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Introduction: An increasing shortage of donor blood is expected, considering the demographic change in Germany. Due to the short shelf life and varying daily fluctuations in consumption, the storage of platelet concentrates (PCs) becomes challenging. This emphasizes the need for reliable prediction of needed PCs for the blood bank inventories. Therefore, the objective of this study was to evaluate multimodal data from multiple source systems within a hospital to predict the number of platelet transfusions in 3 days on a per-patient level. Methods: Data were collected from 25,190 (42% female and 58% male) patients between 2017 and 2021. For each patient, the number of received PCs, platelet count blood tests, drugs causing thrombocytopenia, acute platelet diseases, procedures, age, gender, and the period of a patient's hospital stay were collected. Two models were trained on samples using a sliding window of 7 days as input and a day 3 target. The model predicts whether a patient will be transfused 3 days in the future. The model was trained with an excessive hyperparameter search using patient-level repeated 5-fold cross-validation to optimize the average macro F2-score. Results: The trained models were tested on 5,022 unique patients. The best-performing model has a specificity of 0.99, a sensitivity of 0.37, an area under the precision-recall curve score of 0.45, an MCC score of 0.43, and an F1-score of 0.43. However, the model does not generalize well for cases when the need for a platelet transfusion is recognized. Conclusion: A patient AI-based platelet forecast could improve logistics management and reduce blood product waste. In this study, we build the first model to predict patient individual platelet demand. To the best of our knowledge, we are the first to introduce this approach. Our model predicts the need for platelet units for 3 days in the future. While sensitivity underperforms, specificity performs reliably. The model may be of clinical use as a pretest for potential patients needing a platelet transfusion within the next 3 days. As sensitivity needs to be improved, further studies should introduce deep learning and wider patient characterization to the methodological multimodal, multisource data approach. Furthermore, a hospital-wide consumption of PCs could be derived from individual predictions. [ABSTRACT FROM AUTHOR]

• Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy alters the microbiome and metabolome of lung sputum within the first year of therapy • Alpha-diversity of the microbiome increased, and the metabolome becomes highly varied across subjects while on therapy • No single bacterium was significantly different before and after ETI, but the ratio of pathogens to anaerobes significantly decreased • The largest changes were seen in the metabolome as decreases in the abundance of peptides and amino acids • These metabolite changes associated with a decrease in classic CF pathogens Elexacaftor-Tezacaftor-Ivacaftor (ETI) therapy is showing promising efficacy for treatment of cystic fibrosis (CF) and is becoming more widely available since recent FDA approval. However, little is known about how these drugs will affect lung infections, which are the leading cause of morbidity and mortality among people with CF (pwCF). We analyzed sputum microbiome and metabolome data from pwCF (n=24) before and after ETI therapy using 16S rRNA gene sequencing and untargeted metabolomics. The sputum microbiome diversity, particularly its evenness, was increased (p=0.036) and the microbiome profiles were different between individuals before and after therapy (PERMANOVA F=1.92, p=0.044). Despite these changes, the microbiomes remained more similar within an individual than across the sampled population. No specific microbial taxa differed in relative abundance before and after therapy, but the collective log-ratio of classic CF pathogens to anaerobes significantly decreased (p=0.013). The sputum metabolome also showed changes associated with ETI (PERMANOVA F=4.22, p=0.002) and was characterized by greater variation across subjects while on treatment. Changes in the metabolome were driven by a decrease in peptides, amino acids, and metabolites from the kynurenine pathway, which were associated with a decrease in CF pathogens. Metabolism of the three small molecules that make up ETI was extensive, including previously uncharacterized structural modifications. ETI therapy is associated with a changing microbiome and metabolome in airway mucus. This effect was stronger on sputum biochemistry, which may reflect changing niche space for microbial residency in lung mucus as the drug's effects take hold. This project was funded by a National Institute of Allergy and Infectious Disease Grant R01AI145925 [ABSTRACT FROM AUTHOR]

Background: An early dietary phosphate intervention (EPI) can provide vital medical benefits supporting self‐management of chronic kidney disease (CKD) in childhood. Objective: To utilise expert consensus to provide early modelling for an EPI to guide clinical practice across a paediatric renal network. Methods: Forty‐eight statements across six domains were constructed following a systematic review and semi‐structured interviews with children and young people (CYP), parents and healthcare professionals (HCP). A three‐round online Delphi survey with parents and paediatric renal multi‐disciplinary healthcare experts was undertaken. Results: Twenty‐one experts agreed on 56 statements over three Delphi rounds. Statements were accepted in all six domains: definition of an EPI (2), rationale (12), intended users (3), delivery (14) (when [1], where [3], who [2], how [8]), other considerations (16) and potential concerns (9). Conclusions: Consensus was reached on a definition and a set of guiding principles, providing some early modelling for implementation and future research on the development of an EPI strategy for CYP with CKD. Highlights: There is a readiness among patients, parents and healthcare professionals for an early dietary phosphate intervention strategy to support the self‐management of children and young people during chronic kidney disease (CKD) stages 1–3. Early dietary phosphate education and self‐management should be offered from the diagnosis period by a paediatric renal dietitian and throughout the CKD journey. Accessible early intervention cookery workshops provide education, upskilling and support to empower and develop agency in the management of CKD. [ABSTRACT FROM AUTHOR]

The use of corticosteroids in the treatment of steroid-sensitive nephrotic (SSNS) syndrome in children has evolved surprisingly slowly since the ISKDC consensus over 50 years ago. From a move towards longer courses of corticosteroid to treat the first episode in the 1990s and 2000s, more recent large, well-designed randomized controlled trials (RCTs) have unequivocally shown no benefit from an extended course, although doubt remains whether this applies across all age groups. With regard to prevention of relapses, daily ultra-low-dose prednisolone has recently been shown to be more effective than low-dose alternate-day prednisolone. Daily low-dose prednisolone for a week at the time of acute viral infection seems to be effective in the prevention of relapses but the results of a larger RCT are awaited. Recently, corticosteroid dosing to treat relapses has been questioned, with data suggesting lower doses may be as effective. The need for large RCTs to address the question of whether corticosteroid doses can be reduced was the conclusion of the authors of the recent corticosteroid therapy for nephrotic syndrome in children Cochrane update. This review summarizes development in thinking on corticosteroid use in SSNS and makes suggestions for areas that merit further scrutiny. [ABSTRACT FROM AUTHOR]

Pain is the major debilitating symptom of osteoarthritis (OA), which is difficult to treat. In OA patients joint tissue damage only poorly associates with pain, indicating other mechanisms contribute to OA pain. Immune cells regulate the sensory system, but little is known about the involvement of immune cells in OA pain. Here, we report that macrophages accumulate in the dorsal root ganglia (DRG) distant from the site of injury in two rodent models of OA. DRG macrophages acquired an M1-like phenotype, and depletion of DRG macrophages resolved OA pain in male and female mice. Sensory neurons innervating the damaged knee joint shape DRG macrophages into an M1-like phenotype. Persisting OA pain, accumulation of DRG macrophages, and programming of DRG macrophages into an M1-like phenotype were independent of Nav1.8 nociceptors. Inhibition of M1-like macrophages in the DRG by intrathecal injection of an IL4-IL10 fusion protein or M2-like macrophages resolved persistent OA pain. In conclusion, these findings reveal a crucial role for macrophages in maintaining OA pain independent of the joint damage and suggest a new direction to treat OA pain. [ABSTRACT FROM AUTHOR]

Molybdenum carbide (Mo2C), an interstitial transition metal carbide, has been used in a myriad of industrial applications due to its refractory nature, extreme hardness and strength, and high electrical and thermal conductivity. It also possesses catalytic activity for many chemical processes such as hydrodeoxygenation, reforming, water-gas shift, and the Fischer-Tropsch reaction. Among the current synthesis methods available to produce β-Mo2C, temperature-programmed reduction yields materials with the highest specific surface areas. The objective of the present work is to perform a detailed investigation of the carburization process and to determine the key intermediate phases that are formed during reduction. To achieve this objective, we performed the carburization process under pulse conditions wherein a small amount of CH4 in each pulse was reacted with a packed bed of MoO2. Our XRD and TEM results demonstrate that the solid-phase transformation from MoO2 to β-Mo2C follows a “plum-pudding” mechanism where Mo metal crystallites are constantly formed as the key intermediate phase throughout the matrix. [ABSTRACT FROM AUTHOR]

The article focuses on the EU Member States' national implementation legislation as the new legislation aims to ensure the EU offers an attractive and favorable environment for carrying out clinical research on a large scale, with high standards of public transparency and safety for clinical trial participants.

The present research investigated the degree of similarity in humour styles between spouses as assessed with the Humour Styles Questionnaire (HSQ). Furthermore, self-esteem was investigated as a potential moderator of partner humour style similarity. A sample of 116 heterosexual, married couples independently completed questionnaires assessing self-reported humour styles across the 32 item HSQ, as well as global self-esteem. Results indicated that there is significant positive association between the humour styles of married partners. This association was moderated by individual self-esteem. Specifically, participants with high self-esteem were found to have greater humour style similarity with their partners. Similarity was also greater for positive compared to negative types of humour. Implications for the use of dyadic data in investigating the roles of humour within couples are discussed. [ABSTRACT FROM AUTHOR]

Cancer chemotherapy resistance (MDR) is the innate and/or acquired ability of cancer cells to evade the effects of chemotherapeutics and is one of the most pressing major dilemmas in cancer therapy. Chemotherapy resistance can arise due to several host or tumor-related factors. However, most current research is focused on tumor-specific factors and specifically genes that handle expression of pumps that efflux accumulated drugs inside malignantly transformed types of cells. In this work, we suggest a wider and alternative perspective that sets the stage for a future platform in modifying drug resistance with respect to the treatment of cancer. [ABSTRACT FROM AUTHOR]

The generation of synthesis gas by catalytic partial oxidation (CPO) from renewable liquid fuels for solid oxide fuel cell applications has been the target of several studies. Typically, noble metals or nickel are employed as the active catalyst for fuel reforming, but they present drawbacks in terms of high cost and deactivation due to carbon deposition, respectively. Thermodynamically, the CPO of the model biodiesel compound, methyl oleate (C 19 H 36 O 2 ), was found to be favorable at temperatures > 800 °C. Under these conditions, we report a high catalytic activity of molybdenum dioxide (MoO 2 ) toward the reformation of methyl oleate into synthesis gas, while overcoming the disadvantages of coking and methane formation. For an O 2 /C molar ratio between 0.60 and 0.70 and a WHSV up to 10 h −1 , the CPO reaction shows a fuel carbon conversion above 80%, relatively good H 2 and CO yields, and the catalyst exhibits high redox stability. It is proposed that the lattice oxygen present in the oxide promotes the CPO reaction via the Mars–van Krevelen mechanism. [ABSTRACT FROM AUTHOR]

A correction to the article "Optimizing the corticosteroid dose in steroid-sensitive nephrotic syndrome" that was published online on February 24, 2022 is presented.

We report the first record of ocelot (Leopardus pardalis) for the Municipality of Calvillo, Aguascalientes, we obtaining a digital photograph by the method of camera traps. With this record the number of felids reported for the Sierra del Laurel rises from two to three. [ABSTRACT FROM AUTHOR]

Objective This investigation focused on a comparison of clinical and histological characteristics after sinus floor augmentation with biphasic calcium phosphate ( BCP, Straumann BoneCeramic®), anorganic bovine bone ( ABB, Geistlich Bio-Oss®), mineralized cancellous bone allograft ( MCBA, Zimmer Puros®), or autologous bone ( AB). Materials and methods Thirty consecutive patients with a posterior edentulous maxillary situation and a vertical bone height less than or equal to 4 mm were included in this study. A two-stage procedure was carried out. After augmentation of the maxillary sinus with ABB, BCP, MCBA, or AB followed by a healing period of 5 months, biopsies were taken with simultaneous implant placement. The samples were analyzed using microradiography and histology. Results Ninety-four implants were placed in the augmented positions and 53 bone biopsies were taken and evaluated. The bone volume fraction of newly formed bone was measured as 30.28 ± 2.16% for BCP, 24.9 ± 5.67% for ABB, 41.74 ± 2.1% for AB, and 35.41 ± 2.78% for MCBA with significant increases in bone volume of AB vs. BCP and ABB, and MCBA vs. ABB samples. Significantly different residual bone substitute material was measured as 15.8 ± 2.1% in the BCP group and 21.36 ± 4.83% in the ABB group. Conclusion As it provides the highest rate of de novo bone formation, AB can be considered to remain the gold standard in sinus floor augmentation. All tested control materials showed comparable results and are suitable for maxillary sinus augmentation. [ABSTRACT FROM AUTHOR]

This article discusses the discovery of four new records of spiders in the state of Guanajuato, Mexico, whose scientific names are Argiope argentata, Castianeira dorsata, C. plorans, and Selenops gracilis. The authors comment on the natural history of these spider species as well as their known numbers in the region.

Abstract: We and others have shown central roles of the Na+/H+ exchanger NHE1 in cell motility. The aim of this study was to determine the roles of NHE1 and of the Na+, cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (ΔNErbB2). ΔNErbB2 expression elicited NBCn1 upregulation, Ser703-phosphorylation of NHE1, and NHE1-inhibitor (EIPA)-sensitive pericellular acidification, in conjunction with increased expression of β1 integrin and ERM proteins. Active ERM proteins and NHE1 colocalized strongly to invadopodial rosettes, the diameter of which was increased by ΔNErbB2. Adhesion and migration on collagen-I were augmented by ΔNErbB2, unaffected by the NBC inhibitor S0859, and further stimulated by EIPA in a manner potentiated by PI3K-Akt-inhibition. These findings demonstrate that NHE1 inhibition can enhance cancer cell motility, adding an important facet to the understanding of NHE1 in cancer. [Copyright &y& Elsevier]

We previously demonstrated that the primary cilium coordinates platelet-derived growth factor (PDGF) receptor (PDGFR) α-mediated migration in growth-arrested fibroblasts. In this study, we investigate the functional relationship between ciliary PDGFR-α and the Na[sup +]/H[sup +] exchanger NHE1 in directional cell migration. NHE1 messenger RNA and protein levels are up-regulated in NIH3T3 cells and mouse embryonic fibroblasts (MEFs) during growth arrest, which is concomitant with cilium formation. NHE1 up-regulation is unaffected in Tg737[sup orpk] MEFs, which have no or very short primary cilia. In growth-arrested NIH3T3 cells, NHE1 is activated by the specific PDGFR-α ligand PDGF-AA. In wound-healing assays on growth-arrested NIH3T3 cells and wild-type MEFs, NHE1 inhibition by 5′-(N-ethyl-N-isopropyl)amiloride potently reduces PDGF-AA-mediated directional migration. These effects are strongly attenuated in interphase NIH3T3 cells, which are devoid of primary cilia, and in Tg737[sup orpk] MEFs. PDGF-AA failed to stimulate migration in NHE1-null fibroblasts. In conclusion, stimulation of directional migration in response to ciliary PDGFR-α signals is specifically dependent on NHE1 activity, indicating that NHE1 activation is a critical event in the physiological response to PDGFR-α stimulation. [ABSTRACT FROM AUTHOR]

The use of food and its nutrients as a remedy for diseases is historically and culturally well rooted in plenty of societies. An example of this is the use of Hibiscus sabdariffa to treat conditions like hypertension or high blood glucose. Furthermore, the natural biocompounds present in this plant have been demonstrated by several authors to be hypotensive, antioxidant, anticarcinogenic, antiobesogenic, etc. One of these compounds is Delphinidin-3-Sambubiosid (DS3), the most representative anthocyanin of Hibiscus sabdariffa, and as such, it has been proposed to have the beneficial effects previously mentioned. However, little is known about the molecular targets of DS3. Therefore, we conducted an in silico analysis using different bioinformatic tools to determine the possible molecular targets of this molecule and the potential impact the modification of its targets could have on the proteins and/or pathways of humans. We used the Swiss Target Prediction site to identify all the molecular targets of DS3, and then ShinnyGo 0.77, KEGG, and Stringdb were used to identify key pathways and hub genes related to them. Also, a literature search was conducted in PubMed, where each of the hub genes was linked to DS3 so we could gather information that complemented the results of the bioinformatic tools. The results show that DS3 can modify the behavior of genes related to nitrogen and glucose metabolism, inflammation, angiogenesis, and cell proliferation. Additionally, DS3 has direct effects on the PI3K-AKT pathway, which could be a key finding promoting further research, especially to determine the implications associated with changes in the aforementioned pathway. [ABSTRACT FROM AUTHOR]

The NATALEE study showed a significant benefit in invasive disease-free survival (iDFS) for patients with HR+/HER2− early breast cancer (eBC) at intermediate and high risk of recurrence who were treated with the CDK4/6 inhibitor Ribociclib in combination with endocrine therapy (ET). This retrospective study aims to apply the NATALEE inclusion criteria to a representative real-world cohort to estimate the proportion of HR+/HER2− breast cancer patients eligible for adjuvant Ribociclib therapy. Patients who underwent full surgical treatment for eBC between January 2018 and December 2020 at two large German university breast cancer centers (University of Ulm, University of Tuebingen) were included. Descriptive statistics were used to characterize the patient population eligible for Ribociclib treatment based on the NATALEE study's inclusion criteria. Out of 2384 enrolled patients, 1738 had HR+/HER2− eBC, of whom 43% (747/1738) met the NATALEE inclusion criteria. Of note, these patients were older, received less chemotherapy and presented with less advanced tumor stages compared to the NATALEE study cohort. Additionally, compared to the NATALEE study cohort, fewer patients had lymph node involvement (72.4% vs. 88.7%). Our analysis suggests that approximately 43% of all HR+/HER2− breast cancer patients will qualify for Ribociclib treatment. Given the numerous treatment options for patients with HR+/HER2− eBC, as well as the differences between the NATALEE cohort and patients in the real-world clinical setting, future analyses will be needed to determine which patients would benefit most from adjuvant CDK4/6 inhibitor treatment. [ABSTRACT FROM AUTHOR]

Background: Early dietary change can provide vital medical benefits supporting childhood chronic disease self-management.Objective: To explore factors influencing the initiation of early dietary change in the management of childhood chronic disease, as described by children, parents', and other stakeholders, to inform practice change in early paediatric service delivery.Methods: This systematic review crossed seven databases from 2000-2018 to identify empirical research (qualitative, quantitative, and mixed-method designs), including grey literature. Methodological quality was appraised using validated scoring systems.Results: Six studies met our criteria for inclusion in the review. Four themes of early dietary change emerged from these studies: (1) the role of education; (2) parents/caregivers' roles; (3) the role of self-management, and the (4) identification of enablers and barriers to dietary change.Conclusion: Obtaining the perspectives of children, parents' and other stakeholders' on factors influencing early dietary change is key to the self-management of childhood chronic disease.Practice Implications: Early dietary change provides an essential resource in the self-management of many chronic diseases. In collaboration, children, parents' and healthcare professionals recognise the value of regular, engaging education, supported by workshops to empower and upskill, enabling change in everyday dietary habits, while using enablers and recognising challenges. [ABSTRACT FROM AUTHOR]

Light-responsive microgels are interesting colloidal systems with potential applications in the biotechnology and medicine. However, synthesis of light-responsive microgels with high loading of photoswitchable molecules is still very challenging. Herein we developed a new method to synthesize light and temperature dual-responsive spiropyran-modified poly(N -vinylcaprolactam) microgels. The novel and straightforward microgels synthesis route involved: a) synthesis of poly(N -vinylcaprolactam- co -vinylformamide) copolymers via RAFT polymerization followed by the hydrolysis to obtain primary amine groups, b) attachment of carboxyl-modified spiropyran molecules to polymer chains via coupling, and c) crosslinking of spiropyran-modified polymer chains in W/O miniemulsion to form microgels. Via this method, we successfully synthesized poly(N -vinylcaprolactam) microgels containing more than 10 mol% spiropyran. The reversible light responsiveness of the spiropyran-modified copolymers and microgels in aqueous solution, which originates from the spiropyran photoisomerization under irradiation with different wavelengths, was demonstrated by UV–Vis spectroscopy. Spiropyran-modified copolymers demonstrate shift of the lower critical solution temperature (LCST) due to the polarity change of spiropyran molecules under dark, UV and visible light. Surprisingly, dynamic light scattering (DLS) results show that the microgels based on the same copolymers are less affected by UV irradiation. Microgels are swollen in darkness when spiropyran molecules are in the polar, merocyanine form, and collapse after irradiation with visible light, due to the transformation of spiropyran to the relatively nonpolar, closed spirocyclic form. In addition, the spiropyran-modified microgels exhibit reversible temperature responsiveness by presenting a volume phase transition in water from a swollen state to a collapsed state with increasing temperature and the transition temperature decreased compared to the pristine microgels due to the hydrophobicity of spiropyran units. [ABSTRACT FROM AUTHOR]

Simple Summary: Targeted therapies are increasingly used in patients with early breast cancer and a high clinical risk of relapse. Patients with clinical high-risk HER2-negative early breast cancer might be eligible for olaparib treatment. A prerequisite for olaparib treatment is a germline BRCA1/2 mutation. In the clinical routine, patients undergo BRCA1/2 mutation testing if they show family breast or ovarian cancer history. However, it is not known whether all patients that are potentially eligible for olaparib treatment are recommended to undergo BRCA1/2 mutation assessment based on family history. Thus, the aim of this study was to analyze which patients are eligible for olaparib treatment based on the OlympiA trial and to clarify which of these patients do not undergo BRCA1/2 mutation testing in the clinical routine. Background: Approximately 6% of women with breast cancer carry pathogenic germline variants in predisposition genes such as BRCA1 and BRCA2. Depending on personal and family cancer history, it is therefore recommended to test for hereditary breast cancer. Moreover, as shown by the phase III OlympiA trial, olaparib significantly improves overall survival in patients with HER2 negative (HER2−) early breast cancer who (1) carry a BRCA1 or BRCA2 germline mutation (gBRCA1/2-positive), (2) have received (neo)adjuvant chemotherapy and (3) are at high clinical risk. The objective of the current analysis was to determine the number of patients with early HER2− breast cancer who are at high clinical risk, according to the inclusion criteria of OlympiA, and to estimate how many of these patients would meet the criteria for hereditary cancer testing in a real-world analysis. Methods: All patients included in this retrospective analysis were treated for early breast cancer (eBC) at the Department of Gynecology and Obstetrics, Ulm University Hospital, Germany, and the Department of Women's Health at Tuebingen University Hospital, Germany, between January 2018 and December 2020. Patients were identified as high risk, in line with the clinicopathological determiners used in the OlympiA trial. The criteria of the German Consortium for Hereditary Breast and Ovarian Cancer were used to identify patients who qualify for hereditary cancer testing. Results: Of 2384 eligible patients, 1738 patients (72.9%) showed a hormone receptor positive (HR+)/HER2− tumor biology, 345 patients (14.5%) displayed HER2+ breast cancer and 301 patients (12.6%) suffered from HR-/HER2− breast cancer (TNBC). Of 2039 HER2− breast cancer patients, 271 patients (13.3%) were at high clinical risk. This cohort encompassed 130 of the 1738 patients with HR+/HER2− breast cancer (7.5%) and 141 of 301 patients with TNBC (46.8%). A total of 121 of 271 patients (44.6%) with high clinical risk met the criteria for hereditary cancer testing (34 of 130 (26.2%) HR+/HER2− patients and 87 of 141 (61.7%) patients with TNBC). Conclusion: Approximately one in ten patients with HR+/HER2−, and half of the patients with TNBC, meet the high-risk criteria according to OlympiA. Half of these patients do not meet the criteria for hereditary cancer testing and should therefore be tested for the presence of gBRCA1/2 mutations, irrespective of their own or family cancer history. The overall number of patients with early breast cancer benefiting from olaparib needs to be investigated in future studies. [ABSTRACT FROM AUTHOR]

Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85–90% of patients attain complete remission of proteinuria within 4–6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70–80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given. [ABSTRACT FROM AUTHOR]

Background: Vesico‐ureteral reflux (VUR) is considered to be a risk factor for recurrent febrile urinary tract infections and impaired renal transplant survival. Methods: An online survey supported by the European Society for Paediatric Nephrology was designed to evaluate current management strategies of VUR in native and transplanted kidneys of recipients aged <18 years. Results: Seventy‐three pediatric transplant centers from 32 countries contributed to the survey. All centers performed urological evaluation prior to pediatric kidney transplantation (KTx) with subsequent interdisciplinary discussion. Screening for VUR in native kidneys (30% in all, 70% in selected patients) led to surgical intervention in 78% (11% in all, 89% in selected patients) with a decided preference of endoscopic intervention over ureterocystoneostomy. Following KTx, continuous antibiotic prophylaxis was applied in 65% of the patients and screening for allograft VUR performed in 93% of selected patients. The main management strategies of symptomatic allograft VUR were continuous antibiotic prophylaxis (83%) and surgical treatment (74%) (endoscopic intervention 55%, redo ureterocystoneostomy 26%). Conclusions: This survey demonstrates the high variability in the management of VUR in pediatric KTx recipients, points to knowledge gaps, and might serve as a starting point for improving the care for patients with VUR in native and transplanted kidneys. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence of good short-term and medium-term outcomes of ABO incompatible (ABOi) and HLA incompatible (HLAi) kidney transplantation with pre-transplant positive crossmatches in paediatric practice. However, there remain concerns regarding the higher risks of infective complications and antibody-mediated rejections. The aim of our study is to show longer-term follow-up on all ABOi and HLAi paediatric kidney transplant recipients (pKTR) in the UK. Methods: Questionnaires specifying kidney transplant type, desensitisation requirement and kidney allograft function were sent to 13 paediatric nephrology centres that performed kidney transplantation in children and young people under 18 years of age who received an ABOi and/or HLAi transplant between 1 January 2006 and 31 December 2016. Patient and kidney allograft survival were compared between ABOi, HLAi and ABO/HLA compatible (ABOc/HLAc) groups. Results: Among 711 living donor kidney transplants performed in the UK, 23 were ABOi and 6 were HLAi. Patient survival was 87%, 100% and 96% in ABOi, HLAi and ABOc/HLAc groups, respectively, at median follow-up of 6.8 (3.6–14.0) years post-transplant. Death-censored kidney allograft survival was 100% in all 3 groups at last follow-up. There were no cases of primary non-function in ABOi or HLAi groups, but 2% in the ABOc/HLAc group. There was one reported case of Epstein-Barr viral-induced post-transplant lymphoproliferative disorder. Conclusion: Longer term follow-up has shown that ABOi and HLAi kidney transplantation are feasible for pKTR where no compatible donors are available, and that minimising desensitisation should be achieved where possible. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Background: Chronic disease of childhood may be delayed by early dietary intervention. The purpose of this systematic review is to provide decision-makers with a perspective on the role of early dietary intervention, as a form of self-management, to delay disease progression in children with early chronic disease, as described by children, parents and other stakeholders. Methods: The study will systematically review empirical research (qualitative, quantitative and mixed method designs), including grey literature, using a narrative synthesis. A four-stage search process will be conducted involving a scoping search, the Scottish Intercollegiate Guidelines Network (SIGN) Patient Issues search filter on MEDLINE, the search of seven databases using a chronic disease and chronic kidney disease (CKD) search strategy, and hand searching the reference lists of identified papers for additional studies. All studies retrieved during the search process will undergo a screening and selection process against the inclusion/exclusion criteria. Methodological quality of relevant studies will be assessed using a validated Mixed Studies Review scoring system, before inclusion in the review. Relevant grey literature will be assessed for methodological quality and relative importance using McGrath et al.'s framework and the Academy Health advisory committee categories, respectively. Data extraction will be guided by the Centre for Review and Dissemination guidance and Popay et al.'s work. The narrative synthesis of the findings will use elements of Popay et al.'s methodology of narrative synthesis, applying recognised tools for each of the four elements: (1) developing a theory of how the intervention works, why and for whom; (2) developing a preliminary synthesis of findings of included studies; (3) exploring relationships in the data; and (4) assessing the robustness of the synthesis. Discussion: This mixed studies systematic review with a narrative synthesis seeks to elucidate the gaps in current knowledge and generate a fresh explanation of research findings on early dietary self-management in chronic disease, with particular application to CKD, from the stakeholders' perspective. The review will provide an important platform to inform future research, identifying the facilitators and barriers to implementing early dietary interventions. Ultimately, the review will contribute vital information to inform future improvements in chronic disease. The lead author has a particular interest in CKD paediatric service delivery. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the second most common cause of death of any cancer-related cases in the world, and is also in the top 5 most common malignancy cancers in general. There are plenty of well-distributed treatments, offering better hygiene, more robust and complete nutrition, and the eradication of pathogens such as Helicobacter pylori. Currently, there is still the need for more treatments, especially those of lower cost, like those coming from already easily available products. Quercetin (QRC) is a natural phenolic compound present in a wide variety of products, e.g., in plants like Hibiscus sabdariffa, onions, grapes, broccoli, and citrus fruits. This product has been shown to have great potential therapeutic effects, and it has also been suggested that it could be useful in combating different types of cancer; however, information regarding the targets or mechanisms that QRC has on cancer cells is still unclear. Therefore, this study aims to identify the targets that QRC has, like anti-cancer treatment for GC using different bio-informatic tools and databases. From MalaCards and SwissTargetPrediction, both QRC and GC molecular targets were defined, and then they were matched with the Venny 2.1.0 platform. From this, 31 genes were gathered, and then they were analyzed using the ShinnyGo0.77 and DAVID-Bioinformatic Resources. Furthermore, StringDB was used to identify the protein—protein interactions, and Citoscape 3.6.0 12 hub genes were obtained. Those hub genes were then subject to Gene Expression Profiling Interactive Analysis and TISIDB. Finally, molecular docking studies were performed using the SwissDock database. The results suggest that, according to the gene ontology data, QRC has a relationship with the regulation of cell death, response to stress, cell motility, response to amyloid-beta, cellular response to reactive oxygen species, and apoptotic processes. Some genes like EGFR were correlated with an abundance of CD8 and Neutrophil infiltration but didn't show to improve the survival rate. Furthermore, molecular docking results show that QRC can bind to multiple molecules of interest. These results complement some of the currently available information alluding to the effectiveness of plants rich with QRC as part of the treatment used for different kinds of cancer, but it also suggests a plethora of new targets that this molecule has in GC, while at the same time giving a clearer idea of the mechanisms that are affected in GC by QRC. However, as with any other study that primarily uses bioinformatic tools, these final results are to be used for more direct and precise research, especially if experimental protocols are used. [ABSTRACT FROM AUTHOR]

Purpose: Chronic kidney disease (CKD) can place restrictions upon biopsychosocial development in children; consequently, assessment of self-reported quality of life (QoL) is important in patient evaluations. This research aimed to evaluate a generic and renal-specific self-report QoL scale, assess children's attitudes towards living with CKD and propose an appropriate tool for future individual clinical use or departmental audit.Methods: Seventy-one children (41 male, 30 female; mean age = 13.60 years, range = 6.00-18.96) with CKD completed the Generic Children's QoL Measure (GCQ), PedsQL 3.0 End Stage Renal Disease Module (PedsQL) and Child Attitude Toward Illness Scale (CATIS). Descriptive and cross-sectional analyses were performed, along with an examination of associations between scores on each measure.Results: The mean GCQ score for patients was comparable with normative data (p = 0.27). Generic QoL, disease-specific QoL and attitudes towards CKD did not vary by CKD stage, age, time since diagnosis or duration of current treatment. Gender was not associated with QoL, although males had more negative CATIS scores than females (p < 0.05). Pre-emptive transplant patients had more positive GCQ and PedsQL scores (p < 0.05 for each), but there was no relationship between treatment and CATIS scores. Scores on all scales were moderately correlated (r = 0.35-0.59), suggesting that clinicians may choose the most appropriate measure for assessment of psychological/psychosocial functioning based on clinical judgement.Conclusions: This study further confirmed that using child self-reported QoL measures is possible and may help psychosocial teams to individualise work. The GCQ is simple and convenient, and could be used as an annual screening tool to facilitate discussion of QoL with children and young people. Further work is necessary before such things as cut-off scores can be recommended. [ABSTRACT FROM AUTHOR]

Coral holobionts are multi-species assemblages, which adds significant complexity to genotype-phenotype connections underlying ecologically important traits like coral bleaching. Small scale heterogeneity in bleaching is ubiquitous in the absence of strong environmental gradients, which provides adaptive variance needed for the long-term persistence of coral reefs. We used RAD-seq, qPCR and LC-MS/MS metabolomics to characterize host genomic variation, symbiont community and biochemical correlates in two bleaching phenotypes of the vertically transmitting coral Montipora capitata. Phenotype was driven by symbiosis state and host genetic variance. We documented 5 gene ontologies that were significantly associated with both the binary bleaching phenotype and symbiont composition, representing functions that confer a phenotype via host-symbiont interactions. We bred these corals and show that symbiont communities were broadly conserved in bulk-crosses, resulting in significantly higher survivorship under temperature stress in juveniles, but not larvae, from tolerant parents. Using a select and re-sequence approach, we document numerous gene ontologies selected by heat stress, some of which (cell signaling, antioxidant activity, pH regulation) have unique selection dynamics in larvae from thermally tolerant parents. These data show that vertically transmitting corals may have an adaptive advantage under climate change if host and symbiont variance interact to influence bleaching phenotype. Selective breeding of corals with different bleaching phenotypes demonstrates the potential for climate adaptation in vertically transmitting species. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVE: In this retrospective study, we aimed to investigate a new 3D evaluation method for evaluating bone regeneration after cystectomy of odontogenic cysts. METHODS: The study included 26 patients who underwent cystectomies between 2012 and 2017 and had received either fillings or non-fillings with autologous iliac crest. Bony regeneration was analyzed using 3D imaging software and comparing identical regions of interest (ROIs) that were determined by exact overlays of the postoperative cone beam computer tomography (CBCT) or computer tomography (CT) images. Outcome measures, including volume changes according to the defect size and configuration, patient age, the entity and distribution of the cysts, were collected. RESULTS: Twenty-six patients (5 women and 21 men) had 30 defects, including nine keratocysts, seven radicular cysts and 14 dentigerous cysts. A total of 73% of the defects were in the mandible. The mean 3D follow-up time was 12 months. According to the 3D evaluation of bony regeneration, the defect size and configuration showed no significant differences between the groups (filled or non-filled with 15 defects per group). CONCLUSIONS: By establishing a standardized 3D method for evaluating bone regeneration, healing can be better monitored and evaluated. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present study was the qualitative and quantitative evaluation of osseous graft consolidation using allogeneic bone blocks for vertical bone augmentation in an animal model. Material and methods: Standardised allogeneic and autologous bone blocks were fixed on the frontal skull of 20 adult female pigs and covered with a resorbable collagen membrane. Animals were sacrificed after 2 and 6 months. Specimens were histologically and histomorphometrically analysed focusing on the amount of vital bone, residual bone substitute material and connective tissue. Furthermore, the amount of expression of bone matrix proteins (collagen type I and osteocalcin) and de novo vessel formation (von Willebrand factor) were quantified by immunohistochemistry. Results: Significantly more allogeneic bone blocks failed for both evaluation time points (p < 0.05). Allogeneic blocks showed significantly less vital bone with more connective tissue formation compared to autologous bone blocks. Increased vessel formation could be detected for both evaluation time points in the contact area of autologous bone with local bone. The expression of collagen type I and osteocalcin was significantly lower in the allogeneic bone graft. Conclusions: Allogeneic cancellous bone blocks showed a significantly higher failure rate compared to autologous bone blocks. Allogeneic bone blocks seemed to negatively affect bone formation or negatively influence the host in the long term, and increased connective tissue formation and block loss should be anticipated. Clinical relevance: In order to maintain patient safety and treatment success clinicians should be persuaded to make a conscious choice of the applied biomaterials with regard to their components and structure. [ABSTRACT FROM AUTHOR]

Background: The objective of the IMPROVE study was patients' preference for either endocrine-based therapy or combined chemo- and anti-angiogenic therapy in advanced HR-positive/HER2-negative breast cancer.Methods: In this randomized, cross-over phase IV study, 77 patients were recruited in 26 sites in Germany. Patients were randomized 1:1 to receive either capecitabine plus bevacizumab (Cap+Bev) as first-line therapy followed by cross-over to everolimus plus exemestane (Eve+Exe) as second-line therapy (Arm A) or the reverse sequence (Arm B). The primary endpoint was patients' preference for either regimen, assessed by the Patient Preference Questionnaire 12 weeks after cross-over. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and quality of life (QoL).Results: 61.5% of patients preferred Cap+Bev (p = 0.1653), whereas 15.4% preferred Eve+Exe and 23.1% were indecisive. Physicians showed a similar tendency towards Cap+Bev (58.1%) as the preferred regimen versus Eve+Exe (32.3%). Median first-line PFS was longer for Cap+Bev than for Eve+Exe (11.1 months versus 3.5 months). Median second-line PFS was similar between Cap+Bev and Eve+Exe (3.6 months versus 3.7 months). Median OS was comparable between Arm A (28.8 months) and Arm B (24.7 months). 73.0% and 52.6% (first-/second-line, Cap+Bev) and 54.1% and 52.9% (first-/second-line, Eve+Exe) of patients experienced grade 3/4 TEAEs. No treatment-related deaths occurred. QoL and treatment satisfaction were not significantly different between arms or treatment lines.Conclusions: Patients tended to favor Cap+Bev over Eve+Exe, which was in line with physicians' preference. Cap+Bev showed superior first-line PFS, while QoL was similar in both arms. No new safety signals were reported.Trial Registration: EudraCT No: 2013-005329-22. Registered on 19 August 20. [ABSTRACT FROM AUTHOR]

Background: Late acute cellular rejection (LACR) is associated with poorer graft outcomes and non-adherence. Non-adherence to tacrolimus can be indirectly assessed by the intra-patient variability (IPV) of tacrolimus trough levels. The threshold of IPV associated with rejection is not known. Methods: We conducted a case-control study comparing 25 patients with biopsy-proven LACR against 25 stable controls matched for age group, primary diagnosis and time post-transplant. IPV was calculated using coefficient of variance (CV) and mean absolute deviation (MAD) using tacrolimus levels in the preceding 12 months. We also assessed the percentage time for tacrolimus levels < 4 μg/L (Tac < 4) and the concentration/weight-adjusted dose (C/D) ratio as a proxy marker of tacrolimus metaboliser status. Results: LACR patients had higher CV (median, IQR 44%, 36–61% v. 24%, 19–35%, p < 0.0001) and higher MAD (33%, 25–48% v. 19%, 15–26%, p < 0.0001). The MAD was less affected by outlying tacrolimus results. Receiver operating curve analysis of the MAD resulted in a sensitivity of 76% and specificity of 76% at a threshold of 26% (AUC 0.85, p < 0.05). LACR patients had more Tac < 4 (50% v. 26%, p < 0.05). There was no difference in C/D suggesting that good IPV can be maintained in fast metabolisers. Patients with LACR had significantly increased creatinine at 12-month follow-up despite treatment (108 v. 5 umol/L increase from baseline) and four patients lost their allograft. Conclusions: Monitoring of tacrolimus IPV using the MAD may be a clinical marker for LACR. A threshold IPV of 26% can potentially be used as a therapeutic target pending further validation studies. [ABSTRACT FROM AUTHOR]

Objectives: The non-interventional study (NIS) NADIR (DRKS00005711) evaluated the effectiveness and safety of prophylaxis with lipegfilgrastim, a glycopegylated granulocyte-colony stimulating factor, in 2500 patients undergoing chemotherapy in routine clinical practice. Primary objective was the incidence of chemotherapy-induced severe neutropenia, febrile neutropenia (FN), and neutropenia-associated complications. Methods: NADIR was a prospective NIS conducted in 201 study centers in Germany. Results: The analysis included 2489 patients. Main tumor types were breast cancer (n = 1198, 48.1%), lung cancer (n = 303, 12.2%), non-Hodgkin lymphoma (NHL; n = 337, 13.5%), and prostate cancer (n = 111, 4.5%). Nine hundred and ten (36.6%) patients were aged ≥65 years (regarded as "elderly" patients). Severe neutropenia (CTCAE grade 3/4) was reported in 26.8% (n = 666) and 25.2% (n = 229) of the total population and elderly patients, respectively. FN was documented in 2.7% (n = 68) of the total population vs 3.0% (n = 27) of elderly patients. Primary prophylaxis with lipegfilgrastim among patients with high risk of FN (>20%) was documented in 83.5% of the total population and 75.1% of elderly patients. Infections (CTCAE grade 3/4) were documented in 99 patients (4.0%) in the total population vs 47 (5.1%) elderly patients. Fatal infections were reported in 14 (0.6%) patients in the total population vs 11 (1.2%) elderly patients. Overall, most frequent lipegfilgrastim-related adverse events (AEs) included bone pain (8.0%), anemia (3.2%), leucocytosis (2.7%), and thrombocytopenia (2.5%). Of the patients, 18.0% had ≥1 documented serious AE; none of the fatal events (2.7%) was lipegfilgrastim-related. Conclusions: Lipegfilgrastim administered to patients with solid tumor/NHL undergoing chemotherapy in routine clinical practice showed similar effectiveness and safety compared to the pivotal trials. [ABSTRACT FROM AUTHOR]

Objective: Rituximab is an effective treatment for children with steroid dependent or frequently relapsing nephrotic syndrome. The optimum dosing schedule for rituximab has not been established. We hypothesized that a single low dose of 375 mg/m2 would have comparable outcomes to higher doses in reducing the frequency of relapse and time to B cell reconstitution.Methods: We conducted a multicenter retrospective observational cohort study of children with steroid-sensitive frequently relapsing nephrotic syndrome. Data were extracted from clinical records including the dates of diagnosis, treatment, relapses, the use of concomitant immunosuppression, and lymphocyte subset profiling. Patients treated earlier received variable doses of rituximab, although typically two doses of 750 mg/m2. Later, patients received the current regimen of a single dose of 375 mg/m2. The primary outcome was an absence of clinically confirmed relapse 12 months following rituximab administration. Secondary outcomes were median time to relapse, probability of being relapse-free at 6 and 24 months and time to reconstitution of CD19+ B cells.Results: Sixty patients received 143 courses of rituximab. Seven different dosing regimen strategies were used, ranging between 375 and 750 mg/m2 per dose, with administration of 1-4 doses. There was no significant difference in event-free survival at 12 months between dosing strategies. The median time to reconstitution of B cells was not significantly different between groups.Conclusions: Use of a single low-dose regimen of rituximab in the management of frequently relapsing nephrotic syndrome does not affect the probability of relapse at 12 months or time to B cell reconstitution compared to a conventional higher dose. [ABSTRACT FROM AUTHOR]

The article discusses answers to a quiz that appeared within the issue of "Pediatric Nephrology," which focused on renal failure from birth. It is noted that through ultrasonography, having large bright kidneys are suggestive of acute kidney injury (AKI). Information about the Denys-Drash syndrome (DDS) is presented, which is caused by heterozygous mutations on WT1 on chromosome 11p13.

Background Relapses of childhood steroid-sensitive nephrotic syndrome (SSNS) are treated with a 4- to 8- week course of high-dose oral prednisolone, which may be associated with significant adverse effects. There is a clear association between upper respiratory tract infection (URTI) and relapse development. Previous studies in developing nations have suggested that introducing a 5- to 7-day course of daily prednisolone during an URTI may prevent a relapse developing and the need for a treatment course of high-dose prednisolone. The aim of PREDNOS 2 is to evaluate the effectiveness of a 6-day course of daily prednisolone therapy during an URTI in reducing the development of a subsequent relapse in a developed nation. Methods/design The subjects will be 300 children with relapsing SSNS (⩾2 relapses in preceding year), who will be randomised to receive either a 6-day course of daily prednisolone or no change to their current therapy (with the use of placebo to double blind) each time they develop an URTIover 12 months. A strict definition for URTI will be used. Subjects will be reviewed at 3, 6, 9 and 12 months to capture data regarding relapse history, ongoing therapy and adverse effect profile, including behavioural problems and quality of life. A formal health economic analysis will also be performed. The primary end point of the study will be the incidence of URTI-related relapse (3 days of Albustix +++) following the first infection during the 12- month follow-up period. DNA and RNA samples will be collected to identify a potential genetic cause for the disease. Subjects will be recruited from over 100 UK centres with the assistance of the Medicines for Children Research Network. PREDNOS 2 is funded by the National Institute for Health Research Health Technology Assessment Programme (11/129/261) Discussion We propose that PREDNOS 2 will be a pivotal study that will inform the future standard of care for children with SSNS. If it is possible to reduce the disease relapse rate effectively and safely, this will reduce the morbidity and cost associated with drug treatment, notwithstanding hospital admission and parental absence from employment. Trial registration Current Controlled Trials (ISRCTN10900733). [ABSTRACT FROM AUTHOR]

We and others have shown central roles of the Na(+)/H(+) exchanger NHE1 in cell motility. The aim of this study was to determine the roles of NHE1 and of the Na(+), HCO(3)(-) cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (ΔNErbB2). ΔNErbB2 expression elicited NBCn1 upregulation, Ser(703)-phosphorylation of NHE1, and NHE1-inhibitor (EIPA)-sensitive pericellular acidification, in conjunction with increased expression of β1 integrin and ERM proteins. Active ERM proteins and NHE1 colocalized strongly to invadopodial rosettes, the diameter of which was increased by ΔNErbB2. Adhesion and migration on collagen-I were augmented by ΔNErbB2, unaffected by the NBC inhibitor S0859, and further stimulated by EIPA in a manner potentiated by PI3K-Akt-inhibition. These findings demonstrate that NHE1 inhibition can enhance cancer cell motility, adding an important facet to the understanding of NHE1 in cancer. [ABSTRACT FROM AUTHOR]

Bone marrow plasma cell infiltration is a crucial parameter of disease activity in monoclonal plasma cell disorders. Until now, the only way to quantify such infiltration was bone marrow biopsy or aspiration. Diffusion-weighted imaging (DWI) is a magnetic resonance imaging-technique that may mirror tissue cellularity by measuring random movements of water molecules. To investigate if DWI is capable of assessing bone marrow cellularity in monoclonal plasma cell disease, we investigated 56 patients with multiple myeloma or monoclonal gammopathy of undetermined significance, and 30 healthy controls using DWI of the pelvis and/or the lumbar spine. In 25 of 30 patients who underwent biopsy, bone marrow trephine and DWI could be compared. Of the patients with symptomatic disease 15 could be evaluated after systemic treatment. There was a positive correlation between the DWI-parameter apparent diffusion coefficient (ADC) and bone marrow cellularity as well as micro-vessel density ( P < 0·001 respectively). ADC was significantly different between patients and controls ( P < 0·01) and before and after systemic therapy ( P < 0·001). In conclusion, DWI enabled bone marrow infiltration to be monitored in a non-invasive, quantitative way, suggesting that after further investigations on larger patient groups this might become an useful tool in the clinical work-up to assess tumour burden. [ABSTRACT FROM AUTHOR]

A home wireless monitoring system for sleep monitoring incorporated 14 sensors with a cell phone data transfer. Fidelity was the same as measurements in a laboratory. Ten subjects in this small study were successfully monitored. [ABSTRACT FROM AUTHOR]

Libraries, as we know them today, can be defined by the term Library 1.0. This defines the way resources are kept on shelves or at a computer behind a login. These resources can be taken from a shelf, checked out by the library staff, taken home for a certain length of time and absorbed, and then returned to the library for someone else to avail of. Library 1.0 is a one-directional service that takes people to the information they require. Library 2.0 - or L2 as it is now more commonly addressed as - aims to take the information to the people by bringing the library service to the Internet and getting the users more involved by encouraging feedback participation. This paper presents an overview of Library 2.0 and introduces web 2.0 concepts. [ABSTRACT FROM AUTHOR]

In the article by Möst et al., entitled "Osseous ingrowth in allogeneic bone blocks applied for vertical bone augmentation: a preclinical randomized controlled study. [ABSTRACT FROM AUTHOR]

A case is presented of a neonate born at 32 weeks of gestation with intra-uterine growth retardation. The renal scan performed at 31 weeks showed oligohydramnios but normal kidneys. The neonate was oliguric from birth and required early peritoneal dialysis. Her urine showed heavy proteinuria, and the plasma albumin was very low. Post-natal ultrasonography showed large bright kidneys with reduced corticomedullary differentiation but no dysplastia; arterial and venous flow was normal on Doppler ultrasound. The quiz discusses the differential diagnosis with particular reference to whether this picture represents acute kidney injury with expected improvement or chronic kidney disease. Further questions discuss mechanisms of renal failure in this situation. Finally, with reference to previous case reports and series, a correlation between a specific mutation and this severe phenotype is proposed. [ABSTRACT FROM AUTHOR]

Background: Relapses of childhood steroid-sensitive nephrotic syndrome (SSNS) are treated with a 4- to 8-week course of high-dose oral prednisolone, which may be associated with significant adverse effects. There is a clear association between upper respiratory tract infection (URTI) and relapse development. Previous studies in developing nations have suggested that introducing a 5- to 7-day course of daily prednisolone during an URTI may prevent a relapse developing and the need for a treatment course of high-dose prednisolone. The aim of PREDNOS 2 is to evaluate the effectiveness of a 6-day course of daily prednisolone therapy during an URTI in reducing the development of a subsequent relapse in a developed nation.Methods/design: The subjects will be 300 children with relapsing SSNS (≥2 relapses in preceding year), who will be randomised to receive either a 6-day course of daily prednisolone or no change to their current therapy (with the use of placebo to double blind) each time they develop an URTI over 12 months. A strict definition for URTI will be used. Subjects will be reviewed at 3, 6, 9 and 12 months to capture data regarding relapse history, ongoing therapy and adverse effect profile, including behavioural problems and quality of life. A formal health economic analysis will also be performed. The primary end point of the study will be the incidence of URTI-related relapse (3 days of Albustix +++) following the first infection during the 12-month follow-up period. DNA and RNA samples will be collected to identify a potential genetic cause for the disease. Subjects will be recruited from over 100 UK centres with the assistance of the Medicines for Children Research Network.PREDNOS 2 is funded by the National Institute for Health Research Health Technology Assessment Programme (11/129/261).Discussion: We propose that PREDNOS 2 will be a pivotal study that will inform the future standard of care for children with SSNS. If it is possible to reduce the disease relapse rate effectively and safely, this will reduce the morbidity and cost associated with drug treatment, notwithstanding hospital admission and parental absence from employment.Trial Registration: Current Controlled Trials (ISRCTN10900733). [ABSTRACT FROM AUTHOR]