Viral infection in cell culture and tissue is modeled with delay reaction-diffusion equations. It is shown that progression of viral infection can be characterized by the viral replication number, time-dependent viral load and the speed of infection spreading. These three characteristics are determined through the original model parameters including the rates of cell infection and of virus production in the infected cells. The clinical manifestations of viral infection, depending on tissue damage, correlate with the speed of infection spreading, while the infectivity of a respiratory infection depends on the viral load in the upper respiratory tract. Parameter determination from the experiments on Delta and Omicron variants allows the estimation of the infection spreading speed and viral load. Different variants of the SARS-CoV-2 infection are compared confirming that Omicron is more infectious and has less severe symptoms than Delta variant. Within the same variant, spreading speed (symptoms) correlates with viral load allowing prognosis of disease progression.
Objective: To evaluate the functional capacity, pulmonary function and quality of life of children and adolescents with sickle cell anemia (SCA) and to test the reproducibility of functional capacity tests in this population. Method: Cross-sectional study with volunteers with SCA genotype Hb-SS (SCAG), aged 6 to 18 years matched in age and gender to the control group (CG). Spirometry, 5-repetition sit-to-stand test (5STS-test), modified shuttle walk test (MSWT), and Pediatric Quality of Life Questionnaire (PedsQL) were performed. The reproducibility of 5STS-test and MSWT was evaluated: Results: 48 volunteers of SCAG and 48 of CG were evaluated. Pulmonary function of SCAG (FVC: 92 ± 15% pred.; FEV 1 /FVC: 84 ± 8% pred.) was worse than the CG (104 ± 15% pred.; FEV 1 /FVC: 90 ± 6% pred.) p < 0.05. SCAG had worse functional capacity registered by distance walked: 576m (515-672m) and 5STS-test: 8 seconds (7.4-8.9seconds) compared to the CG who showed distance walked: 1010m (887- 1219m) and 5STS-test: 7 seconds (7.0-8.1seconds), p < 0.001. SCAG had worse quality compared to CG, p < 0.05. The reproducibility was good of MSWT (ICC 0.99 (0.98-0.99 IC-95%)) and 5STS-test (ICC 0.80 (0.69 – 0.88), p < 0.001 . Conclusion: Children and adolescents with sickle cell anemia showed worse capacity to walk or run, and to perform sit-to-stand test. Additionally, they have poor quality of life when compared with their control peers. The MSWT and 5STS-test showed reproducible to be applied in pediatric individual with SCA.
Previous studies showed a sequence encoding an auxiliary protein (PlaS) downstream of the phospholipase A1 (PlaA1) gene of Serratia marcescens. There is an interaction between PlaA1 and PlaS, which may be closely related to the high enzymatic activity property of phospholipase A1. In order to further investigate the interaction mechanism, it is necessary to explore binding sites of the interaction between PlaA1 and PlaS and the regulatory mechanism for enzymatic properties by molecular docking and site-directed mutagenesis. The results showed that the active center site of PlaA1 was encapsulated internally, and a “catalytic pocket” was formed externally by Leu197-Ser249. The docking process of PlaA1 and PlaS involved 29 and 30 amino acids, respectively, of which Phe186 and Lys238 of PlaA1 are involved in forming π-bonds and multiple hydrogen bonds. Therefore, Phe186 and Lys238 were site-directed mutated to Ala to obtain the mutant enzymes PlaA1 F186A and PlaA1 K238A, respectively. The results showed that the mutant enzymes showed no significant changes in optimum temperature and pH but poor stability. The kinetic parameters indicated that the affinity between PlaA1 and substrates was weakened, and the catalytic efficiency was reduced after mutation. Therefore, it demonstrated that Phe186 and Lys238 of PlaA1 provided non-covalent bonds conducive to the enzymatic activity and stability in the interaction between PlaA1 and PlaS, which would provide some theoretical basis for further rational design and modification of phospholipase A1 subsequently.
The ithomiine butterflies (Nymphalidae: Danainae) represent the largest known radiation of Mullerian mimetic butterflies. They dominate by number the mimetic butterfly communities, which include species such as the iconic neotropical Heliconius genus. Despite recent studies carried out on ithomiine ecology and genetic structure, no reference genome was available for the tribe. Here, we generated high-quality, chromosome-scale genome assemblies of two Melinaea species, Melinaea marsaeus and Melinaea menophilus, and a draft genome of Ithomia salapia. We obtained genomes with a size ranging from 396 Mb to 503 Mb across the three species and scaffold N50 of 40.5 Mb and 23.2 Mb for the two chromosome-scale assemblies. Using collinearity analyses we identified massive rearrangements between the two closely related Melinaea species. A detailed annotation of transposable elements and genes was performed, resulting in the identification of 24,341, 31,081 and 31,976 genes in I. salapia, M. marsaeus and M. menophilus, respectively. We used a specialist annotation to target chemosensory genes, which is crucial for host plant detection and mate recognition in mimetic species. A comparative genomic approach revealed independent gene expansions in ithomiines and particularly in gustatory receptor genes. These first three genomes of ithomiine mimetic butterflies constitute a valuable addition and a welcome comparison to existing biological models of mimicry, such as Heliconius, and will enable further understanding of the mechanisms of adaptation and the genetic bases underpinning mimicry.
Background: Dexmedetomidine could be an ideal adjuvant to propofol during gastrointestinal endoscopy because it provides both analgesia and sedation without respiratory depression. This study investigates the effect of different doses of dexmedetomidine on the median effective concentration of propofol during gastrointestinal endoscopy. Methods: 90 adult patients were randomly assigned to Group Control , Group DEX0.5 (0.5 μg/kg dexmedetomidine), or Group DEX1.0 (1.0 μg/kg dexmedetomidine) . Anaesthesia during endoscopy was implemented by plasma target-controlled infusion (TCI) of propofol with different doses of dexmedetomidine. TCI concentration of the first patient for each group was 2.5 μg/ml and the consecutive adjacent concentration gradient was 0.5 μg/mL. EC50 of TCI propofol for gastrointestinal endoscopy was determined by using the modified Dixon’s up-and-down method. Cardiovascular variables were also measured. Results: EC50 of TCI propofol and 95% confidence interval (CI) for gastrointestinal endoscopy were, 3.77 (3.48-4.09), 2.51 (2.27-2.78) and 2.10 (1.90-2.33) μg/mL in Group Control, Group DEX0.5 and Group DEX1.0. The average percent change from baseline in HR was 2.8 (8.9), -7.4 (7.7) and -10.5 (8.8) (P＜0.001), and the average percent change from baseline in MAP was -10.6 [-24.7; 3.5], -9.5 [-29.2; 11.4] and -4.0 [-27.3; 15.5] (P = 0.034) in Group Control, Group DEX0.5 and Group DEX1.0, respectively. Conclusions: Dexmedetomidine reduced the EC50 of TCI propofol. A 0.5-1 μg/kg dexmedetomidine caused a decrease in HR without bradycardia. The decrease in dosage of propofol with increasing doses of dexmedetomidine caused more stable MAP. Dexmedetomidine is an ideal adjuvant drug to propofol during gastrointestinal endoscopy.
In this case, we reported a 24-day-old infant with a rare combination of the anomalous origin of coronary artery and the type A interrupted aortic arch, who presented with significant shortness of breath. Besides these anomalies, further cardiac examination including transthoracic echocardiography and CT angiogram revealed ventricular septum defect, patent foramen ovale and patent ductus arteriosus at the same time. Surgical procedures including repair of ventricular septum defect, ligation of patent ductus arteriosus, unroofing of right coronary artery and end-to-side aortic anastomosis were performed to cure the infant. This patient stayed in ICU for few days without any major complications and discharged from hospital at the tenth day after surgery.
Background and Purpose: (S)-ketamine induced rapid-acting antidepressant effects have revolutionized pharmacotherapy of major depression, however this medication produces also psychotomimetic effects including timing distortion. In contrast, (R)-ketamine appears to produce less of dissociative effects, but its antidepressant actions were less studied. It has been suggested that opioid receptors are involved in the antidepressant effect of ketamine. In addition, recent report suggests that while (S)-ketamine induced time underestimation, the (R)-isomer did not affect timing. Experimental approach: (R)- and (S)-ketamine, and fluoxetine as a positive control were tested in the differential-reinforcement-of-low-rate (DRL) 72-s schedule of reinforcement in male rats following naloxone pretreatment. Several DRL classic metrics as well as peak deviation analyses served to determine antidepressant-like actions and those associated with timing. Key Results: Antidepressant-like effect of (S)-ketamine (30-60 mg/kg) resembled fluoxetine (2.5-10 mg/kg) actions. Fluoxetine and (S)-ketamine increased reinforcement rate and peak location, suggesting increased performance, reduced premature responses, suggesting time underestimation and decreased Weber’s fraction, suggesting increased timing precision. In contrast, (R)-ketamine (60 mg/kg) increased reinforcement rate and peak location without affecting premature responses. Only fluoxetine decreased burst responses, suggesting decreased impulsivity. Naloxone pretreatment did not block ketamine enantiomers’ actions, but unexpectedly, increased fluoxetine’ performance. Conclusions & Implications: Fluoxetine’ and (S)- but not (R)- ketamine induced time underestimation could be associated with their antidepressant effects. The potentiation of DRL performance of fluoxetine by naloxone was unexpected and warrants further clinical studies.
Background: Increased liver stiffness can be result of increased liver iron concentration (LIC) which may not yet be reflected in the liver fibrotic status. The objective of our study was to examine relationship between hemochromatosis, liver stiffness, and serum ferritin level in transfusion-dependent patients. Methods: All transfusion-dependent patients aged between seven and 60 years referred for evaluating LIC status by magnetic resonance imaging (MRI) followed by two-dimensional ultrasonography shear wave elastography (2D-SWE) were included in this study. Results: The optimal cut point for prediction of severe hemochromatosis using median SWE (kPa) and SWV (m/s) was ≥ 7.0 kPa and ≥ 1.54 m/s, respectively, with sensitivity of 0.76 (95% confidence interval [CI] 0.55, 0.91) and, specificity of 0.69 (95%CI 0.53, 0.82). When combing the optimal cut point of SWE (kPa) at ≥ 7.0 and serum ferritin ≥ 4123 ng/mL, the sensitivity increased to 0.84 (95%CI 0.64, 0.95) with specificity of 0.67 (95%CI 0.50, 0.80), positive predictive value (PPV) of 0.60 (95%CI 0.42, 0.76), and negative predictive value (NPV) of 0.88 (95%CI 0.71, 0.96). Simultaneous tests of 2D-SWE and serum ferritin for prediction of severe hemochromatosis showed the highest sensitivity of 84% (95%CI 0.64-0.95), as compared to 2D-SWE alone at 76% (95%CI 0.55, 0.91) or serum ferritin alone at 44% (95%CI 0.24-0.65). Conclusions: We recommend measuring both 2D-SWE and serum ferritin in short interval follow up patients. Adding 2D-SWE to the management guideline will help in deciding if aggressive adjustments of iron chelating medication in indicated in patients suspicious for severe hemochromatosis.
Purpose : To determine whether extent of surgical resection of the primary tumour correlates with survival in patients with International Neuroblastoma Staging System (INSS) stage 4, high-risk neuroblastoma. Methods : Data were extracted for patients with newly diagnosed INSS stage 4, high-risk neuroblastoma between 2001-2019 from the national Cancer in Young People in Canada (CYPC) database. Complete resection was defined as gross total resection of primary tumour based on operative reports. Primary endpoints were 3 and 5-year event-free (EFS) and overall survival (OS). Survival analyses were completed using log-rank test and Cox proportional hazards regression including covariates of age, sex, decade of treatment (2001-2009 vs. 2010-2019), immunotherapy, and tandem stem-cell transplant (SCT). Results : One-hundred and forty patients with complete surgical data were included. On univariate analysis, 3-year EFS and OS for patients that had complete vs. incomplete resection was 71% (95% CI 57-80%) vs. 48% (36-60%) and 86% (75-93%) vs. 64% (51-74%), p=0.008 and p=0.002, respectively. 5-year EFS and OS for patients with complete resection also demonstrated significantly improved survival. On Cox Proportional Hazards models adjusted for age, immunotherapy, tandem SCT and surgical resection, only complete resection was associated with statistically significant improved 3 yr EFS and OS, HR=0.48 (0.29-0.81; p=0.006) and HR=0.42 (0.24-0.73; p=0.002). Conclusions : In a large Canadian INSS stage 4 high-risk neuroblastoma cohort, complete surgical resection was associated with increased EFS and OS. Within the constraints of a retrospective study, these results suggest that the ability to achieve primary tumor complete resection in patients with metastatic high-risk disease is associated with improved survival.
Introduction: Acute bronchiolitis (AB) is the main cause of hospitalization in children under two years of age, with a regular winter seasonality, mostly due to the respiratory syncytial virus (RSV). Objectives: To describe the epidemiology of bronchiolitis hospitalizations in our centre in the last twelve years, and analyse the changes in clinical characteristics, microbiology, and adverse outcomes during the SARS-CoV2 pandemic. Methods: Ambispective observational study including patients admitted for bronchiolitis between April 2010 and December 2021 in a Spanish tertiary paediatric hospital. Relevant demographic, clinical, microbiological, and adverse outcome variables were collected in an anonymized database. The pandemic period (April 2020 to December 2021) was compared to 2010-2015 seasons using appropriate statistical tests. Results: There were 2138 bronchiolitis admissions, with a mean of 195.6 per year between 2010-2019 and a 2–4-month peak between November and March. In the winter of 2020, there was a 94.4% reduction of bronchiolitis hospitalizations, with only eleven cases admitted in the first year of the pandemic. Bronchiolitis cases increased during the summer of 2021 in a six-month long peak, reaching a total of 171 cases. Length of stay was significantly shorter during the pandemic, but no differences were found in clinical and microbiological characteristics or other adverse outcomes. Conclusions: The SARS-CoV2 pandemic has modified the seasonality of bronchiolitis hospitalizations, with a dramatic decrease in cases during the winter of 2020-2021, and an extemporaneous summer-autumn peak in 2021 with longer duration but similar patient characteristics.
Respiratory syncytial virus (RSV) causes annual epidemics of acute respiratory disease in large part because antibody levels fall rapidly after infection. RSV is able to infect cultured dendritic cells (DCs) and persist in these cells. Given the importance of DCs in antigen presentation, RSV infection and persistence is likely to be an evolutionary adaptation that can subvert the host immune response. This study aimed to demonstrate infection and persistence of RSV in lung DCs using an in vivo model of RSV infection. Mice were infected with a modified strain of RSV which expresses a red fluorescent protein (RSV-RFP) when replicating. Clinical symptoms of infection were monitored using weight change and inflammatory cell counts from bronchoalveolar lavage, which were correlated to RSV viral titre (quantitative PCR). Lung tissues were collected at 3, 5, 7 and 21 days post-infection (dpi) to assess leukocyte populations by flow cytometry. Clinical symptoms and RSV viral load peaked at 5 dpi. RSV-RFP was most prevalent in macrophages at 3 dpi and observed in B cells and DCs. At 21 dpi, RSV-RFP remained evident in a subset of conventional DCs (CD103 +CD11b +) even though clinical symptoms and pulmonary inflammation had resolved. This data indicates that RSV infects, replicates in and persists in a sub-population of lung cDCs after resolution of symptoms and clearance of virus from the airways. Understanding the implications of this adaptation is likely to provide crucial insights into the virus’s ability to generate annual epidemics of respiratory disease.
Morphology-based taxonomic research frequently applies linear morphometrics (LMM) in skulls to quantify species distinctions. The choice of which measurements to collect generally relies on the expertise of the investigators or a set of standard measurements, but this practice may ignore less obvious or common discriminatory characters. In addition, taxonomic analyses often ignore the potential for subgroups of an otherwise cohesive population to differ in shape purely due to size differences (or allometry). Geometric morphometrics (GMM) is more complicated as an acquisition technique, but can offer a more holistic characterization of shape and provides a rigorous toolkit for accounting for allometry. In this study, we used linear discriminant analysis to assess the discriminatory performance of four published LMM protocols and a 3D GMM dataset for three clades of antechinus known to differ subtly in shape. We assessed discrimination of raw data (which are frequently used by taxonomists); data with isometry removed; and data after allometric correction. We found that group discrimination among raw data was high for LMM, possibly inflated relative to GMM when visualised in PCA plots. However, GMM produced better results in group discrimination after the size and allometry treatments. High measurement redundancy in LMM protocols appears to result in relatively high allometry but low discriminatory performance. These findings suggest that taxonomic measurement protocols might benefit from GMM-based pilot studies, because this offers the option of differentiating allometric and non-allometric shape differences between species, which can then inform on the development of the easier-to-apply LMM protocols.
Background and Purposes: Substantial evidence indicates trace amines can induce vasoconstriction independently of noradrenaline release. However, the mechanism underlying noradrenaline-independent vasoconstrictor responses to trace amines has not yet been established. This study evaluates the role of trace amine-associated receptor 1 (TAAR1) and other biogenic amine receptors in mediating trace amine-induced vasoconstriction. Experimental Approach: Vasoconstrictor responses to β-PEA and the TAAR1-selective agonist, RO5256390 were assessed in vitro in endothelium-denuded aortic rings and third-order mesenteric arteries of male Sprague Dawley rats. Key Results: β-PEA and RO5256390 induced concentration-dependent vasoconstriction of aortic rings but not third-order mesenteric arteries. Vasoconstrictor responses in aortic rings were insensitive to antagonists of 5-HT and dopamine. The murine-selective TAAR1 antagonist, EPPTB, had no effect on either β-PEA or RO5256390-induced vasoconstriction. The α1-adrenoceptor antagonist, prazosin, and the α2-adrenoceptor antagonist, yohimbine, induced a small but significant shift of the β-PEA concentration response curve that could not be ascribed to blockade of α1- or α2-adrenoceptors. Conclusion and Implications: Vasoconstrictor responses to trace amines are not mediated by classical biogenic amine neurotransmitter receptors. Although β-PEA vasoconstrictor responses were insensitive to ETTP, it has low affinity for rat TAAR1. Therefore, we propose that TAAR1 remains the most likely candidate receptor mediating vasoconstrictor responses to trace amines and that prazosin and yohimbine have some affinity for TAAR1.
Pump thrombosis is a rare and infrequent complication of HeartMate III left ventricular assist device (LVAD). While there are reports of pump thrombosis in the postoperative period, to our knowledge, there have been no prior reports on pump thrombosis in the intraoperative period. Here we present a case of a 24-year-old female who required HeartMate III LVAD implantation for progressive heart failure and the intraoperative period was complicated with pump thrombosis (PT). Managing PT in the intraoperative period is challenging and time-sensitive because of its rare occurrence and paucity of recommendations in diagnosing the PT.
Aortic valve stenosis is the most common adult valve disease in industrialized countries. The ageing population and the increase in comorbidities urge the development of safer alternatives to the current surgical treatment. Sutureless bioprosthesis have shown promising results, especially in complex procedures and in patients requiring concomitant surgeries. Objectives: Assess the clinical and hemodynamic performance, safety, and durability of the Perceval ® prosthetic valve. Methods: This single center retrospective longitudinal cohort study collected data of all adult patients with aortic valve disease who underwent aortic valve replacement with a Perceval ® prosthetic valve between February 2015 and October 2020. Of the 196 patients included (mean age 77.20±5.08 years; 45.4% female; mean EuroSCORE II 2.91±2.20%), the majority had aortic stenosis. Results: Overall mean cross-clamp and cardiopulmonary bypass times were 33.31±14.09 and 45.55±19.04 minutes, respectively. Mean ICU and hospital stay were 3.32±3.24 and 7.70±5.82 days, respectively. Procedural success was 98,99%, as two explants occurred. 4 valves were reimplanted due to intra-operative misplacement. Mean transvalvular gradients were 7.82±3.62 mmHg. Pacemaker implantation occurred in 12.8% of patients, new-onset atrial fibrillation in 21.9% and renal replacement support was necessary in 3.1%. Early mortality was 2.0%. We report no structural valve deterioration, strokes or endocarditis and one successfully treated valve thrombosis. Conclusions: Our study confirms the excellent clinical and hemodynamic performance and safety of a truly sutureless aortic valve, up to 5-year follow-up. These results were consistent in isolated and concomitant interventions, solidifying this device as a viable option for treatment of isolated aortic valve disease.
Objective: To assess obstetrical outcomes, perceptions of childbirth experience and emotional adjustment in women with dyspareunia. Design: Cross-sectional study. Setting: The maternity ward of a single medical center. Population: Four-hundred forty women, recruited within two days postpartum. Methods: We administered self-report questionnaires addressing demographic and reproductive background, dyspareunia, pain and perceived threat during delivery, sense of control during labour, perceived professional support, and maternal adjustment (i.e., perinatal dissociation, acute stress disorder (ASD), bonding, anticipated maternal self-efficacy depression and positive and negative affect). Obstetrical information was retrieved from clinical files. Main outcomes measures: Obstetrical outcomes and emotional adjustment to childbirth in women with dyspareunia versus comparisons. Results: Three-hundred eighty-eight women filled the dyspareunia questionnaire. The dyspareunia group included 71 women (18.3%) and the comparison group 317 (81.7%). Demographic data were similar between groups. No difference was observed in labour onset, analgesia, route of delivery and perineal tears. More participants with dyspareunia had premature delivery versus comparisons (14.1% vs 5.6%, p=0.02). Women with dyspareunia reported lower sense of control (p=0.01), lower perceived support (p<0.001), more perinatal dissociation (p<0.001), ASD symptoms (p<0.001), depression (p=0.02), negative affect (p<0.001), lower maternal bonding (p<0.001) and anticipated maternal self-efficacy (p=0.01). Women who experienced pain during pelvic exams were less likely to have spontaneous labor onset, more likely to need cervical ripening (p=0.02), and reported higher levels of negative affect (p=0.03). Conclusion: Dyspareunia was associated with more premature deliveries, more emotional distress and poorer maternal adjustment. Perinatal caregivers should be cognizant of such emotional reactions during prenatal care.
Background: Pediatric brain tumor survivors can experience detrimental effects from radiation treatment. Proton radiation therapy (PRT), which enables better targeting of radiation to tumors, may result in fewer sequelae. This follow-up cross-sectional study examined psychosocial and executive functioning in children and young adults treated with PRT. Procedure: Psychosocial and executive functioning was assessed by standardized parent rating scales for 187 patients. The sample was divided by age at baseline (<6 years [35.8%] and ≥6 years [64.2%]) and PRT field (craniospinal irradiation (CSI [36.9%]) and focal [63.1%]). Rates of impairment were calculated. Results: Mean age was 8.49 years at baseline; mean follow-up interval was 3.84 years. All mean scores were within the normal range and within normative expectation. Younger CSI group had significantly more problem behaviors and lower adaptive skills compared to older CSI or focal groups; however, no significant differences were found between younger PRT groups. There were no significant differences in executive functioning between the four age-by-PRT-field groups. Rates of impairment exceeded expected rates in social withdrawal, somatic concerns, activities of daily living, and metacognitive executive functioning. Age group was not significantly related to impairment rates, although the younger group had more problems with withdrawal, anxiety, activities of daily living, and executive functioning with relatively higher anxiety and withdrawal in the younger CSI group. Conclusions: Psychosocial and executive functioning was within the normal range at follow-up. Younger patients, particularly those treated with CSI, appeared more vulnerable. Screening and proactive intervention are needed to support psychosocial well-being and executive functions.
Flexural or membrane-coupled or capillary gravity wave scattering by a submerged or a piercing vertical porous barrier is analytically studied based on a connection that involves the solution potentials and few auxiliary potentials. The problems for the auxiliary potentials are relatively easy to handle for their solutions. The original problem is decomposed into two scattering or radiation problems of this type. The solution wave potential is determined in terms of those resolved wave potentials. Numerical results for the explicitly obtained scattering quantities are also presented.