Etoposide combined with cytarabine and pegfilgrastim for poorly mobilizing patients with multiple myeloma and lymphoma: A prospective multicentre study.

A chemotherapy-based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single-arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18-75 years. The EAP regimen consisted of etoposide 75 mg/m2/day on days 1-2, cytarabine 300 mg/m2 every 12 h on days 1-2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 106 CD34+ cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34+ cells was 9.2 (range 2.1-92.7) × 106/kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2-3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma.

Efficient estimation of propagator anisotropy and non-Gaussianity in multishell diffusion MRI with micro-structure adaptive convolution kernels and dual Fourier integral transforms.

PURPOSE: We seek to reformulate the so-called Propagator Anisotropy (PA) and Non-Gaussianity (NG), originally conceived for the Mean Apparent Propagator diffusion MRI (MAP-MRI), to the Micro-Structure adaptive convolution kernels and dual Fourier Integral Transforms (MiSFIT). These measures describe relevant normalized features of the Ensemble Average Propagator (EAP). THEORY AND METHODS: First, the indices, which are defined as the EAP's dissimilarity from an isotropic (PA) or a Gaussian (NG) one, are analytically reformulated within the MiSFIT framework. Then a comparison between the resulting maps is drawn by means of a visual analysis, a quantitative assessment via numerical simulations, a test-retest study across the MICRA dataset (6 subjects scanned five times) and, finally, a computational time evaluation. RESULTS: Findings illustrate the visual similarity between the indices computed with either technique. Evaluation against synthetic ground truth data, however, demonstrates MiSFIT's improved accuracy. In addition, the test-retest study reveals MiSFIT's higher degree of reliability in most of white matter regions. Finally, the computational time evaluation shows MiSFIT's time reduction up to two orders of magnitude. CONCLUSIONS: Despite being a direct development on the MAP-MRI representation, the PA and the NG can be reliably and efficiently computed within MiSFIT's framework. This, together with the previous findings in the original MiSFIT's article, could mean the difference that definitely qualifies diffusion MRI to be incorporated into regular clinical settings.

Comparing oral case presentation formats on internal medicine inpatient rounds: a survey study.

BACKGROUND: Oral case presentations - structured verbal reports of clinical cases - are fundamental to patient care and learner education. Despite their continued importance in a modernized medical landscape, their structure has remained largely unchanged since the 1960s, based on the traditional Subjective, Objective, Assessment, Plan (SOAP) format developed for medical records. We developed a problem-based alternative known as Events, Assessment, Plan (EAP) to understand the perceived efficacy of EAP compared to SOAP among learners. METHODS: We surveyed (Qualtrics, via email) all third- and fourth-year medical students and internal medicine residents at a large, academic, tertiary care hospital and associated Veterans Affairs medical center. The primary outcome was trainee preference in oral case presentation format. The secondary outcome was comparing EAP and SOAP on 10 functionality domains assessed via a 5-point Likert scale. We used descriptive statistics (proportion and mean) to describe the results. RESULTS: The response rate was 21% (118/563). Of the 59 respondents with exposure to both the EAP and SOAP formats, 69% (n = 41) preferred the EAP format as compared to 19% (n = 11) who preferred SOAP (p < 0.001). EAP outperformed SOAP in 8 out of 10 of the domains assessed, including advancing patient care, learning from patients, and time efficiency. CONCLUSIONS: Our findings suggest that trainees prefer the EAP format over SOAP and that EAP may facilitate clearer and more efficient communication on rounds, which in turn may enhance patient care and learner education. A broader, multi-center study of the EAP oral case presentation will help to better understand preferences, outcomes, and barriers to implementation.

Reliability and Validity of the East Asia-Pacific Early Child Development Scales: A Longitudinal Validation Study in China.

This study examined the test-retest reliability and predictive validity of the East Asia-Pacific Early Child Development Scales (EAP-ECDS) Short Form. In China, preschools typically provide children with educational activities in age-segregated classrooms - Kindergarten Level 1 (K1) (3 to 4 years), Kindergarten Level 2 (K2) (4 to 5 years), and Kindergarten Level 3 (K3) (5 to 6 years). A total of 709 children in K2 (Mage = 57.85 months, SD = 4.77) were randomly selected from 29 kindergartens in Shanghai municipality and Guizhou province of China. Children were assessed using the EAP-ECDS in K2 and K3. School readiness was assessed in K3, and literacy and mathematics achievement were assessed in Grade 2. Pearson's correlation coefficient and intraclass correlation coefficient (ICC = 0.73) indicated that the tool had good test-retest reliability across K2 and K3. Regarding predictive validity, K2 EAP-ECDS predicted K3 school readiness (ß = 0.26), Grade 2 language and literacy (ß = 0.18) and mathematics (ß = 0.22) after adjusting for age, gender, socioeconomic status, and region. Findings support using the tool to measure the holistic development of preschool-aged children in China and the region.

Comparison of acute myeloid leukemia and myelodysplastic syndromes with TP53 aberrations.

TP53 aberrations are found in approximately 10% of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and are considered early driver events affecting leukemia stem cells. In this study, we compared features of a total of 84 patients with these disorders seen at a tertiary cancer center. Clinical and cytogenetic characteristics as well as immunophenotypes of immature blast cells were similar between AML and MDS patients. Median overall survival (OS) was 226 days (95% confidence interval [CI], 131-300) for the entire cohort with an estimated 3-year OS rate of 11% (95% CI, 6-22). OS showed a significant difference between MDS (median, 345 days; 95% CI, 235-590) and AML patients (median, 91 days; 95% CI, 64-226) which is likely due to a different co-mutational pattern as revealed by next-generation sequencing. Transformation of TP53 aberrant MDS occurred in 60.5% of cases and substantially reduced their survival probability. Cox regression analysis revealed treatment class and TP53 variant allele frequency as prognostically relevant parameters but not the TP53-specific prognostic scores EAp53 and RFS. These data emphasize similarities between TP53 aberrant AML and MDS and support previous notions that they should be classified and treated as a distinct disorder.

Mechanisms underlying pre- and postnatal development of the vomeronasal organ.

The vomeronasal organ (VNO) is sensory organ located in the ventral region of the nasal cavity in rodents. The VNO develops from the olfactory placode during the secondary invagination of olfactory pit. The embryonic vomeronasal structure appears as a neurogenic area where migratory neuronal populations like endocrine gonadotropin-releasing hormone-1 (GnRH-1) neurons form. Even though embryonic vomeronasal structures are conserved across most vertebrate species, many species including humans do not have a functional VNO after birth. The vomeronasal epithelium (VNE) of rodents is composed of two major types of vomeronasal sensory neurons (VSNs): (1) VSNs distributed in the apical VNE regions that express vomeronasal type-1 receptors (V1Rs) and the G protein subunit Gαi2, and (2) VSNs in the basal territories of the VNE that express vomeronasal type-2 receptors (V2Rs) and the G subunit Gαo. Recent studies identified a third subclass of Gαi2 and Gαo VSNs that express the formyl peptide receptor family. VSNs expressing V1Rs or V2Rs send their axons to distinct regions of the accessory olfactory bulb (AOB). Together, VNO and AOB form the accessory olfactory system (AOS), an olfactory subsystem that coordinates the social and sexual behaviors of many vertebrate species. In this review, we summarize our current understanding of cellular and molecular mechanisms that underlie VNO development. We also discuss open questions for study, which we suggest will further enhance our understanding of VNO morphogenesis at embryonic and postnatal stages.

Efficient and accurate EAP imaging from multi-shell dMRI with micro-structure adaptive convolution kernels and dual Fourier Integral Transforms (MiSFIT).

A number of computational techniques have been lately devised to image the Ensemble Average Propagator (EAP) within the white matter of the brain, propelled by the deployment of multi-shell acquisition protocols and databases: approaches like Mean Apparent Propagator Imaging (MAP-MRI) and its Laplacian-regularized version (MAPL) aim at describing the low frequency spectrum of the EAP (limited by the maximum b-value acquired) and afterwards computing scalar indices that embed useful descriptions of the white matter, e. g. the Return-to-Origin, Plane, or Axis Probabilities (RTOP, RTPP, RTAP). These methods resort to a non-parametric, bandwidth limited representation of the EAP that implies fitting a set of 3-D basis functions in a large-scale optimization problem. We propose a semi-parametric approach inspired by signal theory: the EAP is approximated as the spherical convolution of a Micro-Structure adaptive Gaussian kernel with a non-parametric orientation histogram, which aims at representing the low-frequency response of an ensemble of coherent sets of fiber bundles at the white matter. This way, the optimization involves just the 2 to 3 parameters that describe the kernel, making our approach far more efficient than the related state of the art. We devise dual Fourier domains Integral Transforms to analytically compute RTxP-like scalar indices as moments of arbitrary orders over either the whole 3-D space, particular directions, or particular planes. The so-called MiSFIT is both time efficient (a typical multi-shell data set can be processed in roughly one minute) and accurate: it provides estimates of widely validated indices like RTOP, RTPP, and RTAP comparable to MAPL for a wide variety of white matter configurations.

Melatonin attenuates prostatic inflammation and pelvic pain via Sirt1-dependent inhibition of the NLRP3 inflammasome in an EAP mouse model.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male genitourinary system disease. As a neuroendocrine hormone, melatonin possesses a variety of biological functions, among which its anti-inflammatory effects have recently drawn substantial attention. The purpose of the current research was to study the effect of melatonin on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP). METHODS: The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. On Day 42, hematoxylin-eosin staining was used to evaluate the histological appearance of prostate tissues. Chronic pelvic pain development was assessed by suprapubic allodynia. The levels of inflammation-related cytokines, such as interferon-γ, interleukin (IL)-17, and IL-1ß, were detected by enzyme-linked immunosorbent assay. Then, we explored the anti-inflammatory effects of melatonin on CP/CPPS by Western blotting and immunohistochemical staining, by measuring the expression of silent information regulator 1 (Sirt1) and NLRP3 inflammasome-related proteins in EAP mice. RESULTS: The EAP model mice exhibited severe diffuse leukocyte infiltration and significantly increased pelvic pain compared to the control mice. In the melatonin treatment group, the histological appearance of the prostate tissues, pelvic pain development, and the levels of proinflammatory cytokines were significantly alleviated compared to the EAP + dimethyl sulfoxide group. Furthermore, we found that the protective effects of melatonin were achieved through activation of the Sirt1 pathway and downregulation of the NLRP3 inflammasome. CONCLUSIONS: The results indicated that melatonin could attenuate prostate inflammation and pelvic pain by inhibiting the NLRP3 inflammasomes signaling pathway through the activation of Sirt1 in mice with EAP, and these efforts should provide a promising therapeutic strategy for CP/CPPS.

IRF2BPL Is Associated with Neurological Phenotypes.

Interferon regulatory factor 2 binding protein-like (IRF2BPL) encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals who carry damaging heterozygous variants in IRF2BPL and are affected with neurological symptoms. Five individuals who carry IRF2BPL nonsense variants resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The IRF2BPL bioinformatics signature based on population genomics is consistent with a gene that is intolerant to variation. We show that the fruit-fly IRF2BPL ortholog, called pits (protein interacting with Ttk69 and Sin3A), is broadly detected, including in the nervous system. Complete loss of pits is lethal early in development, whereas partial knockdown with RNA interference in neurons leads to neurodegeneration, revealing a requirement for this gene in proper neuronal function and maintenance. The identified IRF2BPL nonsense variants behave as severe loss-of-function alleles in this model organism, and ectopic expression of the missense variants leads to a range of phenotypes. Taken together, our results show that IRF2BPL and pits are required in the nervous system in humans and flies, and their loss leads to a range of neurological phenotypes in both species.

Apparent propagator anisotropy from single-shell diffusion MRI acquisitions.

PURPOSE: The apparent propagator anisotropy (APA) is a new diffusion MRI metric that, while drawing on the benefits of the ensemble averaged propagator anisotropy (PA) compared to the fractional anisotropy (FA), can be estimated from single-shell data. THEORY AND METHODS: Computation of the full PA requires acquisition of large datasets with many diffusion directions and different b-values, and results in extremely long processing times. This has hindered adoption of the PA by the community, despite evidence that it provides meaningful information beyond the FA. Calculation of the complete propagator can be avoided under the hypothesis that a similar sensitivity/specificity may be achieved from apparent measurements at a given shell. Assuming that diffusion anisotropy (DiA) is nondependent on the b-value, a closed-form expression using information from one single shell (ie, b-value) is reported. RESULTS: Publicly available databases with healthy and diseased subjects are used to compare the APA against other anisotropy measures. The structural information provided by the APA correlates with that provided by the PA for healthy subjects, while it also reveals statistically relevant differences in white matter regions for two pathologies, with a higher reliability than the FA. Additionally, APA has a computational complexity similar to the FA, with processing-times several orders of magnitude below the PA. CONCLUSIONS: The APA can extract more relevant white matter information than the FA, without any additional demands on data acquisition. This makes APA an attractive option for adoption into existing diffusion MRI analysis pipelines.

CaMK4-dependent phosphorylation of Akt/mTOR underlies Th17 excessive activation in experimental autoimmune prostatitis.

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) is a complicated syndrome characterized by genitourinary pain in the absence of bacterial infection. Th17 cell-driven autoimmunity has been proposed as a cause of CP/CPPS. However, the factors that promote Th17-driven autoimmunity in experimental autoimmune prostatitis (EAP) and the molecular mechanisms are still largely unknown. Here, we showed that Th17 cells were excessively activated, and blockade of IL-17A could effectively ameliorate various symptoms in EAP. Furthermore, we revealed that calcium/calmodulin-dependent kinase Ⅳ (CaMK4), especially Thr196 p-CaMK4 was increased in the Th17 cells of the EAP group, which were activated by intracellular cytosolic Ca2+ . Pharmacologic and genetic inhibition of CaMK4 decreased the proportion of Th17 cells, and the protein and mRNA level of IL-17A, IL-22, and RORγt. The phosphorylation of CaMK4 was dependent on the increase in intracellular cytosolic Ca2+ concentration in Th17 cells. A mechanistic study demonstrated that inhibition of CaMK4 reduced IL-17A production by decreasing the phosphorylation of Akt-mTOR, which was well accepted to positively regulate Th17 differentiation. Collectively, our results demonstrated that Ca2+ -CaMK4-Akt/mTOR-IL-17A axis inhibition may serve as a promising therapeutic strategy for CP/CPPS.

Facile and effective repair of Pt/Nafion IPMC actuator by dip-coating of PVP@AgNPs.

Ionic polymer metal composite (IPMC) always takes big risks of electrode cracking and peeling, which lead to energy wasting, waterloss, and uneven electric field distribution, thus hamper its commercial applications. To address this issue, we propose a facile and effective technique to repair the electrode fatigue by coating polyvinylpyrrolidone (PVP) encapsulated Ag nanoparticles (PVP@AgNPs) on the long-term used IPMC surface. To improve the electrochemical stability, the silver nanoparticles (Ag NPs) with a diameter of ∼34 nm are encapsulated by a 1.3 nm thick PVP film, thus forming a shell-core structure to resist corrosion from the electrolyte solution. Physiochemical investigations reveal that, PVP@AgNPs closely attach to the interior and exterior surfaces of the original Pt nanograin electrode, thus refreshing its electronic conductivity; the repaired IPMC actuator exhibits better electromechanical properties compared to its precursor actuator: 7.62 folds in displacement output, 9.38 folds in force output, and 9.73 folds in stable working time.

The eIF4E-binding protein Eap1 has similar but independent roles in cell growth and gene expression with the cytoplasmic deadenylase Ccr4.

eIF4E-binding proteins (4E-BPs) are translational repressors that compete with eIF4G for binding to eIF4E. Here we investigated the roles of yeast 4E-BPs, Eap1, and Caf20 in cell wall integrity pathway and gene expression. We found that eap1∆ mutation, but not caf20∆ mutation, showed synthetic growth defect with mutation in ROM2 gene encoding Rho1 GEF. The eap1∆ mutation also showed synthetic lethality with mutation in CCR4 gene encoding cytoplasmic deadenylase. Ccr4 functions in the degradation of LRG1 mRNA encoding Rho1 GAP. Eap1-Y109A L114A, which could not bind to eIF4E, did not suppress the synthetic lethality of eap1∆ ccr4∆ mutant, suggesting that 4E-binding of Eap1 is important for its function. We also found that eap1∆ mutant showed the derepression of stress response gene HSP12. 4E-binding of Eap1 was also required for the repression of HSP12 expression. Our results indicate that Eap1 has similar but independent roles in cell growth and gene expression with Ccr4.

Experimental Autoimmune Prostatitis Induces Learning-Memory Impairment and Structural Neuroplastic Changes in Mice.

Patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) commonly experience learning and memory decline and the underlying pathogenesis remains unclear. Therefore, we aimed to study the effects of CP/CPPS on cognitive function by using a mouse model of experimental autoimmune prostatitis (EAP). Non-obese diabetic mice were immunized subcutaneously by prostate antigen and adjuvant twice and tested for cognitive performance by Morris water maze and novel object recognition test after the EAP induction. Then, dendritic complexity and spine densities were measured by using the Golgi-Cox procedure. Transmission electron microscopy was used to observe the synaptic morphology. In addition, activation of microglia and its association with synapses were also investigated by immunofluorescence staining. Our results showed that EAP induced a notable decrease in the learning and memory ability of mice, simultaneously causing a reduction in dendritic complexity detected by Sholl analysis. Likewise, the spine densities and synaptic proteins including synaptophysin and postsynaptic density protein 95 (PSD95) were significantly decreased in the EAP group. These observations were also accompanied by structural changes in synaptic plasticity. Additionally, EAP mice showed microglial activation in the hippocampus, and these activated microglia further increased contact with synaptic terminals. Taken together, our data are the first to indicate that EAP induces cognitive declines and structural neuroplastic changes in mice, accompanied by microglial activation and microglia-synapse contacts.

Enterprise Security for the Internet of Things (IoT): Lightweight Bootstrapping with EAP-NOOB.

The emergence of radio technologies, such as Zigbee, Z-Wave, and Bluetooth Mesh, has transformed simple physical devices into smart objects that can understand and react to their environment. Devices, such as light bulbs, door locks, and window blinds, can now be connected to, and remotely controlled from, the Internet. Given the resource-constrained nature of many of these devices, they have typically relied on the use of universal global shared secrets for the initial bootstrapping and commissioning phase. Such a scheme has obvious security weaknesses and it also creates undesirable walled-gardens where devices of one ecosystem do not inter-operate with the other. In this paper, we investigate whether the standard Extensible Authentication Protocol (EAP) framework can be used for secure bootstrapping of resource-constrained devices. EAP naturally provides the benefits of per-device individual credentials, straightforward revocation, and isolation of devices. In particular, we look at the Nimble out-of-band authentication for EAP (EAP-NOOB) as a candidate EAP authentication method. EAP-NOOB greatly simplifies deployment of such devices as it does not require them to be pre-provisioned with credentials of any sort. Based on our implementation experience on off-the-shelf hardware, we demonstrate that lightweight EAP-NOOB is indeed a way forward to securely bootstrap such devices.

Secure Authentication and Credential Establishment in Narrowband IoT and 5G.

Security is critical in the deployment and maintenance of novel IoT and 5G networks. The process of bootstrapping is required to establish a secure data exchange between IoT devices and data-driven platforms. It entails, among other steps, authentication, authorization, and credential management. Nevertheless, there are few efforts dedicated to providing service access authentication in the area of constrained IoT devices connected to recent wireless networks such as narrowband IoT (NB-IoT) and 5G. Therefore, this paper presents the adaptation of bootstrapping protocols to be compliant with the 3GPP specifications in order to enable the 5G feature of secondary authentication for constrained IoT devices. To allow the secondary authentication and key establishment in NB-IoT and 4G/5G environments, we have adapted two Extensible Authentication Protocol (EAP) lower layers, i.e., PANATIKI and LO-CoAP-EAP. In fact, this approach presents the evaluation of both aforementioned EAP lower layers, showing the contrast between a current EAP lower layer standard, i.e., PANA, and one specifically designed with the constraints of IoT, thus providing high flexibility and scalability in the bootstrapping process in 5G networks. The proposed solution is evaluated to prove its efficiency and feasibility, being one of the first efforts to support secure service authentication and key establishment for constrained IoT devices in 5G environments.

Redundant and Distinct Roles of Secreted Protein Eap and Cell Wall-Anchored Protein SasG in Biofilm Formation and Pathogenicity of Staphylococcus aureus.

Chronic and fatal infections caused by Staphylococcus aureus are sometimes associated with biofilm formation. Secreted proteins and cell wall-anchored proteins (CWAPs) are important for the development of polysaccharide-independent biofilms, but functional relationships between these proteins are unclear. In the present study, we report the roles of the extracellular adherence protein Eap and the surface CWAP SasG in S. aureus MR23, a clinical methicillin-resistant isolate that forms a robust protein-dependent biofilm and accumulates a large amount of Eap in the extracellular matrix. Double deletion of eap and sasG, but not single eap or sasG deletion, reduced the biomass of the formed biofilm. Mutational analysis demonstrated that cell wall anchorage is essential for the role of SasG in biofilm formation. Confocal laser scanning microscopy revealed that MR23 formed a rugged and thick biofilm; deletion of both eap and sasG reduced biofilm ruggedness and thickness. Although sasG deletion did not affect either of these features, eap deletion reduced the ruggedness but not the thickness of the biofilm. This indicated that Eap contributes to the rough irregular surface structure of the MR23 biofilm and that both Eap and SasG play roles in biofilm thickness. The level of pathogenicity of the Δeap ΔsasG strain in a silkworm larval infection model was significantly lower (P < 0.05) than those of the wild type and single-deletion mutants. Collectively, these findings highlight the redundant and distinct roles of a secreted protein and a CWAP in biofilm formation and pathogenicity of S. aureus and may inform new strategies to control staphylococcal biofilm infections.

Feasibility testing of the Core set of quality Indicators for Paediatric Primary Care in Europe, COSI-PPC-EU.

There is a need to measure and improve the quality of paediatric primary care in Europe where major differences in the delivery and outcomes of child health care exist. A collaborative panel of paediatric senior experts developed a Core Set of Indicators for Paediatric Primary Care in Europe by compiling 42 quality indicators in a modified consensus process following the RAND/UCLA appropriateness method. The aim of this study was to explore the feasibility of the quality indicator set in European paediatric primary care practices. Seventy-nine practices from eight countries participated in a detailed online interview. The practices rated the applicability, relevance, reliability and acceptance of the 42 quality indicator as well as the availability, technical feasibility and effort to retrieve the needed data from their medical records. Most quality indicators were considered applicable, available, reliable, acceptable and relevant for monitoring quality of care in paediatric primary care. Respondents rated feasibility and effort to retrieve the data lowest because of difficulties collecting the data from the medical records.Conclusion: European paediatric primary care practices generally agree with the proposed quality indicator set. They document most of the parameters. However, the collection of specific needed values from available routine patient-data is considered technically difficult and time-consuming. What is Known? • Paediatric primary care systems in Europe show striking differences in their performance. Pre-existing sets of quality indicators are predominantly limited to national populations, specific diseases and hospital care. • A Core Set of 42 quality indicators for paediatric primary care in Europe was developed by European paediatricians using a systematic literature review and a consensus process following a modified RAND/UCLA appropriateness method. What is New? • Paediatric primary care providers in Europe agree with the idea to use COSI-PPC-EU to monitor and improve the quality of care. The set was considered applicable, available, reliable, acceptable, and relevant for quality improvement. • The score for feasibility and effort to retrieve the data was low, because of technical reasons; the electronical or paper-based medical documentation in most cases does not allow convenient access to all necessary data.

Morphological reseach on expression of inflammatory mediators in murine models of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) induced by T2 antigen.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common clinical syndrome with unknown aetiology. In this study, we used the T2 peptide in C57BL/6 (B6) mice and Sprague Dawley (SD) rats model during different stages. We sought to understand the role of CD4+ T cells and macrophages in CP/CPPS. A total of 16 B6 mice and 18 SD rats were divided into five groups: B6-naïve (n = 6), B6 model (n = 10), SD-naïve (n = 6), SD-45-day model (n = 6) and SD-56-day model (n = 6). The B6 model group was subcutaneously injected with 0.2 ml of (225µg/ml) T2 peptide on 0 and 14th day and was finally sacrificed on 28th day. The SD-45- and SD-56-day model groups were subcutaneously injected with 1ml of (50 µg/ml) T2 peptide on 0 and 14th day and were finally sacrificed on 45th and 56th day respectively. An equivalent volume of normal saline (NS) solution was injected to the naïve groups and analysed the pain and voiding behaviour. We have calculated the prostate index, H&E staining and immunofluorescence of CD4+ T cells and macrophages (CD68) in each group. T2 peptide immunization in B6 mice and SD rats caused severe prostatitis and cell infiltration, mainly composed of CD4+ T cells and macrophages. The SD-56-day model group showed more severe inflammatory cells infiltration than SD-45-day model group. Moreover, inflammatory cells infiltration and red secretions in B6 model were less than SD model. Expression of CD4+ T cells and macrophages was also consistent with H&E results. These results indicated that different stages of CP/CPPS, inflammatory response, and the inflammation of the rat were stronger than the mouse. Our study suggests that CD4+ T cells and macrophages are key factors in the development of CP/CPPS.