Enhanced protection conferred by mucosal BCG vaccination associates with presence of antigen-specific lung tissue-resident PD-1+ KLRG1- CD4+ T cells.

BCG, the only vaccine licensed against tuberculosis, demonstrates variable efficacy in humans. Recent preclinical studies highlight the potential for mucosal BCG vaccination to improve protection. Lung tissue-resident memory T cells reside within the parenchyma, potentially playing an important role in protective immunity to tuberculosis. We hypothesised that mucosal BCG vaccination may enhance generation of lung tissue-resident T cells, affording improved protection against Mycobacterium tuberculosis. In a mouse model, mucosal intranasal (IN) BCG vaccination conferred superior protection in the lungs compared to the systemic intradermal (ID) route. Intravascular staining allowed discrimination of lung tissue-resident CD4+ T cells from those in the lung vasculature, revealing that mucosal vaccination resulted in an increased frequency of antigen-specific tissue-resident CD4+ T cells compared to systemic vaccination. Tissue-resident CD4+ T cells induced by mucosal BCG displayed enhanced proliferative capacity compared to lung vascular and splenic CD4+ T cells. Only mucosal BCG induced antigen-specific tissue-resident T cells expressing a PD-1+ KLRG1- cell-surface phenotype. These cells constitute a BCG-induced population which may be responsible for the enhanced protection observed with IN vaccination. We demonstrate that mucosal BCG vaccination significantly improves protection over systemic BCG and this correlates with a novel population of BCG-induced lung tissue-resident CD4+ T cells.

Audit of the aetiology and prevalence of pulmonary hypertension in a tertiary hospital setting.

Appropriate diagnosis and initiation of disease-specific treatment is an important therapeutic goal in idiopathic pulmonary arterial hypertension. We evaluated the prevalence and aetiology of moderate-to-severe pulmonary hypertension in a cohort of patients referred for inpatient echocardiography, with significant pulmonary hypertension documented in 4.6%. Pulmonary hypertension complicating left heart disease was the most common aetiology, with idiopathic pulmonary arterial hypertension less frequent.

Upregulation of IL-17A, CXCL9 and CXCL10 in early-stage granulomas induced by Mycobacterium bovis in cattle.

To gain further insight into the immunopathogenesis of bovine tuberculosis (bTB), the cytokine and chemokine expression of cattle experimentally infected with Mycobacterium bovis was analysed in TB granulomas, using immunohistochemistry (IHC) and laser capture microdissection (LCM) followed by qPCR. Immunohistochemistry was conducted for cell types using labelling for CD68, CD3, CD4, CD8, WC1 and CD79a and for the cytokines IFN-γ, TNF-α and TGF-ß as well as inducible form of nitric oxide synthase (iNOS). qPCR was conducted for mRNA expression of IFN-γ, TNF-α, TGF-ß, IL-17A, IL-22, IL-2, granzyme A and the chemokines CXCL9 and CXCL10. Early stages of granuloma were primarily comprised of epithelioid MΦs expressing high levels of IFN-γ and iNOS, with significantly upregulated expression of CXCL9 and CXCL10 when compared with control tissue. These chemokines displayed a trend of decreasing mRNA expression as lesion progressed, suggesting a higher level of importance during the early stages of the immune response to mycobacterial infection. IL-22 levels showed a strong trend of decrease through granuloma development, and IL-17A was shown to be upregulated, supporting its investigation as a potential biomarker of bTB. The use of LCM and qPCR may prove especially useful for the study of IL-17A as previous attempts to analyse its expression using IHC and in situ hybridization proved unsuccessful.

Transplantation prospects for the inner retina.

Transplantation of stem or progenitor cells is an attractive new approach for treating neurodegenerative conditions of the central nervous system, which aims to protect or replace neurons and improve function. Proof of principle has already been shown in the retina that photoreceptors may be replaced by transplantation of neural progenitor cells. However, the task of retinal ganglion cell replacement is much more complex, as new cells will need to establish complex connections within the retina and also extend axons to precise targets in the brain. Although progress has been made in this field, it is likely that neuroprotective clinical applications will be established more quickly. Our laboratory has focused on the intraocular transplantation of cells to treat inner retinal disease, either by neuronal replacement or neuroprotection of existing cells. We have investigated the efficacy and effects of transplanting a variety of cell types, including human Müller stem cells (MIO-M1), oligodendrocyte precursor cells (OPCs), and bone marrow-derived mesenchymal stromal cells (MSCs) in a rat model of experimentally induced glaucoma. We also have developed and characterized a novel in vitro organotypic retinal explant culture system for exploring the methods of enhancing the efficacy of cell transplantation for the inner retina. In this review, we discuss the potentially beneficial effects of intraocular cell injections, identify current shortcomings of retinal stem cell therapy, and suggest directions for future research.

Stem cells for neuroprotection in glaucoma.

Stem cell transplantation is currently being explored as a therapy for many neurodegenerative diseases including glaucoma. Cellular therapies have the potential to provide chronic neuroprotection after a single treatment, and early results have been encouraging in models of spinal cord injury and Parkinson's disease. Stem cells may prove ideal for use in such treatments as they can accumulate at sites of injury in the central nervous system (CNS) and may also offer the possibility of targeted treatment delivery. Numerous stem cell sources exist, with embryonic and fetal stem cells liable to be superseded by adult-derived cells as techniques to modify the potency and differentiation of somatic cells improve. Possible neuroprotective mechanisms offered by stem cell transplantation include the supply of neurotrophic factors and the modulation of matrix metalloproteinases and other components of the CNS environment to facilitate endogenous repair. Though formidable challenges remain, stem cell transplantation remains a promising therapeutic approach in glaucoma. In addition, such studies may also provide important insights relevant to other neurodegenerative diseases.

[Efficacy of an intervention programme on burnout symptoms of partners of depressed patients]. / Wirksamkeit eines Interventionsprogramms auf die Burnout-Belastung von Lebenspartnern depressiv Erkrankter.

AIM OF THE STUDY: A newly developed group intervention programme was evaluated with regard to its effectiveness to decrease the burnout symptoms of the partners of depressed patients. METHODS: Within a period of six months, a group of 66 persons has taken part in the intervention for a total of twelve group sessions. A control group consisted of 50 persons without any intervention. Burnout was assessed using the German version of the Maslach Burnout Inventory (MBI). To evaluate the time effect, the burnout dimensions were used as independent variables in random effects models. RESULTS: Over the analyzed period of time no significant positive effect was measured on any of the assessed burnout dimensions. CONCLUSIONS: An increased inclusion of depressed patients in the intervention as well as an increased intensity and a lowering of the admission threshold for the heavily burdened relatives could increase the effectiveness of the program.

[A programme to assist close relatives and lifelong partners in caring for persons suffering from depressions or schizophrenic disorders]. / Ein Unterstützungsprogramm für Lebenspartner von Menschen mit depressiven oder schizophrenen Störungen.

OBJECTIVE: Lifelong partners or close relatives of persons suffering from mental disorders will naturally step in to help by assuming a great variety of tasks. By witnessing their relative's illness on a daily basis, they are exposed to many burdens with a negative impact on their own well-being. Hence, supporting the relatives of persons with mental disorders appears imperative. While there are various approaches to working with relatives, there are hardly any specific programmes for working with certain groups of relatives such as spouses, children or siblings. METHODS: Basing on a discussion of the various approaches to looking after relatives, development of a programme is described aimed at specifically supporting spouses of persons suffering from depression or schizophrenia. RESULTS: The concept of our programme is presented and results of its evaluation by participants are reported. CONCLUSION: The initial experiences with the support programme are quite promising. An evaluation of its effects, based on a case-control-design, is currently under way.

Work-related injuries and occupational health and safety factors in smaller enterprises--a prospective study.

The aim of this study was to determine whether any of the health, environmental and safety (HES) factors registered by visiting small mechanical enterprises in Norway at the start of the study could predict the risk of occupational injuries in subsequent years. Twelve HES factors, including injury awareness, programme for action, employee participation, training and use of personal safety devices, were registered. A questionnaire was completed by interviewing the employer and observing production. Two variables based on observation of the use of safety equipment were significantly correlated with occupational injuries. There is potential for prevention in smaller enterprises by increasing the use of personal protection devices and safety equipment on machines. Frequent inspection with feedback to the workers is probably the most effective means of attaining the desired result of reducing injuries.

Brood insurance via protogyny: a source of female-biased sex allocation.

Sex allocation patterns and colony productivity are examined in Exoneura nigrescens, a social allodapine bee. As for previous studies on Australian allodapine bees, numerical sex ratios were strongly female biased in the smallest broods, but neared equality in larger broods. Local fitness enhancement has been suggested previously to explain female-biased allocation in allodapine bees. Here, we propose an alternative model, the 'insurance model', which predicts protogyny and, as a consequence, female-biased sex allocation in small broods with decreasing bias in larger broods. Because allodapine broods are reared progressively in an open burrow, broods require that adult females be present throughout their development in order to survive to maturity. If mothers invest in daughters (alloparents) first, these daughters can rear younger, dependent brood in cases in which orphaning occurs. If such daughters behave as surrogate mothers, then investment in them by mothers should not be regarded as investment in female sex allocation per se, giving rise to apparently female-biased broods. The model predicts a pattern of sex ratios as a function of total brood size that very closely match empirical data from E. nigrescens.

Differential perturbation of neuronal and glial glutamate transport systems in retinal ischaemia.

Glutamate is the major excitatory neurotransmitter in the retina and is removed from the extracellular space by an energy-dependent process involving neuronal and glial cell transporters. The radial glial Müller cells express the glutamate transporter, GLAST, and preferentially accumulate glutamate. However, during an ischaemic episode, extracellular glutamate concentrations may rise to excitotoxic levels. Is this catastrophic rise in extracellular glutamate due to a failure of GLAST? Using immunocytochemistry, we monitored the transport of the glutamate transporter substrate, D-aspartate, in the retina under normal and ischaemic conditions. Two models of compromised retinal perfusion were compared: (1) Anaesthetised rats had their carotid arteries occluded for 7 days to produce a chronic reduction in retinal blood flow. Retinal function was assessed by electroretinography. D-aspartate was injected into the eye for 45 min. Following euthanasia, the retina was processed for D-aspartate, GLAST and glutamate immunocytochemistry. Although reduced retinal perfusion suppresses the electroretinogram b-wave, neither retinal histology, GLAST expression, nor the ability of Müller cells to uptake D-aspartate is affected. As this insult does not appear to cause excitotoxic neuronal damage, these data suggest that GLAST function and glutamate clearance are maintained during periods of reduced retinal perfusion. (2) Occlusion of the central retinal artery for 60 min abolishes retinal perfusion, inducing histological damage and electroretinogram suppression. Although GLAST expression appears to be normal, its ability to transport D-aspartate into Müller cells is greatly reduced. Interestingly, D-aspartate is transported into neuronal cells, i.e. photoreceptors, bipolar and ganglion cells. This suggests that while GLAST is vitally important for the clearance of excess extracellular glutamate, its capability to sustain inward transport is particularly susceptible to an acute ischaemic attack. Manipulation of GLAST function could alleviate the degeneration and blindness that result from ischaemic retinal disease.

Occupational injuries to fisheries workers in Norway reported to insurance companies from 1991 to 1996.

Fisheries work is one of the occupations at highest risk for occupational accidents in many countries. It is necessary to understand the injuries in order to prevent them. This study of occupational injury claims by fisheries workers in Norway made to insurance companies from 1991 to 1996 analysed the workers' age, time of injury, injury type, part of the body involved, injury event and cost. The highest injury incidence rates were among the younger fisheries workers and during the winter months. Bruises and fractures were the most frequent injury types, and fingers and hands were most often affected, whereas falls and accidents related to machines were the most common causes. Safety measures should be taken on board to prevent falls and machine-related injuries, and young fisheries workers should have better on-the-job training.

Mechanisms of occupational injuries reported to insurance companies in Norway from 1991 to 1996.

BACKGROUND: To study the association of injury events, types of movements and types of objects involved in relation to occupation, age, and gender in serious occupational injuries to determine where preventive measures should be implemented. METHODS: The occupational injury claims made to the insurance companies in Norway for 1991-1996, which were stored in a database, were analyzed. RESULTS: Falls were the most frequent injury event in both genders and in all occupational groups, and the incidence rate increased with age. Among men, the most common action when the injury occurred was handling of goods or materials, whereas for women it was moving without goods or materials. Primary economic activity and manufacturing had the highest injury rates. CONCLUSIONS: Priority should be given to reduce the occurrence of falls in both genders, and especially among older workers.

Compensation for occupational injury and disease in Norway: ranking of job groups.

The health risk of various job groups in Norway was estimated by ranking them according to the annual occupational insurance costs per capita. This was done by dividing the costs of work-related injury and disease from 1991 to 1996 in various job groups by the number of workers in these groups. Occupational groups were also ranked according to total annual costs. The five occupational groups with the highest total costs were metalworkers, woodworkers, nursing-related workers, fisheries workers, and teachers. The groups with the highest annual cost per worker were shoe and leather workers, oil and gas extractors, fisheries workers, miners and quarry workers, and ship's officers. Fisheries workers and ship's officers were ranked among the top 10 positions on both lists and deserve priority in preventive measures.

[Skin reaction after St Lucia holiday celebration]. / Hudreaksjon etter luciafeiring.

A 37-year-old man developed contact dermatitis on the front head after being exposed to dripping candles. The candles were placed in a crown on his head as he played St. Lucia in the traditional Lucia Day (13th December) pageant, trying to entertain the administrative staff of the University of Bergen where he was employed. Afterwards he washed his head with a soap he normally did not use. Probably the contact dermatitis is a skin reaction to the soap, but it is difficult to say whether the reaction was irritative or allergic. A similar case has not been reported earlier. It is of importance that noone stops celebrating the Lucia Day. However, proper precautions must be taken, with routines for avoiding exposure to stearine or unfamiliar soaps on the head of Lucia.

Occupational injuries reported to insurance companies in Norway from 1991 to 1996.

Occupational injuries represent a relatively high proportion of the total number of injuries in Norway and thereby deserve more attention than they are currently receiving. Occupational injury claims made to insurance companies in Norway from 1991 to 1996 were analyzed for determination of their patterns. The types of injury with the highest incidence rates among men were fractures; among women, the highest rates were for those for sprains. The injury rates were more than twice as high in young men as in young women; this difference declined with increasing age. Young men had an increased risk of finger injuries, compared with older age groups. The injury rates increased with increasing age, especially for fractures and contusions. A somewhat higher number of injuries per working day occurred in January and February than in the other months. Action should be taken to prevent fractures and contusions among older workers.

Influence of paternal exposure to oil and oil products on time to pregnancy and spontaneous abortions.

The objective of this study was to evaluate the influence of exposure to oil and oil products among men on the time taken for their wives to conceive and on the incidence of spontaneous abortion among them. A cross-sectional study was performed by posting questionnaires to 1,269 men employed as offshore mechanics, offshore operators, offshore drilling personnel, car mechanics (the 'exposed' occupations) and carpenters ('unexposed'). The married men were asked to give a separate questionnaire to their wives for details about their pregnancies. The time elapsed between the beginning of coitus without contraception and the wife becoming pregnant (time to pregnancy) was analyzed with Cox regression analysis by calculating fecundability ratios for the pregnancies for the men exposed to oil and oil products as compared with the men who were not exposed. Spontaneous abortions were analyzed with logistic regression by calculating odds ratios for the pregnancies in which the men were exposed vs. not exposed. A total of 741 (58%) men returned the questionnaires. A total of 301 pregnancies were analyzed for time taken to conceive and 580 for spontaneous abortion. The results were adjusted for variables that could significantly influence conception time (previous infections of the reproductive system and coffee drinking) or the incidence of spontaneous abortion (mother's age, parity and smoking). The outcomes between the exposed and unexposed pregnancies showed no significant differences. Car mechanics had a lower fecundability ratio before 1992 than after 1992. Paternal exposure to hydrocarbons in the occupations studied did not seem to have had a major influence on time to conception or the incidence of spontaneous abortion among the wives of the men exposed to oil products.

Dietary habits, food consumption, and nutrient intake during adolescence.

Adolescents and young adults adopt eating patterns which may well form the basis of their dietary habits for much of their lives. At the same time, this section of the population can come under considerable pressure from the world at large, to conform to the current trends in fashion, language, behavior, or foods. Recent developments in Western dietary practice have tended to leave adolescents vulnerable to low intakes of energy and of some nutrients, as snacking accounts for an increasing proportion of dietary intake. Achieving a balanced diet is more difficult when the most popular and widely available snack foods are high in sugar or in fat. Results from major British studies, together with a review of data from other developed countries, support the need for more effective dietary education for adolescents and for children generally.

Affects, demographic variables, and health.

The revised Multiple Affect Adjective Check List (MAACL-R) was given to a national probability sample that consisted of 1,543 adults who also were interviewed, which provided demographic data and self-ratings of health, medication use, and social activities. Standardization procedures have reduced markedly the acquiescence factor and the correlations among the dysphoric affect scales in the MAACL-R. The demographic variables of sex, race, age, education, occupation, income, marital status, religion, geographical area of residence, and size of town or city were related to some of the scales. Positive affect was related directly to self-ratings of health; dysphoric affect was related negatively to these ratings. Frequencies of volunteer activities and social activities in general correlated negatively with depression and positively with positive affect scales.