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Grégoire Jacques Noël Cozon,1 Pierre Clerson,2 Annaïk Dokhan,3 Yann Fardini,2 Taylor Pindi Sala,4 Jean-Charles Crave4 1Department of Clinical Immunology and Rheumatology, Edouard Herriot Hospital, Lyon, France; 2Soladis Clinical Studies, Roubaix, France; 3KPL, Paris, France; 4Octapharma France, Boulogne, France Purpose: Patients with primary immunodeficiency (PID) often receive immunoglobulin replacement therapy (IgRT). Physicians and patients have the choice between various methods of administration. For subcutaneous immunoglobulin infusions, patients may use an automated pump (P) or push the plunger of a syringe (rapid push [RP]). P infusions are performed once a week and last around 1 hour. RP decreases the duration of administration, but requires more frequent infusions.Patients and methods: Eight out of 30 patients (coming from a single center) who had participated in the cross-over, randomized, open-label trial comparing P and RP participated in a focus group or underwent in-depth interviews. Patients had a long history of home-based subcutaneous immunoglobulin using P. The trial suggested that RP had slightly greater interference on daily life than P, but similar efficacy and better cost-effectiveness. When asked about the delivery method they had preferred, around one-third of patients pointed out RP rather than P. In-depth interviews may reveal unforeseen reasons for patients’ preferences. Results: Interviews underlined the complexity of the relationship that the patients maintain with their disease and IgRT. Even if they recognized the genetic nature of the disease and claimed PID was a part of them, patients tried not to be overwhelmed by the disease. IgRT by P was well integrated in patients’ routine. By contrast, RP too frequently reminded the patients of their disease. In addition, some patients pointed out the difficulty of pushing the plunger due to the viscosity of the product. Coming back too frequently, RP was not perceived as time saving over a week. Long-lasting use of P could partly explain patients’ reasonable reluctance to change to RP.Conclusion: In-depth interviews of PID patients highlighted unforeseen reasons for patients’ preference that the physician needs to explore during the shared medical decision-making process. Keywords: in-depth interviews, primary immunodeficiency, patients’ expectations, preference, immunoglobulins, immunoglobulins replacement therapy, pump, rapid push, syringe

Aubergine (eggplant) is susceptible to fungal wilts caused by Fusarium oxysporum f. sp. melongenae (Fom) and Verticillium dahliae (Vd). Wild and allied relatives represent a good source of resistance, and introgression lines (ILs) have been obtained through introgression of the Rfo-sa1 locus conferring resistance to Fusarium oxysporum from Solanum aethiopicum into cultivated aubergine. In this work, a deep phenotype characterization was performed according to two parameters: progression of symptoms along the stem and disease severity in leaves. This analysis showed that the Fom-resistant ILs carrying introgression of the Rfo-sa1 locus displayed significantly improved tolerance to Verticillium attack after a preliminary inoculation with F. oxysporum. This positive effect was particularly evident when Verticillium inoculation was performed simultaneously or after Fusarium inoculation. Transcript profiling carried out using a combination of suppression subtractive hybridization ( SSH), microarray and qRT-PCR analyses of roots inoculated with selected combinations of fungal pathogens enabled the identification of 164 differentially expressed genes between inoculated and uninoculated plants or between different stages after pathogen infection. Overall, the results highlighted a number of candidate genes putatively involved in early defence responses or signalling pathways activated upon infection of aubergine with either Fom and/or Vd, and thus leading to a broad Rfo-sa1-mediated tolerance against both these wilt pathogens. [ABSTRACT FROM AUTHOR]

Background: Timely recognition of sepsis in emergency department (ED) is challenging. We evaluated the impact of implementing the biomarker monocyte distribution width (MDW) at bedside, on the time to anti-infective administration., Methods: We conducted a before-and-after cohort study in the ED of an academic hospital in Paris, to compare sepsis patients care and outcomes, before and after the implementation of point of care (POC) MDW measurement in the ED. During post-implementation period (period-2), MDW was measured with complete blood count by ED nurses with results given in 2 min: if above 21.5 units, ED physicians were asked to consider sepsis and to start an anti-infectious as soon as possible. Primary endpoint was time to anti-infectious administration (TTA) from ED arrival, and secondary endpoints were TTA from sepsis onset (TTAS), length of stay, mortality, and hospitalization rates., Results: In total, 255 patients (period-1) and 180 patients (period-2) with sepsis were included. The TTA was 5.4 h (3.5-7.7) period-1 and 4.9 h (IQR 2.5-7.1) in period-2 (p = 0.06). MDW implementation significantly reduced the median TTAS from to 3.7 h (IQR 1.5-5.8) in period-1, to 2.2 h (IQR 0.5-4.5) in period-2 (p < 0.001). Mortality rates remained similar between the two periods (18% vs. 16% respectively, p = 0.4), as did hospitalization rates (93% vs. 91%, p = 0.4) and ED length of stay (7.2 h (5.3-9.8) vs 7.0 (5.4-9.4), p = 0.7)., Conclusion: Implementing POC MDW measurement in the ED protocols enhances the timeliness of anti-infective administration from sepsis onset, meeting current sepsis management guidelines., (© 2024. The Author(s).)

Common beans are a common staple food with valuable nutritional qualities, but their high contents in antinutritional factors (ANFs) can decrease the bioavailability of (i) fat-soluble micronutrients including carotenoids and (ii) minerals. Our objective was to select ANF-poor bean lines that would not interfere with carotenoid and mineral bioavailability. To achieve this objective, seeds of commercial and experimental Phaseolus vulgaris L. bean lines were produced for 2 years and the bean's content in ANFs (saponins, phytates, tannins, total polyphenols) was assessed. We then measured carotenoid bioaccessibility and mineral solubility (i.e. the fraction of carotenoid and mineral that transfer into the aqueous phase of the digesta and is therefore absorbable) from prepared beans using in vitro digestion. All beans contained at least 200 mg/100 g of saponins and 2.44 mg/100 g tannins. The low phytic acid (lpa) lines, lpa1 and lpa1 2 exhibited lower phytate levels (≈ - 80%, p = 0.007 and p = 0.02) than their control BAT-93. However, this decrease had no significant impact on mineral solubility. HP5/1 (lpa + phaseolin and lectin PHA-E free) bean line, induced an improvement in carotenoid bioaccessibility (i.e., + 38%, p = 0.02, and + 32%, p = 0.005, for phytofluene bioaccessibility in 2021 and 2022, respectively). We conclude that decrease in the phytate bean content should thus likely be associated to decreases in other ANFs such as tannins or polyphenols to lead to significant improvement of micronutrient bioaccessibility., (© 2024. The Author(s).)

In recent decades, scarcity of available resources, population growth and the widening in the consumption of processed foods and of animal origin have made the current food system unsustainable. High-income countries have shifted towards food consumption patterns which is causing an increasingly process of environmental degradation and depletion of natural resources, with the increased incidence of malnutrition due to excess (obesity and non-communicable disease) and due to chronic food deprivation. An urgent challenge is, therefore, to move towards more healthy and sustainable eating choices and reorientating food production and distribution to obtain a human and planetary health benefit. In this regard, legumes represent a less expensive source of nutrients for low-income countries, and a sustainable healthier option than animal-based proteins in developed countries. Although legumes are the basis of many traditional dishes worldwide, and in recent years they have also been used in the formulation of new food products, their consumption is still scarce. Common beans, which are among the most consumed pulses worldwide, have been the focus of many studies to boost their nutritional properties, to find strategies to facilitate cultivation under biotic/abiotic stress, to increase yield, reduce antinutrients contents and rise the micronutrient level. The versatility of beans could be the key for the increase of their consumption, as it allows to include them in a vast range of food preparations, to create new formulations and to reinvent traditional legume-based recipes with optimal nutritional healthy characteristics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lisciani, Marconi, Le Donne, Camilli, Aguzzi, Gabrielli, Gambelli, Kunert, Marais, Vorster, Alvarado-Ramos, Reboul, Cominelli, Preite, Sparvoli, Losa, Sala, Botha and Ferrari.)

Proteases, including serine proteases, are involved in the entire life cycle of plants. Proteases are controlled by protease inhibitors (PI) to limit any uncontrolled or harmful protease activity. The role of PIs in biotic and abiotic stress tolerance is well documented, however their role in various other plant processes has not been fully elucidated. Seed development is one such area that lack detailed work on the function of PIs despite the fact that this is a key process in the life cycle of the plant. Serine protease inhibitors (SPI) such as the Bowman-Birk inhibitors and Kunitz-type inhibitors, are abundant in legume seeds and act as antinutrients in humans and animals. Their role in seed development is not fully understood and present an interesting research target. Whether lowering the levels and activity of PIs, in order to lower the anti-nutrient levels in seed will affect the development of viable seed, remains an important question. Studies on the function of SPI in seed development are therefore required. In this Perspective paper, we provide an overview on the current knowledge of seed storage proteins, their degradation as well as on the serine protease-SPI system in seeds and what is known about the consequences when this system is modified. We discuss areas that require investigation. This includes the identification of seed specific SPIs; screening of germplasms, to identify plants with low seed inhibitor content, establishing serine protease-SPI ratios and lastly a focus on molecular techniques that can be used to modify seed SPI activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vorster, Westhuizen, Plessis, Marais, Sparvoli, Cominelli, Camilli, Ferrari, Le Donne, Marconi, Lisciani, Losa, Sala and Kunert.)

Background: Long-term therapeutic adherence remains an essential challenge for better management of chronic diseases. It is estimated at 50% in developed countries., Objective: The study aimed to evaluate, under real conditions, the influence of satisfaction with Flexig use on adherence to subcutaneous immunoglobulin home-treatment therapy in a sample of French patients with chronic dysimmune diseases., Methods: This is a 2-year prospective cohort involving 241 patients from several hospitals in France whose data were extracted from the Flexig 2.0 mHealth application. Satisfaction was assessed by System Usability Scale (SUS) and user experience by User Experience Questionnaire (UEQ). Adherence to Ig therapy was assessed by medication possession rate. We analyzed the relationship between Flexig user satisfaction and adherence to treatment, as well as determinants of adherence., Results: Most patients (82.7%) were being treated for an immunodeficiency, versus 17.3% for a chronic autoimmune and inflammatory disease. Almost all patients (97.9%) received subcutaneous immunoglobulin therapy. The patients' ages (means ± SDs) were 36.5 ± 18.3 years, disease duration was about 6 years, and 58.5% were men. Flexig user satisfaction was 76.2 ± 8 (System Usability Scale), associated with good user experience reported on UEQ. Adherence rate was 99.7%. Time on app, disease duration, and Flexig user satisfaction were statistically predictive of adherence to IgG therapy. High adherence to Ig therapy was associated with good satisfaction with using Flexig ( P  < .0001)., Conclusion: Adherence to Ig therapy in chronic dysimmune disease was strong and was associated with good satisfaction among Flexig users, suggesting that electronic support may be a valuable compliance aid., (© 2023 The Authors.)

The Asparagus genus includes approximately 240 species, the most important of which is garden asparagus ( Asparagus officinalis L.), as this is a vegetable crop cultivated worldwide for its edible spear. Along with garden asparagus, other species are also cultivated (e.g., Asparagus maritimus L.) or have been proposed as untapped sources of variability in breeding programs (e.g., Asparagus acutifolius L.). In the present work, we applied reduced-representation sequencing to examine a panel of 378 diverse asparagus genotypes, including commercial hybrids, interspecific lines, wild relatives of garden asparagus, and doubled haploids currently used in breeding programs, which enabled the identification of more than 200K single-nucleotide polymorphisms (SNPs). These SNPs were used to assess the extent of linkage disequilibrium in the diploid gene pool of asparagus and combined with preliminary phenotypic information to conduct genome-wide association studies for sex and traits tied to spear quality and production. Moreover, using the same phenotypic and genotypic information, we fitted and cross-validated genome-enabled prediction models for the same set of traits. Overall, our analyses demonstrated that, unlike the diversity detected in wild species related to garden asparagus and in interspecific crosses, cultivated and wild genotypes of A. officinalis L. show a narrow genetic basis, which is a contributing factor hampering the genetic improvement of this crop. Estimating the extent of linkage disequilibrium and providing the first example of genome-wide association study and genome-enabled prediction in this species, we concluded that the asparagus panel examined in the present study can lay the foundation for determination of the genetic bases of agronomically important traits and for the implementation of predictive breeding tools to sustain breeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sala, Puglisi, Ferrari, Salamone, Tassone, Rotino, Fricano and Losa.)

Common bean seeds are an excellent source of protein as well as of carbohydrates, minerals, vitamins, and bioactive compounds reducing, when in the diet, the risks of diseases. The presence of bioactive compounds with antinutritional properties (e.g., phytic acid, lectins, raffinosaccharides, protease inhibitors) limits, however, the bean's nutritional value and its wider use in food preparations. In the last decades, concerted efforts have been, therefore, made to develop new common bean genotypes with reduced antinutritional compounds by exploiting the natural genetic variability of common bean and also applying induced mutagenesis. However, possible negative, or positive, pleiotropic effects due to these modifications, in terms of plant performance in response to stresses or in the resulting technological properties of the developed mutant genotypes, have yet not been thoroughly investigated. The purpose of the perspective paper is to first highlight the current advances, which have been already made in mutant bean characterization. A view will be further provided on future research directions to specifically explore further advantages and disadvantages of these bean mutants, their potential use in innovative foods and representing a valuable genetic reservoir of combinations to assess the true functional role of specific seed bioactive components directly in the food matrix., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cominelli, Sparvoli, Lisciani, Forti, Camilli, Ferrari, Le Donne, Marconi, Juan Vorster, Botha, Marais, Losa, Sala, Reboul, Alvarado-Ramos, Waswa, Ekesa, Aragão and Kunert.)

Violence perpetrated by an intimate partner (IPV) is an important human rights and public health problem worldwide and when experienced during pregnancy is of special concern due to the harmful impact on maternal and child health. Women living in Vanuatu, and especially Sanma Province, experience high rates of IPV, however little is known about their experiences of violence when pregnant. The aim was to describe the prevalence, patterns and determinants of IPV among women who are pregnant in Sanma Province, Vanuatu. A cross-sectional survey was used. All healthy adult women attending Northern Provincial Hospital antenatal clinic from late May to late July 2019 were eligible and invited to participate. Psychological, physical and sexual IPV and controlling behaviours were assessed with a modified version of the World Health Organization Violence Against Women Instrument administered as an individual interview. Descriptive statistics were used to analyse prevalence and patterns of IPV and logistic regression models to identify determinants. Of 214 women who expressed interest in participating, 192 women contributed data. Overall 64.2% of women had experienced any IPV during their lifetime and 42.2% had experienced IPV during their current pregnancy. Experience of co-occurrence of violence types was common, and it was more common for IPV to continue than to cease during pregnancy. Factors which increased likelihood of experiencing IPV included being employed, occupying a lower socioeconomic position, having a partner who was unemployed or used alcohol or illicit substances at least once a week. IPV, in all its forms, is a common problem faced by women who are pregnant and living in Vanuatu.

Background: We aimed to describe the association between ni-Vanuatu women's experiences of violence perpetrated by their intimate partner (IPV) during pregnancy, and health outcomes, including self-reported general health, antenatal care attendance, psychological distress and suicidal thoughts/behaviours., Methods: A cross-sectional survey of a consecutive cohort of women attending the antenatal clinic at Northern Provincial Hospital, Vanuatu from May to July 2019. Psychological, physical and sexual IPV were measured using the WHO Violence Against Women Instrument. Psychological distress was measured using the 20-item WHO Self-Reporting Questionnaire. Data were collected in confidential individual interviews with a trained local interviewer. Logistic regression models were used to investigate the relationship between IPV and health outcomes while controlling for confounding variables., Findings: 192 women contributed data, among whom 188 answered the questions about IPV. Of these, 80 women had experienced any form of IPV during the current pregnancy. Women who experienced IPV were more likely than those who did not to report poorer general health (aOR:2.97, 95%CI:1•42-6•22), higher levels of psychological distress (aOR:4.77, 95%CI:2•02-11.24) and suicidal thoughts (aOR:3•78, 95%CI:1•71-8.33) and/or behaviours (aOR:1.98, 95%CI:0•69-5.64) in the previous four weeks. Late antenatal attendance was widespread, but not related to IPV., Interpretation: IPV perpetrated against women who are pregnant is a serious public health problem in Vanuatu and is related to worse antenatal physical and psychological health., Funding: JF is supported by the Finkel Professorial Fellowship, funded by the Finkel Family Foundation; TT is supported by a Monash Strategic Bridging Fellowship. Monash University provided a student research grant to SMcK. Soroptimist International Gippsland provided a grant to fund small gifts for the participants., Competing Interests: The authors declare that there are no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd.)

Eggplant ( Solanum melongena L.) represents the third most important crop of the Solanaceae family and is an important component of our daily diet. A population of 164 F6 recombinant inbred lines (RILs), derived from two eggplant lines differing with respect to several key agronomic traits, "305E40" and "67/3," was grown to the commercial maturation stage, and fruits were harvested, separated into peel and flesh, and subjected to liquid chromatography Liquid Chromatography/Mass Spectrometry (LC/MS) analysis. Through a combination of untargeted and targeted metabolomics approaches, a number of metabolites belonging to the glycoalkaloid, anthocyanin, and polyamine classes and showing a differential accumulation in the two parental lines and F1 hybrid were identified. Through metabolic profiling of the RILs, we identified several metabolomic quantitative trait loci (mQTLs) associated with the accumulation of those metabolites. Each of the metabolic traits proved to be controlled by one or more quantitative trait loci (QTLs); for most of the traits, one major mQTL (phenotypic variation explained [PVE] ≥ 10%) was identified. Data on mQTL mapping and dominance-recessivity relationships of measured compounds in the parental lines and F1 hybrid, as well as an analysis of the candidate genes underlying the QTLs and of their sequence differences in the two parental lines, suggested a series of candidate genes underlying the traits under study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sulli, Barchi, Toppino, Diretto, Sala, Lanteri, Rotino and Giuliano.)

The most common peripheral nervous system manifestations in Sjogren's syndrome are small fiber sensory neuropathies (SFPN) and axonal sensorimotor polyneuropathies. Currently, treatment in small fiber neuropathy is mainly symptomatic and based on anti-depressors and anti-epileptics. The benefit of treatment with polyvalent immunoglobulins for SFPN has been reported in small series of patients, although transient in several cases. The medium-to-long-term effects of polyvalent immunoglobulins (Ig) in SFPN in patients with Sjogren's syndrome who are refractory to conventional treatments remain an unmet medical need. We present our experience related to the persistent improvement of Ig in a case series of SFPN in Sjogren's syndrome and relevant data in the literature regarding the benefits of immunoglobulins, for this indication.

Azathioprine (AZA), an oral immunosuppressant, is safe during pregnancy. Some reports suggested different impairments in the offspring of mothers with autoimmune diseases (AI) exposed in utero to AZA. These observations are available from retrospective studies or case reports. However, data with respect to the long-term safety in the antenatally exposed child are still lacking. The aim of this study is to summarize the current knowledge in this field and to focus on the need for a prospective study on this population. We performed a PubMed search using several search terms. The actual data show that although the risk of congenital anomalies in offspring, as well as the infertility risk, are similar to those found in general population, there is a higher incidence of prematurity, of lower weight at birth and an intra-uterine delay of development. There is also an increased risk of materno- fetal infections, especially cytomegalovirus infection. Some authors raise the interrogations about neurocognitive impairment. Even though the adverse outcomes might well be a consequence of maternal illness and disease activity, interest has been raised about a contribution of this drug. However, the interferences between the external agent (in utero exposure to AZA), with the host (child genetic susceptibility, immune system anomalies, emotional status), environment (public health, social context, availability of health care), economic, social, and behavioral conditions, cultural patterns, are complex and represent confounding factors. In conclusion, it is necessary to perform studies on the medium and long-term outcome of children born by mothers with autoimmune diseases, treated with AZA, in order to show the safety of AZA exposure. Only large-scale population studies with long-term follow-up will allow to formally conclude in this field. TAKE HOME MESSAGES., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2020. Published by Elsevier B.V.)

Eggplant is the second most important solanaceous berry-producing crop after tomato. Despite mapping studies based on bi-parental progenies and GWAS approaches having been performed, an eggplant intraspecific high-resolution map is still lacking. We developed a RIL population from the intraspecific cross '305E40', (androgenetic introgressed line carrying the locus Rfo-Sa1 conferring Fusarium resistance) x '67/3' (breeding line whose genome sequence was recently released). One hundred and sixty-three RILs were genotyped by a genotype-by-sequencing (GBS) approach, which allowed us to identify 10,361 polymorphic sites. Overall, 267 Gb of sequencing data were generated and ~773 M Illumina paired end (PE) reads were mapped against the reference sequence. A new linkage map was developed, including 7249 SNPs assigned to the 12 chromosomes and spanning 2169.23 cM, with iaci@liberoan average distance of 0.4 cM between adjacent markers. This was used to elucidate the genetic bases of seven traits related to anthocyanin content in different organs recorded in three locations as well as seed vigor. Overall, from 7 to 17 QTLs (at least one major QTL) were identified for each trait. These results demonstrate that our newly developed map supplies valuable information for QTL fine mapping, candidate gene identification, and the development of molecular markers for marker assisted selection (MAS) of favorable alleles., Competing Interests: The authors declare that they have no conflict of interest.

Immunoglobulins are 2nd or 3rd-line treatments in dermatomyositis (DM) or polymyositis (PM) refractory to high-dose corticosteroids and immunosuppressants. Immunoglobulins (2 g/kg/mo) are usually administered intravenously (IVIg) once a month and the patients stay at hospital for a few days. Recently, subcutaneous injections (SCIg) were proposed 2 to 3 times per week, in some dysimmune diseases. SCIg are administered at home preferably by the patient or by a nurse. We investigated the needs and attitudes of DM and PM patients with experience of IVIg and SCIg.Seven patients (6 PM and 1 DM) from a single center participated in a focus group (N = 6) or underwent in-depth interview (N = 1). Six had the experience of both IVIg at hospital and SCIg at home; 1 has received only IVIg at hospital. Verbatim was recorded and transcribed for further content analysis and computer-aided textual analysis.Clinical profiles and stories were heterogeneous. At diagnosis, muscle weakness, severe pain, and fatigue were at the forefront of patients' complaints impairing daily life. Patients reported considerable improvement with immunoglobulins. SCIg were described as easy, less disruptive for daily life, well tolerated, and less time-consuming. SCIg self-administration at home restored the feeling of autonomy and control.Interviews of DM and PM patients revealed that recovering autonomy and control was a central advantage of home-based SCIg that were efficient, well tolerated, and perceived as a good compromise between treatment burden and efficacy.

With approximately 450 species, spiny Solanum species constitute the largest monophyletic group in the Solanaceae family, but a high-quality genome assembly from this group is presently missing. We obtained a chromosome-anchored genome assembly of eggplant (Solanum melongena), containing 34,916 genes, confirming that the diploid gene number in the Solanaceae is around 35,000. Comparative genomic studies with tomato (S. lycopersicum), potato (S. tuberosum) and pepper (Capsicum annuum) highlighted the rapid evolution of miRNA:mRNA regulatory pairs and R-type defense genes in the Solanaceae, and provided a genomic basis for the lack of steroidal glycoalkaloid compounds in the Capsicum genus. Using parsimony methods, we reconstructed the putative chromosomal complements of the key founders of the main Solanaceae clades and the rearrangements that led to the karyotypes of extant species and their ancestors. From 10% to 15% of the genes present in the four genomes were syntenic paralogs (ohnologs) generated by the pre-γ, γ and T paleopolyploidy events, and were enriched in transcription factors. Our data suggest that the basic gene network controlling fruit ripening is conserved in different Solanaceae clades, and that climacteric fruit ripening involves a differential regulation of relatively few components of this network, including CNR and ethylene biosynthetic genes.

Background. HPC2/ELAC2 has been identified as a prostate cancer (PC) susceptibility gene. Ser- Leu changes at amino acid 217 have been one of the most studied variants of this gene. Several reports have shown association of this variant with PC in samples of men drawn from families with hereditary PC and even sporadic cases. Aim. This study aimed at assessing this association and the prevalence of the Ser217Leu variant of ELAC2 in populations of the Littoral Region of Cameroon. Method. 103 PC case subjects and 80 randomly selected controls identified from the study population participated in the study. 2 milliliters of blood samples was collected from each of the consented participants and used for human genomic DNA extraction and genotyping of the ELAC2 gene by the nonenzymatic salting out and PCR-RFLP methods, respectively. Results. The frequencies of the wild type (SS), heterozygous mutant (SL), and homozygous mutant (LL) genotypes were, respectively, 28.2%, 49.5%, and 22.3% in prostate cancer patients and 28.8%, 67.5%, and 3.7% in controls. Comparing the LL with SS and (SL+LL) with SS showed that the presence of two copies of the L allele confers a high risk of prostate cancer as compared to the presence of only one L allele which presents no risk of prostate cancer (OR = 6.080 and 1.030, respectively). Analysis of our results also suggested an association ( P = 0.0012) of the Ser217Leu variant with increased risk of prostate cancer. Conclusion. Alterations in the ELAC2 gene contribute to prostate cancer susceptibility in men living in the Littoral Region of Cameroon.

Background: Ensuring equitable and timely access to Cognitive Behaviour Therapy (CBT) is challenging within Canada's service delivery model. The current study aims to determine acceptability and effectiveness of 4-session, large, Cognitive Behaviour Therapy with Mindfulness (CBTm) classes., Methods: A retrospective chart review of adult outpatients (n = 523) who attended CBTm classes from 2015 to 2016. Classes were administered in a tertiary mental health clinic in Winnipeg, Canada and averaged 24 clients per session. Primary outcomes were (a) acceptability of the classes and retention rates and (b) changes in anxiety and depressive symptoms using Generalized Anxiety Disorder 7-item (GAD-7) and Patient Health Questionnaire 9-item (PHQ-9) scales., Results: Clients found classes useful and > 90% expressed a desire to attend future sessions. The dropout rate was 37.5%. A mixed-effects linear regression demonstrated classes improved anxiety symptoms (GAD-7 score change per class = - 0.52 [95%CI, - 0.74 to - 0.30], P < 0.001) and depressive symptoms (PHQ-9 score change per class = - 0.65 [95%CI, - 0.89 to - 0.40], P < 0.001). Secondary analysis found reduction in scores between baseline and follow-up to be 2.40 and 1.98 for the GAD-7 and PHQ-9, respectively. Effect sizes were small for all analyses., Conclusions: This study offers preliminary evidence suggesting CBTm classes are an acceptable strategy to facilitate access and to engage and maintain clients' interest in pursuing CBT. Clients attending CBTm classes experienced improvements in anxiety and depressive symptoms. Symptom improvement was not clinically significant. Study limitations, such as a lack of control group, should be addressed in future research.

The transfer of phase coherence from an ultrastable master laser to a distributed feedback diode laser, using an optical comb as a transfer oscillator, is obtained via a new scheme allowing continuous scanning across the whole tuning range of the slave laser together with absolute frequency determination. This is accomplished without phase lock loops, through a robust high-bandwidth feed-forward control acting directly on the slave laser output radiation. The correction is obtained by means of a dual-parallel Mach-Zehnder interferometer used as an optical single-sideband modulator. Coherence transfer across a master-slave frequency gap of 14 THz yields an ∼10 kHz linewidth providing high injection efficiency of an optical cavity with finesse 250 000. This allows demonstrating a cavity ring-down absorption spectrum of low-pressure ambient air over a 300 GHz spectral window.

Immunoglobulin (Ig) therapy is used to treat a wide range of immunodeficiencies and autoimmune diseases; While, its clinical benefit has been demonstrated in several studies, Ig therapy is associated with a risk of systemic adverse effects. As such, Onset of renal impairment, including acute renal failure, osmotic nephrosis and renal insufficiency, after immunoglobulin administration is rare, but is one of the most significant concerns related to intravenous Ig use at immunomodulatory doses. However, only few studies have investigated the safety of subcutaneous Ig (SCIg) in relation to these rare conditions. The aim of this prospective study is to describe the safety of SCIg (Gammanorm), specifically with regards to renal function, in inflammatory myopathies including mainly polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM). Twenty-four cases were included: 10 patients with PM, 6 with IBM, 5 with DM, 2 with mixed connective-tissue disease (MCTD) and 1 patient with scleromyositis. SCIg was given two to three times per week at 2 g/kg/month in all patients. Patients were treated for a mean duration of 24.6 ± 11.4 months (range 8-37 months) and received a median of 78 SCIg infusions. Renal function was stable over the study period in all patients. High-dose SCIg was well tolerated; the treatment was not withdrawn during the first year in any patient for safety issues. These results suggest that the use of high-dose SCIg is generally feasible and safe in patients with inflammatory myopathies., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Endogenous housekeeping genes are traditionally employed to normalize the expression of target genes in RT-qPCR studies. Assuming that a perfect housekeeping suitable for every condition does not exist, expression stability of the chosen reference gene should be evaluated at every new experiment. The housekeeping selection process reveals furthermore complicated and time-consuming when different conditions have to be compared in the same experimental dataset. As an alternative strategy, we spiked an external reference transcript (ERT) into all RNA samples of our dataset (eggplant roots subjected to different biotic stresses), and used it to normalize the expression levels of native candidate housekeeping. ERT expression resulted highly stable across all samples and enabled to indicate glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as the most stable endogenous housekeeping. This result was confirmed by the use of GeNorm, Normfinder, and BestKeeper algorithms. This method might be generally applied to expedite the selection process of the best reference gene.

Evidence that anxiety disorders are associated with general medical conditions is growing. While it is known that medical and mental conditions are often comorbid, research demonstrates that there may be underlying causal mechanisms. Furthermore, comorbid anxiety and general medical conditions are associated with poorer patient outcomes than either condition alone. Comorbid general medical and mental disorders not only affect individual patient health but also strain existing medical systems. Growing health care expenditures and increasing time pressures on clinicians create a challenging environment for intensive therapy in traditional settings. Effective screening, diagnosis, and treatment of individuals with comorbid conditions require health systems that are based on interprofessional collaboration, including integrative and collaborative care services. These models encourage the provision of patient care within a network of health care professionals, working together and sharing expertise for more efficient and holistic care. Research on the design and implementation of these systems within the context of anxiety disorders and comorbid general medical conditions is in its infancy. Given the staggeringly high rates of anxiety disorders within the general population and the continued rise of many chronic medical conditions coinciding with the increasing lifespan, mental health and primary care providers should consider how they might implement integrative care methods within their own practice., (Copyright © 2017 by the American Psychiatric Association.)

Current phylogenetic sampling reveals that dioecy and an XY sex chromosome pair evolved once, or possibly twice, in the genus Asparagus Although there appear to be some lineage-specific polyploidization events, the base chromosome number of 2n = 2× = 20 is relatively conserved across the Asparagus genus. Regardless, dioecious species tend to have larger genomes than hermaphroditic species. Here, we test whether this genome size expansion in dioecious species is related to a polyploidization and subsequent chromosome fusion, or to retrotransposon proliferation in dioecious species. We first estimate genome sizes, or use published values, for four hermaphrodites and four dioecious species distributed across the phylogeny, and show that dioecious species typically have larger genomes than hermaphroditic species. Utilizing a phylogenomic approach, we find no evidence for ancient polyploidization contributing to increased genome sizes of sampled dioecious species. We do find support for an ancient whole genome duplication (WGD) event predating the diversification of the Asparagus genus. Repetitive DNA content of the four hermaphroditic and four dioecious species was characterized based on randomly sampled whole genome shotgun sequencing, and common elements were annotated. Across our broad phylogenetic sampling, Ty-1 Copia retroelements, in particular, have undergone a marked proliferation in dioecious species. In the absence of a detectable WGD event, retrotransposon proliferation is the most likely explanation for the precipitous increase in genome size in dioecious Asparagus species., (Copyright © 2016 Harkess et al.)

Eggplant berries are a source of health-promoting metabolites including antioxidant and nutraceutical compounds, mainly anthocyanins and chlorogenic acid; however, they also contain some anti-nutritional compounds such as steroidal glycoalkaloids (SGA) and saponins, which are responsible for the bitter taste of the flesh and with potential toxic effects on humans. Up to now, Quantitative Trait Loci (QTL) for the metabolic content are far from being characterized in eggplant, thus hampering the application of breeding programs aimed at improving its fruit quality. Here we report on the identification of some QTL for the fruit metabolic content in an F2 intraspecific mapping population of 156 individuals, obtained by crossing the eggplant breeding lines "305E40" × "67/3." The same population was previously employed for the development of a RAD-tag based linkage map and the identification of QTL associated to morphological and physiological traits. The mapping population was biochemically characterized for both fruit basic qualitative data, like dry matter, °Brix, sugars, and organic acids, as well as for health-related compounds such chlorogenic acid, (the main flesh monomeric phenol), the two peel anthocyanins [i.e., delphinidin-3-rutinoside (D3R) and delphinidin-3-(p- coumaroylrutinoside)-5-glucoside (nasunin)] and the two main steroidal glycoalkaloids, solasonine, and solamargine. For most of the traits, one major QTL (PVE ≥10%) was spotted and putative orthologies with other Solanaceae crops are discussed. The present results supply valuable information to eggplant breeders on the inheritance of key fruit quality traits, thus providing potential tools to assist future breeding programs.

An integrated single-sideband modulator is used as the sole wide-bandwidth frequency actuator in a Pound-Drever-Hall locking loop. Thanks to the large modulation bandwidth, the device enables a locking range of ±75 MHz and a control bandwidth of 5 MHz without the need for a second feedback loop. As applied to the coupling of an extended-cavity diode laser at 1.55 μm to a high-finesse optical cavity, the in-loop frequency noise spectral density reaches a minimum of 1 mHz/Hz(1/2) at 1 kHz.

Scope: Cystine-knot miniproteins are bioactive molecules with a broad range of potential therapeutic applications. Recently, it was demonstrated that two tomato cystine-knot miniproteins (TCMPs) exhibit in vitro antiangiogenic activity on human umbilical vein cells. The aim of the present study was to investigate the effects of a fruit-specific cystine-knot miniprotein of tomato on in vitro endothelial cell migration and in vivo angiogenesis using a zebrafish model., Methods and Results: The cystine-knot protein purified from tomato fruits using gel filtration LC and RP-HPLC inhibited cell migration when tested at 200 nM using the wound healing assay, and reduced nitric oxide formation probed by 4-amino-5-methylamino-27-difluorofluoscescin diacetate. RT-PCR and Western blot analyses demonstrated that vascular endothelium growth factor A dependent signaling was the target of TCMP bioactivity. Angiogenesis was inhibited in vivo in zebrafish embryos treated with 500 nM TCMP., Conclusion: Our results demonstrate that cystine-knot miniproteins present in mature tomato fruits are endowed with antiangiogenic activity in vitro and in vivo. These molecules may confer beneficial effects to tomato dietary intake, along with lycopene and other antioxidants. Further investigation is warranted to explore the potential of these compounds as model scaffolds for the development of new drugs., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)