Efficacy and tolerance of oral versus parenteral cyanocobalamin supplement in hypocobalaminaemic dogs with chronic enteropathy: a controlled randomised open-label trial.

OBJECTIVES: Determine comparative tolerance of daily oral and weekly parenteral cobalamin supplementation, in hypocobalaminaemic dogs with chronic enteropathy. Determine whether oral is as effective as parenteral supplementation at achieving eucobalaminaemia, in hypocobalaminaemic dogs with protein-losing enteropathy, severe hypocobalaminaemia or high canine inflammatory bowel disease activity index at inclusion. MATERIALS AND METHODS: Thirty-seven client-owned dogs with hypocobalaminaemia and clinical signs of chronic enteropathy were prospectively enrolled in three UK referral centres. Dogs were randomly allocated to daily oral for 12 weeks or weekly parenteral cobalamin supplementation for 6 weeks and one additional dose 4 weeks later. Serum cobalamin, body condition score, canine inflammatory bowel disease activity index and bodyweight were assessed at inclusion, weeks 7 and 13. Serum methylmalonic acid concentration was evaluated at inclusion and at week 13. Owners completed treatment adherence, palatability, tolerance and satisfaction questionnaires at week 13. RESULTS: Nineteen dogs completed the study. All dogs orally supplemented achieved normal or increased cobalaminaemia at weeks 7 and 13. There was no statistical difference in cobalamin concentration at week 13 in dogs treated with oral or parenteral supplementation, regardless of presence of protein-losing enteropathy, severity of hypocobalaminaemia or canine inflammatory bowel disease activity index at inclusion. Serum methylmalonic acid concentration was not significantly different between oral and parenteral groups, neither were treatment adherence, satisfaction, and tolerance scores at week 13. CLINICAL SIGNIFICANCE: Oral is as effective and as well-tolerated as parenteral cobalamin supplementation in hypocobalaminaemic dogs with chronic enteropathy and severe clinical or biochemical phenotypes, and should be considered as a suitable treatment option regardless of disease severity.

Tumor-agnostic plasma assay for circulating tumor DNA detects minimal residual disease and predicts outcome in locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Forty to fifty percent of patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) relapse despite multimodal treatment. Circulating tumor DNA (ctDNA) has the potential to detect minimal residual disease (MRD) after curative-intent therapy and to identify earlier which patients will progress. We developed a tumor-agnostic plasma ctDNA assay to detect MRD in unselected LA SCCHN with the aim of predicting progression-free survival (PFS) and overall survival without the need for tumor sequencing. PATIENTS AND METHODS: A 26-gene next-generation sequencing panel was constructed that included the most frequently mutated genes in SCCHN and two HPV-16 genes. MRD was assessed in each patient through an in-house informatic workflow informed by somatic mutations identified in the corresponding pre-treatment plasma sample. The presence of MRD was defined as the detection of ctDNA in one plasma sample collected within 1-12 weeks of the end of curative treatment. The primary endpoint was the PFS rate at 2 years. At least 32 patients were planned for inclusion with the hypothesis that PFS at 2 years was >80% in MRD-negative patients and <30% in MRD-positive patients (α = 0.05, ß = 0.9). RESULTS: We sequenced DNA from 116 plasma samples derived from 53 LA SCCHN patients who underwent curative-intent treatment. ctDNA was detected in 41/53 (77%) patients in the pre-treatment samples. Out of these 41 patients, 17 (41%) were MRD positive after treatment. The 2-year PFS rate was 23.53% (9.9% to 55.4%) and 86.6% (73.4% to 100%) in MRD-positive and MRD-negative patients, respectively (P < 0.05). Median survival was 28.37 months (14.30 months-not estimable) for MRD-positive patients and was not reached for the MRD-negative cohort (P = 0.011). CONCLUSIONS: Our ctDNA assay detects MRD in LA SCCHN and predicts disease progression and survival without the need for tumor sequencing, making this approach easily applicable in daily practice.

Incidence and presentation of new-onset type 1 diabetes in children and adolescents from Germany during the COVID-19 pandemic 2020 and 2021: Current data from the DPV Registry.

AIMS: To determine whether the incidence of type 1 diabetes mellitus (T1D), autoantibody-negative diabetes, and diabetic ketoacidosis (DKA) at diabetes onset in 2020 and 2021 changed when compared to long-standing trends. METHODS: Our study is based on diabetes manifestation data of the 0.5-<18-year-old children/adolescents from the German multicenter Diabetes Prospective Follow-up Registry. Based on long-term pre-pandemic trends from 2011 to 2019, we estimated adjusted incidence rate ratios (IRR) for T1D and DKA, and prevalence rate ratios (PRR) regarding autoantibody status with 95 % confidence intervals (CI) for the years 2020 and 2021 (observed versus predicted rates), using multivariable negative binomial or beta-binomial regression, respectively. RESULTS: We analyzed data of 30,840 children and adolescents with new-onset T1D. The observed incidences were significantly higher than the predicted incidences (IRR2020 1.13 [1.08-1.19]; IRR2021 1.20 [1.15-1.26]). The prevalence of autoantibody-negative diabetes did not change (PRR2020 0.91 [0.75-1.10]; PRR2021 1.03 [0.86-1.24]). The incidence of DKA during the pandemic was higher than predicted (IRR2020 1.34 [1.23-1.46]; IRR2021 1.37 [1.26-1.49]). CONCLUSIONS: An increase in the incidences of T1D and DKA, but not of autoantibody-negative diabetes was observed during both pandemic years. Further monitoring and efforts for DKA prevention at onset are necessary.

Temporary threshold shift after noise exposure in hypobaric hypoxia at high altitude: results of the ADEMED expedition 2011.

OBJECTIVES: To evaluate whether there is an increased risk for noise-induced hearing loss at high altitude rsp. in hypobaric hypoxia. METHODS: Thirteen volunteers got standard audiometry at 125, 250, 500, 750, 1000, 1500, 2000, 3000, 4000, 6000, and 8000 Hz before and after 10 min of white noise at 90 dB. The system was calibrated for the respective altitude. Measurements were performed at Kathmandu (1400 m) and at Gorak Shep (5300 m) (Solo Khumbu/Nepal) after 10 days of acclimatization while on trek. Temporary threshold shift (TTS) was analyzed by descriptive statistics and by factor analysis. RESULTS: TTS is significantly more pronounced at high altitudes. Acclimatization does not provide any protection of the inner ear, although it increases arterial oxygen saturation. CONCLUSION: The thresholds beyond which noise protection is recommended (> 80 dB) or necessary (> 85 dB) are not sufficient at high altitudes. We suggest providing protective devices above an altitude of 1500 m ("ear threshold altitude") when noise level is higher than 75 dB and using them definitively above 80 dB. This takes the individual reaction on hypobaric hypoxia at high altitude into account.

Proposal for rational antibacterial use in the diagnosis and treatment of dogs with chronic diarrhoea.

Chronic diarrhoea is a frequent complaint in canine practice and the diagnostic path is often characterised by numerous diagnostic tests and stepwise empirical treatments, often applied before gastrointestinal endoscopy/mucosal biopsies. These include dietary interventions (novel protein, hydrolysed protein diet), parasiticides and still, in many cases, antibacterials. Indiscriminate use of antibacterial drugs risks detrimental consequences for both the individual patient (antimicrobial resistance, long-term disruption of intestinal bacterial populations, potential worsening of gastrointestinal signs) and the general public. For that reason, in this Perspective essay we advocate use of antibacterials only after histopathologic evaluation of gastrointestinal biopsies or, for those cases in which endoscopy is not possible, after other therapeutic trials, such as diet/pre-probiotics or anti-inflammatory drugs have proven unsuccessful. They should be reserved, after appropriate dietary trials, for those canine chronic diarrhoeic patients with signs of true primary infection (i.e. signs of systemic inflammatory response syndrome or evidence of adherent-invasive bacteria) that justify antibacterial use.

Superior biocompatibility and comparable osteoinductive properties: Sodium-reduced fluoride-containing bioactive glass belonging to the CaO-MgO-SiO2 system as a promising alternative to 45S5 bioactive glass.

Bioactive glasses (BGs) are promising bone substitute materials. However, under certain circumstances BGs such as the well-known 45S5 Bioglass® (composition in wt%: 45.0 SiO2, 24.5 Na2O, 24.5 CaO, 6.0 P2O5) act cytotoxic due to a strong increase in pH caused by a burst release of sodium ions. A potential alternative is a sodium-reduced fluoride-containing BG belonging to the CaO-MgO-SiO2 system, namely BG1d-BG (composition in wt%: 46.1 SiO2, 28.7 CaO, 8.8 MgO, 6.2 P2O5, 5.7 CaF2, 4.5 Na2O), that has already been evaluated in-vitro, in-vivo and in preliminary clinical trials. Before further application, however, BG1d-BG should be compared to the benchmark amongst BGs, the 45S5 Bioglass® composition, to classify its effect on cell viability, proliferation and osteogenic differentiation of human mesenchymal stem cells (MSCs). Therefore, in this study, the biocompatibility and osteogenic potential of both BGs were investigated in an indirect and direct culture setting to assess the effect of the ionic dissolution products and the BGs' physical presence on the cells. The results indicated an advantage of BG1d-BG over 45S5 Bioglass® regarding cell viability and proliferation. Both BGs induced an earlier onset of osteogenic differentiation and accelerated the expression of late osteoblast marker genes compared to the control group. In conclusion, BG1d-BG is an attractive candidate for further experimental investigation. The basic mechanisms behind the different impact on cell behavior should be assessed in further detail, e.g. by further alteration of the BG compositions.

Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN).

Background: To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR). Results: Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type. Conclusion: Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity. Clinical trial registration: ClinicalTrials.gov: NCT01538381.

Anxiety affects disability and quality of life in patients with painful diabetic neuropathy.

BACKGROUND: Painful diabetic neuropathy (PDN) is known to negatively affect psychosocial functioning as expressed by enhanced levels of anxiety and depression. The aim of this study was to specify diabetes and pain-related fears. METHODS: This questionnaire-based cross-sectional study included 154 patients with PDN (mean age 65.7 ± 6.6 years). Correlation analyses corrected for age, gender, pain intensity, pain duration and insulin treatment were performed to assess the associations of fear of hypoglycaemia (Hypoglycaemia Fear Survey, HFS), kinesiophobia (Tampa Scale of Kinesiophobia, TSK), fear of pain (Pain Anxiety Symptom Scale, PASS-20), fear of falling (Falls Efficacy Scale-I, FES-I), fear of fatigue (Tampa Scale of Fatigue, TSF) and fear of negative evaluation (Brief Fear of Negative Evaluation Scale, BFNE), with quality of life (QoL) (Norfolk Quality of Life Questionnaire, Diabetic Neuropathy Version, QOL-DN) and disability (Pain Disability Index, PDI), respectively. RESULTS: In univariate analyses, all fears were independently associated with QOL-DN and PDI (p < 0.001 for all variables). Linear regression models including all fears and confounders, showed that pain intensity, pain duration and FES-I were significantly associated with QOL-DN (R2  = 0.603). Pain intensity, male gender and FES-I were significantly associated with PDI (R2  = 0.526). CONCLUSIONS: After controlling for confounders, levels of pain intensity, duration of pain and fear of falling were negatively associated with QoL in patients with PDN. Pain intensity, male gender and fear of falling were positively associated with disability. Specifying fears enables us to identify potential targets for behavioural interventions that aim to improve psychosocial well-being in patients with PDN. SIGNIFICANCE: This study shows that patients with PDN suffer from various fears, which should enable us to design a treatment strategy that directly targets these fears, hereby improving physical and psychosocial well-being in these patients.

Knowledge and Implementation of the S3 Guideline on Gestational Diabetes among Gynecologists and Diabetologists Four Years after Publication: Results of a Survey of 773 Gynecologists and 76 Diabetologists on their Knowledge of the Guideline on Gestational Diabetes (AWMF 057-008, 2011).

BACKGROUND: An S3 guideline on the diagnosis and differentiated management of gestational diabetes (GDM) was published in Germany in 2011. This guideline replaced the previously applicable recommendations for the diagnosis and treatment of GDM and, for the first time, compiled evidence-based recommendations for the care of patients with GDM. The new guideline has focused particularly on the counselling offered to all patients with GDM about the associated long-term health risks. In this study we investigated the state of knowledge about the guideline among gynecologists and diabetologists in Thuringia and Lower Saxony. METHOD: A questionnaire with 23 questions was sent out to 773 gynecologists and 76 diabetologists providing outpatient care in Lower Saxony and Thuringia. The statistical analysis was descriptive and inferential for comparisons between groups. RESULTS: The response rate was 54 %; an average of 47.6 % of the individual questions were answered correctly in the completed questionnaires. The questions were answered correctly significantly more frequently by persons in the group with a good knowledge of the guidelines (75 vs. 61 %, p < 0.001). There were no significant differences between groups when differences between federal states or medical specialties were compared. CONCLUSIONS: The results of our study show a good general state of knowledge of the guideline and point to a high level of willingness to implement the recommendations of the S3 guideline on GDM. With regard to the follow-up care provided to patients with GDM and depression, this study found a significant need for further training.

Retrospective characterisation and outcome of canine idiopathic mesenteric purulent lymphadenitis and lymph node abscesses at a teaching hospital from 2005 to 2015.

BACKGROUND: Idiopathic purulent mesenteric lymphadenitis or lymph node abscessation, even though rare in dogs, are important diseases in which rapid diagnosis and treatment is critical. This study aimed to characterise the typical features of these conditions in dogs. MATERIAL AND METHODS: Archived records from 2005 to 2015 were retrospectively evaluated for the occurrence of idiopathic purulent mesenteric lymphadenitis or lymph node abscesses in dogs. History, physical and clinicopathological abnormalities, diagnostic tests performed, treatment and outcome were reviewed. RESULTS: A total of 14 cases with histopathologic and/or cytologic confirmation were identified. Typically, there were gastrointestinal signs including abdominal pain and elevated body temperature. Blood analysis revealed non-specific inflammatory changes including elevated C-reactive protein. Half of the bacterial cultures from lymph nodes showed growth of various bacteria. A primary cause was not identified in any case. Out of 14 cases, 10 cases underwent surgery and all dogs were discharged from the hospital. Three suffered from a relapse between 1 and 5 months after discharge but were successfully managed with antibiotics. CONCLUSION AND CLINICAL RELEVANCE: Idiopathic purulent mesenteric lymphadenitis or lymph node abscessation are infrequent but clinically important diseases. Surgical, symptomatic and antibiotic treatment led to resolution of clinical signs in the evaluated cases. Thorough and standardised diagnostic workup and treatment of future cases are necessary to investigate possible pathogeneses and optimal therapeutic options. Outcome was favourable overall.

[Canine peritoneal larval cestodosis caused by Mesocestoides spp. larval stages]. / Kanine peritoneale larvale Zestodose durch Mesocestoides spp.

In a female dog with unspecific clinical symptoms, sonography detected a hyperechoic mass in the middle abdomen and blood analysis a middle grade systemic inflammatory reaction. Laparotomy revealed a peritoneal larval cestodosis (PLC). The diagnosis of an infection with tetrathyridia of Mesocestoides spp. was confirmed by parasitological examination and molecularbiological analysis. Reduction of the intra-abdominal parasitic load as well as a high dose administration of fenbendazole over 3 months led to a successful treatment which could be documented sonographically and by decreased concentrations of C-reactive protein (CRP). Seven months after discontinuation of fenbendazole administration, PLC recurred, pre-empted by an elevation of serum CRP values. According to the literature a life-long fenbendazole treatment was initiated. In cases of unclear chronic granulomatous inflammations in the abdominal cavity in dogs, PLC should be considered. CRP concentration and sonographic examinations are suitable to control for treatment success and a possibly occurring relapse.

Differentiation of healthy and malignant tissue in colon cancer patients using optical spectroscopy: A tool for image-guided surgery.

BACKGROUND: Surgery for colorectal cancer aims for complete tumor resection. Optical-based techniques can identify tumor and surrounding tissue through the tissue specific optical properties, absorption and scattering, which are both influenced by the biochemical and morphological composition of the tissue. OBJECTIVE: To evaluate the feasibility of dual-modality Diffuse Reflectance Spectroscopy-Fluorescence Spectroscopy (DRS-FS) for discrimination between healthy and malignant tissue in colorectal surgery. METHODS: Surgical specimens from colorectal cancer patients were measured immediately after resection using a fiber-optic needle capable of dual-modality DRS-FS. Model-based analyses were used to derive scattering and absorption coefficients and intrinsic fluorescence. Volume fractions of chromophores were estimated. Furthermore, optical data were recorded along a trajectory from healthy tissue towards tumor. RESULTS: Spectral characteristics were identified in 1,273 measured spectra from 21 specimens. Combined DRS and FS discriminated tumor from surrounding tissue with a sensitivity of 95% and a specificity of 88%. Significant spectral changes were seen along the trajectory from healthy tissue to tumor. CONCLUSION: This study demonstrates that dual-modality DRS-FS can identify colorectal cancer from surrounding healthy tissue. The quantification of comprehensible parameters allows robust classification and facilitates extrapolation towards the clinical setting. The technique, here demonstrated in a needle like probe, can be incorporated into surgical tools for optically guided surgery in the near future. Lasers Surg. Med. 47:559-565, 2015. © 2015 Wiley Periodicals, Inc.

A prospective, randomized, blinded, placebo-controlled pilot study on the effect of Enterococcus faecium on clinical activity and intestinal gene expression in canine food-responsive chronic enteropathy.

BACKGROUND: Canine chronic enteropathies (CE) are believed to be caused by an aberrant immune response towards the intestinal microbiome. Administration of probiotics can alleviate colitis in people. In vitro effects of the probiotic Enterococcus faecium NCIMB 10415 E1707 (EF) previously have been evaluated using canine cells (e.g., whole blood, intestinal biopsies), but data on in vivo efficacy are lacking. HYPOTHESIS/OBJECTIVES: Administration of EF to dogs with food-responsive CE will improve clinical outcome and decrease the intestinal inflammatory profile. ANIMALS: Dogs diagnosed with CE were prospectively recruited to receive a hydrolyzed elimination diet plus either a synbiotic product containing EF or placebo for 6 weeks. Both veterinary staff and owners were blinded to the treatment. METHODS: Clinical severity index (CCECAI), clinicopathological data and gene expression using intestinal biopsies (TLR2/4/5/9, IL-17A, IL-22, IL-23p19, RORC, IL-2, IL-12p35, TNFα, IL-4, IFNy, IL-10, TGFß, IL-1ß, IL-18, NLRP3, casp-1, TFF1, TFF3 and PPARy) before and after 6 weeks of treatment were analyzed using linear mixed modeling. RESULTS: Of the 45 cases recruited, 12 finished the clinical trial. Seven received the synbiotic and 5 the placebo product. There was no difference between groups or treatments regarding clinical efficacy, histology scores or expression of any of the investigated genes. CONCLUSIONS AND CLINICAL IMPORTANCE: Standard dietary treatment induced rapid clinical response in all cases. Because the study was underpowered, it was not possible to determine whether or not EF had an additional effect within the time period of 6 weeks.

[Turnover of Non-medical Staff in Outpatient Oncology Practices: Is Building Social Capital a Solution?]. / Fluktuation bei nicht-ärztlichem Personal in onkologischen Schwerpunktpraxen: Sozialkapitalaufbau als Lösungsansatz?

STUDY AIM: While a lot is known about potential and actual turnover of non-medical hospital staff, only few data exist for the outpatient setting. In addition, little is known about actual instruments which leaders can use to influence staff turnover in physician practices. In the literature, the social capital of an organisation, which means the amount of trust, common values and reciprocal behaviour in the organisation, has been discussed as a possible field of action. In the present study, staff turnover as perceived by outpatient haematologists and oncologists is presented and analysed as to whether social capital is associated with that staff turnover. In conclusion, measures to increase the social capital of a practice are presented. METHODS: The present study is based on data gathered in a questionnaire-based survey with members of the Professional Organisation of -Office-Based Haematologists and Oncologists (N=551). The social capital of the practice was captured from the haematologists and oncologists using an existing and validated scale. To analyse the impact of the practice's social capital on staff turnover, as perceived by the physicians, bivariate correlations and linear regression analyses were calculated. RESULTS: In total, 152 haematologists and oncologists participated in the study which represents a response rate of 28%. In the regression analyses, social capital appears as a significant and strong predictor of staff turnover (beta=-0.34; p<0.001). CONCLUSIONS: Building social capital within the practice may be an important contribution to reducing staff turnover although the underlying study design does not allow for drawing causal conclusions regarding this relationship. To create social capital in their practice, outpatient physicians may apply measures that facilitate social interaction among staff, foster trust and facilitate cooperation. Such measures may already be applied when hiring and training new staff, but also continuously when leading employees and when organising work tasks, e.g., by establishing regular team meetings.

Stimulation of duodenal biopsies and whole blood from dogs with food-responsive chronic enteropathy and healthy dogs with Toll-like receptor ligands and probiotic Enterococcus faecium.

The composition of the microbiome plays a significant role in the pathogenesis of inflammatory bowel disease (IBD) in humans and chronic enteropathies (CE) in dogs. The administration of probiotic micro-organisms is one way of modulating the microbiome, but experiments elucidating mechanisms of action of probiotics in the intestine of healthy and CE dogs are lacking. The aim of our study was to investigate the effects of different Toll-like receptor (TLR) ligands and Enterococcus faecium (EF) on ex vivo cultured duodenal samples and whole blood (WB) from dogs with food-responsive chronic enteropathy (FRE) when compared to healthy dogs. Biopsy stimulation was performed in 17 FRE and 11 healthy dogs; WB stimulation was performed in 16 FRE and 16 healthy dogs. Expression of TLR2, 4, 5 and 9, IL-17A, IL-22, IFNy, TNFα, IL-4, IL-10, TGFß and PPARy was determined in biopsies by quantitative polymerase chain reaction (PCR). In addition, production of TNFα, IL-10, IFNy and IL-17A protein in WB and biopsy supernatants was assessed by ELISA. Treatment with individual TLR ligands or EF induced a variety of changes in the expression of different TLRs and cytokines, but not necessarily a consistent change with a single stimulating agent. Even though cytokine protein could not be detected in supernatants from ex vivo stimulated biopsies, we found TNFα protein responses in blood to be opposite of the transcriptional responses seen in the biopsies. Stimulation of canine duodenal biopsies with TLR ligands can potentially induce anti-inflammatory gene expression, especially in healthy tissue, whereas the effects of EF were limited.

Can a stressed oncologist be good in a consultation? A qualitative study on the oncologists' perception.

The aim of this exploratory study was to examine how the working conditions and job stress of private practice oncologists (PPOs) affect their interaction with patients. Data for the study were collected through semi-structured interviews with PPOs selected based on purposeful sampling criteria. The data were evaluated using content analysis. Factors perceived by PPOs to influence their level of stress and patient care were some of their own personal characteristics as well as working conditions both within and outside their practices. Apart from being able to name specific stressors (e.g., dysfunctional organisational workflow and interruptions during medical encounters), the oncologists also mentioned individual and organisational resources (e.g., professional experience, well-educated nurses and good work organisation) for coping with job stress and improving interaction with patients. Within this study, we identified some obstacles on the individual and organisational level for good patient care, as working conditions which might lead to time pressure and stress, which subsequently have an impact on quality in patient care (e.g., less time for personal issues during patient consultations). Future stress research should conduct a more in-depth investigation of these and other interventions at both the individual and organisational levels in order to improve patient care.

Primary undifferentiated carcinoma of the trachea.

BACKGROUND: Primary undifferentiated or lymphoepithelial carcinoma mainly occurs in the nasopharynx. Tracheal localization is exceedingly rare. To the best of our knowledge, only four cases have been reported previously, all in Asian patients. CASE REPORT: A 61-year-old male European patient presented with hemoptysis and cough for several months. The workup revealed a primary tracheal tumor without regional or distant metastasis. The patient was treated with tracheal resection followed by end-to-end reconstruction. Pathologic analysis of the tumor, including immunohistochemistry, confirmed the diagnosis of lymphoepithelioma-like carcinoma. Testing for Epstein-Barr virus by hybridization in situ was massively positive. With a follow-up at 15 months, the patient is alive and free of disease. CONCLUSION: We report the first case of lymphoepithelioma-like carcinoma in the trachea in the European population. Treatment possibilities are discussed. They should be based on each patient's clinical presentation and the results of their preoperative workup.

Hydrous mantle transition zone indicated by ringwoodite included within diamond.

The ultimate origin of water in the Earth's hydrosphere is in the deep Earth--the mantle. Theory and experiments have shown that although the water storage capacity of olivine-dominated shallow mantle is limited, the Earth's transition zone, at depths between 410 and 660 kilometres, could be a major repository for water, owing to the ability of the higher-pressure polymorphs of olivine--wadsleyite and ringwoodite--to host enough water to comprise up to around 2.5 per cent of their weight. A hydrous transition zone may have a key role in terrestrial magmatism and plate tectonics, yet despite experimental demonstration of the water-bearing capacity of these phases, geophysical probes such as electrical conductivity have provided conflicting results, and the issue of whether the transition zone contains abundant water remains highly controversial. Here we report X-ray diffraction, Raman and infrared spectroscopic data that provide, to our knowledge, the first evidence for the terrestrial occurrence of any higher-pressure polymorph of olivine: we find ringwoodite included in a diamond from Juína, Brazil. The water-rich nature of this inclusion, indicated by infrared absorption, along with the preservation of the ringwoodite, is direct evidence that, at least locally, the transition zone is hydrous, to about 1 weight per cent. The finding also indicates that some kimberlites must have their primary sources in this deep mantle region.

Bcl-2/caspase 3 mucosal imbalance favors T cell resistance to apoptosis in dogs with inflammatory bowel disease.

Canine idiopathic inflammatory bowel disease (IBD) is believed to result from complex interplay between genetic, microbial, and immunologic factors. Abnormal cell death by apoptosis may result in the persistence of activated intestinal T cells that contribute to mucosal inflammation and clinical severity. To test this hypothesis, we investigated the mucosal expression of pro- and anti-apoptotic proteins in different intestinal compartments and their association with inflammatory indices in dogs with IBD. Apoptosis of lamina propria (LP) T cells in duodenal, ileal, and colonic tissues in control and IBD dogs was analyzed by caspase 3/Bcl-2 immunohistochemistry and TUNEL assays. Densities and distributions of LP caspase 3 and Bcl-2 cells were correlated to histopathologic lesions and the clinical activity index (CIBDAI). Compared to control tissues, IBD dogs had significantly (P<0.01) fewer caspase 3 cells in colonic mucosa. Double immunostaining identified the majority of apoptotic cells as TUNEL(+)/caspase 3(+). Within intestinal mucosa of IBD dogs, there were significantly greater numbers of Bcl-2 cells at the apical and basilar villus in the duodenum as compared to the colon and to the apical and basilar villus in the ileum (P<0.001 for all comparisons). There were significantly greater numbers of Bcl-2 cells at the apical and basilar villus of the duodenum but significantly fewer numbers of Bcl-2 cells at the apical villus of the ileum in IBD dogs compared with controls (P<0.001, P<0.001, and P<0.02, respectively). There was a significant association between the number of Bcl-2 cells in the duodenum of IBD dogs and the CIBDAI (P<0.001 each for mild, moderate and severe clinical IBD). In conclusion, apoptosis of T lymphocytes varies within intestinal compartments of dogs with IBD. Mucosal imbalance of Bcl-2/caspase 3 expression favors T cell resistance to apoptosis which may contribute to T cell accumulation and chronic intestinal inflammation, similar to human IBD.