Lymphadenopathy: The Solo Presentation of Visceral Leishmaniasis

The Arabidopsis thaliana population has been exposed to unexperienced biotic and abiotic stresses as a result of range expansion or environmental change. To obtain a global picture of the genetic adaptations in the population history of A. thaliana, we constructed a database of the phenotypic-adaptations (p-adaptations) and gene expression-adaptations (e-adaptations). We analysed the dynamics of the allele frequencies at the 23,880 QTLs of 174 traits and 8,618 eQTLs of 1,829 genes with respect to the total SNPs in the genomes, and identified 650 p-adaptations and 3,925 e-adaptations (FDR=0.05). The population underwent large scale p-adaptations and e-adaptations along four lineages, the eastward migration to Central Asia and South Siberia, Russia, the northward migration to Sweden, the migration to Azerbaijan, and the migration of the German population to the United States. Extremely cold winters and short summers prolonged seed dormancy, and expanded the root system architecture. Low temperatures prolonged the growing season and low light intensity required the increased chloroplast activity. The subtropical and humid environment enhanced phytohormone signaling pathways in response to the biotic and abiotic stresses. Exposure to heavy metals selected for alleles underlying low heavy metal uptake from soil, lower growth rate, lower resistance to bacteria, and higher expression of photosynthetic genes were selected. The database of p-adaptations and e-adaptations, which complements studies focusing on specific aspects of adaptation, may be useful for future studies to understand the biological adaptations of A. thaliana throughout its population history.

A document by Adriana Urbina. Click on the document to view its contents.

Restoring Flow: Percutaneous Coronary Intervention for ST-elevation Myocardial InfarctionMahfujul Z. Haque, BS1Muhammad B. Qureshi, BS2Frass Ahmed, BS1Mashkur Husain, MD31Michigan State University College of Human Medicine, Grand Rapids, MI, USA2Mayo Clinic Alix School of Medicine, Scottsdale, MI, USA3Downriver Heart and Vascular, Interventional Cardiology, Downriver, MI, USAWord Count: 99/100Table/Figure Count: 0Supplemental Video: 1Reference Count: 2/2Acknowledgements: N/AFunding Sources: NoneConflicts of Interest: None

The clinical efficacy of biological immunomodulators in patients refractory to standard therapy of intravenous immunoglobulin (IVIg) and glucocorticoids remains unclear. This review aimed to outline real-world data on the clinical outcomes of biological immunomodulators using Ovid-Medline, EMBASE, Cochrane CDSR, and the Korean database, KMBASE from September 2021 to August 2022. Among 251 studies , 10 were selected, of which two were observational studies with control groups receiving a standard therapy of IVIg and/or glucocorticoids. In total, 145 patients were treated with biological agents. In the first study with a control group, anakinra-treated group exhibited a lower left ventricular ejection fraction at baseline (54% vs. 60%, P = 0.08). Patients in the infliximab group of second study showed lesser additional treatment requirements (31% vs. 65%, P = 0.01), and lower rate of newly developed left ventricular dysfunction (4% vs. 20%, P = 0.05). The remaining eight single-arm studies did not report the clinical outcomes of each type of biological immunomodulator individually, limiting further interpretation. The findings of this review imply the potential of biological immunomodulators as a feasible therapeutic option for refractory MIS-C.

Current study examined the magnetohydrodynamic (MHD) Prandtl nanofluid of a thermal double-diffusive flow through an exponentially vertical surface in association with heat generation, and thermophoresis effect. The novelty of this study is due to the analysis of Prandtl nanofluid model with Soret mechanism and chemically responding fluids. The fluid flow phenomenon is characterized by nonlinear coupled differential equations involving two or more independent variables. A suitable numerical technique is used to handle the set of governing equations along with a stability and convergence analysis. According to recent study, the fluid velocity increases since all the parameters are set to higher levels. For the various parametric values, isotherms and streamlines have been explored. This suggested model is beneficial since it can significantly advance the domains of thermal and industrial engineering. For instance, thermal radiation is crucial in designing sophisticated energy-transformed systems that operate at high temperatures. On the other hand, the phenomenon of Soret is useful in separating isotopes in chemical engineering. These studies have several applications in the manufacturing and biomedical fields, petrochemical industries, automobiles, medical sciences, and various production processes in industries.

Inverse PCR (IPCR) is an accurate, simple, feasible, and ideal technique for obtaining unknown sequences. In this study, we used the model monocot Brachypodium distachyon (ecotype Bd21) to standardize the conditions and materials required for successfully performing the IPCR. Analysis of the amplified sequences led us to the following conclusions. First, the distance between the restriction endonuclease cleavage site and the unknown–known sequence boundary should be at least 400 bp. Second, a 6 bp restriction endonuclease such as NdeI produces condensed bands in a size gradient with good specificity, and therefore is a better choice than a 4 bp cutter such as HhaI. Third, a distance of approximately 200 bp between the second primer and the boundary sequence leads to a better amplification effect and effectively ensures the integrity of the unknown flanking sequence. The experimental conditions established in this study serve as a theoretical basis for the amplification of unknown genome sequences of Gramineae crops and other species.

Mechanical properties of living cells play an important role in helping to understand cell physiology and pathology. However, to ensure reliability, it is important to precisely define the experimental conditions of these mechanical test. In this study, viscoelastic properties of the outer layer (cytoplasm and membrane) were extracted using standard linear solid model. Finite element modeling of the two-layer cell was performed and the model was validated by experimental data. In the two-layer model, the effect of the radius of the nucleus and the location of the nucleus on the whole cell behavior were investigated. By increasing nucleus size, the whole cell properties follow the nucleus properties and the role of the nucleus becomes more dominant. By dislocating nucleus inside the cytoplasm, the cell behavior changes significantly and becomes more similar to that of nucleus properties. Similarly, changing the aspiration pressure and rate, impacts the observed behavior drastically. The results demonstrate that the location of the nucleus and the ratio of the radius of the cytoplasm to the radius of the nucleus can effectively influence the viscoelastic properties and mechanical behavior of the cell.

In this paper, we consider propagation direction, which can be used to predict which species will occupy the habitat or win the competition eventually, of bistable wave for a 3-species time-periodic lattice competition system with bistable nonlinearity, aiming to address an open problem proposed in [J.-S. Guo et al, The sign of traveling wave speed in bistable dynamics, Discret. Contin. Dyn. Syst., 40 (2020), 3451]. As a first step, by transforming the competition system to a cooperative one, we study the asymptotic behavior for the bistable wave profile and then prove the uniqueness of the bistable wave speed. Secondly, we utilize comparison principle and build up two couples of upper and lower solutions to judge the sign of the bistable wave speed which provides partially the answer to the open problem. As an application, we reduce the time-periodic system to a space-time homogeneous system, we obtain the corresponding criteria and carry out numerical simulations to illustrate the availability of our results. Moreover, an interesting phenomenon we found is that the two weak competitors can wipe out the strong competitor under some circumstances.

Many herbs and herbal formulae have been proven to offer safe and effective treatment for hyperlipidemia. However, the molecular mechanisms of their treatment have not been fully elucidated. Here, a total of 103 herbal formulae, including 146 individual herbs used to treat hyperlipidemia, were screened. Next, 40 common targets of core herbs and hyperlipidemia were extracted, representing potential targets of the herbal medicines for the treatment of hyperlipidemia. Further analysis revealed that the seven proteins most relevant to hyperlipidemia treatment were IL6, AKT1, IL1B, PTGS2, VEGFA, PPARG, and NOS3. Surprisingly, KEGG pathway enrichment analysis suggested that the herbs may treat hyperlipidemia by influencing the lipid and atherosclerosis pathway and the pathway in cancer. Molecular docking revealed significant affinity between bioactive compounds such as physciondiglucoside and baicalin with proteins involved in cancer pathways. Three active compounds, including 3-beta-hydroxymethyllenetanshiquinone, dan-shexinkum d, and physciondiglucoside have good binding ability with AKT1, PTGS2, and PPARG. The anti-hyperlipidemia activity of herbal medicines may be mediated via regulating proteins with roles in cancer. This study provides further evidence supporting the potential pharmacotherapeutic candidates for the combined treatment of hyperlipidemia and cancer in the future.

A document by Yuqian Huang. Click on the document to view its contents.

An animal’s movement is influenced by a plethora of internal and external factors, leading to individual- and habitat-specific movement characteristics. This plasticity is thought to allow individuals to exploit diverse environments efficiently. We tested if the movement characteristics of white sharks Carcharodon carcharias differ across ontogeny and among habitats along the coast of Central California. In doing so, we elucidate how changes in internal state (physiological changes coinciding with body size) and external environments (differing seascapes and/or diel phases) shape the movement of this globally distributed predator. White sharks, from small juveniles to large adults, were equipped with motion-sensitive biologging tags at four contrasting seascapes: two islands, a headland, and an inshore cove. From multi-sensor biologging data, 20 metrics characterising movement were derived and subjected to multivariate analyses. Movement characteristics were most different across seascapes, followed by ontogeny and diel phase. Juvenile sharks, that were only encountered at the cove, displayed the most distinct movement characteristics. Sharks at this seascape remained close to the shore and were comparatively less active than sub-adult and adult sharks tagged elsewhere. Distinct night-time movements and dive patterns were recorded from sharks at an island seascape but not from those at the headland or inshore cove. The availability of prey and access to deeper water are likely drivers, with greater numbers of Northern elephant seals Mirounga angustirostris at the island seascapes and harbour seals Phoca vitulina at the headland seascape, while the offshore island group is also closer to the continental shelf edge. Juvenile sharks at the inshore cove are piscivorous and their habitat was not adjacent to pinniped haul out areas nor deeper water. This study demonstrates plasticity in the movements of a top predator, that adapts its routine to suit the habitat it forages within.

Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia with an increasing incidence and prevalence in older age groups compared to younger individuals and the general population. Younger patients with AF often have different clinical characteristics, risk factors, and outcomes. Because AF among the young has not been studied in Middle Eastern populations, we conducted this study to provide valuable insights into the differences in the baseline clinical characteristics and the one-year adverse events between young and older AF patients, and thus contribute to formulate future treatment strategies and improve health outcomes. Methods: Consecutive adult patients previously or newly diagnosed with AF in 30 hospitals and out-patient cardiology clinics were enrolled in the Jordan AF study from May 2019 to October 2020. All patients were followed-up for one year. Baseline clinical characteristics and the one-year adverse events were assessed in young (<50 years) and older (≥ 50 years) adult patients with AF. Results: Of the 2020 AF patients enrolled in the study, 201 (10%) were young. Young patients were more likely to be men (75.6% vs. 43.8%, p<0.001), and had a lower prevalence of hypertension (31.3% vs. 79.3%, p<0.001), diabetes mellitus (10.4% vs. 47.2%, p<0.001), and previous stroke (9.0% vs. 16.1%, p=0.027) compared to older patients. Furthermore, young patients had a lower mean CHA 2DS 2-VASc score (1.1±1.4 vs. 3.9±1.7, p<0.001) and mean HAS-BLED score (0.6±0.7 vs. 1.8±1.1, p<0.001). The use of oral anticoagulant agents was significantly lower in young patients (39.3% vs. 75.0%, p<0.001). Young patients also had lower one-year all-cause mortality (1.1% vs. 13.7%, p=0.001), cardiovascular mortality (1.1% vs. 7.7%, p=0.04) and major bleeding (0% vs. 2.7%, p=0.021) compared to older patients. The rate of stroke and systemic embolization was similar in both groups (3.4% vs. 4.4%) Conclusion: The findings of the Jordan AF study suggest that young patients (<50 years of age) comprise a small proportion (10%) of the overall AF patient population. They had more favorable baseline clinical characteristics and risk scores compared to older patients. The one-year mortality and major bleeding rates in young patients were also lower than that in older patients.

INTRODUCTION:Tubercular meningitis is a severe form of meningitis caused by tuberculosis bacteria. 1It is a rare condition, but in India, it is a significant public health concern, as the country has a high incidence of tuberculosis. 2 This disease affects the protective layers surrounding the brain and spinal cord, leading to inflammation and the formation of blood clots in the veins of the brain. These clots can lead to a condition called cortical venous thrombosis, which can be life-threatening. In this case, an 18-year-old man in India has been experiencing symptoms of tubercular meningitis complicated by cortical venous thrombosis. He has been suffering from a severe headache, fever, and neck stiffness, which are typical symptoms of meningitis, and are signs of confusion and disorientation.We immediately started treatment for this patient’s condition, which included a combination of antibiotics to fight the tuberculosis bacteria and anticoagulant medication to prevent further blood clots from forming. We also monitored his intracranial pressure to prevent any further complications. These symptoms are concerning as they indicate a worsening of his condition, and we closely monitored him to prevent any further complications.In India, tuberculosis is a significant public health concern, and the country has implemented several programs to control the spread of the disease like the National Tuberculosis elimination program.3 These include early detection, treatment, and prevention strategies such as vaccination and contact tracing.

We present a 77-year-old man suffer from suspected cardiac infiltration of diffuse large B-cell lymphoma manifesting as sustained ventricular tachycardia. Neither antiarrhythmic drugs nor defibrillation can terminate VT episodes. the ECG showed sustained wide QRS tachycardia with left bundle branch block (LBBB) morphology and QRS complex positive in lead I and aVL, which inferred the tachy-arrhythmia would originated from the anterior wall of the right ventricle, this was consistent with the exact location of the tracer high-uptake on prior PET-CT. Chemotherapy was started urgently, the electrical-storm was eliminated within 48 hours and did not recur during three months of follow up. We will discuss the clinical presentation, diagnostic procedure, treatment and some reflections.

Aim: To evaluate the accuracy of the diagnostic criteria for determining the origin of outflow tract ventricular arrhythmia (OTVA) and develop an electrocardiography (ECG) algorithm to predict its origin. Method: We analyzed the ECGs of 100 patients with OTVA who underwent successful ablation. The QRS complex was measured during sinus rhythm and ventricular arrhythmia (VA). After the ECG algorithm was developed, it was validated in an additional 100 patients from two different hospitals. Results: In this retrospective study, among the parameters without restrictions in the transition lead, the V2S/V3R index (AUC = 0.89) was significantly better in predicting VA originating from the right ventricular outflow tract (RVOT). Further, the larger ISA in V1 and V2 (AUC = 0.90) was significantly better in predicting VAs originating from the left ventricular outflow tract (LVOT). Among the parameters with the transition lead in V3, the V2S/V3R index (AUC = 0.82) was significantly better in predicting VAs originating from the RVOT. On the other hand, the V3 R-wave deflection interval (AUC = 0.81) was significantly better in predicting VAs originating from the LVOT. The algorithm combining the V2S/V3R index and the larger ISA in V1 and V2 could predict OTVA origin with an accuracy of 85.00%, a sensitivity of 75.68%, a specificity of 90.48%, a positive predictive value (PPV) of 82.35%, and a negative predictive value (NPV) of 86.36%. In the validation study, the algorithm exhibited excellent accuracy (95.00%) and AUC (AUC = 0.95), with a sensitivity of 94.12%, a specificity of 95.45%, a PPV of 91.43%, and an NPV of 96.92%. Conclusion: Our developed algorithm can reliably predict OTVA origin without restrictions in the transition lead.

Monkeypox (Mpox) is a re-emerging zoonotic disease caused by Monkeypox virus. Several countries in the world have been reported Mpox outbreak recently besides West and Central Africa where it is an endemic disease which is a warning signal and it becomes a global public health concern. The infection can be transmitted from one infected person or animal to another. Fever, rash and lymphadenitis are the most common symptoms. Smallpox vaccines can be used for prevention of Mpox along with general measures. This review article covers the epidemiology, current outbreak and preventive measures of Mpox.

This paper proposes an explicit reference governor-based control scheme for the velocity-free spacecraft attitude maneuver problem subject to the pointing constraint, the angular velocity constraint, and the input constraint. The proposed two-layer control scheme guarantees asymptotic stability of the attitude while satisfying the aforementioned constraints. The inner layer relies on output feedback control via an immersion and invariance technology-based angular velocity observer, enabling attitude stabilization without measuring angular velocity. By analyzing the geometry of the pointing constraint, the upper bound of the angular velocity, and the optimization solution of the control input, the safety boundary described by the invariant set is obtained in the reference layer. Additionally, we introduce the dynamic factor related to the angular velocity estimation error into the invariant set to prevent states from exceeding the constraint set due to unmeasurable angular velocity information. The shortest guidance path is then designed in the reference layer. Finally, we verify the effectiveness of the proposed constrained attitude control algorithm through numerical simulations.

This paper focuses on the distributed model predictive control for multi-agent systems subject to packet loss and actuator saturation. The multi-agent systems, which can be decoupled into several subsystems, have a coupled global cost function. By decoupling the global cost function, the distributed model predictive control for multi-agent systems is approximately cast into centralized model predictive control for each agent with a cost function including the states of the neighboring agents. The exchange of states between adjacent agents realized by communication network may subject to packet loss which is assumed to obey a Bernoulli distribution with probability being known. Actuator saturation is also considered and dealt with by the Nth-step set invariance approach. To ensure the multi-agent systems is asymptotically stable, a compatibility condition is provided. The problem of controller design for agent is converted into a Linear matrix inequality optimization problem involving compatibility constraint. Furthermore, a control algorithm is obtained to ensure the asymptotic stability of the global closed-loop system as well as the recursive feasibility of the optimization problem. Finally according to a simulation example, it is concluded that the presented method is effective.

A new method is developed to estimate the contemporary effective population size (Ne) from linkage disequilibrium between SNPs without information on their location, which is the usual scenario in non-model species. The general theory of linkage disequilibrium is extended to include the contribution of full-sibs to the measure of LD, leading naturally to the estimation of Ne in monogamous and polygamous mating systems, as well as in multiparous species, and non-random distributions of full-sib family size due to selection or other causes. The prediction of confidence intervals for Ne estimates was solved using a small artificial neural network trained on a dataset of over 105 simulation results. The method, implemented in a user-friendly and fast software (currentNe) is able to estimate Ne even in problematic scenarios with large population sizes or small sample sizes, and provides confidence intervals that are more consistent than parametric methods or resampling.

A document by Sara Khaleel Ibrahim. Click on the document to view its contents.

A document by Hussein I. Al-Lami. Click on the document to view its contents.

Evidence for spatially varying selection and adaptive variation can provide insight into a species’ ability to adapt to different environments. However, despite recent advances in genomics, it remains difficult to detect footprints of spatially varying selection in natural populations. Here we analysed ddRAD sequencing data (21,892 SNPs) in conjunction with geographic climate variation to search for signatures of adaptive differentiation in twelve populations of the bank vole (Myodes/Clethrionomys glareolus) distributed across Europe. To identify the loci subject to spatially varying selection and associated with climate variation, we applied multiple genotype-environment association (GEA) methods, two univariate and one multivariate, and controlled for the effect of population structure. In total, we identified 213 candidate adaptive loci, 74 of which were located within genes. In particular, we identified signatures of selection in candidate genes with functions related to lipid metabolism and the immune system. Using the results of redundancy analysis (RDA), we demonstrated that population history and climate have joint effects on the genetic variation in the pan-European metapopulation. Furthermore, by examining only candidate loci, we found that annual mean temperature is an important factor shaping adaptive genetic variation in the bank vole. By combining landscape genomic approaches, our study sheds light on genome-wide adaptive differentiation and the spatial distribution of variants underlying adaptive variation in bank voles that are influenced by local climate.

Remission: Mission Possible in Chronic Rhinosinusitis with Nasal Polyposis?To the Editor,Remission is emerging as the penultimate goal in the management of several chronic diseases. Recent application of these concepts to the management of inflammatory airway disease has promoted the concept of clinical remission, using a “Treat to Target” approach. The concept of remission, now well-established in Rheumatology as well as Gastroenterology (GI), is emerging in Respiratory Medicine with recent publication of definitions of clinical remission for asthma (1). It is interesting to consider whether the disease remission concept might successfully be applied to Otolaryngology-Head and Neck Surgery (OHNS) in the management of chronic rhinosinusitis with nasal polyposis (CRSwNP).In the treatment of asthma, ‘remission’ is defined as the elimination of exacerbations and stabilization of symptoms, with the possibility of normalizing inflammatory markers, which indirectly reflect lung function and inflammation. Guidelines for inflammatory digestive diseases are similar to those in asthma, in terms of their symptomatic endpoints and rigorous control of disease (2). However, for inflammatory bowel disorders unlike in asthma, an additional endoscopic criterion which documents epithelial and mucosal recovery from disease is also included. The nasal endoscope provides similar characterization for the control criteria in CRSwNP, incorporating symptom control signifying clinical remission with endoscopic remission demonstrating normal sinonasal mucosa, which can also incorporate inflammatory markers highlighting biochemical remission.A consensus statement from tertiary Canadian rhinologists has previously combined symptomatic and endoscopic assessments to define success after endoscopic sinus surgery (ESS), with ‘optimal’ results reported as absence of symptoms and normal appearance of the sinus mucosa on sinonasal endoscopy (3). However, it was unclear how frequently this ‘optimal’ outcome could be achieved. An estimate of remission rates in CRS care is now afforded by two recent studies in CRSwNP which employed a clinical endpoint very similar to the remission definition used in GI for inflammatory bowel diseases. The first study, a prospective trial which assessed outcomes after treatment of CRSwNP with endoscopic sinus surgery (4), and the second, a double-blinded, placebo-controlled prospective trial evaluating refractory CRSwNP managed with long-term, low dose azithromycin (5).After ESS, clinical endpoints resembling remission were attained in 50% of all subjects, but with different rates of remission for different populations distinguished by co-morbidities. At four months after surgery, 72% individuals undergoing primary ESS for CRSwNP attained remission, while those with a history of previous surgery showed lesser response, with a 42% remission rate. Asthmatic subjects did considerably worse than non-asthmatic subjects: non-asthmatics attained remission in 60%, while patients with asthma or with aspirin exacerbated respiratory disease (AERD) only showed remission in 23% and 23.5% of cases, respectively. For the azithromycin trial, there was a 54% remission rate overall. Again, asthma was associated with a worse outcome: non-asthmatics had a remission rate of 88%, while asthmatics achieved only 38% remission, and only in 14% of AERD patients. Individuals demonstrating remission were characterized by parameters of epithelial recovery and healing, approaching those of optimal control as suggested for inflammatory digestive diseases (6).Conclusion: Remission is indeed a concept that can be attained in CRSwNP, even in patients who failed previous surgery, as demonstrated by these findings. Some patient groups apparently have more difficult disease evolution, and asthma emerges as an important treatable trait in patients with CRSwNP. Better defining this outcome through consensus-based definitions will allow for the identification and stratification of clinical scenarios where patients have complete relief from their disease symptomatically in addition to biochemical and endoscopic normalization which penultimately achieving remission.Respectfully submitted,Yvonne Chan, Andrew Thamboo, Joseph Han, Martin Desrosiers