First molecular characterization of Giardia duodenalis from goats in Malaysia

In the present study, 310 faecal samples from goats from eight different farms in Malaysia were tested for the presence of Giardia using a PCR-coupled approach. The nested PCR for SSU amplified products of the expected size (∼200 bp) from 21 of 310 (6.8%) samples. Sixteen of these 21 products could be sequenced successfully and represented six distinct sequence types. Phylogenetic analysis of the SSU sequence data using Bayesian Inference (BI) identified Giardia assemblages A, B and E. The identification of the ‘zoonotic’ assemblages A and B suggests that Giardia-infected goats represent a possible reservoir for human giardiasis in Malaysia

Chemoattractant Receptor Homologous to the T Helper 2 Cell (CRTH2) Is Not Expressed in Human Amniocytes and Myocytes

BACKGROUND: 15-deoxy-Δ 12,14- Prostaglandin J2 (15dPGJ2) inhibits Nuclear factor kappa B (NF-κB) in human myocytes and amniocytes and delays inflammation induced preterm labour in the mouse. 15dPGJ2 is a ligand for the Chemoattractant Receptor Homologous to the T helper 2 cell (CRTH2), a G protein-coupled receptor, present on a subset of T helper 2 (Th2) cells, eosinophils and basophils. It is the second receptor for Prostaglandin D2, whose activation leads to chemotaxis and the production of Th2-type interleukins. The cellular distribution of CRTH2 in non-immune cells has not been extensively researched, and its identification at the protein level has been limited by the lack of specific antibodies. In this study we explored the possibility that CRTH2 plays a role in 15dPGJ2-mediated inhibition of NF-κB and would therefore represent a novel small molecule therapeutic target for the prevention of inflammation induced preterm labour. METHODS: The effect of a small molecule CRTH2 agonist on NF-κB activity in human cultured amniocytes and myocytes was assessed by detection of p65 and phospho-p65 by immunoblot. Endogenous CRTH2 expression in amniocytes, myocytes and peripheral blood mononuclear cells (PBMCs) was examined by PCR, western analysis and flow cytometry, with amniocytes and myocytes transfected with CRTH2 acting as a positive control in flow cytometry studies. RESULTS: The CRTH2 agonist had no effect on NF-κB activity in amniocytes and myocytes. Although CRTH2 mRNA was detected in amniocytes and myocytes, CRTH2 was not detectable at the protein level, as demonstrated by western analysis and flow cytometry. 15dPGJ2 inhibited phospho-65 in PBMC'S, however the CRTH2 antagonist was not able to attenuate this effect. In conclusion, CRTH2 is not expressed on human amniocytes or myocytes and plays no role in the mechanism of 15dPGJ2-mediated inhibition of NF-κB

From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on "New frontiers in cardiovascular research"

In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients' cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia-reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients' outcome

Hepcidin-mediated hypoferremia disrupts immune responses to vaccination and infection

Background: How specific nutrients influence adaptive immunity is of broad interest. Iron deficiency is the most common micronutrient deficiency worldwide and imparts a significant burden of global disease; however, its effects on immunity remain unclear. Methods: We used a hepcidin mimetic and several genetic models to examine the effect of low iron availability on T cells in vitro and on immune responses to vaccines and viral infection in mice. We examined humoral immunity in human patients with raised hepcidin and low serum iron caused by mutant TMPRSS6. We tested the effect of iron supplementation on vaccination-induced humoral immunity in piglets, a natural model of iron deficiency. Findings: We show that low serum iron (hypoferremia), caused by increased hepcidin, severely impairs effector and memory responses to immunizations. The intensified metabolism of activated lymphocytes requires the support of enhanced iron acquisition, which is facilitated by IRP1/2 and TFRC. Accordingly, providing extra iron improved the response to vaccination in hypoferremic mice and piglets, while conversely, hypoferremic humans with chronically increased hepcidin have reduced concentrations of antibodies specific for certain pathogens. Imposing hypoferremia blunted the T cell, B cell, and neutralizing antibody responses to influenza virus infection in mice, allowing the virus to persist and exacerbating lung inflammation and morbidity. Conclusions: Hypoferremia, a well-conserved physiological innate response to infection, can counteract the development of adaptive immunity. This nutrient trade-off is relevant for understanding and improving immune responses to infections and vaccines in the globally common contexts of iron deficiency and inflammatory disorders

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Theoretical analysis and fabrication of tapered fiber

Adiabaticity criteria and optimal shapes for tapered fiber are theoretically analyzed. In the analysis, it is discovered that a narrower taper waist can be achieved by using a small hot-zone length or increases the elongation distance. The tapered fiber fabrication based on flame brushing technique is then demonstrated using a homemade fiber tapering rig. The heat source comes from an oxy-butane torch with a flame width of 1 mm. Two stepper motors are incorporated in the rig to control the movement of the torch and translation stage. A biconical tapered fiber with a waist diameter as small as 400 nm can be achieved with the rig. To achieve low loss tapered fibers, the shape of the taper should be fabricated according to adiabaticity criteria, whereby the longer transition length is desirable. Tapered fibers with linear and decaying-exponential profiles have been successfully fabricated

Increased left atrial volume index is an independent predictor of raised serum natriuretic peptide in patients with suspected heart failure but normal left ventricular ejection fraction: implication for diagnosis of diastolic heart failure

BACKGROUND: Left atrial volume index (LAVI) is increasingly recognised as a relatively load-independent marker of left ventricular (LV) filling pressures. We assessed the capacity of LAVI to predict LV diastolic dysfunction in comparison with N-terminal pro B-type natriuretic peptide (NTproBNP) in patients with suspected heart failure and a normal ejection fraction (EF). METHODS: 137 patients with suspected heart failure (HF), referred from the community for echocardiography, prospectively underwent Doppler echocardiography, LAVI and NTproBNP estimation. Raised LAVI and reduced LV systolic function were defined as >26 ml/m2 and LV EF <50% respectively. RESULTS: Of 137 patients, 21 were excluded (2 with significant mitral valve disease and 19 with atrial fibrillation). Of the remaining 116 subjects, 92 showed normal LV systolic function. The univariate predictors of serum log NTproBNP were age (p < 0.001), LA dimension (p = 0.001), LAVI (p < 0.001), A wave (p = 0.001), E:A (p = 0.07) and septal wall thickness (p = 0.004). However on multivariate analysis, LAVI was found to be the most consistent and significant predictor of NTproBNP. The area under the curve of the receiver operating characteristic (ROC) curve for NTproBNP in detecting patients with LVEF > or = 50% and LAVI >26 ml/m2 was 0.81 (p < 0.0001) and for patients with LAVI > 26 ml/m2 with and without LVEF > or = 50% was 0.82 (p < 0.0001). CONCLUSION: This data confirms that LAVI on resting echocardiography, specifically in patients with suspected HF and normal LV systolic function is a powerful independent predictor of LV diastolic dysfunction as predicted by serum NTproBNP. In a population with a high suspicion of diastolic heart failure, LAVI may significantly contribute to diagnostic precision

Relationship between myocardial perfusion with myocardial contrast echocardiography and function early after acute myocardial infarction for the prediction of late recovery of function

Background: Following ST elevation acute myocardial infarction (STEMI) and reperfusion therapy, there are often persistent wall thickening (WT) abnormalities and perfusion defects due to variable degree of myocardial stunning and necrosis. We hypothesised that following STEMI and reperfusion therapy, the extent of residual perfusion assessed by myocardial contrast echocardiography (MCE) and not the extent of WT abnormalities would predict subsequent global recovery of left ventricular (LV) function. Methods: Accordingly, 112 patients with STEMI underwent simultaneous assessment of WT abnormality and perfusion using MCE 7 ± 2 days after AMI and reperfusion therapy. Both WT and perfusion were scored on a 16 segment LV model. Contrast perfusion index (CPI), and global LV function were calculated. Echocardiography was repeated 12 weeks after reperfusion to assess recovery of LV function. Results: Of the 112 patients recruited, follow up echocardiography 12 weeks after reperfusion was available in 98 patients. CPI was significantly higher (p < 0.0001) in the 66 patients, who showed late recovery of LV function (1.67 ± 0.27) compared to those who did not show recovery of function (1.25 ± 0.04). No significant difference was noted in the indices of baseline LV function in patients with (1.67 ± 0.32) and without (1.80 ± 0.36) recovery of LV function. The multivariable predictors of late recovery of function were MCE (p = 0.02), absence of diabetes (p = 0.02) and lower peak creatine kinase (p = 0.01). Conclusion: The extent of residual contrast perfusion and not WT abnormalities predicts late recovery of global LV function after acute myocardial infarction and reperfusion therapy. © 2008 Elsevier Ireland Ltd. All rights reserved