We report a case presentation of an asymptomatic 18-year-old girl with a recurrent severe aortic regurgitation and moderately dilating ventricle as a result of right cusp replacement done at 15 years of age that became necessary severe regurgitation after the performance of balloon dilatation at 3 months. A successful redo right coronary cusp replacement was implemented with a cryopreserved decellularized glutaraldehyde-treated autopericardial patch. We observed improvement in left ventricle function and a good hemodynamic profile of aortic valve at 3 years of follow-up. Autologous cryopreserved decellularized glutaraldehyde-treated pericardium appeared to facilitate aortic valve reconstruction by providing a reproducible off-the-shelf material to preclude Ross- and mechanical valve replacement-associated drawbacks for a time.

Introduction: In 2009, the World Health Organization reported a new pandemic. In Brazil, almost 90,000 cases of severe acute respiratory syndrome were confirmed. This study aims to investigate the factors associated with the 2009 pandemic influenza rate in Brazilian capitals. Methods: Ecological study, in which data were collected from the government information system. Thematic maps were built to describe the rate by sex and age group. Chi-square tests were used to evaluate the association between pandemic influenza incidence and the following factors: age group, sex, climate, Gross Domestic Product per capita, and region. The adjusted rate ratio of influenza was estimated using the multilevel Poisson model. Fixed effects were age group, sex, climate, GDP, and interaction terms. Random effects were capital (intercept) and region (slope). Results: A total of 13,171 confirmed cases of pandemic influenza were reported in 2009, in which 56% occurred in women, 39% in the 20-39 years age group, and 43% in the Southeast. The 2009 global rate of pandemic influenza in Brazilian capitals was 35.70/100,000. Women, 20-39 years of age group and subtropical climate showed the highest risk of getting ill. The highest and the lowest rates of pandemic influenza were observed in capitals of the South and Northeast regions, respectively. Conclusions: The 2009 pandemic influenza evidence high risk in adults and adolescents, female and subtropical climate. Continued social and health interventions to prevent and tackle influenza outbreaks and a robust surveillance information system are necessary to effectively control the disease.

Purpose: To explore the effects of conventional sepsis treatment, including classical antibiotherapy and IgG-A-M combinations, on liver function tests in patients with severe sepsis. Material and method: Our study retrospectively examined the effects of Immunoglobulin G-A-M combination (Pentoglobin®) on liver function test and mortality rate in patients who were in the septic process. We administered the Immunoglobulin G-A-M combination infusion lasting 12 hours at a dose of 5mg/kg for three days to the patients we enrolled in the study. We administered this protocol to a total of 70 patients who met the study criteria. Results: Immunoglobulin G-A-M combination therapy had no statistically significant effect on liver function tests and mortality in sepsis. Conclusion: Sepsis is a clinical condition that continues to have a high mortality rate despite advances in treatment modalities. Although anti-infective And anti-inflammatory treatments are used, there is no clear daya on their efficacy.However, early diagnosis of sepsis, early initiation of antibiothearpy, early source control And timely initiation of appropriate fluid therapy play a key role in succsess of sepsis treatment. For this purpose, as emphasized in the sepsis 3 guideline, we think that raising awareness by physicians And practitioners in early diagnosis of sepsis is the Most important step in the treatment of this clinical condition. Keywords: sepsis, liver function tests, immunoglobulin G-A-M

A document by Maurizio Bonati. Click on the document to view its contents.

1. Mixture effect on stand productivity is usually apprehended through a substitutive approach, whereby productivity in mixed stands is compared to productivity in monocultures, at equivalent stand density. This approach has proved that in many cases mixed stands perform better than monospecific forests, however, we do not yet have a solid theory about species behaviour in the mixture or even guidelines for combining species. The addition of a second tree species to an existing mono-specific stand has received much less consideration. Yet, this approach has the potential to separate the facilitation effect from the complementarity effect. 2. We compared the effect of tree species substitution vs. addition on the productivity of maritime pine and silver birch in a young tree diversity experiment implemented in 2008 in SW France. 3. Substituting pines with birches to create two-species mixtures resulted in an increase of tree productivity at stand level beyond what was expected from monocultures (i.e., overyielding). In contrast, creating mixture through the addition of birches to pine stands had no effect on the maritime pine stand productivity (transgressive mixture effect not significant). This absence of effect is produced by two distinct density-dependence responses at an individual level. 4. Our results allow clarifying the cases in which a mixed stand can be considered as an alternative to a monoculture of a productive species. In particular, the addition of a pioneer and soil low-demanding species during young developmental stages is a possibility to diversify the stand and potentially to increase ecosystem services without altering the productivity of the target species.

There have been numerous very disappointing results of Convalescent Plasma Therapy (CPT) in active infections with COVID-19 virus, raises a question of how to account for this, given the huge history of seeming benefit of CPT in a variety of infectious diseases over more than the past 100 years. We propose the following as a possible explanation, based on our experimental evidence. In CPT there is a collision between developed desirable viral resistance promoting hyper-immune antibodies and undesirable convalescent exosomes antigen (Ag)-specifically suppressing cellular immune responses stimulated by the prior now recovered acute viral disease. These inhibiting exosomes, that act to suppress Ag presenting cells and anti-COVID-19-Ag-specific effector T cells, are appropriate to convalescence, but when given early in infection may interfere with endogenous early developing profitable cellular immune anti-viral responses. To account for the high incidence of the Long Haulers post COVID patients, we postulate that these are due to immune reactivity to Ag remnants of the virus and not residual infection. These are postulated to held by and augmented by remnants of highly pathogenetic neutrophil extracellular traps (NETs). We propose that CPT with its content of potential broadly COVID Ag-specific suppressive exosomes be considered for possible effective treatment of the COVID-19 Long Hauler Syndromes. This certainly is so compared to the purported value of therapy with vaccines, as the diverse Ag-specific extracellular vesicles in the convalescent plasma would be an inhibitory influence on multiple COVID Ag-specific responses, beyond just to the spike protein of the virus.

Background: SARS-CoV-2 serology testing is key for assessing seroprevalence and community transmission in both symptomatic and asymptomatic contexts. Robust assay development requires assessment in asymptomatic and non-hospitalised individuals to determine if serological assays are sensitive to detect mild antibody-responses. Our study evaluated the performance characteristics between two high-throughput SARS-CoV-2 IgG nucleocapsid assays (Abbott and Roche) and The binding site (TBS) Anti-Spike IgG/A/M ELISA kit in healthcare workers. Methods: 252 samples were collected from Portsmouth Hospital University NHS Trust (PHU) and The Dudley Group NHS Trust and analysed for SARS-CoV-2 serology. We derived concordance, agreement and assay performance as well as using receiver operating characteristic (ROC) curves to redefine the assay threshold of the Abbott assay Results: Result concordance between the Abbott and TBS was 66%. Discrepant samples were analysed using the Roche assay which showed 100% agreement with the TBS assay. In samples analysed >58 days post-PCR, the sensitivity of Abbott and Roche was 100%. In samples analysed >100 days post-PCR the sensitivity of the Abbott assay dropped to 77.2% but remained at 100% for the Roche assay. A redefined Abbott threshold of 0.64 increased the sensitivity to 90% giving results similar to the Roche and TBS assays. Conclusion: This study demonstrated use of manufacturer cut-off threshold for Abbott SARS-CoV-2 IgG immunoassay induced lower sensitivity and higher false negative outcomes in comparison to TBS and Roche. Our findings established TBS can be implemented as a viable alternative for SARS-CoV-2 serology testing where high-throughput assays are not available on site.

Objectives: To determine vitamin D supplementation frequency among infants, factors that influence adherence, and reasons for discontinuation of initiated vitamin D. Methods: This cross-sectional study was conducted using a questionnaire administered to the mothers via face-to-face interview of 560 infants aged from 1 to 24 months admitted to outpatient clinics from June to December 2017. Results: A total of 351 infants were administered vitamin D, and the rate of supplementation in the first year of life was 83%, while it was only 28% between 13 and 24 months. The rate of vitamin D supplementation was higher among exclusively formula-fed infants (p<.05). When the data were analyzed using logistic regression analysis, only visit family physicians statistically significant independent variable in increasing supplementation (p<.05). Compared with family refusal, the rate of discontinuation of vitamin D by the healthcare providers was higher after the first year of life (p<.05). The rate of vitamin D discontinuation by healthcare providers, especially by nurses who considered the duration of supplementation adequate, was statistically significantly higher when compared with the fontanel closure and other independent variables (p<0.05). Conclusions: The rate of vitamin D supplementation was higher among families who visited family physicians, which suggests the importance of well-baby visits. Since vitamin D supplementation was less common among exclusively breastfed infants, mothers should be educated. Healthcare professionals need further education about the importance of vitamin D supplementation and indications for discontinuation.

This paper concerns the cluster consensus for multi-agent systems with fractional-order nonlinear dynamics. The agents can be divided into several clusters and Cluster consensus means that states/outputs of all agents in the same cluster converge to fixed values or paths which are different between clusters. A sufficient condition is investigated for proving Mittag-Leffler stability of the considered closed loop system. In addition, cluster formation of fractional-order multi-agent systems with nonlinear dynamics is studied in this paper which means each cluster makes the specific pattern. The performance improvement of the considered control law by using fractional-order Lyapunov stability and graph theories is shown. It is shown that if there is a directed spanning tree in the graph and the information exchange between two clusters is balanced, the cluster formation can be obtained. Finally, a number of examples are simulated to show the performance of the obtained results.

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte apoptosis characterized by nonmalignant lymphadenopathy, splenomegaly, immune dysregulation, and autoimmune cytopenias. Langerhans cell histiocytosis (LCH) is a neoplasm of myeloid precursor cells, primarily presenting as bone, soft tissue, lung, skin, and pituitary lesions. The association between the two diagnoses is uncharacterized. Here we describe a patient presenting with fever of unknown origin, cytopenias, and failure to thrive. She was diagnosed with ALPS, then subsequently LCH, within three months. This case highlights the diagnostic and management challenges associated with these two rare diagnoses.

This study deals with the biological treatment of saline wastewaters generated by olive oil and fish canning industries using Yarrowia lipolytica. The ability of the halophilic yeast Y. lipolytica was studied on the dephenolated olive mill wastewater (DOMW) / tuna wash processing wastewater (TWPW) mixtures at different proportions. Our results showed that DOMW/TWPW (75:25) is the suitable mixture for the highest Y. lipolytica biomass production reaching 11.3 g L-1 after 7 days. In addition, our results showed significant removal of chemical oxygen demand (COD) and phosphorous of 97.49 % and 98.90 %, respectively. As well as, a total removal of nitrogen was observed at the end of the experiment. On the other hand, Y. lipolytica was found to be effective in removing salts from these mixtures reaching 92.21 %. Moreover, the analytical results using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) confirmed the biosorption of NaCl on the surface of the yeast as nanocrystals form. Hence, Y. lipolytica can be considered as a promising candidate for the simultaneous remediation and desalination of saline food wastewater.

Background and Purpose A simplistic assumption in setting up a competition assay is that a low affinity labelled ligand can be more easily displaced from a target protein than a high affinity ligand, which in turn produces a sensitive assay. An often-cited paper recommends the use of the highest affinity ligand available for all competition-based screens. We demonstrate that this suggestion can lead to reduced assay sensitivity, increased false negatives and ultimately, the discarding of potentially valuable active compounds. Experimental Approach Using our recently developed PyBindingCurve software for mechanistic understanding of complex biological interaction systems, we have simulated competition experiments using protein, ligand, and inhibitor concentrations common to drug screening campaigns. Key Results Our simulations reveal a labelled ligand affinity range based on assay parameters, rather than a general rule to optimise assay sensitivity. We provide source code to carry out these simulations, a video summarising the key findings, along with a simple lookup table allowing all scientists the ability to identify and visualise optimal dynamic ranges for a competition assay. Conclusion and Implications In primary drug screening the highest assay sensitivity is required to not miss low affinity binders like for protein-protein interactions. Compounds are prioritised for hit to lead phase projects in which more detailed inhibitor affinity determination is achieved. The application of our freely available software and lookup tables will reduce false negative rates and lead to the consistent creation of more performant primary screens identifying valuable compounds.

BACKGROUND AND PURPOSE Esophageal squamous cell carcinoma (ESCC) is one of the major subtypes of esophageal cancer. More than half of the ESCC patients in the world are in China, and the 5-year survival rate is less than 10%. As a new oral proteasome inhibitor, ixazomib has shown strong therapeutic effect in many solid tumors. In this study, we aimed to investigate the effects of ixazomib on the proliferation inhibition and apoptosis of ESCC cells. EXPERIMENTAL APPROACH We used four human ESCC cell lines, cell viability assay, cell cycle and apoptosis assay, RT-PCR, Western blot, immunohistochemistry and ESCC xenografts model to clarify the roles of the therapeutic effect and mechanism of ixazomib in ESCC. KEY RESULTS Ixazomib significantly inhibited the proliferation and induced apoptosis in ESCC cells. RT-PCR results showed that the expression of endoplasmic reticulum stress-related gene NOXA and c-Myc significant increase after treatment with ixazomib in ESCC cell. Then we knockdown the NOXA and c-Myc by siRNA, the therapeutic effect of ixazomib markedly decrease, which confirmed that c-Myc/NOXA pathway played a key role in the treatment of ESCC with ixazomib. In vivo, the xenograft ESCC model mice were given 10 mg/kg of ixazomib every other day for 30 days. The results showed that the tumor size in the treatment group was significantly smaller than the control group CONCLUSIONS AND IMPLICATIONS These results suggested that ixazomib is known to suppress proliferation and induce apoptosis in an ESCC cell lines, and this effect was likely mediated by increased activation of the c-Myc/NOXA signaling pathways.

The pathogenic role of the overactivated ABL1 tyrosine kinase (TK) pathway is well recognized in some forms of BCR-ABL1 like acute lymphoblastic leukemia (ALL); TK inhibitors represent a useful therapeutic choice in these patients who respond poorly to conventional chemotherapy. Here we report a novel peptide biosensor (PABL)-ELISA assay to investigate ABL1 activity in four immortalized leukemic cell lines with different genetic background. The PABL sequence comprises an ABL1 tyrosine (Y) phosphorylation site and a targeting sequence which increases the specificity for ABL1; additional peptides (Y-site-mutated (PABL-F) and fully-phosphorylated (PPHOSPHO-ABL) biosensors) were included in the assay. After incubation with whole cell lysates, average PABL phosphorylation was significantly increased (basal versus PABL phosphorylation: 6.84 ± 1.46% versus 32.44 ± 3.25%, p-value < 0.0001, two-way ANOVA, Bonferroni post-test, percentages relative to PPHOSPHO-ABL in each cell line). Cell lines expressing ABL1-chimeric proteins (K562, ALL-SIL) presented the higher TK activity on PABL; a lower signal was instead observed for NALM6 and REH (p<0.001 and p<0.05 versus K562, respectively). Phosphorylation was ABL1-mediated, as demonstrated by the specific inhibition of imatinib (p<0.001 for K562, NALM6, ALL-SIL and p<0.01 for REH) in contrast to ruxolitinib (JAK2-inhibitor), and occurred on the ABL1 Y-site, as demonstrated by PABL-F whose phosphorylation was comparable to basal levels. While requiring further optimization and validation in leukemic blasts to be of clinical interest, the PABL-based ELISA assay provides a novel in vitro tool for screening both the aberrant ABL1 activity in BCR-ABL1 like ALL leukemic cells and their potential response to TK inhibitors.

Background: Brazil has one of the highest numbers of births with sickle cell disease in the Americas. Despite the risk of severe illnesses and death due to both vaccine-preventable viral and bacterial infections, the vaccination uptake in pediatric patients with SCD in Brazil is unknown. Material and methods: children under 18 years with SCD presenting to routine medical consultations at the Hematology Clinic had their vaccination status evaluated according to the national recommendations when each vaccine scheme was administered. Data obtained was classified in Adequate, Delayed, or Missing vaccination and compared younger children with older ones. Results: From 117 children screened, 100 had their vaccination card available. Vaccination coverage of routine vaccines was above 95% for all primary series and both age groups, with varied rates of delays and low missing doses. Among SCD extended vaccination, the most frequently delayed and missed vaccines were those specifically recommended to individuals with SCD as per national guidelines – and particularly those against encapsulated bacteria. Significant and varied rates of missing doses occurred in primary series and booster doses for PPSV23, Hib, menC, hepatitis A and varicella. The average influenza vaccination rate was 69.5%, with higher rates among younger children. Conclusions: by detecting alarming under-vaccination rates in children with SCD, we suggest the basic prevention strategies in Brazil should be reassessed in this specific population.

Transplant-associated thrombotic microangiopathy (TA-TMA) is an under-recognized yet potentially devastating complication of hematopoietic stem cell transplantation which had increased awareness in recent years. This report summarizes territory-wide experience of paediatric TA-TMA in the Hong Kong Children’s Hospital from 1 April 2019 to 31 March 2021. Total six patients were identified among 73 transplants performed. Median duration of onset was 2.5 months post-HSCT. Three patients died while all 3 survivors suffered from stage 2 to 5 chronic kidney disease despite administration of eculizumab. To conclude, recognition and diagnosis of TA-TMA is challenging. Clinical utility of complement blockage with eculizumab is limited.

Severe hypercholesterolemia mediated by graft-versus-host disease of liver in patients underwent allogeneic hematopoietic stem cell transplantation is a recognized yet overlooked phenomenon. Reports in literature is limited in both adult and pediatric population and none had been reported in Chinese children to date. As lipoprotein X hypercholesterolemia is due to regurgitation of cholesterol and bile salts into systemic circulation rather than overproduction by hepatocytes, usage of statins to downregulate cholesterol synthesis is not effective. Here we report 2 local cases to increase awareness of transplant physicians and endocrinologists of this association and avoid unnecessary and ineffective usage of statins.

The possibility that the bats could act as amplifying/reservoir host for Rift valley Fever virus (RVFV) during the inter-epidemic period was investigated. Four-hundred different samples were obtained from 100 Egyptian insectivorous and frugivorous bats (comprising two species) and tested by real-time RT-PCR assay (rRT-PCR). Pooled liver from insectivorous but not frugivorous bat samples were found positive for RVFV RNA, Partial S and M genome segments sequencing, and phylogenetic analysis showed that these viruses are genetically close to those circulated in livestock and humans during the previously reported RVFV outbreaks in Egypt 1977-1978, 1993 and 2003. To our knowledge, this is the first evidence of the RVFV genome in insectivorous bats in Egypt.

The novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in china and has rapidly spread to many countries around the world. The effective pharmacotherapy can reduce the mortality of COVID-19. Antiviral medications are the candidate therapies for the management of COVID-19. Molnupiravir is an antiviral drug with anti-RNA polymerase activity and currently is under investigation for the treatment of patients with COVID‐19. This review focuses on summarizing published literature for the mechanism of action of molnupiravir in COVID-19, safety, efficacy, and clinical trials of molnupiravir in the treatment of COVID‐19 patients.

A manifest nodoventricular accessory pathway with unusual electrophysiological manifestationsLonghai Tian MM，Long YANG MD, Yidong ZHAO MM，Qifang Liu MDDepartment of Cardiology，Guizhou Provincial People’s Hospital, Guiyang , ChinaCorresponding author: Qifang Liu E-mail：liuxu19782000 @163.comDisclosures:（None）Funding：This study was supported by Clinical Research Center Project of Department of science and technology of Guizhou Province.Key Words: Nodoventricular pathway, Preexcitation, Decremental conductionAbstractWe present an unusual case of a nodoventricular accessory pathway showing the degree of anterograde decremental conduction was more than the atrioventricular node decremental Conduction. In the patient，there was no rapid antegrade conduction and inducible reentrant tachycardias during electrophysiologic examine and no ablation was performed.Case reportA 24-year-old male was diagnosed to have preexcitation suggestive of a septal accessory pathway by a 12-lead ECG (Figure 1). Given his occupation, he was referred to our hospital for electrophysiologic testing and radiofrequency catheter ablation. During sinus rhythm, intracardiac electrograms revealed preexcitation with an A-H interval 80ms and H-V interval of 20ms. Ventricular overdrive pacing at a cycle length of 400ms resulted in ventriculoatrial dissociation. Atrial extra-stimuli (AES) were introduced during sinus rhythm with a cycle length of 500 ms, The coupling interval was reduced from 400 to 280 ms. This resulted in a gradual prolongation of the atrio-His interval that was associated with a prolongation of the H-V interval and a decrease in the degree of preexcitation (figure2). A decremental atrioventricular pathway was noted. Interestingly, This electrophysiologic phenomenon of decremental conduction suggests that the degree of anterograde decremental conduction of accessory pathway was more than the atrioventricular node (AVN).Atrial overdrive pacing (AOD) resulted in intermittent loss of preexcitation, PR prolongation, and Mobitz II atrioventricular block. At atrial pacing with cycle length of 300 ms, the H-V interval was suddenly increased to 102 ms and the QRS complex morphology showed a right bundle branch block pattern. This suggests anterograde conduction over accessory pathway and the QRS complex morphology presenting fully preexcitation (figure3). The ventricular insertion site of accessory pathway could have been predicted by the fully pre-excited QRS complex morphology. Spontaneous junctional beat was seen during electrophysiologic study. Consequently, the H-V interval was still 28ms and the QRS complex morphology remained minimal preexcitation，indicating the proximal insertion site of accessory pathway is AV node (figure 2).DISCUSSIONNodoventricular pathways（NVP） are rare accessory pathway that connect the posterior extensions of the AVN to the crest of the ventricular septum [1]. These pathways were anatomically described in 1941 by Mahaim and Winston. The diagnosis of manifest NVP is based on the following evidence: (1) upper insertion site is AVN, (2) lower insertion site is ventricular, (3) proving accessory pathway presence with decremental conduction manifestations and excluding fasciculoventricular pathway.In our case，the patient present preexcitation without symptoms of arrhythmias. The electrophysiologic study demonstrated evidence of anterograde decremental conduction in response to programmed atrial pacing. The QRS morphology and H-V intervals remained changed during AES, excluding a fasciculoventricular fiber. If the pathway was fasciculoventricular, preexcitation should remained fixed and H-V remained constant when conducting over either fast or slow pathways. Catheter pressure over AVN region resulted in junctional ectopy that remained preexcitation, indicating the proximal insertion site of accessory pathway is AV node. The sudden appearance of infra-His conduction block by AOD resulted in complete ventricular preexcitation，we can confirmed the distal insertion site is the septal of left ventricular based on fully pre-excited QRS morphology. All these findings indicate the presence of a manifest NVP pathway in the patient.In this case, on programmed atrial stimulation testing, there was decremental conduction over the pathway, resulting in a longer A–V and H-V time as the A1–A2 coupling interval decreased. As far as we are aware, this case is unique since the nodoventricular fiber show the degree of anterograde decremental conduction was more than the atrioventricular node. In contrast, most of the NVP bypass only a portion of the AV node with decremental conduction properties. Therefore, the preexcitation degree may increase and the H-V interval may decrease even to negative values during AES [2]. As far as our patient is concerned，The electrophysiologic features of anterograde decremental conduction may be due to the anisotropic conduction of the transitional area of the AV node and variability in the space construction of tissue[3]. In addition, the differential expression of connexin isoforms in the nodal area also may be responsible for more degree decremental conduction of NVP than AVN[4].[1] Nazer B, Walters TE, Dewland TA, et al. Variable Presentations and Ablation Sites for Manifest Nodoventricular/Nodofascicular Fibers. Circ Arrhythm Electrophysiol. 2019;12(9):e007337.[2] Ali H, Sorgente A, Lupo P, et al. Nodo- and fasciculoventricular pathways: Electrophysiological features and a proposed diagnostic algorithm for preexcitation variants. Heart Rhythm. 2015 ;12(7):1677-1682.[3] Katritsis DG, Marine JE, Latchamsetty R, et al. Coexistent Types of Atrioventricular Nodal Re-Entrant Tachycardia: Implications for the Tachycardia Circuit. Circ Arrhythm Electrophysiol. 2015;8(5):1189-1193.[4] Anderson RH, Quintana DS, Mori S, et al. Re-evaluation of the structure of the atrioventricular node and its connections with the atrium. Europace. 2020 ;22(5):821-830.Figure 1：Twelve-lead electrocardiographic recordings showing fixed and minimal preexcitation during sinus rhythm.Figure 2：Intracardiac recordings during programmed atrial stimulation demonstrating decreased preexcitation with a prolongation of the H-V interval. The last spontaneous junctional beat still showing a preexcitation morphology. Note that the QRS complex morphology change of the lead I and V1. His electrograms are recorded on the RV pole and red arrows indicate His potentials.Figure 3：Intracardiac recordings during atrial overdrive stimulation, demonstrating a longer HV interval and QRS complex morphology with fully preexcitation. Red arrows indicate His potentials.

Nitrate contamination of groundwater often occurs in urban and industrial areas due to point and non-point sources of anthropological activities. Groundwater constitutes a significant portion of the water supply system for Bahir Dar City in Ethiopia, though the level of groundwater pollution is not known. This study was conducted to assess the extent of the aquifer and groundwater pollution (nitrate) based on contaminant vulnerability risk mapping using the GIS integrated modified DRASTIC model. A field survey was conducted to collect samples from boreholes for nitrate analysis and to modify the DRASTIC model. Compared to the original intrinsic vulnerability assessment, land use as external factors changed from moderate-high to high vulnerability class from 18 % to 88 %. The FR-APH modified model showed a good correlation (0.53) compared to the other methods. Based on the FR-APH modified model, about 31% of the area was under moderate to high and high vulnerability range, 39% was under moderate vulnerability range while 30% was under low and moderate to low vulnerability range. The integrated vulnerability map showed high risk in the central part of the City due to the flat slope and shallow depth to groundwater. Besides, the sensitivity analysis indicated that the contribution of aquifer media and vadose zone to contaminant risk was found trivial. In general, groundwater at Bahir Dar city was found vulnerable to nitrate contamination and needs proper management.

Increasing interspecific and intraspecific diversity in agricultural systems provides promising solutions for sustainably increasing crop yield. Most research so far has focused on understanding plant–plant interactions to develop productive crop mixtures. The role of specific plant varieties in mediating such interactions is relatively understudied. Common bean is a widely cultivated crop in North Macedonia, usually grown in monocultures. Drought is one of the main yield limiting factors for beans in the country. Our study is part of a project that aims to improve bean production in North Macedonia by using measures such as intercropping. We first conducted a greenhouse experiment to determine drought tolerant bean varieties. The chosen varieties were further grown in a second greenhouse experiment with additional crop species in different species and cultivar mixtures. The aim of our study was to select plant/cultivar mixtures that result in higher bean yield and that can be trialed in farmer fields in North Macedonia. We hypothesized that the interaction of beans with the additional crop species will be influenced by water stress and by the identity of bean varieties. Overall, we recorded sorghum and chickpea presence to increase bean yield and sunflower presence to reduce bean yield, irrespective of drought stress. However, the effect of these additional species on bean yield varied across different bean varieties. This could partially be explained by variation in growth rate between varieties, where the fastest growing variety recorded the highest yield increase in crop mixtures. Our study highlights the role that crop genetic variation can play in mediating interspecific plant interactions. We suggest that to develop crop mixtures, it is not only important to consider the functional traits of the interacting plant species, but also of the different plant varieties.

Allergic diseases have a substantial epidemiological impact on pediatric population. Small molecule-based medicines have been traditionally used to manage the diseases. Omalizumab is the first monoclonal antibody-based medicine used in children’s allergy and shows great promises. It binds to free IgE and prevents it from binding to IgE receptor, thus interrupting the IgE-dependent allergic inflammatory cascade. Vast amounts of data demonstrates its effectiveness and well tolerance by patients, including the children. However, the drug was only approved to use in allergic asthma and chronic spontaneous urticaria (CSU), though other applications were explored in clinical trials. In this review, we summarized current pediatric applications of Omalizumab in allergic diseases, focusing on its usages beyond asthma and CSU, including allergic rhinitis, allergic bronchopulmonary aspergillosis, vernal keratoconjunctivitis, food allergy, and atopic dermatitis. In addition, we highlighted the unmet need and controversial issues of anti-IgE therapy.

Background: The effects of early-life exposure to house dust mite allergen and endotoxin on the development of asthma are unclear in the literature. We investigated the association of early-life exposure (0-36 months old) to house dust mite allergen and endotoxin with asthma incidence. Methods: In this novel, large-scale, nationwide birth cohort study, 5,017 participants were randomly selected from those who met the eligibility criteria. House dust was vacuum-sampled from the children’s bed within homes and assayed for the presence of dust mite allergen (Der 1) and endotoxin. The participants were classified into four quartiles (Q1-Q4) according to exposure levels. We defined the incidence of asthma and wheezing using a questionnaire at 12, 24, and 36 months old. Odds ratios (ORs) of the incidence of asthma and wheezing by age in Der 1 and endotoxin exposure level were estimated using logistic regression. Results: The cumulative incidence rates of asthma and wheezing during 0-36 months were 10.4% and 38.1%, respectively. Significant ORs were observed in asthma onset during 12-24 months old, asthma onset during 24-36 months old, and wheezing onset during 0-12 months old in the Q4 Der 1 group. In the Q4 endotoxin group, significant positive associations between endotoxin exposure and asthma (OR 2.00, 95% confidence interval [CI]: 1.03-3.85) and wheezing (OR 1.78, 95% CI: 1.01-3.12) onset during 24-36 months old were found. Conclusions: Our results indicated that high levels of early-life exposure to Der 1 and endotoxin in mattresses may be involved in the development of asthma.