Benchmarking palliative care practices in neurooncology: a german perspective.

PURPOSE: To benchmark palliative care practices in neurooncology centers across Germany, evaluating the variability in palliative care integration, timing, and involvement in tumor board discussions. This study aims to identify gaps in care and contribute to the discourse on optimal palliative care strategies. METHODS: A survey targeting both German Cancer Society-certified and non-certified university neurooncology centers was conducted to explore palliative care frameworks and practices for neurooncological patients. The survey included questions on palliative care department availability, involvement in tumor boards, timing of palliative care integration, and use of standardized screening tools for assessing palliative burden and psycho-oncological distress. RESULTS: Of 57 centers contacted, 46 responded (81% response rate). Results indicate a dedicated palliative care department in 76.1% of centers, with palliative specialists participating in tumor board discussions at 34.8% of centers. Variability was noted in the initiation of palliative care, with early integration at the diagnosis stage in only 30.4% of centers. The survey highlighted a significant lack of standardized spiritual care assessments and minimal use of advanced care planning. Discrepancies were observed in the documentation and treatment of palliative care symptoms and social complaints, underscoring the need for comprehensive care approaches. CONCLUSION: The study highlights a diverse landscape of palliative care provision within German neurooncology centers, underscoring the need for more standardized practices and early integration of palliative care. It suggests the necessity for standardized protocols and guidelines to enhance palliative care's quality and uniformity, ultimately improving patient-centered care in neurooncology.

Quality of life and olfactory function after suprasellar craniopharyngioma surgery-a single-center experience comparing transcranial and endoscopic endonasal approaches.

The endoscopic endonasal approach to suprasellar craniopharyngiomas has become popular as alternative to transcranial approaches. However, the literature lacks data regarding quality of life and olfactory function. The assessment of the long-term quality of life and olfactory function of all patients harboring a suprasellar craniopharyngioma who underwent surgery in our department has been done. Patient characteristics and perioperative data were gathered in a prospectively maintained database. At the last follow-up visit, the olfactory function and the quality of life (ASBQ, SNOT-22) as well as visual and pituitary function were assessed. Thirteen and 17 patients underwent surgery via a transcranial (T) and endonasal (E) route, respectively. No differences were seen in ASBQ, SNOT-22, and olfactory function between T and E, but in E were more full-time worker and less obesity. CSF leaks occurred in 15% of T and 29% of E (p = 0.43). Patients from group E had a superior visual outcome which was most pronounced in the visual field. The degree of new anterior and posterior pituitary gland deficiency after surgery and in the follow-up was lower in group E. The general and sinonasal quality of life and the olfactory function are equal in E and T. E is associated with a superior visual outcome, lower rates of diabetes insipidus, and lower rates of obesity, but has a higher risk for postoperative CSF leaks.

Depletion of Lipocalin 2 (LCN2) in Mice Leads to Dysbiosis and Persistent Colonization with Segmented Filamentous Bacteria.

Lipocalin 2 (LCN2) mediates key roles in innate immune responses. It has affinity for many lipophilic ligands and binds various siderophores, thereby limiting bacterial growth by iron sequestration. Furthermore, LCN2 protects against obesity and metabolic syndrome by interfering with the composition of gut microbiota. Consequently, complete or hepatocyte-specific ablation of the Lcn2 gene is associated with higher susceptibility to bacterial infections. In the present study, we comparatively profiled microbiota in fecal samples of wild type and Lcn2 null mice and show, in contrast to previous reports, that the quantity of DNA in feces of Lcn2 null mice is significantly lower than that in wild type mice (p < 0.001). By using the hypervariable V4 region of the 16S rDNA gene and Next-Generation Sequencing methods, we found a statistically significant change in 16 taxonomic units in Lcn2-/- mice, including eight gender-specific deviations. In particular, members of Clostridium, Escherichia, Helicobacter, Lactococcus, Prevotellaceae_UCG-001 and Staphylococcus appeared to expand in the intestinal tract of knockout mice. Interestingly, the proportion of Escherichia (200-fold) and Staphylococcus (10-fold) as well as the abundance of intestinal bacteria encoding the LCN2-sensitive siderphore enterobactin (entA) was significantly increased in male Lcn2 null mice (743-fold, p < 0.001). This was accompanied by significant higher immune cell infiltration in the ileum as demonstrated by increased immunoreactivity against the pan-leukocyte protein CD45, the lymphocyte transcription factor MUM-1/IRF4, and the macrophage antigen CD68/Macrosialin. In addition, we found a higher expression of mucosal mast cell proteases indicating a higher number of those innate immune cells. Finally, the ileum of Lcn2 null mice displayed a high abundance of segmented filamentous bacteria, which are intimately associated with the mucosal cell layer, provoking epithelial antimicrobial responses and affecting T-helper cell polarization.

GD2 targeting by dinutuximab beta is a promising immunotherapeutic approach against malignant glioma.

PURPOSE: Disialoganglioside GD2 is expressed by glioblastoma multiforme (GBM) cells representing a promising target for anti-GD2 immunotherapeutic approaches. The aim of the present study was to investigate anti-tumor efficacy of the chimeric anti-GD2 antibody (Ab) dinutuximab beta against GBM. METHODS: Expression levels of GD2 and complement regulatory proteins (CRP; CD46, CD55 and CD59) on well-known and newly established primary tumor originated GBM cell lines were analyzed by flow cytometry. Ab-dependent cellular (ADCC) and complement-dependent cytotoxicity (CDC) mediated by dinutuximab beta against GBM cells were determined by a non-radioactive calcein-AM-based assay. RESULTS: Analysis of primary GBM cells revealed a heterogeneous GD2 expression that varied between the cell lines analyzed with higher expression levels in the tumor surface compared to the core originated cells. Both GD2-positive and -negative tumor cells were detected in every cell line analyzed. In contrast to CDC, ADCC mediated by dinutuximab beta was observed against the majority of GBM cells. Importantly, CDC-resistant cells showed high expression of the CRP CD46, CD55 and CD59. CONCLUSION: Our present data show anti-tumor effects mediated by dinutuximab beta against GBM cells providing a rationale for a GD2-directed immunotherapy against GBM. Due to high CRP expression, a combining of GD2-targeting with CRP blockade might be a further treatment option for GBM.

Endoglin: An 'Accessory' Receptor Regulating Blood Cell Development and Inflammation.

Transforming growth factor-ß1 (TGF-ß1) is a pleiotropic factor sensed by most cells. It regulates a broad spectrum of cellular responses including hematopoiesis. In order to process TGF-ß1-responses in time and space in an appropriate manner, there is a tight regulation of its signaling at diverse steps. The downstream signaling is mediated by type I and type II receptors and modulated by the 'accessory' receptor Endoglin also termed cluster of differentiation 105 (CD105). Endoglin was initially identified on pre-B leukemia cells but has received most attention due to its high expression on activated endothelial cells. In turn, Endoglin has been figured out as the causative factor for diseases associated with vascular dysfunction like hereditary hemorrhagic telangiectasia-1 (HHT-1), pre-eclampsia, and intrauterine growth restriction (IUPR). Because HHT patients often show signs of inflammation at vascular lesions, and loss of Endoglin in the myeloid lineage leads to spontaneous inflammation, it is speculated that Endoglin impacts inflammatory processes. In line, Endoglin is expressed on progenitor/precursor cells during hematopoiesis as well as on mature, differentiated cells of the innate and adaptive immune system. However, so far only pro-monocytes and macrophages have been in the focus of research, although Endoglin has been identified in many other immune system cell subsets. These findings imply a functional role of Endoglin in the maturation and function of immune cells. Aside the functional relevance of Endoglin in endothelial cells, CD105 is differentially expressed during hematopoiesis, arguing for a role of this receptor in the development of individual cell lineages. In addition, Endoglin expression is present on mature immune cells of the innate (i.e., macrophages and mast cells) and the adaptive (i.e., T-cells) immune system, further suggesting Endoglin as a factor that shapes immune responses. In this review, we summarize current knowledge on Endoglin expression and function in hematopoietic precursors and mature hematopoietic cells of different lineages.

WHO grade of intracranial meningiomas differs with respect to patient's age, location, tumor size and peritumoral edema.

PURPOSE: To analyse whether the WHO grade of intracranial meningiomas differs itself depending on patients and meningioma characteristics at diagnosis. METHODS: Single center retrospective study of a series of consecutive patients with primary intracranial meningiomas who underwent surgery between January 2007 and March 2014. Patients (age, sex, outcome) and meningioma characteristics (histological diagnosis, tumor location, WHO grading, size, extend of peritumoral edema and tumor recurrence rate) were analysed. RESULTS: Of 240 included patients, 184 (76.7%) were female and 56 (23.3%) were male. 17 patients (7.1%) were in age group 20-40 years, 112 (46.7%) in group 41-60 years and 111 (46.3%) were in age group > 60 years. 189 patients (78.8%) were diagnosed with WHO grade I, 49 (20.4%) WHO grade II and 2 (0.8%) had a WHO grade III meningioma. WHO grade II meningiomas were significantly more frequent in the age group 20-40 years compared to age group 41-60 years (chi-square p < 0.05). Convexity meningiomas were significantly more frequent classified as WHO grade II meningiomas compared to all other locations (chi-square, p < 0.01). Mean calculated tumor volume and the tumor volume determined by volumetric measurement was significantly larger in grade II meningioma patients compared to grade I (46.3 ± 40.5 cc grade II versus 21.8 ± 27.8 cc grade I and 45.3 ± 38.2 cc versus 23.1 ± 30.0 cc respectively; t test < 0.01). Extend of the peritumoral edema was significantly larger in patients with grade II meningiomas (Wilcoxon test, p < 0.05). Short term outcome did not differ between different age groups nor was it associated with tumor size. During a mean follow up of 49 months (min 3, max 144 months) recurrence rate was significantly higher in WHO grade II (4 out of 49 [8.2]%) compared to WHO grade I patients (3 out if 186, [1.6%]; Chi-square, p < 0.05). CONCLUSION: In this series atypical meningioma was associated with younger age, location on the convexity, larger tumor size and more peritumoral edema.

July 2012 Greenland melt extent enhanced by low-level liquid clouds.

Melting of the world's major ice sheets can affect human and environmental conditions by contributing to sea-level rise. In July 2012, an historically rare period of extended surface melting was observed across almost the entire Greenland ice sheet, raising questions about the frequency and spatial extent of such events. Here we show that low-level clouds consisting of liquid water droplets ('liquid clouds'), via their radiative effects, played a key part in this melt event by increasing near-surface temperatures. We used a suite of surface-based observations, remote sensing data, and a surface energy-balance model. At the critical surface melt time, the clouds were optically thick enough and low enough to enhance the downwelling infrared flux at the surface. At the same time they were optically thin enough to allow sufficient solar radiation to penetrate through them and raise surface temperatures above the melting point. Outside this narrow range in cloud optical thickness, the radiative contribution to the surface energy budget would have been diminished, and the spatial extent of this melting event would have been smaller. We further show that these thin, low-level liquid clouds occur frequently, both over Greenland and across the Arctic, being present around 30-50 per cent of the time. Our results may help to explain the difficulties that global climate models have in simulating the Arctic surface energy budget, particularly as models tend to under-predict the formation of optically thin liquid clouds at supercooled temperatures--a process potentially necessary to account fully for temperature feedbacks in a warming Arctic climate.

ITIH5 induces a shift in TGF-ß superfamily signaling involving Endoglin and reduces risk for breast cancer metastasis and tumor death.

ITIH5 has been proposed being a novel tumor suppressor in various tumor entities including breast cancer. Recently, ITIH5 was furthermore identified as metastasis suppressor gene in pancreatic carcinoma. In this study we aimed to specify the impact of ITIH5 on metastasis in breast cancer. Therefore, DNA methylation of ITIH5 promoter regions was assessed in breast cancer metastases using the TCGA portal and methylation-specific PCR (MSP). We reveal that the ITIH5 upstream promoter region is particularly responsible for ITIH5 gene inactivation predicting shorter survival of patients. Notably, methylation of this upstream ITIH5 promoter region was associated with disease progression, for example, abundantly found in distant metastases. In vitro, stably ITIH5-overexpressing MDA-MB-231 breast cancer clones were used to analyze cell invasion and to identify novel ITIH5-downstream targets. Indeed, ITIH5 re-expression suppresses invasive growth of MDA-MB-231 breast cancer cells while modulating expression of genes involved in metastasis including Endoglin (ENG), an accessory TGF-ß receptor, which was furthermore co-expressed with ITIH5 in primary breast tumors. By performing in vitro stimulation of TGF-ß signaling using TGF-ß1 and BMP-2 we show that ITIH5 triggered a TGF-ß superfamily signaling switch contributing to downregulation of targets like Id1, known to endorse metastasis. Moreover, ITIH5 predicts longer overall survival (OS) only in those breast tumors that feature high ENG expression or inversely regulated ID1 suggesting a clinical and functional impact of an ITIH5-ENG axis for breast cancer progression. Hence, we provide evidence that ITIH5 may represent a novel modulator of TGF-ß superfamily signaling involved in suppressing breast cancer metastasis.

Endoglin in human liver disease and murine models of liver fibrosis-A protective factor against liver fibrosis.

BACKGROUND & AIMS: Liver fibrosis is the outcome of chronic liver injury. Transforming growth factor-ß (TGF-ß) is a major profibrogenic cytokine modulating hepatic stellate cell (HSC) activation and extracellular matrix homeostasis. This study analyses the effect of Endoglin (Eng), a TGF-ß type III auxiliary receptor, on fibrogenesis in two models of liver injury by HSC-specific endoglin deletion. METHODS: Eng expression was measured in human and murine samples of liver injury. After generating GFAPCre(+) EngΔHSC mice, the impact of Endoglin deletion on chronic liver fibrosis was analysed. For in vitro analysis, Engflox/flox HSCs were infected with Cre-expressing virus to deplete Endoglin and fibrogenic responses were analysed. RESULTS: Endoglin is upregulated in human liver injury. The receptor is expressed in liver tissues and mesenchymal liver cells with much higher abundance of the L-Eng splice variant. Comparing GFAPCre(-) Engf/f to GFAPCre(+) EngΔHSC mice in toxic liver injury, livers of GFAPCre(+) EngΔHSC mice showed 39.9% (P < .01) higher Hydroxyproline content compared to GFAPCre(-) Engf/f littermates. Sirius Red staining underlined these findings, showing 58.8% (P < .05) more Collagen deposition in livers of GFAPCre(+) EngΔHSC mice. Similar results were obtained in mice subjected to cholestatic injury. CONCLUSION: Endoglin isoforms are differentially upregulated in liver samples of patients with chronic and acute liver injury. Endoglin deficiency in HSC significantly aggravates fibrosis in response to injury in two different murine models of liver fibrosis and increases α-SMA and fibronectin expression in vitro. This suggests that Endoglin protects against fibrotic injury, likely through modulation of TGF-ß signalling.

Investigation of knee control as a lower extremity injury risk factor: A prospective study in youth football.

This prospective study in youth football examined the relationship between frontal plane knee projection angle (FPKPA) during the single-leg squat and sustaining an acute lower extremity injury or acute non-contact lower extremity injury. Secondly, side-to-side asymmetry in FPKPA and sex as injury risk factors were explored. In addition, we investigated the influence of age, sex, and leg dominance on the FPKPA. A total of 558 youth football players (U11 to U14) participated in the single-leg squat test and prospective injury registration. FPKPA was not found as a risk factor for injuries at this age. There was no difference in the mean FPKPA between sexes. However, FPKPA was associated with age; oldest subjects displayed the smallest FPKPA. Among boys, the frontal plane knee control improved by age. Among girls, the relationship between age and FPKPA was not as clear, but the oldest girls displayed the smallest mean FPKPA in the study (12.2° ± 8.3°). The FPKPA was greater on the dominant kicking leg compared to the non-dominant support leg (P < .001 for boys, P = .001 for girls). However, side-to-side asymmetry in FPKPA was not associated with future injuries. In conclusion, frontal plane knee control in the single-leg squat was not associated with lower extremity injuries among young football players. As the single-leg squat to 90° knee flexion was too demanding for many subjects, easier single-leg squat test procedure or a different movement control test, such as a double-legged squat, could be more suitable for the young football players.

Adenoviral CCN gene transfers induce in vitro and in vivo endoplasmic reticulum stress and unfolded protein response.

The endoplasmic reticulum (ER) is primarily recognized as the site of synthesis and folding of secreted membrane-bound and certain organelle-targeted proteins. Optimum protein folding requires several factors, including ATP, Ca2+ and an oxidizing environment to allow disulphide-bond formation. ER is highly sensitive to stress that perturb cellular energy levels, the redox state or the Ca2+ concentration. Such stresses reduce the protein folding capacity of the ER, resulting in the accumulation and aggregation of unfolded proteins, a condition referred to as unfolded protein response (UPR). Matricellular proteins of the CCN (CYR61, CTGF, NOV) family play essential roles in extracellular matrix signaling and turnover. They exhibit a similar type of organization and share a closely related primary structure, including 38 conserved cysteine residues. Since CCN1/CYR61 overexpression in hepatic stellate cells (HSC) induces ER stress-related apoptosis, we endeavored to investigate whether the adenovirus mediated gene transfer of other members of CCN proteins incurs ER stress in primary HSC and hepatocytes. We found Ad5-CMV-CCN2, Ad5-CMV-CCN3 and Ad5-CMV-CCN4 to induce ER stress and UPR comparable to Ad5-CMV-CCN1. UPR is a pro-survival response to reduce accumulation of unfolded proteins and restore normal ER functioning. If, however protein aggregation is persistent and the stress cannot be resolved, signaling switches from pro-survival to pro-apoptosis. The observed CCN-induced UPR is relevant in wound healing responses and essential for hepatic tissue repair following liver injury. Adenoviral gene transfer induced massive amounts of matricellular proteins proving to effectively mitigate liver fibrosis if targeted cell specific in HSC and myofibroblasts.

ITIH5 mediates epigenetic reprogramming of breast cancer cells.

BACKGROUND: Extracellular matrix (ECM) is known to maintain epithelial integrity. In carcinogenesis ECM degradation triggers metastasis by controlling migration and differentiation including cancer stem cell (CSC) characteristics. The ECM-modulator inter- α-trypsin inhibitor heavy chain family member five (ITIH5) was recently identified as tumor suppressor potentially involved in impairing breast cancer progression but molecular mechanisms underlying its function are still elusive. METHODS: ITIH5 expression was analyzed using the public TCGA portal. ITIH5-overexpressing single-cell clones were established based on T47D and MDA-MB-231 cell lines. Colony formation, growth, apoptosis, migration, matrix adhesion, traction force analyses and polarization of tumor cells were studied in vitro. Tumor-initiating characteristics were analyzed by generating a metastasis mouse model. To identify ITIH5-affected pathways we utilized genome wide gene expression and DNA methylation profiles. RNA-interference targeting the ITIH5-downstream regulated gene DAPK1 was used to confirm functional involvement. RESULTS: ITIH5 loss was pronounced in breast cancer subtypes with unfavorable prognosis like basal-type tumors. Functionally, cell and colony formation was impaired after ITIH5 re-expression in both cell lines. In a metastasis mouse model, ITIH5 expressing MDA-MB-231 cells almost completely failed to initiate lung metastases. In these metastatic cells ITIH5 modulated cell-matrix adhesion dynamics and altered biomechanical cues. The profile of integrin receptors was shifted towards ß1-integrin accompanied by decreased Rac1 and increased RhoA activity in ITIH5-expressing clones while cell polarization and single-cell migration was impaired. Instead ITIH5 expression triggered the formation of epithelial-like cell clusters that underwent an epigenetic reprogramming. 214 promoter regions potentially marked with either H3K4 and /or H3K27 methylation showed a hyper- or hypomethylated DNA configuration due to ITIH5 expression finally leading to re-expression of the tumor suppressor DAPK1. In turn, RNAi-mediated knockdown of DAPK1 in ITIH5-expressing MDA-MB-231 single-cell clones clearly restored cell motility. CONCLUSIONS: Our results provide evidence that ITIH5 triggers a reprogramming of breast cancer cells with known stem CSC properties towards an epithelial-like phenotype through global epigenetic changes effecting known tumor suppressor genes like DAPK1. Therewith, ITIH5 may represent an ECM modulator in epithelial breast tissue mediating suppression of tumor initiating cancer cell characteristics which are thought being responsible for the metastasis of breast cancer.

Knee function among elite handball and football players 1-6 years after anterior cruciate ligament injury.

The aim of the study was to describe objective and self-reported knee function for athletes who have returned to elite handball and football play after an ACL injury, comparing these to non-injured players at the same level. A total of 414 handball and 444 football players completed baseline tests from 2007 through 2014, examining lower extremity strength, dynamic balance, knee laxity, and knee function (KOOS questionnaire). Measures were compared between injured and non-injured legs and between injured legs and legs of controls. Eighty (9.3%) of the 858 players reported a previous ACL injury, 1-6 years post-injury (3.5±2.5 years), 49 handball (61.3%) and 31 football players (38.7%). We found no difference in strength or dynamic balance between previously ACL-injured (N=80) and non-injured players legs (N=1556). However, lower quadriceps (6.3%, 95% CI: 3.2-9.2) and hamstrings muscle strength (6.1%, 95% CI: 3.3-8.1) were observed in previously ACL-injured legs compared to the non-injured contralateral side (N=80). ACL-injured knees displayed greater joint laxity than the contralateral knee (N=80, 17%, 95% CI: 8-26) and healthy knees (N=1556, 23%, 95% CI: 14-33). KOOS scores were significantly lower for injured knees compared to knees of non-injured players. ACL-injured players who have successfully returned to elite sport have comparable strength and balance measures as their non-injured teammates. Subjective perception of knee function is strongly affected by injury history, with clinically relevant lower scores for the KOOS subscores Pain, Function, Sport, and Quality Of Life.

German translation and content validation of the OSTRC Questionnaire on overuse injuries and health problems.

OBJECTIVE: The aim of this study was to translate, culturally adapt and validate the Oslo Sports Trauma Research Centre (OSTRC) Questionnaire on Health Problems into the German context. METHODS: A slightly modified back-translation method was used to translate the questionnaire. Validation was done in 24 high-level Paralympic athletes followed over 20 consecutive weeks. RESULTS: The translated version of the questionnaire showed a very high internal consistency and good test-retest reliability (Cronbach's α 0.92, intraclass correlation coefficient 0.91). Additionally, we observed high acceptance and compliance from our cohort of athletes, whose mean weekly response rate was 91.5%. Overall, 114 training days were lost because of illness or injury within the 20 weeks and, on average, 5 athletes per week (20.8%) reported health problems. CONCLUSIONS: This study demonstrates that the translated German version of the OSTRC Questionnaire is a reliable and valid tool with high internal consistency for the medical monitoring of German athletes. The OSTRC-G now offers the opportunity for a continued surveillance of high-level German athletes.

The anti-fibrotic effects of CCN1/CYR61 in primary portal myofibroblasts are mediated through induction of reactive oxygen species resulting in cellular senescence, apoptosis and attenuated TGF-ß signaling.

UNLABELLED: Cysteine-rich protein 61 (CCN1/CYR61) is a CCN (CYR61, CTGF (connective tissue growth factor), and NOV (Nephroblastoma overexpressed gene)) family matricellular protein comprising six secreted CCN proteins in mammals. CCN1/CYR61 expression is associated with inflammation and injury repair. Recent studies show that CCN1/CYR61 limits fibrosis in models of cutaneous wound healing by inducing cellular senescence in myofibroblasts of the granulation tissue which thereby transforms into an extracellular matrix-degrading phenotype. We here investigate CCN1/CYR61 expression in primary profibrogenic liver cells (i.e., hepatic stellate cells and periportal myofibroblasts) and found an increase of CCN1/CYR61 expression during early activation of hepatic stellate cells that declines in fully transdifferentiated myofibroblasts. By contrast, CCN1/CYR61 levels found in primary parenchymal liver cells (i.e., hepatocytes) were relatively low compared to the levels exhibited in hepatic stellate cells and portal myofibroblasts. In models of ongoing liver fibrogenesis, elevated levels of CCN1/CYR61 were particularly noticed during early periods of insult, while expression declined during prolonged phases of fibrogenesis. We generated an adenovirus type 5 encoding CCN1/CYR61 (i.e., Ad5-CMV-CCN1/CYR61) and overexpressed CCN1/CYR61 in primary portal myofibroblasts. Interestingly, overexpressed CCN1/CYR61 significantly inhibited production of collagen type I at both mRNA and protein levels as evidenced by quantitative real-time polymerase chain reaction, Western blot and immunocytochemistry. CCN1/CYR61 further induces production of reactive oxygen species (ROS) leading to dose-dependent cellular senescence and apoptosis. Additionally, we demonstrate that CCN1/CYR61 attenuates TGF-ß signaling by scavenging TGF-ß thereby mitigating in vivo liver fibrogenesis in a bile duct ligation model. CONCLUSION: In line with dermal fibrosis and scar formation, CCN1/CYR61 is involved in liver injury repair and tissue remodeling. CCN1/CYR61 gene transfer into extracellular matrix-producing liver cells is therefore potentially beneficial in liver fibrotic therapy.

Sports injuries and illnesses during the European Youth Olympic Festival 2013.

BACKGROUND: The European Youth Olympic Festival (EYOF) is a biennial sporting event of nine Olympic Summer Sports for talented athletes, aged 13-18 years, from all over Europe. OBJECTIVE: To analyse the injuries and illnesses that occurred during the multisport event (14-19 July 2013), with the long-term aim of enabling international sports federations, the National Olympic Committees, and the European Olympic Committee to improve protection of athletes' health in youth. METHODS: Daily occurrence or non-occurrence of injuries and illnesses was recorded by using the IOC injury and illness surveillance system for multisport events. All National Olympic Committee physicians and healthcare providers and physicians of the Local Organizing Committee were invited to participate. RESULTS: In total, 2272 athletes from 49 countries took part in the EYOF 2013. During the five competition days of EYOF, 207 injuries and 46 illnesses were reported, resulting in an incidence of 91.1 injuries and 20.2 illnesses per 1000 athletes. Almost 10% of the athletes sustained at least one injury or illness. CONCLUSIONS: This study is the first multisport surveillance study on injuries and illnesses during the EYOF or any other summer Games organised for youth elite athletes. The data form the basis for further research on risk factors and injury mechanisms for this cohort. This research is needed to gain more knowledge and finally to implement effective injury and illness prevention measures.

Forest biodiversity monitoring for REDD+: a case study of actors' views in Peru.

The climate change mitigation mechanism Reducing Emissions from Deforestation and Forest Degradation in developing countries (REDD+) is currently being negotiated under the United Nations Framework Convention on Climate Change (UNFCCC). Integrating biodiversity monitoring into REDD+ facilitates compliance with the safeguards stipulated by the UNFCCC to exclude environmental risks. Interviews with actors engaged in REDD+ implementation and biodiversity conservation at the national and sub-national level in Peru (n = 30) and a literature review (n = 58) were conducted to pinpoint constraints and opportunities for monitoring effects of REDD+ management interventions on biodiversity, and to identify relevant biodiversity data and indicators. It was found that particularly sub-national actors, who were frequently involved in REDD+ pilot projects, acknowledge the availability of biodiversity data. Actors at both the national and sub-national levels, however, criticized data gaps and data being scattered across biodiversity research organizations. Most of the literature reviewed (78 %) included indicators on the state of certain biodiversity aspects, especially mammals. Indicators for pressure on biodiversity, impacts on environmental functions, or policy responses to environmental threats were addressed less frequently (31, 21, and 10 %, respectively). Integrating biodiversity concerns in carbon monitoring schemes was considered to have potential, although few specific examples were identified. The involvement of biodiversity research organizations in sub-national REDD+ activities enhances monitoring capacities. It is discussed how improvements in collaboration among actors from the project to the national level could facilitate the evaluation of existing information at the national level. Monitoring changes in ecosystem services may increase the ecological and socioeconomic viability of REDD+.

Dynamics of anti-Toxoplasma gondii antibodies and seroconversion during pregnancy and lactation in naturally infected goats.

The objective of this work was to evaluate the dynamics of anti-T. gondii antibodies and seroconversion in naturally infected goats from the last third of pregnancy to 100 days of lactation and relate it to hematological and dehydration parameters. Blood samples were obtained from 56 goats in the different physiological states (pregnancy, kidding and lactation) as in different years (2019, 2021 and 2022). A total of 266 serum samples were obtained and evaluated by indirect fluorescent antibody test (IFAT) to end titer. The overall T. gondii seropositivity was 80.4% (45/56), with titers ranging from 100 to 25.600. The goats older than 3 years (4967 ± 1329) had significantly higher IFAT titers than the younger goats (2705 ± 681). The highest rate of positive seroconversion 31.1% (14/45) was found between kidding and 70 days of lactation; and of negative seroconversion 28.9% (13/45) between late pregnancy and kidding. The highest proportion of slightly dehydrated animals was found in the last third of pregnancy (14/25) and kidding (9/28). The correlation between seroconversion and T. gondii antibody titers was negative to the established dehydration index. These data suggest that in all physiological states and at different ages of goats, there is seroconversion which is not related to hydration status. Pregnancy, kidding and peak of lactation are stressful physiological periods, facilitating the reactivation of chronic T. gondii infections which are expressed by higher antibodies titers.

The impact of mental health on health-related quality of life in patients with NF2-related Schwannomatosis.

NF2-related schwannomatosis (NF2-SWN) is a rare genetic disorder and is associated with progressive morbidities. This study aimed to investigate the relationship between NF2-SWN disease severity, health-related Quality of Life (QoL), and mental health aspects of patients. Standardised questionnaires assessing mental health problems (symptoms of depression, anxiety, and somatic burden), psychological factors (resilience, loneliness, and personality functioning), and health-related QoL were administered to 97 patients with NF2-SWN. The results of these questionnaires were compared with physician-rated disease severity. Questionnaires were completed by 77 patients. Physician-rated disease severity scores were available for 55 patients. NF2-SWN patients showed a high prevalence of clinically relevant symptoms of depression (30%), anxiety (16%), and somatic burden (32%). Almost all variables showed moderate to high correlations with NF2-SWN-related QoL. NF2-SWN-related QoL was associated with physician-reported disease severity (r = 0.614). In the stepwise hierarchical linear regression analysis, a significant model with four predictors (disease severity type, depression symptoms, personality functioning, and gender) explained 64% of the variance in NF2-SWN-related QoL. Our results showed a strong association between NF2-SWN-related QoL and depression symptoms. Moreover, personality functioning is an important influencing factor, representing a modifiable construct that can be targeted by prevention programs or psychotherapy.