The two faces of presbyacusis: hearing impairment and psychosocial consequences

A study of hearing disability and handicap was performed in a sample of elderly persons living in an urban area of G?teborg, Sweden. The aim was to describe the psychosocial consequences of presbyacusis. For this purpose, elderly persons with fairly uncontaminated presbyacusis were chosen. The study group consisted of 154 persons (59 men and 95 women) between the ages of 70 and 91 with a median age of 78 years. The methods used included a self-assessed hearing instrument, pure-tone audiometry, and registration of desired services regarding rehabilitative audiology. The questionnaire included 26 items, 20 of them within four areas: assessment of normality, communication, quality of life and environment/orientation. The results showed that the assessment, whether the hearing was normal or not, was correlated with audiometrically measured hearing. Many of the participants expressed concern that their hearing had deteriorated. Communication situations with background noise were troublesome for many of the participants, but they had only minor problems when performing daily activities like shopping. The quality of life in general was only mildly affected by hearing loss. Items regarding environment and orientation showed varying results. Some everyday aspects of listening were related to hearing ability, but directional hearing was not correlated with measured hearing. In spite of the participants' worry about hearing deterioration, only 8% requested hearing aids as a result of the examination.     

Accumulation of a potent gammadelta T-cell stimulator after deletion of the lytB gene in Escherichia coli

Activation of human Vgamma9/Vdelta2 T cells by many pathogens depends on the presence of small phosphorylated non-peptide compounds derived from the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway of isoprenoid biosynthesis. We here demonstrate that in Escherichia coli mutants deficient in lytB, an essential gene of the MEP pathway, a potent Vgamma9/Vdelta2 T-cell activator accumulates by a factor of approximately 150 compared to wild-type E. coli. The compound responsible for the strong immunogenicity of this E. coli mutant was subsequently characterized and identified as a small pyrophosphorylated metabolite, with a molecular mass of 262 Da, derived from the MEP pathway. Stimulation of human peripheral blood mononuclear cells (PBMC) with extracts prepared from the lytB-deficient E. coli mutant led to upregulation of T-cell activation markers on the surface of Vgamma9/Vdelta2 T cells as well as proliferation and expansion of Vgamma9/Vdelta2 T cells. This response was dependent on costimulatory growth factors, such as interleukin (IL)-2, IL-15 and IL-21. Significant levels of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were secreted in the presence of IL-2 and IL-15, but not in the presence of IL-21, demonstrating that proliferating phosphoantigen-reactive Vgamma9/Vdelta2 T cells do not necessarily produce proinflammatory cytokines.     

Hearing confirms existence and identity--experiences from persons with presbyacusis

The purpose of the present qualitative study was to describe how elderly persons with presbyacusis experience living with that type of hearing loss. The ultimate goal is for these experiences to be used in personal-adjustment counselling in audiological rehabilitation. The study included seven men and seven women with mild-to-moderate hearing impairment of the typical presbyacusis type. Open-ended interviews were conducted with each person. The interviewees were analysed according to the phenomenographic approach, and 10 categories emerged: 'Conversation takes away or maintains identity', 'It's other people's fault that I can't hear', 'Other people make you realize you can't hear', 'Society makes you think you shouldn't mind about your hearing loss', 'It's natural to hear badly when you are old', 'You should hear well all your life', 'You want to keep a feeling of continuity in your daily life in spite of your hearing loss', 'You don't need to hear everything', 'You want to hear so you feel that you're alive', and 'You want to hear so you understand and keep yourself informed'. All these categories deal with identity or existence and form the basis for how the hearing impairment is experienced and managed. The subjects protected their identity in various ways, but above all by blaming their poor hearing on old age, and managing it with simple everyday strategies that did not break the feeling of continuity in everyday life. Not until they experienced the lack of sound as a lack of contact with life was there any interest in help in the form of hearing technology. There is a need for information about the possibility of rehabilitating presbyacusis, as hearing is important not only for communication and spatial orientation, but also as affirmation of our existence as human beings.     

Chronic sorrow in next of kin of patients with multiple sclerosis

The well-being of patients' next of kin can be an important factor with regard to the care and rehabilitation of patients with multiple sclerosis (MS). The aim of this qualitative study was to explore the presence and meaning of chronic sorrow in a group of next of kin of patients with MS. Using a semistructured interview guide as a basis, 44 next of kin were interviewed. The results showed that 35 (80%) of the participants were considered to have chronic sorrow based on predetermined criteria. Three main themes characterized the meaning of chronic sorrow: loss of security, loss of sense of community in family life, and loss of joy and recreation. This study indicates that nurses need to devote greater attention to the well-being of next of kin, offering support programs to help them cope with chronic sorrow.     

Genetically attenuated Plasmodium berghei liver stages induce sterile protracted protection that is mediated by major histocompatibility complex Class I-dependent interferon-gamma-producing CD8+ T cells

At present, radiation-attenuated plasmodia sporozoites ( gamma -spz) is the only vaccine that induces sterile and lasting protection in malaria-naive humans and laboratory rodents. However, gamma -spz are not without risks. For example, the heterogeneity of the gamma -spz could explain occasional breakthrough infections. To avoid this possibility, we constructed a double-knockout P. berghei parasite by removing 2 genes, UIS3 and UIS4, that are up-regulated in infective spz. We evaluated the double-knockout Pbuis3(-)/4(-) parasites for protective efficacy and the contribution of CD8(+) T cells to protection. Pbuis3(-)/4(-) spz induced sterile and protracted protection in C57BL/6 mice. Protection was linked to CD8(+) T cells, given that mice deficient in beta (2)m were not protected. Pbuis3(-)/4(-) spz-immune CD8(+) T cells consisted of effector/memory phenotypes and produced interferon- gamma . On the basis of these observations, we propose that the development of genetically attenuated P. falciparum parasites is warranted for tests in clinical trials as a pre-erythrocytic stage vaccine candidate.     

A possible mechanism for endogenous activation of the type I interferon system in myositis patients with anti-Jo-1 or anti-Ro 52/anti-Ro 60 autoantibodies

OBJECTIVE: To investigate type I interferon (IFN) system activation and its correlation with autoantibodies and organ manifestations in polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. METHODS: Sera from 30 patients and 16 healthy controls, or purified IgG, were combined with material released from necrotized cells to stimulate IFNalpha production by peripheral blood mononuclear cells (PBMCs) from healthy blood donors. Muscle biopsy specimens from 25 patients and 7 healthy controls were investigated for blood dendritic cell antigen 2 (BDCA-2)-positive plasmacytoid dendritic cells (PDCs) and IFNalpha/beta-inducible myxovirus resistance 1 (MX-1) protein. RESULTS: Sera from 13 patients who were positive for anti-Jo-1 or anti-Ro 52/anti-Ro 60 autoantibodies induced IFNalpha production in PBMCs when combined with necrotic cell material. In addition, IgG prepared from anti-Jo-1-positive PM sera induced IFNalpha with necrotic material, but not when the latter was treated with RNase. BDCA-2 expression in PDCs in muscle tissue was increased in PM patients with anti-Jo-1 autoantibodies, while MX-1 staining in capillaries was increased in DM patients, compared with healthy individuals. IFNalpha-inducing capacity correlated with interstitial lung disease, while MX-1 expression in the capillaries correlated with DM. CONCLUSION: Immune complexes containing anti-Jo-1 or anti-Ro 52/anti-Ro 60 autoantibodies and RNA may act as endogenous IFNalpha inducers that activate IFNalpha production in PDCs. These PDCs could be of importance for inducing myositis, whereas in DM patients without autoantibodies the presence of MX-1 protein in capillaries suggests another cellular IFNalpha source and induction mechanism. Consequently, the type I IFN system may be of importance in both PM and DM, but via different pathways.     

Plasmodium liver stage developmental arrest by depletion of a protein at the parasite-host interface

Plasmodium parasites of mammals, including the species that cause malaria in humans, infect the liver first and develop there into clinically silent liver stages. Liver stages grow and ultimately produce thousands of first-generation merozoites, which initiate the erythrocytic cycles causing malaria pathology. Here, we present a Plasmodium protein with a critical function for complete liver stage development. UIS4 (up-regulated in infective sporozoites gene 4) is expressed exclusively in infective sporozoites and developing liver stages, where it localizes to the parasitophorous vacuole membrane. Targeted gene disruption of UIS4 in the rodent model malaria parasite Plasmodium berghei generated knockout parasites that progress through the malaria life cycle until after hepatocyte invasion but are severely impaired in further liver stage development. Immunization with UIS4 knockout sporozoites completely protects mice against subsequent infectious WT sporozoite challenge. Genetically attenuated liver stages may thus induce immune responses, which inhibit subsequent infection of the liver with WT parasites.