Aims: The present study was conducted to evaluate the safety of celery seed extract (Apium graveolens), as a medicinal herb with active ingredients such as 3-n-butylphthalide (NBP), in hypertensive patients. Methods: This study was a randomized, triple-blind, placebo-controlled, cross-over clinical trial. Hypertensive patients (51 participants) received 4 celery seed capsules (a total of 1.34g extract per day) or 4 placebo capsules per day for 4-weeks as a supplement to their usual medication regimen. Results: The results indicated that the celery seed capsule not only was safe for hypertensive patients but caused a reduction in BP, FBS, and lipid profile values. Also, it had beneficial effects on kidney and liver functions. No significant change was observed in blood cells and serum electrolytes (P>0.05). The mean reduction in BUN and SCr were 3.43 and 0.075 mg/dL, and in SGPT and SGOT were 4.08 and 3.03 U/L, respectively (P<0.05). FBS reduced from 108.53 to 97.96 mg/dL after 4-weeks of celery administration (P<0.01). The decrease in TC, TG, LDL, and increase in HDL were 16.37, 16.22, 11.84, and 2.52 mg/dL, respectively (P<0.001). Conclusions: According to the promising results of this clinical trial, celery seed extract can be considered a safe supplement for hypertensive patients.

Background: Allergic rhinitis (AR) is a major non-communicable disease that affects the health-related quality of life (HRQoL) of patients. AR is significantly related to asthma also affecting HRQoL. However, data on HRQoL and symptom control in AR patients with comorbid asthma are lacking. Objective: To assess the differences of symptom control and HRQoL in AR patients with and without comorbid asthma. Methods: In this multicentre, cross-sectional study, patients with AR were screened and administered questionnaires of demographic characteristics and health conditions (symptoms/diagnosis of AR and asthma, disease severity level, and allergic conditions). HRQoL was assessed using a modified version of the RHINASTHMA questionnaire and symptom control was evaluated by a modified version of the Control of Allergic Rhinitis/Asthma Test (CARAT). Results: Out of 643 patients with AR, 500 (78%) had asthma as a comorbidity, and 54% had moderate-severe intermittent AR, followed by moderate-severe persistent AR (34%). Patients with both AR and asthma had significantly higher RHINASTHMA scores than the patients with AR alone (e.g., median RHINASTHMA-total score 84 vs. 48.5, respectively). Conversely, CARAT scores were significantly lower in AR with comorbid asthma than in the patients with AR alone (median CARAT-total score 16.5 vs. 23, respectively). Upon stratifying asthma based on severity, AR patients with severe persistent asthma had worse HRQoL and control than AR patients with mild persistent asthma. Conclusions: Our observation of poorer HRQoL and symptoms control in AR patients with comorbid asthma supports the importance of a comprehensive approach for the management of AR in case of a comorbid allergic condition.

IntroductionCovid-19 Pandemic has changed the entire world economy and impacted most of the businesses. It caused a transformation in the way people live, interact and make purchase decisions. Even under these conditions, banks are responsible for maintaining liquidity flows and should continue their duty to finance the economy, to continue to lend to individuals and business and to maintain their customer base. So banks are trying to transform their strategies that define their future and to rethink their entire flow of activities. The current crisis is an opportunity to change the banking business as well as a rethinking of the development of the bank-customer relationship. These involve not only the digitalization and modernization of financial activity of banks, but also the development of skills and the promotion of a sustainable bank-customer relationship.Covid-19 pandemic has imposed a different approach to the banking activity in order to facilitate its consumers’ access to the banking operations. It accelerated digitalization in the banking system. Banks noticed a shift in customer approach towards digital or electronic banking. So that banks have provided customers with online banking tools thereby they can perform their simple and convenient operations at anytime and anywhere. Mobile banking allows the users to access their accounts, check the status of the services online, timely update and handle transactions and communication with bank, anytime, anywhere around the world. Mobile banking wallets has boosted the banking sector and enhances daily transactions in an efficient and safe mode.

Objective: To assess clinical outcomes of Transcatheter Aortic Valve Replacement in stenotic bicuspid aortic valve patients. Methods: The search of clinical articles was conducted by using Pubmed, Embase, The Cochrane Library databases. We compared clinical outcomes of efficacy and safety endpoints between stenotic bicuspid aortic valve(BAV) and tricuspid aortic valve(TAV) patients according to Valve Academic Research Consortium-2 criteria. Results: 20 studies were included in the current meta analysis. BAV groups showed higher post-procedural paravalvular leakage and stroke rate compared with TAV groups. No discrepancy were detected in the mean aortic gradient and aortic valve area between two groups. The 30-day and 1-year mortality were similar in both groups. BAV group was more likely to be associated with lower device success and higher incidence of conversion to surgical aortic valve replacement, second valve implantation and annular rupture. No difference was found in the incidence of permanent pacemaker implantation, acute kidney disease, life-threatening bleeding and myocardial infarction between bicuspid and tricuspid patients. Conclusion: The efficacy and safety of TAVR in BAV patients were not as ideal as those in TAV patients. Cautious and adequate discussion must be made before we decide to perform TAVR procedure for BAV patients.

The isohydric-anisohydric continuum describes the relative stringency of stomatal control of leaf water potential ( ψleaf) during drought. Hydroscape area ( HA) – the water potential landscape over which stomata regulate ψleaf – has emerged as a useful metric of the iso/anisohydric continuum because it is strongly linked to several hydraulic, photosynthetic, and structural traits. Previous research on HA focused on broad ecological patterns involving several plant clades. Here we investigate relationships of HA to climatic conditions and functional traits across ecologically diverse but closely related species while accounting for phylogeny. Across a macroclimatic moisture gradient, defined by the ratio of mean annual precipitation to mean annual pan evaporation ( P/Ep), HA decreased with P/Ep for ten Eucalyptus species. Greater anisohydry reflects lower turgor loss points and greater hydraulic safety, mirroring global patterns. More isohydric species have mesophyll photosynthetic capacity that is more sensitive to ψleaf, consistent with an earlier model for optimal stomatal behavior. Hydroscapes exhibit little plasticity in response to variation in water supply, and the extent of plasticity does not vary with P/Ep of native habitats. These findings strengthen the case that HA is a useful metric for characterizing drought tolerance and water-status regulation.

Oleogels and emulgels were developed with winterized algal oil from Schizochytrium spp. rich in ω-3 fatty acids (FAs) to overcome physical limitations of using a highly unsaturated lipid source in food applications. Both gel types were developed using monolaurin or a combination of mono- and diacylglycerols (MAG/DAG) as the gelator at concentrations of 8, 10, or 12%, w/w, in oil or emulsion. A 14-day accelerated oxidation study was conducted using peroxide value, p-Anisidine value, and change in FA composition to measure the level of oxidation. Oleogel and emulgel samples exhibited a higher oxidative stability than bulk algal oil and oil-in-water emulsion as control groups, respectively. The 12% monolaurin oleogel outperformed others in oxidative stability, preventing oxidation of approximately 17.96% and 20.43% of EPA and DHA, respectively, compared to algal oil. Physical characteristics including thermal behavior, solid fat content (SFC), rheology, morphology, and polymorphism were studied. Results indicated that MAG/DAG oleogels and monolaurin emulgels were the most physically stable. The SFC of 12% MAG/DAG oleogel at 30 °C was 10.27% whereas 12% monolaurin oleogel was only 4.51%. Both gel types developed with monolaurin and MAG/DAG could be used for different applications as they exhibited desirable qualities such as oxidative stability and improved physical characteristics.

A Pneumothorax in the Setting of COVID-19 Associated Pneumatoceles in a Pediatric PatientEsther Blondeau-Lecomte, BA1, Nancy Joseph, MBBS11Department of Pediatrics, University of Florida, Gainesville, FL, USA

Cogan syndrome is an autoimmune disorder characterized with ocular and vestibular symptoms and only minority (less than 15%) of patients suffer from systemic disease which is explained by autoimmuune vasculitis.Cardiovascular involvement of Cogan syndrome is rare and  effects mostly subclavian and carotid arteries, aortic valve or aorta.Mitral valve involvement is rare. Below, we report a case with mitral valve involvement and Cogan syndrome. 39 year old male patient had admitted to our hospital with shortness of breath. He had history of previous aortic valve implantation in 2012. His transthorasic echocardiography demonstrated massively thickened mitral leaflets as well as moderate to severe mitral regurgitation.Transoesaphageal echocardiography revealed moderate to severe mitral regurgitation, severe thickening in both mitral leaflets and and mild restriction in leaflet motions.. Surgery was decided in case progressive dyspnea develops. Cogan syndrome is a vasculitis which effects medium sized arteries and aortic valve. Mitral valve involvement is rare. Differential diagnoses , as well as using certain medical treatments and rheumatic valve disease, were ruled out. This case is one of the rare examples of Cogan syndrome with mitral valve thickening.

Adaptive habitat construction is a process by which individuals alter their environment so as to increase their (inclusive) fitness. Such alterations are a subset of the myriad ways that individuals condition their environment. We present an individual-based model of habitat construction to explore what factors might favor selection when the benefits of environmental alterations are shared by individuals of the same species. Our results confirm the predictions of inclusive fitness and group selection theory and expectations based on previous models that construction will be more favored when its benefits are more likely to be directed to self or near kin. We found that temporal variation had no effect on the evolution of construction. For spatial heterogeneity, construction was disfavored when the spatial pattern of movement did not match the spatial pattern of environmental heterogeneity, especially when there was spatial heterogeneity in the optimal amount of construction. Under those conditions, very strong selection was necessary to favor genetic differentiation of construction propensity among demes. We put forth a constitutive theory for the evolution of adaptive habitat construction that unifies our model with previous verbal and quantitative models into a formal conceptual framework.

This paper is devoted to dealing with the following nonlinear Kirchhoff type problem with general convolution nonlinearity and variable potential: $$\left\{\begin{array}{ll} -({a + b\int_{{\R^3}} | \nabla u{|^2}dx})\Delta u + V(x)u =(I_{\alpha}\ast F(u))f(u),\quad \text{in}\ \ \R^3,\\ u \in H^{1} (\R^{3}), \end{array}\right.$$ where $a>0$, $b\geq0$ are constants, $V\in C^1(\R^3,[0,+\infty))$, $f\in C(\R,\R)$, $F(t)=\int_{0}^{t}f(s)ds$, $I_{\alpha}:\R^{3}\rightarrow \R$ is the Riesz potential, $\alpha\in(0,3)$. By applying some new analytical tricks introduced by [X.H. Tang, S.T. Chen, Adv. Nonlinear Anal. 9 (2020) 413-437], the existence results of ground state solutions of Poho\v{z}aev type for the above Kirchhoff type problem are obtained under some mild assumptions on $V$ and the general “Berestycki-Lions assumptions” on the nonlinearity $f$. Our results generalize and improve the ones in [P. Chen, X.C. Liu, J. Math. Anal. Appl. 473 (2019) 587-608.] and other related results in the literature.

Chemotherapy-induced hepatic toxicity is a frequent problem, with some patients developing liver failure. Unfortunately, therapeutic possibilities are still lacking. Here, we describe two patients that developed important liver toxicity in our center following high-dose chemotherapy and were successfully treated with high-dose N-acetylcysteine.

Objective To evaluate the optimal Kryptor threshold for sFlt-1/PlGF on PE among the hypertensive pregnant women. Design A single centre prospective study. Setting Guangzhou Women and Children’s Medical Care Center. Population or Sample 565 singleton pregnant women with hypertension from January 2018 to June 2021. Methods PlGF/sFlt-1 and perinatal data were collected and logistic regression was used to explore the cutoffs of sFlt-1/PlGF for PE from different hypertension types in HDP. Main outcome measures PlGF/sFlt-1 cutoff of PE and chrHBP with PE in HDP . Results: The sFlt-1 /PlGF ratio in PE and chrHBP with PE were significantly higher than GH & chrHBP, in which early-onset were higher. For gestatioanl hypertension, sFlt-1 /PlGF ratio> 36.44 could rule in PE occurence(AUC=76.17% - 78.39%) in 1-4week with PPV 0.91-0.94 & NPV 0.67 before 34 weeks, while sFlt-1 /PlGF ratio< 51.52 could rule out PE occurrence (AUC=75.29% - 78.39%) in 1-4 weeks with NPV 0.91-0.96 & PPV 0.62-0.73 after 34 weeks. For chronic hypertension, sFlt-1 /PlGF ratio> 47.78 could rule in PE occurrence (AUC=82.5% - 86.36%) in 1-4 weeks with PPV 0.9-0.96 & NPV 1.0 before 34 weeks, while sFlt-1 /PlGF ratio< 28.61 could rule out PE occurence(AUC=72.41% - 73.03%) in 1-4 weeks with NPV 0.88 & PPV 0.43-0.79 after 34 weeks. Conclusion: Lower sFlt-1/PlGF had high positive potential to identify the patients to develop early onset PE from gestational and chronic hypertension, which could complement the strategy to hypertensive disorders in pregnany. Funinding Guangzhou science and technology Program Project (202102010163) .

This is a commentary on a single-institution retrospective review that describes the short-term outcomes of the pediatric patients who underwent re-operative surgery for residual or recurrent coarctation after a previous coarctation repair. There were 51 patients over 12 years.

The volcanic aquifer of Bilate river basin (BRB) that situated on the southwestern side of the MER serve as sole reservoir of water supply for urban and rural people found in the basin. This study investigates residence time and groundwater recharge process in the Bilate river basin. For the first time, this research work delivers information on the resident time and groundwater recharge on the basis of multi tracer approach (CFC’s, Cl, δ 18O and δD). The δ 18O and δD value of groundwater found in the range of -4.9 to -1.1‰ and -31 to 5.3‰, respectively. It is shown that stable isotopic value of groundwater drawn along or close to AAMWL and GMWL, indicates that groundwater recharge is of meteoric origin. The groundwater of BRB volcanic aquifer comprises substantial amount of CFCs concentration. It is observed from CFC data that the oldest component of groundwater was recharged prior 1950, while the younger component recharged in different time as of 1950. The relation found between CFC’s indicates that groundwater comprise mainly of binary mixture with young groundwater in the age of 20-25-year-old and that of groundwater older than 60 years. The fraction of young water in the groundwater ranges from 0.134 to 0.89 and shows decreasing trend from highland towards the rift. CFC-113 is conservative in the system and used to determine groundwater lifetime in the Bilate river basin that ranges from 26 to 63 years. The conservative chloride method i.e. chloride mass balance employed to Bilate river basin calculated yearly average groundwater recharge to be 219 mm/y which accounted for 21% of the mean annual areal rainfall. This research can help us better understand how groundwater circulation and recharge mechanism works, as well as how long groundwater stays underground in the complex hydrogeological setting of rift volcanic aquifer.

Introduction- Necrotising fasciitis is a rapidly progressive disease with high morbidity and mortality. Head and neck necrotising fasciitis is a rare clinical entity but may be admitted under an ENT specialist team. An understanding of the presenting features and the need for prompt management is imperative. Case Series-We present a series of patients admitted to hospitals across Greater Glasgow, United Kingdom under Otoloryngology and Maxillofacial surgical teams with head and neck necrotising fasciitis over an 8-year time period. Discussion-8 patients were identified in this case series. We highlight the clinical features, patient demographics and operative courses of this patient group. We highlight the need to recognise peri-ocular necrotising fasciitis, especially in the paediatric population which has not been discussed in the otolaryngology literature previously.

This work presents a thoroughgoing theoretical study on the OH-initiated combustion chemical kinetics and atmospheric degradation of C4F9N by employing high-level quantum chemical methods and RRKM/master-equation theory. All the stationary points on potential energy surface were cautiously investigated at B3LYP/6-311++G(d,p) level for geometry optimizations, and thereby their single-point energies were refined by applying CCSD(T)/6-311++G(d,p) method. Based on quantum calculations, kinetics and branching ratios for the major channels were predicted within 300-3000 K and 0.01-100 atm by solving the RRKM/master-equations. The addition of OH to C4F9N generating M1 dominates the overall kinetics at low temperatures. Subsequently, its two β-scission channels of C-C bonds forming CF3CF2N=CF(OH)+CF3 (P8) and CF2=NCF(OH)CF3+CF3 (P9) become competitive and play a lead role in whole C4F9N+OH system at the corresponding high temperatures and elevated pressures. The formation of CF3 radical prompts two routes to potentially have the significant contribution to flame inhibition in actual applications. Additionally, the complex degradation pathways of C4F9N were also looked into by successively reacting with various oxides, including OH, O2, NO, HO2, to finally generate the removal products CF3CF2N(OOH)CF(OH)CF3 (Pd2), CF3CFO (Pd3-2), and CF3CF2NO (Pd4). The atmospheric lifetime of C4F9N is evaluated as 72 years regarding to one step addition between C4F9N and OH radical.

Tea is a popular cash crop in Asian and African countries that can be grown from tropical to subtropical climates with high humidity and heavy rainfall. India is the second-largest producer of Tea worldwide, having approximately 567 thousand hectares under tea cultivation. Interestingly, rainfall partitioning parameters (i.e., throughfall (TF), stem flow (SF) and interception (IC)) for Tea plantation do not appear to have been investigated. Therefore, this study aims to experimentally monitor TF, and SF for Tea. For this study, a Tea plantation of nearly 27-year-old grown in an area of 1.3 acres at the experimental farm of IIT Kharagpur campus, West Bengal, India was selected. IC was derived from the in-situ measured TF and SF values, against the 106 nos. rainfall events (RE) recorded during 2017-2018. RE depth varied from 3 mm- 60 mm with a coefficient of variance (CV) of 84%. However, relative portion of rainfall as TF (TF%), SF (SF%), and I (IC%) varied from 59-89%, 0.1-2%, 10%-40% with CV as 10%, 29% and 27%, respectively. Thus, the portion of rainfall that reaches SF was insignificant (≤2%) than TF. Therefore, SF can be omitted considering a negligible portion, and IC can be derived directly from TF for Tea plantation. Average values of TF and IC were obtained as 72% and 27% of incident R. Furthermore, the response of all these partitioning parameters were analyzed against RE characteristics such as RE depth, intensity, and duration. These results are the first of their kind in respect of TF, SF, and IC values for Tea plantation besides being also consistent with those reported elsewhere for other plantations, and are useful for pragmatic applications.

Severe RSV infection in infancy is associated with increased risk of recurrent wheezing in childhood. Both acute and long-term alterations in airway functions are thought to be related to inefficient anti-viral immune response. The airway epithelium, the first target of respiratory syncytial virus (RSV), normally acts as an immunological barrier able to elicit an effective immune reaction but may also be programmed to directly promote a Th2 response, independently from Th2 lymphocyte involvement. Recognition of RSV transcripts and viral replication intermediates by bronchial epithelial cells brings about release of TSLP, IL-33, HMGB1 and IL-25, dubbed “alarmins”. These epithelial cell-derived proteins are particularly effective in stimulating innate lymphoid cells 2 (ILC2) to release IL-4, IL-5, and IL-13. ILC2, reflect the innate counterparts of Th2 cells and, when activate, are potent promoters of airway inflammation and hyperresponsiveness in RSV bronchiolitis and childhood wheezing/asthma. Long-term epithelial progenitors or persistent epigenetic modifications of the airway epithelium following RSV infection, may play a pathogenetic role in the short and long-term increased susceptibility to obstructive lung diseases in response to RSV in the young. Additionally, ILC2 function may be further regulated by RSV-induced changes in gut microbiota community composition that can be associated with disease severity in infants. A better understanding of the alarmin-ILC interactions in childhood might provide insights into the mechanisms characterizing these immune-mediated diseases and indicate new targets for prevention and therapeutic interventions.

Abstract: Most grouper species are functional protogynous hermaphrodites, but the genetic basis and the molecular mechanisms underlying regulation of this unique reproductive strategy remain enigmatic. In this study, we reported a high-quality chromosome-level genome assembly of the representative orange-spotted grouper (Epinephelus coioides). No duplication or deletion of sex differentiation related genes was found in the genome, suggesting that sex development in this grouper may be related to changes in regulatory sequences or environmental factors. Transcriptomic analyses showed that aromatase and retinoic acid are probably critical to promote ovarian fate determination, and follicle-stimulating hormone triggers the female-to-male sex change. Socially controlled sex-change studies revealed that the brain of sex-changing fish in response to social environment may be mediated by activation of phototransduction cascade and the melatonin synthesis pathway. In summary, our genomic and experimental results provide novel insights into the molecular mechanisms of sex differentiation and sex change in the protogynous grouper.

Viscous flow through a reservoir with porous boundary is studied via rigorous asymptotic analysis. Under the assumption of periodicity of the pores, the effective boundary condition of the Darcy type is derived, using homogenization and boundary layer techniques. Further asymptotic analysis with respect to the porosity yields a recursive sequence of boundary value problems showing that the large pressure jump occurs on the boundary.

We describe a case of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) to multiple CFTR modulators and piperacillin in an 8 year old female with CF. To our knowledge this is the first reported case of delayed type, T-cell mediated hypersensitivity to multiple CFTR modulators described in literature. Our findings suggest possible cross-reactivity between CFTR modulators or multiple sensitisations, which should be taken into account in similar cases.

OMALIZUMAB MAY FACILITATE DRUG DESENSITIZATION IN PATIENTS FAILING STANDARD PROTOCOLSTo the Editor,Nephrotic syndrome (NS) is a common glomerular disorder in children, for which steroids are the first-line treatment. While most children with NS respond to steroid therapy, 20% of children are resistant to steroids. Some children with steroid-responsive NS develop a frequently relapsing or steroid-dependent course and experience significant side effects of steroid therapy. Alternative medications such as calcineurin inhibitors, mycophenolate mofetil, cyclophosphamide, and rituximab, an anti-CD20 monoclonal antibody, are being considered for such patients with difficult-to-treat NS (1,2).Hypersensitivity reactions to monoclonal antibodies are quite limited in clinical practice, such as the release of cytokines that occur during intravenous infusion. However, IgE-mediated reactions may also occur. Life-threatening IgE-mediated reactions such as anaphylaxis lead to discontinuation of treatment or conversion to a less beneficial treatment. Rapid drug desensitization (RDD) is a therapeutic option that allows continuation of treatment with the causative drug (3). Omalizumab is a recombinant humanized anti-IgE monoclonal antibody. Treatment indications include severe asthma and idiopathic chronic urticaria. However, the efficacy of omalizumab has also been described in food allergy, as a bridge to oral immunotherapies, atopic dermatitis, idiopathic anaphylaxis, and mastocytosis (4). Previous studies have reported the use of omalizumab for rapid desensitization to chemotherapeutic agents (5). Here, we describe a patient with steroid-resistant NS who developed anaphylaxis on the first infusion of rituximab and subsequent type 1 hypersensitivity reactions during desensitization trials with rituximab using 12-, 16-, and 20-step protocols.A 4-year-old boy diagnosed with steroid-resistant NS and unresponsive to calcineurin inhibitors, either cyclosporine A or tacrolimus, and in their combination with mycophenolate mofetil, received rituximab. After premedication with methylprednisolone at a dose of 2 mg/kg, rituximab 375 mg/m2 was administered intravenously. During the infusion, he developed anaphylaxis (vomiting and dyspnea). The infusion was stopped and intramuscular epinephrine was administered, and a 12-step rapid desensitization protocol was planned for further infusions (Table 1). He was premedicated with H1 blockers and systemic steroids. However, the patient developed breakthrough reactions (urticaria) that required additional antihistamines at the 4th step. Infusion was resumed at a slower rate. Ten minutes after re-administration, generalized urticaria and angioedema developed. Montelukast was administered according to ENDA/EAACI recommendations for rapid desensitization in drug allergy (6). After 7 days, the protocol was modified to administer 375 mg/m2 rituximab in 16 steps with premedication (Table 2). The patient developed generalized urticaria and angioedema again at the 4th step. The next week, the desensitization protocol was designed with 375 mg/m2 rituximab in 20 steps (Table 3). Again, generalized urticaria and angioedema occurred in the 2nd step. A skin prick test was performed 3 weeks after the initial reaction. During the skin prick test, the patient developed generalized urticaria.In the absence of alternative treatment options for NS, desensitization with omalizumab treatment was suggested to prevent hypersensitivity reactions to rituksimab. Omalizumab (patient weight: 17.5 kg; total IgE:71 UI /ml; dose: 150 mg/ every 2 weeks) was added to treatment. The last omalizumab dose was administered 1 day before the following desensitization. After premedication, 375 mg/m2rituximab was administered in 20 steps. In the 5th step, the patient developed local urticaria requiring an antihistamine. The infusion was resumed and successfully completed. Under omalizumab treatment, the patient was administered 375 mg/m2 rituximab for the second time in a 20-step protocol. After the 6th dose, the interval of omalizumab treatment was changed to every 4 weeks. The rituximab dose was then increased to 750 mg/m2 at the third infusion. After premedication, the 20-step desensitization protocols were successfully applied in the following days.Rituximab is a chimeric monoclonal antibody that targets the CD20 antigen on the surface of B cells and causes elimination of B lymphocytes by complement- and antibody-dependent cellular cytotoxicity for 6-12 months (2). Efficacy has also been demonstrated in the treatment of steroid-resistant NS (7). Rituximab is one of the most common biologic agents with infusion-related reactions. Rituximab-associated hypersensitivity reactions can be classified as infusion-related reactions, cytokine release, IgE-mediated/non-IgE-mediated hypersensitivity reactions, mixed reactions, type 3 and type 4 hypersensitivity reactions (8).Omalizumab is a recombinant humanized IgG1 monoclonal antibody and prevents degranulation in effector cells by specifically binding to the FceRI receptor site of free IgE, causing a decrease in the level of free IgE in serum, and causing downregulation of FceRI receptors (9). Omalizumab has previously been used as a co-adjuvant in RDD along with insulin, the enzyme elosulfase alpha, chemotherapeutic agents, and aspirin (9). In a randomized, double-blind, placebo-controlled trial by Lang et al, desensitization was achieved after 16 weeks treatment with omalizumab. In other case reports, omalizumab treatment was generally started 7-14 days before RDD; only in one case report was the first omalizumab dose given 4 days before RDD (9). In previous studies, omalizumab dosing in allergic asthma was based on patient weight and total IgE. In our case, we administered 6 doses of omalizumab (150 mg/dose) every two weeks before desensitization and continued treatment once a month until completion of rituximab therapy. In patients with successful RDD on omalizumab, RDD steps can be reduced on subsequent infusions. Arroaberran et al. (10) presented a patient who tolerated elosulfase alpha enzyme without desensitization after omalizumab treatment.In conclusion, omalizumab may facilitate desensitization protocols and allow continuation of the preferred treatment.1Hatice Betul Gemici Karaaslan,

Several inborn errors of immunity are caused by defects in the general DNA repair machinery as exemplified by the T-B- RS-SCID condition owing to impaired resolution of programmed DNA double strands breaks introduced by RAG1/2 during V(D)J recombination. The genome instability generally associated with these conditions results in an increased propensity to develop malignancies requiring genotoxic based anti-cancer treatments. Moreover, the extent of immune deficiency often calls for hematopoietic stem cell transplantation as a definitive treatment, thus also demanding genotoxic based conditioning regimen prior to transplantation. In both cases, the underlying general DNA repair defects may result in catastrophic iatrogenic consequences. It is therefore of paramount importance to assess the functionality of the DNA repair apparatus prior to any genotoxic treatment when the exact molecular cause of the disease is unknown. For this purpose, two simple assays can be used on patient’s derived peripheral blood lymphocytes. 1) The PROMIDISα biomarker, based on the next generation sequencing analysis of the TCRα will highlight specific signatures of DNA repair deficiencies. 2) Direct analysis of the sensitivity of peripheral lymphocytes to ionizing radiations will formally identify patients at risk to develop toxicity towards genotoxic based treatments.

Temporal variation of effective population size and gene flow determine current patterns of genetic diversity within species, and hence the genetic variation upon which natural selection can act. Although such demographic processes are well understood in terrestrial organisms, they remain largely unknown in the ocean, where species diversity is still being described. Here, we present one of the first population genomic studies in a cephalopod, Octopus insularis, which is distributed in coastal and oceanic island habitats in the Atlantic Ocean, Mexican Gulf and the Caribbean Sea. Using genomic data, we identify the South Equatorial current as the main barrier to gene flow between southern and northern parts of the range, followed by discontinuities in the habitat associated with depth. We find that genetic diversity of insular populations significantly decreases after colonization from the continental shelf, also reflecting low habitat availability. Using demographic modelling, we find signatures of a stronger population expansion for coastal relative to insular populations, consistent with estimated increases in habitat availability since the Last Glacial Maximum. The direction of gene flow is coincident with unidirectional currents and bidirectional eddies between otherwise isolated populations, suggesting that dispersal through pelagic paralarvae is determinant for population connectivity. Together, our results show that oceanic currents and habitat breaks are determinant in the diversification of marine species, shaping standing genetic variability within populations. Moreover, our results show that insular populations are particularly vulnerable to current human exploitation and selective pressures, calling the revision of their protection status.