A Literature Review of Blood-Disseminated P. marneffei Infection and a Case Study of this Infection in an HIV-Negative Child with Comorbid Eosinophilia.

BACKGROUND: The typical manifestations of Penicillium marneffei (nowadays Talaromyces marneffei) infection in children without human immunodeficiency virus (HIV) remain unclear. The current work presents the case of a child without an underlying disease who was infected with P. marneffei comorbid with eosinophilia. CASE PRESENTATION: A 2-year-old male was infected with P. marneffei. A physical examination revealed a high-grade fever, ulcerated lesions in the oral mucosa, anemia, pruritic erythematous papules on the sac and thigh and watery diarrhea. A chest enhanced computed tomography scan showed multiple small, nodular, high-density shadows in the lungs, multiple lymphadenectasis in the hilum of the lungs and mediastinum, and liquid in the right pleural cavity. The patient's plasma was negative for HIV. Routine blood tests initially indicated that the patient had leucopenia; however, later tests indicated that he had leukocytosis. This peak was caused by a significant increase in eosinophils. The total IgE and specific allergen levels were normal. The stool was negative for parasite eggs. Aspergillus antigen (galactomannan, GM) levels were significantly increased and were present in the serum for a relatively long period. CONCLUSIONS: Eosinophilia can occur during P. marneffei infection, and this finding might provide additional information on the activity of this intracellular parasite. In addition, GM detection might be useful for monitoring the effect of antifungal treatments; however, this theory requires more data for verification.

Two novel bursting patterns in the Duffing system with multiple-frequency slow parametric excitations.

This paper aims to report two novel bursting patterns, the turnover-of-pitchfork-hysteresis-induced bursting and the compound pitchfork-hysteresis bursting, demonstrated for the Duffing system with multiple-frequency parametric excitations. Typically, a hysteresis behavior between the origin and non-zero equilibria of the fast subsystem can be observed due to delayed pitchfork bifurcation. Based on numerical analysis, we show that the stable equilibrium branches, related to the non-zero equilibria resulted from the pitchfork bifurcation, may become the ones with twists and turns. Then, the novel bursting pattern turnover-of-pitchfork-hysteresis-induced bursting is revealed accordingly. In particular, we show that additional pitchfork bifurcation points may appear in the fast subsystem under certain parameter conditions. This creates multiple delay-induced hysteresis behavior and helps us to reveal the other novel bursting pattern, the compound pitchfork-hysteresis bursting. Besides, effects of parameters on the bursting patterns are studied to explore the relation of these two novel bursting patterns.

Inverse period-doubling bifurcations determine complex structure of bursting in a one-dimensional non-autonomous map.

We propose a simple one-dimensional non-autonomous map, in which some novel bursting patterns (e.g., "fold/double inverse flip" bursting, "fold/multiple inverse flip" bursting, and "fold/a cascade of inverse flip" bursting) can be observed. Typically, these bursting patterns exhibit complex structures containing a chain of inverse period-doubling bifurcations. The active states related to these bursting can be period-2(n) (n = 1, 2, 3,…) attractors or chaotic attractors, which may evolve to quiescence by a chain of inverse period-doubling bifurcations when the slow excitation decreases through period-doubling bifurcation points of the map. This accounts for the complex inverse period-doubling bifurcation structures observed in bursting patterns. Our findings enrich the possible routes to bursting as well as the underlying mechanisms of bursting.

The TRPA1 Channel Mediates Mechanical Allodynia and Thermal Hyperalgesia in a Rat Bone Cancer Pain Model.

Background: Bone cancer pain (BCP) significantly affects patient quality of life, results in great bodily and emotional pain, and creates difficulties in follow-up treatment and normal life. Transient receptor potential ankyrin 1 (TRPA1) is an essential transduction ion channel related to neuropathic and inflammatory pain. However, the role of TRPA1 in BCP remains poorly understood. This study aimed to explore the relationship between TRPA1 and BCP. Methods: A BCP model was induced by Walker256 cells to the left tibia. The sham group was induced by normal saline to the left tibia. Thereafter, pain behaviors and TRPA1 expression between the BCP group and the sham group were observed on the 14th day of modeling. The TRPA1 antagonist A967079 (10 mg/kg) was injected via tail vein. TRPA1 antisense oligodeoxynucleotide (AS-ODN, 5 nmol/10 µl) and missense oligodeoxynucleotide (MS-ODN, 5 nmol/10 µl) were intrathecally delivered via a mini-osmotic pump for 5 consecutive days to assess the effect of TRPA1 on BCP. Behavioral tests were assessed preoperatively and postoperatively. Real-time quantitative PCR and western blot analyses were used to measure TRPA1 levels among the different groups. Results: The BCP model was successfully established via X-ray and pathological sections at 14 days. Compared to the sham group, the BCP group was more sensitive to mechanical stimuli, cool stimuli and hot stimuli. Intravenously injected A967079 can relieve paw mechanical withdrawal threshold and paw withdrawal thermal latency in rats with BCP. Moreover, AS-ODN can relieve paw mechanical withdrawal threshold and paw withdrawal thermal latency in rats with BCP. Additionally, relative mRNA and protein expression of TRPA1 in the BCP group were much higher than those in the sham group (14.55 ± 1.97 vs. 1 ± 0.04, P < 0.01). Compared to the BCP group, the relative mRNA and protein expression of TRPA1 in the BCP+AS-ODN group was reduced (14.55 ± 1.97 vs. 2.59 ± 0.34, P < 0.01). Conclusions: The TRPA1 channel mediates mechanical allodynia and thermal hyperalgesia in a rat BCP model.

The MERS-CoV N Protein Regulates Host Cytokinesis and Protein Translation via Interaction With EF1A.

Middle East respiratory syndrome coronavirus (MERS-CoV), a pathogen causing severe respiratory disease in humans that emerged in June 2012, is a novel beta coronavirus similar to severe acute respiratory syndrome coronavirus (SARS-CoV). In this study, immunoprecipitation and proximity ligation assays revealed that the nucleocapsid (N) protein of MERS-CoV interacted with human translation elongation factor 1A (EF1A), an essential component of the translation system with important roles in protein translation, cytokinesis, and filamentous actin (F-actin) bundling. The C-terminal motif (residues 359-363) of the N protein was the crucial domain involved in this interaction. The interaction between the MERS-CoV N protein and EF1A resulted in cytokinesis inhibition due to the formation of inactive F-actin bundles, as observed in an in vitro actin polymerization assay and in MERS-CoV-infected cells. Furthermore, the translation of a CoV-like reporter mRNA carrying the MERS-CoV 5'UTR was significantly potentiated by the N protein, indicating that a similar process may contribute to EF1A-associated viral protein translation. This study highlights the crucial role of EF1A in MERS-CoV infection and provides new insights into the pathogenesis of coronavirus infections.

Modified American Joint Committee on Cancer Tumor-Node-Metastasis Staging System Based on the Node Ratio Can Further Improve the Capacity of Prognosis Assessment for Gastric Cancer Patients.

Background and Objectives: Our aim was to investigate whether the modified American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system based on the node ratio can further improve the capacity of prognosis assessment for gastric cancer (GC) patients regardless of the number of lymph nodes examined (eLNs). Methods: A total of 17,187 GC patients in the Surveillance, Epidemiology, and End Results (SEER) database were included. On the basis of a training set of 7,660 GC patients, we built the tumor-node ratio-metastasis (TNrM) staging system, which was then externally validated with a validation set of 9,527 GC patients. Results: For the training set, the C-index value of the TNrM staging system was significantly higher than that of the AJCC 8th TNM staging system to predict survival for GC patients (C-index: 0.688 vs. 0.671, P < 0.001). Moreover, the C-index value of the TNrM staging system was significantly higher than that of the 8th TNM staging system to predict survival for GC patients with ≤15 eLNs (C-index: 0.682 vs. 0.673, P < 0.001), as well as for GC patients with >15 eLNs (C-index: 0.700 vs. 0.694, P < 0.001). Similar results were found in the validation set. Conclusions: The TNrM staging system predicted survival more accurately and discriminatively than the AJCC 8th TNM staging system for GC patients regardless of the number of eLNs.

Route to bursting via pulse-shaped explosion.

This Rapid Communication reports on the discovery of a route to bursting, called a pulse-shaped explosion (PSE), for a paradigmatic class of nonlinear oscillators. We find that both an equilibrium and a limit cycle can exhibit pulse-shaped sharp quantitative changes in relation to the variation of system parameters, which are interesting explosive behaviors, the PSE. It leads to large-amplitude oscillations in the rest phase (i.e., small-amplitude oscillations) of bursting, giving rise to additional active phases alternating with the rest phase, and finally determines compound bursting structures. This way, the route to complex bursting dynamics by PSE is explained and its robustness is shown. PSE opens different ways for the control dynamics of complex systems.

Obtaining amplitude-modulated bursting by multiple-frequency slow parametric modulation.

Amplitude-modulated bursting (AMB), characterized by oscillations appearing in the envelope of the active phase of bursting, is a novel class of bursting rhythms reported recently. The present paper aims to report a simple and effective method, i.e., the multiple-frequency slow parametric modulation (MFSPM) method, for obtaining such a bursting pattern. We show that the MFSPM can be well controlled so that it may exhibit multiple continuous ups and downs in the active area. Then, the amplitude of the traced active state alternates between increases and decreases accordingly, which leads to oscillations in the envelope of the active phase, and AMB is thus created. Based on this, the route to AMB by the MFSPM is presented. The validity of the approach is demonstrated by several examples. The proposed approach does not depend on specific systems or bifurcations and thus is a general method.

Fast-slow analysis for parametrically and externally excited systems with two slow rationally related excitation frequencies.

We present a general method for analyzing mixed-mode oscillations (MMOs) in parametrically and externally excited systems with two low excitation frequencies (PEESTLEFs) for the case of arbitrary m:n relation between the slow frequencies of excitations. The validity of the approach has been demonstrated using the equations of Duffing and van der Pol, separately. Our study shows that, by introducing a slow variable and finding the relation between the slow variable and the slow excitations, PEESTLEFs can be transformed into a fast-slow form with a single slow variable and therefore MMOs observed in PEESTLEFs can be understood by the classical machinery of fast subsystem analysis of the transformed fast-slow system.

Carotid proliferative plaque formation in a canine model of chronic hypertension.

BACKGROUND: There are few reports describing arterial plaque formation induced by hypertension alone. The aim of this study was to establish a canine model of chronic hypertension and investigate carotid plaque development. METHODS: Ten beagles were studied; 5 underwent bilateral renal artery constriction via a novel vascular clip, and 5 sham-operated animals served as controls. Systolic blood pressure (SBP), diastolic blood pressure (DBP), lipid values, the intima-media thickness, and the carotid artery plaque score were investigated during 1 year after placement of the clips. RESULTS: The mean SBP and DBP over time were significantly greater in the constriction group (P < 0.001 for SBP, P < 0.01 for DBP). There were no significant differences in blood lipid levels or other biochemical parameters. Carotid plaques were demonstrated at 4 months postoperation in the constriction group; and in the constriction group, intima-media thickness became significantly greater at 4 months (P < 0.05), and plaque scores became significantly higher at 8 months (P = 0.034) after clip placement. Carotid stenosis was proved by digital subtraction angiography 1 year after clip placement, and histological examination revealed that the plaques were mainly comprised of smooth muscle cells, proteoglycans, and collagen fibers, but few macrophages and little lipid. CONCLUSIONS: Carotid proliferative plaques were developed in a canine model of chronic hypertension induced by a novel vascular clip. The plaques were mainly comprised of smooth muscle cells, proteoglycans, and collagen fibers.