Menoci: lightweight extensible web portal enhancing data management for biomedical research projects.

BACKGROUND: Biomedical research projects deal with data management requirements from multiple sources like funding agencies' guidelines, publisher policies, discipline best practices, and their own users' needs. We describe functional and quality requirements based on many years of experience implementing data management for the CRC 1002 and CRC 1190. A fully equipped data management software should improve documentation of experiments and materials, enable data storage and sharing according to the FAIR Guiding Principles while maximizing usability, information security, as well as software sustainability and reusability. RESULTS: We introduce the modular web portal software menoci for data collection, experiment documentation, data publication, sharing, and preservation in biomedical research projects. Menoci modules are based on the Drupal content management system which enables lightweight deployment and setup, and creates the possibility to combine research data management with a customisable project home page or collaboration platform. CONCLUSIONS: Management of research data and digital research artefacts is transforming from individual researcher or groups best practices towards project- or organisation-wide service infrastructures. To enable and support this structural transformation process, a vital ecosystem of open source software tools is needed. Menoci is a contribution to this ecosystem of research data management tools that is specifically designed to support biomedical research projects.

Maintaining Mental Health Through Positive Writing: Effects of a Resource Diary on Depression and Emotion Regulation.

OBJECTIVE: The present study investigated the beneficial effects of the resource-oriented positive writing intervention resource diary (RD) on mental health variables among patients recently discharged from psychiatric inpatient treatment. METHOD: Eighty-nine patients were randomly assigned to either an intervention group completing RD over the course of 4 weeks (n = 45) or a control group receiving no intervention (n = 44). To measure changes in mental health, patients filled out a number of self-report questionnaires on depression, emotion regulation, and resource activation before and after the intervention.  RESULTS: Participants completing RD had significantly lower depression scores than controls and reported an increased use of the functional emotion regulation strategy "reappraisal" 5 weeks after discharge. A decreased use of the dysfunctional strategy "expressive suppression" was found in the female subsample. No differences were found for resource activation. CONCLUSION: These findings suggest that a resource-oriented positive writing intervention has potential for stabilizing mental health after psychiatric discharge and could therefore present an economical alternative or addition to established aftercare programs.

Sequence-based methods for detecting and evaluating the human gut mycobiome.

UNLABELLED: We surveyed the fungal microbiota in 16 faecal samples from healthy humans with a vegetarian diet. Fungi were identified using molecular cloning, 454 pyrosequencing and a Luminex analyte-specific reagent (ASR) assay, all targeting the ITS region of the rRNA genes. Fungi were detected in each faecal sample and at least 46 distinct fungal operational taxonomic units (OTUs) were detected, from two phyla - Ascomycota and Basidiomycota. Fusarium was the most abundant genus, followed by Malassezia, Penicillium, Aspergillus and Candida. Commonly detected fungi such as Aspergillus and Penicillium, as well as known dietary fungi Agaricus bisporus and Ophiocordyceps sinensis, are presumed to be transient, allochthonous members due to their abundance in the environment or dietary associations. No single method identified the full diversity of fungi in all samples; pyrosequencing detected more distinct OTUs than the other methods, but failed to detect OTUs in some samples that were detected by cloning and/or ASR assays. ASRs were limited by the commercially available assays, but the potential to design new, optimized assays, coupled with speed and cost, makes the ASR method worthy of further study. SIGNIFICANCE AND IMPACT OF THE STUDY: Fungi play a role in human gut ecology and health. The field lags immensely behind bacterial gut microbiota research, and studies continue to identify new fungi in faecal samples from healthy humans. However, many of these 'new' species are incapable of growth in the human GI tract, let alone making a meaningful contribution to the gut microbial community. Fungi actually inhabiting and impacting the gut likely constitute a small set of species, and an optimized, targeted, probe-based assay may prove to be the most sensible way of quantifying their abundances.

Imaging of respiratory network topology in living brainstem slices.

Topology of neuronal networks contributes to their functioning but the structure-function relationships are not yet understood. In order to reveal the spatial organisation of the respiratory network, we expressed enhanced green fluorescent proteins in neurons in brainstem slices containing the respiratory kernel (pre-Bötzinger complex). The expression was neuron specific due to use of adeno-associated viral vector driving transgene expression from synapsin 1 promoter. Both neuronal cell bodies and their dendrites were labelled with high efficacy. This labelling allowed for enhanced spatial resolution as compared to conventional calcium-sensitive dyes. Neurons occupied about 10% of tissue volume and formed an interconnected network. Using custom-developed software, we quantified the network structure that had a modular structure consisting of clusters having transverse (dorso-ventral) orientation. They contained in average seven neurons and connections between the cells in different clusters were less frequent. This novel in situ imaging technique is promising to gain new knowledge about the fine structure and function of neuronal networks in living slice preparations.

Technical considerations in distraction osteogenesis.

Five cases are presented to exemplify technical difficulties and complications which may be encountered when performing distraction osteogenesis in the facial skeleton. The procedure should be performed under close supervision by the surgical and orthodontic colleagues. Errors in the choice of vector may be managed by earlier removal of the distractor and subsequent traction on the previously osteotomized segments using orthodontic appliances and principles. Multiple distractors may be inserted in the same jaw and bimaxillary procedures are possible, increasing the likelihood of encountering technical difficulties. Detailed planning and close follow-up, with early recognition and active management of the complications, may be useful in ensuring a successful outcome of this versatile procedure.

Metastatic malignant solitary fibrous tumour to the infra-temporal fossa.

Malignant solitary fibrous tumours (MSFTs) are rare tumours of fibrous origin, which can occur at all anatomical sites and represent 20% of solitary fibrous tumours. Fine-needle aspiration cytology is not able to distinguish benign from malignant disease, and sufficient tissue has to be obtained for accurate histological diagnosis to be made. Lesions > 10 cm in diameter and incomplete resection or non-resectability are predictive factors for poor long-term survival. We present a 57-year-old patient with a presumably metastatic MSFT from the peritoneal cavity to the skull-base who is in a stable state 17 months after surgical debulking of the skull-base and removal of the peritoneal lesion, followed by post-operative chemotherapy. We suggest the terminology metastatic malignant solitary fibrous tumour for a description of this disease.

Follow-up of collagen crosslink excretion in patients with oral squamous cell carcinoma and analysis of tissue samples.

The presence of an oral squamous cell carcinoma (OSCC) may be associated with increased urinary excretion of the markers of collagen degradation, hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). We investigated the possibility of these markers predicting the presence of active disease. Patients from a current study on HP and LP were included as follows: Group 1a (OSCC with confirmed mandibular bony infiltration, n=12), group 1b (group 1a patients >6 months after successful treatment), group 2a (OSCC without evidence of mandibular bone infiltration, n=8), group 2b (group 2a patients >6 months after successful treatment), group 3a (recurrent OSCC, n=8), group 3b (group 3a patients >6 weeks later, symptoms unchanged) and group 4 (control group, n=74). Tissue samples from tumour tissue and adjacent healthy mucosa were additionally investigated for HP and LP concentrations (n=8). The decrease in the urinary concentrations of HP and LP was statistically significant between groups 1a and 1b (P<0.001 for HP and LP), but not between groups 2a and 2b (P=0.07 for HP and LP), while values in groups 1b and 2b were within the normal range. When comparing groups 3a and 3b, a significant increase was observed for LP (P=0.050), but not HP (P=0.208). In conclusion, successful treatment of OSCC with bony involvement may be associated with a reduction of urinary HP and LP, whereas ongoing disease may result in an increase of LP. HP and LP may both be useful markers of tumour progression in patients with OSCC.

Collagen crosslink excretion and staging of oral cancer.

Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen crosslink residues of which the urinary concentration reflects the level of connective-tissue turnover. HP is ubiquitous in tissue, whereas LP is specific for bone. The purpose of this investigation was to assess the sensitivity and specificity of an increased urinary concentration of both HP and LP in indicating infiltration of mandibular bone by an oral squamous cell carcinoma (OSCC) or recurrence of the disease after successful therapy. We investigated the history and urine levels in 116 adult patients, who were divided into the following groups. Group 1: patients with OSCC with bone infiltration (n=17); group 2: patients with confirmed OSCC (n=12) without evidence of bone infiltration; group 3: patients with recurrence of an OSCC (n=13); group 4: patients without clinical evidence of disease (n=74). The range and upper limit of normal values (HP(max) and LP(max)) were measured from the normal controls in group 4. Levels of LP and HP were measured by HPLC and fluorescence detection. There was a significant difference in the average urinary levels of LP and HP between groups 1-4 (P<0.001). The presence of mandibular bone infiltration could be detected with a sensitivity and specificity of 100% when comparing groups 1 and 2. Presence of tumour tissue could be detected with a sensitivity of 90%. In conclusion, a normal LP concentration in patients with an OSCC strongly suggests that bone invasion by the disease has not taken place. If both urinary HP and LP are elevated, disease recurrence is highly likely.

Adaptive adjustment of the adolescent porcine mandibular condyle.

The effect of occlusal support during primary dentition on the mandibular condyle remains controversial. We sought to determine whether unilateral loss of occlusal support leads to quantifiable adaptive changes of the condyle. Quantitative analysis of condylar growth and spongy bone volume after unilateral removal of teeth on the left side in adolescent minipigs was examined over a period of 4 months. Serial sagittal sections of the temporomandibular joint were examined using microradiography, fluorescence microscopy, and light microscopy. The condyles on the nonextracted side showed a higher growth rate than those on the extracted side, with a 1.56-fold thicker (p = 0.003) additional vertical bone layer. This factor was greater ventrally than dorsally (p = 0.0311), increasing from dorsomedial (1.33) to ventrolateral (2.38). There was therefore a reciprocal change of the condylar surface curve between the left and right condyles. Increased condylar growth correlated with a lower subchondral spongy bone volume (7.38% difference, p = 0.002). The amount of mineralized bone matrix generated was estimated to be about 1.33-fold higher in the nonextraction side condyles compared with those on the extraction side. Thus, unilateral loss of occlusal support was shown to lead to quantifiable alterations of condylar vertical growth and spongy bone volume in minipigs.

[Clinical pilot study of interstitial photodynamic therapy for treatment of advanced head and neck tumors]. / Klinische Pilotstudie zur interstitiellen photodynamischen Therapie für die Behandlung von fortgeschrittenen Kopf-Hals-Tumoren.

BACKGROUND: Photodynamic therapy is a new treatment modality which uses a photochemical reaction to destroy tumour tissue. To date this treatment has only been applied effectively to the surface of small, superficial tumours due to the limitations imposed by light penetration. With the use of fibres introduced into the substance of the tumour, more bulky lesions can be treated successfully. STUDY: We describe the first clinical use of such a treatment in the management and, specifically, the amelioration of advanced head and neck cancer. We describe our results in 12 patients, in 11 of whom we were able to improve quality of life. In one patient there was no observable effect. The side-effects were minimal. DISCUSSION: We suggest that interstitial photodynamic therapy may be of use in the palliative care of patients with advanced disease and bulky tumours. It may also be of use in benign, bulky tumors, but this point requires further study.

Cellular neurothekeoma of the oral mucosa.

Cellular neurothekeoma is an unusual benign neoplasm which, despite its name, is of uncertain origin. This report describes a cellular neurothekeoma of the cheek mucosa, the first at this site. The tumour presented in a 29-year-old man as a discrete mucosal thickening. Histology showed a generally well circumscribed, but unencapsulated, solid tumour which replaced the entire lamina propria and permeated between minor salivary glands and bundles of striated muscle in the submucosa. There was a sub-epithelial Grenz zone. The tumour was composed of nodules of pale, epithelioid cells separated by fascicles of spindle cells, with smaller strands and nests superficially. The nuclei were vesicular and, though mainly bland, occasionally atypical. The stroma was moderately infiltrated by mixed chronic inflammatory cells. Prominent nerves and blood vessels were seen at the periphery of the lesion, and neoplastic cells were noted within intact striated muscle fascicles. With immunohistochemistry, all the neoplastic cells strongly expressed NKI/C3, synaptophysin, neurone-specific enolase and vimentin, some expressed smooth muscle actin and PGP 9.5, but all were negative for S100, factor XIIIa, CD34, CD56, CD57, CD68, chromogranin A, desmin, epithelial membrane antigen and von Willebrand factor. The origin of the lesion is thus speculative. It was, however, completely excised and in 12 months there has been no recurrence.

Cell surface presentation of recombinant (poly-) peptides including functional T-cell epitopes by the AIDA autotransporter system.

For the efficient surface presentation and release of virulence factors especially pathogenic Gram-negative bacteria have developed several distinct secretion mechanisms. An increasing number of pathogens in various species employs a mechanism denoted the 'autotransporter' pathway. This pathway is characterised by an outer membrane translocator module representing the C-terminal domain of the transported protein itself. An intriguing potential application of such systems involves the transport and surface expression of recombinant proteins or peptides, like e.g. the presentation of antigens for the generation of live oral vectors as vaccine carriers. Here we report on the incorporation of heterologous (poly-) peptides in permissive sites of the translocator module of the adhesin-involved-in-diffuse-adherence (AIDA) autotransporter system. We demonstrate the presentation of the B subunit of the heat labile enterotoxin of Escherichia coli (LTB) as well as of functional T-cell epitopes of Yersinia enterocolitica heat-shock protein 60 (Y-hsp60) on the surface of E. coli.

Optical biopsy systems for the diagnosis and monitoring of superficial cancer and precancer.

Histopathology is the gold standard in the diagnosis of cancer and dysplasia. Screening for the disease in high-risk populations(6,15) and choosing the correct site for biopsy have implications for the choice of follow-up intervals and therapy. Sully & Field(12) suggest that molecular genetic analysis, such as the polymerase chain reaction, for detecting progressive loss of heterozygosity, may be a more accurate predictor of the clinical course of oral cancer. This technique is now semi-automated and compares favourably with the time taken for histopathology (commonly 1-2 weeks). Recent developments suggest that the fluorescent and spectroscopic features may distinguish diseased from healthy tissue, and below follows an introduction for the clinician to this fascinating and complex field. It is possible to obtain a diagnosis in real-time and, with the appropriate use of photochemicals and image enhancement, it may be possible to treat and monitor the effects of treatment in real-time.

Ocular psychiatric disorders in maxillofacial injuries. Two case reports and a review of psychogenic ocular symptoms.

Ocular signs and symptoms associated with facial trauma can be a manifestation of an underlying psychiatric disorder which may exist prior to the traumatic incident, or even develop as a result of the stressful traumatic experience in a psychologically vulnerable individual. Two such cases are presented. A brief review of psychogenic ocular symptoms as well as suggestions for evaluation and treatment are discussed.

Processing of the AIDA-I precursor: removal of AIDAc and evidence for the outer membrane anchoring as a beta-barrel structure.

The AIDA-I adhesin known to be responsible for the diffuse adherence (DA) phenotype of the diarrhoeagenic Escherichia coli (DAEC) strain 2787 has been shown previously to be synthesized as a precursor protein and to undergo additional C-terminal processing. Here, the C-terminal processing of the AIDA-I precursor and the outer membrane topology of the cleaved C-terminal fragment, AIDAc, were investigated. By isolation of the cleaved AIDAc fragment and N-terminal sequencing, the C-terminal cleavage site was identified between Ser-846 and Ala-847 thereby indicating a molecular mass of 47.5 kDa for AIDAc. The correct processing to AIDA-I and AIDAc in OmpT, OmpP and DegP protease-deficient E. coli strains as well as in avirulent salmonellae and shigellae points to an autocatalytic cleavage mechanism. The cleaved AIDAc was localized in the outer membrane. A leader sequence-AIDAc fusion was efficiently routed to the outer membrane. Analysis by protease digestion, secondary-structure prediction and modelling, by comparison with structurally related bacterial proteins like the IgA1 protease from neisseria, the vacuolating toxin from Helicobacter pylori, and the VirG protein of Shigella flexneri, strongly indicates that AIDAc is present in the outer membrane as a beta-barrel structure.

Genetic analysis of the regulatory putP region (coding for proline permease) in Klebsiella pneumoniae M5a1: evidence for regulation by the nac system.

During a search for nitrogen-controlled promoters on the Klebsiella pneumoniae M5a1 chromosome, the regulatory region of putP (coding for proline permease) was cloned, sequenced and analyzed. The region contained a weak sigma 70-dependent promoter and putative binding sites for the cAMP-CAP complex and the Nac regulatory protein, the latter probably providing a link with the nitrogen regulation (Ntr) system. Using a lacZ gene fusion, evidence for control of putP transcription by both Nac and Ntr was obtained.