Specific electrical conductivity (SC) is a basic, effective indicator of water quality. The recent increase in SC data collected with high-frequency sensors has created a strong need for algorithms that can aid interpretation of these data. This study presents an algorithm that finds and quantifies SC temporal patterns and applies that algorithm to a data set from a forested catchment. During and after rain events, we show three patterns that emerge in SC time series: a solute flush, resulting in an initial increase in SC, followed by a dilution, followed by the SC’s recovery toward pre-rain conditions. We compared these SC patterns to precipitation amount and intensity, antecedent wetness, and seasonality. Our results indicate that the magnitude of the flush was driven primarily by precipitation intensity and total rainfall during a storm, and secondarily by antecedent moisture conditions. The magnitude of the dilution was driven mainly by precipitation amount. The rate of SC recovery was driven by precipitation amount and was correlated with the dilution. Overall, the algorithm successfully extracted event-driven characteristics in the SC time series, allowing the development of functional relationships with hydrologic drivers. Applying similar methodologies to more catchments in the future will help identify functional relationships at more sites and use these relationships to identify catchments most sensitive to future precipitation changes.

Objective: Hyperuricemia increases the risk of gout and cardiovascular diseases. Obesity increase the risk of hyperuricemia while weight loss (>5 kg) has been reported to decrease urate. The effects of orlistat on serum uric acid is still controversial. The aim of this meta-analysis was to evaluate the influence of orlistat on serum uric acid level in adults. Methods: Relevant studies, published up to May 2020, were searched systematically through PubMed/Medline, Scopus, and Google Scholar. All relevant randomized controlled clinical trials were included. Meta-analysis was performed using random-effect model. Subgroup analysis, sensitivity analysis, and meta-regression were also carried out Results: Overall 7 trials (9 dataset) that enrolled 1786 subjects were included. Orlistat showed in significant change in serum uric acid level (Difference in means: -17.661μmol, 95% CI: -31.615 to -3.707, P=0.01). A low heterogeneity observed across the studies (I^2 = 25.119%). After categorizing studies on the basis of duration and sample size the effect of orlistat on serum uric acid was significant. The results of meta-regression were showed that significant relationships were not found between orlistat and serum uric acid in duration of intervention. Conclusion: We found a significant reduction in serum uric acid following orlistat therapy in adults.

In the mechanisms of stomatal opening, the transports of osmotic materials between the guard cell cytoplasm and vacuole have not been studied much. There were also important lacks of understanding about tonoplast transport proteins and channels. Tonoplast has been found to have many types of channels related to K+ transport, among which are inward-K+ channels/FV, outward-K+ channels/FV, outward-TPK/VK channels and TPC1/SV channels. The two H+ transport enzymes in tonoplast, H+-ATPase and H+-PPase, transport H+ from the cytoplasm to vacuole very actively. They serve to create an ideal pH condition between vacuole and cytoplasm to facilitate the many metabolisms in the cell. The cytosolic K+ cannot easily enter the vacuole to fill the charge balances, because vacuole is too full of positive charges. Therefore, in order to increase the osmotic pressure of the guard cell vacuole, it is necessary to transport solute that can replace K+. Tonoplast contains sucrose-H+ antiports, an active transport protein that can transport cytoplasmic sucrose to vacuole. Although various solutes including K+ are required for stomata to open, sucrose is believed to be the most important substance that can increase the vacuole’s osmotic pressure.

The present study evaluated three wheat genotypes (SD-28, SD-32 and Chirya-1) were evaluated for physiological attributes like Relative Water Content, Proline Content, Membrane Stability Index and Chlorophyll Content where Opata was used as a control check under three different levels of drought stress (100% FC, 80% FC and 60% FC). Results revealed that chlorophyll content was significantly affected under stressed conditions in all the studied genotypes and genotypes. Molecular diagnosis of the selected wheat genotypes and genotypes was carried out with RT-PCR using expression profile of 06 genes (TaLhca1, TaLhca2, TaLhca3, TaLhcb1, TaLhcb4 and TaLhcb6) that encodes for LHCI and LHCII proteins. RT–PCR indicated variable expression of the selected genes in response to different level of drought stress. The results obtained clearly showed the relation between genotypes and severity of drought stress condition. Among the studied genotypes Chirya-1 and SD-28 performed well with higher level of gene expression under drought stress condition; and may be considered drought tolerant genotypes with potential to enrich the genetic background of locally adapted wheat lines against drought stress.

Objective: The aim of this study was to evaluate the effect of using uterine fundal pressure during the second stage of delivery on obstetric anal sphincter injury (OASI), among primiparous women using three-dimensional transperineal ultrasonography. Design: Case control study Setting: Tertiary Urogynecology Unit Population: Nulliparous women with term, singleton, cephalic presentation gestation delivered with fundal pressure in second stage of labour. Main Outcome Measure: Complete, incomplete IAS and EAS defect in transperineal tomographic ultrasound imaging Method: A total of 73 women who had their first vaginal birth were included in the study, 37 of them applied fundal pressure and 36 of them delivered spontaneously without fundal pressure. Tomographic ultrasound imaging with 3D transperineal assessment was performed within 48 h of delivery, IAS and EAS defect were determined. Results: Five (13.5%) women in the fundal pressure group, 7 (20%) women in the control group had complete EAS (p = 0.4). Complete IAS was observed in 1 (2.7%) women in the fundal pressure group and 2 (5.7%) women in the control group (p = 0.5). Half-moon sign was observed in 1 woman in both groups (p = 0.9). The rate of other signs were similar in both groups. Multivariate regression models revealed that none of, age, episiotomy, length of second stage of labour, fundal pressure application status and number were independent predictor of complete IAS or EAS defect. Conclusions: Fundal pressure during the second stage of delivery is not cause increase in rate of OASI detected with ultrasonography.

Study Objective: To examine the correlation between the occurrence of adenomyosis and the outcome of vaginal repair of cesarean scar defects (CSD). Design: A retrospective observational cohort study. Setting: University hospital. Patients: A total of 278 women with CSD were enrolled at the Shanghai First Maternity & Infant Hospital between January 2013 and August 2017. Interventions: Vaginal excision and suture of CSD. Measures and Main Results: According to preoperative magnetic resonance imaging (MRI) findings, patients were divided into two groups, the adenomyosis group (group A) and the non-adenomyosis group (group B). For group A patients, the mean duration of menstruation at 3- and 6-months follow-up was shorter and the TRM at the median-month follow-up was significantly thinner than those in group B patients (p < 0.05). There were more patients with class-A healing in group B compared with group A (44.7% vs 30.0%; p < 0.05). Furthermore, 59.3% (32/54) of women tried to conceive after vaginal repair. The pregnancy rates of women with and without adenomyosis were 66.7% (8/12) and 61.9% (26/42), respectively. The duration of menstruation decreased significantly from 13.4 ± 3.3 days to 7.6 ± 2.3 days after vaginal repair in 25 patients (p < 0.001). The TRM increased significantly from 2.3 ± 0.8 mm to 7.6 ± 2.9 mm after vaginal repair (p < 0.001). Conclusion: Vaginal repair reduced postmenstrual spotting and improve fertility in patients with CSD. Adenomyosis might be an adverse factor in the repair of uterine incisions.

Abstract Background Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse drug reaction associated with human herpesvirus reactivation. However, the risk factors for viral reactivation and their impact on outcomes remain unclear.We aimed to explore the impact of viral reactivation on DRESS outcomes and potential risk factors for reactivation. Methods This was a retrospective cohort study in an academic medical center. Cases were validated in-hospital cases of DRESS from 2009 to 2017. Results Overall, 100 patients fulfilled the case criteria. Ninety-three patients had at least one viral marker tested. HHV6, EBV and CMV reactivation occurred in 24 out of 85 cases (28%), 15 out of 87 (17%) cases, and 18 out of 89 (20%) cases respectively. Viral reactivation cases were associated with higher 1-year mortality, dialysis initiation, recurrent flares of disease, and longer hospital stay (all p<0.05). Risk of inpatient mortality (OR, 5.8; 95% CI, 1.7-20.7; p<0.01) and 1-year mortality (OR, 10.0, 95% CI, 2.9-34.9; p<0.01) increased with multiple viral reactivations. Viral reactivation was independent of demographics, comorbidities, treatment or causative drug. Conclusion Human herpesviridae viral reactivation in DRESS, particularly multiple viral reactivations, is associated with poorer clinical outcomes.

Identification of carriers of fragile X syndrome (FXS) with the subsequent prenatal diagnosis, and knowledge of FXS-associated genetic profiles are essential for intervention in specific populations. We report the results of carrier screening of 39,458 East Asian adult women and prenatal diagnosis from 87 FXS carriers. The prevalence of FXS carriers and incidence of full mutation fetuses in carrier pregnancies were found to be 1/556 and 11.0%, respectively. We confirmed the validity of the current threshold of CGG repeats for FMR1 categorization; the integral risks of full mutation expansion were approximately 6.0%, 43.8%, and 100% for premutation alleles with 55-74, 75-89, and ≥90 CGG repeats, respectively. The protective effect of AGG interruption in East Asian populations was validated, which is important in protecting premutation alleles with 75-89 CGG repeats from full mutation expansion. Lastly, family history was shown not an effective indicator for FXS carrier screening in East Asian populations and population-based screening was more cost-effective. This study provides an insight into the largest carrier screening and prenatal diagnosis for FXS in East Asian populations to date. The FXS-associated genetic profiles of East Asian populations are delineated and population-based carrier screening is shown to be promising for FXS intervention.

Familial Colorectal Cancer Type X (FCCTX) is a term used to describe a group of families with an increased predisposition to colorectal and other related cancers, but an unknown genetic basis. Whole-exome sequencing in two cancer-affected and one healthy members of a FCCTX family revealed a truncating germline mutation in PTPRT [c.4090dup, p.(Asp1364GlyfsTer24)]. PTPRT encodes a receptor phosphatase and is a tumor suppressor gene found to be frequently mutated at somatic level in many cancers, having been proven that these mutations act as drivers that promote tumor development. This germline variant shows a compatible cosegregation with cancer in the family and results in the loss of a significant fraction of the second phosphatase domain of the protein, which is essential for PTPRT’s activity. In addition, the tumors of the carriers exhibit epigenetic inactivation of the wild-type allele and an altered expression of PTPRT downstream target genes, consistent with a causal role of this germline mutation in the cancer predisposition of the family. Although PTPRT’s role cancer initiation and progression has been well studied, this is the first time that a germline PTPRT mutation is linked with cancer susceptibility and hereditary cancer, which highlights the relevance of the present study.

Bi-allelic loss-of-function variants of OTOA are a well-known cause of moderate-to-severe hearing loss. Whereas non-allelic homologous recombination-mediated deletions of the gene are well known, gene conversions to pseudogene OTOAP1 have been reported in the literature but never fully described nor their pathogenicity assessed. Here, we report two unrelated patients with moderate hearing-loss, who were compound heterozygotes for a converted allele and a deletion of OTOA. The conversions were initially detected through sequencing depths anomalies at the OTOA locus after exome sequencing, then confirmed with long range polymerase chain reactions. Both conversions lead to loss-of-function by introducing a premature stop codon in exon 22 (p.Glu787*). Using genomic alignments and long read nanopore sequencing, we found that the two probands carry stretches of converted DNA of widely different lengths (at least 9 kbp and around 900 bp, respectively).

In this research, we offer two new quantum integral equalities for recently defined $q^{b}$-integral and derivative, the derived equalities then used to prove quantum integral inequalities of Simpson’s and Newton’s type for preinvex functions. We also considered the special cases of established results and offer several new and existing results inside the literature of Simpson’s and Newton’s type inequalities.

Background: Immune rejection is still the main cause of transplant failure of corneal transplantation which mechanism is not fully understood. The purpose of this study is to investigate the differential expression of long noncoding RNAs (lncRNAs) in corneal allograft rejection and to construct a network diagram of the interaction between lncRNAs and microRNAs(miRNAs). Methods: The lncRNAs expression profile of rat corneal transplantation was constructed by high throughput sequencing. The co-expressed mRNA was analyzed by gene ontology (GO), gene and genomic Kyoto encyclopedia (KEGG). An interaction network diagram of lncRNAs, miRNA and rejection related target genes was constructed. Part of the prediction was verified by real-time polymerase chain reaction (qPCR). Results: A total of 285 lncRNAs expressions were detected between the normal group and the autograft group, with 239 lncRNAs significantly upregulated and 46 lncRNAs downregulated, while 162 lncRNAs were upregulated and 20 downregulated between the allograft group and the autograft group. Go and KEGG were used to enrich and analyze the co-expression of mRNA. By analyzing the interaction between lncRNAs, miRNAs and target genes related to corneal allograft rejection, 56 upregulated lncRNAs,7 downregulated lncRNAs, 6 upregulated miRNAs and 4 downregulated miRNAs were found in allograft and autograft group. Three of the possible pathways were confirmed and verified by qPCR . Conclusions: The results showed that there was a difference in lncRNA expression between normal ,autograft and allograft group. LncRNAs may be a new molecular target in the treatment of corneal injury and corneal allograft rejection by interact with miRNAs.

In this article, imperssive exact solutions and hence effective regulations to the non-fractional order and the time-fractional order of the biological population models are achevied for the first time in the framwork of the Paul-Painlevé approach. When the variables appearing in the exact solutions take specific values, the solaitry wave solutions will be easily satisfied.The realized results prove the efficiency of this technique.

In this paper, we consider a region occupied by viscous or inviscid compressible magnetohydrodynamic fluids, and surrounded by vacuum. It is shown that the fluid region will expand at least linearly in time as soon as there are no singularities. The expanding rate is proportional to initial total energy and is inversely proportional to initial mass. The result indicates an interesting fact that the expansion of the viscous monatomic fluids seems similar to the inviscid fluids.

This paper provides a further understanding of the peak load effect on the damage mechanics and residual stress relaxation. The comprehensive numerical simulations using the finite element method are applied to take into account simultaneously the effect of the surface roughness and residual stresses on the crack formation in sandblasted S690 high strength steel surface under peak load condition. A ductile fracture criterion is introduced for the prediction of damage initiation and evolution. This study investigates especially the influences of compressive peak load, effective parameters on fracture locus, surface roughness, and residual stress on damage mechanism and the formed crack size. Results indicate that under peak load conditions, surface roughness has a far more important influence on microcrack formation than residual stress. Moreover, it is shown that the effect of peak load range on damage formation and crack size is significantly higher in comparison with the influence of residual stress. It is found the crack size has been developed exponentially with increasing peak load magnitudes.

Surfactant, which was first identified in the 1920s is pivotal to lower the surface tension in alveoli of the lungs and helps to lower the work of breathing and prevents atelectasis. Surfactant proteins, such as surfactant protein B and surfactant protein C contribute to normal functioning of surfactant. Additionally, Adenosine Triphosphate Binding Cassette 3 and Thyroid Transcription Factor-1 are also integral for the normal structure and functioning of pulmonary surfactant. Through the study and improved understanding of surfactant over the decades, there is increasing interest into the study of childhood interstitial lung diseases (chILD) in the context of surfactant protein deficiencies. Surfactant protein deficiency syndrome (SPDS) is a group of rare diseases within the chILD group that is caused by genetic mutations of SFTPB, SPTPC, ABCA3 and TTF1 genes. This review article seeks to provide an overview of surfactant protein deficiencies in the context of chILD.

Background: Airway malacia is a condition of excessive airway collapsibility, which causes expiratory reduction in the cross-sectional luminal area during respiration. As this disorder may lead to life threatening events and even death in children, it is important to recognise and treat it. Aims: In this study, we aimed to evaluate clinical and radiological features, prognoses, and associated disorders of the patients with lower airway malacia. Methods: A total of 65 patients with lower airway malacia diagnosed by flexible bronchoscopy were included in this study. Demographic and clinical features, radiological findings, video image records of bronchoscopy and prognoses of the patients were evaluated retrospectively. Results: Lower airway malacia was diagnosed in 65 (16.6%) children with a median age of 1 year and 2 months (range: 1 month-16 years and 8 months). Thirty-five (53.8%) of them were male. The numbers of children with isolated tracheomalacia, isolated bronchomalacia and tracheobronchomalacia were nine (13.8%), 48 (73.8%) and eight (12.3%), respectively. The most common reason for admission was recurrent and/or prolonged respiratory infection (46.2%) and the most common physical examination finding was stridor (36.9%). Fifty-eight (89.2%) patients had other co-morbidities associated with airway malacia. Inhaled ipratropium bromide therapy was started for 37 (56.9%) patients. Ten (15.4%) patients required continuous positive pressure support.. Conclusion: Lower airway malacia is an important disorder in children with respiratory problems and flexible bronchoscopy is a valuable diagnostic method. Sharing experiences in terms of diagnosis and treatment modalities would help patients as well as clinicians.

Objective: There is a crucial balance between oxidant and antioxidant defense mechanisms. We aimed to evaluate the role of the balance of these systems in community-acquired pneumonia (CAP) in children. Methods: We analyzed serum oxidant and antioxidant stress parameters according to the clinical and demographic data of children with CAP and compared them with healthy controls. Serum total antioxidant status (TAS), total oxidant status (TOS), and levels of ischemia-modified albumin (IMA), antioxidant enzymes, non-enzymatic antioxidant factors, and plasma thiol were evaluated and compared between the groups. Results: Of 160 children evaluated, 106 had CAP (54 outpatients, 52 inpatients) and the other 54 were healthy subjects (control group). Total thiol and native thiol levels were significantly lower in the inpatient group compared to the outpatient group (p=0.004, p=0.005). Serum IMA differed significantly among the groups (p=0.001), with inpatients showing the highest level. A positive correlation was found between serum IMA and C-reactive protein levels in patients with pneumonia (r=0.351; p=0.001). Conclusion: Parameters that provide information about antioxidant capacity may be useful in the diagnosis and prognosis of pneumonia. Both thiol homeostasis parameters and IMA level seem likely to be influenced by disease severity. Our results suggest that plasma thiol levels and IMA may be good candidate biomarkers to predict the severity of pneumonia in children.

Background: Environmental tobacco smoke (ETS) exposure and sleep associated problems can lead to serious health problems in children. We aimed to evaluate association between ETS and sleep disturbance in children. Methods: We enrolled 209 children without chronic health problems or acute infections aged 4 to 12 years between June 2019 and March 2020 to this cross-sectional study. Parents’ smoking habits and ETS exposure of children were questioned and Children’s Sleep Habits Questionnaire (CSHQ) was administered to screen for the most common sleep problems in children. “Sleep disturbance” was defined as a score ≥41 in CSHQ. Plasma cotinine levels were measured in all subjects enrolled and levels ≥ 3 ng/mL were defined as ETS exposure. Results: Total 115 children (55 %) were in the “sleep disturbance” group according to CSHQ, and 66 (57.3%) of them were exposed to ETS according to parental report. The children with parent reported ETS exposure had increased risk of sleep disturbance (adjusted OR: 1.3). All 209 children had plasma cotinine levels ≥3 ng/ml, with a mean (SD) 50.55 (13.78) ng/ml, revealing that all of them were exposed to ETS although only 105 of them were parent reported. Multivariable analysis of risk factors for sleep disturbance revealed that parent reported ETS exposure was associated with increased risks of sleep disturbance (p=0.023, adjusted OR: 1.9 and 95%CI: 1.09-3.3) Conclusions: Parent reported ETS exposure is associated with sleep disturbance in their children however parental reports about smoking habits may not be compatible with plasma cotinine levels of the children.

This work proposes a high brightness light emitting diode (HB-LED) driver circuit based on a full-bridge LC series resonant converter with series DC bus for low power applications with a dimming feature. The proposed configuration consists of full-bridge LC series resonant converter with a series DC bus. The idea behind the concept is to supply the light emitting diode (LED) threshold voltage directly from the constant DC bus - and the control voltage, which is used for current regulation, is supplied through a full-bridge LC resonant converter. Since the control voltage responsible for current regulation is only processed by the full-bridge series resonant converter, the conduction loss is less even if several LED strings are connected to the same converter. The proposed HB-LED driver is characterized by low switching loss, reduced component count, high efficiency, and reduction of output electrolytic capacitor. Further, double pulse width modulation (DPWM) dimming control is designed and used to control the average output currents. The proposed high brightness light emitting diode (HB-LED) driver circuit based on a full-bridge LC series resonant converter is simulated using Orcad/PSpice software. The theoretical analysis and predictions of the proposed full-bridge series resonant converter-based HB-LED driver is in close agreement with the results obtained.  

Fatma Zgolli 1 2, Imen Aouinti 1 2, Ons  Charfi1 2, Sarrah Kastalli1 2, Daghfous Riadh1 2, Sihem EL Aidli 1 2, Ghozlane Lakhoua 1 21National Center Chalbi Belkahia of Pharmacovigilance, 9 Avenue du Dr Zouhaier Essafi 1006, Tunis, Tunisia.2University of Tunis El Manar, Faculty of Medicine, Research unit: UR17ES12, 15 Rue Djebel Lakhdhar, La Rabta, 1007, Tunis, Tunisia.Leukocytoclasticvasculitis (LCV) is a hypersensitivity vasculitis. It may be secondary to infections, drugs, collagen tissue disorders, and malignities(1). Drug-induced LCV represents approximately 10-15% of LCV cases (2). Calcium channel blockers are little involved in this skin impairment. In fact, only few cases of LCV induced by amlodipine and diltiazem LCV were reported (3-5).We report herein an exceptional case of LCV induced by lercanidipine (LER). It was notified in the Tunisian National Centre of Pharmacovigilance.An 87-year-old woman was treated with flecainide and bisoprolol during ten years for cardiac disease. In 2016, she started LER (10 milligram per day). Seven months later, in January 2017, she developed a polymorphic and pruritic cutaneous eruption limited to forearms and legs. A symptomatic treatment (dermocoticoids and antihistamincs) was initiated without improvement of the eruption. Skin examination showed an erythematous maculopapular eruption, necrotic and purpuric lesions and ulcerations. The rest of the physical examination was normal. Laboratory findings showed an accelerated erythrocyte sedimentation rate and a high level of C-Reactive Protein (82mg/l), the serum protein electrophoresis was normal. The diagnosis of vasculitis was suspected by dermatologists. A skin biopsy was performed and revealed characteristic perivascular neutrophilic infiltrates, a leukocytoclasis and extravasated erythrocytes in favour of LCV. The responsibility of LER was suspected and this medication was stopped. The other drugs were continued. The pruritus and cutaneous lesions started to subside few days later after the drug cessation. Symptoms had completely resolved in two weeks.LCV is the inflammation of small blood vessels.Its clinical features are generally a palpable purpura on gravity-dependent body parts. Also it can occur as urticaria, ulcers, nodules or haemorrhagic bullae (6). It is diagnosed by histopathological evaluation of the biopsy from the lesion.LCV is idiopathic up to 50% of the cases.  Infections and drugs are the most common triggers for secondary LCV. Drug-induced LCV is approximately 10-15% of cases (2). Merkel PA had defined drug-induced LCV as “any case of inflammatory vasculitis in which a specific drug is established as a causal agent of disease when other forms of vasculitis are excluded” (7). The onset is typically 1 to 3 weeks after drug initiation (2).The exact pathogenesis of drug-induced LCV remains unclear, but studies suggest that the offending drug may act as a hapten, which stimulates antibody production and immune complex formation. These immune complexes are subsequently deposited in postcapillaryvenules leading to complement activation and vascular damage (8).More than 100 drugs are implicated as causes of drug-induced LCV. Commonly, offending drugs include antibiotics such as beta-lactams, erythromycin, clindamycin, vancomycin, sulfonamides, and other molecules such as furosemide, allopurinol, NSAIDs, amiodarone, gold, thiazides, phenytoin, beta-blockers, TNF-alpha inhibitors, selective serotonin reuptake inhibitors, metformin, warfarin, valproic acid, among many others (2).In our case, the responsibility of LER was retained in front of the onset of the reaction after a compatible delay (seven months after beginning the treatment), and mainly the improvement of the condition after drug withdrawal. According to Naranjo probability scale, the score was 4 (9).In literature, calcium channel blockers are little involved in this skin impairment. After a MEDLINE search (vasculitis, drug-induced vasculitis, leucocytoklasis, calcium channel blockers, lercanidipine, amlodipine, nifedipine, diltiazem), we have only found few cases of LCV induced by amlodipine and diltiazem(3–5). Concerning LER, only one previous case of an enalapril-LER combination induced LCV was reported (10). But, no cases are available on drug-induced LCV associated with LER only. Thus, this is the first reported case of LCV induced by LER.The drug-induced LCV therapeutic approach is based on antigen removal and the treatment of the cutaneous lesions. Withdrawal of the precipitating drug and minimization of stasis by compression, elevation, and use of non steroidal anti-inflammatory drugs are employed. Antihistamines, systemic corticosteroids or other immunosuppressant may be required when the cutaneous lesions are progressive (6,8).This report is, to the best of our knowledge, the first case of LCV induced by LER. Considering the wide use of LER in hypertensive population, prescribers should be aware of the possibility of occurrence of cutaneous LCV as a side effect of this drug.References:1) Goeser MR, Laniosz V, Wetter DA. A Practical Approach to the Diagnosis, Evaluation, and Management of Cutaneous Small-Vessel Vasculitis. Am J ClinDermatol 2014;15(4):299-306.(2) Baigrie D, Bansal P, Goyal A, et al. LeukocytoclasticVasculitis (Hypersensitivity Vasculitis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020.(3) del Río Fernández MC, Plagaro Cordero ME, de FrutosArribas JF, del PozoRomán T, Martín Escudero JC. Leukocytoclasticvasculitis in relation to amlodipine administration. Rev ClinEsp 1995;195(10):738-9.(4) Sheehan-Dare RA, Goodfield MJ. Severe cutaneous vasculitis induced bydiltiazem. Br J Dermatol 1988;119(1):134.(5) Lachapelle J-M, Ramelet A-A. Exercise-induced vasculitis and amlodipine. Louvain Med 2014;133:103-6.(6) Ha YJ, Han YJ, Choi YW, Myung KB, Choi HY. Sibutramine (Reductil®)-Induced Cutaneous LeukocytoclasticVasculitis: A Case Report. Ann Dermatol 2011;23(4):544-7.(7) Merkel PA. Drug-induced vasculitis. Rheum Dis Clin North Am. 2001;27(4):849-862.(8) Gupta M. Levetiracetam-induced leukocytoclasticvasculitis. Indian J Pharmacol. 2017;49(1):124-6.(9) Naranjo CA, Busto U, Sellars EM, et al. A method for estimating the probability of adverse drug reactions. ClinPharmacolTher 1981; 30: 239-45(10) Ouni B, Fathallah N, Ben‐Sayed N, Slim R, Abdessayed N, Anoun J, et al. Enalapril‐lercanidipine combination induced leukocytoclasticvasculitis: A case report. Br J ClinPharmacol 2020; 10.1111/bcp.14346.

The microcrustacean Daphnia is arguably one of the most studied zooplankton species, having a well understood ecology, life history, and a relatively well studied evolutionary history. Despite this wealth of knowledge, species boundaries within this genus often remain elusive and the major evolutionary forces driving the diversity of daphniids remain controversial. This genus contains more than 300 species with multiple cryptic species complexes, with many closely related species able to hybridize. Here we review speciation research in Daphnia within the framework of current speciation theory. We evaluate the role of geography, ecology, and biology in restricting gene flow and promoting diversification. Of the 253 speciation studies on Daphnia, the majority of studies examine geographic barriers (55%). While evidence shows that geographic barriers play a role in species divergence, ecological barriers are also likely prominent in Daphnia speciation. We assess the contribution of ecological and non-ecological reproductive isolating barriers between closely related species of Daphnia and found that none of the reproductive isolating barriers are capable of restricting gene flow completely. Research on reproductive isolating barriers has been disproportionally focused on two species complexes, Daphnia pulex and Daphnia longispina. Lastly, we identify areas of research that remain relatively unexplored and discuss future research directions that build our understanding of speciation in daphniids.

While the identification of microbial eukaryotes using molecular tools is now widespread, additional information are needed to confirm the molecular observation and make the difference between species and population variants, and therefore to better understand the biogeography of microbial eukaryotes. In this issue of Molecular Ecology, Postel et al (2020) not only used three molecular approaches to identify subgroups of Fragilariopsis kerguelensis but also morphology and physiology to better understand the relationship between the three genotypes. They revealed that (1) the three genotypes of the diatom F. kerguelensis have a negligible gene flux; and (2) two of the genotypes are geographically isolated with different physiology but still able to crossbreed; and (3) the last one is omnipresent but reproductively isolated.

Aim: The aim of this study was to develop a population pharmacokinetic (PPK) model in Chinese children for intravenous busulfan, and to develop a novel busulfan dosing regimen to support better area under the concentration-time curve (AUC) targeting. Methods: We collected busulfan concentration-time samples from 69 children who received intravenous busulfan prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT). A population pharmacokinetic model for busulfan was developed by nonlinear mixed effect modelling and was validated by an external dataset (n=14). A novel busulfan dosing regimen was developed through simulation on 1000 patients. Limited Sampling Strategy (LSS) was established by the Bayesian forecasting. Absolute Prediction Error (APE), Mean Absolute Prediction Error (MAPE) and relative Root Mean Squared Error (rRMSE) were calculated to evaluate predictive accuracy. Results: A one-compartment model with first-order elimination best described the data. GSTA1 genotypes, BSA and AST were found to be significant covariates of Bu clearance, and BSA had remarkable impact of the volume. Moreover, recommended dose regimens for children with different GSTA1 genotypes and BSA were developed with a perfect AUC targeting. A two-point LSS, two hours and four hours after dosing, behaved well with acceptable prediction precision. Conclusion: This study developed a PPK model for busulfan that firstly incorporated GSTA1 genotypes in an Asian pediatric population. We recommend a BSA-based dosing for personalizing busulfan therapy in pediatric population. Additionally, an optimal LSS (C2h and C4h) provides convenience for therapeutic drug monitoring (TDM) in the future.