Selective accumulation of the complement membrane attack complex in aging choriocapillaris.
The complement membrane attack complex (MAC) shows increased abundance in the choriocapillaris during normal aging and is especially prevalent in age-related macular degeneration (AMD). While perivascular MAC accumulation occurs in the choroid, it is not well understood whether similar deposition occurs in other aging tissues. In this study we examined the abundance of MAC across multiple human tissues. For studies on fixed tissues, paraffin sections were obtained from six human donor eyes and a commercially available tissue array containing 19 different tissues. Immunohistochemical labeling was performed using antibodies directed against the MAC and intercellular adhesion molecule-1 (ICAM-1), as well as the lectin Ulex europaeus agglutinin-I (UEA-I). The choriocapillaris was the only tissue with high levels of the MAC, which was not detected in any of the 38 additional samples from 19 tissues. ICAM-1 was abundantly expressed in the majority of tissues evaluated, and UEA-I labeled the vasculature in all tissues. A second experiment was performed using unfixed frozen sections of RPE-choroid and 7 extraocular tissues, which confirmed the relatively limited localization of the MAC to the choriocapillaris. In comparison to other tissues assessed, the restricted accumulation of MAC in the choriocapillaris may, in part, explain the specificity of AMD to the neural retina, RPE and choroid, and the relative absence of systemic pathology in this disease.


Combined application of isotropic three-dimensional fast spin echo (3D-FSE-Cube) with 2-point Dixon fat/water separation (FLEX) and 3D-FSE-cube in MR dacryocystography.
To evaluate the image quality of magnetic resonance dacryocystography (MRD) using three-dimesional fast spin-echo -Cube (3D-FSE-Cube) and 3D-FSE-Cube-Flex sequences to examine the lacrimal drainage system (LDS). 21 healthy volunteers underwent 3D-FSE-Cube and 3D-FSE-Cube-Flex MRD after topical administration of compound sodium chloride eye drops. Two radiologists assessed LDS images in a blinded fashion. The signal-to-noise ratio of fluid-filling and the contrast-to-noise ratio of fluid-turbinate were compared between the two sequences. Overall image quality, sharpness, artefacts, visualization of anatomical structures, and visibility of LDS segments were also compared. Overall image quality, visualization of anatomic structures, and artefact were significantly better on 3D-FSE-Cube-Flex MRD (p < 0.001, respectively). when compared to 3D-FSE-Cube. 3D-FSE-Cube showed lower fluid-filling signal-to-noise ratio and fluid-inferior turbinate CNR (all p < 0.001). In comparison with 3D-FSE-Cube-Flex, 3D-FSE-Cube produced superior visibility of the upper drainage segments (superior canaliculi, p = 0.003; common canaliculus, p = 0.033; inferior canaliculi, p < 0.001), but inferior in lower-LDS visibility (lacrimal sac, p = 0.001; nasolacrimal duct, p < 0.001). There was no difference in the total number of segments visualized per LDS between the two sequences (p = 0.068). 3D-FSE-Cube-Flex demonstrated superior image quality and visibility of the lower LDS segments. 3D-FSE-Cube showed an advantage in visualizing the upper LDS segments. The combination of these sequences can improve LDS visibility. 3D-FSE-Cube-Flex provides robust water & fat separation and mitigates lower LDS-associated inhomogeneity artefacts. 3D-FSE-Cube shows optimal upper LDS visualization. The combined application of these sequences is a non-invasive and effective method for assessing LDS disease.


Antifouling Diterpenoids from the Sponge Dendrilla antarctica.
Two nor-diterpenes, 9,11-dihydrogracilin A (1) and the previously unreported 9,11-dihydrogracillinone A (2), were isolated from the sponge Dendrilla antarctica. The sponge was collected by trawling at a depth of 49 m, from the research vessel Puerto Deseado, near the coast of Tierra del Fuego, farther north than the reported habitat for this species. Since these compounds were particularly abundant and the sponge was free from epibionts, both 1 and 2 were included in soluble-matrix paints and tested for antifouling activity in the ocean. The results obtained from these experiments clearly indicated a potent antifouling activity for both compounds against a variety of colonizing organisms, and established a probable role as natural antifoulants for these abundant secondary metabolites and other structurally related compounds previously isolated from Dendrilla spp.


Effects of okchun-san, a herbal formulation, on blood glucose levels and body weight in a model of Type 2 diabetes.
The effective control of blood glucose is the key to preventing or reversing diabetic complications. In this study, we examined the effects of Okchun-San (OCS), a Korean herbal medicine formula, on the blood glucose levels in diabetic C57BL/KsJ db/db mice. Herbal medicines were prepared from dried herbs by adding Coicis semen (OCS-C) or Oryzae semen (OCS-O). The experimental animals were divided into a control group and three sample groups; the sample groups received OCS-C (200 mg/kg), OCS-O (200 mg/kg), or acarbose (5 mg/kg) orally once a day for 12 days. On days 5 and 12, the fasting blood glucose levels of vehicle-treated db/db mice were significantly higher than day 0, while those of OCS-C, OCS-O, or acarbose-treated mice had not increased compared to the control group (p<0.01). During intraperitoneal glucose tolerance test (IPGTT), OCS-C group showed improved glucose sensitivity compared to the control group. These results suggest that OCS-C can be useful as an anti-diabetic therapy for Type 2 diabetic patients by lowering the blood glucose level.


Streamlined Total Synthesis of Shishijimicin A and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues thereof and Practical Syntheses of PhthNSSMe and Related Sulfenylating Reagents.
Shishijimicin A is a scarce marine natural product with highly potent cytotoxicities, making it a potential payload or a lead compound for designed antibody-drug conjugates. Herein, we describe an improved total synthesis of shishijimicin A and the design, synthesis, and biological evaluation of a series of analogues. Equipped with appropriate functionalities for linker attachment, a number of these analogues exhibited extremely potent cytotoxicities for the intended purposes. The synthetic strategies and tactics developed and employed in these studies included improved preparation of previously known and new sulfenylating reagents such as PhthNSSMe and related compounds.


Proton NMR resonance assignments and surface accessibility of tryptophan residues of a dimeric phospholipase A2 from Trimeresurus flavoviridis.
Proton NMR spectra of a dimeric phospholipase A2 from Trimeresurus flavoviridis have been recorded. N-1 proton resonances of the tryptophan indole rings have been detected and assigned to specific positions, Trp-3/Trp-30, Trp-68 and Trp-108, by comparing the spectra of the enzyme derivatives with tryptophans oxidized to differing extents. Photo-CIDNP experiments have revealed that Trp-68 and Trp-108 are exposed while Trp-3 and Trp-30 are buried in the molecule. This is consistent with the X-ray crystal structure of a homologous phospholipase A2 from Crotalus atrox where residues 3 and 30 are located at a dimer interface, but inconsistent with the results of stepwise oxidation of tryptophan residues.


Transfusion utilization during adnexal or peritoneal cancer surgery: effects on symptomatic venous thromboembolism and survival.
To determine whether perioperative packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusions during ovarian, tubal, or peritoneal cancer surgery increase the risk of symptomatic postoperative venous thromboembolism (VTE) and adversely affect overall survival. We conducted a retrospective review of all cases of surgical exploration for resection of stage IIIC-IV adnexal/peritoneal cancer between November 1998 and May 2002 at Memorial Sloan-Kettering Cancer Center. Patients with a history of prior or active preoperative VTE were excluded. Routine intraoperative and postoperative VTE prophylaxis including lower extremity external pneumatic compression with or without postoperative subcutaneous heparin was utilized in all cases. Symptomatic postoperative VTE was diagnosed by lower extremity Doppler or computerized tomography (excluding cases with only ovarian vein thrombosis). Clinical parameters were examined by a logistic regression analysis to identify independent prognostic predictors of postoperative symptomatic VTE, which occurred within 30 days of surgery. Survival was calculated using the Kaplan-Meier method. In all, 174 patients underwent exploratory surgery, and 6 (3.4%) were excluded due to active or prior history of VTE. Of the remaining 168 patients, 71 (42%) received at least one perioperative transfusion of PRBC or FFP. Postoperative VTE was documented in 5 of 46 (11%) patients who received a postoperative transfusion compared to 3 of 122 (2.5%) patients who did not (P = 0.04; odds ratio, 4.8); moreover, VTE was noted in 3:16 (19%) patients who received postoperative FFP compared to 5:152 (3.3%) patients who did not (P = 0.01, odds ratio of 6.78). Age, stage, body mass index, length of the operation, blood loss, presence of ascites, volume of ascites, residual disease status, preoperative hemoglobin level and coagulation profile were not associated with increased risk for VTE. When survival results were stratified by transfusion utilization and controlling for optimal debulking status, perioperative transfusions had no apparent effect on overall survival. In women with stage IIIC-V disease, postoperative blood product transfusions particularly FFP were associated with increased risk of DVT and PE, but transfusions had no impact on overall survival.


Effects of long-term theophylline treatment on adenosine A1-receptors in rat brain: autoradiographic evidence for increased receptor number and altered coupling to G-proteins.
The effects of 2 weeks' treatment with theophylline (20 mg/kg i.p.) on the binding to adenosine A1-receptors was studied by autoradiography using the agonist [3H]N6-cyclohexyladenosine ([3H]CHA) and the antagonist [3H]8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX) as ligands. A significant increase (10%) in [3H]CHA binding was measured only in the frontoparietal cortex. However, if the brain sections were incubated in the presence of 5 microM guanosine-5'-triphosphate (GTP), which by itself decreased binding by between 15 and 80% depending on the region, the increase in the frontoparietal cortex was larger (30%) and significant increases of the same magnitude were also seen in several other structures, e.g. the caudate putamen and the central gray matter of the midbrain. In some regions, for example the hippocampus and the cerebellar cortex, small or no increases were seen. GTP 100 microM practically eliminated [3H]CHA binding in both control and treated animals, suggesting that these receptors are all coupled to G-proteins. The binding of [3H]DPCPX was increased significantly only in the frontoparietal and striate cortex (5-10%). These results suggest that the theophylline treatment had little on the total receptor number but may have altered the coupling between A1-receptors and regulatory GTP-binding proteins.


Acrokeratoelastoidosis treated with etretinate.
Acrokeratoelastoidosis is a chronic condition manifested by acral hyperkeratotic papules. There have been no reports of effective treatment. We report a case that responded to etretinate.


Toll like receptor 4 signaling pathway participated in Salmonella lipopolysaccharide-induced spleen injury in young chicks.
Spleen is one of the crucial sites for cellular and humoral immunity but it easily damaged during pathogenic infections resulting in immunosuppression. The current study was therefore performed to explore the mechanism of acute spleen injury induced by salmonella lipopolysaccharide (LPS) in young chicks. Healthy one-day-old Cobb strain broiler chicks were intra-peritoneally injected with saline or LPS. LPS treatment caused significant decreases in body and spleen weights at 36 and 72 h. Histological analysis showed the changes of ellipsoid structures with beginning of nuclear pyknosis and karyolysis similar to steatosis at 12 h, maximum histopathological lesions were seen at 36 h, however these were disappeared at 72 h post LPS stimulation. Cell proliferation was decreased (low PCNA positivity) and apoptosis increased (high ssDNA positivity) in the spleen at 12 and 36 h after LPS treatment. The expression levels of mRNA for caspase-3, caspase-8, B-cell lymphoma 2 (BCL-2), tumor protein p53 or p53 and Bcl-2 homologous antagonist killer (BAK) showed slight increase at some time points following LPS stimulation. LPS treatment also induced significant up-regulation in toll like receptor 4 (TLR4) at 36 h post LPS stimulation and slight increase in expressions of its downstream molecules (MyD88 and NF-κB) at 12 h post LPS treatment. The keystone cytokines (TNF-α and IL-6) exhibited significant up-regulation at 12 h following LPS stimulation. Our findings provided novel information about the histopathological as well as apoptotic and proliferative alterations in spleen mediated by TLR4 signaling induced by Salmonella LPS in avian species.


Referential communication in Alzheimer's type dementia.
This paper investigates factors that underlie reduced informative content and lack of reference in the discourse of patients with Alzheimer's Type Dementia (DAT). Patients with DAT, fluent aphasics and normal controls were given a referential communication task structured to assess lexical encoding of information, pragmatic/conceptual elaboration of information and effectiveness in establishing reference. The subjects also received standardised aphasia tests (CADL, Holland, 1980; and Cookie Theft Picture Description, Nicholas and Brookshire, 1993). Comparable reduction of lexical encoding of information was found in the discourse of aphasic and DAT participants both on the referential communication task measures and on the standardised evaluation with the Cookie Theft Picture Description test. However, the DAT subjects' discourse on the referential communication task was less efficient in establishing reference than that of the aphasics since the former presented more misunderstandings and required more explicit prompts from the listener. Furthermore, the DAT language on the referential communication task contained confounding and irrelevant information; also, the number of these errors correlated negatively with their referring abilities. Results of the CADL test confirmed that the DAT participants had less communicative effectiveness than their lexical deficit alone predicted. Finally, examination of the performance of individual DAT subjects showed that lexical encoding of information could dissociate from effectiveness in making reference. These findings support the view that difficulty in pragmatic/conceptual elaboration of discourse information content plays a substantial role in the development of reduced information content and lack of reference of DAT "empty speech". These results are discussed in the framework of the hypothesis of early attentional/executive impairment in DAT (Perry and Hodges, 1999).


Finding Optimal Mid-Infrared Nonlinear Optical Materials in Germanates by First-Principles High-Throughput Screening and Experimental Verification.
Owing to wide infrared (IR) transparency ranges, high laser damage thresholds, and being easy to grow in open air, germanates are emerging as promising mid-infrared (mid-IR) nonlinear optical (NLO) materials. However, the germanates as NLO materials have not been investigated comprehensively and the crystals with large second harmonic generation (SHG) response have not been identified. Herein, we used the first-principles high-throughput screening pipeline for NLO materials to search for excellent NLO crystals from germanates collected in the inorganic crystal structure database. After two steps of screening, three crystals are picked out from 128 structures based on their predicted energy gaps, birefringences, and SHG coefficients. Subsequently, the three germanates are synthesized and measured. The results show that Pb3Ga2Ge4O14 and Ba2TiGe2O8 exhibit a wide energy gap (>3.1 eV) and a strong phase-matchable SHG intensity that are comparable to the benchmark AgGaS2 (0.8 and 1.2 × AgGaS2, respectively). In addition, the statistical analyses of different categories classified according to their cations show that the d0-transition metal and lone pair cations are more conducive to achieving a larger SHG response and birefringence compared to other cations in germanates. It gives a guideline for exploring new mid-IR NLO materials.


Mutational and recombinational events in carcinogen-modified plasmid DNA. Influence of host-cell repair genes.
A plasmid containing the STR operon has been modified in vitro (i) by irradiation with UV light, (ii) by reaction with ethyl methanesulphonate (EMS), (iii) by reaction with N-acetoxy-2-acetylaminofluorene (AcO-AAF), (iv) by reaction with (+/-)trans-benzo[a]pyrene-7, 8-dihydrodiol-9,10-epoxide (BPDE), and (v) by heating at 70 degrees C to produce apurinic sites. Suitably modified plasmid DNA was then used to transform both repair-proficient and repair-deficient strains of Escherichia coli, and the mutation frequency in the plasmid-encoded rspL+ gene measured. The influence of host mutations in the uvrB+, recA+, umuC+ and lexA+, genes on the mutation frequency have been investigated. Transformation into a uvrB strain significantly decreased survival and increased the level of mutations observed for UV- and AcO-AAF-modified plasmid DNA, while only a small increase in mutation frequency was seen with EMS-modified DNA and no increase in mutation frequency with plasmid DNA containing apurinic sites. Mutagenesis in UV- and BPDE-modified DNA (and probably also DNA containing apurinic sites) was totally dependent on he recA+ gene product, while EMS and AcO-AAF induced mutagenesis was only partially independent on the recA+ gene. Transformation of UV- or BPDE-modified DNA into a umuC or lexA strain, on the other hand, showed no change in mutation frequency from that observed with wild-type strain. Pre-irradiation of the wild-type host with UV light before transformation led to a significant increase in mutation frequency for UV- and BPDE-modified plasmid DNA. These results are discussed in terms of mutational or recombinational pathways which may be available to act on modified plasmid DNA, and suggest that the majority of the mutational events measured in this system are due to recombination between homologous regions on the plasmid and chromosomal DNA.


13-Cis-retinoic acid: pharmacology, toxicology, and clinical applications for the prevention and treatment of human cancer.
Retinoids, particularly 13-cis-retinoic acid, have shown great promise against a number of benign, but serious dermatological conditions. In animal models, 13-cis-retinoic acid functions is a potent antipromoter whether a cancer has been initiated by chemical, physical, or viral agents. Additionally, substantial antiproliferative activity of this compound has been demonstrated in vitro in many culture systems. Clinical activity noted against several types of skin malignancies has led to several investigations to determine the anticancer activity of 13-cis-retinoic acid. Response of a variety of preneoplastic and neoplastic lesions of epithelial histology has been demonstrated. The toxicity of 13-cis-retinoic acid largely reflects its tissue distribution with skin and subcutaneous side-effects limiting dose escalation. The pharmacology and pharmacokinetics of 13-cis-retinoic acid has been explored in a number of patients and a long terminal half-life demonstrated. This review will discuss 13-cis-retinoic acid as a good model for a biological response modifier.


Long-term persistence of transcriptionally active 'defective' HIV-1 proviruses: implications for persistent immune activation during antiretroviral therapy.
People with HIV-1 (PWH) on effective antiretroviral therapy (ART) continue to exhibit chronic systemic inflammation, immune activation, and persistent elevations in markers of HIV-1 infection [including HIV-DNA, cell-associated HIV-RNA (CA HIV-RNA), and antibodies to HIV-1 proteins] despite prolonged suppression of plasma HIV-RNA levels less than 50 copies/ml. Here, we investigated the hypothesis that nonreplicating but transcriptionally and translationally competent 'defective' HIV-1 proviruses may be one of drivers of these phenomena. A combined cohort of 23 viremic and virologically suppressed individuals on ART were studied. HIV-DNA, CA HIV-RNA, western blot score (measure of anti-HIV-1 antibodies as a surrogate for viral protein expression in vivo ), and key biomarkers of inflammation and coagulation (IL-6, hsCRP, TNF-alpha, tissue factor, and D-dimer) were measured in peripheral blood and analyzed using a combined cross-sectional and longitudinal approaches. Sequences of HIV-DNA and CA HIV-RNA obtained via 5'-LTR-to-3'-LTR PCR and single-genome sequencing were also analyzed. We observed similar long-term persistence of multiple, unique, transcriptionally active 'defective' HIV-1 provirus clones (average: 11 years., range: 4-20 years) and antibody responses against HIV-1 viral proteins among all ART-treated participants evaluated. A direct correlation was observed between the magnitude of HIV-1 western blot score and the levels of transcription of 'defective' HIV-1 proviruses ( r = 0.73, P < 0.01). Additional correlations were noted between total CD8 + T-cell counts and HIV-DNA ( r = 0.52, P = 0.01) or CA HIV-RNA ( r = 0.65, P < 0.01). These findings suggest a novel interplay between transcription and translation of 'defective' HIV-1 proviruses and the persistent immune activation seen in the setting of treated chronic HIV-1 infection.


Intraspinal application of endothelin results in focal ischemic injury of spinal gray matter and restricts the differentiation of engrafted neural stem cells.
Previous data have shown that pluripotent stem cells engrafted into the contused spinal cord differentiate only along an astrocytic lineage. The unknown restrictive cues appear to be quite rigid as even neuronal-restricted precursors fail to differentiate to the mature potential they exhibit in vitro after similar grafting into the contused spinal cord. It has been hypothesized that this potent lineage restriction is, in part, the result of the significant loss of both gray and white matter observed following spinal contusion, which elicits a massive acute inflammatory response and is manifested chronically by dramatic cystic cavitation. To evaluate the gray matter component, we developed a clinically relevant model of focal gray matter ischemic injury using the potent vasoconstrictor endothelin (ET-1) and characterized the differentiation of pluripotent stem cells transplanted into this atraumatic vascular SCI. Results demonstrate that low dose ET-1 microinjection into cervical spinal gray matter results in an inflammatory response that is temporally comparable to that observed following traumatic SCI, as well as chronic gray matter loss, but without significant cystic cavitation or white matter degeneration. However, despite the preservation of host spinal parenchyma, no elaboration of neuronal phenotypes was observed from engrafted stem or precursor cells. These results suggest that a common pathologic component responsible for this lineage restriction exists between contusive SCI and ET-1 mediated focal ischemic SCI.


A Content Analysis of Coronavirus Tweets in the United States Just Prior to the Pandemic Declaration.
This study examined public comments on Twitter about coronavirus in the weeks after news stories across the globe on the coronavirus outbreak. A total of 600 tweets were assessed (N = 600) for sentiment, risks presented, attribution of blame, and outrage. A sample of 300 tweets was taken from Sunday, February 9, through Wednesday, February 19, 2020, and an additional 300 tweets from Sunday, March 1, through Wednesday, March 11, 2020, to assess how public communication changed over time. Results show that risk, blame, and outrage differed significantly between February and March in a variety of ways. Specifically, more significant risks were noted in February than in March, with the majority of March tweets not noting any specific risks. Although most tweets did not present any specific blame, more blame was presented in February than in March, although more tweets in March attributed blame to countries and governments. Finally, outrage varied in several ways, with hazards generally being higher in February and outrage being higher in March.


Design, Synthesis and Biological Evaluation of Novel PEG-Rakicidin B1 Hybrid as Clostridium difficile (CD) Targeted Anti-Bacterial Agent.
Rakicidin B1 was isolated and purified from the culture broth of a marine Streptomyces sp. as a potent anti-cancer agent, and lately the compound and its derivatives have firstly been found to possess anti-Clostridium difficile (CD) activity but with high cytotoxicity. Herein, following our previous discovery on anti-CD activity of Rakicidin B1, structure modification was performed at the OH position of Rakicidin B1 and a new Rakicidin B1-PEG hybrids FIMP2 was facilely designed and synthesized by conjugating the PEG2000 with the scaffolds of Rakicidin B1 via the linkage of carbamate. The cytotoxicity of the FIMP2 was first evaluated against three different cancer cell lines, including HCT-8 cells, PANC-1, and Caco-2, with IC50 values at 0.519 μM, 0.815 μM, and 0.586 μM, respectively. Obviously, as compared with a positive control group treated with Rakicidin B1, the IC50 value of FIMP2 increased by nearly 91-fold, 50-fold, and 67-fold, suggesting that the PEGylation strategy significantly reduced the cytotoxicity of FIMP2. Thus, this preliminary result may be beneficial to increase its safety index (SI) value due to the decreased cytotoxicity of FIMP2. In addition, this decreased cytotoxicity of FIMP2 was further confirmed based on a zebrafish screening model in vivo. Thereafter, the anti-CD activity of FIMP2 was evaluated in vivo, and its efficacy to treat CDI was found to be better than that of vancomycin. The mortality and recurrence rate of FIMP2 is not as low compared with that of vancomycin; these results demonstrated that compound FIMP2 is a new, promising anti-CD agent with significant efficacy against CD recurrence with low cytotoxicity towards bodies.


Protective effect of suppressor of cytokine signalling 1-based therapy in experimental abdominal aortic aneurysm.
Abdominal aortic aneurysm (AAA) is a multifactorial disease characterized by chronic inflammation, oxidative stress and proteolytic activity in the aortic wall. Targeting JAK/signal transducer and activator of transcription (JAK/STAT) pathway is a promising strategy for chronic inflammatory diseases. We investigated the vasculo-protective role of suppressor of cytokine signalling-1 (SOCS1), the negative JAK/STAT regulator, in experimental AAA. A synthetic, cell permeable peptide (S1) mimic of SOCS1 kinase inhibitory domain to suppress STAT activation was evaluated in the well-established mouse model of elastase-induced AAA by monitoring changes in aortic diameter, cellular composition and gene expression in abdominal aorta. S1 function was further evaluated in cultured vascular smooth muscle cells (VSMC) and macrophages exposed to elastase or elastin-derived peptides. S1 peptide prevented AAA development, evidenced by reduced incidence of AAA, aortic dilation and elastin degradation, partial restoration of medial VSMC and decreased inflammatory cells and oxidative stress in AAA tissue. Mechanistically, S1 suppressed STAT1/3 activation in aorta, down-regulated cytokines, metalloproteinases and altered the expression of cell differentiation markers by favouring anti-inflammatory M2 macrophage and contractile VSMC phenotypes. In vitro, S1 suppressed the expression of inflammatory and oxidative genes, reduced cell migration and reversed the phenotypic switch of macrophages and VSMC. By contrast, SOCS1 silencing promoted inflammatory response. This preclinical study demonstrates the therapeutic potential of SOCS1-derived peptide to halt AAA progression by suppressing JAK/STAT-mediated inflammation and aortic dilation. S1 peptide may therefore be a valuable option for the treatment of AAA.


Intraarticular viscosupplementation following arthroscopic anterior cruciate ligament reconstruction: A systematic review.
Pain, swelling and joint stiffness are the major problems following arthroscopic ACL reconstruction (ACLR) surgery that restrict early return to sports and athletic activities. The patients often receive prolonged analgesic medications to control the inflammatory response and resume the pre-injury activities. This systematic review aims to evaluate the safety and efficacy of intraarticular (IA) hyaluronic acid (HA) injection following ACLR. A literature search of electronic databases and a manual search of studies reporting clinical effectiveness of IA HA following ACLR was performed on 1st November 2020. The quality of the methodology and risk of bias was assessed using the Cochrane Collaboration Risk of Bias Tool and Newcastle-Ottawa scale for randomized-controlled trial and prospective cohort studies, respectively. Of 324 studies retrieved, four studies (3 RCTs and one prospective cohort study) were found to be suitable for inclusion in this review. These studies had a low to moderate risk of bias. There were 182 patients in the HA group and 121 patients in the control group. The demographic characteristics of the patients were similar in all studies. The pooled analysis of studies evaluating pain at different follow up periods (2-week, 4-6 weeks, 8-12 weeks) after ACLR revealed no significant difference between the HA and control groups (p > 0.05). The knee swelling was significantly less in the HA group at two weeks (MD -7.85, 95% CI: [-15.03, -0.68], p = 0.03, I2 = 0%), but no such difference was noted after 4-6 weeks and 8-12 weeks. The functional outcome score was not significantly different between the groups (SMD 0.00, 95% CI: 0.38 to 0.38, p = 0.99, I2 = 0%). Although the individual study demonstrated a short-term positive response regarding pain control and swelling reduction, the pooled analysis did not find any clinical benefit of IA HA injection following ACLR surgery. II.


Catabolite and transient repression in Escherichia coli do not require enzyme I of the phosphotransferase system.
Transient and catabolite repression with changes in intracellular concentrations of cyclic adenosine 3',5-monophosphate is produced by glycerol and by glucose-6-phosphate in a strain with a partial deletion of the structural gene for enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system.


Impact of rifampicin on the pharmacokinetics of clarithromycin and 14-hydroxy clarithromycin in patients with multidrug combination therapy for pulmonary Mycobacterium avium complex infection.
Clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP) combination therapy is used to treat pulmonary Mycobacterium avium complex (MAC) infection; however, serum CAM concentration decreases due to RFP-mediated induction of CYP3A activity. Therefore, we investigated the pharmacokinetics of CAM, 14-hydroxy clarithromycin (14-OH CAM), EB, and RFP in patients receiving this three-drug combination therapy. CAM monotherapy was started, EB was added 2 weeks later, and RFP was added 2 weeks after that. Serum CAM, 14-OH CAM, EB, and RFP concentrations were measured before and at 2, 4, 6, and 12 or 24 h after administration on days 14, 28, and 42, and pharmacokinetic parameters were calculated. Median area under the curve (AUC) of CAM decreased by 92.1% from 0 to 12 h after concomitant administration of RFP compared with CAM monotherapy [1.7 (interquartile range [IQR], 1.4-1.8) μg·h/mL vs. 21.5 (IQR, 17.7-32.3) μg·h/mL, respectively]. In contrast, median AUC of 14-OH CAM was not significantly different between concomitant administration of RFP [9.1 (IQR, 7.9-10.9) μg·h/mL] and CAM monotherapy [8.2 (IQR, 6.3-9.3) μg·h/mL]. AUCs of CAM and 14-OH CAM did not change in CAM+EB combination therapy. When RFP is combined with CAM in the treatment of pulmonary MAC infection, the blood concentration of CAM significantly decreased and that of the active metabolite 14-OH CAM increased, but not significantly. Our results suggest that combination therapy with CAM and RFP needs to be reconsidered and may require dose modification in the treatment of pulmonary MAC infection.


Adolescent bariatric surgery.
Overall it is clear that bariatric surgical intervention in appropriately selected adolescents is effective at both adequate weight loss and resolution of weight related co-morbidities in the short and medium term. Long-term results are being conducted currently to assess durability of bariatric surgical interventions. We believe that adolescents undergoing bariatric evaluation have unique needs and until more long-term data are available, the indications for surgery should be stricter than those used in adults. All of the bariatric procedures discussed must be performed in the background of positive behavioral modifications over a period of time. If lifestyle modification fails, these adolescents can gain weight by overcoming the physiologic effects of the surgery as they eat high calorie foods at very frequent intervals. Finally, close postoperative follow-up is required with active management of weight loss/gain, co-morbidities, and postoperative complications should they occur.


Ethical issues in primary health care: a survey of practitioners' perceptions.
While most health care is provided at the primary care level, little research has been done to document the ethical issues of such care. A stratified random sample of 702 physicians, nurses, physical therapist, and physician assistants within one southeastern state was surveyed to determine the frequency of ethical issues in primary care. The most frequently occurring issue concerned moral decisions about the amount of time to spend with each patient. A comparison of physician and nonphysician professional groups revealed significant differences in frequencies of the issues. Age had a slight impact on the responses, while gender, religion, and region of practice had none. The study showed that the most frequently occurring issues are pragmatic, not dramatic, and center on patient self-determination, adequacy of care and professional responsibility, and distribution of resources.


The biomedicalization of psychiatry: a critical overview.
The biomedical model currently dominates psychiatric clinical practice and research. Unfortunately, this dominance had led increasingly to biological reductionism. This paper examines the historical and sociopolitical underpinnings of the biomedical model, and illustrates some of the common scientific distortions of reductionistic thinking. These observations are applied to recent directions in mental health policy and are used to provide a basis for alternative perspectives of mental illness and psychiatric research.


Alteration of circRNA and lncRNA expression profile in exosomes derived from periodontal ligament stem cells undergoing osteogenic differentiation.
This study investigated circRNA and lncRNA expression profile in exosomes derived from periodontal ligament stem cell (PDLSC) before and after its osteogenic differentiation. Exosomes derived from PDLSCs before (EX0) and after osteogenic induction for 5 (EX5) and 7 (EX7) days were harvested and exosomal circRNAs and lncRNAs were analyzed by RNA sequencing. Certain RNAs showing significantly altered expression were selected for qRT-PCR verification. The circRNA-miRNA-mRNA network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. All groups of exosomes showed typical characteristics under nanoparticle tracking analysis, flow cytometry assay and transmission electron microscopy. 69-557 circRNAs and 2907-11581 lncRNAs were found in EX0, EX5 and EX7, which were broadly distributed across the 24 pairs of human chromosomes. Compared with EX0, 3 circRNAs and 2 lncRNAs were up-regulated and 39 circRNAs and 5 lncRNAs down-regulated consistently through out of EX5 and EX7, p < 0.05. qRT-PCR confirmed certain those consistently expressed RNAs, such as circ lysophosphatidic acid receptor 1 (LPAR1). KEGG analysis showed that those consistent expressed RNAs closely related to TGF-beta pathway, MAPK pathway, mTOR pathway and FoxO signaling pathways regulating pluripotency of stem cells. Exosomal circRNAs and lncRNAs had significant expression changes during the early phase of osteogenic differentiation of PDLSCs. Further study would be taken for understanding the roles of exosomal circRNAs and lncRNAs playing in osteogenic differentiation of PDLSCs.


Antinuclear antibodies in patients with polymorphic light eruption: a long-term follow-up study.
Previous studies have shown elevated titres of antinuclear antibodies (ANA) in 2.9-19% of patients with polymorphic light eruption (PLE). A diagnosis of lupus erythematosus (LE) was finally established in some of these ANA-positive patients. To investigate whether the presence of ANA in patients with PLE merely represents an epiphenomenon or is associated with an increased risk of eventual progression to LE. We identified 472 patients with PLE who had received prophylactic photo(chemo)therapy between 1986 and 2003 and were routinely tested for the presence of ANA. All ANA-positive (ANA titre of>or=1:80) patients were asked to attend for a follow-up examination comprising a medical history, complete skin inspection and a detailed laboratory analysis including ANA and antibodies against extractable nuclear antigens. Of all the patients, 55 (11.7%) were found to be ANA positive on one or several occasions, and three (0.6%) also had antibodies to SS-A/Ro. Thirty-nine (71%) of all ANA-positive patients including all Ro+ subjects were available for follow-up after a median follow-up period of 8 years (interquartile range 5-11.5). Twenty-five patients showed persistence of ANA positivity with a median titre of 1:160 (range 1:80-1:640), whereas in 14 patients ANA titres had returned to normal levels. None of the patients revealed additional clinical, histopathological or laboratory abnormalities suggestive of LE. After a median follow-up period of 8 years none of the ANA-positive patients developed LE. Our findings indicate that PLE is a benign disease without tendency to progress to LE.


Tetrastatin, the NC1 domain of the α4(IV) collagen chain: a novel potent anti-tumor matrikine.
NC1 domains from α1, α2, α3 and α6(IV) collagen chains were shown to exert anti-tumor or anti-angiogenic activities, whereas the NC1 domain of the α4(IV) chain did not show such activities so far. We demonstrate in the present paper that the NC1 α4(IV) domain exerts a potent anti-tumor activity both in vitro and in an experimental human melanoma model in vivo. The overexpression of NC1 α4(IV) in human UACC-903 melanoma cells strongly inhibited their in vitro proliferative (-38%) and invasive (-52%) properties. MT1-MMP activation was largely decreased and its cellular distribution was modified, resulting in a loss of expression at the migration front associated with a loss of migratory phenotype. In an in vivo xenograft model in athymic nude mice, the subcutaneous injection of NC1 α4(IV)-overexpressing melanoma cells induced significantly smaller tumors (-80% tumor volume) than the Mock cells, due to a strong inhibition of tumor growth. Exogenously added recombinant human NC1 α4(IV) reproduced the inhibitory effects of NC1 α4(IV) overexpression in UACC-903 cells but not in dermal fibroblasts. An anti-αvβ3 integrin blocking antibody inhibited cell adhesion on recombinant human NC1 α4(IV) substratum. The involvement of αvβ3 integrin in mediating NC1 α4(IV) effect was confirmed by surface plasmon resonance (SPR) binding assays showing that recombinant human NC1 α4(IV) binds to αvβ3 integrin (K(D) = 148 ± 9.54 nM). Collectively, our results demonstrate that the NC1 α4(IV) domain, named tetrastatin, is a new endogenous anti-tumor matrikine.


An age-of-infection model with both symptomatic and asymptomatic infections.
We formulate a general age-of-infection epidemic model with two pathways: the symptomatic infections and the asymptomatic infections. We then calculate the basic reproduction number [Formula: see text] and establish the final size relation. It is shown that the ratio of accumulated counts of symptomatic patients and asymptomatic patients is determined by the symptomatic ratio f which is defined as the probability of eventually becoming symptomatic after being infected. We also formulate and study a general age-of-infection model with disease deaths and with two infection pathways. The final size relation is investigated, and the upper and lower bounds for final epidemic size are given. Several numerical simulations are performed to verify the analytical results.


Regeneration: did you hear the news?
In mammalian cochlea, hair cell death is irreversible. New work shows that the stem cells might exist in the inner ear of the mouse, opening a door to the possibility of repopulating damaged sensory epithelia in humans.


[Autism Spectrum Disorders in Adulthood: Empirical Findings on Comorbidities, Differential Diagnoses, and the Clinical Utility of the AQ].
AUTISM: spectrum disorders (ASD) often remain undiagnosed until adulthood. The aim of this study is to report differential diagnoses (DDX) and comorbidities of adults without intellectual impairment suspected of having an ASD and to test the self-assessment questionnaire Autism Quotient (AQ) for its suitability for screening. DDX and comorbidities were recorded with standardized scales in an autism outpatient clinic in 106 individuals. The AQ was tested against the expert judgment of an interdisciplinary case conference using ROC analysis. Affective disorders were common in both groups (48%); other DDX were phobias (33%) and personality disorders (22%). The AQ showed an AUC of 0,527 with sensitivity/specificity of 70%/35%. Adults suspected of having autism are highly burdened by DDX and comorbidities. An interdisciplinary diagnostic procedure based on standardized scales is useful, whereas the AQ hardly differentiates between persons with and without ASD.


Left Ventricular Longitudinal Dyssynchrony by CMR Feature Tracking Is Related to Adverse Prognosis in Advanced Arrhythmogenic Cardiomyopathy.
Objectives: Left ventricular (LV) involvement has been associated with unfavorable prognosis in arrhythmogenic cardiomyopathy (ACM). We aim to evaluate LV mechanics by cardiovascular magnetic resonance-feature tracking (CMR-FT) in ACM patients with right ventricular (RV) dysfunction. Methods: We retrospectively recruited ACM patients diagnosed according to the revised Task Force Criteria (rTFC) from January 2015 to July 2017. All patients underwent CMR examinations and collections of clinical, electrocardiographic data. The strain and dyssynchrony parameters of LV and RV were analyzed. These patients were followed, and primary study outcome was defined as a composite of cardiovascular events (arrhythmic events and heart transplantation), secondary study outcome included arrhythmic events. Results: Eighty-nine ACM patients (40.40 ± 13.98 years, 67.42% male) were included. LV and RV ejection fractions were 49.12 ± 12.02% and 22.28 ± 10.11%, respectively. During a median (IQR) follow-up for 18.20 (11.60-30.04) months, 30 patients experienced cardiovascular events which included 22 patients who experienced arrhythmic events. Patients with cardiovascular events had impaired LV global longitudinal strain (-10.82 ± 2.77 vs. -12.61 ± 3.18%, p = 0.010), impaired LV global circumferential strain (-11.81 ± 2.40 vs. -13.04 ± 2.83%, p = 0.044), and greater LV longitudinal dyssynchrony (LVLD) (80.98 ± 30.98 vs. 64.23 ± 25.51 ms, p = 0.012) than those without. After adjusting for age, sex, and other confounding factors, LVLD ≥89.15 ms was an independent risk factor for cardiovascular events (HR: 4.50, 95% CI: 1.94 to 10.42; p = 0.001) and for arrhythmic events (HR: 4.79, 95% CI: 1.74 to 13.20; p = 0.003). Conclusions: LVLD by CMR-FT was an independent risk factor for cardiovascular and arrhythmic events in ACM patients in advanced stage, which could provide prognostic value for this subtype.


Viscoelastic Separation and Concentration of Fungi from Blood for Highly Sensitive Molecular Diagnostics.
Isolation and concentration of fungi in the blood improves sensitivity of the polymerase chain reaction (PCR) method to detect fungi in blood. This study demonstrates a sheathless, continuous separation and concentration method of candida cells using a viscoelastic fluid that enables rapid detection of rare candida cells by PCR analysis. To validate device performance using a viscoelastic fluid, flow characteristics of 2 μm particles were estimated at different flow rates. Additionally, a mixture of 2 μm and 13 μm particles was successfully separated based on size difference at 100 μl/min. Candida cells were successfully separated from the white blood cells (WBCs) with a separation efficiency of 99.1% and concentrated approximately 9.9-fold at the center outlet compared to the initial concentration (~2.5 × 107 cells/ml). Sequential 1st and 2nd concentration processes were used to increase the final number of candida cells to ~2.3 × 109 cells/ml, which was concentrated ~92-fold. Finally, despite the undetectable initial concentration of 101 CFU/ml, removal of WBCs and the additional buffer solution enabled the quantitative reverse transcription (RT)-PCR detection of candida cells after the 1st concentration (Ct = 31.43) and the 2nd concentration process (Ct = 29.30).


The effect of some general anaesthetics on the surface potential of lipid monolayers.
1 This study sought to investigate the report by Ginsberg (1978) that 0.7 M ethanol brought about a + 100 mV change (DeltaDeltaV) in the surface potential of glyceryl monooleate (GMO) monolayers formed on KCl, although he predicted that a DeltaDeltaV of -10 mV should have been found.2 The effect of general anaesthetics such as n-alkyl alcohols and pentobarbitone on surface potential (DeltaV) and surface tension (gamma) of lipid monolayers formed on 145 mM KCl from either glyceryl monooleate (GMO) or phosphatidyl choline (PC) was examined with an Americium-241 air electrode assembly (DeltaV) and a platinized platinum dipping plate and force balance (gamma).3 It was found that, as predicted by Ginsberg (1978), addition of 0.7 M ethanol to the aqueous phase bathing either PC or GMO monolayers brings about a negative-going change in interfacial potential (DeltaDeltaV).4 The magnitude of DeltaDeltaV is dependent in a linear fashion on ethanol concentration.5 Longer chain length alcohols up to n-decanol also bring about a negative going change in DeltaDeltaV, and the dependence of DeltaDeltaV on anaesthetic activity, with respect to increasing chain length of anaesthetic, is consistent with Traube's law.6 Pentobarbitone added to the aqueous phase bathing the monolayer also elicits a negative DeltaDeltaV, a finding which rules out the possibility of adsorption of the volatile alcohols to the measuring electrode.7 The findings are discussed in terms of the proposition that increasing disorder in an array of fixed dipoles, such as might occur in a bilayer exposed to anaesthetic, would result in a lowering of the electrostatic barrier to the predominantly impermeable cation.


A consensus checklist to help clinicians interpret clinical trial results analysed by Bayesian methods.
In the context of an increasing number of publications of trial data analysed by Bayesian methods, clinicians need support to better understand Bayesian statistical methods. The existing checklists are intended for people who already know these methods. We aimed to establish and validate a checklist that contains a group of items considered crucial in interpreting the results of a phase III RCT analysed with Bayesian methods. A team of biostatisticians created a checklist of previously reported items and additional items identified from a literature review. Using three different articles in three rounds, the items were then validated by residents in anaesthesiology with no skills in statistics. Based on an initial item list, three rounds led to a consensus checklist. Eleven items were considered important information to be specified for understanding the validity of the results. Of these, three were considered essential: specification of the prior, source of the prior (when prior is informative), and the effect size point estimate with its credible interval. The checklist can help clinicians interpret the results of a phase III randomised clinical trial analysed by Bayesian methods, even clinicians with no particular knowledge of statistics, to ensure that the major elements of the statistical section are present and valid. Care should be taken in interpreting the results of a trial analysed by Bayesian methods that are not reported with these three essential items because the validity of the results cannot be established.


Enhanced communication skills for medical students through drawing.
A course in drawing was offered to medical students as part of a humanities "selective" program. The week-long, 22-hour course exposed students to various drawing techniques and audio-visual presentation techniques designed to heighten their awareness of the role of communications in the dissemination of medical knowledge.


High bilateral fenestration of the internal jugular vein.
Duplications and fenestrations of the internal jugular vein (IJV) are rare anatomic variations. There were previously found mostly unilateral fenestrated internal jugular veins, either empty, or traversed by the spinal accessory nerves. It was documented the computed tomography angiogram of a 65 year-old female patient and bilateral high fenestrations of the IJVs were found. On both sides, the superior ends of the fenestrations were in the jugular foramina. On the right side the fenestration had 3.8 cm length and was located in front of the transverse processes of the first two cervical vertebrae. On the opposite side the fenestration had 1.5 cm length and was antero-lateral to the transverse process of the atlas vertebra. On both sides the antero-medial arms of the fenestrations received the inferior petrosal sinuses and anterior condylar veins. Such highly placed fenestrations of the IJVs should be carefully documented either preoperatively, or prior to central venous access.


Induction of specific anti-actin antibodies and their measurement by ELISA technique.
Using the ELISA technique we have been able to quantify antibodies directed against actin and to follow the kinetics of antibody production. Specific anti-actin antisera have been raised in rabbits by immunization with chemically modified white muscle rabbit actin. Two or three dinitrophenyl groups linked per actin molecule were sufficient to break natural tolerance, while linkage of three phosphorylcholine groups to actin was not.


Isolation and characterization of the 5'-upstream and untranslated regions of the mouse type II iodothyronine deiodinase gene.
The type II iodothyronine deiodinase (D2) catalyzes the 5'-deiodination of thyroxine to yield the biologically active form, 3,3',5,-tri-iodothyronine, and is a member of the selenoproteins. We isolated a 17.5 kb mouse genomic clone containing the entire coding and 5'-untranslated regions of the D2 gene (mdio2). We also isolated the entire 5'-UTR of the mouse D2 cDNA, which was 753 bp in length and contained five ATG codons. An additional 258 bp ORF from the fourth ATG codon was found in the same reading frame as the coding region reported previously, and this additional ORF contained a TGA codon, which could encode selenocysteine. The proximal promoter of mdio2 contained a TATA box and several potential transcription factor-binding sequences, including CRE, C/EBP and GATA binding sites. The 1.3 kb 5'-upstream region exhibited a promoter activity by reporter assay using Mm5MT and JAR cells, which have a D2 transcript, but not HepG2 cells that have no detectable level of D2 transcript.


Vancomycin-resistant Enterococcus faecium at a university hospital in Taiwan, 2002-2015: Fluctuation of genetic populations and emergence of a new structure type of the Tn1546-like element.
Vancomycin resistance increased significantly to 31.3% among Enterococcus faecium in 2006 and remained high thereafter at a university hospital in Taiwan. A longitudinal study was retrospectively conducted to characterize these vancomycin-resistant E. faecium (VRE-fm). A total of 378 non-repetitive VRE-fm blood isolates collected during 2002-2015 were studied. Multilocus sequence typing, pulsed-field gel electrophoresis, analysis of van genes and the Tn1546 structure, and conjugation experiments were performed. The majority (78.0%) of the isolates were associated with hospital-acquired infections. Molecular typing revealed nine major pulsotypes and five predominant sequence types (STs): ST17 (33.9%), ST78 (18.3%), ST414 (14.6%), ST18 (10.6%), and ST203 (7.4%). Fluctuation of these prevailing STs among the study years in association with some major pulsotypes was noted. All isolates carried vanA genes, except that in four isolates vanB genes were found. Among the vanA-carrying Tn1546-like elements, one predominant structure type (Type I, 55.9%) was noted throughout the study years. Since 2009, another predominant structure type (Type II, 40.1%) has emerged firstly in ST414 and gradually spread to other 11 STs in subsequent years. Isolates carrying these Type II Tn1546-like elements have become the most predominant population since 2014, majorly found in ST78 and ST17. Preliminary experiments indicated that plasmids carrying the Type II Tn1546-like elements demonstrated ten-fold higher efficiency than those carrying the Type I Tn1546-like elements. Dissemination of some major STs and horizontal transfer of plasmids carrying two major structure types of Tn1546-like elements may have together contributed to the increase of VRE-fm infection.


Challenges of tracheostomy in COVID-19 patients in a tertiary centre in inner city London.
The rapid global spread of SARS-CoV-2, the causative agent of COVID-19, has dominated healthcare services, with exponential numbers requiring mechanical ventilation in the intensive care unit (ICU). Tracheostomy facilitates respiratory and sedative weaning but risks potential viral transmission. This study reviewed the tracheostomy provision, techniques, and outcomes for a single-centre prospective cohort during the resource-pressured COVID-19 period. Seventy-two of 176 patients underwent tracheostomy at a median 17 days: 44 surgical (open), 28 percutaneous. Their median age was 58 years, the male to female ratio was 2.4:1, 75.1% were of BAME backgrounds, 76% had a BMI≥25kg/m2, and 65% had ≥2 major co-morbidities. Seventy-nine percent of patients were weaned from sedation at a median 2 days, 61% were weaned from mechanical ventilation at a median 10 days, 39% were discharged from the ICU at a median 11.5 days, and 19.4% were discharged home at a median 24 days. All patients survived the procedure. The mortality rate was 9.7% at a median 12 days. No clinician reported COVID-19 symptoms within 14 days of the procedure. The role of tracheostomy in COVID-19 is currently unclear. Delivery of tracheostomy by maxillofacial surgeons relieved the workload pressure from ICU clinicians. The choice of technique was influenced by the patient and resource factors, resulting in a mixed cohort of open and percutaneous tracheostomy in COVID-19 patients. Preliminary data suggest that open tracheostomy is as favourable as percutaneous tracheostomy for COVID-19 patients, and is safe for clinicians.


The human egomotion network.
All volitional movement in a three-dimensional space requires multisensory integration, in particular of visual and vestibular signals. Where and how the human brain processes and integrates self-motion signals remains enigmatic. Here, we applied visual and vestibular self-motion stimulation using fast and precise whole-brain neuroimaging to delineate and characterize the entire cortical and subcortical egomotion network in a substantial cohort (n=131). Our results identify a core egomotion network consisting of areas in the cingulate sulcus (CSv, PcM/pCi), the cerebellum (uvula), and the temporo-parietal cortex including area VPS and an unnamed region in the supramarginal gyrus. Based on its cerebral connectivity pattern and anatomical localization, we propose that this region represents the human homologue of macaque area 7a. Whole-brain connectivity and gradient analyses imply an essential role of the connections between the cingulate sulcus and the cerebellar uvula in egomotion perception. This could be via feedback loops involved updating visuo-spatial and vestibular information. The unique functional connectivity patterns of PcM/pCi hint at central role in multisensory integration essential for the perception of self-referential spatial awareness. All cortical egomotion hubs showed modular functional connectivity with other visual, vestibular, somatosensory and higher order motor areas, underlining their mutual function in general sensorimotor integration.


PRP-1 protective effect against central and peripheral neurodegeneration following n. ischiadicus transection.
We investigated the action of the new hypothalamic proline-rich peptide (PRP-1), normally produced by neurosecretory cells of hypothalamic nuclei (NPV and NSO), 3 and 4 weeks following rat sciatic nerve transection. The impulse activity flow of interneurons (IN) and motoneurons (MN) on stimulation of mixed (n. ischiadicus), flexor (n. gastrocnemius--G) and extensor (n. peroneus communis--P) nerves of both injured and symmetric intact sides of spinal cord (SC) was recorded in rats with daily administration of PRP-1 (for a period of 3 weeks) and without it (control). On the injured side of SC in control, there were no responses of IN and MN on ipsilateral G and P stimulation, while responses were elicited on contralateral nerve stimulation. The neuron responses on the intact side of SC were revealed in a reverse ratio. Thus, there were no effects upon stimulation of the injured nerve distal stump in the control because of the absence of fusion between transected nerve stumps. This was also testified by the atrophy of the distal stump and the absence of motor activity of the affected limb. In PRP-1-treated animals, the responses of SC IN and MN in postaxotomy 3 weeks on the injured side of SC at ipsilateral nerve stimulation and on the intact side at contralateral nerve stimulation were recorded because of the obvious fusion of the severed nerve stumps. The histochemical data confirmed the electrophysiological findings. Complete coalescence of transected fibers together with restoration of the motor activity of the affected limb provided evidence for reinnervation on the injured side. Thus, it may be concluded that PRP-1 promotes nerve regeneration and may be used clinically to improve the outcome of peripheral nerve primary repair.


Decreased expression of H19/miR-675 ameliorates muscle atrophy by regulating the IGF1R/Akt/FoxO signaling pathway.
Long non-coding RNA (lncRNA) H19 is one of the most highly expressed and conserved transcripts in mammalian development, and its functions have been fully discussed in many contexts including tumorigenesis and skeletal muscle development. However, its exact role in muscle atrophy remains largely unknown. This study investigated the effect of lncRNA H19 on muscle atrophy and the potential underlying mechanism. Hindlimb suspension (HS) of C57BL/6 mice and starvation of C2C12 cells with PBS were conducted to induce atrophy. Real-time PCR and Western blotting were used to measure the expression of RNAs and proteins. LncRNA H19 and its encoded miR-675 were overexpressed or inhibited in different models of muscle atrophy. Immunofluorescence was carried out to examine the cross-sectional area (CSA) and minimal Feret's diameter (MFD) of myofibers and myotube diameter. The expression levels of lncRNA H19 and miR-675 were significantly reduced in both the soleus and gastrocnemius muscles in response to HS. Overexpression of lncRNA H19 led to an increase in Atrogin-1 mRNA expression, and this effect was reversed by inhibiting miR-675. The overexpression of miR-675 aggravated both HS- and starving-induced muscle atrophy by inhibiting the IGF1R/Akt signaling pathway and promoting FoxO/Atrogin-1 expression. Conversely, miR-675 inhibition had the opposite effects. The lncRNA H19/miR-675 axis can induce muscle atrophy, and its downregulation in mice with HS-induced muscle atrophy may act as a protective mechanism against this condition.


Choroidal thinning in pseudoexfoliation syndrome detected by enhanced depth imaging optical coherence tomography.
To measure choroidal thickness in patients with pseudoexfoliation (PEX) syndrome and to compare the values with control eyes using enhanced depth imaging optical coherence tomography (EDI-OCT). Thirty-four patients with PEX syndrome and 30 age- and sex-matched healthy subjects were included in this study. Only one eye of each of the patients was included. Choroidal thickness was measured manually from the outer border of the retinal pigment epithelium to the inner scleral border at the subfovea, 3 mm temporal to the fovea, and 3 mm nasal to the fovea using EDI-OCT. A total of 34 eyes from 34 consecutive patients with PEX syndrome (19 women and 15 men; mean age 75.3 ± 6.6 years) were included in the analysis. The mean subfoveal, temporal, and nasal choroidal thickness was significantly thinner in the PEX syndrome group compared with the control group (p<0.05, at all points). The mean choroidal thickness in the PEX syndrome group was as follows: 259 ± 33 µm, 211 ± 29 µm, and 106 ± 24 µm, subfoveal, temporal, and nasal to the fovea, respectively. In comparison, the mean choroidal thickness in the control group was 274 ± 23 µm, 225 ± 17 µm, and 117 ± 17 µm, at the subfovea, 3 mm temporal to the fovea, and nasal to the fovea, respectively. In PEX syndrome, there is choroidal thinning subfoveal, temporal, and nasal to the fovea on EDI-OCT. Decreased choroidal thickness, probably due to increased vascular resistance, and reduced blood flow, is seen in PEX syndrome.


Juxtacentromeric region of human chromosome 21: a boundary between centromeric heterochromatin and euchromatic chromosome arms.
We have analysed the genomic structure and transcriptional activity of a 2.3-Mb genomic sequence in the juxtacentromeric region of human chromosome 21. Our work shows that this region comprises two different chromosome domains. The 1.5-Mb proximal domain: (i) is a patchwork of chromosome duplications; (ii) shares sequence similarity with several chromosomes; (iii) contains several gene fragments (truncated genes having an intron/exon structure) intermingled with retrotransposed pseudogenes; and (iv) harbours two genes (TPTE and BAGE2) that belong to gene families and have a cancer and/or testis expression profile. The TPTE gene family was generated before the branching of Old World monkeys from the great ape lineage, by intra- and interchromosome duplications of the ancestral TPTE gene mapping to phylogenetic chromosome XIII. By contrast, the 0.8-Mb distal domain: (i) is devoid of chromosome duplications; (ii) has a chromosome 21-specific sequence; (iii) contains no gene fragments and only one retrotransposed pseudogene; and (iv) harbours six genes including housekeeping genes. G-rich sequences commonly associated with duplication termini cluster at the boundary between the two chromosome domains. These structural and transcriptional features lead us to suggest that the proximal domain has heterochromatic properties, whereas the distal domain has euchromatic properties.


Severe glomerulonephritis complicated by coagulopathy: treatment with anticoaguland and immunosuppresive drugs.
Serial determinations, using plasma fibrinogen gel chromatography as well as standard methodology, demonstrated that six children with severe glomerulonephritis, characterized on renal biopsy by glomerular necrosis and crescent formation, had persistent evidence of intravascular coagulation. Based on these observations, therapy with anticoagulants and azathicoagulants and azathioprine was instituted for one year; treatment with anticoagulants was continued for a second year. Anticoagulant therapy was initiated with heparin, followed by oral anticoagulation with phenindione and dipyridamole. In contrast to our earlier experience with similar patients, each of the present patients improved. Urinalyses returned to normal and glomerular filtration rates to near normal values in all patients at the end of the treatment period and have remained so for up to 3.9 years since treatment has been completed. Post-treatment biopsies showed remarkable improvement, with virtually no glomerulosclerosis even in patients who had had a high incidence of glomerular crescents before treatment. It is suggested that the therapeutic regimen favorably influenced the natural history of disease and that plasma fibrinogen chromatographic findings may be helpful in selecting patients likely to benefit from the use of anticoagulant therapy.


'Not acceptable': NMC fails to answer 13% of phone calls.
The Nursing and Midwifery Council has been criticised for allowing more than 60,000 telephone calls to go unanswered last year.


Preoperative atrial histological changes are not associated with postoperative atrial fibrillation.
Atrial fibrillation (AF) remains the most common complication of cardiac surgery. Prophylactic therapies have been studied, but their utility has been limited by the inability to accurately identify patients who will develop this complication. Recent studies have suggested that atrial myolysis and lipofuscin pigmentation are associated with post-coronary artery bypass grafting (CABG) AF. We sought to determine whether there is an association between preoperative atrial histology and subsequent post-CABG AF. Samples of right atrial appendage were obtained from 94 patients undergoing CABG. Tissue was formalin fixed and paraffin embedded. Sections 4 mum thick were cut, stained with hematoxylin and eosin, and examined for the following parameters: fibrosis, myolysis, inflammation, nuclear size, pericardial exudates, lipofuscin pigment, arteriolar hypertrophy, contraction banding, mesothelial hyperplasia, and atrial diverticula. Results were graded as absent, mild, moderate, or severe by two independent observers who were blinded to the clinical outcomes. Univariate and multivariate analyses were carried out. Thirty-six (38%) patients developed AF. No correlation was found between the 10 features assessed, including myolysis and lipofuscin pigmentation, and the development of AF. Simple morphology of right atrial appendages does not predict the development of postoperative AF.


Open endotracheal tubes may be safely left on an ED airway cart for 48 hours.
To determine if endotracheal tubes (ETTs) that are opened, prepared, and stored in an ED airway cart are prone to bacterial contamination. A prospective study conducted in the ED of a level 1 trauma center. A study group of 50 endotracheal tubes were opened, preloaded with a stylet, the cuff checked for integrity by air inflation, and then stored in an ED airway cart. The study group was subdivided into 5 groups of 10 ETTs each, cultured at different time intervals. The ETTs were cultured at 6, 12, 24, 36, and 48 hours for the presence of bacterial contamination. The control group consisted of 10 ETTs that were left in their sterile packing in the ED airway cart and then removed at 48 hours and cultured. In the study group, 7 (14%) ETTs resulted in a positive culture; 43 ETTs cultured negative for bacteria. In the control group, 2 (20%) ETTs cultured positive, the remainder was all negative. There was no statistically significant difference between the 2 groups (P = .63). If only clinically significant bacteria are considered, defined as a culture with 5 or more colony-forming units, 3 ETTs in the study group cultured positive; there were no clinically significant bacteria cultured in the control group. Once again, there was no statistically significant difference between the 2 groups, with a P value of .57. It appears that opening, preparing, and storing ETTs in an ED airway cart for up to 48 hours does not increase the risk of bacterial contamination of the ETTs.


Who takes the lead in the development of ulcerative colitis-associated colorectal cancers: mutator, suppressor, or methylator pathway?
Although several genetic alterations have been identified in patients with ulcerative colitis (UC), it remains unclear whether these changes indicate an increased risk for malignancy. This paper analyzes the involvement of suppressor, mutator, and methylator pathways in malignant transformation associated with UC. A total of 60 colonic samples (47 affected non-neoplastic mucosa, 7 dysplasia, and 6 carcinoma) from 51 UC patients were analyzed for 22 microsatellite markers. p53 gene exons 5-8 were analyzed by single-strand conformational polymorphism, and APC gene by denaturing gradient gel electrophoresis (exons 1-14) and protein truncation test (exon 15). Methylation studies for MLH1 and CSPG2 genes were also performed. Microsatellite instability was absent in all samples whereas allelic imbalance (AI) and loss of heterozygosity (LOH) were detected mainly in samples with neoplastic transformation (P<0.0001). AI and/or LOH at loci located on chromosomes 5, 9, and 18 were significantly more frequent in neoplastic samples (P<0.01), as were TP53 gene mutations (P<0.007). A single mutation was detected for APC gene in a cancer sample. MLH1 gene methylation was absent in all analyzed samples, whereas CSPG2 gene methylation was detected in a single non-neoplastic sample. Our results suggest that the suppressor pathway plays the main role in UC associated tumorigenic progression. LOH at specific loci located on chromosomes 5, 9, and 18 appears to be specifically associated with malignancy risk.


Takotsubo cardiomyopathy in amyotrophic lateral sclerosis.
To investigate the frequency, features, and prognosis of takotsubo cardiomyopathy (TTC) in patients with amyotrophic lateral sclerosis (ALS). We reviewed detailed clinical, laboratory, and cardiovascular data from 64 ALS patients (38 men and 26 women) who underwent echocardiographic evaluation for various reasons at a single referral center between January 2011 and December 2015. TTC was diagnosed in 9 ALS patients (4 men and 5 women). Mean age was 61.3years (range 55-71years), and median disease duration was 51.5months (range 18-134months). All patients were bulbar or cervical onset, and were at advanced stages of ALS when TTC was diagnosed. Acute exacerbation of dyspnea was an invariable presentation, and chest discomfort mimicking acute coronary syndrome was present in 2 patients. Six patients had significant hypotension requiring intravenous fluid challenge and inotropic support. Three patients showed altered mentality, and 2 of them suffered cardiopulmonary arrest. TTC should be suspected in ALS patients presenting with acute exacerbation of dyspnea and chest discomfort, particularly at advanced stages of the disease. This study highlights the need for proper evaluation and management of cardiac dysfunction in ALS.


Polyethylene microplastics impede the innate immune response by disrupting the extracellular matrix and signaling transduction.
Microplastics (MPs) can accumulate in animal organs. Numerous studies have linked MPs with immune system. However, the impact of MPs on immune response remains unclear. This study examined the innate immune response of mice exposed to 5 μm MPs. In the lipopolysaccharide challenge, mice treated with MPs exhibited lower levels of serum immune factors and activated immune cells. MPs disrupted immune-related receptors and cause dysfunction in cell signal transduction within the liver and spleen. Proteomic analysis revealed that MPs impede the activation of serum immune-related signals. In addition, the tissue section imaging exhibited a significant enrichment of MPs in the extracellular matrix (ECM), consistent with the ECM dysfunction and immune receptor suppression. Therefore, our data suggest excessive MPs accumulation in ECM inhibits cell signaling pathways, thereby suppressing the activation of immune responses. We propose the biotoxicity of MPs is partly through the MP disruption of ECM (MPDEM).


Suboptimal medication adherence in Parkinson's disease.
Patients take less medication than prescribed in many disease areas but evidence for suboptimal therapy adherence in Parkinson's disease (PD) is limited. A single-center observational study of antiparkinsonian medication was undertaken using electronic monitoring (MEMS; Aardex, Zug, Switzerland) over 3 months. Of 68 patients approached, 6 declined and 8 dropped out, leaving 54 patients (taking 117 preparations) with available data. Poorer compliance was associated significantly with younger age, with taking more antiparkinsonian tablets per day, with higher depression scores, and with poorer quality of life. Of the 54 evaluable patients, 11 (20%) had average total compliance of under 80% (underusers) and 43 (80%) had average total compliance of over 80% (satisfactory adherence). Underusers had median total compliance of 65% (interquartile range, 37-74) versus 98% (interquartile range, 93-102) in the satisfactory adherence group. Timing compliance (number of doses taken in the correct time interval) was poor in both underusers (median, 11%; interquartile range, 2-20) and those with satisfactory adherence (median, 25%; interquartile range, 11-73). In conclusion, poorer compliance is associated with younger age, depression, and more tablets per day, and one-fifth of PD patients underuse medication. Consideration of drug therapy adherence has implications in the management of PD.


Necrotizing fasciitis following endoscopic harvesting of the greater saphenous vein for coronary artery bypass graft.
The greater saphenous vein (GSV) remains the most commonly harvested conduit for revascularization in coronary artery bypass grafting (CABG). Published literature shows that minimally invasive vein harvesting techniques have a significantly lower incidence of wound infection rates than conventional open vein harvesting techniques have. We report a case of necrotizing fasciitis, an infection with a mortality rate of 30% to 50%, after endoscopic harvesting of the greater saphenous vein to be used as a conduit in a CABG procedure. Though minimally invasive vein harvesting techniques have advantages of smaller incisions and a decreased overall rate of wound infection, clinicians should be aware of this potentially lethal infection that may occur.


BRAFV600 variant allele frequency predicts outcome in metastatic melanoma patients treated with BRAF and MEK inhibitors.
The prognostic impact of variant allele frequency (VAF) on clinical outcome in BRAFV600 mutated metastatic melanoma patients (MMPs) receiving BRAF (BRAFi) and MEK inhibitors (MEKi) is unclear. A cohort of MMPs receiving first line BRAFi and MEKi was identified by inspecting dedicated databases of three Italian Melanoma Intergroup centres. VAF was determined by next generation sequencing in pre-treatment baseline tissue samples. Correlation between VAF and BRAF copy number variation was analysed in an ancillary study by using a training and a validation cohort of melanoma tissue samples and cell lines. Overall, 107 MMPs were included in the study. The VAF cut-off determined by ROC curve was 41.3%. At multivariate analysis, progression-free survival (PFS) was significantly shorter in patients with M1c/M1d [HR 2.25 (95% CI 1.41-3.6, p < 0.01)], in those with VAF >41.3% [HR 1.62 (95% CI 1.04-2.54, p < 0.05)] and in those with ECOG PS ≥1 [HR 1.82 (95% CI 1.15-2.88, p < 0.05)]. Overall survival (OS) was significantly shorter in patients with M1c/M1d [HR 2.01 (95% CI 1.25-3.25, p < 0.01)]. Furthermore, OS was shorter in patients with VAF >41.3% [HR 1.46 (95% CI 0.93-2.29, p = 0.06)] and in patients with ECOG PS ≥1 [HR 1.52 (95% CI 0.94-2.87, p = 0.14)]. BRAF gene amplification was found in 11% and 7% of samples in the training and validation cohort, respectively. High VAF is an independent poor prognostic factor in MMP receiving BRAFi and MEKi. High VAF and BRAF amplification coexist in 7%-11% of patients.


Food selection by the silver leaf monkey,Trachypithecus auratus sondaicus, in relation to plant chemistry.
Samples of leaves and fruits exploited as food items byTrachypithecus auratus sondaicus were analysed for nitrogen content, acid detergent fibre (ADF), pepsin cellulase digestibility (CDIG), condensed tannins (CT), total phenolics (TP) and protein precipitation capacity (PP) and compared with fruits and leaves not eaten. Differences in chemical measures for items eaten and not eaten were not statistically significant but trends indicate that leaves may have been selected for their lower fibre content and greater digestibility. Fruits eaten also had a higher mean level of CDIG and lower mean level of ADF than fruits not eaten but these measures are not considered to be of major importance in fruit selection as CDIG was lower and ADF higher in fruits eaten than in leaves eaten. Levels of CT, TP and PP capacity were higher in fruits eaten than in fruits not eaten but lower in leaves eaten than in leaves not eaten. The role of tannins and phenolics in food selection is discussed. Leaves (and fruits) were not strongly selected on the basis of protein content. Approximately half the dietary intake ofT. auratus sondaicus was leaves, a protein-rich food source. Possibly, protein levels in foliage at Pangandaran were sufficient that selection for this nutrient was not required. A nutrient other than protein (for example, soluble carbohydrates) may have been maximised through food selection. The protein/ADF ratio may provide an indicator of the acceptability of foliage in a habitat as potential food for a colobine. However, this ratio did not govern food selection byT. auratus sondaicus at Pangandaran.


Association of novel biomarkers with future cardiovascular events is influenced by ethnicity: results from a multi-ethnic cohort.
We sought to define the influence of ethnicity on associations between novel biomarkers and cardiovascular disease (CVD) events among Multi-Ethnic Study of Atherosclerosis (MESA) study participants, a community based population of asymptomatic US adults. Baseline (log transformed) levels of biomarkers namely C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), D-dimer, plasmin-antiplasmin complex (PAP) and factor VIII were used to predict the cumulative incidence of all CVD events in an ethnicity stratified study cohort from Cox-proportional hazard analysis where models were adjusted for relevant confounders. Ethnic cohorts included 2362 Caucasians, 1601 African Americans, 1353 Hispanics, and 751 Chinese. At mean 4.6 years of follow-up, 286 CVD events were identified with cumulative incidence of 11.3% in Caucasians, 9.8% in African Americans, 11.3% in Hispanics and 6.9% in Chinese. Biomarker risk association with CVD events incidence was significantly influenced by ethnicity with positive association (HR, 95% CI, p value) being shown for: CRP among Caucasians only (1.23, 1.04-1.47, <0.01) IL-6 among African Americans only (1.69, 1.15-2.48, <0.01) and fibrinogen among Caucasians (3.05, 1.21-7.69, 0.02), African Americans (3.51, 1.09-11.2, 0.03) and Hispanics (4.16, 1.23-14.1, 0.02) only. None of the biomarkers were able to predict CVD in Chinese. Association between above biomarkers and CVD was bi-directional: cases with CVD events had higher mean levels of biomarkers; cases in higher quartiles of biomarkers had increased cumulative incidence of CVD events. Study results from a vast, ethnically diverse, asymptomatic US adult population suggest that biomarker association with incident CVD events is significantly influenced by ethnicity.


Morphological and electrophysiological properties of trigeminal neurones projecting to the accessory abducens nucleus of the cat.
Horseradish peroxidase was injected into the somata or axons of neurones located in the nucleus oralis of the spinal trigeminal complex and projecting to the accessory abducens nucleus. A group of 43 axons with electrophysiologically identified responses to the stimulation of three different areas of the face were studied. The latencies of their orthodromic responses following trigeminal stimulation and their pattern of discharges were compared to those of secondary trigeminal neurones and retractor bulbi motoneurones. Labelled trigeminal axons were found to generate collaterals for the accessory abducens nucleus. Terminal ramifications are present in the rostro-caudal part of the motor nucleus where the dendritic arborization of the motoneurones has been described. Connections to facial and trigeminal motor nuclei were also present, suggesting that secondary trigeminal axons distributed the information to the three motor targets at the brain stem level. It is suggested that the trigemino-retractor bulbi reflex is part of facial reflexes involved in orienting reactions, and protective responses resulting in coordinated movements of the facial musculature.


Prophylactic subconjunctival cefuroxime during cataract surgery in patients with a penicillin allergy.
The incidence of cross-reaction after subconjunctival cefuroxime following cataract surgery in penicillin allergy patients is not common and therefore cefuroxime with its better spectrum of action and lower toxicity is probably a better choice than gentamycin.


Correction for intravascular activity in the oxygen-15 steady-state technique is independent of the regional hematocrit.
The oxygen-15 steady-state technique to measure the regional cerebral metabolic rate for oxygen requires a correction for the nonextracted intravascular molecular oxygen-15. To perform this correction, an additional procedure is carried out using RBCs labeled with 11CO or C15O. The previously reported correction method, however, required knowledge of the regional cerebral to large vessel hematocrit ratio. A closer examination of the underlying model eliminated this ratio. Both molecular oxygen and carbon monoxide are carried by RBCs and are therefore similarly affected by a change in hematocrit.


Mitral valve replacement in the young patient with rheumatic heart disease. Early and late results in 118 subjects.
During a 14 year period, 118 young patients between 9 and 20 years of age underwent mitral valve replacement. In view of the acknowledged advantage of durability and minimal thrombogenicity, we chose the Starr-Edwards valve prosthesis in the large majority of our subjects. Other prostheses have also been used. Hospital mortality has been only 3% in the past 5 years. Frail, severely incapacitated children and adolescents have had an impressive spurt in growth and weight and have returned to normal activities. Nine of the patients have had a normal pregnancy and have borne children. The remarkable clinical improvement has been corroborated by hemodynamic benefit. Follow-up over a period 1 to 15 years (mean 5.09 +/- 3.3) showed a very low incidence of embolic phenomena. In Third World countries, rheumatic heart disease continues to be a daunting challenge with pronounced disability resulting in death. Mitral valve replacement in the young subject with significant rheumatic valve disease should not be delayed until severe pulmonary vascular changes and myocardial damage pose a major deterrent.


Super-Anticorrosive Materials Based on Bifunctionalized Reduced Graphene Oxide.
The design of new materials with two or more functional groups must be strongly considered to achieve multifunctional coatings with outstanding properties such as active-passive protection against corrosion, low-friction, antifouling, and sensing, among others. In this sense, nanocomposites based on solvent-free epoxy resin/bifunctionalized reduced graphene oxide layers with NH2 and NH3+ groups (ER/BFRGO) with super-anticorrosive properties are for the first time reported here. The amine groups (-NH2) act as cross-linker agents, which react with epoxy terminal groups from resin, thus closing the gap between the BFRGO layers and the polymeric matrix. Meanwhile, the ammonium ions (-NH3+) are effective trapping agents of negatively charged atoms or molecules (e.g., Cl-). This novel combination enables us to obtain nanocomposite coatings with passive-active protection against corrosion. ER/BFRGO deposited onto A36 mild steel exhibited a remarkably enhanced barrier against corrosion into a saline medium (1 M NaCl; 58.4 g/L), wherein the corrosion current density (icorr) was diminished 6 orders of magnitude (icorr = 5.12 × 10-12 A/cm2), with respect to A36 mild steel coated only with ER (icorr = 2.34 × 10-6 A/cm2). Also, the highest polarization resistance Rp = 6.04 × 107 Ω/cm2 was obtained, which represents the lowest corrosion rate and corresponds to 3 orders of magnitude higher than A36 mild steel coated with ER (Rp = 1.43 × 104 Ω/cm2). The strategy of bifunctionalization proposed herein to obtain bifunctionalized reduced GO with NH2 and NH3+ groups has not been disclosed in the literature before; in consequence, this work opens a new pathway toward the design of smart materials based on multifunctional nanomaterials.


Interaction of neurotensin with the substance P receptor mediating histamine release from rat mast cells and the flare in human skin.
1 Substance P induced histamine release from rat peritoneal mast cells in a dose-dependent manner over the concentration range 1 to 10 microM. 2 At concentrations in the range 2.5 to 1 0 microM, neurotensin produced only about 5% release of histamine, which was substantially less than the maximum effect obtained with substance P. 3 Neurotensin, 2.5 to 10 microM produced graded inhibition of histamine release induced by substance P. The inhibitory effect of neurotensin was not seen when histamine release was induced by an antigen-antibody effect of neurotensin was not seen when histamine release was induced by an antigen-antibody reaction or by the ionophore, A 23187. Some evidence was obtained to suggest that compound 48/80 may interact with the same receptor as substance P and neurotensin. 4 [D-Arg8]neurotensin, [D-Arg9]neurotensin, xenopsin and the C-terminal octapeptide of substance P (SP4-11) all inhibited histamine release by substance P, but physalaemin did not. 5 Neurotensin inhibited the wheal and flare reactions induced by substance P in human skin. 6 [D-Trp7,9]substance P released histamine from rat mast cells and was about 12 times more potent than substance P itself. [D-Trp7,9]SP1-11 also produced wheal and flare responses in human skin, being 1.8 times more potent than substance P in the production of flare.


Pediatric Infraorbital Nerve schwannoma-A Rare Case Report.
Infraorbital nerve schwannoma is an infrequent entity that is rarely reported in the paediatric population. This case report is a summed-up report of this infrequent diagnosis, its presentation, and management from an otorhinolaryngologist's perspective. It is reported here for its rarity, inherent surgical challenge, and academic interest. We report a case of a 13-year-old boy with infraorbital nerve schwannoma arising from its two terminal branches. We performed its surgical excision without any disabling deformity. The peculiarity of this case gives insight into the varied presentation of schwannoma. It is important to identify such cases with a high degree of suspicion and treat them accordingly.


Epidemiological aspects and molecular characterization of the hepatitis B virus among blood donors in Lubumbashi, Democratic Republic of Congo.
The strains of HBV circulating among blood donors in Lubumbashi, Democratic Republic of Congo (DRC), are not yet characterized. The purpose of this study was to determine seroprevalence, changes in biochemical parameters during HBV infection and molecular characterization of HBV in blood donors in Lubumbashi. The detection of HBsAg was carried out by rapid diagnostic test then confirmed by the Liaison XL® Quant HBsAg technique. PCR targeting the P gene was carried out on LightCycler® 96 and genotyping by the sequencing technique on ABI 3500. The seroprevalence was 7.9%. The genotypes E (53.1%), A (41.8%), A3/E (3.8%), A1/E (1.3%) and some drug resistance mutations were identified. Disturbances of HDL-cholesterol, direct bilirubin, transaminases (ASAT and ALAT), PAL, GGT and albumin have been observed in HBsAg positive blood donors. The results of our study indicated that Lubumbashi is in a region with high endemicity for HBV and report for the first time HBV of genotypes A, E, A1/E and A3/E. They highlight the need to implement strategies to improve transfusion safety in blood transfusion centers and hospital blood banks in Lubumbashi in order to reduce HBV infection in recipients. They could also contribute to the implementation of treatment strategies and the development of mapping of circulating HBV genotypes in the DRC.


Hemostasis in Endoscopic Sinus Surgery.
Intraoperative bleeding during endoscopic sinus surgery poses an additional dimension to an already technically challenging surgical approach because of the narrow sinonasal surgical field, single working hand, and the use of endoscopic instruments. Poor visualization is one of the most important factors that increase the risk of intraoperative complications such as inadvertent injury to major vessels and nerves, and incomplete surgery. This article provide a logical approach to improving the surgical field, minimizing risk of inadvertent vascular injury, and managing intraoperative bleeding.


Can prehospital Modified Early Warning Score identify non-trauma patients requiring life-saving intervention in the emergency department?
We aim to investigate whether prehospital Modified Early Warning Score (MEWS) can identify non-trauma patients requiring life-saving intervention (LSI) within 4 h of presentation to the ED. It was a prospective study of non-trauma ED patients by ambulance who were 16 years or older from 1 to 27 November 2013. Prehospital MEWS was calculated according to vital signs measured by the ambulance crew. Data on patients' demographics, triage category, LSI within 4 h of ED presentation and 24 h mortality were retrieved. LSI was defined as emergency interventions to airway, breathing and circulation, emergency procedures and medications administered. The performance of prehospital MEWS was analysed with sensitivity, specificity, predictive values (PV), likelihood ratios (LR) and the receiver operating characteristic curve. Recruited during the study period were 1493 patients. The median age was 78 years. Of the patients, 49.9% belonged to critical, emergent or urgent triage categories. LSI was required in 321 patients (21.5%). Thirteen died within 24 h of ED presentation. The area under the receiver operating characteristic curve of prehospital MEWS relating to LSI was 0.72 (95% confidence interval 0.69 to 0.75). The sensitivity, specificity, positive PV, negative PV, positive LR and negative LR were 0.57, 0.76, 0.40, 0.87, 2.43 and 0.56, respectively, when prehospital MEWS ≥3 was chosen as the cut-off value. Prehospital MEWS is useful in identifying non-trauma patients requiring LSI within 4 h of ED presentation. This may in turn enhance the triage accuracy in the ED in addition to clinical assessment.


Analysis of IL-12 p40 subunit gene and IFN-gamma G5644A polymorphisms in Idiopathic Pulmonary Fibrosis.
Genes encoding cytokine mediators are prime candidates for genetic analysis in conditions with T-helper (Th) cell disease driven imbalance. Idiopathic Pulmonary Fibrosis (IPF) is a predominantly Th2 mediated disease associated with a paucity of interferon-gamma (IFN-gamma). The paucity of IFN-gamma may favor the development of progressive fibrosis in IPF. Interleukin-12 (IL-12) plays a key role in inducing IFN-gamma production. The aim of the current study was to assess whether the 1188 (A/C) 3'UTR single nucleotide polymorphism (SNP) in the IL-12 p40 subunit gene which was recently found to be functional and the 5644 (G/A) 3' UTR SNP of the IFN-gamma gene were associated with susceptibility to IPF. We investigated the allelic distribution in these loci in UK white Caucasoid subjects comprising 73 patients with IPF and 157 healthy controls. The SNPs were determined using the polymerase chain reaction in association with sequence-specific primers incorporating mismatches at the 3'-end. Our results showed that these polymorphisms were distributed similarly in the IPF and control groups We conclude that these two potentially important candidate gene single nucleotide polymorphisms are not associated with susceptibility to IPF.


Amino acids and glucose in human cerebrospinal fluid after acute ischaemic brain damage.
In the search for potential biochemical markers of value for prognosis after acute hypoxic brain damage, amino acids and glucose were assessed in the cerebrospinal fluid (CSF) and glucose in blood. Samples were taken by lumbar puncture 4, 28, 76 and 172 h after resuscitation from 20 patients and once from 10 control patients. Eight of the resuscitated patients recovered neurologically but 12 remained comatose. The concentrations of alanine (P less than 0.001) and phenylalanine (P less than 0.035) differed most in 4-h samples between the groups. The concentration of alanine was higher in all patient groups with hypoxic brain damage as compared to the controls, the concentrations in patients dying within 76 h (disabled-s group) being higher than in the recovered patients. Phenylalanine in the disabled-s group was significantly higher than the control value. Furthermore, there were significant differences between various patient groups in the concentrations of glutamine, isoleucine, leucine, lysine, serine, tyrosine and valine. When taking into account the permeability of the BBB to these amino acids, alanine, valine and isoleucine most clearly represent brain amino acid metabolism. CSF glucose in the control group and in the recovered patients was lower than in patients dying within 76 h.


Discharge of pursuit-related neurons in the caudal part of the frontal eye fields in juvenile monkeys with up-down pursuit asymmetry.
The smooth-pursuit system uses retinal image-slip-velocity information of target motion to match eye velocity to actual target velocity. The caudal part of the frontal eye fields (FEF) contains neurons whose activity is related to direction and velocity of smooth-pursuit eye movements (pursuit neurons), and these neurons are thought to issue a pursuit command. During normal pursuit in well-trained adult monkeys, a pursuit command is usually not differentiable from the actual eye velocity. We examined whether FEF pursuit neurons signaled the actual eye velocity during pursuit in juvenile monkeys that exhibited intrinsic differences between upward and downward pursuit capabilities. Two, head-stabilized Japanese monkeys of 4 years of age were tested for sinusoidal vertical pursuit of target motion at 0.2-1.2 Hz (+/-10 degrees, peak target velocity 12.5-75.0 degrees/s). Gains of downward pursuit were 0.8-0.9 at 0.2-1.0 Hz, and peak downward eye velocity increased up to approximately 60 degrees/s linearly with target velocity, whereas peak upward eye velocity saturated at 15-20 degrees/s. The majority of downward FEF pursuit neurons increased the amplitude of their discharge modulation almost linearly up to 1.2 Hz. The majority of upward FEF pursuit neurons also increased amplitude of modulation nearly linearly as target frequency increased, and the regression slope was similar to that of downward pursuit neurons despite the fact that upward peak eye velocity saturated at approximately 0.5 Hz. These results indicate that the responses of the majority of upward FEF pursuit neurons did not signal the actual eye velocity during pursuit. We suggest that their activity reflected primarily the required eye velocity.


SHEPHARD: a modular and extensible software architecture for analyzing and annotating large protein datasets.
The emergence of high-throughput experiments and high-resolution computational predictions has led to an explosion in the quality and volume of protein sequence annotations at proteomic scales. Unfortunately, sanity checking, integrating, and analyzing complex sequence annotations remains logistically challenging and introduces a major barrier to entry for even superficial integrative bioinformatics. To address this technical burden, we have developed SHEPHARD, a Python framework that trivializes large-scale integrative protein bioinformatics. SHEPHARD combines an object-oriented hierarchical data structure with database-like features, enabling programmatic annotation, integration, and analysis of complex datatypes. Importantly SHEPHARD is easy to use and enables a Pythonic interrogation of largescale protein datasets with millions of unique annotations. We use SHEPHARD to examine three orthogonal proteome-wide questions relating protein sequence to molecular function, illustrating its ability to uncover novel biology. We provided SHEPHARD as both a stand-alone software package (https://github.com/holehouse-lab/shephard), and as a Google Colab notebook with a collection of precomputed proteome-wide annotations (https://github.com/holehouse-lab/shephard-colab).


Detection and analysis of (O-linked beta-N-acetylglucosamine)-modified proteins.
Glycosylation is one of the most common and complex forms of posttranslational modifications of proteins in eukaryotes. Seven different protein-carbohydrate linkages have been characterized on nuclear and cytoplasmic glycoproteins, the most widespread of which is the modification of Ser/Thr residues with monosaccharides of O-linked beta-N-acetylglucosamine (O-GlcNAc). O-GlcNAc modification is concentrated in nuclear proteins. O-GlcNAc is thought to regulate protein function in a manner analogous to phosphorylation; and is implicated in the regulation of transcription, the proteasome, insulin and MAP kinase signaling, the cell cycle, and the cellular stress response. In this chapter we focus on methods for the detection of O-GlcNAc-modified proteins and discuss general techniques for the detection and subsequent analysis of other protein-carbohydrate conjugates.