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Background: Asthma is associated with low-grade systemic inflammation, prothrombotic state, and premature atherosclerosis. Objective: To evaluate the relationships between asthma, inflammatory biomarkers, and parameters of endothelial dysfunction. Material and Methods: We analyzed flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasound in 92 clinically stable adult asthmatics and 62 well-matched controls. We also measured blood levels of selected inflammatory and asthma-specific biomarkers, including interleukin (IL) 4, IL-5, IL-6, IL-10, IL-12 (p70), IL-17A, IL-23, and interferon γ, as well as a disintegrin and metalloproteinase domain–containing protein 33 (ADAM-33). In addition, we assessed endothelial damage using 2 laboratory biomarkers: circulating von Willebrand factor (vWF) and pentraxin-3. We analyzed relationships between the study variables and asthma severity, lung function abnormalities, airway remodeling indices on computed tomography, and transthoracic echocardiography parameters. Results: Asthmatics had higher IL-6, IL-10, and ADAM-33 levels. They were also characterized by 23% lower FMD% and 15% thicker IMT, as compared with controls (P

Scholars and practitioners often promote direct engagement between policymakers, health workers and researchers as a strategy for overcoming barriers to utilizing scientific knowledge in health policy. However, in many settings public health officials rarely have opportunities to interact with researchers, which is a problem further exacerbated by the coronavirus disease 2019 pandemic. One prominent theory argues that policy actors will trust and utilize research findings when they perceive them to be salient, credible and legitimate. We draw on this theory to examine the conditions facilitating greater uptake of new knowledge among health officials when engagement is out of reach and they are instead exposed to new ideas through written mass communication. Using data from a survey experiment with about 260 health workers and administrators in Honduras, we find that messages from a technocratic sender based on statistical evidence improved perceptions of salience, credibility and legitimacy (SCL). Additionally, perceptions of SCL are three contextual features that operate as joint mediators between knowledge and action, and several individual characteristics also influence whether officials trust research findings enough to apply them when formulating and implementing health policies. This research can help inform the design of context-sensitive knowledge translation and exchange strategies to advance the goals of evidence-based public health, particularly in settings where direct engagement is difficult to achieve.

Background and objectives Despite significant improvement in the treatment of tendon injuries, the full tissue recovery is often not possible because of its limited ability to auto-repair. The transplantation of mesenchymal stromal cells (MSCs) is considered as a novel approach in the treatment of tendinopathies. The question about the optimal culture conditions remains open. In this study we aimed to investigate if serum reduction, L-ascorbic acid supplementation or a combination of both factors can induce tenogenic differentiation of human adipose-derived MSCs (ASCs). Methods and results Human ASCs from 3 healthy donors were used in the study. The tested conditions were: 0.5 mM of ascorbic acid 2-phosphate (AA-2P), reduced serum content (2% FBS) or combination of these two factors. The combination of AA-2P and 2% FBS was the only experimental condition that caused a significant increase of the expression of all analyzed genes related to tenogenesis (SCLERAXIS, MOHAWK, COLLAGEN_1, COLLAGEN_3, DECORIN) in comparison to the untreated control (evaluated by RT-PCR, 5th day of experiment). Moreover, this treatment significantly increased the synthesis of SCLERAXIS, MOHAWK, COLLAGEN_1, COLLAGEN_3 proteins at the same time point (evaluated by Western blot method). Double immunocytochemical staining revealed that AA-2P significantly increased the extracellular deposition of both types of collagens. Semi-quantitative Electron Spin Resonance analysis of ascorbyl free radical revealed that AA-2P do not induce harmful transition metals-driven redox reactions in cell culture media. Conclusions Obtained results justify the use of reduced content of serum with the addition of 0.5 mM of AA-2P in tenogenic inducing media.

While common MRI characteristics for schwannomas exist, diagnosis by imaging alone remains challenging. Detailed analysis of symptoms reported by the patient is very important in the differential diagnosis between meningioma and schwannoma in cases where MRI images are not sufficient for determining the tumor type. The pain, its classification of the character, and the timing seem to be an important predictive symptom in the differential diagnosis of spinal schwannoma.

Purpose The biggest problem with the occurrence of breast cancer is late diagnosis, which is associated with high mortality rates. The aim of the study was to appraise the number of circulating endothelial precursors and the concentration of vascular endothelial growth factor A (VEGF-A) and the soluble forms of its receptors, sVEGFR1 and sVEGFR2, in breast cancer patients with respect to clinicopathological features. Material and methods The study involved 85 women of Caucasian ethnicity aged 45–66 with primary breast cancer without distant metastases (M0). Inclusion criteria were as follows: histopathological examination confirming the diagnosis of primary breast cancer, without previous radiotherapy and chemotherapy. Immunohistochemistry evaluation of oestrogen and progesterone receptors, human epidermal growth factor receptor 2, Ki67 expression was made in all cases. In the EDTA-plasma, the concentrations of VEGF-A and its soluble receptors, sVEGFR1 and sVEGFR2, were measured applying immunoassay techniques. Circulating endothelial progenitor cells (EPCs) were identified with the immune-phenotype CD45−, CD34+, CD133+, CD31+ using flow cytometry. Results Older women with breast cancer had significantly higher concentrations of VEGF-A as well as sVEGFR2 compared with their younger counterparts. A significantly higher concentration of the soluble form of VEGF receptor type 1 in patients with T1 breast cancer in relation to T2 cases was noted. Also, negative correlations between circulating EPCs and histological grading as well as a soluble form of VEGFR2 with histological grading of breast cancer according to the Elston-Ellis classification were observed. Conclusions Anti-angiogenic potential is divergent in relation to the clinicopathological determinants.

Despite considerable advances in developing new and more sophisticated impact evaluation methodologies and toolkits, policy research continues to suffer from persistent challenges in achieving the evaluation trifecta: identifying effects, isolating mechanisms, and influencing policy. For example, evaluation studies are routinely hampered by problems of establishing valid counterfactuals due to endogeneity and selection effects with respect to policy reform. Additionally, robust evaluation studies often must contend with heterogeneity in treatment, staggered timing, and variation in uptake. And finally, on practical grounds, researchers frequently struggle to involve policymakers and practitioners throughout the research process in order to engender the type of trust needed for policy influence. While it can be difficult to generalize about appropriate evaluation methodologies across contexts, prominent policy interventions like governance reforms for improving health services delivery nonetheless demand rigorous and comprehensive evaluation strategies that can produce valid results and engage policymakers. Drawing on illustrations from our research on health sector decentralization in Honduras, in this paper we present a quasi-experimental, multi-method, and participatory approach that addresses these persistent challenges to policy evaluation.

Background. Cellular therapy is proposed for tendinopathy treatment. Bone marrow- (BM-MSC) and adipose tissue- (ASC) derived mesenchymal stromal cells are candidate populations for such a therapy. The first aim of the study was to compare human BM-MSCs and ASCs for their basal expression of factors associated with tenogenesis as well as chemotaxis. The additional aim was to evaluate if the donor age influences these features. Methods. Cells were isolated from 24 human donors, 8 for each group: hASC, hBM-MSC Y (age≤45), and hBM-MSC A (age>45). The microarray analysis was performed on RNA isolated from hASC and hBM-MSC A cells. Based on microarray results, 8 factors were chosen for further evaluation. Two genes were additionally included in the analysis: SCLERAXIS and PPARγ. All these 10 factors were tested for gene expression by the qRT-PCR method, and all except of RUNX2 were additionally evaluated for protein expression or secretion. Results. Microarray analysis showed over 1,400 genes with a significantly different expression between hASC and hBM-MSC groups. Eight of these genes were selected for further analysis: CXCL6, CXCL12, CXCL16, TGF-β2, SMAD3, COLLAGEN 14A1, MOHAWK, and RUNX2. In the subsequent qRT-PCR analysis, hBM-MSCs showed a significantly higher expression than did hASCs in following genes: CXCL12, CXCL16, TGF-β2, SMAD3, COLLAGEN 14A1, and SCLERAXIS (p<0.05, regardless of BM donor age). In the case of CXCL12, the difference between hASC and hBM-MSC was significant only for younger BM donors, whereas for COLLAGEN 14A1—only for elder BM donors. PPARγ displayed a higher expression in hASCs compared to hBM-MSCs. In regard to CXCL6, MOHAWK, and RUNX2 gene expression, no statistically significant differences between groups were observed. Conclusions. In the context of cell-based therapy for tendinopathies, bone marrow appears to be a more attractive source of MSCs than does adipose tissue. The age of cell donors seems to be less important than cell source, although cells from elder donors show slightly higher basal tenogenic potential than do cells from younger donors.

Autologous stem cell transplant (autoSCT), the standard consolidation therapy for multiple myeloma, improves disease-free survival, but is not curative. This could be an ideal setting for immunologic therapy. However, the immune milieu is impaired after autoSCT. We hypothesized that autologous lymphocyte infusion would restore immune competence, allowing immunotherapies such as cancer vaccines to elicit tumor antigen–specific immunity in the setting of autoSCT. In this pilot study (NCT01380145), we investigated safety, immunologic, and clinical outcomes of autologous lymphocyte infusion combined with peri-autoSCT immunotherapy with recombinant MAGE-A3 (a multiple myeloma–associated antigen) and adjuvant. Thirteen patients with multiple myeloma undergoing autoSCT were enrolled. Autologous lymphocyte infusion and MAGE vaccination were well tolerated. Combination immunotherapy resulted in high-titer humoral immunity and robust, antigen-specific CD4+ T-cell responses in all subjects, and the responses persisted at least one year post-autoSCT. CD4+ T cells were polyfunctional and Th1-biased. CD8+ T-cell responses were elicited in 3 of 13 subjects. These cells recognized naturally processed MAGE-A3 antigen. Median progression-free survival was 27 months, and median overall survival was not reached, suggesting no differences from standard-of-care. In 4 of 8 subjects tested, MAGE-A protein expression was not detected by IHC in multiple myeloma cells at relapse, suggesting therapy-induced immunologic selection against antigen-expressing clones. These results demonstrated that autologous lymphocyte infusion augmentation of autoSCT confers a favorable milieu for immunotherapies such as tumor vaccines. This strategy does not require ex vivo manipulation of autologous lymphocyte products and is an applicable platform for further investigation into combination immunotherapies to treat multiple myeloma.

Increased airway wall thickness and remodeling of bronchial mucosa are characteristic of asthma and may arise from altered integrin signaling on airway cells. Here, we analyzed the expression of β1-subfamily integrins on blood and airway cells (flow cytometry), inflammatory biomarkers in serum and bronchoalveolar lavage, reticular basement membrane (RBM) thickness and collagen deposits in the mucosa (histology), and airway geometry (CT-imaging) in 92 asthma patients (persistent airflow limitation subtype: n = 47) and 36 controls. Persistent airflow limitation was associated with type-2 inflammation, elevated soluble α2 integrin chain, and changes in the bronchial wall geometry. Both subtypes of asthma showed thicker RBM than control, but collagen deposition and epithelial α1 and α2 integrins staining were similar. Type-I collagen accumulation and RBM thickness were inversely related to the epithelial expression of the α2 integrin chain. Expression of α2β1 integrin on T-cells and eosinophils was not altered in asthma. Collagen I deposits were, however, more abundant in patients with lower α2β1 integrin on blood and airway CD8+ T-cells. Thicker airway walls in CT were associated with lower α2 integrin chain on blood CD4+ T-cells and airway eosinophils. Our data suggest that α2β1 integrin on inflammatory and epithelial cells may protect against airway remodeling advancement in asthma.

Recently, there is great interest in vasculogenesis, a process of the formation of new blood vessels from progenitor cells or angioblasts, in the pathogenesis of cancer. To the best of our knowledge, the evaluation of endothelial progenitor cells (EPCs) in Hodgkin's lymphoma has not yet been reported. The aim of the present study was to assess the number of EPCs and selected cytokines, such as vascular endothelial growth factor (VEGF-A) and stromal cell-derived factor (SDF-1α) involved in vasculogenesis in Hodgkin's lymphoma patients. The study was conducted in a group of 42 patients with Hodgkin's lymphoma (eight patients with relapsed Hodgkin's lymphoma and 34 patients before the first treatment) and 30 healthy controls. The number of EPCs defined as CD31(+), CD34(+), CD45(-), CD133(+) was analysed on FacsCalibur flow cytometer and the concentration of VEGF-A and SDF-1α was assessed by ELISA. The study showed that there was a significantly higher EPCs number and VEGF-A concentration in the blood of Hodgkin's lymphoma patients compared to healthy individuals (8.20 vs. 0.55 cells/μl; P < 0.000001; 85.10 vs. 25.33 pg/ml, P = 0.000017; respectively). Detailed analysis revealed that there was elevated EPCs number in both study subgroups as compared to the control group. However, there was no difference in VEGF concentration between recurrent Hodgkin's lymphoma patients and the control group. A significant positive correlation was found between the number of EPCs and VEGF-A concentration (R = 0.31, P = 0.047). Significantly higher EPCs number combined with increased VEGF-A concentration, found in Hodgkin's lymphoma patients before the first treatment, suggest stimulation of new blood vessels formation, which may in turn contribute to tumour growth and metastasis in these patients.

Background: In recent years, great progress has been made in the treatment of breast cancer, but it is still one of the ten leading causes of death in women. The aim of the study was to evaluate the heparanase concentration of invasive breast cancer (IBrC) patients, before and after cancer adjuvant treatment. Methods: Eighty patients with stage IA to IIB IBrC receiving adjuvant treatment were included prospectively in this study. The heparanase concentrations were determined by an enzyme-linked immunosorbent assay. A univariate analysis was used to estimate the factors influencing the low or high pre-treatment concentration of heparanase and the low or high numerical decrease in heparanase concentration after completion of adjuvant treatment. Results: Treatment reduced the concentration of heparanase by almost four times in the general IBrC cohort. Higher levels of pre- and post-treatment heparanase were noted in oestrogen receptor-negative cancers than in positive ones. A higher post-treatment concentration of heparanase was found in patients with a triple-negative tumour compared to patients with a luminal B HER2 negative type of IBrC. Overweight IBrC subjects and those with a tumour diameter of ≥2 cm demonstrated a lower chance of a lower pre-treatment heparanase concentration. Interestingly, a pre-treatment heparanase concentration is the main predictor of the changes in heparanase concentration after adjuvant treatment. Follow-up revealed significantly lower progression-free survival (PFS) rates in IBrC patients with a pre-treatment concentration of heparanase higher than 181.46 pg/mL (PFS = 80%). Conclusions: Our findings provide supporting evidence that IBrC therapy reduced the heparanase levels, regardless of treatment patterns and a pre-treatment concentration of heparanase may serve as a prognostic indicator for future outcomes.

Simple Summary This prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters—vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs)—for estimating the probability of disease relapse in invasive breast cancer (IBrC) patients. Kaplan–Meier plots and log-rank and F Cox tests were used to determine the clinical outcomes in terms of disease-free survival (DFS). Patients with a combination of SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138); thus, the combination of these two factors shows strong diagnostic power for the prediction of disease relapse. Abstract (1) Background: Tumour angiogenesis is critical for the progression of neoplasms. A prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters for estimating the probability of disease relapse in 84 primary, operable invasive breast cancer (IBrC) patients (40 (48%) with stage IA and 44 (52%) with stage IIA and IIB). (2) Methods: We explored the prognostic value of the plasma levels of SDF-1α, vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs) in breast cancer patients. The median follow-up duration was 58 months, with complete follow-up for the first event. (3) Results: According to ROC curve analysis, the optimal cut-off point for SDF-1α (for discriminating between patients at high and low risk of relapse) was 42 pg/mL, providing 57% sensitivity and 75% specificity. Kaplan–Meier curves for disease-free survival (DFS) showed that concentrations of SDF-1α lower than 42 pg/dL together with a VEGFR1 lower than 29.86 pg/mL were significantly associated with shorter DFS in IBrC patients (p = 0.0381). Patients with both SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138). (4) Conclusions: Our results imply the clinical usefulness of SDF-1α, sVEGFR1 and the number of circulating EPCs as prognostic markers for breast cancer in clinical settings.

Background Heterogeneity of asthma complicates search for targeted treatment against airway hyperresponsiveness and remodeling. We conducted a systems biology approach study to establish differential co-expression of genes (DCG) in eosinophilic and non-eosinophilic asthma patients and infer their role in the disease. Materials and Methods N = 40 Caucasian adult moderate to severe non-smoking asthma patients (half with eosinophilic asthma) undergone bronchial brush biopsy sampling for mRNA expression using hybridization to cDNA microarray. Mechanistic interpretation of DCG was inferred from existing literature. Results Differentially co-expressed genes bear significance in airway viral infection (ATP1B1, EPS15), arachidonic acid metabolism (CLC, FADS6), cell migration (EPS8L1, STOML3, RhoBTB2), surface receptors endocytosis (STRN4, EPS15, ATP1B1) or decreased expression (CCT7), oxidative stress (DIO3, RhoBTB2), decreased adhesion (ATP1B1, RAPH1, STOML3), epithelial-mesenchymal transition (ASB3, RADX, CCT7, MRPL14, PPP2R3B, RPS13, SLC19A1), myofibroblast differentiation (CCT7), smooth muscle proliferation (ASB3, ATP1B1), airway hyperreactivity (RECK, STOML3, ATP1B1, OR52I1), extracellular matrix remodeling (FBN3, RECK), angiogenesis (GPI, RhoBTB2) and neuronal pathogenesis of asthma (OR52I1, STRN4, TTC3P1, GPI, CABP5) and were linked to asthma in genome- (MRPL14, ASB3, RPS13) and epigenome-wide (CLC, EPS15, GPI, SSCRB4, STRN4) association studies. Signaling pathways involved (especially TGF-β/Smad2/3) are inferred from the co-expression pattern. Conclusion Activity of genes and pathways of known or tentative role in asthma pathogenesis was established in regard to a condition cognizable in clinical practice.

Airway remodeling in asthma is characterized by reticular basement membrane (RBM) thickening, likely related to epithelial structural and functional changes. Gene expression profiling of the airway epithelium might identify genes involved in bronchial structural alterations. We analyzed bronchial wall geometry (computed tomography (CT)), RBM thickness (histology), and the bronchial epithelium transcriptome profile (gene expression array) in moderate to severe persistent (n = 21) vs. no persistent (n = 19) airflow limitation asthmatics. RBM thickness was similar in the two studied subgroups. Among the genes associated with increased RBM thickness, the most essential were those engaged in cell activation, proliferation, and growth (e.g., CDK20, TACC2, ORC5, and NEK5) and inhibiting apoptosis (e.g., higher mRNA expression of RFN34, BIRC3, NAA16, and lower of RNF13, MRPL37, CACNA1G). Additionally, RBM thickness correlated with the expression of genes encoding extracellular matrix (ECM) components (LAMA3, USH2A), involved in ECM remodeling (LTBP1), neovascularization (FGD5, HPRT1), nerve functioning (TPH1, PCDHGC4), oxidative stress adaptation (RIT1, HSP90AB1), epigenetic modifications (OLMALINC, DNMT3A), and the innate immune response (STAP1, OAS2). Cluster analysis revealed that genes linked with RBM thickness were also related to thicker bronchial walls in CT. Our study suggests that the pro-fibrotic profile in the airway epithelial cell transcriptome is associated with a thicker RBM, and thus, may contribute to asthma airway remodeling.

The goal of this preliminary research is to present an automated segmentation of abdominal organs: pancreas and duodenum. The paper shows the automatic extraction of pancreas and duodenum in clinical abdominal computed tomography (CT) scans. The proposed method allows building a feature vector that automates and streamlines the fuzzy connectedness (FC) method. All described steps of the presented methodology have been implemented in MATLAB and tested on clinical abdominal CT scans. The atlas based segmentation combined with the FC method gave Dice index results at the following level: 70.18–84.82% for pancreas and 68.90–88.06% for duodenum.

Relapsed/refractory multiple myeloma patients treated with pomalidomide and dexamethasone have an overall response rate (ORR) of ∼30% and median progression-free survival (PFS) of 4-5 months. Previous studies explored addition of weekly cyclophosphamide, but we hypothesized that daily dosing allows for better synergy. We report the open-label, single-center phase II study of pomalidomide, daily cyclophosphamide and weekly dexamethasone (PCD). Thirty-three patients were evaluable for efficacy and underwent 28-day cycles of pomalidomide (4 mg/day, D1-21), cyclophosphamide (50 mg b.i.d., D1-21) and weekly dexamethasone. All were lenalidomide-refractory and 55% were refractory to lenalidomide and proteasome inhibitor. ORR was 73%; median PFS and overall survival were 13.3 months and 57.2 months respectively. Grade 3/4 toxicities were primarily hematologic but manageable with dose reductions. Early disease progression correlated with MYC expression and flow cytometry demonstrates an activated microenvironment post-PCD. Addition of metronomic cyclophosphamide to pomalidomide and dexamethasone is a cost-effective, oral regimen with encouraging PFS.

BACKGROUND: Endothelial and platelet activation as well as a disruption of haemostatic balance are crucial in cancer-dependent venous thromboembolism development. OBJECTIVE: The aim of this study was to investigate the influence of von Willebrand factor (VWF), sE-selectin, sP-selectin as well as VWF/sE-selectin and sP-selectin/sE-selectin ratios on the probability of disease relapse in invasive breast carcinoma (IBrC) cases. METHODS: Eighty-four patients with IA-IIB stage of IBrC who passed a comprehensive clinicopathologic evaluation were included in the study. Follow-up was completed in all patients with a 15.48 % recurrence rate. An immunoassay of VWF antigen, sE-selectin, sP-selectin, as well as an immunohistochemistry of oestrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2) and Ki67 was performed in all cases. RESULTS: The VWF/sE-selectin ratio was significantly higher in patients with poorly differentiated tumours than in those with high-differentiated tumours. A positive correlation between VWF concentration and tumour grade was noted. Eleven of 13 events happened in patients with VWF value below 600 mU/mL with recurrence rate of 25%, but only two events occurred in subject with VWF values above the 600 mU/mL (5%; P= 0.0028). CONCLUSIONS: Our study show that VWF could be considered as a suitable biomarker of breast cancer relapse.

Background: This study addressed differences between parent&ndash, child dyads with excessive body mass (overweight or obesity) and dyads with normal body mass in obesity determinants, derived from social-ecological models. It was hypothesized that parents and their 5&ndash, 11 years-old children with excessive body mass would (1) report lower availability of healthy food at home, (2) perceive fewer school/local community healthy eating promotion programs, (3) report lower persuasive value of food advertising. Methods: Data were collected twice (T1, baseline, T2, 10-month follow-up), including n = 129 parent&ndash, child dyads with excessive body mass and n = 377 parent&ndash, child dyads with normal body mass. Self-reported data were collected from parents and children, with body weight and height assessed objectively. General linear models (including analysis of variance with repeated measures) were performed to test the hypotheses. Results: Compared to dyads with normal body mass, dyads of parents and children with excessive body mass perceived lower availability of healthy food at home and fewer healthy eating promotion programs at school/local community (T1 and T2). These effects remained significant after controlling for sociodemographic variables. No significant differences in persuasive value of food advertising were found. Conclusions: Perceptions of availability of healthy food at home and healthy nutrition promotion may be relatively low in parent&ndash, child dyads with excessive weight which, in turn, may constitute a risk factor for maintenance of obesity.

The main aim of this new approach dedicated to knee arthroplasty is to provide an automated method for determining the cutting planes of both the head of femur and the head of tibia in knee replacement surgery. This paper shows a new approach differing from standard procedures associated with manual determination of the mechanical axis of the lower extremity (during surgery) and replacing them with a procedure based on the imprints (with selected cutting planes) of the two heads of bones. Both these imprints have been performed on the basis of the toposcan of the lower limb (before surgery). This methodology has been implemented in MATLAB and tested in clinical CT images of the lower limb in the coronal and transverse planes (61 studies) and in clinical MRI studies of the knee joint in coronal plane (107 studies). Correct results were obtained for about 90% cases.

Phase 3 studies combining histone deacetylase inhibitors with bortezomib were hampered by gastrointestinal (GI) intolerance, which was not observed when combined with immunomodulatory drugs. This study is a single-center phase 2 study of panobinostat with lenalidomide and dexamethasone (FRD). Twenty-seven relapsed multiple myeloma patients were enrolled. Twenty-two patients (81%) were lenalidomide refractory and 9 (33%), 14 (52%), and 7 (26%) were refractory to pomalidomide, bortezomib, and carfilzomib, respectively. High-risk molecular findings were present in 17 (63%) patients. Responses included 2 complete responses (CRs), 4 very good partial responses (VGPRs), 5 partial responses (PRs), and 9 minimal responses (MRs) for an overall response rate of 41%, clinical benefit rate of 74%, and a disease control rate of 96%. The median progression-free survival (PFS) was 7.1 months. In the 22 lenalidomide-refractory patients, there were 1 CR, 4 VGPRs, 3 PRs, and 7 MRs, with a median PFS of 6.5 months. Median overall survival was not reached. Grade 3/4 toxicities were primarily hematologic. Gene expression profiling of enrollment tumor samples revealed a set of 1989 genes associated with short (90 days) PFS to therapy. MAGEA1 RNA and protein expression were correlated with short PFS, and laboratory studies demonstrated a role for MAGE-A in resistance to panobinostat-induced cell death. FRD demonstrates durable responses, even in high-risk, lenalidomide-refractory patients, indicating the essential role of panobinostat in attaining responses. MAGEA1 expression may represent a functional biomarker for resistance to panobinostat. In contrast to PANORAMA 1, there were no significant GI toxicities and primarily expected hematologic toxicities. This trial was registered at www.clinicaltrials.gov as #NCT00742027.

Objective: Although there is substantial evidence corroborating the within-individual associations between depression, social support, moderate-to-vigorous physical activity (MVPA), and body mass, much less is known about across-individual associations. This study investigated the indirect associations between parental depression and objectively measured body mass in children. In particular, it was hypothesized that higher levels of parental depression (measured at Time 1, T1), would explain higher levels of child body mass in children (assessed at Time 2, T2), via three mediators, namely parental reports of provision of MVPA support (T1), child reports of receipt of MVPA support (T1), and child MVPA (T2). Design: Parent-child dyads provided self-reports twice, at the baseline (T1) and 7- to 8-month follow-up (T2). A total of 879 dyads were enrolled (1,758 individuals; 5- to 11-year-old children, 52.4% girls, 83.2% mothers). Body weight and height were measured objectively. Manifest path analyses were performed to test the indirect effects. Results: Analyses corroborated the assumed indirect effects: high levels of depression in parents (T1) were indirectly associated with high levels of body mass in children (T2), via three mediators: low levels of parental support provision (T1), low levels of child support receipt (T1), and low levels of child MVPA (T2). The alternative models, assuming that either parental support provision or child support receipt can be excluded as the mediators yielded poor model-data fit. The hypothesized mediation effects were corroborated when controlling for the baseline levels of parental and child MVPA and body mass. Conclusion: The findings confirm complex across-individual effects of parental depression on high levels of body mass in children. Parental mental health may contribute to the childhood obesity epidemic.

© 2018, The Author(s). Purpose: Theoretical models, such as the transdiagnostic model of eating disorders highlight the role of cognitive factors (e.g., the way people perceive their bodies) and their associations with maladaptive weight management behaviors resulting in underweight. This paper aims at testing the indirect association of adolescent’s body satisfaction and body mass index (BMI) through restrictive dieting, healthy eating or unhealthy eating as well as moderating role of adolescent’s weight status. Methods: The study was conducted in 16 public middle and high schools in Central and Eastern Poland. A sample of 1042 under- and healthy-weight white adolescents aged 13–20 (BMI: 12.63–24.89) completed two self-reported questionnaires (fruit, vegetable, and energy-dense food intake) with a 11-month interval. Weight and height were measured objectively. Multiple mediation analysis and moderated multiple mediation analysis were conducted to test the study hypotheses. Results: Adolescents less satisfied with their bodies were more likely to diet restrictively and at the same time ate more unhealthy energy-dense food rather than healthy food, which in turn predicted lower BMI. No moderating effects of weight status were found. Conclusions: Low body satisfaction is a risk for restrictive diet and unhealthy food intake. Prevention programs may target under- and healthy-weight adolescents who are highly dissatisfied with their bodies, have a high intake of energy-dense food and apply a restrictive diet at the same time. Level of evidence: Level III: longitudinal cohort study.

Histone H3 is citrullinated in the process of epigenetic chromatin remodelling and neutrophil extracellular trap (NET) formation. In 76 adult asthmatics and 54 well-matched controls we measured circulating level of citrullinated histone H3 (CitH3) using Cayman ELISA kit. In asthma we also determined the airway cross-sectional geometry of two distal and two peripheral bronchi in lung computed tomography (CT) and performed bronchoscopy with bronchoalveolar lavage (BAL). We assessed blood and BAL biomarkers, including cytokines: IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A, IL-23, INFγ, together with periostin and blood level of disintegrin and metalloproteinase domain-containing protein (ADAM33). We found that CitH3 was higher in asthmatics than controls (16.6 [11.5-21.7] vs. 13.9 [7.14-18.8] ng/ml, p=0.02), independently of asthma severity. Weak correlation was demonstrated between CitH3 and FEV1/VC index (β=-0.15 [-0.27- -0.04]), but none of the CT remodelling indices. In asthma, but not in controls, CitH3 was related to the number of leukocytes (β=0.26 [0.15-0.38]), neutrophils (β=0.25 [0.14-0.37]) monocytes (β=0.42 [0.31-0.53]), erythrocytes (β=0.27 [0.15-0.38]) and platelets (β=0.22 [0.1-0.33]) in peripheral blood. In both groups CitH3 remained in positive relationships with cholesterol levels, but not inflammatory markers. CitH3 was associated with circulating ADAM33 (β=0.19 [0.11-0.18]) and BAL biomarkers: INFγ, IL-5, IL-17A and IL-10 (β=0.19 [0.07-0.31], β=0.22 [0.1-0.33], β=0.19 [0.1-0.3], β=-0.14 [-0.26- -0.02], respectively). Conclusions: We have shown that blood NETs formation might be involved in asthma pathology independently of its severity. Funding: National Science Centre, No DEC-2013/09/B/NZ5/00758

Airway structural changes are important in asthma pathology and require investigations. In 105 adult asthmatics (53 with fixed obstruction) we determined the airway cross-sectional geometry of two distal and two peripheral bronchi and quantified the low-attenuation lung area (LAA%). We also performed bronchoscopy with BAL and endobronchial biopsy with histological examination. We assessed blood and BAL biomarkers, including IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A, IL-23, INFγ and periostin, together with circulating ADAM33, and investigated interplays between analyzed variables with cluster analyses. Results: Patients with fixed airflow limitation had lower lumen area, higher airway area, increased wall area and wall thickness ratios of peripheral airways, accompanied by raised LAA%. They had also increased blood neutrophils and eosinophils, BAL eosinophilia, higher circulating fibrinogen, INFγ, periostin, and ADAM33. Blood neutrophilia, increased serum HDL, TSH, urea, and shorter APTT were determinants of thicker reticular basement membrane (RBM) of bronchial mucosa. BAL eosinophilia was the only positive predictor of collagen I accumulation. We observed a negative correlation between RBM thickness and collagen I deposit. A cluster analysis revealed three well-separated clusters, characterized by different lung function, biomarkers, collagen I deposit and RBM thickness. Conclusions: Unfavourable airway structural changes are related to the Th2 immunity, higher ADAM33, INFγ, and neutrophil count in blood. Thicker RBM might play a protective role against collagen I accumulation and mucosa fibrosis. Funding: National Science Centre, decision No DEC-2013/09/B/NZ5/00758

© 2019, The Author(s). Purpose: This study aims at investigating prospective associations between body areas satisfaction (BAS), actual (objectively measured)–ideal body weight discrepancy, actual (self-reported)–ideal body weight discrepancy and BMI among adolescents from the general population. Methods: Data were collected at three measurement points: baseline (T1), 2-month follow-up (T2), 13-month follow-up (T3) among 1011 adolescents (59.3% girls) aged 13–19 years (M = 16.30, SD = 0.82) with BMIs ranging from 15.20 to 38.78 (M = 20.01, SD = 3.33). Adolescents completed questionnaires regarding BAS (T1), actual and ideal body weight (T2). Body weight and height were measured objectively (T1 and T3). Results: Adolescents satisfied with most areas of their bodies had lower levels of actual (objectively measured)–ideal body weight discrepancy, which in turn predicted higher BMI, while lower levels of actual (self-reported)–ideal body weight discrepancy predicted lower BMI. No moderating effect of gender was found. Conclusions: Actual–ideal weight discrepancies may operate in complex manner prompting opposite effects on BMI. Level of evidence: Level III, longitudinal study without control group.

A study on computer aided diagnosis of posterior cruciate ligaments is presented in this paper. The diagnosis relies on T1-weighted magnetic resonance imaging. During the image analysis stage, the ligament region is automatically detected, localized, and extracted using fuzzy segmentation methods. Eight geometric features are defined for the ligament object. With a clinical reference database containing 107 cases of both healthy and pathological cases, a Fisher linear discriminant is used to select 4 most distinctive features. At the classification stage we employ five different soft computing classifiers to evaluate the feature vector suitability for the computerized ligament diagnosis. Among the classifiers we introduce and specify the particle swarm optimization based Sugeno-type fuzzy inference system and compare its performance to other established classification systems. The classification accuracy metrics: sensitivity, specificity, and Dice index all exceed 90% for each classifier under consideration, indicating high level of the proposed feature vector relevance in the computer aided ligaments diagnosis.

Cell therapy is emerging as an alternative treatment of stress urinary incontinence. However, many aspects of the procedure require further optimization. A large animal model is needed to reliably test cell delivery methods. In this study, we aim to determine suitability of the goat as an experimental animal for testing intraurethral autologous cell transplantation in terms of urethral anatomy and cell culture parameters. The experiments were performed in 12 mature/aged female goats. Isolated caprine muscle derived cells (MDC) were myogenic in vitro and mesenchymal stem cells (MSC) population was able to differentiate into adipo-, osteo- and chondrogenic lineages. The median yield of cells after 3 weeks of culture amounted 47 × 10(6) for MDC and 37 × 10(6) for MSC. Urethral pressure profile measurements revealed the mean functional urethral length of 3.75 ± 0.7 cm. The mean maximal urethral closure pressure amounted 63.5 ± 5.9 cmH2 O and the mean functional area was 123.3 ± 19.4 cm*cmH2 O. The omega- shaped striated urethral sphincter was well developed in the middle and distal third of the urethra and its mean thickness on cross section was 2.3 mm. In the proximal part of the urethra only loosely arranged smooth muscle fibers were identified. To conclude, presented data demonstrate that caprine MDC and MSC can be expanded in vitro in a repeatable manner even when mature or aged animals are cell donors. Results suggest that female caprine urethra has similar parameters to those reported in human and therefore the goat can be an appropriate experimental animal for testing intraurethral cell transplantation. Anat Rec, 00:000-000, 2016. © 2016 Wiley Periodicals, Inc. Anat Rec, 300:577-588, 2017. © 2016 Wiley Periodicals, Inc.

Sudden sensorineural hearing loss seems to become a serious social health problem in modern societies. According to the World Health Organization (WHO) reports, adult-onset sensorineural hearing loss is found to be one of the leading diseases at the global level, especially in high-income countries, and is foreseen to move up from the 14th to 7th leading cause of the global burden of diseases by the year 2030. Although the direct mortality rate of this disease is very low, its influence on quality of life is huge; that is the reason why the implementation of the most effective and the safest therapies for the patient is crucial for minimizing the risk of complications and adverse reactions to treatment. The aim of this paper is to present hyperbaric oxygen therapy (HBOT) as a medical procedure useful in the treatment of sudden sensorineural hearing loss as adjunctive therapy of high efficacy. This paper focuses on the molecular mechanisms of action and clinical effectiveness of HBOT in the treatment of idiopathic sudden deafness, taking into consideration both the benefits and potential risks of its implementation.

To date, lateral differences of invasive breast cancer (IBrC) with respect to the angiogenic and hemostatic profiles were never studied. Here, we aimed to determine the relationship of tumor laterality with various clinical and pathological parameters including angiogenic and hemostatic profiles. A total of 92 women that were initially non-metastatic and treated by surgery were included in this single-center prospective study. Patients were grouped according to tumor localization. A four-year follow-up was accomplished in all patients with a 15.22% recurrence rate. An immunoassay of selected angiogenic and hemostatic parameters, as well as immunohistochemistry of estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and Ki67, was comparatively performed in groups with right- and left-sided IBrC. The same analysis was carried out in a subgroup of patients with luminal A molecular subtype of cancer. Patients with right-sided tumors free of nodal involvement had a significantly longer overall survival compared to their left-sided counterparts (p = 0.0491). Additionally, right-sided tumors had a higher predisposition to be a luminal-A subtype of IBrC (p = 0.0016). Furthermore, 10% of left-sided tumors exhibited an overexpression of HER2, while only 2% patients suffering right-sided tumors displayed a positive score (p = 0.0357). Our findings revealed a significantly higher concentration of vascular endothelial growth factor (VEGF)-A (p = 0.0136), lower anti-angiogenic ratios (sVEGFR1/VEGF-A (p = 0.0208) and sVEGFR2/VEGF-A (p = 0.0068)), and elevated plasminogen activator inhibitor type 1 (PAI-1) (p = 0.0229) in patients with breast cancer localized in the left breast, regardless of the molecular subtype of IBrC. Our study showed that left-sided breast tumors without lymph node metastases demonstrate worse overall survival. Laterality of IBrC is associated with pro-angiogenic and pro-thrombotic conditions. We propose to consider laterality as a prognostic factor of IBrC.

Percutaneous ablation methods are used to treat primary and metastatic liver tumors. Image guided navigation support minimally invasive interventions of rigid anatomical structures. When working with the displacement and deformation of soft tissues during surgery, as in the abdomen, imaging navigation systems are in the preliminary implementation stage. In this study a multi-stage approach has been developed to support percutaneous liver tumors ablation. It includes CT image acquisition protocol with the amplitude of respiratory motion that yields images subjected to a semi-automatic method able to deliver personalized abdominal model. Then, US probe and ablation needle calibration, as well as patient position adjustment method during the procedure for the preoperative anatomy model, have been combined. Finally, an advanced module for fusion of the preoperative CT with intraoperative US images was designed. These modules have been tested on a phantom and in the clinical environment. The final average Spatial calibration error was 1,7 mm, the average error of matching the position of the markers was about 2 mm during the entire breathing cycle, and average markers fusion error 495 mm. The obtained results indicate the possibility of using the developed method of navigation in clinical practice.

Background Indicators of emotional processes (positive experiences with physical exercises) and functional processes (mobility) were previously found to be associated with positive cognitive resources (meaning in life), and the key outcome in the rehabilitation, namely physical quality of life (QOL). Yet, the mediating roles of such processes were not tested. Therefore, this prospective study investigated whether the relationship between meaning in life and physical QOL was mediated by positive experiences with physical exercises and mobility. Methods Prospective data were collected at two measurement points, 1 month apart. A total of N = 339 participants (aged 19–84 years old, 57.9% women) provided data at Time 1 (T1) at the beginning of inpatient rehabilitation from central nervous system diseases (CNSD, e.g., stroke; n = 89) or musculoskeletal system diseases (MSD, e.g., dorsopathies; n = 250), and n = 234 at Time 2 (T2, the end of rehabilitation; 4 weeks after T1). Mediation analysis with meaning in life as predictor (T1), positive experiences with physical exercises and mobility as sequential mediators (T2), and physical QOL (T2) as the outcome was conducted. Results Higher meaning in life (T1) predicted more positive experiences with physical exercises (T2), which were associated with a higher level of mobility (T2), which in turn was associated with better physical quality of life (T2). Conclusions Meaning in life at the beginning of inpatient rehabilitation may trigger positive experiences with physical exercises and functional changes in mobility levels, leading to better physical quality of life. Screening for low meaning in life may allow to identify patients who are at risk for a lack of improvement of mobility and physical quality of life during rehabilitation.

The main aim of this research is presenting an automated image matching methodology being used in the field of medicine for inter- and intraobjectional image matching. This paper shows a different approach avoiding the standard procedures associated with performing four main steps of the registration process: feature detection, feature matching, mapping function design and image transformation with resampling, and replacing them with the fuzzy image concept combined with the use of similarity measures. This methodology has been implemented in MATLAB and tested on clinical T1- and T2-weighted magnetic resonance imaging (MRI) slices of the knee joint in coronal and sagittal plane.

Background Cell therapy constitutes an attractive alternative to treat stress urinary incontinence. Although promising results have been demonstrated in this field, the procedure requires further optimization. The most commonly proposed cell types for intraurethral injections are muscle derived cells (MDCs) and mesenchymal stem/stromal cell (MSCs). The aim of this study was to evaluate the effects of MDC-MSC co-transplantation into the urethra. Methods Autologous transplantation of labeled MDCs, bone marrow MSCs or co-transplantation of MDC-MSC were performed in aged multiparous female goats (n = 6 in each group). The mean number of cells injected per animal was 29.6 × 106(± 4.3 × 106). PBS-injected animals constituted the control group (n = 5). Each animal underwent urethral pressure profile (UPP) measurements before and after the injection procedure. The maximal urethral closure pressure (MUCP) and functional area (FA) of UPPs were calculated. The urethras were collected at the 28th or the 84th day after transplantation. The marker fluorochrome (DID) was visualized and quantified using in vivo imaging system in whole explants. Myogenic differentiation of the graft was immunohistochemically evaluated. Results The grafted cells were identified in all urethras collected at day 28 regardless of injected cell type. At this time point the strongest DID-derived signal (normalized to the number of injected cells) was noted in the co-transplanted group. There was a distinct decline in signal intensity between day 28 and day 84 in all types of transplantation. Both MSCs and MDCs contributed to striated muscle formation if transplanted directly to the external urethral sphincter. In the MSC group those events were rare. If cells were injected into the submucosal region they remained undifferentiated usually packed in clearly distinguishable depots. The mean increase in MUCP after transplantation in comparison to the pre-transplantation state in the MDC, MSC and MDC-MSC groups was 12.3% (± 11.2%, not significant (ns)), 8.2% (± 9.6%, ns) and 24.1% (± 3.1%, p = 0.02), respectively. The mean increase in FA after transplantation in the MDC, MSC and MDC-MSC groups amounted to 17.8% (± 15.4%, ns), 15.2% (± 12.9%, ns) and 17.8% (± 2.5%, p = 0.04), respectively. Conclusions The results suggest that MDC-MSC co-transplantation provides a greater chance of improvement in urethral closure than transplantation of each population alone.

Objective This study tested the reciprocal relationships between automatic thoughts about eating and the actual–ideal weight discrepancies, and their role in the formation and maintenance of eating disorders (ED) symptoms in a non-clinical sample of adolescents. In particular, we investigated whether thoughts about eating mediated the effects of weight discrepancies on ED formation and whether weight discrepancies mediated the effects of thoughts about eating on ED formation were investigated. Method Data were collected three times, with a 2-month interval between Time 1 (T1) and Time 2 (T2), and a 9-month interval between T2 and Time 3 (T3). Adolescents (N = 55) aged 15–18 filled out the SCOFF Questionnaire, assessing eating disorders symptoms, and the Eating Disorder Thoughts Questionnaire, evaluating automatic thoughts. To assess weight discrepancies questions about actual (subjectively reported) and ideal body weight were asked followed by objective measurement of height and weight. Results Negative thoughts about eating (T2) mediated the relation between weight discrepancies (T1) and symptoms of anorexia and bulimia (T3). In addition, the association between negative thoughts (T1) and eating disorders symptoms (T3) was mediated by weight discrepancies (T2). Conclusion The negative thoughts and the actual (both subjectively reported and objectively measured)–ideal weight discrepancies constitute a vicious cycle, related to higher ED symptoms. Prevention of eating disorders should be directed to adolescents who manifest large weight discrepancies or high levels of negative thoughts about eating, as they are at risk for developing eating disorder symptoms.

Objective This study investigated whether the relationships between perceived parental behaviors (dietary behaviors, physical activity, and verbal pressure) and changes in adolescents' body mass index (BMI) were mediated by adolescents' physical activity and dietary behaviors. The associations were tested among overweight and obese adolescents. Design Longitudinal data were collected three times, with a 2-month interval between Time 1 (T1) and Time 2 (T2), and a 13-month interval between T2 and Time 3 (T3) in the group of adolescents (N = 100) aged 13–19. There was no experimental manipulation. Mediation analyses with two sequential mediators were conducted. Main measures Participants completed the questionnaires assessing their dietary behaviors, physical activity (mediators), perceived parental behaviors, and verbal pressure (independent variables). Adolescents' weight and height were measured objectively (with BMI constituting the outcome variable). Results Adolescents who perceived that their parents engaged in a healthy diet and frequent physical activity (T1) self-reported a healthier diet (T2 and T3), higher levels of physical activity (T2 and T3), and their combined index of healthy lifestyle was higher (T2 and T3). In turn, adolescents' behaviors (T2 and T3) were related to lower BMI (T3). Perceived behaviors of parents had a significant, indirect effect on a BMI reduction. There were no effects of the perceived parental verbal pressure (T1) through adolescents' behaviors (T2) on adolescents' BMI (T3). Conclusion Perceived parental modeling of healthy diet and frequent physical activity, but not verbal pressure, predicted adolescents' behaviors (diet, physical activity, and a combined lifestyle index) and, in turn, a reduction in their BMI. The role of parents' health behaviors (diet and physical activity) should be taken into account when considering adolescents' overweight and obesity prevention and treatment programs.

A multi-step methodology resulting in a three-dimensional visualization and construction of feature vector of posterior cruciate ligament is presented. In the first step the location of the posterior cruciate ligament is established using the fuzzy image concept. The fuzzy image concept is based on the entropy measure of fuzziness extended to two dimensions. In order to reduce the area of analysis, the region of interest including the ligament structures is detected. In this case, the fuzzy C -means algorithm with median modification helping to reduce blurred edges was implemented. After finding the region of interest, the fuzzy connectedness procedure was performed. This procedure permitted to extract the ligament structures. On the basis of the extracted posterior cruciate ligament structures, the three-dimensional visualization of this ligament was built and, with the support of experts’ knowledge, an appropriate feature vector was constructed and its values assigned for normal and pathological cases. Correct results were obtained for over 88% of 97 cases.

The crystals of a new aqua-(diethylenetriamine-N, N′, N′′)-copper(II) sulfate monohydrate have been synthesized by direct interaction of solid copper(II) sulfate pentahydrate with diethylenetriamine (deta). The crystal structure of [Cu(deta)H2O]SO4⋅H2O (1) has been determined by X-ray diffraction methods at 100 K and characterized using X-ray powder diffraction pattern: space group P 1 ¯ , a = 7.2819(4), b = 8.4669(4), c = 8.7020(3) A, α = 83.590(3), β = 89.620(4), γ = 84.946(4)°, Z = 2. The environment of the Cu(II) atom is a distorted, elongated square pyramid which consists of three nitrogen atoms of the deta molecule and oxygen atom of the water molecule in the basal plane of the square pyramid (the average lengths of the in-plane Cu–N and Cu–O bonds are 2.00 A). The apical position of the coordination polyhedron is occupied by complementary oxygen atom of the sulfate anion (the length of the axial Cu–O bond is 2.421(1) A). The crystal packing is governed by strong hydrogen bonds of O–H⋯O and N–H⋯O types. The ab initio quantum-chemical calculations have been performed by the restricted Hartree–Fock method with a basis set 6-31∗G using the structural data of [Cu(deta)H2O]SO4⋅H2O. It has been ascertained that the degenerate d-orbitals of the Cu2+ ion split under the co-action of both the square-pyramidal coordination and the chelation. It is significant that visually observed crystals color (blue-violet) of the [Cu(deta)H2O]SO4⋅H2O complex is in good agreement with the calculated value of wavelength of visible light (λ = 5735 A) which is closely related to the energy of the absorbed photon (Δ = 2.161 eV). Furthermore, the stereo-chemical aspect of influence of the CuSO4 upon combustibility of modified epoxy-amine polymers has been scrutinized.

Background This study investigated the relationships between global perfectionism (its functional and dysfunctional aspects) and three types of health behaviors: fruit and vegetable intake (FVI), consumption of sweet and salty snacks, and physical activity. It was hypothesized that indices of functional perfectionism would predict engaging in healthy behavior, with gender moderating these associations. Participants and procedures Data were collected among 845 adolescents (59.20% girls) aged 13 to 20 years old (M = 16.52, SD = 0.92). At the baseline, participants filled out the Frost Multidimensional Perfectionism Scale and measures of nutrition behavior and physical activity. The measurement of nutrition behavior and physical activity was repeated at 12-month follow-up. Results The moderator analysis indicated that FVI as well as consumption of sweet and salty snacks measured at 12-month follow-up were explained by functional global perfectionism (Organization and Personal Standards dimensions), but this effect was stronger among girls. Physical activity measured at 12-month follow-up was explained by functional perfectionism (Organization and Personal Standards dimensions), but this effect was stronger among boys. The effects were found after controlling for respective behaviors assessed at the baseline. Dysfunctional dimensions of global perfectionism (Concern over Mistakes, Parental Expectations, Parental Criticism, Doubts about Actions) were unrelated to indices of behavior at follow-up. Conclusions Functional global perfectionism may represent an individual resource variable, facilitating uptake and maintenance of healthy diet and physical activity, and therefore foster prevention of obesity among adolescents.

Supplemental Digital Content is available in the text, Rationale: According to the World Health Organization reports, adult-onset hearing loss is the 15th leading cause of burden of disease, and is projected to move up to 7th by the year 2030, especially in high-income countries. Sudden sensorineural hearing loss is considered by otologists as a true otologic emergency. The current standard treatment for sudden hearing loss is a tapered course of oral high-dose corticosteroids. The described clinical case points to the validity of undertaking early hyperbaric oxygenation (HBO) therapy together with corticosteroids for full recovery of adult onset idiopathic sudden sensorineural hearing loss. Patient concerns: A 44-year-old woman complained of an abrupt hearing deterioration in the left ear with the sensation of aural fullness and loud tinnitus presented for 48 hours. The patient was admitted to the Department of Otolaryngology of Public Hospital for diagnosis and treatment. Diagnoses: The patient was diagnosed with unilateral sudden idiopathic sensorineural hearing loss, assessed by measuring the tonal audiograms. Interventions: The patient received treatment including oral high-dose corticosteroids combined with HBO protocol including 15 daily 1-hour exposures to 100% oxygen at 2.5 atmosphere absolute. Outcomes: A pharmacotherapy combined with early HBO resulted in full recovery of hearing. Lessons: Early implementation of HBO to the pharmacotherapy in sudden sensorineural hearing loss may lead to full recovery of hearing. There is a need for systematic research to establish guidelines for optimal number of HBO sessions in relation to the timeframe from hearing loss symptoms onset to implementation of HBO therapy.

Thrombosis is one of the leading causes of mortality in cancer patients. The aim of the study was to evaluate the concentrations and activities of selected haemostatic parameters in the plasma of patients diagnosed with breast cancer (BrCa) and to make an attempt at finding associations with their levels and selected clinicopathological factors; clinical classification, histological grading, and molecular subtype of BrCa. The study involved 145 Caucasian ethnicity women. Eighty-five women aged 45–66 with primary BrCa without distant metastases (M0). Inclusion criteria were as follows: histopathological examination confirming the diagnosis of primary BrCa, without previous radiotherapy and chemotherapy. The control group consisted of 60, post-menopausal women, aged 45–68. Haemostatic profile expressed by concentrations and activities of tissue factor (TF) and its inhibitor (TFPI) as well as concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured applying immunoassay techniques. A significantly higher concentration of PAI-1 was noted in patients with BrCa localized in the left breast. We observed significantly lower activity of TFPI and significantly higher concentration of PAI-1 in the group of patients with invasive ductal carcinoma as compared with invasive lobular carcinoma. A significantly higher concentration of t-PA in patients with pT2 BrCa in relation to pT1 cases was noted. Based on comprehensive analysis of haemostatic profile depending on clinicopathological features, we suggest that haemostatic parameters play crucial roles in invasion and metastases of malignant tumours.

Aims The efficacy of cell therapy in patients with stress urinary incontinence (SUI) is lower than expected. The aim of this study was to determine the injection accuracy rate both with transurethral and periurethral route. Methods Autologous intraurethral cell transplantation was performed in female goats. The cells were injected either periurethrally (PERI group, two depots/animal, n = 8) or transurethrally (TRANS group, eight depots/animal, n = 11). Transurethral injections were performed under endoscopic guidance. The number and distribution of cell depots in urethras were analyzed in the three-step protocol: 1) screening of whole explants by in vivo imaging system; 2) systematic microscopic analysis of raw 10 μm cross-sections; 3) immunohistochemistry. As control, four urethras collected 1 day after transurethral transplantation were used. Episodes of cell suspension leakages after needle withdrawal were noted. Results In all experimental animals depots were identified in the urethral wall 28 days after transplantation. The mean percentage of depots located in the urethral wall in relation to all performed injections amounted to 68.7% and 67.0% for PERI and TRANS groups, respectively. The mean proportions of depots which were identified in external urethral sphincter (EUS) amounted 18.8% and 17.1%, respectively. Suspension leakage was observed in 19% of transurethral injections. Conclusions Although majority of cell depots were administrated accurately into the urethral wall, the precise delivery of cells into EUS is limited regardless of injection method. The insufficient accuracy of cell delivery into EUS and cell suspension leakage can contribute to the low efficacy of cell therapy in human patients with SUI.