Foraging by consumers acts as a biotic filtering mechanism for biodiversity at the trophic level of resources. Variation in foraging behaviour have cascading effects on abundance, diversity, and functional trait composition of the community of resource species. Here we propose diversity at giving-up density (DivGUD), when foragers quit exploring a patch, as a novel concept and simple measure to quantify these effects at multiple spatial scales. In experimental landscapes, patch residency of wild rodents decreased local α-DivGUD (via elevated mortality of species with large seeds) and regional γ-DivGUD, while dissimilarity among patches in a landscape (ß-DivGUD) increased. Thus, DivGUD provides a framework linking theories of adaptive foraging behaviour with community ecology allowing to investigate cascading indirect predation effects across multiple trophic levels e.g. the ecology-of-fear framework; feedbacks between functional trait composition of resource species and consumer communities; and effects of inter-individual differences among foragers on the biodiversity of resource communities.
The paper discusses various partial solutions used for estimating fatigue life under variable amplitude multiaxial loading in the high-cycle fatigue domain. The concurring effects are treated, and their proposed solutions are commented upon. The major focus is on the categories of the phase shift effect and of cycle counting, and on the scope and quality of data, which support discussed theories. Results of own new experimental data set on specimens from S355 steel are provided. Fatigue life estimates for McDiarmid and Findley multiaxial methods and for two different methods of load path decomposition to cycles are shown to highlight some of the points open for discussion. It is concluded that the available experimental data are not sufficient to substantiate a clear decision to follow a definite algorithm.
The Heteroduplex mobility assay (HMA) has proven to be a robust tool for the detection of genetic variation. Here, we describe a simple and rapid application of the HMA by microfluidic capillary electrophoresis, for phylogenetics and population genetic analyses (pgHMA). We show how commonly applied techniques in phylogenetics and population genetics have equivalents with pgHMA: phylogenetic reconstruction with bootstrapping, skyline plots, and mismatch distribution analysis. We assess the performance and accuracy of pgHMA by comparing the results obtained against those obtained using standard methods of analyses applied to sequencing data. The resulting comparisons demonstrate that: (1) there is a significant linear relationship (R = 0.992) between heteroduplex mobility and genetic distance; (2) phylogenetic trees obtained by HMA and nucleotide sequences present nearly identical topologies; (3) clades with high pgHMA parametric bootstrap support also have high bootstrap support on nucleotide phylogenies; (4) skyline plots estimated from the UPGMA trees of HMA and Bayesian trees of nucleotide data reveal similar trends, especially for the median trend estimate of effective population size; and (5) optimized mismatch distributions of HMA are closely fitted to the mismatch distributions of nucleotide sequences. In summary, pgHMA is an easily-applied method for approximating phylogenetic diversity and population trends. KEYWORDS: bootstrap, heteroduplex mobility assay, mismatch distribution, phylogenetics, skyline plot
A 48-year -old male patient with Type 2 diabetes mellitus(T2D) on insulin replacement therapy, glipizide and Dapagliflozin admitted for generalized weakness found him in euglycemic diabetic ketoacidosis which means normal or near normal glucose levels with high anion gap metabolic acidosis recovered on insulin drip per DKA protocol.
Electrogram-guided Endomyocardial Biopsy Yield in Patients with Suspected Cardiac SarcoidosisAbbas Hoteit MD, Marwan M. Refaat, MDDivision of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, LebanonRunning Title: Electrogram-guided Biopsy in Cardiac SarcoidosisWords: 819 (excluding the title page and references)Keywords: Cardiac Sarcoidosis, Heart Diseases, Cardiovascular Diseases, Cardiac ArrhythmiasFunding: NoneDisclosures: NoneCorresponding Author:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FASE, FESC, FACP, FAAMAAssociate Professor of MedicineDirector, Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyDepartment of Biochemistry and Molecular GeneticsAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonUS Address: 3 Dag Hammarskjold Plaza, 8th Floor, New York, NY 10017, USAOffice: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Sarcoidosis is a multisystem disease that is characterized by T-cell mediated formation of noncaseating granulomas in affected organs. The disease commonly might involve hilar lymphadenopathy, lungs, liver, spleen, heart, and other organs. The natural course and prognosis of the disease generally depends on the extent of the disease and the organs affected where spontaneous remission occurs in around two-thirds of patient.1 Involvement of the heart is recognized in around 30% of patients and is associated with poor prognosis.2 The presentation of patients with cardiac sarcoidosis varies significantly; it can range from mild to severe disease such as heart failure and fatal arrhythmias. Patients with cardiomyopathies might require implantable cardiac defibrillators or cardiac resynchronization therapy for sudden death prevention.3,4 Cardiac sarcoidosis can either present alongside extracardiac manifestations or isolated.5Diagnosis of cardiac sarcoidosis presents a particular challenge since there is no gold standard diagnostic tool and the presentation is variable.6 There are no disease-specific biomarkers that can reliably be used for diagnosis. Clinicians typically rely on current published guidelines for diagnostic criteria of cardiac sarcoidosis such as those of Heart Rhythm Society (HRS) and the Japanese Ministry of Health and Welfare (JMHW). The revised JMHW criteria provide a diagnosis either through histological evidence on biopsy or through the fulfillment of major and minor criteria that do not include cardiac PET whereas the HRS criteria provide either a definite pathway for diagnosis through histology or a clinical pathway for diagnosis of probable cardiac sarcoidosis that includes both cardiac PET and CMR as criteria.7,8 A definitive diagnosis of cardiac sarcoidosis can be obtained if endomyocardial biopsy can show noncaseating granulomas in the context of suspected cardiac sarcoidosis and other granulomatous diseases are excluded. However, endomyocardial biopsy has a low sensitivity of 20-30% since it is limited by several factors such as technique, sampling, patchy distribution of granulomas, location of lesions, and stage of the disease at the time of biopsy.5 Areas of inflammation and scarring typically show abnormal electrogram morphology, hence, it is thought that electrogram guidance may help in increasing the yield of endomyocardial biopsies. Electrogram guidance would potentially help avoiding normal myocardium during biopsy leading to increased yield and sensitivity.9In their study, Ezzedine et al. assessed the diagnostic yield of electrogram-guided endomyocardial biopsy and investigated association between positive endomyocardial biopsy and prognosis in patients with suspected cardiac sarcoidosis.10 This retrospective observational study included seventy-nine patients between 2011 and 2019 who had suspected cardiac sarcoidosis based on clinical presentation and findings on late gadolinium-enhancement cardiac magnetic resonance and/or cardiac positron emission tomography-computed tomography with N-13 NH3 perfusion imaging and F-18 fluorodeoxyglucose. Biopsy was done in patients suspicious of cardiac sarcoidosis in patients without extracardiac sarcoidosis or those with extracardiac disease but atypical/equivocal findings of cardiac sarcoidosis on imaging and meeting criteria in HRS guidelines as per the routine practice in Mayo Clinic. Mapping of the heart was performed prior to biopsy with partial guidance based on pre-procedural cardiac imaging. In patients with no identifiable abnormalities on electrogram, biopsies were taken from areas corresponding to those with abnormalities on pre-procedural imaging. Collected specimens were processed according to protocol and assessed by a blinded specialist. These specimens were considered positive if there was a combination of non-necrotizing granulomas, interstitial fibrosis, and scatted eosinophils. The study showed that electrogram-guided endomyocardial biopsy was associated with an adequate negative predictive value but low positive predictive value. A diagnosis of probable cardiac sarcoidosis can be made in patients with extracardiac manifestations according to established guidelines whereas in patients with suspected isolated cardiac sarcoidosis this is more difficult and as such biopsies play a more major role here. This study showed that, when guided by electrograms, endomyocardial biopsies had a higher diagnostic yield (41%) than that established in literature around 20-25%. Utilizing both abnormalities seen on both electrograms and on CMR or PET showed the highest diagnostic yield in endomyocardial biopsies. This acts as an important point of consideration for further research because accurate and timely diagnosis is paramount due to the diagnostics challenges and poor prognosis seen in cardiac sarcoidosis.10Previous evidence had shown that a positive endomyocardial biopsy for sarcoidosis was associated with poor prognosis.11However, LVAD and transplantation-free survival was found to be similar regardless of status of endomyocardial biopsy in this study.10 The authors explained that this could be explained by earlier detection of disease, differences in treatment, or more subtle detection of areas of involvement through electrograms. This study was well conducted but has been limited by its nature of being a retrospective observational study. Also, mapping was mostly limited to the right ventricle which may have underestimated the diagnostic yield of biopsies. This study represents the management done in a single tertiary care center which may not represent the same practice in other institutions with different facilities. Further multicenter and prospective studies are warranted to corroborate the data here and assess diagnostic and therapeutic modalities and long-term outcomes in patients.ReferencesStatement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med Aug 1999 ;160(2):736-55.Sekhri V, Sanal S, Delorenzo LJ, Aronow WS, Maguire GP. Cardiac sarcoidosis: a comprehensive review. Arch Med Sci Aug 2011; 7(4):546-54.AlJaroudi WA, Refaat MM, Habib RH, Al-Shaar L, Singh M, Gutmann R, Bloom HL, Dudley SC, Ellinor PT, Saba SF, Shalaby AA, Weiss R, McNamara DM, Halder I, London B; for the Genetic Risk Assessment of Defibrillator Events (GRADE) Investigators. Effect of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock: Insights from the GRADE Multicenter Registry. Am J Cardiol Apr 2015; 115 (7): 115(7):924-31.Refaat M, Mansour M, Singh JP, Ruskin JN, Heist EK: Electrocardiographic Characteristics in Right Ventricular Versus Biventricular Pacing in Patients With Paced Right Bundle Branch Block QRS Pattern. J Electrocardiol Mar-Apr 2011; 44 (2): 289-95.Isobe M, Tezuka D. Isolated cardiac sarcoidosis: Clinical characteristics, diagnosis and treatment. Int J Cardiol Mar 2015; 182:132-40.Ahmed AI, Abebe AT, Han Y, Alnabelsi T, Agrawal T, Kassi M, Aljizeeri A, Taylor A, Tleyjeh IM, Al-Mallah MH. The prognostic role of cardiac positron emission tomography imaging in patients with sarcoidosis: A systematic review. J Nucl Cardiol Jul 2021; doi: 10.1007/s12350-021-02681-z. Online ahead of print.Sharma A, Okada DR, Yacoub H, Chrispin J, Bokhari S. Diagnosis of cardiac sarcoidosis: an era of paradigm shift. Ann Nucl Med Feb 2020;34(2):87-93.Ha FJ, Agarwal S, Tweed K, Palmer SC, Adams HS, Thillai M, Williams L. Imaging in Suspected Cardiac Sarcoidosis: A Diagnostic Challenge. Curr Cardiol Rev 2020;16(2):90-97.Liang JJ, Hebl VB, DeSimone CV, Madhavan M, Nanda S, Kapa S, Maleszewski JJ, Edwards WD, Reeder G, Cooper LT , Asirvatham SJ. Electrogram guidance: a method to increase the precision and diagnostic yield of endomyocardial biopsy for suspected cardiac sarcoidosis and myocarditis. JACC Heart Fail Oct 2014;2(5):466-73.Ezzedine FM, Kapa S, Rosenbaum A, Blauwet L, Deshmukh AJ, AbouEzzeddine OF, Maleszewski JJ, Asirvatham SJ, Bois JP, Schirger JA, Chareonthaitawee P, Siontis KC. Electrogram-guided Endomyocardial Biopsy Yield in Patients with Suspected Cardiac Sarcoidosis and Relation to Outcome. J Cardiovasc Electrophysiol Jul 2021; In Press.Ardehali H , Howard DL, Hariri A, Qasim A, Hare JM, Baughman KL, Kasper EK. A positive endomyocardial biopsy result for sarcoid is associated with poor prognosis in patients with initially unexplained cardiomyopathy. Am Heart J Sep 2005 ;150(3):459-63.
Atypical porcine pestivirus (APPV) belongs to the genus Pestivirus within the family Flaviviridae. Recently, APPV has been identified as the causative agent of congenital tremor (CT) type AII. The disease is a neurological disorder that affects newborn piglets and is characterized by mostly generalized trembling of the animals and often splay legs. CT is well known worldwide, and the virus seems to be highly prevalent in major swine producing areas. However, little is known about the epidemiology of the infection, the transmission and spread of the virus between herds. Here, we show the high prevalence of APPV in processing fluid samples collected from Hungarian pig herds which led us to investigate the cellular targets of the virus in the testicles of newborn piglets affected by CT. By the development of an RNA in situ hybridization assay and the use of immunohistochemistry on consecutive slides, we identified the target cells of APPV in the testicle: interstitial Leydig cells, peritubular myoid cells and endothelial cells of medium-sized arteries. Previous studies have shown that APPV can be found in the semen of sexually mature boars suggesting the role of infected boars and their semen in the transmission of the virus similar to many other members of the Flaviviridae family. As in our case, the virus has not been identified in cells beyond the blood-testis barrier, further studies on infected adult boars’ testicles are needed to analyze the possible changes in the cell tropism that enable the virus to be excreted by the semen.
Vascular access for percutaneous coronary intervention (PCI) is usually obtained through the radial or femoral, and to lesser extent the brachial or ulnar artery. We describe the transcarotid approach for PCI in a patient with severe peripheral artery disease. No adverse neurological or cardiac events were observed.
Subacute thyroiditis (SAT) is an inflammatory thyroid disease of post-viral origin; linked with many viruses such as SARS-COVID-2. The objective of this work is to report a case of SAT associated with COVID-19 vaccination, in a healthy patient with no history of previous COVID-19 or upper respiratory tract infection.
Background: Various variants of the covid-19 have started to attract attention recently. The clinical course of these variants and possible predictive parameters are being investigated. This study aimed to examine the relationship between thiol levels, which are indicators of oxidative stress, and variant covid-19 types. Methods: In this cross-sectional study, patients with a diagnosis of classic covid-19 and patients with a diagnosis of variant covid-19 with mild and moderate symptoms followed in the clinical observatory of Ankara city hospital were included in the study group. The patients were divided into two groups according to the covid-19 type as variant and classic covid-19, and a healthy control group is added for comparison. A complete blood count and thiol analysis are performed from the venous blood samples. Obtained results were compared between groups, and the ROC analysis is performed. Results: Thiol levels were significantly lower in patients with a diagnosis of Covid-19 compared to the control group. In terms of WBC, lymphocyte, neutrophil, NLR, ferritin and thiol parameters, patients with variant covid-19 differed significantly from patients with a classic covid-19 diagnosis. Thiol levels’ cut-off values to distinguish between variant covid-19 patients and control group from classical covid-19 patients were almost identical (423 and 422 µmol/L, respectively). Conclusions: It seems possible to use thiol as a sensitive, specific and cost-effective marker to suspect variant covid-19 cases. Since this study is probably the first example in this subject, it would form a basis for further studies. Keywords: Covid-19, SARS-CoV-2, variant covid-19, thiol, oxidative stress.
The transcription machinery of archaea can be roughly classified as a simplified version of eukaryotic organisms. The basal transcription factor machinery binds to the TATA-box found around 28 nucleotides upstream of the transcription start site; however, some transcription units lack a clear TATA-box and still have TBP/TFB binding over them. This apparent absence of conserved sequences could be a consequence of sequence divergence associated with the upstream region, operonic and gene organization. Furthermore, earlier studies have found that a structural analysis gains more information compared to a simple sequence inspection. In this work, we evaluated and coded 3630 archaeal promoter sequences of three organisms, Haloferax volcanii, Thermococcus kodakarensis, and Sulfolobus solfataricus into DNA duplex stability, enthalpy, curvature, and bendability parameters. We also split our dataset into conserved TATA and degenerated TATA promoters in order to identify differences among these two classes of promoters. The structural analysis reveals variations in archaeal promoters’ architecture, i.e., a distinctive signal is observed in the TFB, TBP, and TFE binding sites independently of these being TATA-conserved or TATA-degenerated. In addition, the promoter encountering method was validated with upstream regions of 13 other archaea, suggesting that there might be promoter sequences among them. Therefore, we suggest a novel method for locating promoters within the genome of archaea based on energetic/structural features.
The case report by Sicim et al. is the placement of extra-anatomical bypasses in bilateral common carotid arteries. The similar previous reports of the extra-anatomical bypass usually indicate unilateral bypass. Whether or not the Willis' circle is incomplete is difficult to judge during emergency surgery, and the authors' judgment seems to have been correct in the sense that it could maintain cerebral perfusion reliably and quickly. The direct perfusion and extraanatomical bypass of carotid artery is a reasonable strategy in patients with cerebral malperfusion.
Protein allergens is a health risk for consumption of soybeans. To understand allerginicity mechanism, T cell epitopes of 7 soybean allergens were predicted and screened by abilities to induce cytokine interleukin 4. The relationships among amino acid composition, properties, allergenicity and pepsin hydrolysis sites were analyzed. Among the 138 T cell epitopes identified, YIKDVFRVIPSEVLS, KDVFRVIPSEVLSNS, DVFRVIPSEVLSNSY of Gly m 6.0501 (P04347), and AKADALFKAIEAYLL, ADALFKAIEAYLLAH of Gly m 4.0101 (P26987) were the most possible epitope candidates. In T cell epitopes pattern, the frequencies of amino acids Q, D, E, P and G decreased, while F, I, N, V, K and H increased. Hydrophobic residues at positions p1 and p2 and positively charged residues in positions p13 might contribute to allergenicity. Most of epitopes could be hydrolyzed by pepsin into small polypeptides within 12 residues length, and the anti-digestive epitope regions contained I, V, S, N, and Q residues. T cell epitopes EEQRQQEGVIVELSK from Gly m 5.03 (P25974) showed resistantence to pepsin hydrolysis and would cause a higher Th2 cell response. This research provides basis for the development of hypoallergenic soybean products in the soybean industry as well as for the immunotherapy design for protein allergy.
Rheumatic heart disease is the most common cause of mitral valve stenosis. Left atrial appendage thrombus is associated with mitral stenosis, but in rare cases the thrombus can extend to the left atrial cavity. We present a case of a severe rheumatic mitral stenosis and associated large left atrial thrombus, with embolic sequelae.
CASP (Critical Assessment of Structure prediction) conducts community experiments to determine the state of the art in computing protein structure from amino acid sequence. The process relies on the experimental community providing information about not yet public or about to be solved structures, for use as targets. For some targets, the experimental structure is not solved in time for use in CASP. Calculated structure accuracy improved dramatically in this round, implying that models should now be much more useful for resolving many sorts of experimental difficulty. To test this, selected models for seven unsolved targets were provided to the experimental groups. These models were from the AlphaFold2 group, who overall submitted the most accurate predictions in CASP14. Four targets were solved with the aid of the models, and, additionally, the structure of an already solved target was improved. An a-posteriori analysis showed that in some cases models from other groups would also be effective. This paper provides accounts of the successful application of models to structure determination, including molecular replacement for X-ray crystallography, backbone tracing and sequence positioning in a Cryo-EM structure, and correction of local features. The results suggest that in future there will be greatly increased synergy between computational and experimental approaches to structure determination.