Resting respiratory tract dendritic cells preferentially stimulate T helper cell Type 2(Th2) responses and require obligatory cytokine signals for induction of Th1 immunity

Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the “default” T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II lo, endocytosishi, and mixed lymphocyte reactionlo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G1 responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2–3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-γ by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing– associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor α or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli

Current Status of Herbal Drugs in India: An Overview

Herbal drugs constitute a major share of all the officially recognised systems of health in India viz. Ayurveda, Yoga, Unani, Siddha, Homeopathy and Naturopathy, except Allopathy. More than 70% of India’s 1.1 billion population still use these non-allopathic systems of medicine. Currently, there is no separate category of herbal drugs or dietary supplements, as per the Indian Drugs Act. However, there is a vast experiential-evidence base for many of the natural drugs. This offers immense opportunities for Observational Therapeutics and Reverse Pharmacology. Evidence-based herbals are widely used in the diverse systems and manufactured, as per the pharmacopoeial guidelines, by a well-organised industry. Significant basic and clinical research has been carried out on the medicinal plants and their formulations, with the state-of-the-art methods in a number of Institutes/Universities. There are some good examples. Indian medicinal plants also provide a rich source for antioxidants that are known to prevent/delay different diseased states. The antioxidant protection is observed at different levels. The medicinal plants also contain other beneficial compounds like ingredients for functional foods. Hence, the global knowledge about Ayurveda and Indian herbals will hopefully be enhanced by information on the evidence-base of these plants. This will yield rich dividends in the coming years

The strong Atiyah conjecture for right-angled Artin and Coxeter groups

We prove the strong Atiyah conjecture for right-angled Artin groups and right-angled Coxeter groups. More generally, we prove it for groups which are certain finite extensions or elementary amenable extensions of such groups.Comment: Minor change

TPC-H Analyzed: Hidden Messages and Lessons Learned from an Influential Benchmark

The TPC-D benchmark was developed almost 20 years ago, and even though its current existence as TPC H could be considered superseded by TPC-DS, one can still learn from it. We focus on the technical level, summarizing the challenges posed by the TPC-H workload as we now understand them, which w

A qualitative screening tool to identify athletes with ‘high-risk’ movement mechanics during cutting: The cutting movement assessment score (CMAS)

Objective To assess the validity of the cutting movement assessment score (CMAS) to estimate the magnitude of peak knee abduction moments (KAM) against three-dimensional (3D) motion analysis, while comparing whole-body kinetics and kinematics between subjects of low (bottom 33%) and high CMASs (top 33%). Design Cross-sectional study. Setting Laboratory. Participants Forty-one participants (soccer, rugby, netball, and cricket). Main outcome measures Association between peak KAM and CMAS during a 90° cut. Comparison of 3D whole-body kinetics and kinematics between subjects with low (bottom 33%) and high CMASs (top 33%). Results A very large significant relationship (ρ = 0.796, p < 0.001) between CMAS and peak KAM was observed. Subjects with higher CMASs displayed higher-risk cutting postures, including greater peak knee abduction angles, internal foot progression angles, and lateral foot plant distances (p ≤ 0.032, effect size = 0.83–1.64). Additionally, greater cutting multiplanar knee joint loads (knee flexion, internal rotation, and abduction moments) were demonstrated by subjects with higher CMASs compared to lower (p ≤ 0.047, effect size = 0.77–2.24). Conclusion The CMAS is a valid qualitative screening tool for evaluating cutting movement quality and is therefore a potential method to identify athletes who generate high KAMs and “high-risk” side-step cutting mechanics

Novel bi- and trifunctional inhibitors of tumor-associated proteolytic systems

Serine proteases, cysteine proteases, and matrix metalloproteinases (MMPs) are involved in cancer cell invasion and metastasis. Recently, a recombinant bifunctional inhibitor (chCysuPA(19-31)) directed against cysteine proteases and the urokinasetype plasminogen activator (uPA)/plasmin serine protease system was generated by introducing the uPA receptor (uPAR)binding site of uPA into chicken cystatin (chCysWT). In the present study, we designed and recombinantly produced multifunctional inhibitors also targeting MMPs. The inhibitors comprise the Nterminal inhibitory domain of human TIMP-1 (tissue inhibitor of matrix metalloproteinase-1) or TIMP-3, fused to chCysuPA(19-31) or chCysWT. As demonstrated by various techniques, these fusion proteins effectively interfere with all three targeted protease systems. In in vitro Matrigel invasion assays, the addition of recombinant inhibitors strongly reduced invasion of ovarian cancer cells (OVMZ-6\#8). Additionally, OVMZ 6\#8 cells were stably transfected with expression plasmids encoding the various inhibitors. Synthesis and secretion of the inhibitors was verified by a newly developed ELISA, which selectively detects the recombinant proteins. Invasive capacity of inhibitorproducing cells was significantly reduced compared to vectortransfected control cells. Thus, these novel, compact, and smallsize inhibitors directed against up to three different tumorassociated proteolytic systems may represent promising agents for prevention of tumor cell migration and metastasis

Acute presentations of HIV are still missed in low prevalence areas

Objectives To evaluate missed opportunities and delays in the diagnosis of HIV in a low prevalence setting over a 24 year period. Methods Patients with acute presentations of HIV were included in a retrospective note based review. Data were compared from acute presentations in 1985e2001 (88/241 new patients) with 2005e2007 (99/136 new patients). The number of recorded clinical and laboratory clues to infection and subsequent time delays to diagnosis of HIV were evaluated. Results The findings reflect the shifting demographics of HIV in the UK over the past two decades, exemplified by an eightfold increase in tuberculosis at presentation. Despite recording clinical stigmata of HIV (clues) in the notes, the number of missed clues increased, and many clinicians failed to request HIV testing. The median delay between presentation and diagnosis reduced from 5 to 1 day (p<0.001), and mortality dropped from 14% to 4% among patients presenting with acute symptoms. However, there was still a delay of more than 30 days before diagnosis for almost one in five patients. Conclusions Despite some improvement and better awareness, there are still significant delays before hospital doctors consider the diagnosis of HIV for patients in low prevalence areas, even among some patient groups with high risk. Hospitals should consider moving to opt-out routine HIV testing of all medical admission

The cutting movement assessment score (CMAS) qualitative screening tool: application to mitigate anterior cruciate ligament injury risk during cutting

Side-step cutting is an action associated with non-contact anterior cruciate ligament (ACL) injury with a plethora of negative economical, health, and psychological implications. Although ACL injury risk factors are multifactorial, biomechanical and neuromuscular deficits which contribute to “high-risk” and aberrant movement patterns are linked to ACL injury risk due to increasing knee joint loads and potential ACL loading. Importantly, biomechanical and neuromuscular deficits are modifiable; thus, being able to profile and classify athletes as potentially “high-risk” of injury is a crucial process in ACL injury mitigation. The Cutting Movement Assessment Score (CMAS) is a recently validated field-based qualitative screening tool to identify athletes that display high-risk postures associated with increased non-contact ACL injury risk during side-step cutting. This article provides practitioners with a comprehensive and detailed overview regarding the rationale and implementation of the CMAS. Additionally, this review provides guidance on CMAS methodological procedures, CMAS operational definitions, and training recommendations to assist in the development of more effective non-contact ACL injury risk mitigation programmes

Electrocardiogram-gated single-photonemission computed tomography versus cardiacmagnetic resonance imaging for the assessmentof left ventricular volumes and ejection fraction A meta-analysis

AbstractObjectivesThe purpose of this study was to evaluate the accuracy of electrocardiogram (ECG)-gated single-photon emission computed tomography (SPECT) for assessment of left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) compared with the gold standard of cardiac magnetic resonance imaging (MRI).BackgroundSeveral comparisons of ECG-gated SPECT with cardiac MRI have been performed for evaluation of LV volumes and EF, but each has considered few subjects, thus leaving uncertainty about the frequency of discrepancies between the two methods.MethodsWe performed a meta-analysis of data on 164 subjects from nine studies comparing ECG-gated SPECT versus cardiac MRI. Data were pooled in correlation and regression analyses relating ECG-gated SPECT and cardiac MRI measurements. The frequency of discrepancies of at least 30 ml in EDV, 20 ml in ESV and 5% or 10% in EF and concordance for EF ≤40% versus >40% were determined.ResultsThere was an overall excellent correlation between ECG-gated SPECT and cardiac MRI for EDV (r = 0.89), ESV (r = 0.92) and EF (r = 0.87). However, rates of discrepancies for individual subjects were considerable (37% [95% confidence interval {CI}, 26% to 50%] for at least 30 ml in EDV; 35% [95% CI, 23% to 49%] for at least 20 ml in ESV; 52% [95% CI, 37% to 63%] for at least 5% in EF; and 23% [95% CI, 11% to 42%] for at least 10% in EF). The misclassification rate for the 40% EF cutoff was 11%.ConclusionsElectrocardiogram-gated SPECT measurements of EDV, ESV and EF show high correlation with cardiac MRI measurements, but substantial errors may occur in individual patients. Electrocardiogram-gated SPECT offers useful functional information, but cardiac MRI should be used when accurate measurement is required