Loop effects and non-decoupling property of SUSY QCD in gb→tH−g b\to tH^{-}

One-loop SUSY QCD radiative correction to $gb \to tH^{-}$ cross section is calculated in the Minimal Supersymmetric Standard Model. We found that SUSY QCD is non-decoupling if the gluino mass and the parameter $\mu$, $A_t$ or $A_b$ are at the same order and get large. The non-decoupling contribution can be enhanced by large $\tan\beta$ and therefore large corrections to the hadronic production rates at the Tevatron and LHC are expected in the large $\tan\beta$ limit. The fundamental reason for such non-decoupling behavior is found to be some couplings in the loops being proportional to SUSY mass parameters.Comment: 15 pages, 5 PS figures. A proof of non-decouplings of SUSY-QCD, Comments on corresponding QCD correction and references adde

Higgs-boson production associated with a bottom quark at hadron colliders with SUSY-QCD corrections

The Higgs boson production p p (p\bar p) -> b h +X via b g -> b h at the LHC, which may be an important channel for testing the bottom quark Yukawa coupling, is subject to large supersymmetric quantum corrections. In this work the one-loop SUSY-QCD corrections to this process are evaluated and are found to be quite sizable in some parameter space. We also study the behavior of the corrections in the limit of heavy SUSY masses and find the remnant effects of SUSY-QCD. These remnant effects, which are left over in the Higgs sector by the heavy sparticles, are found to be so sizable (for a light CP-odd Higgs and large \tan\beta) that they might be observable in the future LHC experiment. The exploration of such remnant effects is important for probing SUSY, especially in case that the sparticles are too heavy (above TeV) to be directly discovered at the LHC.Comment: Results for the Tevatron adde

Anti-drug Antibody Responses Impair Prophylaxis Mediated by AAV-Delivered HIV-1 Broadly Neutralizing Antibodies

Adeno-associated virus (AAV) delivery of potent and broadly neutralizing antibodies (bNAbs is a promising approach for the prevention of HIV-1 infection. The immunoglobulin G (IgG)1 subtype is usually selected for this application, because it efficiently mediates antibody effector functions and has a somewhat longer half-life. However, the use of IgG1-Fc has been associated with the generation of anti-drug antibodies (ADAs) that correlate with loss of antibody expression. In contrast, we have shown that expression of the antibody-like molecule eCD4-Ig bearing a rhesus IgG2-Fc domain showed reduced immunogenicity and completely protected rhesus macaques from simian-HIV (SHIV)-AD8 challenges. To directly compare the performance of the IgG1-Fc and the IgG2-Fc domains in a prophylactic setting, we compared AAV1 expression of rhesus IgG1 and IgG2 forms of four anti-HIV bNAbs: 3BNC117, NIH45-46, 10-1074, and PGT121. Interestingly, IgG2-isotyped bNAbs elicited significantly lower ADA than their IgG1 counterparts. We also observed significant protection from two SHIV-AD8 challenges in macaques expressing IgG2-isotyped bNAbs, but not from those expressing IgG1. Our data suggest that monoclonal antibodies isotyped with IgG2-Fc domains are less immunogenic than their IgG1 counterparts, and they highlight ADAs as a key barrier to the use of AAV1-expressed bNAbs

The Tpeak – Tend interval as an electrocardiographic risk marker of arrhythmic and mortality outcomes: a systematic review and meta-analysis

Background: The Tpeak – Tend interval, an electrocardiographic marker reflecting transmural dispersion of repolarization, has been used to predict ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death (SCD) in different clinical settings. Objective: This systematic review and meta-analysis evaluated the significance of Tpeak – Tend interval in predicting arrhythmic and/or mortality endpoints. Methods: PubMed, Embase, Cochrane Library and CINAHL Plus databases were searched through 30th November 2016.Results: Of the 854 studies identified initially, 33 observational studies involving 155856 patients were included in our meta-analysis. Tpeak – Tend interval prolongation (mean cut-off: 103.3 ± 17.4 ms) was a significant predictor of the arrhythmic or mortality outcomes (odds ratio (OR): 1.14, 95% CI: 1.11 to 1.17, p < 0.001). When different end-points were analyzed, the ORs are as follows: VT/VF (1.10, 95% CI: 1.06 to 1.13, p < 0.0001), SCD (1.27, 95% CI 1.17 to 1.39, p < 0.0001), cardiovascular death (1.40, 95% CI 1.19 to 1.64, p < 0.0001), and all-cause mortality (4.56, 95% CI 0.62 to 33.68, p < 0.0001). Subgroup analysis for each disease revealed that the risk of VT/VF or death was highest for Brugada syndrome (OR: 5.68, 95% CI: 1.57 to 20.53, p < 0.01), followed by hypertension (OR: 1.52, 95% CI: 1.26 to 1.85, p < .0001), heart failure (OR: 1.07, 95% CI: 1.04 to 1.11, p < .0001) and ischemic heart disease (OR: 1.06, 95% CI: 1.02 to 1.10, p = 0.001). In the general population, a prolonged Tpeak – Tend interval also predicted arrhythmic or mortality outcomes (OR: 1.59, 95% CI: 1.21 to 2.09, p < 0.001).Conclusion: The Tpeak – Tend interval is useful risk stratification tool in different diseases and in the general population

Percutaneous Coronary Intervention Versus Medical Therapy for Chronic Total Occlusion of Coronary Arteries:A Systematic Review and Meta-Analysis

PURPOSE OF REVIEW: Chronic total occlusion (CTO) of the coronary arteries is a significant clinical problem and has traditionally been treated by medical therapy or coronary artery bypass grafting. Recent studies have examined percutaneous coronary intervention (PCI) as an alternative option. RECENT FINDINGS: This systematic review and meta-analysis compared medical therapy to PCI for treating CTOs. PubMed and Embase were searched from their inception to March 2019 for studies that compared medical therapy and PCI for clinical outcomes in patients with CTOs. Quality of the included studies was assessed by Newcastle-Ottawa scale. The results were pooled by DerSimonian and Laird random- or fixed-effect models as appropriate. Heterogeneity between studies and publication bias was evaluated by I2 index and Egger's regression, respectively. Of the 703 entries screened, 17 studies were included in the final analysis. This comprised 11,493 participants. Compared to PCI, medical therapy including randomized and observational studies was significantly associated with higher risk of all-cause mortality (risk ratio (RR) 1.99, 95% CI 1.38-2.86), cardiac mortality (RR 2.36 (1.97-2.84)), and major adverse cardiac event (RR 1.25 (1.03-1.51)). However, no difference in the rate of myocardial infarction and repeat revascularization procedures was observed between the two groups. Univariate meta-regression demonstrated multiple covariates as independent moderating factors for myocardial infarction and repeat revascularization but not cardiac death and all-cause mortality. However, when only randomized studies were included, there was no difference in overall mortality or cardiac death. In CTO, when considering randomized and observational studies, medical therapy might be associated with a higher risk of mortality and myocardial infarction compared to PCI treatment

Immediate and short-term pain relief by acute sciatic nerve press: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Despite much research, an immediately available, instantly effective and harmless pain relief technique has not been discovered. This study describes a new manipulation: a "2-minute sciatic nerve press", for rapid short-term relief of pain brought on by various dental and renal diseases.</p> <p>Methods</p> <p>This randomized, single-blind, placebo-controlled trial ran in three hospitals in Anhui Province, China, with an enrollment of 66 out of 111 solicited patients aged 16 to 74 years. Patients were recruited sequentially, by specific participating physicians at their clinic visits to three independent hospitals. The diseases in enrolled dental patients included dental caries, periodontal diseases and dental trauma. Renal diseases in recruits included kidney infections, stones and some other conditions. Patients were randomly assigned to receive the "2-minute sciatic nerve press" or the "placebo press". For the "2-minute sciatic nerve press", pressure was applied simultaneously to the sciatic nerves at the back of the thighs, using the fists while patients lay prone. For the "placebo press", pressure was applied simultaneously to a parallel spot on the front of the thighs, using the fists while patients lay supine. Each fist applied a pressure of 11 to 20 kg for 2 minutes, after which, patients arose to rate pain.</p> <p>Results</p> <p>The "2-minute sciatic nerve press" produced greater pain relief than the "placebo press". Within the first 10 minutes after sciatic pressure, immediate pain relief ratings averaged 66.4% (p < 0.001) for the dental patients, versus pain relief of 20% for the placebo press, and, 52.2% (p < 0.01) for the renal patients, versus relief of 14% for the placebo press, in median. The method worked excellently for dental caries and periodontal diseases, but poorly for dental trauma. Forty percent of renal patients with renal colic did not report any pain relief after the treatment.</p> <p>Conclusion</p> <p>Two minutes of pressure on both sciatic nerves can produce immediate significant conduction analgesia, providing a convenient, safe and powerful way to overcome clinical pain brought on by dental diseases and renal diseases for short term purposes.</p> <p>Trial registration</p> <p>ACTR 12606000439549</p

Immunization with Radiation-Attenuated Plasmodium berghei Sporozoites Induces Liver cCD8α+DC that Activate CD8+T Cells against Liver-Stage Malaria

Immunization with radiation (γ)-attenuated Plasmodia sporozoites (γ-spz) confers sterile and long-lasting immunity against malaria liver-stage infection. In the P. berghei γ-spz model, protection is linked to liver CD8+ T cells that express an effector/memory (TEM) phenotype, (CD44hiCD45RBloCD62Llo ), and produce IFN-γ. However, neither the antigen presenting cells (APC) that activate these CD8+ TEM cells nor the site of their induction have been fully investigated. Because conventional (c)CD8α+ DC (a subset of CD11c+ DC) are considered the major inducers of CD8+ T cells, in this study we focused primarily on cCD8α+ DC from livers of mice immunized with Pb γ-spz and asked whether the cCD8α+ DC might be involved in the activation of CD8+ TEM cells. We demonstrate that multiple exposures of mice to Pb γ-spz lead to a progressive and nearly concurrent accumulation in the liver but not the spleen of both the CD11c+NK1.1− DC and CD8+ TEM cells. Upon adoptive transfer, liver CD11c+NK1.1− DC from Pb γ-spz-immunized mice induced protective immunity against sporozoite challenge. Moreover, in an in vitro system, liver cCD8α+ DC induced naïve CD8+ T cells to express the CD8+ TEM phenotype and to secrete IFN-γ. The in vitro induction of functional CD8+ TEM cells by cCD8α+ DC was inhibited by anti-MHC class I and anti-IL-12 mAbs. These data suggest that liver cCD8α+ DC present liver-stage antigens to activate CD8+ TEM cells, the pre-eminent effectors against pre-erythrocytic malaria. These results provide important implications towards a design of anti-malaria vaccines

Higher Dispersion Measures of Conduction and Repolarization in Type 1 Compared to Non-type 1 Brugada Syndrome Patients: An Electrocardiographic Study From a Single Center

Background: Brugada syndrome (BrS) is a cardiac ion channelopathy that predisposes affected individuals to sudden cardiac death (SCD). Type 1 BrS is thought to take a more malignant clinical course than non-type 1 BrS. We hypothesized that the degrees of abnormal repolarization and conduction are greater in type 1 subjects and these differences can be detected by electrocardiography (ECG).Methods: Electrocardiographic data from spontaneous type 1 and non-type 1 BrS patients were analyzed. ECG parameters were measured from leads V1 to V3. Values were expressed as median [lower quartile-upper quartile] and compared using Kruskal-Wallis ANOVA.Results: Compared to non-type 1 BrS patients (n = 29), patients with spontaneous type 1 patterns (n = 22) showed similar (P &gt; 0.05) heart rate (73 [64–77] vs. 68 [62–80] bpm), QRS duration (136 [124–161] vs. 127 [117–144] ms), uncorrected QT (418 [393–443] vs. 402 [386–424] ms) and corrected QT intervals (457 [414–474] vs. 430 [417–457] ms), JTpeak intervals (174 [144–183] vs. 174 [150–188] ms), Tpeak− Tend intervals (101 [93–120] vs. 99 [90–105] ms), Tpeak− Tend/QT ratios (0.25 [0.23–0.27] vs. 0.24 [0.22–0.27]), Tpeak− Tend/QRS (0.77 [0.62–0.87] vs. 0.77 [0.69–0.86]), Tpeak− Tend/(QRS × QT) (0.00074 [0.00034–0.00096] vs. 0.00073 [0.00048–0.00012] ms−1), index of Cardiac Electrophysiological Balance (iCEB, QT/QRS, marker of wavelength: 3.14 [2.56–3.35] vs. 3.21 [2.85–3.46]) and corrected iCEB (QTc/QRS: 3.25 [2.91–3.73] vs. 3.49 [2.99–3.78]). Higher QRS dispersion was seen in type 1 subjects (QRSd: 34 [24–66] vs. 24 [12–34] ms) but QT dispersion (QTd: 48 [39–71] vs. 43 [22–94] ms), QTc dispersion (QTcd: 52 [41–79] vs. 46 [23–104] ms), JTpeak dispersion (44 [23–62] vs. 45 [30–62] ms), Tpeak− Tend dispersion (28 [15–34] vs. 29 [22–53] ms) or Tpeak− Tend/QT dispersion (0.06 [0.03–0.08] vs. 0.08 [0.04–0.12]) did not differ between the two groups. Type 1 subjects showed higher (QRSd × Tpeak− Tend)/QRS (25 [19–44] vs. 19 [9–30] ms) but similar iCEB dispersion (0.83 [0.49–1.14] vs. 0.61 [0.34–0.92]) and iCEBc dispersion (0.93 [0.51–1.15] vs. 0.65 [0.39–0.96]).Conclusion: Higher levels of dispersion in conduction and repolarization are found in type 1 than non-type 1 BrS patients, potentially explaining the higher incidence of ventricular arrhythmias in the former group

Gene Therapy for Fibrodysplasia Ossificans Progressiva: Feasibility and Obstacles

Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease, in which soft connective tissue is converted into heterotopic bone through an endochondral ossification process. Patients succumb early as they gradually become trapped in a second skeleton of heterotopic bone. Although the underlying genetic defect is long known, the inherent complexity of the disease has hindered the discovery of effective preventions and treatments. New developments in the gene therapy field have motivated its consideration as an attractive therapeutic option for FOP. However, the immune system\u27s role in FOP activation and the as-yet unknown primary causative cell, are crucial issues which must be taken into account in the therapy design. While gene therapy offers a potential therapeutic solution, more knowledge about FOP is needed to enable its optimal and safe application