Predominant cultivable subgingival flora of renal transplant recipients

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No hypoperfusion is produced in the epicardium during application of myocardial topical negative pressure in a porcine model

ABSTRACT: BACKGROUND: Topical negative pressure (TNP), commonly used in wound therapy, has been shown to increase blood flow and stimulate angiogenesis in skeletal muscle. We have previously shown that a myocardial TNP of -50 mmHg significantly increases microvascular blood flow in the myocardium. When TPN is used in wound therapy (on skeletal and subcutaneous tissue) a zone of relative hypoperfusion is seen close to the wound edge. Hypoperfusion induced by TNP is thought to depend on tissue density, distance from the negative pressure source, and the amount negative pressure applied. When applying TNP to the myocardium, a significant, long-standing zone of hypoperfusion could theoretically cause ischemia, and negative effects on the myocardium. The current study was designed to elucidate whether hypoperfusion was produced during myocardial TNP. METHODS: Six pigs underwent median sternotomy. Laser Doppler probes were inserted horizontally into the heart muscle in the LAD area, at depths of approximately, 1-2 mm. The microvascular blood flow was measured before and after the application of a TNP. Analyses were performed before left anterior descending artery (LAD) occlusion (normal myocardium) and after 20 minutes of LAD occlusion (ischemic myocardium). RESULTS: A TNP of -50 mmHg induced a significant increase in microvascular blood flow in normal myocardium (**p = 0.01), while -125 mmHg did not significantly alter the microvascular blood flow. In ischemic myocardium a TNP of -50 mmHg induced a significant increase in microvascular blood flow (*p = 0.04), while -125 mmHg did not significantly alter the microvascular blood flow. CONCLUSION: No hypoperfusion could be observed in the epicardium in neither normal nor ischemic myocardium during myocardial TNP

Subgingival microbiota of renal transplant recipients

Renal transplant patients undergoing immunosuppressive therapy may experience periodontal side-effects such as gingival overgrowth. This study evaluated the subgingival microbiota of renal transplant recipients with or without periodontal tissue destruction who may have concurrent gingival enlargement. Subgingival paper point samples taken from the deepest probing sites of 38 subjects (one per patient) were examined using direct microscopy and culture techniques. A complex microflora comprising gram-positive and gram-negative cocci, rods and filaments, fusiforms, curved rods and spirochetes was observed using microscopy. Yeasts were occasionally detected. Significantly higher proportions of gram-positive morphotypes, including gram-positive cocci, were observed in samples from periodontally healthy patients. The predominant cultivable microflora from anaerobic culture comprised several species of facultative and obligate anaerobes. Colonization of the subgingival sites by 'foreign' microbes that are normally dermal, intestinal or vaginal flora was detected in up to 50% of the samples. High mean proportions of lost or unidentified species were also occasionally noted. The results showed that the subgingival biofilm of renal transplant recipients with chronic periodontitis comprised mainly gram-negative rods and spirochetes. Besides the usual predominant cultivable subgingival microbiota associated with periodontitis, the high prevalence of unidentified and 'foreign' microbes indicates the possibility of subgingival microbial alteration in renal transplant patients.postprin

Effects of implantation of bone marrow cells on cytokine levels in the ischemic heart tissue. An experimental study

<p>Abstract</p> <p>Background</p> <p>In order to achieve a safe and persistent angiogenic effect, we investigated the potential of bone marrow cells implantation to enhance angiogenesis of ischemic hearts in a rat model, and also we have investigated growth factors accompanying and intermediating the angiogenesis, and the changes occurring in the levels of cytokines and their relations with angiogenesis.</p> <p>Methods</p> <p>30 adult male Wistar albino rats from the same colony were used. After anterior myocardial infarction induced by occlusion of the left anterior descending artery, they were divided into two groups (Group I and Group II). 2 × 10⁷bone marrow cells suspended in 0.1 ml phosphate-buffered saline solution and 0.1 ml phosphate-buffered saline solution were injected at six points in the infarcted area in Group I and Group II respectively. Changes in the vascular density and, vascular endothelial growth factor, vascular cell adhesion molecule and cytokine levels in the infarcted myocardium after bone marrow cells implantation were examined.</p> <p>Results</p> <p>The implantation assay showed that bone marrow cells induced angiogenesis. Light microscopic analysis of the vascular density in the ischemic area showed that, angiogenesis had been induced to higher in Group I than Group II. Levels of vascular endothelial growth factor, vascular cell adhesion molecule and the inflammatory cytokines such as interleukin-1 and tumor necrosis factor-α in Group I were significantly elevated compared with those in Group II.</p> <p>Conclusion</p> <p>Bone marrow cells implantation induced angiogenesis in a rat ischemic heart model as a result of increase of the levels of vascular endothelial growth factor, vascular cell adhesion molecule, interleukin-1, and tumor necrosis factor-α.</p

Continuous subcutaneous insulin infusion therapy is associated with reduced retinopathy progression compared with multiple daily injections of insulin

AIMS/HYPOTHESIS: We aimed to compare diabetic retinopathy outcomes in people with type 1 diabetes following introduction of continuous subcutaneous insulin infusion (CSII) therapy with outcomes in people receiving continuing therapy with multiple daily insulin injections (MDI). METHODS: This is a retrospective cohort study using the Scottish Care Information – Diabetes database for retinal screening outcomes and HbA(1c) changes in 204 adults commenced on CSII therapy between 2013 and 2016, and 211 adults eligible for CSII during the same period but who continued on MDI therapy. Diabetic retinopathy progression (time to minimum one-grade worsening in diabetic retinopathy from baseline grading) was plotted for CSII and MDI cohorts using Kaplan–Meier curves, and outcomes were compared using multivariate Cox regression analysis adjusting for age, sex, baseline HbA(1c), blood pressure, cholesterol, smoking status and socioeconomic quintile. Impact of baseline HbA(1c) and change in HbA(1c) on diabetic retinopathy progression was assessed within CSII and MDI cohorts. RESULTS: CSII participants were significantly younger, were from less socially deprived areas, and had lower HbA(1c) and higher diastolic BP at baseline. There was a larger reduction in HbA(1c) at 1 year in those on CSII vs MDI (−6 mmol/mol [−0.6%] vs −2 mmol/mol [−0.2%], p < 0.01). Diabetic retinopathy progression occurred in a smaller proportion of adults following commencement of CSII vs continued MDI therapy over mean 2.3 year follow-up (26.5% vs 18.6%, p = 0.0097). High baseline HbA(1c) (75 mmol/mol [9%]) was associated with diabetic retinopathy progression in the MDI group (p = 0.0049) but not the CSII group (p = 0.93). Change in HbA(1c) at follow-up, irrespective of baseline glycaemic status, did not significantly affect diabetic retinopathy progression in either group. CONCLUSIONS/INTERPRETATION: CSII was associated with reduced diabetic retinopathy progression compared with continued MDI therapy, and may be protective against diabetic retinopathy progression for those with high baseline HbA(1c). Progression of diabetic retinopathy over 3 years was not associated with a change in HbA(1c). GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-021-05456-w

Behavior and Impact of Zirconium in the Soil–Plant System: Plant Uptake and Phytotoxicity

Because of the large number of sites they pollute, toxic metals that contaminate terrestrial ecosystems are increasingly of environmental and sanitary concern (Uzu et al. 2010, 2011; Shahid et al. 2011a, b, 2012a). Among such metals is zirconium (Zr), which has the atomic number 40 and is a transition metal that resembles titanium in physical and chemical properties (Zaccone et al. 2008). Zr is widely used in many chemical industry processes and in nuclear reactors (Sandoval et al. 2011; Kamal et al. 2011), owing to its useful properties like hardness, corrosion-resistance and permeable to neutrons (Mushtaq 2012). Hence, the recent increased use of Zr by industry, and the occurrence of the Chernobyl and Fukashima catastrophe have enhanced environmental levels in soil and waters (Yirchenko and Agapkina 1993; Mosulishvili et al. 1994 ; Kruglov et al. 1996)

Clinical characteristics and outcomes of patients with acute myelogenous leukemia admitted to intensive care: a case-control study

<p>Abstract</p> <p>Background</p> <p>There is limited epidemiologic data on patients with acute myelogenous (myeloid) leukemia (AML) requiring life-sustaining therapies in the intensive care unit (ICU). Our objectives were to describe the clinical characteristics and outcomes in critically ill AML patients.</p> <p>Methods</p> <p>This was a retrospective case-control study. Cases were defined as adult patients with a primary diagnosis of AML admitted to ICU at the University of Alberta Hospital between January 1^st2002 and June 30^th2008. Each case was matched by age, sex, and illness severity (ICU only) to two control groups: hospitalized AML controls, and non-AML ICU controls. Data were extracted on demographics, course of hospitalization, and clinical outcomes.</p> <p>Results</p> <p>In total, 45 AML patients with available data were admitted to ICU. Mean (SD) age was 54.8 (13.1) years and 28.9% were female. Primary diagnoses were sepsis (32.6%) and respiratory failure (37.3%). Mean (SD) APACHE II score was 30.3 (10.3), SOFA score 12.6 (4.0) with 62.2% receiving mechanical ventilation, 55.6% vasoactive therapy, and 26.7% renal replacement therapy. Crude in-hospital, 90-day and 1-year mortality was 44.4%, 51.1% and 71.1%, respectively. AML cases had significantly higher adjusted-hazards of death (HR 2.23; 95% CI, 1.38-3.60, p = 0.001) compared to both non-AML ICU controls (HR 1.69; 95% CI, 1.11-2.58, p = 0.02) and hospitalized AML controls (OR 1.0, reference variable). Factors associated with ICU mortality by univariate analysis included older age, AML subtype, higher baseline SOFA score, no change or an increase in early SOFA score, shock, vasoactive therapy and mechanical ventilation. Active chemotherapy in ICU was associated with lower mortality.</p> <p>Conclusions</p> <p>AML patients may represent a minority of all critically ill admissions; however, are not uncommonly supported in ICU. These AML patients are characterized by high illness severity, multi-organ dysfunction, and high treatment intensity and have a higher risk of death when compared with matched hospitalized AML or non-AML ICU controls. The absence of early improvement in organ failure may be a useful predictor for mortality for AML patients admitted to ICU.</p

Potent Neutralization of Influenza A Virus by a Single-Domain Antibody Blocking M2 Ion Channel Protein

Influenza A virus poses serious health threat to humans. Neutralizing antibodies against the highly conserved M2 ion channel is thought to offer broad protection against influenza A viruses. Here, we screened synthetic Camel single-domain antibody (VHH) libraries against native M2 ion channel protein. One of the isolated VHHs, M2-7A, specifically bound to M2-expressed cell membrane as well as influenza A virion, inhibited replication of both amantadine-sensitive and resistant influenza A viruses in vitro, and protected mice from a lethal influenza virus challenge. Moreover, M2-7A showed blocking activity for proton influx through M2 ion channel. These pieces of evidence collectively demonstrate for the first time that a neutralizing antibody against M2 with broad specificity is achievable, and M2-7A may have potential for cross protection against a number of variants and subtypes of influenza A viruses

Eastern asian expert panel opinion: designing clinical trials of molecular targeted therapy for hepatocellular carcinoma

The largest burden of hepatocellular carcinoma (HCC) lies in Asia, secondary to hepatitis B virus (HBV) infection. Improved survival with sorafenib has fostered new research but many challenges remain in designing clinical trials. The disease, its management, and populations affected by it are heterogeneous worldwide and within Asia. An expert conference of Eastern Asian oncologists and hepatologists was convened to foster consensus in clinical trial design. The panel identified key areas that need to be addressed to facilitate clinical trials in Asia. Stratification by viral etiology is desirable within Asia and by region in global trials. Antiviral therapy should also be considered as a stratification factor and incorporated into HCC management in trials. The panel agreed that histological diagnosis is not required for trial entry and that Barcelona-Clinic Liver Cancer (BCLC) staging is acceptable for trials as long as portal hypertension can be better defined with standardized methodology. Consensus in treatment must be sought to allow multi-national trials and it must be recognized that first-line sorafenib is not largely feasible in Asia. Finally, Asian nations must be urged to participate in clinical trials, many of which are ongoing, to advance new treatment options in this challenging disease

The removal of multiplicative, systematic bias allows integration of breast cancer gene expression datasets – improving meta-analysis and prediction of prognosis

BACKGROUND: The number of gene expression studies in the public domain is rapidly increasing, representing a highly valuable resource. However, dataset-specific bias precludes meta-analysis at the raw transcript level, even when the RNA is from comparable sources and has been processed on the same microarray platform using similar protocols. Here, we demonstrate, using Affymetrix data, that much of this bias can be removed, allowing multiple datasets to be legitimately combined for meaningful meta-analyses. RESULTS: A series of validation datasets comparing breast cancer and normal breast cell lines (MCF7 and MCF10A) were generated to examine the variability between datasets generated using different amounts of starting RNA, alternative protocols, different generations of Affymetrix GeneChip or scanning hardware. We demonstrate that systematic, multiplicative biases are introduced at the RNA, hybridization and image-capture stages of a microarray experiment. Simple batch mean-centering was found to significantly reduce the level of inter-experimental variation, allowing raw transcript levels to be compared across datasets with confidence. By accounting for dataset-specific bias, we were able to assemble the largest gene expression dataset of primary breast tumours to-date (1107), from six previously published studies. Using this meta-dataset, we demonstrate that combining greater numbers of datasets or tumours leads to a greater overlap in differentially expressed genes and more accurate prognostic predictions. However, this is highly dependent upon the composition of the datasets and patient characteristics. CONCLUSION: Multiplicative, systematic biases are introduced at many stages of microarray experiments. When these are reconciled, raw data can be directly integrated from different gene expression datasets leading to new biological findings with increased statistical power