Antibody response after RSV infection in children younger than 1 year of age living in a rural area of Mozambique

Serological responses have been studied in respiratory syncytial virus (RSV) infected children < 1 year of age attending the outpatient department of the Manhiça District Hospital (Mozambique). Molecular characterization of viral RNA in nasopharyngeal aspirates from the infected children indicated a high level of genetic uniformity among the infecting viruses, all of which belonged to a single genotype of RSV group A. A representative virus strain, Moz00, was isolated from one of the infants and was used, together with the group A strain A2 and the group B strain 8/60, as antigens in the quantification of infant antibody responses. In this study, 97.5% (39/40) and 96.4% (27/28) of infected children produced an antibody response against Moz00 detected by the membrane fluorescent antibody test (MFAT) and the neutralization test (NT), respectively. Seroconversion rates decreased when the A2 and 8/60 strains were used as antigen in MFAT (95.4% and 88.2%, respectively) or NT (81.8% and 54.5%, respectively), indicating that antibody responses had both group‐ and strain‐specific components. Antibodies in convalescent sera of infected children were compared with maternally derived antibodies detected in a group of children also < 1 year of age, but with no evidence of RSV infection. The convalescent sera exhibited reduced neutralizing capacity when the 8/60 strain was used as antigen (P = 0.028), suggesting that the infant antibody response lacks neutralizing capacity against strains of the heterologous virus group. Restricted cross‐reactivity and neutralizing capacity of antibodies generated by young children might be expected to induce only moderate protection in subsequent epidemics against genetically distant strains. J. Med. Virol. 69:579–587, 2003. © 2003 Wiley‐Liss, Inc.     

Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice

CD4⁺ T cells in the mouse can be subdivided into two fractionsbased on the level of expression of the CD45RB determinant.Previous studies have shown that these subsets are functionallydistinct. We have further characterized the properties of thesesubpopulations in vivo by injecting them into C. B-17 scid mice.The animals restored with the CD45RB^highCD4⁺ T cell populationdeveloped a lethal wasting disease with severe mononuclear cellinfiltrates into the colon and elevated levels of IFN- mRNA.In contrast, animals restored with the reciprocal CD45RB^lowsubset or with unfractionated CD4⁺ T cells did not develop thewasting or colitis. Importantly, the co-transfer of the CD45RB^lowpopulation with the CD45RB^high population prevented the wastingdisease and colitis. These data indicate that important regulatoryinteractions occur between the CD45RB^high and CD45RB^lowCD4⁺T cell subsets and that disruption of this mechanism has fatalconsequences.     

The impact of working life on health behavior: the effect of job strain on the cognitive predictors of exercise

The theory of planned behavior (TPB) and R. A. Karasek's (1979) job strain model were used to investigate the predictors of exercise in a group of employees. A total of 241 employees completed an initial questionnaire; 1 week later 213 employees responded to a questionnaire measuring behavior. Employees in high-strain jobs did significantly less exercise than those in low-strain jobs, although they did not intend to do less, suggesting that work may impede the intention implementation. Intenders who failed to exercise had significantly higher work demands and lower exercise self-efficacy than intenders who succeeded in exercising. Work also affected exercise indirectly through self-efficacy. Thus, work may be a target for behavior change intervention because of its impact at 2 stages of the TPB.     

Relapsing diabetes can result from moderately activating mutations in KCNJ11

Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of transient neonatal diabetes (TNDM). Mutations in KCNJ11, which encodes Kir6.2, the pore-forming subunit of the ATP-sensitive potassium channel (K(ATP)), are the commonest cause of permanent neonatal diabetes (PNDM). In addition to diabetes, some KCNJ11 mutations also result in marked developmental delay and epilepsy. These mutations are more severe on functional characterization. We investigated whether mutations in KCNJ11 could also give rise to TNDM. We identified the three novel heterozygous mutations (G53S, G53R, I182V) in three of 11 probands with clinically defined TNDM, who did not have chromosome 6q24 abnormalities. The mutations co-segregated with diabetes within families and were not found in 100 controls. All probands had insulin-treated diabetes diagnosed in the first 4 months and went into remission by 7-14 months. Functional characterization of the TNDM associated mutations was performed by expressing the mutated Kir6.2 with SUR1 in Xenopus laevis oocytes. All three heterozygous mutations resulted in a reduction in the sensitivity to ATP when compared with wild-type (IC(50) approximately 30 versus approximately 7 microM, P-value for is all <0.01); however, this was less profoundly reduced than with the PNDM associated mutations. In conclusion, mutations in KCNJ11 are the first genetic cause for remitting as well as permanent diabetes. This suggests that a fixed ion channel abnormality can result in a fluctuating glycaemic phenotype. The multiple phenotypes associated with activating KCNJ11 mutations may reflect their severity in vitro.     

Modulation of immune responses to Mycobacterium bovis in cattle depleted of WC1(+) gamma delta T cells

It is accepted that cell-mediated immune responses predominate in mycobacterial infections. Many studies have shown that CD4(+) T cells produce Th1 cytokines, such as gamma interferon (IFN-gamma), in response to mycobacterial antigens and that the cytolytic activity of CD8(+) cells toward infected macrophages is important. However, the extent and manner in which gamma delta T cells participate in this response remain unclear. In ruminants, gamma delta T cells comprise a major proportion of the peripheral blood mononuclear cell population. We have previously shown that WC1(+) gamma delta T cells are involved early in Mycobacterium bovis infection of cattle, but their specific functions are not well understood. Here we describe an in vivo model of bovine tuberculosis in which the WC1(+) gamma delta T cells were depleted from the peripheral circulation and respiratory tract, by infusion of WC1(+)-specific monoclonal antibody, prior to infection. While no effects on disease pathology were observed in this experiment, results indicate that WC1(+) gamma delta T cells, which become significantly activated (CD25(+)) in the circulation of control calves from 21 days postinfection, may play a role in modulating the developing immune response to M. bovis. WC1(+)-depleted animals exhibited decreased antigen-specific lymphocyte proliferative response, an increased antigen-specific production of interleukin-4, and a lack of specific immunoglobulin G2 antibody. This suggests that WC1(+) gamma delta TCR(+) cells contribute, either directly or indirectly, toward the Th1 bias of the immune response in bovine tuberculosis--a hypothesis supported by the decreased innate production of IFN-gamma, which was observed in WC1(+)-depleted calves.     

Implementing a Stratified Vocational Advice Intervention for People on Sick Leave with Musculoskeletal Disorders: A Multimethod Process Evaluation

Journal of Occupational Rehabilitation - Purpose To perform a process evaluation of a stratified vocational advice intervention (SVAI), delivered by physiotherapists in primary care, for people on...     

Nutrient-Induced Cellular Mechanisms of Gut Hormone Secretion

The gastrointestinal tract can assess the nutrient composition of ingested food. The nutrient-sensing mechanisms in specialised epithelial cells lining the gastrointestinal tract, the enteroendocrine cells, trigger the release of gut hormones that provide important local and central feedback signals to regulate nutrient utilisation and feeding behaviour. The evidence for nutrient-stimulated secretion of two of the most studied gut hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), along with the known cellular mechanisms in enteroendocrine cells recruited by nutrients, will be the focus of this review. The mechanisms involved range from electrogenic transporters, ion channel modulation and nutrient-activated G-protein coupled receptors that converge on the release machinery controlling hormone secretion. Elucidation of these mechanisms will provide much needed insight into postprandial physiology and identify tractable dietary approaches to potentially manage nutrition and satiety by altering the secreted gut hormone profile.     

Puumala Virus Infection in Family,Switzerland

We report 3 cases of Puumala virus infection in a family in Switzerland in January 2019. Clinical manifestations of the infection ranged from mild influenza-like illness to fatal disease. This cluster illustrates the wide range of clinical manifestations of Old World hantavirus infections and the challenge of diagnosing travel-related hemorrhagic fevers.     

The implementation of an infection control bundle within a Total Care Burns Unit

AimTo evaluate the impact of the implementation of a best practice infection prevention and control bundle on healthcare associated burn wound infections in a paediatric burns unit.BackgroundBurn patients are vulnerable to infection. For this patient population, infection is associated with increased morbidity and mortality, thereby representing a significant challenge for burns clinicians who care for them.MethodsAn interrupted time series was used to compare healthcare associated burn wound infections in paediatric burn patients before and after implementation of an infection prevention and control bundle. Prospective surveillance of healthcare associated burn wound infections was conducted from 2012 to 2014. Other potential healthcare associated infection rates were also reviewed over the study period, including urinary tract infections, pneumonia, upper respiratory tract infections and sepsis. An infection prevention and control bundle developed in collaboration between the paediatric burn unit and infection control clinicians was implemented in 2013 in addition to previous standard practice.ResultsDuring the study period a total of 626 patients were admitted to the paediatric burns unit. Healthcare associated burn wound infections reduced from 34 in 2012 to 0 in 2014 following the implementation of the infection prevention and control bundle. Pneumonia and sepsis also reduced to 0 in 2013 and 2014, however one upper respiratory tract infection occurred in 2013 and urinary tract infections persisted in 2013.ConclusionThe implementation of an infection prevention and control bundle was effective in reducing healthcare associated burn wound infections, pneumonia and sepsis within our paediatric burns unit. Urinary tract infections remain a challenge for future improvement.