Miracle-dz/UniFAR-FTUs huggingface dataset:
Probiotics Reduce Postoperative Infections in Patients Undergoing Colorectal Surgery: A Systematic Review and Meta-Analysis

Background. We performed this meta-analysis to investigate the efficacy of probiotics on prevention of infection-related complications following colorectal resection. Method. PubMed, EMBASE, Cochrane Library, and the Web of Science were searched up to January 2016. According to the results, only randomized controlled trials that compared the efficacy of probiotics on patients with colorectal resection were included for meta-analysis. Results. Nine studies including a total of 1146 patients met the criteria (556 received multistrain probiotic bacteria, 590 with non-multistrain probiotic bacteria). The combination of multistrain probiotics was beneficial in the reduction of total infections (OR = 0.30, 95%CI: 0.15–0.61, p = 0.0009), including surgical site infections (SSI) (OR = 0.48, 95%CI: 0.25–0.89, p = 0.02) and nonsurgical site infections (NSSI) (OR = 0.36, 95%CI: 0.23–0.56, p < 0.00001). However, there was no significant reduction in total infections (OR = 0.74, 95%CI: 0.50–1.09, p = 0.13) or SSI (OR = 0.77, 95%CI: 0.52–1.12, p = 0.17) with the application of non-multistrains of probiotics. Conclusion. Combinations of multistrain probiotic bacteria showed promise in preventing the incidence of infections following colorectal surgery. However, the efficacy of one or two strains of probiotics remains undetermined.
Drosophila Valosin-Containing Protein is required for dendrite pruning through a regulatory role in mRNA metabolism

Significance The ubiquitin–proteasome system (UPS) is required for Drosophila class IV dendritic arborization neuron dendrite pruning. We found that mutants in the ubiquitylation machinery, the ubiquitin-dependent chaperone Valosin-Containing Protein (VCP), and the 19S regulatory particle of the proteasome—but not the 20S core particle—showed defects in pruning gene expression and mislocalization or overexpression of specific mRNA-binding proteins. In the case of VCP inhibition, we were able to detect a specific change in the splicing pattern of a pruning gene that likely contributes to pruning defects. A link between VCP and mRNA-binding proteins had been observed in the context of human neurodegenerative disease. This study implicates a specific function of VCP and ubiquitin in mRNA metabolism. The dendritic arbors of the larval Drosophila peripheral class IV dendritic arborization neurons degenerate during metamorphosis in an ecdysone-dependent manner. This process—also known as dendrite pruning—depends on the ubiquitin–proteasome system (UPS), but the specific processes regulated by the UPS during pruning have been largely elusive. Here, we show that mutation or inhibition of Valosin-Containing Protein (VCP), a ubiquitin-dependent ATPase whose human homolog is linked to neurodegenerative disease, leads to specific defects in mRNA metabolism and that this role of VCP is linked to dendrite pruning. Specifically, we find that VCP inhibition causes an altered splicing pattern of the large pruning gene molecule interacting with CasL and mislocalization of the Drosophila homolog of the human RNA-binding protein TAR–DNA-binding protein of 43 kilo-Dalton (TDP-43). Our data suggest that VCP inactivation might lead to specific gain-of-function of TDP-43 and other RNA-binding proteins. A similar combination of defects is also seen in a mutant in the ubiquitin-conjugating enzyme ubcD1 and a mutant in the 19S regulatory particle of the proteasome, but not in a 20S proteasome mutant. Thus, our results highlight a proteolysis-independent function of the UPS during class IV dendritic arborization neuron dendrite pruning and link the UPS to the control of mRNA metabolism.
AIMP2 promotes TNFα-dependent apoptosis via ubiquitin-mediated degradation of TRAF2

AIMP2 (aminoacyl-tRNA synthetase interacting multifunctional protein 2; also known as JTV-1) was first identified as p38 in a macromolecular protein complex that consisted of nine different aminoacyl-tRNA synthetases and two other auxiliary factors. AIMP2 also plays pivotal roles in the regulation of cell proliferation and death. Although AIMP2 was previously shown to augment TNFα-induced cell death, its working mechanism in this signal pathway was not understood. Here, we investigate the functional significance and mode of action of AIMP2 in TNFα signaling. TNFα-induced cell death was compromised in AIMP2-deficient or -suppressed cells and exogenous supplementation of AIMP2 augmented apoptotic sensitivity to TNFα signaling. This activity was confirmed by the AIMP2-dependent increase of IκB and suppression of NFκB. We found binding of AIMP2 to TRAF2, a key player in the TNFα signaling pathway. AIMP2 augmented the association of an E3 ubiquitin ligase, c-IAP1, with TRAF2, causing ubiquitin-dependent degradation of TRAF2. These findings suggest that AIMP2 can mediate the pro-apoptotic activity of TNFα via the downregulation of TRAF2 expression.
Endothelium-derived haemostatic factors and the antiphospholipid syndrome.

The cause of thrombosis in the antiphospholipid syndrome (APS) is unknown. There have been reports of abnormalities in the antigenic levels or activity of endothelium-derived haemostatic factors, such as tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1); however the data from these studies are conflicting. We studied plasma from nine patients with APS; seven of them had a history of thrombosis, and three had systemic lupus erythematosus (SLE). We also studied nine matched control patients who had SLE without APS, and 14 healthy individuals. We measured t-PA, von Willebrand factor (vWF), anticardiolipin antibody (ACA) and anti-endothelial cell antibody (AECA) levels by enzyme-linked immunoassay (ELISA), PAI-1 activity by a parabolic-rate chromogenic assay, and lupus anticoagulant (LA) activity by a standard mixing test. For t-PA and PAI-1, measurements were made on morning and evening plasma samples. The two groups of patients did not differ significantly with respect to age, sex, plasma lipids or anti-inflammatory drugs. Most APS patients (7/9) but none of the controls were taking warfarin. Between the APS and the control patients no significant differences were detected in t-PA, PAI-1, vWF or AECA levels. When APS patients were considered alone, vWF levels correlated positively with IgG ACA levels (r = 0.81, P < 0.01) and negatively with platelet count (r = -0.68, P < 0.05). There was no correlation between levels of ACA or LA activity and t-PA, PAI-1 or AECA. Compared with healthy volunteers, the diurnal variation of t-PA and PAI-1 was blunted in the two patient groups. (ABSTRACT TRUNCATED AT 250 WORDS)
Speckle Pattern Errors in Self-Mixing Interferometry

We analyze the random errors occurring in interferometric measurements because of the speckle pattern regime, when the remote target is a diffusing surface. First, we review the statistical properties of speckle and discuss amplitude fading that is affecting the self-mixing interferometer (SMI) signal and methods to alleviate it. Second, we derive intra-speckle phase errors using the bivariate conditional probability, and find that the noise-equivalent-displacement for small displacement Δ is proportional to the ratio of Δ to speckle longitudinal size sl. Last, we extend the analysis to inter-speckle displacements (Δ > s1) and, after deriving speckle systematic and random errors, show that operation up to meters on a diffusing surface target is possible with a small (≈ λ) error. Results are mainly focussed on SMI, yet they have general validity for any configuration of interferometry.
Structural Changes and Antibody Enrichment in the Lungs Are Early Features of Anti–Citrullinated Protein Antibody–Positive Rheumatoid Arthritis

It has been suggested that immunologic events in the lungs may be involved in triggering immunity, in particular production of anti–citrullinated protein antibodies (ACPAs) during early phases of rheumatoid arthritis (RA). The aim of this study was to investigate the structural and immunologic features of the lungs in incident cases of early RA in relation to ACPA presence and smoking status.
THE EXPRESSION AND SIGNIFICANCE OF INTRACELLULAR T HELPER CYTOKINES IN SYSTEMIC LUPUS ERYTHEMATOSUS

To analyze the Th1 and Th2 paradigm of peripheral T helper cells in patients with systemic lupus erythematosus (SLE). The intracellular Th1 and Th2 cytokines were analyzed in fresh blood T cells from 20 SLE patients who had not yet received any treatment. Th1 and Th2 cells were quantitated based on their intracellular cytokine content as assessed by flow cytometry. Cytokine expressions were correlated with clinical features, laboratory findings, and disease activities. There was no difference in the expression of intracellular IFN-γ, or IL-4 between SLE patients and healthy controls. However, the IL-2 and IL-10 levels were significantly higher and lower respectively in the lupus patients than in the control group. In addition, patients with arthritis had higher IFN-γ expression than patients without arthritis. Moreover, patients with serositis or CNS involvement had higher IL-4 expression than in patients without these manifestations. There was no correlation between the SLEDAI scores and the cytokine expression levels. However, patients with serum anti-ds DNA antibodies had higher IL-10 levels than in those without these antibodies. The present study demonstrates that a Th1 pattern of intracellular cytokines predominates in patients with SLE prior to treatment. The pattern of particular intracellular T cell cytokines may suggest specific clinical manifestations and disease progression of SLE.
Sudden natural deaths in Edirne, Turkey, from 1984 to 2005

The aim of this study is to evaluate the characteristics of sudden natural deaths (SND) in forensic autopsy cases which were performed in Trakya University Department of Forensic Medicine, Edirne, Turkey. For each case, a complete autopsy, toxicological screening and histological examination were performed. Deaths due to unnatural causes, alcohol, drug overdose and undetermined causes (negative autopsy) were excluded from the study. Autopsy reports of 959 consecutive forensic cases performed in a 22-year period were reviewed. Two hundred and seventy-eight (278) SNDs were identified, involving 232 males (83.4%) and 46 females (16.6%). The age group of 50-59 years accounted for 21.58% of the cases. In the majority (55%) the cause of death was related to the cardiovascular system – principally ischemic heart disease. The second most common cause of SND was related to the respiratory system (19.1%), especially pneumonia. Most of the SNDs occurred in the winter months. Ethyl alcohol was detected in 5.3% of cases. In conclusion, sudden natural deaths related to the cardiovascular system are shown to be a significant problem in the Trakya region of Turkey.
The distribution of dorsal root axons to laminae IV, V, and VI of the macaque spinal cord: A quantitative electron microscopic study

The projections of dorsal root axons to the deeper laminae (IV, V, and VI) of the Macaque spinal cord were examined by the use of experimentally induced degeneration following dorsal rhizotomy or by injection of dorsal root ganglia with tritiated amino acids followed by light and electron mi‐croscopic autoradiography.
Murine antibody responses to the verotoxin 1 B subunit: demonstration of major histocompatibility complex dependence and an immunodominant epitope involving phenylalanine 30

Structurally conserved verotoxin 1 (VT1) mutant derivatives, showing reduced receptor binding and cytotoxicity, may serve as natural toxoids to protect against VT-mediated disease. In this study, the antibody responses to the wild-type VT1 B subunit, a B-subunit mutant (Phe30Ala B), and the corresponding holotoxin (Phe30Ala HT) were examined in three inbred mouse strains. BALB/c (H-2d) and CBA (H-2k) mice produced strong antibody responses to both wild-type and mutant B subunits. VT1 B-raised sera reacted more strongly with VT1 B than with Phe30Ala B in enzyme-linked immunosorbent assays, while Phe30Ala B-raised sera reacted equally with VT1 B and Phe30Ala B. C57BL/6 (H-2b) and congenic BALB/c (BALB x B [H-2b]) mice produced no detectable antibody response to either VT1 B or Phe30Ala B. However, an anti-VT1 B antibody response was detected in H-2b mice immunized with biologically active Phe30Ala HT. Based on these observations, we conclude that the VT1 B subunit possesses a B-cell immunodominant epitope formed partly by phenylalanine 30 and that the B-subunit antibody response is dependent on the H-2 haplotype of the mouse strain. Our results also support a potential role for the A subunit in providing the T-cell help necessary to overcome a deficient B-subunit antibody response in H-2b mice.
Beta‐hydroxy‐beta‐methylbutyrate supplementation and skeletal muscle in healthy and muscle‐wasting conditions

Beta‐hydroxy‐beta‐methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that has been reported to have anabolic effects on protein metabolism. The aims of this article were to summarize the results of studies of the effects of HMB on skeletal muscle and to examine the evidence for the rationale to use HMB as a nutritional supplement to exert beneficial effects on muscle mass and function in various conditions of health and disease.
RpoS Synthesis Is Growth Rate Regulated in Salmonella typhimurium, but Its Turnover Is Not Dependent on Acetyl Phosphate Synthesis or PTS Function

ABSTRACT The RpoS sigma factor of enteric bacteria is either required for or augments the expression of a number of genes that are induced during nutrient limitation, growth into stationary phase, or in response to stresses, including high osmolarity. RpoS is regulated at multiple levels, including posttranscriptional control of its synthesis, protein turnover, and mechanisms that affect its activity directly. Here, the control of RpoS stability was investigated in Salmonella typhimurium by the isolation of a number of mutants specifically defective in RpoS turnover. These included 20 mutants defective inmviA, the ortholog of Escherichia coli rssB/sprE, and 13 mutants defective in either clpP orclpX which encode the protease active on RpoS. Anhns mutant was also defective in RpoS turnover, thus confirming that S. typhimurium and E. coli have identical genetic requirements for this process. Some current models predict the existence of a kinase to phosphorylate the response regulator MviA, but no mutants affecting a kinase were recovered. AnmviA mutant carrying the D58N substitution altering the predicted phosphorylation site is substantially defective, suggesting that phosphorylation of MviA on D58 is important for its function. No evidence was obtained to support models in which acetyl phosphate or the PTS system contributes to MviA phosphorylation. However, we did find a significant (fivefold) elevation of RpoS during exponential growth on acetate as the carbon and energy source. This behavior is due to growth rate-dependent regulation which increases RpoS synthesis at slower growth rates. Growth rate regulation operates at the level of RpoS synthesis and is mainly posttranscriptional but, surprisingly, is independent of hfq function.
Correlation of Vectorcardiogram and Electrocardiogram with Coronary Arteriogram

One hundred patients with suspected coronary heart disease were studied by vectorcardiography (VCG), electrocardiography (ECG), and coronary arteriography. Twenty-eight patients had VCG evidence of anterior infarction; 26 of this group had severe narrowing or obstruction of the left anterior descending branch. Five did not have anterior infarction by ECG.Twenty-seven patients had VCG evidence of diaphragmatic infarction; 25 of this group had severe narrowing of the right coronary artery or the left circumflex branch or both. Six of the 27 did not have ECG evidence of diaphragmatic infarction.Twelve patients had VCG evidence of posterior infarction whereas it was detected by ECG in only two. Only six of the 12, however, had severe narrowing of the nutrient arteries to the posterobasal part of the myocardium.Thirteen patients with infarction had severe narrowing but not total obstruction of a coronary artery. On the other hand, 15 patients had total obstruction of a major coronary vessel without actual infarction.
Inhibition of contractile activity during postconditioning enhances cardioprotection by restoring sarcolemmal dystrophin through phosphatidylinositol 3-kinase.

BACKGROUND Although ischemic postconditioning (IPost) confers cardioprotection by protecting the mitochondria though the activation of phosphatidylinositol 3-kinase (PI3K), a potential drawback of IPost is impairment of aerobic ATP generation during reperfusion by repeated ischemia. This decrease in ATP might inhibit the restoration of sarcolemmal dystrophin, which is translocated during ischemia, and render cardiomyocytes susceptible to contraction-induced oncosis. METHODS AND RESULTS Isolated rat hearts were subjected to 30 min ischemia and 120 min reperfusion. IPost induced by 20 cycles of 10-s reperfusion and 10-s ischemia enhanced the activation of PI3K as evidenced by the increased phosphorylation of Akt, but had no effect on myocardial ATP, restoration of sarcolemmal dystrophin, or cardiomyocyte oncosis during IPost. Administration of the contractile blocker, 2,3-butanedione monoxim (BDM), during IPost increased myocardial ATP and facilitated the redistribution of dystrophin to the sarcolemma. This led to reduced cardiomyocyte oncosis and infarct size, and improved the left ventricular function. The anti-oncotic effect of BDM occurred without changing the anti-apoptotic effect of IPost. The PI3K inhibitor, LY294002, prevented the phosphorylation of Akt, decreased the recovery of ATP and restoration of sarcolemmal dystrophin, and blocked the anti-oncotic and anti-apoptotic effects of IPost. CONCLUSIONS These results suggest that the inhibition of contractile activity during IPost prevents cardiomyocyte oncosis and enhances cardioprotection through PI3K-dependent restoration of sarcolemmal dystrophin.
A new control scheme for circulating current minimization in high frequency AC power distribution architecture with multiple inverter modules operated in parallel

The control issue of multiple inverter module operation (MIMO) is investigated for high frequency AC power distribution architecture, where multiple high frequency resonant inverters are connected in parallel to the high frequency, high voltage low current (HVLC) AC bus, to feed a number of point-of-use-power-supplies. The circulating current in MIMO is analyzed first. A novel control scheme is proposed based on the active and reactive current decomposition concept. In the proposed control, there are two loops, the current sharing control loop and voltage feedback control loop. For the current sharing loop, active current and reactive current are controlled separately. It is shown that the minimization of circulating current can be achieved if both the active currents and reactive currents are evenly distributed among activated inverter modules. This method is superior to the scalar control where only magnitudes of the currents are controlled. Performance is verified for both steady state and transient conditions
Parkinsonism-associated Protein DJ-1/Park7 Is a Major Protein Deglycase That Repairs Methylglyoxal- and Glyoxal-glycated Cysteine, Arginine, and Lysine Residues

Background: Protein glycation is a nonenzymatic covalent reaction between proteins and carbonyl groups resulting in protein denaturation. Results: DJ-1 is the first protein deglycase that repairs proteins from glycation by glyoxals, which constitutes most glycation damage. Conclusion: DJ-1 is a novel protein repair enzyme that protects proteins against glycation. Significance: DJ-1 deglycase activity changes our view on glycation/deglycation and DJ-1-associated Parkinsonism. Glycation is an inevitable nonenzymatic covalent reaction between proteins and endogenous reducing sugars or dicarbonyls (methylglyoxal, glyoxal) that results in protein inactivation. DJ-1 was reported to be a multifunctional oxidative stress response protein with poorly defined function. Here, we show that human DJ-1 is a protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and proteins by acting on early glycation intermediates and releases repaired proteins and lactate or glycolate, respectively. DJ-1 deglycates cysteines, arginines, and lysines (the three major glycated amino acids) of serum albumin, glyceraldehyde-3-phosphate dehydrogenase, aldolase, and aspartate aminotransferase and thus reactivates these proteins. DJ-1 prevented protein glycation in an Escherichia coli mutant deficient in the DJ-1 homolog YajL and restored cell viability in glucose-containing media. These results suggest that DJ-1-associated Parkinsonism results from excessive protein glycation and establishes DJ-1 as a major anti-glycation and anti-aging protein.
Education-based approach to addressing non-evidence-based practice in preventing NSAID-associated gastrointestinal complications.

AIM To evaluate an evidence-based educational program for improving strategies for prevention of nonsteroidal anti-inflammatory drug (NSAID)-associated gastrointestinal (GI) complications. METHODS Four hundred and fifty-six specialists replied to a questionnaire that covered issues related to NSAID-induced adverse effects. They also collected data from their last five consecutive patients before and after they had attended an evidence-based seminar on GI prevention strategies. RESULTS Four hundred and forty-one of 456 specialists (96.7%) participated in the survey, and 382 (83.7%) in the education-based study that recorded data from 3728 patients. The specialists overestimated the risk of GI complications with NSAIDs, underestimated the GI safety profile of coxibs, but were aware of the risk factors and of the current prevention strategies. Proton pump inhibitors were co-prescribed with NSAIDs in > 80% of patients with and without risk factors. The educational program had little impact on prescribing habits. CONCLUSION Specialists are informed of advances in NSAID-associated adverse effects and have high rates of GI-prevention therapy. Our educational program did not alter these rates.
Trypsin IV, a Novel Agonist of Protease-activated Receptors 2 and 4*

Certain serine proteases signal to cells by cleaving protease-activated receptors (PARs) and thereby regulate hemostasis, inflammation, pain and healing. However, in many tissues the proteases that activate PARs are unknown. Although pancreatic trypsin may be a physiological agonist of PAR2 and PAR4 in the small intestine and pancreas, these receptors are expressed by cells not normally exposed pancreatic trypsin. We investigated whether extrapancreatic forms of trypsin are PAR agonists. Epithelial cells lines from prostate, colon, and airway and human colonic mucosa expressed mRNA encoding PAR2, trypsinogen IV, and enteropeptidase, which activates the zymogen. Immunoreactive trypsinogen IV was detected in vesicles in these cells. Trypsinogen IV was cloned from PC-3 cells and expressed in CHO cells, where it was also localized to cytoplasmic vesicles. We expressed trypsinogen IV with an N-terminal Igκ signal peptide to direct constitutive secretion and allow enzymatic characterization. Treatment of conditioned medium with enteropeptidase reduced the apparent molecular mass of trypsinogen IV from 36 to 30 kDa and generated enzymatic activity, consistent with formation of trypsin IV. In contrast to pancreatic trypsin, trypsin IV was completely resistant to inhibition by polypeptide inhibitors. Exposure of cell lines expressing PAR2 and PAR4 to trypsin IV increased [Ca2+]i and strongly desensitized cells to PAR agonists, whereas there were no responses in cells lacking these receptors. Thus, trypsin IV is a potential agonist of PAR2 and PAR4 in epithelial tissues where its resistance to endogenous trypsin inhibitors may permit prolonged signaling.