Live attenuated simian immunodeficiency virus (SIV)mac in macaques can induce protection against mucosal infection with SIVsm

OBJECTIVE: To investigate whether vaccination of macaques with attenuated simian immunodeficiency virus (SIV)macC8 could induce long-term protective immunity against rectal exposure to SIVsm and intravenous exposure to the more divergent HIV-2. DESIGN AND METHODS: Eight months after vaccination with live attenuated SIVmacC8, four cynomolgus monkeys were challenged with SIVsm intrarectally and another four vaccinated monkeys were challenged with HIV-2 intravenously. Sixteen months after SIVmacC8 vaccination, another two monkeys were challenged with SIVsm across the rectal mucosa. Two vaccinees shown to be protected against SIVsm were rechallenged 8 months after the first challenge. Ten naive animals were used as controls. Serum antigenaemia, virus isolation, antibody responses, cell-mediated immunity and CD4+ and CD8+ T-cell subpopulations were monitored. PCR-based assays were used to distinguish between virus populations. RESULTS: At the time of challenge, eight out of 10 vaccinees were PCR-positive for SIVmacC8 DNA but no virus could be isolated from peripheral blood mononuclear cells. After SIVsm challenge, three out of six vaccinees were repeatedly SIVsm PCR-negative. In one of the three infected monkeys, the challenge virus was initially suppressed but the monkey ultimately developed AIDS after increased replication of the pathogenic virus. Rechallenged monkeys remained protected. All HIV-2-challenged vaccinees became superinfected. All controls became infected with either SIVsm or HIV-2. At the time of challenge the vaccinees had neutralizing antibodies to SIVmac but no demonstrable cross-neutralizing antibodies to SIVsm or HIV-2. Titres of antigen-binding or neutralizing antibodies did not correlate with protection. Cytotoxic T-cell responses to SIV Gag/Pol and virus-specific T-cell proliferative responses were low. CONCLUSION: The live attenuated SIVmacC8 vaccine was able to induce long-term protection against heterologous intrarectal SIVsm challenge in a proportion of macaques but not against the more divergent HIV-2, which was given intravenously.     

Oral hygiene and gingivitis in a Swedish adult population 1973, 1983 and 1993

BACKGROUND: Hypertriglyceridaemia is a common metabolic disorder frequently found in patients with coronary heart disease. Numerous studies have revealed an association between the SstI polymorphism in the APOC3 gene and increased plasma apoC3 and triglyceride levels. In addition, two different variants within the promoter region have been recently suggested to be the mutations of the APOC3 gene leading to hypertriglyceridaemia. METHODS: In the present study, we have applied haplotype analysis to investigate whether these promoter polymorphisms are involved in the lipid disorders of patients with distinct types of hypertriglyceridaemia: combined hyperlipidaemia (CHL), familial dysbetalipoproteinaemia (FD) and endogenous hypertriglyceridaemia (HTG). RESULTS: The -482 and -455 polymorphisms were significantly more frequent in FD patients (P = 0. 017) and endogenous HTG patients (P < 0.0001) than in CHL patients and a control group. The SstI polymorphism was only significantly more frequent in HTG patients (P < 0.0001). However, we did not find differences in frequencies for these polymorphisms in the APOC3 gene between CHL patients and a control group. Haplotype analysis indicates that the SstI polymorphism arose on the allele containing both promoter polymorphisms. CONCLUSION: The haplotype containing the SstI polymorphism is found five times more frequently among HTG patients (OR 5.28, 95% CI 1.65-16.90), which strongly suggests it is associated with an increased risk for severe hypertriglyceridaemia.     

The role of intra-abdominal pressure in spinal unloading

Previous studies on how an increase in intra-abdominal pressure (IAP) effects the loading of the lumbar spine during back extension show diverging results. From a critical review of the literature we deduce a simplified, but consistent, model of the mechanisms involved in IAP-induced unloading of the lumbar spine. The model is then expanded by explicitly incorporating equilibrium equations for the pressurised abdomen and the abdominal wall. It is shown that the unloading effect of IAP can be viewed as that of a pressurised column of fixed cross-sectional area, between the rib cage and pelvis. Different abdominal forms are examined and a form with zero longitudinal curvature is found to have some important mechanical benefits for the generation of IAP-induced alleviation of compressive loading of the lumbar spine.     

Operationalising resilience for disaster medicine practitioners: capability development through training,simulation and reflection

Cognition, Technology & Work - Resilience has in recent decades been introduced as a term describing a new perspective within the domains of disaster management and safety management. Several...     

Primary human immunodeficiency virus type 2 (HIV-2) isolates, like HIV-1 isolates, frequently use CCR5 but show promiscuity in coreceptor usage

Coreceptor usage of primary human immunodeficiency virus type 1 (HIV-1) isolates varies according to biological phenotype. The chemokine receptors CCR5 and CXCR4 are the major coreceptors that, together with CD4, govern HIV-1 entry into cells. Since CXCR4 usage determines the biological phenotype for HIV-1 isolates and is more frequent in patients with immunodeficiency, it may serve as a marker for viral virulence. This possibility prompted us to study coreceptor usage by HIV-2, known to be less pathogenic than HIV-1. We tested 11 primary HIV-2 isolates for coreceptor usage in human cell lines: U87 glioma cells, stably expressing CD4 and the chemokine receptor CCR1, CCR2b, CCR3, CCR5, or CXCR4, and GHOST(3) osteosarcoma cells, coexpressing CD4 and CCR5, CXCR4, or the orphan receptor Bonzo or BOB. The indicator cells were infected by cocultivation with virus-producing peripheral blood mononuclear cells and by cell-free virus. Our results show that 10 of 11 HIV-2 isolates were able to efficiently use CCR5. In contrast, only two isolates, both from patients with advanced disease, used CXCR4 efficiently. These two isolates also promptly induced syncytia in MT-2 cells, a pattern described for HIV-1 isolates that use CXCR4. Unlike HIV-1, many of the HIV-2 isolates were promiscuous in their coreceptor usage in that they were able to use, apart from CCR5, one or more of the CCR1, CCR2b, CCR3, and BOB coreceptors. Another difference between HIV-1 and HIV-2 was that the ability to replicate in MT-2 cells appeared to be a general property of HIV-2 isolates. Based on BOB mRNA expression in MT-2 cells and the ability of our panel of HIV-2 isolates to use BOB, we suggest that HIV-2 can use BOB when entering MT-2 cells. The results indicate no obvious link between viral virulence and the ability to use a multitude of coreceptors.     

Dominant pattern extraction from 3-D kinematic data

The experiment examined the anticipatory modulation of grip force with respect to load force during a drawer opening task. An impact force was introduced by a mechanical stop that arrested movement of the pulling hand. The results showed a typical grip force profile which consisted of two evolving phases, one to control drawer movement onset, and the other to secure grip force at the expected impact. Initially, grip force increased with the load force that was developed to overcome the inertia of the drawer. After the first peak, a small decline was observed, followed by a proactive grip force increase prior to the time of impact. During this ramp-like increase of grip force, load force remained unchanged. In addition, a reactive response was triggered by the impact. That anticipatory control with respect to an impact force is not innate but, rather, is learned by experience was evidenced by a comparison of adults and children. Whereas adults made the characteristic grip force adjustments to anticipate the impact, children used a probing strategy with irregular build-up of force until impact. Furthermore, adults calibrated the second phase of the grip force profile in the initial trials of the task, indicating that grip force was rapidly updated with information related to the impact force. The present results demonstrate that grip-load force coordination during manipulation is a necessity for dealing with destabilizing load perturbations produced by self-induced movement and impact forces. It is concluded that grip force is adjusted automatically, but in a flexible manner, to secure grip in accordance with the characteristics of the pulling synergy.     

Effect of strength training on EMG of human skeletal muscle

An 8-year-old white girl with a history of vertigo, nausea, and vomiting developed a progressive hearing loss, bilateral retinal arteriolar narrowing in each eye, vasoproliferation, and subsequent intravitreal hemorrhage. An attempt at peripheral retinal ablation with cryotherapy in the left eye resulted in retinal detachment. Spontaneous retinal detachment occurred in the right eye and was successfully repaired. Repeated intermittent hemorrhages occurred despite intraocular diathermy. Three years after onset, visual acuity was R.E.: 6/21 (20/66) and L.E.: light perception. She remains totally deaf. A 20-year-old white woman developed severe bilateral sensorineural hearing loss with poorly functioning labyrinths, followed by midperipheral retinal arteriolar occlusions and vasoproliferation on the optic nerve head. Progressive retinal neovascularization was followed by rubeosis iridis and repeated episodes of intravitreal bleeding. Six years after onset, visula acuity was R.E.: hand motions, and L.E.: 6/3 (20/100). She remains totally deaf. Both patients were of normal gestation, development, and mentality, without evidence of other systemic disease. The cause of this disease was not found.     

Apparent inhibition to digestion by lignin in normal and brown midrib stems

Lignin, a cell wall component, limits digestibility of plant cell walls. Brown midrib (bmr) mutants of forages have lignin with altered chemical composition compared with their normal counterparts. The objectives of this study were to determine if bmr lignin is more inhibitory to digestion than is normal lignin and if bmr has a consistent effect on rate of digestion across species and environments. Extent and rate of in-vitro cell wall digestion of normal and bmr stems of sorghum (Sorghum bicolor (L) Moench, two comparisons), millet (Pennisetum americanum (L) Leeke) and maize (Zea mays L, two comparisons) were determined. Samples were incubated in rumen fluid, and data were fitted with a first-order, nonlinear model to estimate concentrations of potentially digestible neutral detergent fibre (PDNDF), digestion rate of PDNDF, concentration of indigestible residue (IR), and lag time before digestion. The NDF, acid-detergent fibre (ADF), and acid-detergent lignin (ADL) analyses were conducted sequentially on undigested samples. The IR: ADL ratio was 37% greater for bmr than for normal plants, which indicates that bmr lignin inhibits digestion more than normal lignin per unit of lignin. Digestion rate of PDNDF was faster in bmr than in normal counterparts in one of the two sorghum comparisons (difference of 59%) and in the millet comparison (difference of 27%), but in neither maize comparison. The bmr mutants were lower than normal genotypes in NDF (9%) and ADL (47%) concentrations. The PDNDF concentration was 19% greater for bmr than for normal lines. Thus, decreased lignin concentration in bmr mutants increased the extent of NDF digestion but did not consistently increase the rate of digestion.     

Distribution of periodontal disease in a Swedish adult population 1973, 1983 and 1993

The aim of this study was to compare changes in periodontal status in a Swedish population over a period of 20 years. Cross-sectional studies were carried out in J?nk?ping County in 1973, 1983, and 1993. Individuals were randomly selected from the following age groups: 20, 30, 40, 50, 60, and 70 years. A total of 600 individuals were examined in 1973, 597 in 1983, and 584 in 1993. The number of dentate individuals was 537 in 1973, 550 in 1983, and 552 in 1993. Based on clinical data and full mouth intra-oral radiographs, all individuals were classified into 5 groups according to the severity of the periodontal disease experience. Individuals were classified as having a healthy periodontium (group 1), gingivitis without signs of alveolar bone loss (group 2), moderate alveolar bone loss not exceeding 1/3 of the normal alveolar bone height (group 3), severe alveolar bone loss ranging between 1/3 and 2/3 of the normal alveolar bone height (group 4), or alveolar bone loss exceeding 2/3 of the normal bone height and angular bony defects and/or furcation defects (group 5). During these 20 years, the number of individuals in groups 1 and 2 increased from 49% in 1973 to 60% in 1993. In addition, there was a decrease in the number of individuals in group 3, the group with moderate periodontal bone loss. Groups 4 and 5 comprised 13% of the population and showed no change in general between 1983 and 1993. The individuals comprising these groups in 1993, however, had more teeth than those who comprised these groups in 1983; on the average, the individuals in disease group 4 had 4 more teeth and those in disease group 5, 2 more teeth per subject. In 1973, these 2 groups were considerably smaller, probably because of wider indications for tooth extractions and fewer possibilities for periodontal care which meant that many of these individuals had become edentulous and were not placed in a group. Individuals in groups 3, 4, and 5 were subdivided according to the number of surfaces (%) with gingivitis and periodontal pockets (> or =4 mm). In 1993, 20%, 42%. and 67% of the individuals in groups 3, 4, and 5 respectively were classified as diseased and in need of periodontal therapy with >20% bleeding sites and >10% sites with periodontal pockets > or =4 mm. In conclusion, an increase in the number of individuals with no marginal bone loss and a decrease in the number of individuals with moderate alveolar bone loss can be seen. The prevalence of individuals in the severe periodontal disease groups (4, 5) was unchanged during the last 10 years; however, the number of teeth per subject increased.     

The role of the abdominal musculature in the elevation of the intra-abdominal pressure during specified tasks

A series of standardized tasks, isometric trunk flexion and extension and maximal Valsalva manoeuvres, were used to evaluate the role of the abdominal musculature in developing an increased intra-abdominal pressure (IAP). Seven male subjects were measured for IAP, myoelectric activity of rectus abdominis (RA), obliquus externus and internus (OE and OI respectively), erector spinae (ES) and isometric trunk torque. IAPs in all experimental conditions were markedly greater than those that occurred while relaxed. In isometric trunk flexion, IAPs were increased with accompanying high levels of activity from the abdominal muscles. In contrast, little activity from the abdominal muscles occurred during isometric trunk extension, although levels of IAP were similar to those found in the isometric flexion condition. With maximal voluntary pressurization (Valsalva manoeuvre) slightly higher levels of IAP than those found in torque conditions were recorded, this pressure being produced with abdominal activities (OE and OI) less than one fourth their recorded maximum. When isometric torque tasks were added to the Valsalva manoeuvre, patterns of muscle activity (RA, OE, OI and ES) were significantly altered. For Valsalva with isometric trunk extension, activity from OE and OI was reduced while IAPs remained fairly constant. These findings indicate that in tasks where an IAP extension moment is warranted, abdominal pressure can be increased without the development of a large counter-moment produced by the dual action of the trunk flexors. Activation of other muscles such as the diaphragm and transversus abdominis is suggested as helping provide control over the level of IAP during controlled trunk tasks.