Comment on Platts-Mills T, Caraballo L, Jacquet A, Zarzuk J. Dust mite allergy. In: Dramburg S, Hilger C, Santos AF, de Las Vecillas L, Aalberse RC, Acevedo N, et al. EAACI Molecular Allergology User’s Guide 2.0. Pediatr Allergy Immunol. 2023 Mar;34 Suppl. 28:e13854.

While the impact of biodiversity, notably functional diversity, on ecosystem productivity has been extensively studied, little is known about the effect of individual species. Here, we identified species of high importance for productivity (key species) in over 28,000 diverse grassland communities in the European Alps, and compared their effects with those of community-level measures of functional composition (weighted means, variances, skewness, and kurtosis). After accounting for the environment, the five most important key species jointly explained more deviance than all statistics of functional composition. Key species were generally tall with high specific leaf areas. By dividing the observations according to distinct habitats, the explanatory power of all non-environmental predictors increased considerably, and the relationships between functional composition and productivity varied systematically, presumably because of changing interactions and trade-offs between traits. Our results advocate for a better consideration of species’ individual effects on ecosystem functioning in complement to community-level measures.

Objective Although it may have been criticized and questioned by numerous authors, external fixation holds its place in modern orthopaedics and traumatology. The aim of this paper is to show the applicability of the unilateral 3D external fixation in everyday practice. Methods For external fixation of the bones, we used unilateral 3D external fixators according to Mitkovic. Results In the Republic of Serbia, the Mitkovic unilateral 3D external fixation system has been used in over 30,000 cases. The indication field of applicability of this method is wide. External fixation method was mostly used for the treatment of open and closed tibial fractures at all levels, in open femoral fractures as a part of the “staging” protocol and in fractures of the upper limbs. We used external fixation for the treatment of nonunions, malunions, in the treatment of osteitis, septic pseudoarthrosis, angular knee deformities, post-traumatic deformities, for limb lengthening and in replantation surgery. Conclusion The unilateral external fixator enables 3D biomechanical stability and is suitable for use in everyday traumatology and orthopaedics practice.

First-trimester exposure to tofacitinib in ulcerative colitis: A case report of a healthy newborn and literature reviewArteen Arzivian1,2, Eva Zhang1, Robyn Laube1, Rupert Leong1,21 Department of Gastroenterology and Hepatology, Macquarie University Hospital, Sydney, Australia.2Faculty of Medicine, Health and Human Sciences, Macquarie Medical School, Macquarie University, Sydney, NSW, Australia.

The term “haplotype block” is commonly used in the developing field of haplotype-based inference methods. We argue that the term should be defined based on the structure of the Ancestral Recombination Graph (ARG), which contains complete information on the ancestry of a sample. We use simulated examples to demonstrate key features of the relation between haplotype blocks and ancestral structure, emphasising the stochasticity of the processes that generate them. Even the simplest cases of neutrality or of a “hard” selective sweep produce a rich structure, often missed by commonly used statistics. We highlight a number of novel methods for inferring haplotype structure, based on the full ARG, or on a sequence of trees, and illustrate how they can be used to define haplotype blocks using an empirical dataset. While the arrival of computationally efficient methods makes it possible to apply these concepts broadly, existing and new methods could include tools for the identification and explore haplotype blocks, as we define them. Understanding and applying the concept of the haplotype block will be essential to fully exploit long and linked-read sequencing technologies.

Aims. Right ventricular (RV) dysfunction is a predictor of adverse outcomes among patients with HF with reduced ejection fraction (HFrEF) however, differences in RV parameters in HFrEF patients with ischemic (ICM) and non-ischemic cardiomyopathies (NICM) are not well understood. We investigated echocardiographic characteristics, including RV strain, in patients with acute decompensated heart failure (ADHF) and compared patients with ICM and NICM etiology. Methods. Consecutive patients who presented with ADHF and NYHA class III-IV were prospectively enrolled if they had LVEF <40% and history of ICM or NICM. All patients underwent clinical exam, laboratory evaluation and 2-D echocardiographic assessment of the left ventricular (LV) and RV function, LV and RV global longitudinal strain (LVGLS, RVGLS), and RV free wall strain (RVfwLS). Results. Of 84 patients, 44 had ICM and 40 NICM. The groups had similar blood pressure, NT-proBNP, and echocardiographic parameters of LV function including LVGLS. Absolute RVGLS values were lower than RVfwLS values in both groups. Patients with NICM had significantly lower RVfwLS, but not RVGLS, compared to patients with ICM (-13% to -17%, P=0.006). Similar differences in RVfwLS were seen in patients in NYHA class III (NICM vs ICM: -13% and -17%, respectively, 95% CI: -8.5 to -0.5) and NYHA class IV (NICM vs ICM: -13.8% and -17%, respectively, 95% CI: -6.4 to -0.59). Conclusion. Among patients hospitalized with ADHF, patients with nonischemic etiology compared with the patients with ICM, have worse RV dysfunction measured by RVfwLS, despite similar extent of LV impairment and the same functional limitation class.

In this article, we want to present a patient with Burtonian or lead line at the gum tooth line, a rare presentation of lead poisoning.

Objectives: Transcutaneous Tibial Nerve Stimulation (TTNS) is a non-invasive method used in OAB treatment. We aimed to compare the effectiveness of the once a week and three times a week TTNS procedure in women diagnosed with wet type refractory OAB. Methods: A total of 60 patients diagnosed with wet type OAB was refractory to medical treatment included in the study. Participants were equally and randomly divided into two groups: TTNS treatment was performed with a time duration of 30 minutes for 12 weeks, once a week to Groıp-I and three times a week to Group-II. Pre and post-treatment OAB-V8/ICIQ-SF scores and voiding frequencies recorded in the bladder diary were compared between groups. Results: Four patients in Group-1 and eight in Group-2 left the study without completing the treatment. TTNS was performed in both groups for 12 weeks. There was a significant decrease in the voiding frequency, OAB-V8, ICIQ-SF scores in both group-1 and group-2 (p<0.001). A significant decrease in the OAB-V8 score was observed in the 5th week in Group-1, and on the 3rd week in group-2. Complete response was observed in 6 patients (23.1%) in Group-1 after 12 weeks of TTNS procedure. In group-2, 10 patients (45.5%) had a complete response. After the 12-week TTNS procedure, no significant difference was observed between the groups in terms of treatment response. Conclusion: TTNS can be safely used before invasive treatments in resistant OAB. TTNS procedure three times a week seems more effective than performing it once a week.

Aim A parent-metabolite population pharmacokinetic (popPK) model of iberdomide was developed and the influence of demographic and disease-related covariates on popPK parameters was assessed based on data from three clinical studies of iberdomide (dose range, 0.1 to 6 mg) in healthy subjects (N=81) and subjects with relapsed and refractory multiple myeloma (N=245). Methods Nonlinear mixed effects modeling was used to develop the popPK model based on data from 326 subjects across 3 clinical studies. Results The pharmacokinetics (PK) of iberdomide were adequately described with a two-compartment model with first-order absorption and elimination. A first order conversion rate was used to link the one-compartment linear elimination metabolite model with the parent model. Subject type (multiple myeloma subjects vs. healthy subject) was a statistically significant covariate on apparent clearance (CL/F) and apparent volume of distribution for the central compartment (V1/F), suggesting different PK between subjects with multiple myeloma and healthy subjects. Aspartate aminotransferase (AST), alkaline phosphatase (ALP) and sex were statistically but not clinically relevant covariates on CL/F. Metabolite (M12) PK tracked the PK of iberdomide. The metabolite to parent ratio was consistent across doses and combinations. Conclusion In conclusion, the parent-metabolite population pharmacokinetic model adequately described the time course PK data of iberdomide and M12. Iberdomide and M12 show robust PK exposure, not complicated by demographic factors, combination, hepatic or (mild and moderate) renal impairments. The model can be used to guide the dosing strategy for special patient population and inform future iberdomide study design.

The hypercoagulable state observed in COVID-19 could be responsible for morbidity and mortality. In this retrospective study we investigated whether therapeutic anticoagulation prior to infection has a beneficial effect in hospitalized COVID-19 patients. 1154 COVID-19 patients admitted to 6 hospitals in the Netherlands between March and May 2020 were included. We applied 1:3 propensity score matching to evaluate the association between prior therapeutic anticoagulation use and clinical outcome, with in hospital mortality as primary endpoint. 190 (16%) patients used therapeutic anticoagulation prior to admission. In the propensity score matched analyses, we observed no associations between prior use of therapeutic anticoagulation and overall mortality (RR 1.02 (95% CI; 0.80-1.30) or length of hospital stay (7.0 [4-12] vs 7.0 {4-12] days, p=0.69), although we observed a lower risk of pulmonary embolism (RR 0.19 (95% CI; 0.05-0.80). This study shows that prior use of therapeutic anticoagulation is not associated with improved clinical outcome in hospitalized COVID-19 patients.

We consider a 2-D study of a plate with finite thickness and infinite extent. The upper plate surface is considered traction free and subjected to an axisymmetric heating. The lower surface is thermally insulated and layed on a rigid foundation. A cylindrical heat source affects the plate. This problem is relevant to the generalized thermoelasticity theory with one relaxation time. Laplace and Hankel transforms are considered. We use Inverse Hankel and Laplace transforms numerically. All related functions are showed graphically.

Enzymatic detachment of cells might damage important features of cells and could affect subsequent function of cells in various applications. Therefore, non-enzymatic cell detachment using thermosensitive polymer matrix is necessary for maintaining cell quality after harvesting. In this study, we synthesized thermosensitive PNIPAm-co-AAc-b-PS and PNIPAm-co-AAm-b-PS copolymers and LCST was tuned near to body temperature. Then, polymer solutions (5% w/v, 10% w/v, and 20% w/v) were spin coated to prepare films for cell adhesion and thermal-induced cell detachment. The apha-step analysis and SEM image of the films suggested that the thickness of the films depends on the molecular weight and concentration which ranged from 206 nm to 1330 nm for PNIPAm-co-AAc-b-PS and 97.5 nm to 497 nm for PNIPAm-co-AAm-b-PS. The contact angles of the films verified that the polymer surface was moderately hydrophilic at 37°C. From cell attachment and detachment studies, RAW264.7 cells, were convincingly proliferated on the films to a confluent of >80 % within 48 days. However, relatively more cells were grown on PNIPAm-co-AAm-b-PS (5%w/v) films and thermal-induced cell detachment was more abundant in this formulation. As a result, commercial cytodex 3 microcarrier was coated with PNIPAm-co-AAm-b-PS (5%w/v) and interestingly enhanced cell detachment with preserved potential of recovery was observed at low temperature during 3D culturing. Thus, surface modification of microcarriers with PNIPAm-co-AAm-b-PS could be vital strategy for non-enzymatic cell dissociation and able to achieve adequate number of cells with maximum cell viability, and functionality for various cell-based applications. Keywords: surface coated microcarriers; thermosensitive polymer; non-enzymatic cell detachment

DNA metabarcoding has become a powerful approach for analyzing complex communities from environmental samples, but there are still methodological challenges limiting its full potential. While conserved DNA markers, like 16S and 18S, often are not able to discriminate among closely related species, other more variable markers – like the fungal ITS region, may include considerable intraspecific variation, which can lead to over-splitting of species during DNA metabarcoding analyses. Here we assess the effects of intraspecific sequence variation in DNA metabarcoding, by analyzing local populations of eleven fungal species. We investigated the allelic diversity of ITS2 haplotypes using both Sanger sequencing and high throughput sequencing (HTS), coupled with error correction with the software DADA2. All focal species, except one, included some level of intraspecific variation in the ITS2 region. Overall, we observed a high correspondence between haplotypes generated by Sanger sequencing and HTS, with the exception of a few additional haplotypes detected using either approach. These extra haplotypes, often occurring in low frequencies, were likely due to PCR and sequencing errors or intragenomic variation in the rDNA region. The presence of intraspecific (and possibly intragenomic) variation in ITS2 suggest that haplotypes (or ASVs) should not be used as basic units in ITS-based fungal community analyses, but an extra clustering step is needed to approach species-level resolution.

Coronavirus disease 2019 (COVID-19) may present with different symptoms and complications. Acrocyanosis and digital necrosis may be associated with COVID-19. We describe two patients with COVID-19 who died with acrocyanosis and digital necrosis at the terminal stage of their illness.

Background: This longitudinal cohort study aimed to examine the impact of the first wave of the COVID-19 pandemic in Ireland on parents of children with externalising difficulties, in comparison to parents of children without such difficulties. Method: Parents of 159 children completed online self-report measures at three time points during the first wave of the COVID-19 pandemic; 1) Delay and Mitigation Phase (March 2020 - May 2020), 2) Reopening of Society Phase (June 2020 – July 2020), and 3) Wave 2 Case Acceleration Phase (September 2020 - October 2020). Participants were allocated to the Clinical group if they met the clinical cut off point on the Conduct or Hyperactivity/Inattention subscales of the Strengths and Difficulties Questionnaire at Time 1. Results: Parents of children with externalising difficulties experienced significantly higher levels of stress, lower levels of wellbeing, and engaged in higher levels of avoidant-focused coping strategies longitudinally. There was a significant difference between outcomes at the different phases of the COVID-19 pandemic, for stress related to parenting, personal/family stress related to the impact of the COVID-19, and type of coping strategies employed. Children with externalising difficulties, in comparison to children without externalising difficulties, showed significantly greater adjustment over time for behavioural and emotional difficulties. Conclusions: Results provide important information regarding the trajectory of psychological outcomes in parents of children with externalising difficulties over the first wave of the COVID-19 pandemic, highlighting the need for increased parental supports during, and after, the COVID-19 pandemic.

Meta-analyses often encounter studies with incompletely reported variance measures (e.g. standard deviation values) or sample sizes, both needed to conduct weighted meta-analyses. Here, we first present a systematic literature survey on the frequency and treatment of missing data in published ecological meta-analyses showing that the majority of meta-analyses encountered incompletely reported studies. We then simulated meta-analysis data sets to investigate the performance of 14 options to treat or impute missing SDs and/or SSs. Performance was thereby assessed using results from fully informed weighted analyses on (hypothetically) complete data sets. We show that the omission of incompletely reported studies is not a viable solution. Unweighted and sample size-based variance approximation can yield unbiased grand means if effect sizes are independent of their corresponding SDs and SSs. The performance of different imputation methods depends on the structure of the meta-analysis data set, especially in the case of correlated effect sizes and standard deviations or sample sizes. In a best-case scenario, which assumes that SDs and/or SSs are both missing at random and are unrelated to effect sizes, our simulations show that the imputation of up to 90% of missing data still yields grand means and confidence intervals that are similar to those obtained with fully informed weighted analyses. We conclude that multiple imputation of missing variance measures and sample sizes could help overcome the problem of incompletely reported primary studies, not only in the field of ecological meta-analyses. Still, caution must be exercised in consideration of potential correlations and pattern of missingness.

A Case of Leukemia Cutis Showing Annular Erythema during the Course of Philadelphia Chromosome-Positive Acute B-lymphoblastic LeukemiaHizuru Tomita, MD1, Yoshimasa Nobeyama, MD1, You Sakayori, MD2, Rika Matsumoto, MD1, Satomi Chujo, MD1, Hikaru Suzuki, MD1, Akihiko Asahina, MD11. Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan2. Department of Oncology/Hematology, The Jikei University School of Medicine, Tokyo, JapanCorresponding author:Yoshimasa Nobeyama, MDDepartment of Dermatology, The Jikei University School of Medicine,3-25-8, Minato-ku, Tokyo, 105-8461, JapanE-mail: [email protected] authors received no financial support for this study.The authors have no conflicts of interest to declare.Key words: leukemia cutis, annular erythema, acute B-lymphoblastic leukemia

OBJECTIVE: The objective of this study was to evaluate C-section rates, before and after the implementation of the Project Appropriate Birth based on the Robson 10-group classification system. DESIGN: An observational, cross-sectional study. SETTING: Maternity hospital in South Brazil. POPULATION: All pregnant women attending, April 2016 through April 2017 (phase 1, pre-implementation of the Project Appropriate Birth) and June 2017 through June 2018 (phase 2, post-implementation of the Project Appropriate Birth). METHODS: Maternal and obstetric characteristics were evaluated, including Robson’s classification, based on the characteristics of pregnancy and childbirth. Chi-square test and crude and adjusted prevalence ratios were used to analyze study variables. The significance level was set at 5%. MAIN OUTCOME MEASURES: C-section rate for each group, their contribution to the overall c-section rate and the differences in these contributions before and after PPA implementation. RESULTS: C-section rates decreased from 62.4% to 55.6%, which represented a 10.9% reduction after the implementation of the Project Appropriate Birth. Pregnant women in Robson classification groups 1 through 4 had the greatest decrease in C-section rates, ranging from 49.1% to 38.6%, which represents a 21.5% reduction. The greatest contributors to the overall C-section rates were group 5 and group 2, accounting for more than 60% of the C-section deliveries. CONCLUSION: The Project Appropriate Birth had an important impact on the reduction of C-section rates, especially in Robson classification groups 1 through 4, which indicates that providing mothers with evidence-based interventions for labor and childbirth assistance will contribute to reduce C-section rates.