Meta‐analysis of oral antibiotics, in combination with preoperative intravenous antibiotics and mechanical bowel preparation the day before surgery, compared with intravenous antibiotics and mechanical bowel preparation alone to reduce surgical‐site infections in elective colorectal surgery

Background: Surgical‐site infection (SSI) is a potentially serious complication following colorectal surgery. The present systematic review and meta‐analysis aimed to investigate the effect of preoperative oral antibiotics and mechanical bowel preparation (MBP) on SSI rates. Methods: A systematic review of PubMed, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials was performed using appropriate keywords. Included were RCTs and observational studies reporting rates of SSI following elective colorectal surgery, in patients given preoperative oral antibiotic prophylaxis, in combination with intravenous (i.v.) antibiotic prophylaxis and MBP, compared with patients given only i.v. antibiotic prophylaxis with MBP. A meta‐analysis was undertaken. Results: Twenty‐two studies (57 207 patients) were included, of which 14 were RCTs and eight observational studies. Preoperative oral antibiotics, in combination with i.v. antibiotics and MBP, were associated with significantly lower rates of SSI than combined i.v. antibiotics and MBP in RCTs (odds ratio (OR) 0·45, 95 per cent c.i. 0·34 to 0·59; P < 0·001) and cohort studies (OR 0·47, 0·44 to 0·50; P < 0·001). There was a similarly significant effect on SSI with use of a combination of preoperative oral aminoglycoside and erythromycin (OR 0·40, 0·25 to 0·64; P < 0·001), or preoperative oral aminoglycoside and metronidazole (OR 0·51, 0·39 to 0·68; P < 0·001). Preoperative oral antibiotics were significantly associated with reduced postoperative rates of anastomotic leak, ileus, reoperation, readmission and mortality in the cohort studies. Conclusion: Oral antibiotic prophylaxis, in combination with MBP and i.v. antibiotics, is superior to MBP and i.v. antibiotic prophylaxis alone in reducing SSI in elective colorectal surgery

First Principles Study of Metal Contacts to Monolayer Black Phosphorous

Atomically thin layered black phosphorous (BP) has recently appeared as an alternative to the transitional metal di chalcogenides for future channel material in a MOS transistor due to its lower carrier effective mass. Investigation of the electronic property of source/drain contact involving metal and two-dimensional material is essential as it impacts the transistor performance. In this paper we perform a systematic and rigorous study to evaluate the Ohmic nature of the side-contact formed by the monolayer BP (mBP) and metals (gold, titanium and palladium), which are commonly used in experiments. Employing the Density Functional Theory (DFT), we analyse the potential barrier, charge transfer and atomic orbital overlap at the metal-mBP interface in an optimized structure to understand how efficiently carriers could be injected from metal contact to the mBP channel. Our analysis shows that gold forms a Schottky contact with a higher tunnel barrier at the interface in comparison to the titanium and palladium. mBP contact with palladium is found to be purely Ohmic, where as titanium contact demonstrates an intermediate behaviour.Comment: 10 Pages 13 Figures Accepted in Journal Of Applied Physic

Maltose-binding protein is a potential carrier for oral immunizations

In humans and most animal species such as pigs, vaccination via the oral route is a prerequisite for induction of a protective immunity against enteropathogens. Hereto, live attenuated microorganisms can be used. However, these microorganisms often are either too attenuated to induce sufficient intestinal immunity or are still too virulent resulting in clinical signs. We previously demonstrated that it is possible to induce immunity against enteropathogens by targeting antigen towards enterocytes. Maltose-binding protein (MBP) is part of the maltose/maltodextrin system of Escherichia coli. MBP is a relatively small protein (42.5 kDa) approximately 3 × 4 × 6.5 nm in size with surface residues capable of both hydrogen bonding interactions and hydrophobic interactions. Recombinant proteins are often fused to MPB to improve their yield and to increase their solubility. In mice, these fusion proteins showed an enhanced immunogenicity following systemic immunization. More recently, this has been attributed to interaction of MBP with TLR4 on dendritic cells (DCs). TLR4 is also expressed in the enterocytes of the gut. Therefore, we examined if oral administration of MPB-FedF to 4-week-old pigs could be used to induce an immune response against F18+ verotoxigenic E. coli in pigs. Also we examined if the oral administration of MBP to pigs is able to induce an immune response. In both experiments cholera toxin was used as oral adjuvant

Mathematical Modeling of Arterial Blood Pressure Using Photo-Plethysmography Signal in Breath-hold Maneuver

Recent research has shown that each apnea episode results in a significant rise in the beat-to-beat blood pressure and by a drop to the pre-episode levels when patient resumes normal breathing. While the physiological implications of these repetitive and significant oscillations are still unknown, it is of interest to quantify them. Since current array of instruments deployed for polysomnography studies does not include beat-to-beat measurement of blood pressure, but includes oximetry, it is both of clinical interest to estimate the magnitude of BP oscillations from the photoplethysmography (PPG) signal that is readily available from sleep lab oximeters. We have investigated a new method for continuous estimation of systolic (SBP), diastolic (DBP), and mean (MBP) blood pressure waveforms from PPG. Peaks and troughs of PPG waveform are used as input to a 5th order autoregressive moving average model to construct estimates of SBP, DBP, and MBP waveforms. Since breath hold maneuvers are shown to simulate apnea episodes faithfully, we evaluated the performance of the proposed method in 7 subjects (4 F; 32+-4 yrs., BMI 24.57+-3.87 kg/m2) in supine position doing 5 breath maneuvers with 90s of normal breathing between them. The modeling error ranges were (all units are in mmHg) -0.88+-4.87 to -2.19+-5.73 (SBP); 0.29+-2.39 to -0.97+-3.83 (DBP); and -0.42+-2.64 to -1.17+-3.82 (MBP). The cross validation error ranges were 0.28+-6.45 to -1.74+-6.55 (SBP); 0.09+-3.37 to -0.97+-3.67 (DBP); and 0.33+-4.34 to -0.87+-4.42 (MBP). The level of estimation error in, as measured by the root mean squared of the model residuals, was less than 7 mmHgComment: 4 pages, published in 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC

Two minor determinants of myelin basic protein induce experimental allergic encephalomyelitis in SJL/J mice

Experimental allergic encephalomyelitis (EAE)' is an autoimmune inflammatory demyelinating disease in the central nervous system (CNS) of animals immunized with myelin basic protein (MBP). The disease is directly mediated by Thelper cells that recognize MBP in the context ofclass II antigens of the MHC (1-3). In nude mice, a single clone of adoptively transferred MBP-reactive T helper cells can cause EAE (4), suggesting that these are the only T cells required for disease induction. As a prototypic model of T helper cell-mediated autoimmune disease, observations in EAE could likely be applicable to other T helper cell-mediated diseases such as murine lupus (5), thyroiditis (6), collagen arthritis (7), and adjuvant arthritis (8), as well as human autoimmune diseases. The MBP epitope is determined in part by the MHC. Using proteolytic peptide fragments of MBP, SJL/J (H-2s) and BIO.T(6R) (H-2q) mice were found to develop EAE to the COOH-terminal peptide of MBP, whereas PL/J (H-2u) and A/J (H-2k) mice developed EAE to the NH2-terminal peptide of MBP (9). Recently, by using synthetic peptides that overcome the difficulties of obtaining pure uncontaminated proteolytic peptides, a single T cell encephalitogenic epitope for PL/J mice has been identified . This epitope consists of the first nine NH2-terminal amino acid residues of MBP which must be acetylated at the a amino group to induce disease (10). Similar fine mapping of the encephalitogenic T cell epitope(s) for SJL/J mice has not been done, in part because of the large size of the COOH-terminal peptic fragment of MBP (residues 89-169 of rat MBP, reference 9). MouseMBP consists offour major forms due to differential RNA splicing of exons II and VI (11), resulting in molecular masses of 21, 18.5, 17.5, and 14 kD, in the relative amounts of 1 :10:3.5:35 . Since EAE can also be induced with the small form of rat MBP (14 kD), which has exons II and VI of the MBP gene deleted (12), the COOH-terminal encephalitogenic determinant for SJL/J mice must be present within a segment ofonly 42 amino acid residues . Consistent withthis notion is the observation that this peptide sequence is identical among the MBPs of several mammalian species, including mouse, rat, bovine, guinea pig, and porcine, all of which can induce EAE in SJL/mice (13, 14). To identify the SJL/J encephalitogenic T cell epitope(s), overlapping peptides to the COOH-terminal region ofthe small form of mouse MBP were synthesized. Two overlapping peptides encompassing an 18-amino acid region were found to elicit EAE in SJL/J mice. The finding of a single peptide region of MBP that is responsible for encephalitogenic T cell epitopes in SJL/J mice is analogous to that of the PL/J mice and has implications for the development of specific therapy for T cell-mediated autoimmune diseases

Development of an electrochemical maltose biosensor

In this work, electrochemical maltose biosensors based on mutants of the maltose binding protein (MBP) are developed. A ruthenium II complex (Ru II ), which is covalently attached to MBP, serves as an electrochemical reporter of MBP conformational changes. Biosensors were made through direct attachment of Ru II complex modified MBP to gold electrode surfaces. The responses of some individual mutants were evaluated using square wave voltammetry. A maltose-dependent change in Faradic current and capacitance was observed. It is therefore demonstrated that biosensors using generically this family of bacterial periplasmic binding proteins (bPBP) can be made lending themselves to facile biorecognition element preparation and low cost electrochemical transduction

Myelin basic protein peptide 45–89 induces the release of nitric oxide from microglial cells.

Continuous (24 h) exposure of mixed oligodendrocyte/microglial cells to peptides 45–89 derived from citrullinated C8 isoforms of myelin basic protein (MBP) induces cell death. In contrast, MBP-C8 at the same molecular concentration is not toxic to oligodendrocyte/microglial cells as detected by the MTT test and trypan blue exclusion method. The loss of oligodendrocyte/microglial cells resulted in the release of cytochrome c from mitochondria, suggesting MBP 45–89-induced apoptosis. On the other hand, peptides 45–89 stimulated the secretion of nitric oxide from microglial cells only via induction of iNOS. The addition of peptide 45–89 to the microglial cells led to a decrease of the level of the inhibitory protein IkB, indicating that activation of the transcription factor NF-kB is involved in these processes. We propose that the immunodominant peptide 45–89 induces damage of oligodendrocytes by activation of microglial cells and subsequent generation of nitric oxide, and that this may be the first step in the initiation of autoimmunity