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This review aims to emphasize new insights into the diagnosis, classification, and therapy of bladder cancer (BC). Bladder cancer is a heterogeneous, complex disease on a morphological, molecular, diagnostic, and prognostic level. Cancer stage is still the most important attribute for prognosis and treatment, while early detection with optimal and rapid individual therapeutic and surveillance approach is crucial. The vast majority of patients have a superficial, non-muscle-invasive tumor associated with a good prognosis after resection and adjuvant intravesical maintenance immuno or chemotherapy if needed. On the other hand, muscle-invasive bladder cancer is a highly aggressive disease with high morbidity and mortality. However, it has become a model for oncology success over the last five years with many available targeted therapeutic modalities. Metastatic BC is now amenable to multimodal treatment combining cystectomy and neoadjuvant chemotherapy and immunotherapy and is a target for precision medicine.Conclusion. A new molecular taxonomy for bladder cancer has been proposed and provided insight into BC’s carcinogenesis, with some possible effects on therapy decisions. However, this classification is still not applicable in routine clinical practice. It opens new questions regarding the interplay between tumor genetic signature, intratumoral heterogeneity, therapy implications, and tumor progression.

Neuroendocrine breast cancer (NEBC) is a group of rare tumors, which could benefit from therapy targeting the somatostatin receptors (SSTRs). In particular, SSTR2A and SSTR5 are potential targets given their consistent expression in gastrointestinal and pancreatic primary and metastatic neuroendocrine cancers. Currently, there are no studies describing the expression of SSTRs in NEBC. The purpose of our study was to characterize the immunohistochemical expression of SSTR2A and SSTR5 in a cohort of NEBC. Thirty-one primary NEBC cases were analyzed, and SSTR2A and SSTR5 immunohistochemistry performed and scored using the modified immunoreactive score proposed by Remmele and Stanger. All patients were females with a mean age of 66.6 years (SD = 14). 77% of cases were histological grade 2. SSTR2A showed a weak positivity in 11 cases (35.5%), moderate positivity in 6 cases (19.4%) and strong positivity in 5 cases (16.1%). Nine cases were negative for SSTR2A (29%). SSTR5 showed a weak positivity in 16 cases (51.6%), moderate positivity in 6 cases (19.4%), while no cases showed strong positivity. Nine cases were negative for SSTR5 (29%). Five cases were negative for both SSTR2A and SSTR5. A weak to moderate SSTR2A and SSTR5 expression was observed in 50–70% of the cases. A subset of NEBCs with strong SSR2A expression may benefit from SSTRs targeted therapy. These results need further validation in a larger series including metastatic NEBC, to provide potential therapeutic targets for patients with advanced disease.

We investigated whether the perceived angular velocity following velocity steps of 80°/s in the dark decreased with the repetition of the stimulation in the same direction. The perceptual response to velocity steps in the opposite direction was also compared before and after this unidirectional habituation training. Participants indicated their perceived angular velocity by clicking on a wireless mouse every time they felt that they had rotated by 90°. The prehabituation perceptual response decayed exponentially with a time constant of 23.9 s. After 100 velocity steps in the same direction, this time constant was 12.9 s. The time constant after velocity steps in the opposite direction was 13.4 s, indicating that the habituation of the sensation of rotation is not direction specific. The peak velocity of the perceptual response was not affected by the habituation training. The differences between the habituation characteristics of self-motion perception and eye movements confirm that different velocity storage mechanisms mediate ocular and perceptual responses.

Sustainable development (SD) is a multidimensional issue. However, research findings report a divide between students&rsquo, awareness and behavior. It is identified that study programs are designed more for awareness outcomes, and not so much for behavioral outcomes. For higher-order learning outcomes manifested in a sustainable development behavior, the authors argue for a model based on an understanding of learning as boundary crossing. Based on this model, learning for sustainable development occurs in relating social practices, lifestyles, academic practices, professional practices, and students&rsquo, digital practices. To inform teachers&rsquo, approaches to teaching as an important driver of institutional change, we conducted a survey among students of urban and spatial planning in Slovenia. Examined factors included personal, academic, and digital predictors for sustainable development awareness, lifestyle, and behavioral intention. We hypothesized that a significant predictor for sustainable development behavior, which was measured as sustainable lifestyle and sustainable development behavioral intention, would be learning in social practices, and that learning in social practices would predict preferred teaching methods. The findings of hierarchical regression analysis indicated personal factors as the most important predictors of SD behavioral intention, and academic predictors as the most important factors for SD awareness. Digital practices were found to be the most important predictors of a sustainable lifestyle. Social practices of sustainable lifestyle, digital practices, and perceived teaching methods predicted students&rsquo, preferred teaching methods. We discuss the future directions of sustainable development education, considering digital social media practices as essential boundary crossers.

Inflammatory bowel disease (IBD) has been associated with the development of both gastrointestinal and extraintestinal malignancy. The role of therapy in the development of malignancy in IBD has been controversial. We present the case of a 40-year-old female patient with long-standing mild IBD, who developed an undifferentiated pleomorphic sarcoma of the inguinal region and provide a brief review of the relevant literature. While our case likely represents a coincidence of two unrelated pathological entities, clinicians should keep in mind the possibility of soft tissue sarcomas in patients chronically treated with anti-inflammatory agents.

The microgravity ocular syndrome (MOS) results in significant structural and functional ophthalmic changes during 6-mo spaceflight missions consistent with an increase in cerebrospinal fluid (CSF) pressure compared with the preflight upright position. A ground-based study was performed to assess two of the major hypothesized contributors to MOS, headward fluid shifting and increased ambient CO2, on intracranial and periorbital CSF. In addition, lower body negative pressure (LBNP) was assessed as a countermeasure to headward fluid shifting. Nine healthy male subjects participated in a crossover design study with five head-down tilt (HDT) conditions: −6, −12, and −18° HDT, −12° HDT with −20 mmHg LBNP, and −12° HDT with a 1% CO2 environment, each for 5 h total. A three-dimensional volumetric scan of the cranium and transverse slices of the orbita were collected with MRI, and intracranial CSF volume and optic nerve sheath diameter (ONSD) were measured after 4.5 h HDT. ONSD increased during −6° ( P < 0.001), −12° ( P < 0.001), and −18° HDT ( P < 0.001) and intracranial CSF increased during −12° HDT ( P = 0.01) compared with supine baseline. Notably, LBNP was able to reduce the increases in ONSD and intracranial CSF during HDT. The addition of 1% CO2 during HDT, however, had no further effect on ONSD, but rather ONSD increased from baseline in a similar magnitude to −12° HDT with ambient air ( P = 0.001). These findings demonstrate the ability of LBNP, a technique that targets fluid distribution in the lower limbs, to directly influence CSF and may be a promising countermeasure to help reduce increases in CSF. NEW & NOTEWORTHY This is the first study to demonstrate the ability of lower body negative pressure to directly influence cerebrospinal fluid surrounding the optic nerve, indicating potential use as a countermeasure for increased cerebrospinal fluid on Earth or in space.

Self-inflicted or factitious injuries of the oral mucosa are not rare and may appear in various forms often mimicking other oral lesions. Detailed medical history and clinical examination will usually reveal the underlying cause of the injury. However, if the patient is not aware of the bad habit, it will take longer for the dentist to figure out the underlying cause. Treatment relies on the elimination of the bad habit and lesions could be easily treated with topical corticosteroids in orabase. However, no therapy is successful unless patient does not stop the factitious habit. This article emphasizes that certain lesions of the oral mucosa might result from the self-inflicted habits of which patient is sometimes unaware of.

Participants on spaceflights and international scientific analog Mars missions can encounter medical incidents (accidents, illnesses) and psychological issues (e.g., stress, group interaction, sleep disturbance, emotions). The aim of this study was to examine these parameters in a field crew living in a desert environment similar to Mars (Group 1) and in Mission Support Center (MSC) personnel on "Earth" (Group 2) during a 4-week mission. Of the 107 medical interventions in the field, 73 mainly minor incidents together with four near accidents and 29 medical checkup interventions were recorded. Of the 32 medical interventions, medical treatments for 23 incidents of minor severity were necessary in Group 2. Injuries (Group 1: 1.4/100 h, Group 2: 0.1/100 h) were significantly increased in the field, and illnesses (Group 1: 0.3/100 h, Group 2: 3.0/100 h) in the MSC personnel. Causes of accidents and illnesses are described. Psychological results show that emotions and stress remained stable in both groups. Sympathy, social competence, teamwork, and leadership showed high scores. These scores were lower on "Earth" but significantly increased in the last weeks. The Sahara's nighttime coldness was reflected in an increased wake-up frequency, and a longer sleeping time peaked in the third week, probably as a result of overfatigue. MARS2013 was a successful mission with highly motivated participants and minor medical incidents. For future analog missions and possibly long-distance open-space missions, some recommendations in terms of medical and psychological preparedness are made to reduce risks for field crew members and MSC personnel.

On future human Mars missions, surface sojourn duration and resources will be limited. One possibility to approach a positive cost-benefit ratio of a human Mars mission will be to maximize the scientific research on the martian surface within the operational, environmental, and experimental limitations. Sophisticated mission operations and advanced planning strategies will be a basic requirement for Mars exploration and make operational methods an important research subject during current Mars analog missions conducted by the Austrian Space Forum. The Morocco Mars analog field simulation MARS2013, with a duration of 4 weeks and a simulated time delay of 10 min for communication between field and mission support, was the most advanced Mars analog mission conducted by the Austrian Space Forum so far. Due to these constraints, planning strategies based on real-time adjustments and ground control were not applicable, leading to the development of the "3-days-in-advance" planning strategy. Applying this methodology, 45.7% of the total EVA time was used for scientific experiments that satisfied 75.8% of the planned science goals. Taking into account all activities (donning of the suits included), the fraction of time used for scientific experiments made up only one-third of the total time, whereas it was planned to be above 50%. Here, we present details on the application of the 3-days-in-advance planning and on the results of the efficiency analysis of MARS2013.

Background The hypothalamus is a brain structure involved in the neuroendocrine aspect of stress and anxiety. Evidence suggests that generalized anxiety disorder (GAD) and panic disorder (PD) might be accompanied by dysfunction of the hypothalamus-pituitary-adrenal axis (HPA), but so far structural alterations were not studied. We investigated hypothalamic volumes in patients with either GAD or PD and in healthy controls. Methods Twelve GAD patients, 11 PD patients and 21 healthy controls underwent a 1.5T MRI scan. Hypothalamus volumes were manually traced by a rater blind to subjects' identity. General linear model for repeated measures (GLM-RM) was used to compare groups on hypothalamic volumes, controlling for total intracranial volume, age and sex. Results The hypothalamus volume was significantly reduced ( p =0.04) in GAD patients, with significant reductions in both the left ( p =0.02) and right side ( p =0.04). Patients with PD did not differ significantly ( p =0.73). Anxiety scores were inversely correlated with hypothalamic volumes. Limitations The small sample size could reduce the generalizability of the results while the lack of stress hormone measurements renders functional assessment of the hypothalamus-pituitary-adrenal axis not feasible. Conclusions The present study showed decreased hypothalamic volumes in GAD patients but not in those with PD. Future longitudinal studies should combine volumetric data with measurements of stress hormones to better elucidate the role of the HPA axis in GAD.

Hypothalamic abnormalities in schizophrenia have been associated with endocrine dysfunctions and stress response. The hypothalamus is involved in several pathways found disrupted in schizophrenia (e.g., hypothalamic-pituitary-adrenal axis, HPA axis) ; however the available results on potential structural hypothalamic alterations are still controversial. The aim of the study was to investigate the volumes of the hypothalamus and the mammillary bodies in patients with schizophrenia and healthy controls. Twenty-six patients with schizophrenia and 26 healthy controls underwent a 3 Tesla magnetic resonance imaging (MRI) scan. Hypothalamus and mammillary bodies were manually traced by a rater who was blind to subjects' identity. The General Linear Model was used in group comparisons of the volumes of the hypothalamus and the mammillary bodies. The hypothalamus and mammillary body volumes were significantly larger in patients with schizophrenia than controls, with significant enlargement of the left hypothalamus and trends for significantly increased right hypothalamus and right mammillary body. The size of the mammillary bodies was inversely correlated with negative symptoms and directly correlated with anxiety. This study showed abnormally increased sizes of the hypothalamus and the mammillary bodies in schizophrenia. Mammillary bodies volumes were associated to negative symptoms and anxiety. Future longitudinal studies on the volumes of the hypothalamus and the mammillary bodies with respect to the levels of related hormones will clarify their role in modulating HPA axis in schizophrenia.

This thesis investigates the spoken L3 German of Swedish CLIL learners in lower secondary school (grades 8-9) in comparison to Swedish non-CLIL controls and German native speakers; its main objective is to investigate whether the CLIL approach has a positive impact on L3 production. The study deals with vocabulary size and frequency in the spoken lexicon as well as communicative strategies and is based on data consisting of narratives elicited through the retelling of Mayer’s well-known picture story Frog, where are you? Material was also elicited in the learners’ L1 Swedish and in their L2 English. In addition to being contrastive, the study is also longitudinal, in the sense that recordings of the learners’ foreign language spoken productions were made twice, as opposed to those of their L1 Swedish or the L1 German of the native speaker control group. Albeit both learner groups dispose of a rather limited lexical production compared with the German native speakers, the analysis of vocabulary size shows that the L3 narratives of the CLIL learners are not only longer, but also more varied and thus have a greater lexical richness than those of the non-CLIL controls. There seems to be no clear correlation between the L1 and the L3 productions, neither for the CLIL group nor for the non-CLIL group, which is to say that the progress in the L3 cannot be directly linked to L1 proficiency. Similar positive results for the CLIL group were observed in the L2 English narratives, which may indicate an impact of CLIL on enhanced skills in other foreign languages. In the investigation vocabulary frequency, the analysis points to a higher level of L3 German proficiency for the CLIL group, in that they show a higher number of synsemantic words (such as e.g. pronouns and cohesive ties) and a lower number of basic, so-called nuclear verbs and adjectives. Again, the same positive tendencies could be seen in their L2 English. The analysis of the employment of communication strategies (CS) among the Swedish learners indicates that both learner groups experience communication problems in their L3 German and thus resort to CS. However, the use of L3-based, so-called positive CS is much more frequent among the CLIL learners, whereas their non-CLIL peers display a clearly predominant use of L1-based, so-called negative CS. In contrast to earlier Swedish CLIL evaluations of L2 English, this study points to a positive influence of CLIL on spoken L3 German. Even though no statistically significant results could be obtained due to the fairly small size of the test groups, clear gains are visible in all aspects examined, i.e. vocabulary size, vocabulary frequency and communication strategies. There are several pedagogical implications of this study concerning successful classroom L3 learning. Most importantly, the number of L3 CLIL projects should be enhanced in order to boost progress in L3 skills. Thus, a CLIL module (encompassing e.g. connection between input/output, lexical acquisition and communication strategy use) should be introduced in the teacher education programme for traditional FL education to benefit from. Furthermore, there were no drop-outs during the period of investigation in comparison to a drop-out rate of approx. 35 per cent among the controls, which may suggest that CLIL also fosters motivation for FL learning.

Background A combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DWI) was applied to investigate the neurodevelopment of gray and white matter in autism. Methods Twenty children with autism (mean age = 7 ± 2.75 years old; age range: 4–14; 2 girls) and 22 matched normally developing children (mean age = 7.68 ± 2.03 years old; age range: 4–11; 2 girls) underwent magnetic resonance imaging (MRI). VBM was employed by applying the Template-o-Matic toolbox (TOM), a new approach which constructs the age-matched customized template for tissue segmentation. Also, the apparent diffusion coefficients (ADC) of water molecules were obtained from the analysis of DWI. Regions of interests (ROIs), standardized at 5 pixels, were placed in cortical lobes and corpus callosum on the non-diffusion weighted echo-planar images ( b = 0) and were then automatically transferred to the corresponding maps to obtain the ADC values. Results Compared to normal children, individuals with autism had significantly: (1) increased white matter volumes in the right inferior frontal gyrus, the right fusiform gyrus, the left precentral and supplementary motor area and the left hippocampus, (2) increased gray matter volumes in the inferior temporal gyri bilaterally, the right inferior parietal cortex, the right superior occipital lobe and the left superior parietal lobule, and (3) decreased gray matter volumes in the right inferior frontal gyrus and the left supplementary motor area. Abnormally increased ADC values in the bilateral frontal cortex and in the left side of the genu of the corpus callosum were also reported in autism. Finally, age correlated negatively with lobar and callosal ADC measurements in individuals with autism, but not in children with normal development. Conclusions These findings suggest cerebral dysconnectivity in the early phases of autism coupled with an altered white matter maturation trajectory during childhood potentially taking place in the frontal and parietal lobes, which may represent a neurodevelopmental marker of the disorder, possibly accounting for the cognitive and social deficits.

The nomenclature of 14 taxa from Central and Southern Europe within the Dianthus virgineus group is discussed. Dianthus aggericola Jord., D. collivagus Jord., D. consimilis Jord., D. orophilus Jord., D. saxicola Jord., D. juratensis Jord. are here lectotypified by specimens from the Jordan herbarium in LY, while D. godronianus Jord. by a specimen in P. Dianthus subacaulis Vill. is neotypified by a specimen collected on Mont Ventoux (S. France) and housed in MPU. For D. sylvestris Wulfen, a lectotype is here designated and its previous neotypification is discussed. Dianthus caryophyllus var. tenuifolius Moris, D. caryophyllus f. minor Moris and D. sylvestris var. garganicus Ten. are lectotypified by specimens housed in herbarium Moris (TO) and herbarium Tenore (K). Dianthus virgineus var. tergestinus Rchb. is lectotypified by a drawing from the Icones florae Germanicae & Helveticae, while D. contractus var. evolutus Lojac. is neotypified by a specimen in P. For each taxon the currently accepted name is provided including new synonymies. The type indication is followed by nomenclatural and taxonomic notes, in which the original material found is commented and the reasons for the identification of the types are discussed.