National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project.

BACKGROUND: In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS: Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION: For a future "pandemic preparedness" national and international recommendations and concepts for the care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting.

[Migraine with typical aura without headache; first presentation at older age]. / Visuele verschijnselen bij migraine met typisch aura.

Transient visual phenomena in later life due to a visual aura in migraine are not uncommon and can also occur without headache. This migraine with aura is not always recognized as such. Since visual phenomena can also have a variety of other causes, they can present a diagnostic dilemma in both primary and secondary care. Visual aura phenomena have various and often complex manifestations and are usually observed binocularly. In case of transient visual phenomena, the patient's history is of utmost importance to determine whether there is a mono- or binocular cause of the complaints. Timely recognition of visual phenomena in the context of migraine can prevent unnecessary diagnostics and treatments.

Coxiella burnetii immunogenic proteins as a basis for new Q fever diagnostic and vaccine development.

Coxiella burnetii is the etiological agent of the zoonosis Q fever, which can cause an acute or a chronic, life-threatening disease in humans. It presents a highly stable cell form, which persists in the environment and is transmitted via contaminated aerosols. Ruminants are considered as the main reservoir for human infections but are usually asymptomatic. Subclinical infection in these animals and the occurrence of serologically negative shedders hamper the identification of infected animals with the currently used diagnostic techniques. This suboptimal sensitivity limits reliable identification of infected animals as well as the well-timed implementation of countermeasures. This review summarizes compounds, focusing on C. burnetii seroreactive proteins, which were discovered in recent immunoproteomic studies. We analyzed these proteins regarding their localization, function, frequency of citation, differences seen in various host species as well as sensitivity and specificity. Finally, proteins useful for the development of new diagnostic test systems as well as subunit vaccines were discussed.

TBNET - Collaborative research on tuberculosis in Europe.

Networking is a key feature of scientific success. The Tuberculosis Network European Trialsgroup (TBNET) was founded in 2006 as a non-profit, non-governmental peer-initiated scientific organization to collaboratively address research priorities in the area of tuberculosis in Europe. Today, TBNET is the largest tuberculosis research organization in Europe with nearly 500 members from 22 EU countries and 49 countries worldwide (www.tb-net.org). Apart from small multicenter basic research studies, a particular strength of TBNET is the performance of large collaborative projects, pan-European multicenter studies and database projects. In recent years, research from TBNET has substantially contributed to the understanding of the management, risk and prognosis of patients with multidrug (MDR) and extensively drug-resistant (XDR) tuberculosis and led to a better understanding of the clinical value of novel tests for the identification of adults and children with tuberculosis and latent infection with Mycobacterium tuberculosis. In 2009, two branches of TBNET were founded to specifically address tuberculosis in the pediatric population (ptbnet) and non-tuberculous mycobacterial diseases (NTM-NET). In addition to the research activities, TBNET is developing expert consensus documents for clinical management and provides training and capacity building especially for members from Eastern European countries, where tuberculosis is still a prevalent health problem.

Executive functions recover earlier than episodic memory after microsurgical transsphenoidal resection of pituitary tumors in adult patients--a longitudinal study.

Pituitary tumors may lead to cognitive dysfunction, and the most prevalent deficits are impaired memory and attention. To investigate whether memory and executive functions improve after surgical treatment we performed a prospective longitudinal study comprising 106 patients with pituitary tumors. Psychometric evaluation was performed with the d2-Letter Cancellation test, the Trail Making test, the Digit Span test and the Intelligence Structure test-Verbal Memory test at three timepoints: preoperatively, and at 3 months and 12 months after surgery. The preoperative and postoperative maximum suprasellar tumor extension and hormone status was assessed in all participants. The main finding was that concentration, working memory, and attentional speed improved significantly within the first 3 months after surgery (p<0.05), while improvement of episodic memory was not observed until 12 months after surgery (p<0.001). In the patients harbouring non-functioning adenomas, prolactinomas or other sellar lesions, the most important factor promoting improvement of neurocognitive function was the removal of the suprasellar tumor extension.

Migration of T-cell subsets in multiple sclerosis and the effect of interferon-beta1a.

OBJECTIVES: Migration of inflammatory cells across the blood-brain barrier is a central event in the formation of multiple sclerosis (MS) lesions and is known to be enhanced in MS patients. This study investigates the migration of CD4+ and CD8+ T-cell subsets and the effects of interferon-beta1a (IFN-beta1a) treatment on migration and matrix metalloproteinase-9 (MMP-9) production of these T-cell subsets. MATERIALS AND METHODS: An ex vivo transwell system was established to compare the migratory behaviour of lymphocytes isolated from normal controls and untreated MS patients. In addition, MS patients were investigated longitudinally after initiation of IFN-beta1a treatment. RESULTS: Migration of CD4+ T cells (P < 0.05), but not of CD8+ T cells, was enhanced in untreated MS patients compared with controls and was normalized by treatment with IFN-beta1a. In addition, IFN-beta1a treatment reduced MMP-9 production of CD4+ but not CD8+ T cells. CONCLUSION: Our results indicate that CD4+ T cells, but not CD8+ T cells, contribute to the enhanced ex vivo migration observed in MS.

Deletion of the tissue response against alginate-pll capsules by temporary release of co-encapsulated steroids.

Transplantation of encapsulated living cells is a promising approach for the treatment of a wide variety of diseases. Large-scale application of the technique, however, is hampered by inflammatory responses against the capsules. In the present study, we investigate whether tissue responses against alginate-PLL-alginate capsules can be modulated by co-encapsulation and temporary release of immunomodulating factors such as dexamethasone. Such an approach may be mandatory in order to increase the function and survival of encapsulated tissue since it has been shown that the tissue response can be caused by many, insurmountable factors. In an in vitro assay, we demonstrated an antiproliferative effect of dexamethasone-containing capsules on L929-mouse-fibroblasts. Subsequently, capsules prepared of purified alginate with or without solved dexamethasone were implanted in the peritoneal cavity of rats and retrieved one month later for histological evaluation. Most of the capsules without dexamethasone proved to be overgrown and adherent to the abdominal organs whereas with co-encapsulated dexamethasone the majority of the capsules were found freely floating in the peritoneal cavity without overgrowth. We conclude that co-encapsulation of dexamethasone has a profound effect on fibroblasts and macrophages adherence to immunoisolating capsules.

Biocompatibility and surface structure of chemically modified immunoisolating alginate-PLL capsules.

Grafting of encapsulated living cells has the potential to cure a wide variety of diseases. Large-scale application of the technique, however, is hampered by insufficient biocompatibility of the capsules. A major factor in the biocompatibility of capsules is inadequate covering of the inflammatory poly-L-lysine (PLL) on the capsules' surface. In the present study, we investigate whether tissue responses against alginate-PLL capsules can be reduced by crosslinking the surface of the capsules with heparin or polyacrylic acid. Our transplant study in rats shows a tissue response composed of fibroblasts and macrophages on alginate-PLL-alginate and alginate-PLL-heparin capsules that was completely absent on alginate-PLL-polyacrylic acid capsules. Atomic force microscopy analyses of the capsules demonstrates that the improved biocompatibility of alginate-PLL-capsules by polyacrylic acid coating should not only be explained by a more adequate binding of PLL but also by the induction of a smoother surface. This study shows for the first time that biologic responses against capsules can be successfully deleted by chemically crosslinking biocompatible molecules on the surface of alginate-PLL capsules.

Brain activity related to integrative processes in visual object recognition: bottom-up integration and the modulatory influence of stored knowledge.

We report evidence from a PET activation study that the inferior occipital gyri (likely to include area V2) and the posterior parts of the fusiform and inferior temporal gyri are involved in the integration of visual elements into perceptual wholes (single objects). Of these areas, the fusiform and inferior temporal gyri were more activated by tasks with recognizable stimuli than by tasks with unrecognizable stimuli. We propose that the posterior parts of the fusiform and inferior temporal gyri, compared with the inferior occipital gyri, are involved in higher level integration, due to the involvement of re-entrant activation from stored structural knowledge. Evidence in favor of this interpretation comes from the additional finding that activation of the anterior part of the left fusiform gyrus and a more anterior part of the right inferior temporal gyrus, areas previously associated with access to stored structural knowledge, was found with recognizable stimuli, but not with unrecognizable stimuli. This latter finding also indicates: (i) that subjects may not refrain from (automatically) identifying objects even if they only have to attend to the objects' global shape, and (ii) that perceptual and memorial processes can be dissociated on both functional and anatomical grounds. No evidence was obtained for the involvement of the parietal lobes in the integration of single objects.

The role of action knowledge in the comprehension of artefacts--a PET study.

Activation of the left ventral premotor cortex (PMv) has in previous imaging studies been associated with the processing of visually presented artefacts. It has been suggested that this activation reflects processing of action knowledge and that action knowledge contributes to the comprehension of artefacts. The purpose of the present study was to test whether activation of the left PMv is common for all tasks involving the comprehension of artefacts or whether it is task specific. This was done by comparing performance and regional cerebral blood flow (rCBF) associated with two categorization tasks and two naming tasks divided by category (natural objects vs artefacts). The left PMv (BA 6/44) was more activated by the categorization task for artefacts than by the categorization task for natural objects and the naming task for artefacts. However, the left PMv was not associated with the contrast between the naming task for artefacts and the naming task for natural objects nor with the processing of artefacts in general. If the PMv does mediate action knowledge, these results suggest that action knowledge does not contribute directly to the comprehension of artefacts but may support the categorization of artefacts. The significance of these findings is discussed in relation to category-specific recognition impairments for artefacts.

Endoscopic fluorescence spectroscopy in the upper GI tract for the detection of GI cancer: initial experience.

OBJECTIVE: The aim of this study was to investigate autofluorescence spectroscopy using violet-blue excitation light for the in vivo diagnosis of GI cancer during routine endoscopy. METHODS: Fluorescence spectra were obtained from normal mucosa and cancerous lesions of the esophagus and stomach. The spectroscopic system used comprised a special light source capable of delivering either white or violet-blue light to induce autofluorescence of tissue via the endoscope. Endogenous fluorescence spectra emitted by the tissue were recorded with a fiberoptic probe and analyzed with a spectrographic detector system consisting of a polychromator with a photodiode array and an optical multichannel analyzer. The data of each spectrum were sampled within the range of 450-700 nm and stored in a personal computer. RESULTS: Esophageal squamous cell cancer, adenocarcinoma of the esophagus, and adenocarcinoma of the stomach show specific differences in the emitted fluorescence spectra compared with normal mucosa. CONCLUSIONS: Light-induced fluorescence spectroscopy might be a useful tool for the endoscopic in vivo detection of dysplasia and early carcinoma in the upper GI tract. Further trials are needed to test the validity of this new optical detection system.

Structural similarity causes different category-effects depending on task characteristics.

It has been suggested that category-specific impairments for natural objects may reflect that natural objects are more globally visually similar than artefacts and therefore more difficult to recognize following brain damage [Aphasiology 13 (1992) 169]. This account has been challenged by the finding that the 'normal' disadvantage claimed for natural objects may be reversed when items from the categories of natural objects and artefacts are matched for visual complexity, familiarity and name frequency [Neuropsychologia 37 (1999) 1263]. In the experiments reported here it was investigated whether category effects could be found on object decision tasks (deciding whether pictures represented real objects or not), when the stimulus material was matched across categories. In experiment 1, a disadvantage for natural objects was found on difficult object decision tasks whereas no category difference was found on easy object decision tasks. In experiment 2 an advantage for natural objects was found during object decisions performed under degraded viewing conditions (lateralized stimulus presentation). It is argued that these findings can be accounted for by assuming that natural objects are more globally visually similar than artefacts, but that this difference between categories affects performance in different ways depending on task characteristics. Thus, the greater overlap between natural objects may be a disadvantage when the demand on perceptual differentiation is high (as it is in difficult object decision tasks). However, when viewing conditions are degraded and performance tends to depend on global shape information (carried by low spatial frequency components), natural objects may fare better than artefacts because the global shape of natural objects reveals more of their identity than the global shapes of artefacts.

Light-induced autofluorescence spectroscopy for the endoscopic detection of esophageal cancer.

BACKGROUND: Any innovative optical system that facilitates the early endoscopic detection of neoplastic change in the GI mucosa has the potential to greatly improve survival and quality of life for patients prone to have GI malignancies develop. The present article describes light-induced autofluorescence spectroscopy with violet-blue excitation light for in vivo diagnosis of cancerous tissue of the esophagus during routine endoscopy. METHODS: One hundred twenty-nine endogenous fluorescence spectra were obtained from normal mucosa and malignant lesions in 9 patients with squamous cell cancer and 4 with adenocarcinoma of the esophagus. Following spectrographic measurements, biopsy specimens were obtained for definitive classification of the spectra. A special light source capable of delivering either white or violet-blue light for excitation of tissue autofluorescence by means of an endoscope was used. Endogenous fluorescence spectra emitted by tissues were detected with a fiberoptic probe and analyzed with a spectrograph. RESULTS: Squamous cell cancer and adenocarcinoma of the esophagus exhibit specific changes in the emitted fluorescence spectra as compared with normal mucosa. Based on the results obtained in earlier studies, malignant and benign spectra were differentiated with the aid of a mathematical algorithm. By using this algorithm, a sensitivity of 97% and specificity of 95% were obtained for the diagnosis of esophageal carcinoma. CONCLUSIONS: Light-induced fluorescence spectroscopy is useful for the endoscopic detection of squamous cell cancer and adenocarcinoma of the esophagus. This spectroscopic study provides a basis for the design of a simplified autofluorescence imaging system for detection of esophageal neoplasms.

Gene expression of stromelysin and aggrecan in osteoarthritic cartilage.

OBJECTIVE: To analyze cartilage gene expression of patients with osteoarthritis (OA) in correlation with radiographic and histological findings. MATERIALS AND METHODS: Twenty-one patients with OA of the knee admitted for total knee replacement were analyzed clinically and radiographically by the Kellgren and Lawrence system. During surgery, cartilage samples from the medial and lateral condyles and tibial plateaus were harvested separately. Specimens were analyzed histologically (Mankin score) and total RNA was extracted directly from cartilage tissue. Steady state levels of stromelysin (MMP-3), aggrecan (AGG) and the house-keeping gene beta-actin were measured using quantitative PCR. RESULTS: Histology of medial and lateral knee compartments corresponded to radiographic changes (Spearman correlation coefficient: r = 0.7 (p < 0.01)). There was a positive correlation between MMP-3 and AGG gene expression (r = 0.4; p < 0.01). We found considerable variation of expression levels of MMP-3 and AGG and no correlation of gene expression with histological or radiographic scoring. CONCLUSION: The positive correlation between AGG and MMP-3 suggests a common regulation of anabolic and catabolic metabolism. There was no simple dependency between gene expression and histological and radiological findings in cartilage.

Categorization and category effects in normal object recognition: a PET study.

To investigate the neural correlates of the structural and semantic stages of visual object recognition and to see whether any effects of category could be found at these stages, we compared the rCBF associated with two categorization tasks (subjects decided whether pictures represented artefacts or natural objects), and two object decision tasks (subjects decided whether pictures represented real objects or nonobjects). The categorization tasks differed from each other in that the items presented in the critical scan window were drawn primarily from the category of artefacts in the one task and from the category of natural objects in the other. The same was true for the object decision tasks. The experiment thus comprised a two-by-two factorial design. The factors were Task Type with two levels (object decision vs. categorization) and Category also with two levels (natural objects vs. artefacts). The object decision tasks were associated with activation of areas involved in structural processing (fusiform gyri, right inferior frontal gyrus). In contrast, the categorization tasks were associated with activation of the left inferior temporal gyrus, a structure believed to be involved in semantic processing. In addition, activation of the left premotor cortex was found during the categorization of artefacts compared with both the categorization of natural objects and object decision to artefacts. These findings suggest that the structural and semantic stages are dissociable and that the categorization of artefacts, as opposed to the categorization of natural objects, is based, in part, on action knowledge mediated by the left premotor cortex. However, because artefacts and natural objects often caused activation in the same regions within tasks, processing of these categories is not totally segregated. Rather, the categories differ in their weight on different forms of knowledge in particular tasks.

Light-induced autofluorescence spectroscopy for tissue diagnosis of GI lesions.

BACKGROUND: The present article describes light-induced autofluorescence spectroscopy using violet-blue excitation light for endoscopic in vivo measurements in the upper GI tract. The spectra of normal mucosa, cancer, and dysplastic lesions of the esophagus and stomach are presented and compared. METHODS: Over 120 spectra were obtained in 11 patients of normal mucosa and malignant lesions in the esophagus and stomach during routine endoscopy. A special light source capable of delivering either white or violet-blue light was used for the excitation of tissue auto-fluorescence via the endoscope. Endogenous fluorescence spectra emitted by the tissue were collected with a fiberoptic probe and analyzed with a spectrograph. After spectrographic measurements biopsies were taken for definitive classification of histopathologic status. RESULTS: As compared with normal mucosa, (pre) cancerous lesions were associated with special changes in the emitted fluorescence spectra. The spectrographic records were influenced by the intensity of the illumination and on the position of the probe (distance and angle). CONCLUSION: Fluorescence spectroscopy with a slightly modified conventional light source might be useful for the endoscopic detection of dysplasia and early-stage carcinoma in the upper GI tract. Prospective trials need to determine the sensitivity and specificity of this new method.

Perceptual differentiation and category effects in normal object recognition: a PET study.

The purpose of the present PET study was (i) to investigate the neural correlates of object recognition, i.e. the matching of visual forms to memory, and (ii) to test the hypothesis that this process is more difficult for natural objects than for artefacts. This was done by using object decision tasks where subjects decided whether pictures represented real objects or non-objects. The object decision tasks differed in their difficulty (the degree of perceptual differentiation needed to perform them) and in the category of the real objects used (natural objects versus artefacts). A clear effect of task difficulty was found in both the behavioural and in the PET data. In the PET data, the increase in task difficulty was associated with increased regional cerebral blood flow in the posterior part of the right inferior temporal gyrus and in the anterior part of the right fusiform gyrus. This may be the neural correlate of matching visual forms to memory, and the amount of activation in these regions may correspond to the degree of perceptual differentiation required for recognition to occur. With respect to behaviour, it took significantly longer to make object decisions on natural objects than on artefacts in the difficult object decision tasks. Natural objects also recruited larger parts of the right inferior temporal and anterior fusiform gyri compared with artefacts as task difficulty increased. Differences in the amount of activation in these regions may reflect the greater perceptual differentiation required for recognizing natural objects. These findings are discussed in relation to category-specific impairments after neural damage.

The proliferation-associated nuclear protein Ki-67 in the bovine system: partial characterisation and its application for determination of the proliferation of Theileria-infected bovine cells.

Theileria annulata-infected bovine cells as well as mitogen-stimulated bovine peripheral blood mononuclear cells (PBMC) express a proliferation-associated nuclear protein equivalent to the human Ki-67 protein. In analogy to the human system, the expression of the bovine Ki-67 protein is restricted to proliferating cells only, since (a) Ki-67 expression paralleled [3H]-thymidine incorporation in concanavalin A (Con A)-stimulated bovine PBMC, (b) Ki-67 was not detectable in quiescent bovine cells, and (c) Ki-67 expression in Theileria-infected cells is related to the presence of the parasites within the cytoplasm of the host cells; upon treatment with the theilericidal drug buparvaquone the parasites are destroyed and the cells cease to proliferate and to express the Ki-67 protein. Western-blot analysis of lysates of proliferating bovine cells revealed that the prototype monoclonal antibody Ki-67 and the new equivalent antibody MIB-1 detected one prominent protein band with an apparent molecular weight of 430 kDa. Two cDNA clones (pUC18.B1.Ki-67 and pUC18.B2.Ki-67) were isolated from a lambdagt11 cDNA library of T. annulata-infected bovine cells by immunoscreening with the monoclonal antibody MIB-1. Comparison of these cDNA sequences with those of the human Ki-67 protein revealed 60-70% identity. Within the "Ki-67 motif", identity proved to be 80% at the amino acid level. The remarkable identity between bovine and human Ki-67 proteins suggests that MIB-1 can be used as a marker for cell proliferation in animal research. In this context we could identify proliferating cells in lymph nodes of Theileria-infected animals and, furthermore, we could distinguish between infected and uninfected proliferating cells using MIB-1 and an antiserum against a recombinant parasite protein designated SA288.