system have at least one if not multiple victimizations in their history. Poly-victimized youth or those presenting with complex trauma require specialized assessment and services to prevent deleterious emotional, physical, and social life consequences. Empirical studies have provided information which can guide practitioners work with these youth and families, yet many of the policies and practices of the juvenile justice system are counter to this model. Many youth-serving organizations are beginning to review their operations to better match a trauma-informed approach and in this article the author will highlight how a trauma-informed care model could be utilized to adapt the juvenile justice system.


The structure and function of protein kinase C-related kinases (PRKs).
The protein kinase C-related kinase (PRK) family of serine/threonine kinases, PRK1, PRK2 and PRK3, are effectors for the Rho family small G proteins. An array of studies have linked these kinases to multiple signalling pathways and physiological roles, but while PRK1 is relatively well-characterized, the entire PRK family remains understudied. Here, we provide a holistic overview of the structure and function of PRKs and describe the molecular events that govern activation and autoregulation of catalytic activity, including phosphorylation, protein interactions and lipid binding. We begin with a structural description of the regulatory and catalytic domains, which facilitates the understanding of their regulation in molecular detail. We then examine their diverse physiological roles in cytoskeletal reorganization, cell adhesion, chromatin remodelling, androgen receptor signalling, cell cycle regulation, the immune response, glucose metabolism and development, highlighting isoform redundancy but also isoform specificity. Finally, we consider the involvement of PRKs in pathologies, including cancer, heart disease and bacterial infections. The abundance of PRK-driven pathologies suggests that these enzymes will be good therapeutic targets and we briefly report some of the progress to date.


Ferulic acid alleviates lipopolysaccharide-induced acute lung injury through inhibiting TLR4/NF-κB signaling pathway.
Ferulic acid (FA) exhibits anti-inflammatory, antidiabetic, antihyperlipidemic, antioxidant, neuroprotective, and antihypertensive effects. This study aimed to determine whether FA could ameliorate lipopolysaccharide (LPS)-induced inflammatory responses and acute lung injury (ALI) in mice. Mice were challenged with LPS intratracheally to induce ALI 1 h after 3 days of FA (25, 50, and 100 mg/kg) or dexamethasone (DEX; 5 mg/kg) administration. The lung tissues and bronchoalveolar lavage fluid (BALF) were collected 12 h after the LPS challenge. Pretreatment with FA or DEX could attenuate lung histopathological change, complement deposition, and lung wet-to-dry weight ratio of mice injured by LPS. Meanwhile, the influx of neutrophils and macrophages, as well as the production of proinflammatory cytokine (tumor necrosis factor-alpha, interleukin 1 beta [IL-1β], and IL-6), in BALF of ALI mice was significantly decreased. Moreover, FA or DEX markedly reversed the LPS-induced elevation of myeloperoxidase activity and monocyte chemoattractant protein-1 level in lung tissues of ALI mice. In addition, the Western blot analysis demonstrated that FA or DEX effectively inhibited the LPS-induced activation of the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway in lung tissues. The current study suggested that the alleviating effect of FA against LPS-induced ALI might be partially due to the inhibition of the inflammatory response via inactivation of the TLR4/NF-κB signaling pathway.


CaSR stimulates secretion of Wnt5a from colonic myofibroblasts to stimulate CDX2 and sucrase-isomaltase using Ror2 on intestinal epithelia.
To understand whether extracellular calcium-sensing receptor (CaSR) expression on colonic myofibroblast cells (18Co) contributed to epithelial homeostasis, we activated the CaSR with 5 mM Ca(2+), screened by RT-PCR Wnt family members, and measured their secretion. Transcripts for Wnt 1, 2, 2b, 3a, 4, and 7a were either absent or unchanged whereas Wnt3 decreased and Wnt5a increased. We assessed Wnt5a secretion by Western blot. High Ca(2+) (5 mM) substantially increased Wnt5a secretion; small interfering RNA (siRNA) against the CaSR reduced this to constitutive amounts. Expression of Wnt5a plasmid but not Wnt1 or Wnt3a increased caudal homeodomain factor CDX2 transcripts and protein in HT-29 adenocarcinoma cells. Wnt5a increased activity of a sucrase-isomaltase (SI) promoter in Caco-2BBE cells. Wnt5a protein stimulation of CDX2 transcripts and protein and SI reporter were increased by overexpression of wild-type Ror2, a Wnt5a receptor, and reduced with siRNA against Ror2. CaSR activation of HT-29 cells increased Ror2 protein expression. Ror2 protein was expressed in mouse jejunum from crypt base to villus tip and in the colon on surface epithelia. Our results show that activation of a G protein-coupled receptor, the CaSR, stimulates secretion of Wnt5a from myofibroblasts. Stimulation of epithelia by the CaSR increased the expression of a receptor for Wnt5a, the tyrosine kinase Ror2, suggesting existence of a unique paracrine relationship for CDX2 homoeostasis in the intestine and revealing new contributions of CaSR-activated myofibroblasts to intestinal stem cell niche microenvironments.


Simultaneous determination of five coumarins in Angelicae dahuricae Radix by HPLC/UV and LC-ESI-MS/MS.
Rapid, simple and reliable HPLC/UV and LC-ESI-MS/MS methods for the simultaneous determination of five active coumarins of Angelicae dahuricae Radix, byakangelicol (1), oxypeucedanin (2), imperatorin (3), phellopterin (4) and isoimperatorin (5) were developed and validated. The separation condition for HPLC/UV was optimized using a Develosil RPAQUEOUS C(30) column using 70% acetonitrile in water as the mobile phase. This HPLC/UV method was successful for providing the baseline separation of the five coumarins with no interfering peaks detected in the 70% ethanol extract of Angelicae dahuricae Radix. The specific determination of the five coumarins was also accomplished by a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source (LC-ESI-MS/MS). Multiple reaction monitoring (MRM) in the positive mode was used to enhance the selectivity of detection. The LC-ESI-MS/MS methods were successfully applied for the determination of the five major coumarins in Angelicae dahuricae Radix. These HPLC/UV and LC-ESI-MS/MS methods were validated in terms of recovery, linearity, accuracy and precision (intra- and inter-day validation). Taken together, the shorter analysis time involved makes these HPLC/UV and LC-ESI-MS/MS methods valuable for the commercial quality control of Angelicae dahuricae Radix extracts and its pharmaceutical preparations.


Inhibitions of several antineoplastic drugs on serum sialic Acid levels in mice bearing tumors.
Six murine tumors, including ascetic tumors HepA, EC, P388 leukemia, S180 and solid tumor S180, and Lewis lung carcinoma, were employed in this work. The free sialic acid concentrations in both blood and ascites were measured in tumor-bearing mice. The results showed that the content of sialic acids in blood was increased in tumor growth and certain tumor types. Higher sialic acid content was observed in ascites than that present in blood. The influence of antineoplastic agents (vincristine, thiotepa, adriamycin, probimane, cisplatin, oxalysine, cortisone, nitrogen mustard, lycobetaine, Ara-C, harringtonine, and cyclophosphamide) on the content of sialic acids in mice blood bearing solid tumors of either S180 or Lewis lung carcinoma was observed. Different inhibitions of antineoplastic drugs on both tumor growth and serum sialic acid levels in mice bearing tumors were found. Among these antineoplastic drugs, probimane, cisplatin, nitrogen mustard, and lycobetaine were able to decrease the serum sialic acid levels in mice bearing tumors. Since these four antineoplastic drugs are all DNA chelating agents, it was proposed that the inhibition of tumor sialic acids by these drugs might be through the DNA template via two ways. Since we have found no effect of antineoplastic drugs on serum sialic acid levels in normal mice, this suggests that the inhibition of antineoplastic drugs on sialic acids is by tumor involvement.


Adherence of different Candida dubliniensis isolates in the presence of fluconazole.
The recently described yeast species Candida dubliniensis is closely related to C. albicans and has been recovered predominantly from the oral cavities of HIV-infected individuals and AIDS patients who are often receiving fluconazole as prophylactic or therapeutic treatment for oropharyngeal candidiasis. Like C. albicans, C. dubliniensis secretes aspartic proteinases which in C. albicans have been shown to be involved in adherence. To explain the increasing prevalence of C. dubliniensis in AIDS patients and to investigate the virulence factors of this yeast. An in vitro assay was developed to compare the adherence to epithelial cells of C. dubliniensis from HIV-patients with that of C. albicans. All C. albicans isolates adhered better than the 22 C. dubliniensis isolates. In the presence of fluconazole, the C. dubliniensis isolates tested showed increased adherence as compared with controls without fluconazole. In contrast, all C. albicans isolates decreased in adherence to epithelial cells in the presence of fluconazole independently of their in vitro susceptibility to this drug. Proteinase antigens are present on the surface of C. dubliniensis cells adherent to epithelial target cells. In the presence of fluconazole this proteinase antigen was more strongly expressed. Increased adherence of C. dubliniensis strains in the presence of fluconazole could explain its high recovery rate from HIV-positive patients in recent years. The induction of proteinase secretion in the presence of fluconazole found for most of the C. dubliniensis isolates could be one of the factors involved in adherence.


[Nephroblastoma with intestinal differentiation].
Available are two cases of Wilms's tumor with focal intestinal differentiation. Goblet- and endocrine-like cells as well as those similar to enterocytes were identified in one of the tumors upon electron microscopy. Squamous epithelial, cartilaginous cells, rabdomyoblasts presented in both cases. Problems of histogenesis and prognosis are under discussion.


Neuroprotection through flavonoid: Enhancement of the glyoxalase pathway.
The glyoxalase pathway functions to detoxify reactive dicarbonyl compounds, most importantly methylglyoxal. The glyoxalase pathway is an antioxidant defense mechanism that is essential for neuroprotection. Excessive concentrations of methylglyoxal have deleterious effects on cells, leading to increased levels of inflammation and oxidative stress. Neurodegenerative diseases - including Alzheimer's, Parkinson's, Aging and Autism Spectrum Disorder - are often induced or exacerbated by accumulation of methylglyoxal. Antioxidant compounds possess several distinct mechanisms that enhance the glyoxalase pathway and function as neuroprotectants. Flavonoids are well-researched secondary plant metabolites that appear to be effective in reducing levels of oxidative stress and inflammation in neural cells. Novel flavonoids could be designed, synthesized and tested to protect against neurodegenerative diseases through regulating the glyoxalase pathway.


Brachiocephalic artery thrombosis in adult nephrotic syndrome.
Thrombotic events are known to occur in nephrotic syndrome, as these patients have a hypercoagulable state. Venous thrombosis is well recognized, but arterial thrombosis is rare and is mainly noted in pediatric population. In the present study, we report a case of thrombosis of right brachiocephalic artery, embolic occlusion of right axillary artery, and right middle cerebral artery territory infarction due to thromboembolism in an adult patient with nephrotic syndrome (Minimal change disease). Patient underwent thromboembolectomy in the right axillary artery followed by anticoagulation therapy.


Copper-Catalyzed Aerobic Cross-Dehydrogenative Coupling of β-Oxime Ether Furan with Indole.
Heterobiaryls serve as relevant structural motifs in many fields of high applicative importance such as drugs, agrochemicals, organic functional materials etc. Cross-dehydrogenative coupling involving direct oxidation of two C-H bonds to construct a C-C bond is actively being pursued as a more benign and 'greener' alternative for synthesizing heterobiaryls. Herein, we report a Cu(I)-catalyzed cross-dehydrogenative coupling of indoles and furans, two of the most important aromatic heterocycles using air as the terminal oxidant. The reaction proceeds with regio- and chemoselectivity to give the cross-coupled products in good to excellent yields generally. A broad substrate scope with respect to both the coupling partners has been demonstrated to prove the generality of this reaction. This represents the hitherto unexplored cross-dehydrogenative coupling methodology to obtain an indole-furan biaryl motif.


Risk Assessment and Antithrombotic Strategies in Antiphospholipid Antibody Carriers.
Antiphospholipid antibodies (aPL) are a cluster of autoantibodies directed against plasma proteins with affinity for membrane phospholipids. The most frequently tested aPL are lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and anti-β2-glycoprotein I antibodies (anti-β2GPI). aPL play a key pathogenic role in the development of the antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by recurrent thrombotic and/or pregnancy complications in patients with persistent aPL. However, aPL positivity is occasionally documented in patients with no previous history of thrombotic or pregnancy morbidity. LA activity, multiple aPL positivity, high-titer aPL, and a concomitant systemic autoimmune disease are recognized risk factors for future thrombotic events in asymptomatic carriers. Moreover, an accelerated atherosclerosis with increased cardiovascular (CV) risk has also been associated with aPL positivity, thus exposing aPL carriers to fatal complications and chronic disability requiring cardiac rehabilitation. Overall, an accurate risk stratification is recommended for aPL-positive subjects in order to prevent both venous and arterial thrombotic complications. In this review, we provide an overview of the main antithrombotic and risk assessment strategies in aPL carriers.


Peroneal tubercle and its variations in the Indian calcanei.
A total number of 1,410 calcanei of either sex belonging to people of Agra and Lucknow region were studied and classified into 4 types depending upon the pattern of peroneal tubercle. A significant difference in the incidence of various types in the two regions were observed.


Ferroptosis-related gene expression in the pathogenesis of preeclampsia.
Background: Preeclampsia (PE) is one of the leading causes of maternal and fetal morbidity and mortality worldwide. Placental oxidative stress has been identified as a major pathway to the development of PE. Ferroptosis is a new form of regulated cell death that is associated with iron metabolism and oxidative stress, and likely mediates PE pathogenesis. The aim of the study was to identify the key molecules involved in ferroptosis to further explore the mechanism of ferroptosis in PE. Methods: Gene expression data and clinical information were downloaded from the GEO database. The limma R package was used to screen differentially expressed genes (DEGs) and intersected with ferroptosis genes. The GO and KEGG pathways were then analyzed. Next, hub genes were identified via weighted gene co-expression network analysis (WGCNA). Receiver operating curves (ROCs) were performed for diagnostic and Pearson's correlation of hub genes and clinicopathological characteristics. Immunohistochemistry and Western blot analysis were used to verify the expression of hub genes. Results: A total of 3,142 DEGs were identified and 30 ferroptosis-related DEGs were obtained. In addition, ferroptosis-related pathways were enriched by GO and KEGG using DEGs. Two critical modules and six hub genes that were highly related to diagnosis of PE were identified through WGCNA. The analysis of the clinicopathological features showed that NQO1 and SRXN1 were closely correlated with PE characteristics and diagnosis. Finally, Western blot and immunohistochemistry analysis confirmed that the expression of the SRXN1 protein in the placental tissue of patients with PE was significantly elevated, while the expression of NQO1 was significantly decreased. Conclusions: SRXN1 and NQO1 may be key ferroptosis-related proteins in the pathogenesis of PE. The study may provide a theoretical and experimental basis for revealing the pathogenesis of PE and improving the diagnosis of PE.


Constitutive expression of ETHYLENE-RESPONSE-FACTOR1 in Arabidopsis confers resistance to several necrotrophic fungi.
Infection of a plant by a pathogen induces a variety of defense responses that imply the action of several signaling molecules, including salicylic acid (SA), jasmonic acid (JA) and ethylene (E). Here we describe the role of ETHYLENE-RESPONSE-FACTOR1 (ERF1) as a regulator of ethylene responses after pathogen attack in Arabidopsis. The ERF1 transcript is induced on infection by Botrytis cinerea, and overexpression of ERF1 in Arabidopsis is sufficient to confer resistance to necrotrophic fungi such as B. cinerea and Plectosphaerella cucumerina. A positive co-operation between E and SA pathways was observed in the plant response to P. cucumerina. Infection by Pseudomonas syringae tomato DC3000, however, does not affect ERF1 expression, and activation of ethylene responses by ERF1 overexpression in Arabidopsis plants reduces tolerance against this pathogen, suggesting negative crosstalk between E and SA signaling pathways, and demonstrating that positive and negative interactions between both pathways can be established depending on the type of pathogen.


Human immunodeficiency virus type 1 Nef protein targets CD4 to the multivesicular body pathway.
The Nef protein of human immunodeficiency virus type 1 downregulates the CD4 coreceptor from the surface of host cells by accelerating the rate of CD4 endocytosis through a clathrin/AP-2 pathway. Herein, we report that Nef has the additional function of targeting CD4 to the multivesicular body (MVB) pathway for eventual delivery to lysosomes. This targeting involves the endosomal sorting complex required for transport (ESCRT) machinery. Perturbation of this machinery does not prevent removal of CD4 from the cell surface but precludes its lysosomal degradation, indicating that accelerated endocytosis and targeting to the MVB pathway are separate functions of Nef. We also show that both CD4 and Nef are ubiquitinated on lysine residues, but this modification is dispensable for Nef-induced targeting of CD4 to the MVB pathway.


Influenza-like illness in Norway: clinical course, attitudes towards vaccination and preventive measures during the 2009 pandemic.
To document clinical characteristics of influenza-like illness, reported use of health preventive measures and attitudes towards vaccination among patients with influenza-like illness in general practice during the influenza pandemic in 2009. Cross-sectional survey in general practice. Patients, who were identified as having influenza-like illness during the peak of the influenza pandemic activity in Norway, were eligible for inclusion in the study. A questionnaire was sent 2-4 weeks after the patients visit to the GP with influenza-like illness diagnosis during October to December 2009, from general practices in Norway. A sample of responders >18 years also had a blood test to check for serological response to the pandemic H1N1 virus. Questionnaires were sent to 1324 patients, and 357 (27%) were returned. Fever (91% versus 49%, P < 0.01), cough (85% versus 73%, P = 0.016) and gastrointestinal symptoms (58% versus 38%, P < 0.01) were more frequent in the age group <18 years compared to older patients. Serological H1N1 responses were analysed in 72 patients; 34 (47%) were positive (haemagglutination inhibition assay titres ≥ 40). There were no statistically significant differences in symptoms between seropositive and seronegative patients. Women reported better adherence to personal protective measures, such as hand washing and cough etiquette than men. Women were also more concerned about possible adverse effects of the pandemic influenza vaccine than men. Discrimination between influenza and other viral upper respiratory tract infections is difficult in daily clinical practice, even during an influenza pandemic. A gender difference was found in reported precautions to prevent influenza.


Role of Hub Genes in the Occurrence and Development of Testicular Cancer Based on Bioinformatics.
Testicular cancer severely affects male health, so finding effective diagnosis and prognostic indicators and exploring its pathogenesis are very important. This study aims to explore the hub genes that play important roles in the occurrence and development of testicular germ cell tumor (TGCT). Data were obtained from Gene Expression Omnibus datasets (GSE3218 and GSE1818) and verified in The Cancer Genome Atlas database and the Genotype-Tissue Expression database and the Human Protein Atlas database. A protein-protein interaction network was constructed to obtain hub genes. GEO2R, R software and packages were used to analyze differentially expressed genes (DEGs), receiver operating characteristic curve assessment, Cox regression analysis, Kaplan-Meier survival curve assessment, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, the relationship with clinicopathological information, gene set enrichment analysis, the correlation with immune cells' infiltration, and the expression in pan-cancers of the hub genes. PLK4, TRIP13, TPR, KIF18A, CDKN3, HMMR, PBK, PTTG1, CKS2, SYCP1, HSPA2, and MKI67 were selected as the hub genes. mRNA of PLK4, TRIP13, CDKN3, SYCP1, HSPA2, and MKI67 had high diagnostic values, and higher expression of CDKN3 and HSPA2 mRNA were poor prognostic factors for progression-free interval of TGCT. The hub genes involved organelle division and cell cycle, chromosome and centromeric region, heat shock protein binding, and more. Downregulated TPR and PLK4 were selected as research targets for continued study, and they may participate in multiple signaling pathways. The expression of TPR and PLK4 correlated with the infiltration of a variety of immune cells and differed in pan-cancers. The mRNA levels of multiple hub genes have high diagnostic and prognostic values for TGCT. TPR and PLK4 may play a role in the occurrence and development of TGCT through cancer-related signaling pathways.


Finite Element Modeling of Magnitude and Location of Brain Micromotion Induced Strain for Intracortical Implants.
Micromotion-induced stress remains one of the main determinants of life of intracortical implants. This is due to high stress leading to tissue injury, which in turn leads to an immune response coupled with a significant reduction in the nearby neural population and subsequent isolation of the implant. In this work, we develop a finite element model of the intracortical probe-tissue interface to study the effect of implant micromotion, implant thickness, and material properties on the strain levels induced in brain tissue. Our results showed that for stiff implants, the strain magnitude is dependent on the magnitude of the motion, where a micromotion increase from 1 to 10 μm induced an increase in the strain by an order of magnitude. For higher displacement over 10 μm, the change in the strain was relatively smaller. We also showed that displacement magnitude has no impact on the location of maximum strain and addressed the conflicting results in the literature. Further, we explored the effect of different probe materials [i.e., silicon, polyimide (PI), and polyvinyl acetate nanocomposite (PVAc-NC)] on the magnitude, location, and distribution of strain. Finally, we showed that strain distribution across cortical implants was in line with published results on the size of the typical glial response to the neural probe, further reaffirming that strain can be a precursor to the glial response.


Gentamicin decreases the abundance of aquaporin water channels in rat kidney.
The present study was performed to examine whether the gentamicin-induced urinary concentration defect is related to an altered regulation of aquaporin (AQP) water channels in the kidney. Male Sprague-Dawley rats were subcutaneously injected with gentamicin (20, 50 or 100 mg/kg per day) for 6 days. The protein expression of AQP1-3 channels and the catalytic activity of adenylyl cyclase were determined in the kidney. Gentamicin treatment resulted in renal failure associated with decreased tubular free water reabsorption and increased urinary flow rate. The expression of AQP2 proteins was significantly decreased in the kidney, in which the cortex was most susceptible, followed by the outer medulla and inner medulla in order. Gentamicin treatment also decreased the shuttling of AQP2, as evidenced by a decrease of its expression in the membrane fraction in proportion to that in the cytoplasmic fraction. The protein expression of AQP1 as well as that of AQP3 was also decreased in the cortex by treatment with the highest dose of gentamicin. The cAMP generation in response to arginine vasopressin or sodium fluoride was decreased by gentamicin, while that to forskolin was not significantly altered. These findings suggest that the primary impairment in the pathway leading to the generation of cAMP lies at the level of G proteins, resulting in a decreased expression of cAMP-mediated AQP channels. The gentamicin-induced urinary concentration defect may in part be accounted for by a reduced abundance of AQP water channels in the kidney.


Cesarean deliveries among Nepalese mothers: changes over time 2001-2011 and determinants.
To examine the most recent trends of cesarean delivery in Nepal and the association with socio-demographic characteristics of mothers. Nationally representative cross-sectional data was used from three Demographic and Health Surveys conducted in Nepal in 2001 (N = 4,745), 2006 (N = 4,066) and 2011 (N = 4,148). Cesarean section delivery was measured in two categories with yes and no responses for the delivery in their latest pregnancy. Data on socio-demographic variables was obtained by interviewing the participants. The data was analysed using logistic regression models. The prevalence of cesarean section delivery was increased by more than 4 times from 2001 to 2011 both among rural and urban residents. After adjusting for mother's age, number of births in last 5 years and mother's education the prevalence of cesarean section delivery among all mothers was 1.71 times higher in 2006 (OR = 1.71, 95 % CI 1.23-2.37) and increased further in 2011 (OR = 2.42, 95 % CI 1.78-3.30) compared with year 2001. When adjusted for all the variables simultaneously, all variables except births in last 5 years remained significantly associated with cesarean section delivery of the mother. Older age, urban resident, being educated, having educated partners and being rich according to wealth index were associated with cesarean section delivery. The prevalence of cesarean section delivery continues to rise but still lower than the World Health Organization recommended rates. More studies are needed to examine the non-medical reason of increasing rates of cesarean section deliveries and their effect in maternal and infant morbidity and mortality in Nepal.


ILA, a member of the human nerve growth factor/tumor necrosis factor receptor family, regulates T-lymphocyte proliferation and survival.
ILA, a gene induced by lymphocyte activation, is a member of the human nerve growth factor tumor necrosis factor receptor family and the human homologue of murine 4-1BB. The present study analyzed the role of ILA in the regulation of human peripheral blood T-lymphocyte function. Antibodies raised against different fusion proteins recognized ILA on activated lymphocytes. These antibodies significantly increased anti-CD3--induced T-lymphocyte proliferation. When anti-CD3--stimulated cells were incubated on ILA-expressing CHO cells, proliferation was inhibited. CHO cells transfected with a control construct and not expressing ILA did not reduce T-cell proliferation. A purified fusion protein containing the extracellular domain of ILA and the constant domain of human IgG (ILA-IgG) also inhibited lymphocyte proliferation. Results obtained by 3H-thymidine incorporation were confirmed by cell cycle analysis that showed a decrease in the number of lymphocytes in S phase. Lymphocyte morphology in cultures with ILA-expressing CHO cells was suggestive of apoptosis. Flow cytometry on propidium iodide-stained cells showed a time-dependent increase in the number of hypodiploid apoptotic cells when lymphocytes were cultured on ILA-expressing CHO cells. Internucleosomal DNA cleavage was seen in these cultures, but not in the presence of ILA-negative CHO cells. Studies on the mechanism by which ILA regulates T-cell function showed that ILA-IgG inhibited anti-CD3-induced T-cell proliferation when presented in immobilized but not in soluble form. These results suggest that ILA may act by cross-linking its ligand and thereby inhibit T-cell proliferation.


Psychrometric pressure-volume analysis of osmoregulation in roots, shoots, and whole sporophytes of salinized ceratopteris.
Osmotic and turgor adjustment in roots, shoots, and whole sporophytes of a NaCl-tolerant mutant and a NaCl-sensitive wild-type strain of the fern Ceratopteris richardii Brongn. were characterized following exposure to 60 millimolar NaCl, using a psychrometric approach to pressure-volume analysis. Water potential components of whole plants and shoots at full or ambient hydration were similar between strains. Roots of the mutant, however, had osmotic potentials at full turgor and water potentials at zero turgor which were lower (0.32 and 0.46 megapascal, respectively) than those in roots of the wild type after salinization. Although compromised in the absence of NaCl, sporophytes of the mutant strain were larger and much less necrotic in 60 millimolar NaCl after 17 days, compared to the wild type. Root growth in the mutant strain was unaffected by salinization and far exceeded root growth in the wild type. Correlation coefficients of the linear regression and the general consistency and precision of the pressure-volume data demonstrated the feasibility of using PV curves for estimating water potential components of roots. The technique should also provide a means of studying osmoregulation in a variety of other rapidly equilibrating plant tissues.


Inner-ear decompression sickness: 'hubble-bubble' without brain trouble?
Inner-ear decompression sickness (DCS) is an incompletely understood and increasingly recognized condition in compressed-air divers. Previous reports show a high association of inner-ear DCS with persistent foramen ovale (PFO), suggesting that a moderate-to-severe right-to-left shunt might represent a major predisposing factor, and more properly defining it as an event from arterial gas embolism (AGE). However, other conditions characterized by bubbles entering the arterial circulation, such as open-chamber cardiac surgery, do not produce inner-ear involvement, while sometimes damaging the brain extensively. Moreover, in other sites, such as the spinal cord, the prevailing mechanism for DCS is not AGE, but more likely local bubble formation with subsequent compression of venules and capillaries. Thus, AGE might be, more properly, a predisposing condition, neither sufficient, nor possibly even strictly necessary for inner-ear DCS. A 'two-hit hypothesis' has been proposed, implying a locally selective vulnerability of the inner ear to AGE. Modelled kinetics for gas removal are slower in the inner ear compared to the brain, leading to a supersaturated environment which allows bubbles to grow until they eventually obstruct the labyrinthine artery. Since this artery is relatively small, there is a low probability for a bubble to enter it; this might explain the disproportion between the high prevalence of PFO in the general population (25-30%) and the very low incidence of inner-ear DCS in compressed-air diving (approximately 0.005%). Furthermore, given that the labyrinthine artery usually originates either from the anterior inferior cerebellar artery, or directly from the basilar artery, shunting bubbles will more frequently swarm through the entire brain. In this case, however, the brain's much faster gas removal kinetics might allow for them to be reabsorbed without damaging brain tissue. In line with this scenario is the low probability (approx. 15%) of inner-ear DCS presenting with concomitant symptoms suggestive of brain involvement. Interestingly, PFO is a putative risk factor not only for DCS but also for ischaemic stroke, and it has been hypothesized that a predominantly silent ischaemic cerebral burden might represent a meaningful surrogate of end-organ damage in divers with PFO, with implications for stroke or cognitive decline. Here we report the case of a 44-year-old diving instructor (> 350 dives) who suffered from inner-ear DCS about 10 min after a routine dive (5 min/40 metres' fresh water (mfw), ascent 7.5 mfw·min⁻¹, stop 10 min/5 mfw), resulting in severe left cochlear/vestibular impairment (complete deafness and marked vertigo, only the latter slowly receding after a few hours). The patient was not recompressed. A few months later, transcranial Doppler ultrasonography demonstrated a moderate-to-severe shunt (> 30 bubbles), presumably due to a PFO (he refused confirmatory echocardiography), while a brain MRI (1.5 T) was reported as negative for both recent and remote lacunar infarcts (Figure 1). We believe this may be evidence that inner-ear DCS could occur while the brain is completely spared, not only clinically, but also at neuroimaging. This would support either of two hypotheses: (a) that the brain is indeed relatively protected from arterial bubbles that preferentially harm the inner ear where, however, they only rarely infiltrate, or (b) that direct bubble formation within the inner ear cannot be completely discarded, and that the elevated PFO-inner-ear DCS association might be, in this latter case, merely circumstantial. We favour the hypothesis that inner-ear DCS might be related to AGE in an anatomically vulnerable region. More precise data regarding the exact incidence of inner-ear involvement, isolating those subjects with moderate-to-severe shunt, should be obtained before exploring the risk-to-benefit ratio given by transcatheter occlusion of a PFO for prevention of inner-ear DCS; odds that could end up to be sensibly different with respect to other types of DCS presentation.


Cytologic difference between benignity and malignancy in suspicious cases employing urine cytodiagnosis using a liquid-based method.
To follow cases with atypical cells or suspicious cases on first examination by liquid-based cytology (LBC), comparing cases that became negative and those confirmed to be positive (urothelial carcinoma) with regard to the cell morphology. Urine cytology was performed employing LBC in 323 samples. Of 75 suspicious cases on first examination, 5 and 8 cases were identified with (positive) and without (negative) cancer on reexamination, respectively. Cell morphology was investigated in the first suspicious preparations of these cases. Fewer cells were present in the samples of negative cases, and atypia was generally weak. The nuclei were swollen and pale, and hyperchromatism was weak. In contrast, in positive cases, nuclear swelling, flattening, shrinkage, and pale staining were less marked compared with those in negative cases. The nuclei were hyperchromatic and irregular in many cases. Nuclear cannibalism, multinucleation, anisokaryosis, three-dimensionality, and an irregular arrangement were considered to be features strongly suggesting malignancy. The efficiency of diagnosis employing the LBC is high because of the cell collection rate. It was shown that the accuracy of diagnoses made employing the LBC method can be increased by understanding the characteristics of the cell morphology in suspicious cases.


Genome-Scale Metabolic Model of Xanthomonas phaseoli pv. manihotis: An Approach to Elucidate Pathogenicity at the Metabolic Level.
Xanthomonas phaseoli pv. manihotis (Xpm) is the causal agent of cassava bacterial blight, the most important bacterial disease in this crop. There is a paucity of knowledge about the metabolism of Xanthomonas and its relevance in the pathogenic process, with the exception of the elucidation of the xanthan biosynthesis route. Here we report the reconstruction of the genome-scale model of Xpm metabolism and the insights it provides into plant-pathogen interactions. The model, iXpm1556, displayed 1,556 reactions, 1,527 compounds, and 890 genes. Metabolic maps of central amino acid and carbohydrate metabolism, as well as xanthan biosynthesis of Xpm, were reconstructed using Escher (https://escher.github.io/) to guide the curation process and for further analyses. The model was constrained using the RNA-seq data of a mutant of Xpm for quorum sensing (QS), and these data were used to construct context-specific models (CSMs) of the metabolism of the two strains (wild type and QS mutant). The CSMs and flux balance analysis were used to get insights into pathogenicity, xanthan biosynthesis, and QS mechanisms. Between the CSMs, 653 reactions were shared; unique reactions belong to purine, pyrimidine, and amino acid metabolism. Alternative objective functions were used to demonstrate a trade-off between xanthan biosynthesis and growth and the re-allocation of resources in the process of biosynthesis. Important features altered by QS included carbohydrate metabolism, NAD(P)+ balance, and fatty acid elongation. In this work, we modeled the xanthan biosynthesis and the QS process and their impact on the metabolism of the bacterium. This model will be useful for researchers studying host-pathogen interactions and will provide insights into the mechanisms of infection used by this and other Xanthomonas species.


Morphologic analyses of mandible and upper airway soft tissue by MRI of patients with obstructive sleep apnea hypopnea syndrome.
To evaluate the morphological features of the mandible and the volume of the upper airway soft tissues in determining the anatomical risk factors for the upper airway in Japanese male patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Five morphological parameters of the mandible at the mandibular base plane and three volumetric parameters of the upper airway soft tissue were analyzed using three-dimensional (3D) magnetic resonance imaging software in 31 OSAHS and 20 controls. There were no significant differences between the two groups in mandibular internal width (the distance between the internal right and left gonia [IRG and ILG]) and mandibular bony thickness. However, the patients with OSAHS had a significantly wider mandibular divergence (the angle between the spina mentalis (SM)- IRG line and SM- ILG line), a smaller mandibular internal length (the perpendicular distance from SM to the RG- LG line), and a smaller area than the normal subjects at the mandibular base plane. There were no significant differences in these morphological parameters for the mandible between obese and nonobese OSAHS patients. The volumes of the tongue, soft palate, and lateral pharyngeal walls were not significantly different between the OSAHS and the control groups. Japanese male OSAHS patients had specific anatomical features in the bottom part of the mandible; however, obesity seemed to be a less significant risk factor. Investigators and clinicians must realize that ethnicity may modify the effects of obesity and abnormal craniofacial anatomy as risk factors for the pathogenesis of OSAHS.


Fast and accurate multi-channel B1+ mapping based on the TIAMO technique for 7T UHF body MRI.
Current methods for mitigation of transmit field B1+ inhomogeneities at ultrahigh field (UHF) MRI by multi-channel radiofrequency (RF) shimming rely on accurate B1+ mapping. This can be time consuming when many RF channels have to be mapped for in vivo body MRI, where the B1 maps should ideally be acquired within a single breath-hold. Therefore, a new B1+ mapping technique (B1TIAMO) is proposed. The performance of this technique is validated against an established method (DREAM) in phantom measurements for a cylindrical head phantom with an 8-channel transmit/receive (Tx/Rx) array. Furthermore, measurements for a 32-channel Tx/Rx remote array are conducted in a large body phantom and the |B1+| map reliability is validated against simulations of the transmit RF field distribution. Finally, in vivo results of this new mapping technique for human abdomen are presented. For the head phantom (8-channel Tx/Rx coil), the single |B1+| comparison between B1 TIAMO, the direct DREAM measurements, and simulation data showed good agreement with 10-19% difference. For the large body phantom (32-channel Tx/Rx coil), B1TIAMO matched the RF field simulations well. The results demonstrate the potential to acquire 32 accurate single-channel B1+ maps for large field-of-view body imaging within only a single breath-hold of 16 s at 7T UHF MRI. Magn Reson Med 79:2652-2664, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


On the mechanism of cancellous bone preservation in postmenopausal women with mild primary hyperparathyroidism.
Several studies have demonstrated that cancellous bone mass and architecture are preserved in postmenopausal women with primary hyperparathyroidism (PHPT). To investigate the mechanism(s) that could account for this observation, we analyzed features of bone formation in 19 postmenopausal women with PHPT by bone histomorphometry. The results were compared with those from a comparable group of 34 healthy, postmenopausal women. Patients with PHPT were similar to control subjects in cancellous bone area as well as in trabecular width, separation, and number. However, in PHPT, elevations were observed in indexes of bone turnover, such as eroded surface, osteoid surface, mineralizing surface, bone formation rate at the tissue level, and activation frequency. At the level of the bone-remodeling unit, women with PHPT had significantly higher values for the wall width of trabecular bone packets (40.26 +/- 0.36 vs. 34.58 +/- 0.45 mm), the adjusted apposition rate (0.40 +/- 0.04 vs. 0.29 +/- 0.03 mm/day), and the active formation period (67.8 +/- 5.1 vs. 57.3 +/- 2.3 days). These findings are consistent with a stimulatory action of elevated PTH levels on the duration of the active bone formation phase in individual remodeling units and may account at least in part for the preservation of cancellous bone in postmenopausal women with mild PHPT.


Biosynthesis and secretion of plant cuticular wax.
The cuticle covers the aerial portions of land plants. It consists of amorphous intracuticular wax embedded in cutin polymer, and epicuticular wax crystalloids that coat the outer plant surface and impart a whitish appearance. Cuticular wax is mainly composed of long-chain aliphatic compounds derived from very long chain fatty acids. Wax biosynthesis begins with fatty acid synthesis in the plastid. Here we focus on fatty acid elongation (FAE) to very long chains (C24-C34), and the subsequent processing of these elongated products into alkanes, secondary alcohols, ketones, primary alcohols and wax esters. The identity of the gene products involved in these processes is starting to emerge. Other areas of this field remain enigmatic. For example, it is not known how the hydrophobic wax components are moved intracellularly, how they are exported out of the cell, or translocated through the hydrophilic cell wall. Two hypotheses are presented for intracellular wax transport: direct transfer of lipids from the endoplasmic reticulum to the plasma membrane, and Golgi mediated exocytosis. The potential roles of ABC transporters and non-specific lipid transfer proteins in wax export are also discussed. Biochemical-genetic and genomic approaches in Arabidopsis thaliana promise to be particularly useful in identifying and characterizing gene products involved in wax biosynthesis, secretion and function. The current review will, therefore, focus on Arabidopsis as a model for studying these processes.


A seroepidemiological study of leprosy in high- and low-endemic Indonesian villages.
A seroepidemiological study was performed in three different leprosy-endemic areas in Indonesia, including two isolated villages with high endemicity in South Sulawesi (Kaluarang and Hulo) and an area with low endemicity in Java (Jepara). A total of 2430 serum samples were collected from 2672 individuals in these locations. The prevalence of leprosy in these three areas, as determined during this study, was 29/1000, 11/1000, and 7/1000 in Kaluarang, Hulo and Jepara, respectively. Two serological assays were employed in this study to detect antibodies against Mycobacterium leprae. One is an enzyme-linked immunosorbent assay (ELISA) based on the detection of antibodies to the species-specific epitope of phenolic glycolipid-I (PGL-I) of M. leprae. The second test, using inhibition of an ELISA reaction (ELISA-INH) detects antibodies to a species-specific epitope on the 36-kDa protein antigen of M. leprae. In comparison with clinical findings, the specificity of both serological tests was calculated to be 91%. The sensitivity of the ELISA was 97.6% for multibacillary (MB) cases and 56.8% for paucibacillary (PB) cases; for the ELISA-INH, it was 97.6% and 81.8% for MB and PB cases, respectively. Seropositivity rates were shown to be unrelated to sex, to Mitsuda skin-test reactivity, or to BCG vaccination status. The pattern of seropositivity was, however, clearly age-related, with high seropositivity in the age group 10-19 years and decreasing rates of positivity in the older age groups. Age-standardized seropositivity ratios were not correlated to the prevalence of leprosy when comparing the three areas. Therefore, it is not yet clear whether or not seropositivity reflects infection. If it does, other, as yet unidentified, factors may play a role in the natural history of the disease.


Decompositional terminology translation using network analysis.
Biomedical terminologies often contain composite concepts that cannot be translated into single unique synonymous concepts in a target controlled terminology. Such composite concepts need to be decomposed into sets of component concepts present in the target terminology that can serve as the proxy for applications in information retrieval, decision support or data analysis. Towards this goal, we use a "clustering coefficient" over the UMLS Metathesaurus to traverse the closely clustered neighbors of the composite source concept to generate a ranked list of possible component concepts. Using the MeSH Associated Expression mappings as the gold-standard, we show that the proposed approach generates relevant component concepts as compared to existing semantic locality based methods. The topological connectivity of the concepts in the UMLS Metathesaurus is a useful feature that can be coupled with existing lexical and semantic locality based approaches towards terminology translation.


Tube feeding increases the gastric-emptying rate determined by gastroesophageal scintigraphy.
The aim of this study was to determine whether tube feeding affects the rate of gastric emptying determined by gastroesophageal reflux scintigraphy in pediatric patients. Gastroesophageal reflux scintigraphy studies of 700 pediatric patients aged 1 week to 16 years were retrospectively analyzed. From these, 350 subjects received their study meal via a feeding tube, and 350 subjects received their meal as oral feeding. Gastric-emptying rate at 60 minutes was calculated, and the results compared. Stratification analysis for age, sex, and type and volume of administered meal was also performed. The average rate of the gastric emptying was higher in the tube feeding compared with oral feeding group (52.9% ± 17.9% vs 44.2% ± 15.1% gastric emptying at 1 hour, P < 0.01). The prevalence of fast gastric emptying, defined as greater than 50% emptying at 60 minutes, was also higher in the tube feeding group, being registered in 59.7% (209/350 cases) versus only 31.4% (110/350 cases) in the oral feeding group, P < 0.01. The difference persisted following stratification analysis for sex, age, and type and volume of ingested meal. Our findings show that tube feeding increases the rate of gastric emptying determined by gastroesophageal reflux scintigraphy in pediatric patients. The effect proved independent on such factors as sex, age, and type or volume of ingested meal.


Improvement on Natural Enemies of Bemisia tabaci (Hemiptera: Aleyrodidae) Using Extracts of Agrimonia pilosa.
Compared with the numerous natural enemies against insect pests that have been identified, the commercialization of natural biological control resources remains very limited. To increase the use of natural enemies for biological control, determining how to improve the low efficacy, slow speed, and high cost of natural enemies is very important. Mediterranean species of The whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodoidea), increasingly threatens many crops in China, and control primarily depends on chemical insecticides. Here, the effect of ethanol extracts from two plants, Agrimonia pilosa (Ledeb) (Rosales: Rosaceae) and Melia azedarach (Linn) (Meliaceae: Melia), on predominant natural enemies of B. tabaci was investigated using a leaf dipping or spraying method. The results showed that the ethanol extract of A. pilosa significantly improved the infectivity of the fungus Isaria javanica (Friedrichs & Bally) (Ascomycota: Hypocreales), and the mortality of whiteflies caused by the combination of fungus (105 spores/mL) with the extract of A. pilosa (2 mg/mL dried powder of A. pilosa containing 0.0942 mg/mL total polyphenols) was 81.6%, which was significantly higher than that caused by the fungus only. However, the ethanol extract of M. azedarach had no effect on fungus infectivity. Additionally, insecticide tolerance of the predator Pardosa pseudoannulata was also significantly improved by the extract of A. pilosa. The longevity of the parasitoid Encarsia formosa was not affected by the extracts. These findings indicate that the extract of A. pilosa played a dual role that included improving pathogenic fungi infectivity and insecticidal tolerance of a predator and thus could be a synergist in the biological control of B. tabaci.


Decomposing biodiversity data using the Latent Dirichlet Allocation model, a probabilistic multivariate statistical method.
We propose a novel multivariate method to analyse biodiversity data based on the Latent Dirichlet Allocation (LDA) model. LDA, a probabilistic model, reduces assemblages to sets of distinct component communities. It produces easily interpretable results, can represent abrupt and gradual changes in composition, accommodates missing data and allows for coherent estimates of uncertainty. We illustrate our method using tree data for the eastern United States and from a tropical successional chronosequence. The model is able to detect pervasive declines in the oak community in Minnesota and Indiana, potentially due to fire suppression, increased growing season precipitation and herbivory. The chronosequence analysis is able to delineate clear successional trends in species composition, while also revealing that site-specific factors significantly impact these successional trajectories. The proposed method provides a means to decompose and track the dynamics of species assemblages along temporal and spatial gradients, including effects of global change and forest disturbances.


Efficacy and tolerability of cefditoren pivoxil in uncomplicated skin and skin structure infections in Indian patients.
Uncomplicated skin and skin structure infections (uSSSI) are commonly encountered community-acquired infections and are typically confined to the superficial layers of the skin. Hence, they seldom lead to the destruction of skin structures. To evaluate the efficacy and tolerability of cefditoren pivoxil in uSSSI in Indian patients. One hundred and seventy-eight patients diagnosed with uncomplicated SSSI were enrolled in this randomized, comparative, multicentric study. Patients received either cefditoren pivoxil or cefdinir for ten days. Efficacy was assessed both clinically and microbiologically. Safety evaluation consisted of reporting of type, frequency, severity, and causal relationship of adverse events. One hundred and fifty-one patients completed the study. Clinical and bacteriological efficacy of cefditoren pivoxil was comparable to that of cefdinir in the treatment of uSSSI. One hundred and five patients were eligible for per protocol (PP) analysis of bacteriological outcome and clinical efficacy. Clinical cure or improvement was achieved in 98.00% patients treated with cefditoren pivoxil and 98.18% patients treated with cefdinir. In the modified Intent to Treat (mITT) patient population, clinical cure or improvement was recorded in 97.33% patients treated with cefditoren pivoxil and 96.20% patients treated with cefdinir. Microbiological eradication (or presumed eradication) was recorded in 88.00% patients treated with cefditoren pivoxil and 94.55% patients treated with cefdinir. The above differences in the outcome rates between the two drugs were not statistically significant. Six adverse events (AEs) (two in cefditoren group and four in cefdinir group) were reported in this study. Cefditoren pivoxil 200 mg b.i.d. was effective and well tolerated in the treatment of uSSSI.


[Hyperamylasemia, hyperlipasemia and acute pancreatitis in chronic inflammatory bowel diseases].
145 clinical observations of 114 patients with Crohn's disease and 65 observations of 47 patients with ulcerative colitis were analyzed prospectively concerning the prevalence of pathologically elevated levels of serumamylase or -lipase and acute pancreatitis. Painless hyperamylasemia or hyperlipasemia were found in 18 of 114 patients with Crohn's disease (15.8%) and in 10 of 47 patients with ulcerative colitis (21.3%) without morphological abnormalities on ultrasound. Range of elevated serumamylase levels differs from 35 to 68 U/L (Ref.-value less than 34 U/L), range of serumlipase levels varies from 199 to 858 U/L (Ref.-value less than 190 U/L). Pathologically elevated levels of serumamylase and -lipase persisted for 17.7 +/- 9.0 (5-28) days in Crohn's disease and 22.8 +/- 9.8 (7-33) days in ulcerative colitis. No relation to the activity or the duration of the disease, drug treatment or the weight loss of the patients could be shown. Acute pancreatitis was found in 4 of 114 patients (3.5%) with Crohn's disease, whereas in ulcerative colitis acute pancreatitis was diagnosed in 1 of 47 patients (2.1%). Regarding the promoting factors, drugs (azathioprine and salazosulfapyridine) and mechanical alterations of the bile duct (primary sclerosing cholangitis) or the pancreas (pancreas divisum) were found in 4 of the 5 patients. However the case of a 23 year old woman suffering from Crohn's ileocolitis who died of an idiopathic pancreatitis remains obscure.


Expression of cardiac Na channels with appropriate physiological and pharmacological properties in Xenopus oocytes.
The objective of this study was to determine whether the Xenopus laevis oocyte can express an exogenous cardiac Na channel that retains its normal physiological and pharmacological properties. Cardiac Na channels were expressed in oocytes following injection of RNA from guinea pig, rat, and human heart and detailed analysis was performed for guinea pig cardiac Na channels. Average current amplitudes were -351 +/- 37 nA with peak current observed at -8 +/- 1 mV. Steady-state inactivation was half-maximal at -49 +/- 0.6 mV for the expressed channels. All heart Na currents were resistant to block by tetrodotoxin compared to Na currents expressed from brain RNA with IC50 values for guinea pig, rat, and human heart of 651 nM, 931 nM, and 1.3 microM, respectively. In contrast, rat brain Na channels were blocked by tetrodotoxin with an IC50 value of 9.1 nM. In addition, the effects of the cardiac-selective agents lidocaine and DPI 201-106 were examined on Na currents expressed from brain and heart RNA. Lidocaine (10 microM) blocked cardiac Na current in a use-dependent manner but had no effect on brain Na currents. DPI 201-106 (10 microM) slowed the rate of cardiac Na channel inactivation but had no effect on inactivation of brain Na channels. These results indicate the Xenopus oocyte system is capable of synthesizing and expressing cardiac Na channels that retain normal physiological and pharmacological properties.


Effect of high-BDNF microenvironment stem cells therapy on neurogenic bladder model in rats.
The purpose of this study is to explore the effects of high-BDNF microenvironment produced by engineered immortalized mesenchymal stem cells (imMSCs) on the neurogenic bladder (NB) and investigate underlying mechanism. Male Sprague-Dawley rat (12-week-old, weighing about 370-400 g) were purchased from a Korean company (Orient Bio Co. Seongnam, Korea) and divided into the following groups (n=32): sham control group (n=8), NB group (n=8), NB + ImMSCs group (n=8), NB + ImMSCs (BDNF) group (n=8). The major pelvic ganglion (MPG) was observed under anesthesia. Three NB groups of rats were then subjected to bilateral MPG injury. The sham control group of rats was treated with sham surgery. Cystometry were performed before the rats were sacrificed, and then MPG and bladder were collected for histochemical and Western blot analysis. MSCs treatment improves lower urinary tract function, and the NB + ImMSCs (BDNF) group is better than the NB + ImMSCs group (P<0.01). MSCs treatment accelerates recovery of injured nerve tissue, and the NB + ImMSCs (BDNF) group is better than the NB + ImMSCs group (P<0.01). In high BDNF environment, apoptosis was reduced more significantly and muscle tissue recovered more rapidly (P<0.01). High-BDNF microenvironment activates more BDNF/TrkB/CREB signaling pathways (P<0.01). In a rat NB model caused by nerve injury, imMSCs have certain effects on nerve tissue repair. At the same time, it was proved that increasing the expression of BDNF which had specific effect on nerve injury repair could more effectively repair injured MPG in local microenvironment. The mechanism may be related to the activation of the BDNF/TrkB/CREB signaling pathway and the reduction of apoptosis by highly expressed BDNF.


Rh(III)-catalyzed diastereoselective cascade annulation of enone-tethered cyclohexadienones via C(sp2)-H bond activation.
Herein, we report highly diastereoselective arylative cyclization of enone-tethered cyclohexadienones via Rh(III)-catalyzed C-H activation of N-methoxybenzamides. This reaction proceeds through the formation of a five-membered rhodacycle followed by bis-Michael cascade annulation to access functionalized bicyclic scaffolds with four contiguous stereocenters with a broad substrate scope. These products have excellent functional handles, allowing further synthetic transformation to increase the structural complexity. Furthermore, mechanistic studies of arylative cyclization and a gram-scale experiment are also presented.


Linear Dimensional Stability of Irreversible Hydrocolloid Materials Over Time.
The aim of this study was to evaluate the linear dimensional stability of different irreversible hydrocolloid materials over time. A metal mold was designed with custom trays made of thermoplastic sheets (Sabilex, sheets 0.125 mm thick). Perforations were made in order to improve retention of the material. Five impressions were taken with each of the following: Kromopan 100 (LASCOD) [AlKr], which has dimensional stability of 100 hours, and Phase Plus (ZHERMACK) [AlPh], which has dimensional stability of 48 hours. Standardized digital photographs were taken at different time intervals (0, 15, 30, 45, 60, 120 minutes; 12, 24 and 96 hours), using an "ad-hoc" device. The images were analyzed with software (UTHSCSA Image Tool) by measuring the distance between intersection of the lines previously made at the top of the mold. The results were analyzed by ANOVA for repeated measures. Initial and final values were (mean and standard deviation): AlKr: 16.44 (0.22) and 16.34 (0.11), AlPh: 16.40 (0.06) and 16.18 (0.06). Statistical evaluation showed significant effect of material and time factors. Under the conditions in this study, time significantly affects the linear dimensional stability of irreversible hydrocolloid materials.


Relationship between homework completion and outcome in cognitive behaviour therapy.
Homework or between-session learning has long been considered an essential aspect of effective cognitive behaviour therapy. However, it has received relatively less empirical attention than other components of cognitive behaviour therapy. In general, studies have found that homework completion is predictive of outcome in psychotherapy. However, the amount of homework completed by a patient represents only one aspect of this important therapeutic component. This study investigated both the quantity and the quality of homework completed during a 10-week group cognitive and behavioural treatment program for anxious and depressed patients. It explored the relationship between various aspects of homework completion and outcomes on several different variables. A total of 94 patients were included in the analysis. It was found that both quantity and quality of homework completed predicted outcome on measures of depression, anxiety and quality of life at post-treatment and at 1-month follow-up. The results were strongest for the amount of homework completed, suggesting that clinicians should encourage patients to complete homework even if the homework content is not entirely accurate. The results of this study highlight the importance of homework as a central part of effective cognitive and behavioural treatment.


Influence of titanium surface charge on fibroblast adhesion.
Although dental implants have a high success rate, failure owing to the absence of adhesion between the gingival connective tissue and the implant surface is still being reported. This study was designed to evaluate the effect of a titanium surface charge on fibroblast adhesion. An electrical chamber was custom-made to generate negative and positive surface charges on commercially pure titanium cylinders with a potential difference of 4.5 V. Twenty-seven titanium cylinders were divided into three experimental groups. In each group, cell attachment to a positively charged titanium cylinder, a negatively charged titanium cylinder, and a titanium cylinder (control) was studied at three time intervals of 15, 30, and 60 minutes. NCTC clone 929 fibroblasts were used in these experiments. The effect of the potential difference in the pH of Dulbecco's Modified Eagle Medium (DMEM) was also evaluated using two new specimens at time intervals of 15, 30, 60, and 80 minutes. The fibroblast cell attachment was more statistically significant to the positively charged titanium cylinder than the negatively charged titanium cylinder (p =.002) and the control (p=.000), whereas the cell adhesion difference between the control and the negatively charged titanium cylinder was not statistically significant (p=.808). The range of pH difference of the DMEM in the negative and positive parts of the electrical chamber was 0.46 and 0.30, respectively. Within the limitations of this in vitro study, the positive surface charge of the titanium cylinder results in significantly favorable cell adhesion.


Associations of Social Jetlag with Dietary Behavior, Physical Activity and Obesity among Chinese Adolescents.
This study aimed to investigate the associations between social jetlag (SJL), dietary behavior, physical activity, and weight status in Chinese youth. Data were derived from a cross-sectional survey in Wuhan, China in 2019. Information on SJL, the frequency of food and beverage consumption, physical activity, and BMI category were collected via a self-reported questionnaire. The Kruskal-Wallis test and ANOVA were conducted to determine differences in daily consumption frequency of food and beverage groups, BMI category, and physical activity among SJL groups. Logistic regressions and restricted cubic splines were performed to test the association between SJL and the incidence of overweight or obesity. A final sample of 3567 Chinese adolescents [mean (SD) age, 14.67 (1.72) years; 47.41% (1691) female] were included. Our findings demonstrated that adolescents with SJL may consume more unhealthy foods and fewer beneficial foods, while engaging in less moderate to vigorous physical activity (MVPA) and reporting higher BMIs. In addition, adolescents who experience more than 2 h of SJL had significant greater risk of overweight or obesity. Our findings on SJL of Chinese adolescents confirm the harmful effects of SJL and also provide insights into the etiology of obesity in Chinese adolescents.


Acceptability and performance of a nonwoven device for vaginal drug delivery among women and their male partners in KwaZulu-Natal, South Africa.
Background: Multipurpose prevention technologies are needed to provide protection against HIV and sexually transmitted infections. Gel-based vaginal microbicides inserted via an applicator are prone to leakage. A novel device for vaginal drug delivery was developed to contain gel-based formulations, aiming to improve gel retention and reduce leakage. The objectives of this study were to assess acceptability and performance of a nonwoven vaginal delivery device. Methods: A nonwoven vaginal delivery device was prepared, pre-saturated with a commercially available water-based lubricant, with a finger pocket for insertion and string for removal. Quantitative and qualitative methods were used to collect data from interviews with 40 women and 10 male partners recruited from a sexual and reproductive health clinic in Durban, KwaZulu-Natal, South Africa. Women wore one device in the clinic and one device overnight or with their partner during intercourse. The primary endpoint was acceptability including comfort, ease of insertion and removal, and opinions on device attributes. Results: Most women said the device was 'easy' to insert and remove. Six women reported leakage after insertion and 34 reported having sexual intercourse while wearing the device. One woman was lost-to-follow-up and five women only wore the device overnight because their partners did not agree to intercourse with the inserted device. The best-liked attribute was the device's lubrication (22 women, 7 men); the least-liked was the removal string (9 women, 8 men). Conclusions: Data are promising for further development of this nonwoven device for vaginal drug delivery. Plain English summary Multipurpose prevention technologies (MPTs) that protect against HIV and sexually transmitted infections (STIs) are urgently needed. A variety of vaginal gel-based products are actively being researched; however, these products can often have challenges with vaginal leakage and retention. This research investigates the acceptability and performance of a nonwoven device to deliver vaginal gel formulations. The gel used in this study was a currently available marketed personal lubricant. In South Africa, 40 women (and 10 male partners) were recruited and given the opportunity to comment on various device attributes after insertion, overnight wear and sexual intercourse with their male partners. Generally, participants found the device easy to use and acceptable, where many factors possibly contributed to the device's acceptability (i.e., similarity to tampons, saturation with lubricant, minimal leakage, ease of insertion, comfort during intercourse and the male partners' willingness to have vaginal intercourse with the device in place). Further studies of the vaginal delivery device for acceptability, safety and efficacy using a gel-based formulation with an active ingredient are warranted.


[Is there a relationship between a history of spontaneous abortion and low birthweight in Cotonou (West Africa)?].
In Benin, as in other African countries, low birthweight infants is a major health problem with poorly understood causes. In a case-control study of 2114 mothers recruited before discharge from the "Lagune" maternity ward at Cotonou, we examined the relationship between spontaneous abortion and low birthweight infants in women who delivered between 15 June 1990 and 20 July 1991. Information was obtained by interview then on the basis of hospital files. The results indicated that there was no association between spontaneous abortion and premature birth: OR = 1.00 (95% CI = 0.61-1.56). Likewise, the relationship between a past history of spontaneous abortion and intrauterine growth retardation was not significant: OR = 1.19 (95% CI = 0.83-1.71). Adjustment with characteristics of the mothers did not improve the correlations. It is concluded that there is no relationship between a past history of spontaneous abortion and low birthweight.


The effects of defendant conduct on jury damage awards.
Laws of negligence dictate that jurors' decisions about damages be influenced by the severity of plaintiffs' injuries and not by the reprehensibility of defendants' conduct. The authors simulated an automobile negligence trial to assess whether jurors' decisions are in accord with those expectations. Conduct of the defendant and severity of the plaintiff's injuries were manipulated. Jurors listened to the evidence, completed predeliberation questionnaires, deliberated as a jury, and completed postdeliberation questionnaires. Severity of the plaintiff's injury had a strong impact on damage awards, but evidence related to the defendant's conduct was also influential, particularly when the plaintiffs injuries were mild. Here, jurors with any conduct-related evidence gave larger damage awards than jurors with no conduct-related evidence. Findings suggest an effect of defendant conduct on damage awards that may be mediated by judgments that the defendant was negligent.


Nicotinamide and structurally related compounds show halting activity against zoospores of the phytopathogenic fungus Aphanomyces cochlioides.
In a survey of plant secondary metabolites regulating the behavior of phytopathogenic Aphanomyces cochlioides zoospores, we found that leaf extracts of Amaranthus gangeticus and cotyledon extracts of pea (Pisum sativum) remarkably halted the motility of zoospores. Bioassay-directed fractionation of A. gangeticus and pea constituents revealed that the halting activity was dependent on a single chemical factor (halting factor). The active principle was identified as nicotinamide (1) by comparing its biological activity and spectroscopic properties with those of the authentic compound. Nicotinamide (1) showed potent halting activity toward the zoospores of A. cochlioides and A. euteiches, but it exhibited very less activity against other Oomycetes, Pythium aphanidermatum and Phytophthora infestans zoospores. Interestingly, the zoospores halted by nicotinamide (1) encysted within 10-15 min and then the resulting cystospores regenerated zoospores instead of germination. Nicotinamide (1) and related compounds were subjected to the halting activity bioassay to elucidate the structure-activity relationships. These bioassays revealed that part structures of (A) the aromatic ring containing at least one nitrogen atom, (B) carbonyl-like group adjacent to the aromatic ring and (C) hydrogen atoms on the amide group are responsible for the strong activity. So far, this is the first report of halting activity of nicotinamide (1) against fungal zoospores.


Total synthesis of the marine metabolite (±)-polysiphenol via highly regioselective intramolecular oxidative coupling.
(±)-Polysiphenol (1), an atropisomerically stable 4,5-dibrominated 9,10-dihydrophenanthrene from Polysiphonia ferulacea, was prepared by a biomimetically inspired highly regioselective intramolecular oxidative coupling of a dibrominated dihydrostilbene. The installation of the two bromine atoms prior to oxidative coupling prevents further oxidation to a planar aromatized phenanthrene. By this strategy, the synthesis of (±)-polysiphenol was achieved in four steps in 70% overall yield. Synthesis of the naturally occurring 5,5'-(ethane-1,2-diyl)bis(3-bromobenzene-1,2-diol) (2) (the likely biogenetic precursor of polysiphenol) and 5,5'-(ethane-1,2-diyl)bis(3,4,6-tribromobenzene-1,2-diol) (9) are also reported. The origins of the regioselectivity in the oxidative coupling are explored.


Ultrastructural and cytochemical evidence for single impulse initiation zones in vestibular macular nerve fibers of rat.
Cupric ion-ferricyanide labeling methods and related ferrocyanide-stained tissues were used to locate and characterize, at the ultrastructural level, presumptive impulse initiation zones in the three types of vestibular macular nerve fibers. Large-diameter, M-type vestibular nerve fibers terminate in a calyx at the heminode, and labeling is coextensive with the base of the calyx. Intermediate, M/U-type nerve fibers have short, unmyelinated preterminal segments that sometimes bifurcate intramacularly, and small-diameter, U-type nerve fibers have long, unmyelinated preterminal axons and up to three branches. Preterminals of these nerve fibers display ultrastructural heterogeneity that is correlated with labeling patterns for sodium channels and/or associated polyanionic sites. They have a nodelike ultrastructure and label heavily from near the heminode to the base of the macula. Their intramacular branches, less organized ultrastructurally, label only slightly. Results indicate that vestibular nerve fibers have one impulse initiation zone, located near the heminode, that varies in length according to nerve fiber type. Structural heterogeneity may favor impulse conduction in the central direction, and length of the impulse initiation zone could influence nerve discharge patterns.


[ACE inhibitors and its usefulness in the prevention of aspiration pneumonia in chronic cerebrovascular disease patients with asymptomatic swallowing dysfunction].
The double contrast pharyngogram by use of computed radiography (DCP-CR) has been found to be useful in detection of asymptomatic swallowing dysfunction. Following the DCP-CR examination, we investigated the incidence of aspiration pneumonia in 143 patients with chronic cerebrovascular disease (CVD) for 3 years and the effects of ACE inhibitors on the prevention of pneumonia. Aspiration pneumonia occurred in 29 out of 143 patients, and more frequently in the elderly chronic CVD patients with multiple brain lesions. Aspiration pneumonia was confirmed in 26 out of 85 patients (30.6%) with abnormal barium adhesion to the pharyngeal wall on the double contrast pharyngogram image by DCP-CR; whereas pneumonia occurred in 3 out of 58 patients (5.2%) with normal findings of DCP-CR pharyngogram. Among chronic CVD patients with abnormal findings of DCP-CR pharyngogram, the incidence of aspiration pneumonia was significantly lower in the patients treated with ACE inhibitors than in those treated with other antihypertensive agents or without antihypertensive agents (chi 2 value = 7.163, p < 0.05). Accordingly, ACE inhibitors may prevent the aspiration pneumonia and reduce the incidence of aspiration pneumonia in the chronic CVD patients with abnormal DCP-CR pharyngogram images.


Direct determination of pantoprazole enantiomers in human serum by reversed-phase high-performance liquid chromatography using a cellulose-based chiral stationary phase and column-switching system as a sample cleanup procedure.
A direct stereoselective reversed-phase HPLC method is described for the determination of the enantiomers of a proton pump inhibitor, pantoprazole (PAN), in human serum. The enantiomers were separated with high resolution on a cellulose-based chiral stationary phase (Chiralcel OJ-R) following on-line solid phase sample cleanup with a column-switching device. A mixture of acetonitrile and 50 mM sodium perchlorate was used as the mobile phase at a flow rate of 0.5 mliter/min. Pantoprazole enantiomers were detected by monitoring the column effluent with UV light at a wavelength of 290 nm. The calibration curve for each enantiomer was linear from 0.1 to 5.0 micrograms/mliter. Under these conditions, the determination of pantoprazole enantiomers in human serum can be achieved with satisfactory selectivity, sensitivity, precision, and accuracy. The described procedure is very simple and rapid since labor-intensive sample preparation is not required. The method was applied to the analyses of the serum samples obtained from a volunteer who received an 80-mg oral dose of racemic PAN. The samples showed the (+)/(-) isomer ratios ranging from 0.74 to 1.03 up to 6 h after dosing, indicating that there is only a small difference in the concentrations of (+)- and (-)-PAN.


Identification and Computational Analysis of Novel TYR and SLC45A2 Gene Mutations in Pakistani Families With Identical Non-syndromic Oculocutaneous Albinism.
Non-syndromic oculocutaneous albinism (nsOCA) is an inherited disorder of melanin biosynthesis with autosomal recessive mode of inheritance, presenting either hypopigmented or depigmented skin, hair, and eyes. It is genetically heterogeneous with seven loci (OCA1-OCA7) reported to date. In the present study, we have reported three consanguineous families (A, B, C) presenting identical nsOCA phenotypes. Sanger sequencing revealed a novel [NM_000372.5: c.826 T > C, p.(Cys276Arg)] and a recurrent variant [NM_000372.5: c.832C > T, p.(Arg278∗)] in tyrosinase (TYR) in families A and B, respectively. Microsatellite marker-based homozygosity mapping linked family C to OCA4. Sequence analysis identified a novel insertion variant (NM_016180.5: c.1331_1332insA) in the SLC45A2. Further, in silico mutagenesis and dynamic simulation approaches revealed that a novel Cys276Arg variant abolished the cysteine bridge and might contribute toward decreased stability of the TYR protein. Our study expands the mutation spectrum of the TYR and SLC45A2 genes and emphasizes that molecular investigations are essential for accurate disease diagnosis.


Successful treatment of advanced gastric adenocarcinoma with portal tumor thrombosis by total gastrectomy following CDDP and S-1 therapy.
Gastric cancers with portal tumor thrombosis (GCPTs) are a rare entity, often concomitant with hematogenous metastases, and chemotherapy is mainly used to treat them. However, the outcome of GCPT is reported to be dismal. We experienced a case of GCPT with splenic metastases. A 53-year-old man was admitted for anorexia. Upper gastrointestinal scope revealed type 3 gastric cancer of the stomach. Abdominal computed tomography showed a huge tumor thrombus in the splenic vein extending to the hepatic hilus and multiple metastases to the spleen. S-1 was given orally from day 1 to day 21 and 60 mg of CDDP was administered intravenously. The cancerous thrombosis in the portal system and splenic metastases disappeared due to chemotherapy. Total gastrectomy with lymphadenectomy and splenectomy was carried out with curative intent after 10 courses of chemotherapy. Intraoperatively, no tumor thrombosis was identified and the gastric tumor was surgically removed. After surgery, the patient received adjuvant chemotherapy of S-1. After 6 months he is well and has not suffered from tumor relapse. A combination of CDDP + S-1 plus intervention surgery seems to be a promising option for GCPT.