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Purpose To evaluate the feasibility of histogram analysis of T2* value for the detection and grading of degenerative lumbar intervertebral discs (IVDs) and for the characterization of microstructural heterogeneity of discs. Methods Two hundred fourteen lumbar IVDs of 44 subjects with chronic low back pain were examined using sagittal T2WI and axial T2* mapping. All IVDs were classified according to the Pfirrmann grade on T2WI. The correlations between histogram-derived parameters based on T2* values (T2*-HPs) of IVDs and Pfirrmann grade as well as between "red zone ratio" (area of "red zone" on T2* color maps over cross-sectional area of corresponding IVDs) and Pfirrmann grade were calculated. Results The agreement for Pfirrmann grade of IVDs was excellent (κ = 0.808, P less then 0.001). The consistency of the measured T2*-HPs was excellent, with ICCs ranging from 0.828-0.960. Each histogram-derived parameter had a statistically significant relationship with Pfirrmann grade (P less then 0.001). The bright "red zone" on T2* color maps of IVDs displayed as a separated peak relative to the rest of voxels in histograms. The mean area ratio of "red zone" over the corresponding IVD was 9.234% ± 6.680 and ranged from 0.517% to 30.598%. The "red zone ratio" was highly related to Pfirrmann grade (r = - 0.732, P less then 0.001). Conclusion Histogram analysis of T2* value is an effective tool for the detection and grading of degenerative IVDs. Identification of the "red zone" may provide new breakthroughs in the study of disc degeneration initiation and generate new hypotheses in anatomical and histological studies of IVDs.Background The photon sensitivity and spatial resolution of single-photon emission-computed tomography (SPECT) has been significantly improved by solid-state camera systems using cadmium zinc telluride (CZT) detectors. While the diagnostic accuracy of these systems is well established, there is little evidence directly comparing the prognostic utility to conventional NaI cameras. Methods and results Retrospective analysis of patients undergoing SPECT between 2008 and 2012. Visual SPECT assessment was performed utilizing the 17-segment model to determine summed stress scores (SSS). We identified 12,830 consecutive patients, mean age 63.2 ± 13.7 and 56.1% male, 5072 of whom underwent CZT and 7758 NaI imaging. During a median follow-up duration of 7.0 years (IQR 5.5-8.2), a total of 2788 (21.7%) patients died. Compared to SSS 0, minimal perfusion abnormality (SSS 1-3) was associated with increased all-cause mortality with CZT camera (adjusted HR 1.32, P = .017) and NaI camera (adjusted HR 1.29, P = .001, interaction P = .803). Increasing stress abnormality was associated with a similar increase in risk with CZT or NaI imaging (interaction P > .500). In a propensity matched analysis, patients with normal perfusion stress perfusion assessed with a CZT was associated with decreased mortality compared to normal perfusion assessed by a NaI camera system (hazard ratio .88, 95% CI .78-.99, P = .040). Conclusions Increasing stress perfusion abnormality was associated with similar increase in all-cause mortality with CZT or NaI cameras. CZT and NaI camera systems provide similar risk stratification, however, normal myocardial perfusion may be associated with a more benign prognosis when assessed with a CZT camera system.Objectives To correlate contrast-enhanced ultrasound (CEUS) features with pathological prognostic factors of breast invasive ductal carcinomas (IDCs). Methods 169 patients who were admitted to our hospital with confirmed IDCs diagnosed between August 2017 and June 2019 were selected. CEUS indicators included the time of contrast agent entered the lesion, the degree of enhancement, the boundary of the lesion, whether there was perfusion defect and nourishing blood vessels, and etc. These parameters correlated with traditional prognostic factors (tumour size, histological grade, axillary lymph node status) and immunohistochemical biomarkers (ER, PR, c-erbB-2, Ki-67, and TOPO-II). Results Perfusion defects after enhancement were predictive factors of PR negative expression (r = - 0.318, OR = 0.239) and TOPO-II overexpression (r = 0.284, OR = 3.577). Centripetal enhancement was negatively correlated with ER expression (r = - 0.350, OR = 0.246). The lesions with a larger range after enhancement than the conventional ultrasound had a higher histological grade (r = 0.215). Perfusion defects were positively correlated with lymph node metastasis (r = 0.221) and negatively correlated with the expression of ER and PR (r = - 0.342, r = - 0.318). Conclusions Contrast-enhanced ultrasound features of IDCs have a certain correlation with pathological prognostic factors, which is conducive in assessing the prognosis of these patients.Little is known about the permanent pacemaker implantation rate and predictors of permanent pacemaker implantation in patients admitted for complete atrioventricular block (cAVB). The present study was a retrospective analysis based on a multicenter cohort of 797 patients with cAVB (mean age 79.6 ± 10.7 years; males 48.4%) registered with the Tokyo Cardiovascular Care Unit Network multicenter registry between 2013 and 2016. Secondary cAVB due to acute coronary syndrome was excluded. The permanent pacemaker implantation rate was 82.9%. Multivariable logistic regression analysis revealed that systolic blood pressure (SBP) > 140 mmHg [odds ratio (OR) 2.10; 95% confidence interval (CI) 1.38-3.22; P less then 0.001], male gender (OR 1.63; 95% CI 1.07-2.49; P = 0.023), and left ventricular ejection fraction (LVEF) ≥ 50% (OR 2.19; 95% CI 1.16-2.06; P = 0.016) were predictors of permanent pacemaker implantation while pre-admission β-blocker use (OR 0.28; 95% CI 0.17-0.47; P less then 0.001) was associated with a lower risk of permanent pacemaker implantation. Reversible cAVB was not rare in patients admitted for cAVB. Data on SBP on admission, gender, LVEF, and pre-admission β-blocker use may be important for assessing the requirement for permanent pacemaker implantation in the emergency care setting.Protegrin-1 (PG-1), an 18-residue β-hairpin stabilized by two disulfide bonds, is a member of a family of powerful antimicrobial peptides which are believed to act through membrane permeabilization. Here we used a combination of experimental and computational approaches to characterize possible structural arrangements of PG-1 in lipid bilayers mimicking bacterial membranes. We have measured the dose-response function of the PG-1-induced leakage of markers of various sizes from vesicles and found it to be consistent with the formation of pores of two different sizes. The first one allows the release of small dyes and occurs at peptidelipid ratios less then 0.006. Above this ratio, larger pores are observed through which the smallest of dextrans FD4 can be released. In parallel with pore formation, we observe a general large-scale destabilization of vesicles which is probably related to complete rupture of some vesicles. The population of vesicles that are completely ruptured depends linearly on PG-1lipid ratio. Neither pore size, nor vesicle rupture are influenced by the formation of disulfide bonds. Previous computational work on oxidized protegrin is complemented here by all-atom MD simulations of PG-1 with reduced disulfide bonds both in solution (monomer) and in a bilayer (dimer and octamer). The simulations provide molecular insights into the influence of disulfide bonds on peptide conformation, aggregation, and oligomeric structure.The first-line therapy of metastatic bladder cancer (urothelial carcinoma, UC) depends on whether a patient is cisplatin-fit or not. Cisplatin-fit patients should be treated with the standard chemotherapy protocol GC (gemcitabine/cisplatin) or alternatively MVAC (methotrexate/vinblastine/doxorubicin/cisplatin). The optimal first-line therapy for cisplatin-unfit patients remains unclear due to the lack of high level of evidence. Plerixafor nmr One criterion for selecting therapy can be the PD-L1 (programmed cell death ligand 1) status of the tumor. The PD-L1-negative patients (PD-L1 less then 5% for atezolizumab and combined positivity score [CPS] less then 10 for pembrolizumab) seem to have a greater benefit from the combination chemotherapy GCa (carboplatin/gemcitabine). The PD-L1-positive patients (PD-L1 ≥5% or CPS ≥10) on the other hand may have a greater benefit from and a longer response to the two immune checkpoint inhibitors that are currently approved for this indication, namely atezolizumab and pembrolizumab. Two phase 3 trials that compare head-to-head immunotherapy alone or in combination with chemotherapy vs. chemotherapy alone may help to define the optimal first-line therapy for metastatic UC. Preliminary data from one of these studies indicate an advantage for the combination of immunotherapy with chemotherapy in all subgroups.Jessica Flanigan argues that individuals have the right to self-medicate. Flanigan presents two arguments in defense of this right. The first she calls the epistemic argument and the second she calls the rights-based argument. I argue that the right to self-medicate hangs and falls on the rights-based argument. This is because for the epistemic argument to be sound agents must be assumed to be epistemically competent. But, Flanigan's argument for a constitutionally mandated right to self-medicate models agents as epistemically incompetent. For Flanigan, agents are different at the pharmacy than they are at the polls. I identify this behavioral asymmetry and advocate a symmetric and realistic behavioral postulate for both arguments. The result, however, is that the success of the epistemic argument becomes contingent which fails to justify a constitutionally mandated right. I proceed to raise skepticism about the rights-based argument as well. I conclude that there is reason to be skeptical that these arguments can justify a constitutionally mandated right to self-medicate. Ultimately, a bottom-up approach to pharmaceutical ethics is preferable.Background This review introduces various techniques for implantation of a total knee endoprosthesis and scrutinizes the "mechanical alignment" of a total knee endoprosthesis, whereby the various alignment concepts are examined. In particular, kinematic alignment, in terms of its significance, the individual steps of the implantation technique and the data collected, will be examined in more detail. Methods Improvement in the clinical results after implantation of a total knee endoprosthesis can be achieved by a personalized, individualized, physiological implantation that respects the unique anatomical characteristics of each patient. In recent years, many alternative alignment techniques have been developed, some of them showing promising approaches. Results The kinematic implantation technique can be performed reliably and inexpensively, and shows good biomechanical results. Although the first clinical results are encouraging, further studies should be carried out to determine the limits of optimal alignment.Purpose Peritoneal tears occurring during TAPP and TEP are common, and can cause difficulty in continuing surgery, or, if left open can cause postoperative complications. A number of techniques to close the tear in the peritoneum have been described. These techniques are difficult and add to the operating time, and may not be successful in closing the opening in the peritoneum. We describe a simple, effective, fast technique of repairing these tears using the bipolar diathermy. Method We have used bipolar diathermy to seal inadvertent peritoneal tears occurring during TAPP/TEP repairs. This method of sealing the peritoneum has been used by us since 2015. We decided to review our results of sealing the tears in the peritoneum at TAPP/TEP from 01 Jan 2017 to 31 Dec 2019. Results A total of 152 laparoscopic inguinal hernia repair (TAPP/TEP) procedures were done by the authors from 01 January 2017 to 31 December 2019, and of these, 101 cases had some degree of peritoneal tear. All peritoneal tears were very simply sealed using bipolar diathermy.

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