Background: Although allergic reactions to honey are rare, there have been documented systemic allergic reactions following ingestion of honey. Moreover, there have been reports of supplementary bee feeding, honey adulteration and mould contamination in beehives that identify a potential for gluten and allergenic presence in honey. As such, this study aimed to investigate whether honey samples contained detectable levels of gluten, food and mould allergens that could pose a risk to consumers. Methods: Honey samples (n=40) of UK, EU and Non-EU origin were extracted and analysed for gluten using the R5 immunoassay and for major allergen content using quantitative multiplex arrays for allergens from milk, egg, peanut, soy, hazelnut, cashew and moulds. Results: Gluten was identified in 28% of samples analysed at concentrations ranging 2.5 to 13.8ppm. Milk allergens Bos d 5 and Bos d 11 were detected in 7% of samples, in concentrations ranging 0.37mg/kg-0.57mg/kg and 0.03mg/kg-0.18mg/kg respectively. Samples positive for milk allergen also contained detectable levels of gluten. No detectable amounts of egg, peanut, soy, hazelnut, cashew or mould allergen was identified in the samples. Conclusion: This novel study is the first of its kind in the identification of gluten and milk allergens within honey. Consumers may take reassurance in that levels of gluten detected in all samples fell below the current 20ppm ‘gluten free’ threshold. Similarly, none of the samples analysed for milk allergen content exceeded VITAL 3.0 reference doses. However, caution may be required for repeated consumption, leading to accumulating doses of gluten and allergen.

A document by Divya Bhattarai. Click on the document to view its contents.

Citric acid is one of widely used acids in industry and its recovery from waste streams is critical. Emulsion liquid membrane is one of the most effective recovery methods, which has been investigated in recent years. Numerous transport phenomena parameters affect the efficiency of this process. From the process equipment design point of view, optimization based on overall cost is of great importance and important equipment sizing decisions/constraints must be considered. A physics-based model for a full-scale simulation of emulsion liquid membrane systems is very useful. This work is focused on developing and verifying such a model. A coupled particle/mixture simulation was carried out in this work and the modeling results were fitted on the experimental data. The model is capable of simulating similar systems with a reasonable accuracy.

The developed models for separating micropollutant surfactants in bubble columns consider mass balance and not the adsorption thermodynamics of micropollutant surfactants on bubble surfaces. Additionally, the dramatic increase of the surface tension of diluted surfactant solutions with time during the removal of surfactant from solutions was ignored. Thus, the main objective of this work is to examine removal of surfactant micropollutants in a bubble column using a model that considers both mass balance and thermodynamics. The results showed that the removal of surfactant strongly depends on adsorption thermodynamics of surfactant on bubble surfaces particularly at a lower surfactant concentration considering that the surface tension of solutions dramatically increased during the separation process. The best separation performance was typically achieved when gas flow rates and liquid fractions were low. This work demonstrates that adsorption thermodynamics on bubble surfaces should not be ignored when modeling the removal of surfactant micropollutants from liquid.

Aims: Youkenafil is a novel selective phosphodiesterase type 5 inhibitor to treat erectile dysfunction. Since it was mainly metabolized through cytochrome P450 3A4/5 (CYP3A4/5) in vitro, the effects of itraconazole and rifampicin (potent CYP3A4/5 inhibitor and inducer, respectively) on the pharmacokinetics of youkenafil and its main metabolite (M1) were investigated in two clinical studies. Methods: Each study enrolled thirty healthy male subjects. In study 1, subjects were given a single dose of youkenafil (50 mg on Days 1 and 13) and multiple doses of itraconazole (200 mg once daily from Days 6 to 14). In study 2, subjects were given a single dose of youkenafil (100 mg on Days 1 and 20) and multiple doses of rifampicin (600 mg once daily from Days 6 to 20). Results: Itraconazole significantly increased the systemic exposure to youkenafil and M1. The geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) for the AUC0-t, AUC0-∞ and Cmax of youkenafil were 1198.58% (900.33%–1595.63%), 1162.54% (874.69%–1545.11%) and 632.17% (500.40%–798.64%), respectively. Conversely, rifampicin significantly decreased the systemic exposure to youkenafil but had a slight effect on M1. The GMRs (90% CI) for the AUC0-t, AUC0-∞ and Cmax of youkenafil were 1.72% (1.27%–2.33%), 1.80% (1.33%–2.43%) and 1.77% (1.27%–2.47%), respectively. All subjects tolerated well in both studies. Conclusion: Itraconazole increased youkenafil AUC and Cmax by 12- and 6-fold, respectively. Rifampicin decreased youkenafil AUC and Cmax both by about 98%. Therefore, combined administration of youkenafil with potent inhibitors or inducers of CYP3A4/5 should be avoided or carefully monitored.

A bezoar is a packed group of undigestable or partially digested material that often leads to gastrointestinal obstruction. Eating cotton balls to fill up the stomach and avoid hungry may seem harmless, but has serious implications.

Background: In the absence of a clear clinical history of reaction, diagnosis of cashew allergy using skin prick tests (SPT) or cashew-specific IgE requires a high number of oral food challenges (OFC). We recently showed that Ana o 3 sIgE alone, or a two-step diagnostic algorithm using cashew sIgE followed by Ana o 3 sIgE can reduce need for OFC. We aimed to determine if either of these approaches can provide a cost reduction to the health system compared to cashew SPT alone. Methods: Pooled individual level data from 6 studies was used to determine diagnostic accuracy and OFC rate. Two studies used cashew SPT (n=567, 198 allergic), with 95% positive and negative predictive values of ≥12mm and <3mm. Four studies were included in the pathways for Ana o 3 sIgE alone or a 2-step algorithm incorporating cashew and Ana o 3 sIgE (n=271, 156 allergic). Cut-offs used were ≥8.5kUA/L and ≤0.1kUA/L for cashew sIgE and ≥0.35kUA/L and ≤0.1kUA/L for Ana o 3 sIgE. Costs were constructed based on unit prices from hospital inpatient admissions, expenses incurred by families, individual patient data on allergic reaction types and rates and adrenaline autoinjector carriage, applying a health system perspective. Results: Modelled data through the Ana o 3 pathway resulted in a 46.43% cost reduction (\euro307,406/1000 patients) compared to using cashew SPT alone (\euro573,854/1000 patients). The 2-step algorithm resulted in a 44.94% cost reduction compared to SPT alone (\euro315,952.82/1000 patients). Both the Ana o 3 pathway and 2-step algorithm resulted in a 79-80% reduction in OFCs compared to SPT. Conclusions: Using Ana o 3 as a standalone test for cashew allergy diagnosis or a 2-step algorithm incorporating cashew sIgE and Ana o 3 sIgE is accurate and results in a large reduction in both OFCs and health system costs compared to cashew SPT alone.

Background: Sutures act as excellent surfaces that allow bacteria to penetrate wounds. In this way, they cause microbial colonization, biofilm formation, and thus surgical sites infection. Such side effects have a great impact on the human life quality. Therefore, the concerns about this issue are increasing rapidly. At this point, microalgae have been drawn attention with their high-biologically active compounds. In this study, A. platensis, H. pluvialis, C. minutissima, B. braunii and N. muscorum extracts were investigated for their usability potential as surgical suture covering material. Methods: In order to evaluate their biocompatibility, the antibacterial activities and cytotoxic effects of the sutures [PGLA and PDO] coated with these extracts were determined. Major results: The results showed that A. platensis and N. muscorum extracts have acceptable cytotoxic levels on L929 cell line according to ISO 10993-5. Moreover, A. platensis extract was found to be the most promising suture coating material for the human applications. Conclusions: The surgical sutures have been successfully coated with extracts derived from microalgae species. As a result, it has been proven that antibacterial sutures could be obtained, and the biological properties of surgical sutures could be improved by using microalgal antibacterial extracts. In summarize, it appears as microalgal extracts can used in biological materials with potential application in the pharmaceutical industries due to its ingredients.

In this paper, a new numerical method is proposed for solving nonlinear boundary value problems (BVPs) based on Bézier curves. The well-known Falkner-Skan equation which is a third-order nonlinear BVP is considered to examine the efficiency of the presented method in terms of accuracy, convergence and stability. The presented hybrid technique takes advantage of the Method of Adjoint together with a novel predictor-collector multi-step integration procedure based on the Bernstein Polynomials and Bézier curves. In this method, first the governing equation is rewritten as a set of first-order differential equations, and the semi-infinite domain is mapped into a unit interval using appropriate coordinate transformation. The missing initial value is then determined by employing an appropriate iterative algorithm using the Method of Adjoint. Finally, the resulting initial value problem is solved using the new multi-step predictor-corrector scheme. Results of the presented method are compared with those appeared in the literature which show excellent agreement while having higher efficiency. Moreover, the accuracy and efficiency of the method are further examined by comparing predictions for the Falkner-Skan equation with five well-known multistep methods in the literature. Finally, from the stability point of view, the study also revealed that the new technique is more stable in comparison with other prominent methods.

Purpose: Children with unresectable cervico-medullary low-grade glial tumors (CMTs) have poor progression-free survival when treated with conventional chemotherapy and radiation. The BRAFV600E mutation occurs in many low-grade glial tumors that are amenable for targeted therapy using mutation-specific kinase inhibitors. However, these inhibitors’ effectiveness and best treatment duration in these tumors setting are not defined. Method: Retrospective description of three cases of childhood cervico-medullary low-grade tumor with BRAFV600E mutation and their response to BRAF inhibitor therapy with Dabrafenib. Results: Dabrafenib therapy was provided as first line for two patients and second line for one patient with CMTs. All patients experienced rapid tumor regression and significant and durable clinical and radiological improvement. The targeted therapy was tolerated well in two patients despite the long-term use of 3-5 years, while one patient stopped therapy after 1 year due to serious adverse event that was reversible upon discontinuing therapy. Conclusion: Dabrafenib was effective and well-tolerated in two of the three patients. We observed clinical and radiological response that demonstrates the role of targeted therapy as alternative for adjuvant chemotherapy and radiation in BRAFV600E unresectable tumors. These cases indicate the need to re-evaluate the therapeutic approach in children with CMT, the early use of Dabrafenib and the treatment duration and to explore the possible adverse and late effects of this promising therapy.

Background and Purpose. Skeletal muscle relaxants (SMRs) are commonly co-prescribed with potentially interacting medications that may contribute to increased risk of unintentional traumatic injury (hereafter, injury). While prior research has investigated clinical outcomes for some pairwise drug interactions involving SMRs, drug interactions involving more than two drugs, such as drug triads (3DIs), largely remain unexamined. We sought to identify SMR 3DI signals associated with injury via automated high-throughput pharmacoepidemiologic screening of 2000–2019 healthcare data for members of commercial and Medicare Advantage health plans. Experimental Approach. We performed a self-controlled case series study for each drug triad consisting of an SMR base pair (i.e., concomitant use of an SMR with another medication), and a co-dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base pair. We included patients aged ≥16 years with an injury occurring during base pair-exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base pair + candidate interacting precipitant (i.e., triad) versus the SMR-containing base pair alone. Key Results. Among 58,478 triads, 29 were significantly positively associated with injury; confounder-adjusted RRs ranged from 1.39 (95% CI=1.01–1.91) for tizanidine+omeprazole with gabapentin to 2.23 (95% CI=1.02–4.87) for tizanidine+diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated. Conclusions and Implications. We identified 29 SMR 3DI signals associated with increased rates of injury. Future etiologic studies should confirm or refute these SMR 3DI signals.

A document by Mahima Khatri Mahima Khatri. Click on the document to view its contents.

Background: A 12-year-old girl diagnosed with intermediate risk B-ALL in 2017 received chemotherapy according to CCLG-2008 ALL protocol and achieved a complete remission (CR) after induction. However, four years later, she had a first bone marrow relapse and received treatment with HKPHOSG Relapsed ALL 2007 protocol. During maintenance chemotherapy, approximately one year after the first relapse, she developed a second bone marrow relapse with NT5C2 gene mutation detected. Tumor burden was not well controlled after DEAV chemotherapy, with the blasts in bone marrow increasing from 49.3% to 96%. The analysis of high-throughput drug sensitivity of tumor resistant genes was consistent with the poor response to chemotherapy. Procedure: CAR-T cell immunotherapy bridged to HSCT was introduced at this stage. Following peripheral lymphocyte apheresis, the patient received lymphodepleting conditioning with fludarabine and cyclophosphamide three days before CAR-T cell infusion. Dexamethasone and carfilzomib were then given according to the outcome of high-throughput drug sensitivity test. Result: Around 68.6% blasts were detected by flow cytometry at the day of CAR-T cell infusion. The patient experienced grade 1 CRS without ICANS. CR of morphology and molecule biology was achieved on day 28 after CAR-T cell infusion. Finally the child received haploid-HSCT and remained in remission. Conclusion: Overall, this report reveals that the combination of drug sensitivity test with lymphodepleting conditioning could significantly reduce the tumor burden before infusion of CART cells, and patients may achieve deeper remission and obtain opportunity for transplantation.

Blastocystis sp. is a unicellular protozoan and one of the most common gastrointestinal eukaryotic parasites in humans and animals. It is distributed worldwide, but its pathogenic role is still controversial. Blastocystis sp. is subdivided into 33 subtypes, and existing different subtypes imply host specificity in various species. The study aimed to investigate in detail the host range of Blastocystis sp., given the limited studies. A total of 720 fecal samples from 132 animal species, 140 (19.44%) were PCR positive for Blastocystis sp., with 43.67% (31/71), 5.89% (7/119), 34.87% (53/152), 2.56% (1/39), 16.67% (2/12), 22.22% (4/18), 37.50% (3/8) and 12.96% (39/301) in Nonhuman primates, Carnivora, Artiodactyla, Perissodactyla, Proboscidea, Diprotodontia, Rodentia and aves, respectively. Sequence and phylogenetic analysis showed ten known subtypes (ST1, ST2, ST3, ST4, ST5, ST7, ST8, ST10, ST14, and ST23) of Blastocystis sp. in the present study, with ST10 as the predominant subtype in all animals. However, there were differences in dominant subtypes among the eight groups of animals, and ST2 of Non-human primates, ST3 of Carnivora, ST10 of Artiodactyla, ST23 of Proboscidea, ST1 of Diprotodontia, ST1 and ST4 of Rodentia and ST5 of aves, respectively. This is the first report of Blastocystis sp. infection in 48 species to the best of our knowledge. These results not only enriched the host range of Blastocystis sp. and filled the data of vacant animals but also provided a reference for preventing and controlling Blastocystis sp. infection between animals and humans.

We report an uncommon presentation of kidney synovial sarcoma (KSS) in childhood, discovered by abdominal pain and gross hematuria, associated to radiological and pathological challenges to the diagnosis. After necessary biopsy, adequate chemotherapy, following European Pediatric Soft Tissue Sarcoma Study Group Non-Rhabdomyosarcoma NRSTS 2005 Protocol, completely resection was possible. There are just few cases at global literature review of SSR in child, a good response to treatment is performed a completely resection (R0), besides a close follow-up (strongly recommended). The risk of metastasis is strongly correlated that is why diagnosis represent a big deal.

We report a case of recurrent stroke and frequent TIAs to explore the underling mechanisms of her repeated episodes of TIAs and tailored efficient antiplatelet regimen.

Hantaviruses are zoonotic viruses harboured and assumed to be transmitted to humans by rodents. Numerous species of hantaviruses have been identified in a broad range of vertebrate animals expanding the potential reservoirs and range of these viruses. To elucidate ecological patterns influencing hantavirus infection among bats and then the dynamics of hantavirus transmission in south-eastern Brazil, 275 bats were captured from February 2012 to April 2014, in distinct landscapes with varying forest amounts. We investigated potential ecological correlates related to hantavirus infection among 53 bats tested for serological evidence of infection. Areas with low intermediate values for species diversity and high dominance of species had higher infection counts than other areas, but the correlations were non-significant. With intermediate amounts of percentage of forest cover presented higher infection counts were observed. More studies should address differences in probabilities of hantavirus infection across species since they may have different ecological requirements. We report potential ecological correlates for hantavirus infection among bats and provide data on bat diversity and distribution across seven fragmented landscapes compositions in the Neotropics. We suggest that bats may play an underestimated role in the interspecies transmission dynamics of hantaviruses, especially within the context of fragmented landscapes.

In literature until today, many authors have studied special sequences in different number systems. In this paper, using the Leonardo numbers, we in- troduce the bicomplex Leonardo numbers. Also, we give some algebraic prop- erties of bicomplex Leonardo numbers such as recurrence relation, generating function, Binet's formula, D'Ocagne's identity, Cassini's identity, Catalan's identity and Honsberger identity.

BACKGROUND MTX induced neurotoxicity is often associated with LE, and diagnosed by white matter hyperintensities in MRI. This study was done to study: 1) risk and prevalence of LE in ALL receiving MTX through sequential MRI brain. 2) Safety of re-administration of MTX in toxic LE. 3) Relationship of serum homocysteine, B12 and folate with MTX induced LE. METHODOLOGY 34 pediatric ALL/lymphoblastic Lymphoma patients of age ≤18 years between June 2019 and 2020 were enrolled. Induction chemotherapy was initiated as per modified ALL IC BFM 2002 protocol. All patients underwent MRI brain and serum homocysteine, B12, folate level sequentially as per protocol at 4 occasions. 1st – at diagnosis; 2nd – post consolidation; 3rd – post extra compartment therapy; 4th – in maintenance. RESULTS LE secondary to MTX occurred in 7of116(6.03%) on MRI brain in 5of33(15.15%) patients of which 1(3.03%) had symptomatic LE and 4(12.12%) were asymptomatic. There was no difference in incidence with respect to mode of MTX administration. There was no increase in incidence after 4 courses of HD-MTX. MRI at baseline was not a predictor of development of LE. 3of5 LE patients had abnormal B12/folate/homocysteine with corresponding abnormal MRI brain. Low folate and/or b12 levels also led to increased systemic toxicity in few patients post methotrexate therapy. t(1:19) and t(9:22) were associated with leukoencephalopathy but t(12:21) was not associated with LE. CONCLUSION Most patients of MTX induced LE can be rechallenged with MTX. MRI at baseline is not a predictor of development of LE.

Successful water resource planning and management can be ensured by understanding the hydrological response of watersheds and non-point pollutions to land use/land cover and climatic changes. This study aims to present the effects of climate and land-use changes on hydrological processes and NPS pollutions to help prepare accurate water management policies based on their impacts. In this study, the Soil and Water Assessment Tool (SWAT) was applied to predict climate and land-use impacts on flow rate and non-point pollutions (NPS) in Namazgah Dam Basin in Turkey. Two different climate change scenarios, RCP 4.5 and RCP 8.5, and land-use scenarios, conversion of shrubland to forest and conversion of agricultural areas to the forest, were used, and statistical analyses were utilized to assess the results. At the end of this study, it was predicted that there would be an increase in phosphorus and nitrate loads and a decrease in streamflow rate.

Introduction. The H3K27M-mutant diffuse midline glioma (DMG) was first included in the WHO Classification of CNS (central nervous system) tumors in 2016, and confirmed in its fifth edition. The biological behavior and dismal prognosis of this tumor resemble DIPG (diffuse intrinsic pontine gliomas). Homogeneously-treated series are rarely reported. Methods. From 2016 onwards, we treated patients with DMG with radiotherapy and concomitant/adjuvant nimotuzumab/vinorelbine, plus re-irradiation at relapse, as already done for DIPG (DOI10.1007/s11060-014-1428-z). Results. We treated nine patients, seven females, median age at diagnosis of 13 years-old. Tumor sites were: thalamic in five cases, pontocerebellar in two, pineal in one, and paratrigonal with nodular/leptomeningeal dissemination in one. Three patients were biopsied, and six had partial tumor resections. Central review of the pathologists’ diagnoses was performed. The median time to local progression was 12.7 months, and the median overall survival was 17.8 months. Six patients died of tumor progression, one of cerebral bleeding whose tumor was progressing. Two were alive, one in continuous remission, the other after a relapse, at 38.6 and 46.3 months after diagnosis, respectively. Progression-free survival was 33.3% at one year. Overall survival was 88.9%, 33.3% and 22.2% at 1, 2 and 3 years, respectively. Conclusions. This is one of only a handful of reports on homogeneously-treated series. The results obtained are comparable with those seen in patients with DIPG. Given the phenotypically- and molecularly-defined setting of DMG and severe outcome in this orphan population, they should be treated and included in registries and protocols of DIPG.

Temperature has a profound effect on the growth and development of ectothermic animals. However, the extent to which ecologically-driven selection pressures can adjust thermal plastic responses in growth schedules is not well understood. Comparing such responses between sexes provides a promising but underexploited approach to evaluating the evolvability of thermal reaction norms: males and females share largely the same genes and immature environments but experience different ecological selection pressures. In this study, we performed a meta-analysis of sex-specific thermal responses in insect development times. We show that sex-specific responses of development times to temperature variation are broadly similar. Moreover, sex differences in thermal plasticity are considerably less pronounced than sex differences in plastic responses induced by variations in larval diet. Our results point at the existence of substantial constraints on the evolvability of thermal reaction norms in insects, an essential aspect to consider in predicting evolutionary responses to climate warming.

Seagrasses are vital organisms in coastal waters, and the drastic demise of their population in the last decades has worrying implications for marine ecosystems. Spatial models for seagrass meadows provide a mathematical framework to study their dynamical processes and emergent collective behavior. These models are crucial to predict the response of seagrasses to different global warming scenarios, analyze the resilience of existing seagrass distributions, and optimize restoration strategies. In this article, we propose a model that includes interactions among different species based on the clonal growth of seagrasses. We present a theoretical analysis of the model considering the specific case of the seagrass-seaweed interaction between _Cymodocea nodosa_ and _Caulerpa prolifera_. Our simulations successfully reproduce field observations of shoot densities in mixed meadows in the Ebro River Delta in the Mediterranean Sea. Besides, the proposed model allows us to investigate the possible underlying mechanisms that mediate the interaction among the two macrophytes.

Increased atmospheric reactive nitrogen (ARN) has significant impacts on N balance in rice ecosystems. As an important N deposition process, knowledge on direct canopy uptake of rice is limited. A water-culture rice-growing system with 15N labeled nutrient solution was developed to assess canopy uptake of ARN under field conditions. Gross uptake was assessed using plant N partitioning approach and net gain of ARN through canopy uptake was estimated based on N balance in the system. We found gross uptake was 23.1 and 38.2 kg N·ha-1 during transplantation-elongation and elongation-maturity periods, respectively. However, 26.9 kg N·ha-1 of labeled fertilizer N was lost from rice canopy. Therefore, net gain of ARN via canopy exchange was 34.3 kg N·ha-1 over the whole growing season. Our results demonstrate high amount of direct canopy uptake of ARN input to rice ecosystems—an important N process that has not been considered in present N budget establishment.