Background In patients with chronic heart failure, QRS duration is a consistent predictor of poor outcomes. It has been suggested that for indicated patients, cardiac resynchronisation therapy (CRT) could come sooner in the treatment algorithm, perhaps in parallel with the attainment of optimal guideline-directed medical therapy (GDMT). We investigated differences in left ventricular (LV) remodelling in those with narrow QRS (NQRS) compared to wide QRS (WQRS) in the absence of CRT, whether an early CRT strategy resulted in unnecessary implants and the effect of early CRT on outcomes. Methods and results Our cohort consisted of 214 consecutive patients with LV ejection fraction (LVEF) ≤35% who underwent repeat echocardiography 1-year after enrolment. Of these, 116 patients had NQRS, and 98 had WQRS of whom 40 received CRT within 1-year and 58 did not. In the absence of CRT patients with WQRS had less LV reverse remodelling compared to those with NQRS, with differences in ΔLVEF (+9% vs 2 %, p<0.001), ΔLV end-diastolic diameter (-2mm vs -1mm, p=0.095) and ΔLV end-systolic diameter (-4.5mm vs -2mm, p=0.038). LVEF was more likely to improve by ≥10% if patients had NQRS or received CRT (p=0.08). Thirteen (24%) patients with WQRS achieved an LVEF >35% in the absence of CRT, however none achieved >50%. Conclusions A strictly linear approach to HF therapy might lead to delays to optimal treatment in those patients with the most to gain from CRT and the least to gain from GDMT.

Background: Feather duvet lung (FDL) is an underestimated form of acute and chronic hypersensitivity pneumonitis. Serological tests for FDL need to be validated. We investigated the ability of recombinant pigeon Proproteinase E (r-PROE) and Immunoglobulin-lambda-like-polypeptide-1 (r-IGLL1) proteins to support the serological diagnosis of FDL, and propose them as a serological tool for clinicians to differentiate cases from FDL and Bird fancier’s lung (BFL). Methods: Specific IgG antibodies against r-PROE and r-IGLL1, analyzed with ELISA, were measured in patients diagnosed with FDL (n=31), BFL (n=15) controls exposed (n=15) and unexposed to feathers (n=15). Results: The sensitivity and specificity of the r-PROE ELISA for the serological diagnosis of FDL cases versus exposed and unexposed controls were 74.2% and 86.7% respectively, with an index threshold of 0.5. (AUC: 0.9). In addition, this serological test was effective to support the serological diagnosis of FDL and BFL cases with significantly different thresholds. The r-IGLL1 ELISA was only effective for the serological diagnosis of BFL. Also, these two serological tests were useful for the diagnosis of both chronic and acute forms. Conclusions: The new diagnostic test for FDL using r-PROE protein should help to detect overt and hidden cases of FDL. The combination of both test will help the clinician in distinguish between the etiology of birds or feathers duvet.

This study aims to describe and demonstrate the applicability of a novel approach used to develop and test new methods based on species distribution models (SDMs) to establish spatial predictions of EBVs for birds based on bird diversity metrics, such as the distributions of properties of key bird habitats. A major objective of this study is to determine how to build bird SDMs that can be used to derive spatial EBVs for birds at a regional scale. We used as predictors 16 environmental variables considered ecologically meaningful for birds at 100 m spatial resolution, including two bioclimatic variables (Bio17 = precipitation of driest quarter and Bio7 = temperature annual range) for three periods: ‘current’, ‘future 2050’, and ‘future 2070’, eleven land-cover (land use) predictors (forest edge, arable land, coniferous forest, broadleaf forest, clear-cut forest, vineyard, settlement area, river, lake, meadow, and swamp forest), the normalized difference vegetation index (NDVI) and two topographic variables: slope and topography. We used multiple modelling techniques in the biomod2 package in R v3.3 to build presence-only SDMs relating bird presence to environmental features for each species. Here, we show that the suitability estimated according to the SDMs can be used as a spatial ‘species distribution’ EBV (SD EBV) and reflect the habitat quality and trends in climatic and land use impacts on populations of bird species. These developments should facilitate bird monitoring and management across space and time, ultimately helping to identify priority bird conservation areas, estimate habitat suitability and provide early warning signs regarding bird distribution trends. In general, bioclimatic variables, topography and forest structure were indicated to have an important relation to the species probability maps generated on the basis of the SDMs, signifying a dominant role of bioclimatic variable Bio17 in the development of habitat suitability patterns.

Rationale, Aims, and Objectives Quick diagnosis units, a paradigmatic innovative model of hospital ambulatory medicine in Spain, are suggested to be cost-effective. While former studies have been conducted as cost analyses of single units or comparative analyses between these patients and inpatients hospitalized for the same condition, how cost outcomes compare between units of different hospitals and different levels of complexity is unknown. Using micro-costing, the costs of patients managed at quick diagnosis units from a tertiary and a secondary hospital were compared. Methods The study population included 407 patients from each unit who were evaluated over 8 years. Through a bottom-up approach, we analyzed all single cost components that contributed to the mean total cost per patient in both units. Results Patients from the tertiary hospital unit were more likely than those from the secondary hospital to be referred for cancer suggestive symptoms, to have a diagnosis of cancer, and to be referred from the emergency department. Although the ratio of successive/first visits was 3.098 ± 0.6584 in the tertiary vs. 2.123 ± 0.2171 in the secondary hospital unit (P=0.0064), the time to diagnosis was significantly longer in the latter. With a similar mean cost per visit, the cost per patient was \euro577.5 ± \euro219.6 in the tertiary vs. \euro394.7 ± \euro92.58 in the secondary hospital unit (P=0.0559). Personnel and indirect costs including both the monetary estimate and their percent contribution to the mean cost per patient accounted for the main differences between units. Conclusion The ratio of successive/first visits was the main driver of cost differences. A greater complexity of patients from the unit of the tertiary hospital and the inherent characteristics of this type of hospital including volume of patients and staff and staff time justified the differences in the ratio of visits and the cost outcomes.

Introduction: Presence of preferential pathway conduction is mostly detected as fractionated presystolic potentials preceding the QRS onset during premature ventricular contractions (PVCs) and late potentials during sinus rhythm (SR), but the electrophysiologic mechanisms and significance of these potentials have not been fully clarified. We describe a PVC case series in which the preferential pathway conduction was 3-dimensionaly visualized by coherent mapping with the conduction velocity vector. Methods: Five PVCs (2 from the left coronary cusp, 2 from the commissure of the left and right coronary cusps, and 1 from the pulmonary artery) in 4 patients for which a fractionated presystolic potential during the PVCs and late potential during SR were recorded at the successful ablation site were reviewed, and 3-dimensional coherent activation maps with the conduction velocity vector during the PVCs and SR were reconstructed. Results: At the successful ablation site, an “M”-shaped discrete presystolic-potential and “W”-shaped discrete late-potential were recorded in all patients. The configuration of the flipped electrogram of the presystolic-potential nearly matched that of the electrogram exhibiting the late-potential. We created coherent activation maps annotating the onset of the presystolic potentials during the PVCs, and the offset of the late potentials during SR, which suggested bidirectional conduction of the preferential pathway connecting the PVC origin to the myocardium. Conclusion: In this case series, the M-shaped presystolic potential and W-shaped late potential were reversely matched. These reverse potentials, and the coherent activation vector maps during PVCs and SR suggested bidirectional conduction of the preferential pathway in opposite directions.

Background : Early repolarization pattern (ERP) is associated with long-term cardiovascular death. However, the incidence of early repolarization syndrome ( ERS) has never been studied in a general population-based cohort study. Purpose : To determine the prevalence and long-term outcome of ERP as well as the incidence of ERS in a general population-based cohort study. Methods : Participants from the electricity generating authority of Thailand (EGAT) study during 1997 to 2015 were included. The outcomes included cardiovascular death,deaths due to acute myocardial infarction, SCD, and all-cause mortality. A Cox- proportional hazard model was used to determine the association between ERP and the outcomes. Results: 2,689 participants with completed ECGs and risk factor profiles were included for the analysis. Mean follow up duration was 11.2±6.7 years. There were 444 participants with baseline ERP. There were 566 deaths during the follow-ups; of these, 21 were SCD including 6 ERS. The prevalence and incidence of ERS in our study was 0.22% and 0.20 per 1000 person-year. Overall, ERP was not associated with an increased risk of all-cause mortality (hazard ratio [HR]=1.04; 95% confidence interval [CI]:0.81 to 1.34; p =0.75). However, ERP was associated with an increased risk of all-cause mortality in the population ≤55 years old (HR=2.36; 95% CI:1.47-3.77; p <0.01). Conclusion : The prevalence of ERP in the Thai population was higher than the prevalence in other countries in Asia. Our study supports previous studies that ERP is associated with a long-term increased risk of all-cause mortality in the young-middle age population.

Soil bacteria live in patchy and dynamic environments where cells in adjacent microhabitats may realize vastly different generation times ranging from hours to years within small soil volumes. This study links bacterial population demographics with soil conditions to better estimate mean bacterial cell ages by tracking individual lineages over space and time using a mechanistic model of bacterial life in soil. Results show heavy-tailed distributions of generation times that follow a power law across all hydration conditions, implying no simple definition of mean soil bacterial age where soil volumes may harbor cells with very broad range of ages living side by side. The study highlights ubiquitous conditions that support a “genetic reservoir” of physiological traits for each bacterial species that may be preserved in soil cold spots and reintroduced during episodic reunification events (soil wetting).

Background Rapid identification of patients with high suspicion of COVID-19 may become a challenge with the co-circulation of multiple respiratory viruses (RVs). We have identified clinical or biological characteristics to help distinguish SARS-CoV-2 from other RVs. Methods We used a prospective cohort including all consecutive patients admitted through the emergency department’s (ED) and presenting respiratory symptoms from November 2019 to April 2020. Patients were tested for RV using multiplex polymerase chain reaction (mPCR) and SARS-CoV-2 RT-PCR. Results 203/508 patients were positive for an RV during the non-SARS-CoV-2 epidemic period (November to February), and 268/596 patients were SARS-CoV-2 positive during the SARS-CoV-2 epidemic (March to April). Younger age, male gender, fever, absence of expectoration and absence of chronic lung disease were statistically associated with SARS-CoV-2 detection. Combining these variables allowed for the distinguishing of SARS-CoV-2 infections with 83, 65, 75 and 76% sensitivity, specificity, PPV and NPV, respectively. Conclusion Patients’ characteristics associated with a positive PCR are common between SARS-CoV-2 and other RVs, but a simple discrimination of strong SARS-CoV-2 suspicion with a limited set of clinical features seems possible. Such scoring could be useful but has to be prospectively evaluated and will not eliminate the need for rapid PCR assays.

Hemophagocytic lymphohistiocytosis (HLH) is a rare yet potentially fatal systemic disease arising from uncontrolled activation of the immune system. According to the Histiocyte Society’s 2004 guidelines, patients must meet five of eight criteria to be diagnosed with HLH [1]. HLH may be classified into primary and secondary. Primary, or familial, HLH is attributed to underlying defects in genes that control natural killer (NK) and cytotoxic T-lymphocyte (CTL) cell degranulation. Secondary HLH, in contrast, may occur in the context of triggers, such as malignancy, rheumatologic disease, or infection. Systemic-onset juvenile idiopathic arthritis (SoJIA) is a well-recognized trigger of HLH and both share overlapping features (e.g. fever and elevated ferritin). Management of SoJIA includes the immunomodulator Anakinra, an interleukin 1 (IL-1) receptor antagonist hypothesized to dampen an overactive immune system. Three patients treated for HLH with concomitant SoJIA diagnosis at Cook Children’s Medical Center between 2014 and 2019 are described below in order to examine the role of immunomodulators in their clinical course and outcome.Three Hispanic patients (aged 8-15) presented with a constellation of systemic symptoms, including fever, generalized rash, fatigue, and weight loss. Upon fulfilment of necessary criteria and subsequent diagnosis of HLH, they were treated accordingly with HLH-2004 protocol. Case 3, whose HLH was suspected to be secondary to Epstein-Barr Virus (EBV) infection, rapidly responded to treatment and, therefore, briefly discontinued Etoposide; however, she tolerated this poorly and resumed treatment after a six-week hiatus with the addition of weekly Rituximab to mitigate rising EBV titers. All patients achieved remission.Past medical history for case 3 included autoimmune disorders such as celiac disease, type 1 diabetes and suspected idiopathic juvenile arthritis for which she did not require ongoing care prior to presenting with features of secondary HLH. Cases 1 and 2 were diagnosed with SoJIA following their HLH diagnosis. Cases 1 and 3 relapsed with HLH within months of their initial encounter. Due to their concurrent diagnosis of SoJIA, both received daily Anakinra. Case 3 experienced rapid resolution of symptoms. In contrast, Case 1 had unsatisfactory response of musculoskeletal manifestations prompting switch from Anakinra to weekly Tocilizumab—another biologic that antagonizes IL-6 receptor—with favorable response. Case 2 was started on daily Anakinra immediately following his diagnosis of SoJIA and has yet to relapse. In summary, all cases have yet to experience an additional relapse following introduction of Anakinra or Tocilizumab. Figure 1 provides the treatment timelines for Cases 1-3 who had 5.37, 2.87, and 4.62 years of follow up, respectively.The diagnosis of HLH remains elusive and is often accompanied with multiple systemic manifestations that overlap with other disorders. Though traditional therapy for HLH includes intensive courses of etoposide and corticosteroids, biologics represent a newer class of medications highly effective in treating diseases with inflammatory or immune-mediated components [2]. This case series reinforces that immunomodulators, such as Anakinra, are promising treatment options in pediatric patients with HLH secondary to SoJIA.

The treatment landscape for cancer therapy has changed drastically over the past decade. Tisagenlecleucel, the first genetically engineered adoptive cellular therapy approved by the United States Food and Drug Administration, has revolutionized this field by demonstrating impressive clinical success in children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (r/r B-ALL). Now three years since its approval, we have gained a deeper understanding on the basic immunobiology and clinical efficacy of this drug. This review will provide an updated summary of the clinical efficacy of tisagenlecleucel in childhood and young adults with r/r B-ALL, common side effects and their associated management strategies, as well as barriers that remain to be addressed in order to realize the maximum potential of this drug.

Soil salinization seriously affects the movement of water in soil which then affects soil stability and sustainability in industrial and agricultural development. Fly ash, one of the most discarded solid wastes from coal-fired power plants, has been widely used as a recycled resource in recent years. The basic components of soda soil have been investigated through laboratory experiments. Soda soil samples with different amounts of fly ash are tested to study the changes in the characteristics of the material due to changes in water content and evaporation rate during drying. Changes in fractal and crack intensity factor are calculated based on digital image processing technology. The results show that the residual water content of soda soil increases from 8.55% to 16.22% with increases in the fly ash content. Fly ash can improve the water retention capability of soda soil, with a rate of increase of 89.68%. The average length of the surface cracks gradually decreases with increase in fly ash content, which indicates that fly ash can effectively inhibit the development of surface cracking in soil. The rate of cracking is an important measure for characterizing the development of cracks by measuring the area of the cracks. The crack area gradually decreases with increase in the fly ash content with different rates of cracking. The rate of cracking with a fly ash content of 10% is relatively slow, which indicates that 10% fly ash can effectively reduce cracking in soda soil thus resulting in a high residual water content.

Objectives: This study aimed to identify unobserved subgroups of parents of children with hematological malignancies with respect to caregiving ability and examine the associations of the latent class membership with individual characteristics. Methods: A total of 392 parents of children with hematological malignancies in China were surveyed with the Hematologic Malignancies’ Family Caregiver Skills Scale and a study-specific demographic information questionnaire. Latent class analysis(LCA) was applied to identify latent classes of parents based on caregiving ability measures. Multinomial logistic regression model was used to investigate the associations of socio-demographic and clinical characteristics with the latent class membership. Results: Results from the LCA suggested a 3-class solution: Class 1-“high caregiving ability” class(n=131, 33.4%), Class 2-“medium caregiving ability” class(n=170,43.4%), and Class 3-“low caregiving ability” class(n=91, 23.2%). Socio-demographic and clinical characteristics, such as having lower level of education, being married, having higher household income, more daily caregiving time, and having older children, as well as children not diagnosed with leukemia, had significantly larger odds of being classified in Class 1 than in Class 3. When comparing Class 2 with Class 3, the findings remained basically unchanged except that the effect of gender of parent became statistically significant, and the effect of diagnosis of children became insignificant. Conclusion: There existed three distinct priori unknown classes of parents of children with hematological malignancies in regard to caregiving ability. The class membership was significantly associated with parent’s socio-demographics and child’s clinical measures. These findings may be helpful in the development of personalized caregiving ability interventions.

5-fluorouracil (5-FU) is a pyrimidine analogue used to treat adults with a variety of carcinomas but less frequently used in pediatrics. 5-FU is a well-recognized cardiotoxic chemotherapy medications, particularly among adults with underlying cardiovascular disease, however this has rarely been reported in the pediatric population. We report a rare case of 5-FU induced cardiomyopathy in a pediatric patient with nasopharyngeal carcinoma (NPC), successfully managed with milrinone and uridine triacetate, underscoring the need for awareness and prompt recognition and medication administration for this potentially reversible condition.

Forward and reverse successions of karst rocky desertification (KRD) occur simultaneously, and are linked to human activity, thus presenting a mutual feedback loop. Previous studies have focused on the unilateral human-driven mechanism of KRD or the impact of KRD on social-economic activities. These lack quantitative measurement and in-depth understanding of interactions involved. Therefore, this study builds and applies a novel model for measuring the coupling relationship and degree between KRD and social-economic activity in the Guizhou karst region of China. Results show an overall improvement but local deteriorations in KRD from 2000 to 2011; conversely, social-economic activity intensities increased during that time period. With their spatio-temporal variations, positive and negative human–desertification coupling relationships with an increased coupling degree are found. Different coupling relationship types between KRD and social-economic development, including urbanization, economic development and household income, are shown. KRD is found to be high positively coupled with specific human behavior intensities such as population movement, steep slope cultivation and ecological restoration. An inverted U-shaped curve is observed in the coupling index of KRD and urbanization within different development levels. Negative coupling at a low urbanization level indicates the limitation of the karst physical environment on social-economic development. Positive coupling with increasing urbanization implies a conflict between environment protection and social-economic development. A return to negative coupling in several counties with high urbanization levels indicates a win-win for ecology and economy. The effectiveness of the proposed coupling model is demonstrated, informing differentiated strategies for combating KRD and improving social-economic development.

Improving and reusing construction waste soils is now more relevant in light of the need to decrease CO2 emissions. In this paper, four contents of polymer SH (i.e., 0.0%, 3.0%, 3.5%, and 4.0%) were used to strengthen the granite residual soils, which is a kind of construction waste soils. Based on low-velocity impacts and employing scanning electron microscope (SEM) tests, this paper investigated the impact resistance of reinforced granite residual soils combined with polymer SH. Recycling waste granite residual soils can reduce the emissions of CO2 generated during the transportation and disposal. The low-velocity impact tests were performed on specimens at three initial kinetic energy levels (i.e., 124.18J, 243.40J, and 402.36J) achieved by varying the drop height of the weights. The experimental results showed that the impact resistances of granite residual soils were enhanced significantly with a mixture of polymer SH, for which the increment reached the maximum with a 3.5% content of polymer SH. In addition, the microstructures of granite residual soils combined with four contents of polymer SH (i.e., 0.0%, 3.0%, 3.5%, and 4.0%) were investigated using a Scanning Electron Microscope (SEM). The SEM images demonstrated that the interfaces of the granite residual soils particles became less distinct due to cementation with the increasing of the polymer SH content. With the optimal polymer SH content of 3.5%, the pore of granite residual soil was the smallest, resulting in a best enhancement of the impact resistance of the reinforced granite residual soil.

Outcome of vitrified oocyte injected by immotile testicular spermatozo with totally multiple morphological abnormalities of the sperm flagella ：a case report

Objective: Brain-Derived Neurotrophic Factor (BDNF) plays a role in placental development and is involved in the pathogenesis of preeclampsia (PE). In this study, we aimed to investigate the correlation of Val66Met variation in BDNF and PE and further explore the possible relationship between Val66Met and neonatal poor prognosis. Methods: TaqMan probe fluorescent PCR was used to analyze the genotypic and allelic frequency of BDNF Val66Met in 1138 cases of the PE group and 1342 cases of the control group. Besides, 200 pairs pregnant women with PE and their newborn, along with 208 pairs healthy women and their newborn were enrolled to evaluate the mother-fetal transmission effect. Furthermore, we detected the expression level of BDNF in placental tissue at the RNA and protein levels in 21 PE patients and 21 healthy pregnant women. Results: We found that the allele distribution was significantly difference in case group and control group (2=4.657, P=0.031, OR=0.884, 95%CI=0.791-0.989), suggesting BDNF Val66Met may be related to PE susceptibility. While the genotype distribution and additive gene have no significant difference. The analysis of maternal-fetal pairing showed the transitivity of BDNF Val66Met have no significant difference between the case group and the control group. Besides, the mRNA and protein expression level of BDNF in PE group was significantly lower than that in control group. Conclusion: We found that BDNF Val66Met may be associated with the occurrence of PE, and allele G may play a protective role. However, this locus may be not related to the poor neonatal prognosis.

Watershed description:The watershed is underlain by Oligocene tuffaceous and fossiliferous sandstone bedrock, rich in calcite, and clay-rich (Smectite) soils overlie a thick saprolite (Baille et al., 2007). BCI ranges in elevation from 26m asl to 167 m asl, is fully forested, with what has been characterized as a lowland seasonal tropical forest, with a mix of deciduous and evergreen trees. Annual rainfall averages 2,580 mm, with strong seasonality: the dry season is from December to May. BCI is one of the most intensively studied area of the global tropics because of the century-long presence of a research station and ongoing scientific investigation focused mainly on terrestrial forest ecology, entomology, animal behavior and related fields. The Lutz Creek data improve our understanding of basic hydrological processes and inform our ongoing research into the complex terrestrial ecosystems of the island and the region [bibliography below]. BCI is also home to the first of what is now a global network of more than 70 forest research plots known as the Forest Global Earth Observatory (ForestGEO, see https://forestgeo.si.edu/ ). ForestGEO is dedicated to advancing long-term study of the world’s forests to strengthen science capacity in an era of rapidly changing landscapes and climate to understand and predict forest dynamics

This paper quantified the hydrological alteration of the Padma River basin caused by the construction of Ferakka Barrage (FB) using innovative trend analysis (ITA), range of variability approach (RVA), and continuous wavelet analysis (CWA). We also predict flow regime by proposing particle swarm optimization (PSO) based novel hybrid machine learning algorithms. Results of the ITA showed the negative trend of the average discharge in the dry season (January-May), while the RVA analysis indicated that average discharge was lower than environmental flows. The CWA demonstrated a substantial effect of the FB on the periodicity of the streamflow regime. Results showed that PSO-Reduced Error Pruning Tree (REPTree), PSO-random forest (RF), and PSO-M5P were the optimal fit for average, maximum, and minimum discharge prediction (RMSE = 0.14, 0.3, 0.18) respectively.

The development and application of automated baseflow separation algorithms for describing individual discharge components still cover a major part of modern hydrology. A key problem is the applicability of baseflow separation methods in ungauged or anthropogenically impacted catchments due to their complex conceptuali-ty. With increasing anthropogenic impact, the dependence of calculated baseflow rates on measured total runoff also increases. In this study, we suggest statistical approaches for testing the suitability of different hydrograph separation algorithms. For our main study site, the mining-impacted Geisel catchment in the Central Ger-many, we calculated a mean baseflow rate of 0.28 m³/s for the period from 1981 to 2017. First, 14 different algorithms (graphical and statistical methods, digital-filter-approaches, and one physically based algorithm) were tested in seven catchments. The calculated baseflow rates for the Geisel catchment showed questionable curves, in particular a high amplitude. Thus, similarities between measured dis-charge and calculated baseflow were demonstrated (quasi-parallelism), which were quantified with correlation analyses on different time scales. Following this, a pro-found analysis of the baseflow index (BFI) was carried out. Finally, we applied a sta-tistical regionalisation approach to derive validated baseflow information for the Geisel catchment using the calculated baseflow indices and numerical catchment descriptors. As a result, the questionable baseflow hydrographs of the Geisel could be corrected. This promising method enables improved estimations of environmental flow components, improved analyses of the hydrological processes to foster the un-derstanding of anthropogenic impacts, and provides essential information for water management in the Geisel catchment. Furthermore, characteristic properties of long-term BFI values were revealed, which can be used to develop new physically based hydrograph separation procedures by including spatially distributed physical catchment descriptors.

Since cell penetrating peptides are promising tools for delivery of cargo into cells, factors limiting or facilitating their cellular uptake are intensely studied. Using labeling with pH-insensitive and pH-sensitive dyes we report that escape of penetratin from acidic endo-lysosomal compartments is retarded compared to its total cellular uptake. The membrane dipole potential, known to alter transmembrane transport of charged molecules, is shown to be negatively correlated with the concentration of penetratin in the cytoplasmic compartment. Treatment of cells with therapeutically relevant concentrations of atorvastatin, an inhibitor of HMG-CoA reductase and cholesterol synthesis, significantly increased endosomal escape of penetratin in two different cell types. This effect of atorvastatin correlated with its ability to decrease the membrane dipole potential. These results highlight the importance of the dipole potential in regulating cellular uptake of cell penetrating peptides and suggest a clinically relevant way of boosting this process.

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Rhinitis and especially allergic rhinitis (AR) remain the most frequent hypersensitivity condition, affecting up to a quarter of the population and impacting upon the quality of life of individual patients and the health economy. Data, especially in respect to underlying pathophysiological mechanisms mainly derive from adult studies and are subsequently extrapolated in the pediatric population. Therapeutic algorithms for children with rhinitis in children are long based on the same principles as in adults. We explore and describe novel aspects of rhinitis, ranging from mechanisms to disease classification, phenotypes, diagnostic and monitoring tools, and the use of treatments, with focus on the traits of pediatric age groups.

In this paper, we study the existence of periodic peaked solitons to a generalized μ-Camassa-Holm-Novikov equation with nonlocal cubic and quadratic nonlinearities. The equation is a μ-version of a linear combination of the Camassa-Holm, modified Camassa-Holm, and Novikov equations. It is shown that the proposed equation admits a sigle peakons. It is natural extension of the previous results obtained in for the μ-Camassa-Holm, modified μ-Camassa-Holm, and μ-Novikov equations, respectively.