In the subcritical energy case, local well-posedness is established in the radial energy space for a class of fractional inhomogeneous Choquard equations. The best constant of a Gagliardo-Nirenberg type inequality is obtained. Moreover, a sharp threshold of global existence versus blow-up dichotomy is obtained for mass super-critical and energy subcritical solutions.

Based on three fractional-order complex chaotic systems and two integer-order complex chaotic systems, we propose a novel synchronization scenario of complex compound-combination multi switching anti-synchronization (CCCMSAS), which is first of this kind. The CCCMSAS states are completed between three leader and two follower systems by adopting the nonlinear control method and choosing suitable Lyapunov function on the basis of the complex space. Eventually, two typical examples have served as illustrations to show the validity and maneuverability of the proposed scheme.

In the present report, the structural stability order and electronic properties of the transition metal M@Ge12 (M = Co, Pd, Tc, and Zr) doped germanium cage has been carried out at B3LYP/LANL2DZ ECP level by using spin polarized density functional theory. Initially, we selected five lowest energy structure of neutral TM doped Ge12 cluster with high symmetry point like D6h-symmetric hexagonal prism (HP), the D6d-symmetric hexagonal anti-prism (HAP), D2d-symmetric bi-capped pentagonal prism (BPP), perfect icosahedrons (Ih) and Fullerene type structures. Further, we discussed the electronic origin of stability as well as electronic properties by calculating binding energy, HOMO-LUMO gap, charge transfer mechanism and density of states. We indentified that the Pd, Tc, and Zr encapsulated Ge12 cage with hexagonal prism [HP] structures are minimum energy structures while Co@Ge12 cage prefer HAP structure. The magnitudes of binding energy of the clusters indicate that the doping of 4d transition metal gives most stable structure rather than 3d transition metal Co atom. The large HOMO-LUMO gap and natural bond orbital analysis explain the stability of these clusters using closed shell electronic configuration and the contribution of π and σ bond. Charge transfer mechanism shows that the Tc, Pd and Zr atoms play role as an electron donor in the system whereas Co inclined to accept the electrons. The importances of “d” orbital in localized electrons near the Fermi level are also explained through partial density of states.

Contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can occur when contaminated hands touch the mucosa of the mouth, nose, or eyes. Contaminated hands also facilitate indirect contact transmission of the virus from one fomite surface to another. Consequently, hand hygiene is important to prevent the spread of SARS-CoV-2. However, changing plastic gloves or sanitizing hands every time one touches possibly contaminated fomites will need to be frequently performed and is practically impossible. The Japanese Ministry of Economy, Trade and Industry recently reported that SARS-CoV-2 was deactivated by several diluted surfactants1. Wearing cloth gloves wet with a diluted detergent will prevent infection because the virus gets deactivated within a short period of time on these gloves. The virus gets deactivated within a short period of time on these gloves. Unlike ethanol, detergents are not volatile. Thus, gloves can remain wet and effective for long periods of time. Although the thin diluted detergent could remain on the touched sites, it can be rinsed under running water or wiped afterwards, if necessary. In case of contamination, the detergent remaining on the fomites may also deactivate the virus. To avoid skin contact with the detergent, a plastic glove can be worn underneath the wet cloth glove. This method may be especially effective for healthcare workers who deal with COVID-19 patients or people in the city who handle fomites that many people touch. Additionally, wearing gloves wet with diluted detergent may prevent the user from touching his face, which would further prevent contact transmission.Reference1.         Ministry of Economy, Trade and Industry, Surfactants and Hypochlorous Acid Solution for Removal of Coronavirus from Surfaces (Final Announcement), 26 June 2020, www.meti.go.jp/english/press/2020/0626_004.html.

In the present study, to the evaluate genetic diversity and genetic structure of a mutational rice (B810S) with a color marker from China, the entire sequence of the atpH gene of the chloroplast genome from B810S was amplified by polymerase chain reaction (PCR). The PCR products were sequenced, and sequence variations in the atpH gene were then examined. The entire sequence of the atpH gene was 245 bp in size. Compared it with 810S, whichis the male parent of B810S, the results showed a similarity of 51.22%. There are 2 haplotypes in their atpH gene sequences and the haplotype diversity and nucleotide diversity were 1.0000 and 0.41250, respectively. In addition, phylogenetic analysis of B810S and other normal rice strains was conducted and a phylogenetic tree was constructedusing maximum likelihood (ML) method based on the atpH gene sequence from the chloroplast genome. The results of phylogenetic analysis showed that B810S separated from other rice strains formed an independent branch in the phylogenetic tree, which suggests that B810S with a color marker is a new male sterile rice line. The molecular approach employed in this study provides a foundation for further study of the genetic diversity and structure of rices in different geographical regions of China and other regions in the world.

Functional traits are defined such as traits which affect individual fitness. I argue that the use of the term “functional trait” complicates the progress of the field of trait ecology because all traits are potentially linked to fitness. Obviating the potential link of all traits with fitness is related to dismissing (i) the integration of the phenotype, (ii) the spatio-temporal variation of environmental pressures and (iii) the genotype by environment interaction effect on the phenotype. These conceptual gaps could explain the weak predictive power of many functional ecology studies. I develop here some of the reasons why we should consider that all traits are related to fitness -advocating simultaneously for a change in terminology.

Background and Purpose: Choroidal neovascularization (CNV) is the leading cause of blindness in patients with age-related macular degeneration (AMD). Several studies reported increased levels of vascular endothelial growth factor (VEGF) in retinal pigment epithelium (RPE) from AMD patients. The aim of this study was to investigate the efficacy of the VEGF-A targeted peptide nucleic acid (PNA) drug, POL101 eyedrops, in retinal pigment epithelial cell and laser-induced CNV animal model. Experimental Approach: POL101 is a PNA based-Antisense oligonucleotide (ASO) drug which chemically improved properties for stability and delivery to tissue through nano-grade particle size. To evaluate the efficacy of POL101, we performed to in vitro assay in retinal pigment cell and Fundus fluorescein angiography (FFA), optical coherence tomography (OCT) scanning, and electroretinography (ERG) in CNV-induced lesion. Key Results: First, the efficacy of POL101 was verified in ARPE-19 and HUVEC cells. And then, we confirmed that POL101 eyedrops was significantly decreased CNV area to 54.2% compared with vehicle in laser-induced CNV lesion and reduced VEGF level in choroid tissue without cellular apoptosis. Also, Photocoagulation demonstrated that the average CNV lesion area was reduced and recovered retina function in POL101 group. The mRNA expression of VEGF in mouse retina, intracellular adhesion molecule-1 (ICAM-1), matrix metallopeptidases -2 (MMP-2) and 9 (MMP-9) were significantly reduced in POL101 eyedrops-treated group. Conclusion and Implications: In conclusion, POL101 eyedrops was effectively suppressed VEGF-mediated CNV than aflibercept and has the potential to be effective without side effects and could replace biologics.

One form known as pain modulation is the phenomenon of inhibiting pain using a prior pain stimulus. The term CPM (conditioned pain modulation) is used to describe this phenomenon in humans. Serotonin pathways work as both anti- and pro-nociceptive pathways. Ondansetron is a 5HT3 receptor antagonist routinely used to prevent postoperative nausea and vomiting. Therefore, this study’s objective was to evaluate ondansetron’s effect on mechanical and thermal pain thresholds, as well as CPM in humans. 17 volunteers, who were randomly selected and double-blinded, participated in the research. They received an intravenous solution containing 1 - NaCl at 0.9%, in a volume of 20 mL; 2 - NaCl at 0.9% and 8 mg ondansetron in a volume of 20 mL. Using the quantitative sensory test (QST), we obtained the thresholds for detecting warm and cold; pain thresholds to hot and cold; the pressure pain threshold. CPM was evaluated using the parallel paradigm in which two identical nociceptive test stimuli were induced before and simultaneous to a conditioned nociceptive stimulus. Thirty minutes after the intervention, we redid the tests. We repeated the tests one week later but using the different solution so that each participant was their own control (crossover). We used the Wilcoxon test to compare the variables. Ondansetron, intravenously, improved CPM (p<0.05) and influenced thermal detection thresholds (heat and cold p < 0.05). There is evidence that the results related to the antagonism of the 5HT-3 receptor by ondansetron, occur through inhibition of facilitating descending pathways, improving the CPM.

The capacity and extent to which prey species forage is often dependent on the temporal and/or spatial distribution of predators. Predation risk within a given habitat may differ according to the structure of the landscape and ecological community. Predators may frequent selected habitat patches and it is these areas prey are expected to avoid. Aside from the direct removal of prey individuals through predation, the density of prey populations may be altered as a result of a perceived predator presence and the energetically expensive responses initiated. A predator presence may be perceived upon the detection of sensory environmental cues, including a predator’s pheromones. The Landscape of Fear (LOF) concept proposes the exposure to a real or perceived predation threat may disrupt prey distribution and activity. Such an environment may be referred to as a ‘landscape of fear’, though the interspecies complexes and abiotic factors affecting a predator-prey relationship should not be omitted when quantifying the effects of predation. Here, we summarise the initial and more recent publications addressing the LOF theory, identifying known aspects and potential for future research.

BACKGROUND AND PURPOSE Pharmacological inhibition of indoleamine-2,3-dioxygenase 1 activity is now considered to be a potential therapeutic tool for cancer therapy. However, the anti-cancer efficacy may be the biggest obstacle for the clinical application of current IDO1 inhibitors. EXPERIMENTAL APPROACHES HeLa cell-based IDO1/Kyn assay as well as recombinant IDO1 activity assay were used to determine the IDO1 enzyme activity. Interaction was examined by UV-visible spectra, isothermal titration calorimetry assay, cellular thermal shift assay and co-crystallization. Mouse colon cancer CT26 syngeneic model and azoxymethane/dextran sulfate sodium induced colon carcinogenesis model were employed to confirm the anti-tumor effect in vivo. KEY RESULTS B37 effectively and specifically inhibited IDO1 by targeting its heme-free conformation (apo-IDO1). By competing with heme for binding to apo-IDO1, B37 potently inhibited IDO1 activity with IC50 for 22 pM in the HeLa cell based assay. X-ray co-crystal structures of the inhibitor-enzyme complexes showed that unlike the hIDO1-BMS-986205 complex, the B37-hIDO1 complex displayed stronger hydrophobic interactions, which enhanced its binding affinity measured with ITC. Accordingly, stronger non-covalent interactions including π stacking and hydrogen bonds formed between B37 and apo-hIDO1 underlay the enthalpy-driven force for B37 to bind the enzyme. This binding model endowed B37 potent anti-tumor efficacy in mouse colon cancer CT26 syngeneic model and azoxymethane/dextran sulfate sodium induced colon carcinogenesis model by activating the host’s immune system. Moreover, the combination of B37 with a VEGFR2 inhibitor apatinib synergistically inhibited tumor growth. CONCLUSIONS AND IMPLICATIONS These results revealed that B37 may serve as a candidate for apo-IDO1 inhibition mediated immunotherapy.

Background: Immune checkpoint inhibitors (ICIs) cause a variety of inflammatory eruptions. A better understanding of the rash types, histopathological findings, severity, and clinical courses is necessary for appropriate managements of these eruptions. Only a few reports reviewed ICI-induced inflammatory eruptions with detailed histopathological findings. Methods: In this study, we retrospectively reviewed 42 patients who were histopathologically diagnosed with cutaneous immune-related adverse events (irAEs) following ICI therapy between 2014 and 2020 at the Department of Dermatology of Kyushu University Hospital. Results: Of the 42 patients (24 males, 18 females), maculopapular rash (33/42, 78.6%), erythema multiforme (2/42, 4.8%), lichenoid reaction (3/42, 7.1%), psoriasiform reaction (1/42, 2.4%), bullous pemphigoid (1/42, 2.4%), scleroderma-like reaction (1/42, 2.4%), and Stevens-Johnson syndrome (1/42, 2.4%) were observed. The clinical and histopathological findings of these eruptions were equivalent to typical cases of common drug eruptions. The onset of maculopapular rash was relatively early (more than half of events occurred within 1 month), whereas lichenoid reactions and autoimmune diseases occurred relatively late (4–8 m¬¬onths). With appropriate treatment and/or interruption of ICIs, most rashes were improved (40/42, 95.2%). Conclusions: The ICI-induced inflammatory eruptions shared similar clinical and histopathological features with classical inflammatory eruptions, but a variety of inflammatory eruptions may occur with different degrees of severity. Dermatologists play an important role in providing specialized care for cutaneous immune-related adverse events.

I thank Dres. Alnaes and Helnes Bergen for their stimulating comment on my medical algorithm on the Diagnosis and Treatment of Radiocontrast Media Hypersensitivity.1 In their comment, they raised attention to the possible addition of desensitization to radiocontrast media (RCM) management, which was not depicted in the algorithm.2 I have been well aware of several reports on desensitization and have already discussed them in a previous paper, however commented there that “successful desensitization of RCM has been reported for immediate hypersensitivity reactions to RCM, but it is only used anectodically” and concluded not to include this procedure into the algorithm.3In addition to the two papers on desensitization to RCM cited by Dr. Alaes, also a handful other cases have been published, some of them older. To my knowledge, at least as far as I can access these case reports, in none of these patients a proper allergy diagnosis and management has been performed and in most, if not all of these patients, desensitization probably was unnecessary. In the described cases, skin testing has not been performed or was even negative indicating a higher probability for a non-allergic immediate hypersensitivity reaction (IHR), in the history before desensitization was performed in several cases the RCM was not changed, but the same not tolerated RCM was given again and radiologists in vain relied on premedication to prevent recurrent attacks, and no skin test-negative RCM was identified and used. None of the cases published convinced me of the need for desensitization. Performing the examination with a skin test-negative RCM would with a high probability be successful.4 I would expect the success of desensitization was rather due to changing to a different isoosmolar RCM (and probably not to adding premedication) than the desensitization procedure itself, as alone changing the implicated RCM to another one in one study reduced the risk of recurrent IHR by 67.1% (odds ratio: 0.329; P = 0.001), whereas steroid premedication did not show protective effects.5Our group of European Network on Drug Allergy experts have highlighted that rapid desensitization is a procedure that can be used to provide a temporary tolerance to a first-line drug when no alternative is available.6 This implies for RCM hypersensitivity that using a skin-test-negative RCM for the next examination as an alternative drug is next step and not immediate desensitization. One problem with desensitization is that too many doctors employ it uncritically and without prior proper allergy workup, best with drug provocation test. The high rate of successful desensitizations without prior confirmation of drug hypersensitivity in the literature is in part explained by the fact that many of those patients would not have reacted anyway. I have yet to find convincing evidence to add desensitization as a standard therapeutic option to the RCM management algorithm.Having said this, I am eagerly following up the literature on RCM desensitization with great interest to be prepared, should I encounter an own patient, who would react severely to an alternative skin test-negative RCM after following the algorithm. Until now, colleagues and I have not met such a patient, however, I would seriously consider desensitization as an option in such a situation. Thus, I thank Dres. Alnaes and Helsen Bergen for bringing up that interesting topic for discussion.

The novel coronavirus 2019 (COVID-19) pandemic, which has resulted in nearly 700 thousand deaths, is rapidly spreading across the globe despite drastic public and personal health measures. As showed in Figure 1, the direct attack from SARS-CoV-2 and hyperactivated immune response contribute to the progress and deterioration of COVID-19 infection. Eliminating virus and blocking cytokine are important check-points of COVID-19 therapy. Based on our successful experience in Wuhan and current progress of the therapeutic strategies, several agents targeting immunopathology have displayed marked effects on COVID-19 patients, including interferons, immunoglobulin, and glucocorticoid, etc. Here, we want to review the novel progress of therapy strategies related to immunopathology and share our Wuhan experience with the colleagues in the field by reviewing the underlying the pharmacologic mechanisms of these agents.

To the Editor,Folliculin, a protein expressed in various types of cells including airway epithelial cells, encoded by the FLCN gene, is associated with the 5′ AMP-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1) signaling pathways and, it is thought to alter cell-to-cell adhesion and contribute to the pathogenesis of cystic lung disease in Birt-Hogg-Dubé syndrome (1-5). In addition, the geneFLCN regulates the E-cadherin-LKB1-AMPK axis, which controls lung epithelial cell survival and alveoli size (2). In a recent study, serum folliculin levels were found to be higher in patients with asthma than in healthy control groups and high folliculin levels were associated with increased airway hyperresponsiveness in patients with asthma. In vitro data demonstrated the eosinophil-induced release of folliculin from epithelial cells. These clinical and in vitro observations suggest that folliculin may play some role in the interaction between the eosinophils and airway epithelium (6).To investigate the relationship between clinical characteristics and the level of folliculin in asthmatics, the data of a total of 404 patients with asthma and 94 of controls were enrolled and retrospectively reviewed. To correct for the heavily skewed distributions of the serum folliculin levels, values were log-transformed. Study methods, design and definitions used can be found in the online supplement (Study S1).The proportions of males and smokers were significantly higher among the patients with asthma than in the controls, and the mean serum folliculin level in asthmatics was significantly higher than that in controls (4.80 pg/mL versus 4.13 ng/mL; P < 0.001) (Table S1). As the control group was comprised only of males and a significant difference in smoking history was noted, adjusting for sex and smoking history was performed and significantly higher serum folliculin levels were still observed (P < 0.001). We compared the serum folliculin levels between asthmatics and controls subdivided by sex and smoking status. In these subgroups, the serum folliculin levels were still significantly higher in asthmatics than in the control group (Table S2). ROC curve analysis revealed a significant difference in serum folliculin levels between asthmatics and controls (area under the curve = 0.846, confidence interval [CI] 0.80–0.89, P < 0.001); the optimal cut-off value of serum folliculin level that distinguished asthma patients from controls was 4.31 pg/mL after log-transformation, correlating with 83.91% sensitivity and 77.66% specificity (Figure 1). When we perform ROC curve analysis with only the males, the optimal cut-off value of serum folliculin level was 4.33 pg/mL (Figure S1).We compared folliculin levels among the four groups divided by pre- pre-bronchodilator (BD) predicted FEV1 (%) and found a significant difference in serum folliculin level (P < 0.001, Figure S2). Simple and multiple linear regression analysis was performed to determine the correlation between serum folliculin level and lung function in patients with asthma. In simple linear regression analysis, serum folliculin level were significantly correlated with pre-BD FEV1% predicted (β-coefficient = −4.848, P = 0.013), however significance was only marginal after adjusting for age and sex (β-coefficient = −3.199,P = 0.096) in multiple linear regression analysis. This is because, firstly, there was collinearity of folliculin level and age in our data, and secondly, the rate of smokers (85.22%) among males was higher than among females (14.91%), so it seems that lung function in females is higher.Patients with asthma were divided into two groups using the mean value of the logarithmic serum folliculin levels (4.80 pg/mL). Patients in the high-folliculin group were older at the onset of symptoms, heavier smokers and had a significantly lower lung function. The number of acute exacerbations occurring per year was more frequent in the high folliculin group than in the low folliculin group, but no statistical significance was noted (Table 1). When patients with asthma were divided into the upper quartile of folliculin levels and the lower three quartiles combined, those from the high folliculin group in the upper 25 percentile were found to be older and had lower atopy and lung function than the lower folliculin group with the lower 75 percentile combined. (Table S3). Likewise, we also divided the patients into 4 quantile groups according to serum folliculin levels and identified differences in each group in lung function and age (Table S4).A previous in vitro study showed that human airway epithelial cells (HAECs) exposed to leukotriene E4 and peripheral blood eosinophils released folliculin and interleukin (IL)-8, which resulted in the destruction of the integrity of the epithelial cells. The knockdown of folliculin expression resulted in a decrease in IL-8 release and suppression of epithelial cell activation, which restored the epithelial integrity in HAECs. In their study, folliculin was suggested to be associated with a higher serum transforming growth factor-β1 level, which was associated with worsening of airway inflammation and remodeling (6,7). Consistent with theses result, a higher serum folliculin level in patients with asthma than in healthy controls was also observed in our study, in addition, we showed that an increase in serum folliculin level was associated with a decrease in basal lung function. As folliculin is released from bronchial epithelial cells in response to compressive stress that mimics a bronchospasm (8, 9), we postulate that chronic airway inflammation produces mechanical stress on the airway epithelium, thereby inducing oxidative damage and release of folliculin with changes in the epithelial cell structure. Therefore, we assume that folliculin is associated with the airway inflammation and remodeling pathway in patients with asthma. In our study, serum folliculin level showed no association with serum laboratory variables, suggesting that the increase in folliculin level following mechanical stress is independent of other serum inflammatory markers.In conclusion, our study demonstrates for the first time that serum folliculin concentration is higher in patients with asthma, and it is associated with worse lung function independent to other serum inflammatory markers. Thus, folliculin may represent a novel biomarker related to lower pulmonary function in patients with asthma and further studies are warranted to evaluate the mechanism and test our hypothesis.Keywords: asthma; folliculin; biomarker

Producing recombinant proteins in transgenic plant cell suspension cultures in bioreactors provides controllability, reproducibility, scalability, and low-cost production, although low yields remain the major challenge. The studies on scaling-up to pilot-scale bioreactors, especially in conventional stainless-steel stirred tank bioreactors (STB), to produce recombinant proteins in plant cell suspension cultures are very limited. In this study, we scaled-up the production of rice recombinant butyrylcholinesterase (rrBChE), a complex hydrolase enzyme that can be used to prophylactically and therapeutically treat against organophosphorus nerve agents and pesticide exposure, from metabolically-regulated transgenic rice cell suspension cultures in a 40-L pilot-scale STB. Employing cyclical operation together with a simplified-process operation (controlling gas sparging rate rather than dissolved oxygen and allowing natural sugar depletion) identified in lab-scale (5-L) bioreactor studies, we found consistent maximum total active rrBChE production level of 46-58 µg/g fresh weight in four cycles over 82 days of continuous operation. Additionally, maintaining the overall volumetric oxygen mass transfer coefficient (kLa) in the pilot-scale STB to be equivalent to the lab-scale STB improves the maximum total active rrBChE production level and the maximum volumetric productivity to 85 µg/g fresh weight and 387 µg L-1 day-1, respectively, which are comparable to the lab-scale culture. Here, we demonstrate pilot scale bioreactor performance using a metabolically-regulated transgenic rice cell culture for long-term, reproducible, and sustained production of rrBChE.

Size scaling describes the relative growth rates of different body parts of an organism following a positive correlation. The genetic mechanism of the size scaling and how artificial selection influencing the pattern of size scaling remain unexplored. Here we utilise diverse barley panel with genome-wide single nucleotide polymorphisms (SNPs) and the measurement of their plant height and seeds weight to explore the genetic mechanisms that lead to a correlation of the two traits and the influence of domestication and breeding selection on the size scaling. Plant height and seeds weight are heritable and remain positively correlated in domesticated barley regardless of growth type and habit. Genome-wide association studies revealed eight SNPs to be associated with both traits. Linkage decay analysis suggests that a considerable proportion of genetic markers associated with either plant height or seeds weight are closely linked in the chromosome. Common factor analysis revealed twenty SNPs conferring pleiotropic effect on both traits. Genes with multiple functions in plant growth and development are involved in structuring plant height and seeds weight scaling. Pleiotropy forms the genetic bases of plant height and seeds weight scaling in barley. Our results suggest an alternative hypothesis for seeds weight evolution in domestication that the selection in plant size may have constrained variation in seeds weight. Our findings contribute to the understanding of the genetic basis of size scaling and open a new venue for seeking the underlying mechanism of a grand theory on allometric scaling in plants.

Background: Failed delivery of appropriate shocks against fatal arrhythmias can be the result of low impedance on high-voltage leads. This malfunction might be missed on routine interrogation. We describe a case of 66 year-old male with a high-voltage lead short circuit who was successfully rescued with the use of an overcurrent detection and automatic shocking vector adjustment algorithm. Case Report: A 66-year-old male with severe nonischemic cardiomyopathy was admitted after receiving two shocks from his cardiac resynchronization therapy cardioverter-defibrillator (CRT-D). Interrogation confirmed two consecutive episodes of ventricular fibrillation. For each episode, the initial shock therapy was aborted due to low impedance (<10 ohms) detected on the default shocking configuration: right ventricle to superior vena cava/can. As a result, the device algorithm excluded the superior vena cava coil and immediately delivered a shock of 40 joules between the right ventricular coil and the CRT-D can (Figure 1B). This successfully terminated the ventricular fibrillation. All other lead measurements were normal. Conclusions: High voltage lead malfunctions can lead to failed therapy of life threatening arrhythmias. Malfunctions such as low impedance of high-voltage leads may not be detected on routine interrogation. Fortunately, the overcurrent detection algorithm recognized the low impedance and another shocking configuration was selected and successfully terminated the ventricular arrhythmias. With these algorithms - overcurrent detection and automatic shocking vector adjustment, this patient was successfully rescued. We recommend this feature be included in all modern defibrillators.

Background: Multiple strategies have advocation for power titration and catheter movement during atrial fibrillation (AF) ablation. Comparative favoring evidence regarding the efficacy, logistics, and safety of a higher power, shorter duration (HPSD) ablation strategy compared to a lower power, longer duration (LPLD) ablation strategy is insubstantial. We performed a meta-analysis to compare arrhythmia-free survival, procedure times, and complication rates between the two strategies. Methods: We searched MEDLINE, EMBASE and Cochrane Library from inception to April 2020. We included studies comparing patients underwent HPSD and LPLD strategies for AF ablation and reporting either of the following outcomes: freedom from atrial tachyarrhythmia (AT) including AF and atrial flutter, procedure time, or periprocedural complications. We combined data using the random-effects model to calculate odds ratio (OR) and weight mean difference (WMD) with 95% confidence interval (CI). Results: Nine studies from 2006-2020 involving 2,282 patients were included (1,369 patients underwent HPSD strategy and 853 patients underwent LPLD strategy). HPSD strategy was not associated with an increased freedom from AT at 12-month follow-up (OR= 1.41, 95%CI:0.90-2.21). There was a significant reduction in the HPSD group for total procedure (WMD=49.60, 95%CI:29.76-69.44) and ablation (WMD=17.92, 95%CI:13.63-22.22) times, but not for fluoroscopy time (WMD=1.15, 95%CI:-0.67-2.97). HPSD was not associated with a reduction in esophageal ulcer/atrioesophageal fistula (OR=0.35, 95%CI:0.12-1.06) or pericardial effusion/cardiac tamponade rates (OR=0.96, 95%CI:0.24-3.79). Conclusions: When compared to a LPLD strategy, HPSD strategy does not improve recurrent AT nor reduce periprocedural complication risks. However, a HPSD strategy can significantly reduce total procedure and ablation times.

Background: Representation trends of women, older adults, and ethnic/racial minorities in randomized controlled trials (RCTs) of atrial fibrillation (AF) are uncertain. Methods: We systematically reviewed 134 AF related RCTs (phase II and III) encompassing 149,162 participants using Medline and ClinicalTrials.gov through April 2019 to determine representation trends of women, older patients (≥ 75 years), and ethnic/racial minorities. Weighted data on the prevalence of AF from epidemiological studies were used to compare the representation of the studied groups of interest in AF RCTs to their expected burden of the disease. Results: Only 18.7% of the RCTs reported proportion of older patients, and 12.7% RCTs reported ethnic/racial minorities. In RCTs, proportions of women, Hispanics, Blacks, American Indian/Alaskan patients, Asians, native Hawaiian/Pacific Islanders and non-Whites were 35.2%, 11.9%, 1.2%, 0.2%, 14.2%, 0.05%, and 19.5%, respectively. The corresponding proportions in general population were 35.1%, 5.2%, 5.7%, 0.2%, 2.4%, 0.1%, and 22.5%, respectively. The weighted mean age (SD) across the trials was 65.3 (3.2) years which was less than the corresponding weighted mean age of 71.1 (4.5) years in the comparative epidemiological data. Conclusion: The reporting of older patients and ethnic/racial minorities was poor in RCTs of AF. The representation of women and American Indian/Alaskan natives matched their expected population share of disease burden. Hispanics and Asians were over-represented and Blacks, native Hawaiian/Pacific Islanders and non-Whites were under-represented in RCTs of AF. In nearly all studied RCTs, the reporting of racial demographics did not start until later part of last decade.

Atrial standstill is a rare arrhythmia and several cases of atrial standstill have been described in acute myocarditis, hypertrophic cardiomyopathy or dilated cardiomyopathy. However, left atrial standstill with paroxysmal atrial fibrillation and atrial flutter after pericardial effusion has not been reported. Here, we reported a case with left atrial standstill, paroxysmal atrial fibrillation and atrial flutter who successfully received radiofrequency ablation.

Kurose et al. report on a lower number of gaps in RF-lesions compared to Cryo-lesions as determined by late gadolinium enhancement MRI (LGE-MRI). However, unlike claimed by the authors, there is ample evidence based on LGE-MRI in this context. Most importantly we have specifically compared RF and Cryo lesions in a recent case control study on AF Ablation. In contrast to the results of Kurose et al., our study, despite larger sample size, did not detect a difference in the number of gaps between the two energy sources. While numerous factors may account for the conflicting results, two points should be considered in particular. 1. The time point of LGE-MRI at a mean of 55 days post ablation has never been validated for chronic lesion formation, and is considerably earlier than the validated and well-established 3-months timepoint chosen by most groups. In fact, according to previous reports, gadolinium enhancement at earlier time points may, at least in part, reflect a transient inflammatory response rather than chronic scar formation. 2. The method of Kurose et al. is based on the definition of an area of healthy atrial tissue in each patient as an internal reference. However, it appears almost impossible to define a truly healthy area in the atrium of patients with atrial fibrillation. Thus the method is likely to underestimate ablation-induced fibrosis in patients with advanced disease and/or underlying pathologies and to overestimate it in younger, rather healthy patients.

Absent Left circumflex (LCX) artery is a rare coronary artery anomaly usually detected incidentally on angiographic studies. We present a case of absent LCX diagnosed with Computed Tomography Coronary Angiogram (CTCA) in an 80 year old female presenting with atypical chest pain and normal cardiac parameters.

Background: Fever of unknown origin (FUO) is a diagnostic challenge. Positron emission tomography with computed tomography (PET/CT) is expensive and not widely available. We aimed to evaluate the diagnostic yield of PET/CT in the workup of FUO, and identify the patients for whom this test is most useful. Methods: We reviewed the records of all patients admitted to Sheba Medical Center from 2013 to 2017 who were underwent PET/CT for the evaluation of FUO. Results: Of the 128 patients included, PET/CT was helpful in revealing the cause of FUO in 61 (48%). A final diagnosis was made in 95 (74%) patients. Of the 128 PET/CT tests conducted for the workup of FUO, 61 (48%) had true positive results, 25 (20%) false positive results, 24 (19%) true negative results, and 18 (14%) false negative results. In a multivariate analysis, helpfulness of PET/CT was independently associated with weight loss and low hemoglobin. The calculated test sensitivity was 77%, specificity was 49%, positive predictive value was 71% and negative predictive value was 57%. Conclusion: PET/CT is valuable in the diagnostic workup of FUO. When used as a complementary test, it was helpful in diagnosing almost half the patients, and especially in those with low hemoglobin and weight loss.

Objective: We aimed to evaluate the effect of body mass index (BMI) on oncological and surgical outcomes in patients who underwent radical cystectomy (RC) for bladder cancer (BC). Materials and Methods We retrospectively assessed data from patients who underwent RC with pelvic lymphadenectomy and urinary diversion for BC recorded in the bladder cancer database of the Urooncology Association, Turkey between 2007 and 2019. Patients were stratified into three groups according to the BMI cut-off values recommended by the WHO; Group 1 (normal weight, <25 kg/m2), Group 2 (overweight, 25.0–29.9 kg/m2) and Group 3 (obese, ≥30 kg/m2) Results In all, 494 patients were included, of them 429 (86.8%) were male and 65 (13.2%) were female. The median follow-up was 24 months (12-132 months). At the time of surgery, the number of patients in groups 1, 2 and 3 were 202 (40.9%), 215 (43.5%) and 77 (15.6%), respectively. The mean operation time and time to postoperative oral feeding were longer and major complications were statistically higher in Group 3 compared to Groups 1 and 2 (p=0.019, p<0.001 and p=0.025 respectively). Although the mean overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS) and metastasis-free survival (MFS) was shorter in cases with BMI ≥30 kg/m2 compared with other BMI groups, differences were not statistically significant (p=0.532, p=0.309, p=0.751 and p=0.213 respectively). Conclusion Our study showed that, although major complications are more common in obese patients, the increase in BMI does not reveal a significant negative effect on OS, CSS, RFS, and MFS.