Mortality after Hospitalization for Pneumonia among Individuals with HIV, 1995–2008: A Danish Cohort Study

Background

HIV–infected persons are at increased risk of pneumonia, even with highly active antiretroviral treatment (HAART). We examined the impact of pneumonia on mortality and identified prognostic factors for death among HIV–infected.

Methodology/Principal Findings

In a nationwide, population-based cohort of individuals with HIV, we included persons hospitalized with pneumonia from the Danish National Hospital Registry and obtained mortality data from the Danish Civil Registration System. Comparing individuals with and without pneumonia, we used Poisson regression to estimate relative mortality and logistic regression to examine prognostic factors for death following pneumonia. From January 1, 1995, to July 1, 2008, we observed 699 episodes of first hospitalization for pneumonia among 4,352 HIV patients. Ninety-day mortality after pneumonia decreased from 22.4% (95% confidence interval [CI]: 16.5%–28.9%) in 1995–1996 to 8.4% (95% CI: 6.1%–11.6%) in 2000–2008. Mortality remained elevated for more than a year after hospitalization for pneumonia: adjusted mortality rate ratio 5.38 (95% CI: 4.27–6.78), 1.80 (95% CI: 1.36–2.37), and 1.62 (95% CI: 1.32–2.00) for days 0–90, 91–365, and 366+, respectively. The following variables predicted mortality within 90 days following hospitalization for pneumonia (adjusted Odds Ratios): male sex (3.77, 95% CI: 1.37–10.4), Charlson Comorbidity Index score ≥2 (3.86, 95% CI: 2.19–6.78); no current HAART (3.58, 95% CI: 1.83–6.99); history of AIDS (2.46, 95% CI: 1.40–4.32); age per 10 year increase (1.43, 95% CI: 1.11–1.85); and CD4+ cell count ≤200 (2.52, 95% CI: 1.37–4.65).

Conclusions/Significance

The first hospitalization for pneumonia among HIV–infected individuals was associated with elevated risk of death up to more than a year later. Use of HAART decreased the risk, independent of current CD4+ cell count. Prognosis following pneumonia improved over calendar time.     

High Calcium–Magnesium Ratio in Hair Is Associated with Coronary Artery Calcification in Middle-Aged and Elderly Individuals

The interaction between calcium and magnesium as a risk modifier for cardiovascular disease (CVD) has been largely overlooked in previous studies, for the strict regulatory system in blood has been thought to keep such homeostatic interactions under tight control. This study aimed to investigate the association between calcium–magnesium ratio in hair and subclinical coronary artery calcification. Using multiple linear regression analysis, we examined the associations between calcium–magnesium ratio in hair and the coronary calcium score (CCS) in 216 Koreans aged 40 years and above (122 men and 94 women). We found that the calcium-to-magnesium ratio in hair was independently and positively associated with CCS after adjusting for age and sex (regression coefficient 6.051 ± 2.329, P = 0.010). When we assessed the association between the calcium–magnesium ratio and CCS after adjusting for potential cardiovascular risk factors and vascular function modifying drugs, we found that the strength of association with CCS was comparable to before (regression coefficient 5.434 ± 2.523, P = 0.032). Our findings suggest that among middle-aged and elderly Koreans without clinical CVD, the association between coronary artery calcification and hair calcium–magnesium ratio is stronger in those with a higher calcium–magnesium ratio in hair than in those with a lower ratio.     

Does Pet Arrival Trigger Prosocial Behaviors in Individuals with Autism?

Alteration of social interactions especially prosocial behaviors - an important aspect of development - is one of the characteristics of autistic disorders. Numerous strategies or therapies are used to improve communication skills or at least to reduce social impairments. Animal-assisted therapies are used widely but their relevant benefits have never been scientifically evaluated. In the present study, we evaluated the association between the presence or the arrival of pets in families with an individual with autism and the changes in his or her prosocial behaviors. Of 260 individuals with autism - on the basis of presence or absence of pets - two groups of 12 individuals and two groups of 8 individuals were assigned to: study 1 (pet arrival after age of 5 versus no pet) and study 2 (pet versus no pet), respectively. Evaluation of social impairment was assessed at two time periods using the 36-items ADI-R algorithm and a parental questionnaire about their child-pet relationships. The results showed that 2 of the 36 items changed positively between the age of 4 to 5 (t(0)) and time of assessment (t(1)) in the pet arrival group (study 1): "offering to share" and "offering comfort". Interestingly, these two items reflect prosocial behaviors. There seemed to be no significant changes in any item for the three other groups. The interactions between individuals with autism and their pets were more - qualitatively and quantitatively - reported in the situation of pet arrival than pet presence since birth. These findings open further lines of research on the impact of pet's presence or arrival in families with an individual with autism. Given the potential ability of individuals with autism to develop prosocial behaviors, related studies are needed to better understand the mechanisms involved in the development of such child-pet relationship.     

Kleptoparasitic Melees��Modelling Food Stealing Featuring Contests with Multiple Individuals

Kleptoparasitism is the stealing of food by one animal from another. This has been modelled in various ways before, but all previous models have only allowed contests between two individuals. We investigate a model of kleptoparasitism where individuals are allowed to fight in groups of more than two, as often occurs in real populations. We find the equilibrium distribution of the population amongst various behavioural states, conditional upon the strategies played and environmental parameters, and then find evolutionarily stable challenging strategies. We find that there is always at least one ESS, but sometimes there are two or more, and discuss the circumstances when particular ESSs occur, and when there are likely to be multiple ESSs.     

Factors Influencing Turning and Its Relationship with Falls in Individuals with Parkinson’s Disease

Background

Falls are a major problem for people with Parkinson’s disease (PD). Many studies indicate that more than 50% of people with PD have difficulty in turning that may lead to falls during daily activities. The aims of this study were to identify the relationship between turning performance and falls, and to determine the factors that influence turning performance.

Methods

This study examined 45 patients with idiopathic PD (Hoehn and Yahr stage 1–3) using a battery of tests, including 180° turn time, balance, and muscle strength. The levels of disease severity and freezing of gait were also measured. The number of falls in the past 6 months was recorded.

Results

Sixteen out of forty-five participants experienced falls in the past 6 months. A receiver operating characteristic curve showed that turn time was highly related to falls [more affected side: sensitivity = 0.81, specificity = 0.79, area under the curve (AUC) = 0.83; less affected side: sensitivity = 0.88, specificity = 0.76, AUC = 0.83]. The most important factor influencing turn time was balance ability (both sides: p = 0.000) according to the regression model. Correlations between turn time and dynamic balance were further established with reaction time, movement velocity, endpoint excursion, and maximal excursion of the LOS (limits of stability) test.

Conclusion

The time needed to complete a 180° turn during the SQT (step/quick turn) test is a good index to differentiate fallers from non-fallers in persons with PD. Turn time is most influenced by balance. Furthermore, balance control, especially in an anterior or sideways direction, is important for turning performance.     

Molecular Identification of Candida Species in the Oral Microbiota of Individuals with Down Syndrome: A Case–Control Study

Mycopathologia - Candida species are common in the human oral microbiota and may cause oral candidiasis (OC) when the microbiota equilibrium is disturbed. Immunosuppressed individuals are...     

Association of CMV-Specific T Cell-Mediated Immunity with CMV DNAemia and Development of CMV Disease in HIV-1–Infected Individuals

Background

Among HIV-1–infected individuals, cytomegalovirus (CMV) reactivation and disease occur in the setting of advanced immunosuppression. The value of a standardized assessment of CMV-specific T-cell mediated immunity by the CMV QuantiFERON assay (CMV-QFT) has not yet been thoroughly investigated in HIV-1–infected subjects.

Methods

Prospective, longitudinal study in 153 HIV-1–infected subjects with a CD4⁺ T cell count < 350/μL who simultaneously underwent CMV-QFT, CMV serology testing and CMV-DNA quantification. Factors associated with CMV-QFT were evaluated. Clinical screening for CMV manifestations was then performed every 3 months.

Results

Among the 141 CMV IgG-seropositive individuals the CMV-QFT assay yielded reactive results in 84% (118/141), negative results in 15% (21/141) and indeterminate (negative mitogen IFN-gamma response) results in 1% (2/141) of subjects. The mean actual CD4⁺ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, P = 0.015). A significantly lower proportion of CMV-QFT reactive vs. non-reactive patients displayed CMV DNAemia > 100 copies/mL (23% (27/118) vs. 48% (11/23), P = 0.02). Furthermore, a statistically significant inverse association between mitogen IFN-gamma response and CMV-DNAemia > 1000 copies/mL was observed (P < 0.001). During the observational period, 5 CMV end-organ manifestations were observed. In three of the CMV cases the CMV-QFT yielded indeterminate results.

Conclusions

While CMV-QFT reactivity indicates CMV-specific immunity, indeterminate results due to negative mitogen IFN-gamma response might reflect HIV-1-induced immunodeficiency. Thus, dependency upon CD4⁺ T cell count should be considered when interpreting CMV-QFT results.     

Development of Fetal Yawn Compared with Non-Yawn Mouth Openings from 24–36 Weeks Gestation

Background

Although some research suggests that fetuses yawn, others disagree arguing that is it simple mouth opening. Furthermore there is no developmental account of fetal yawning compared with simple mouth opening. The aim of the present study was to establish in a repeated measures design the development of fetal yawning compared with simple mouth opening.

Methodology/Findings

Video recordings were made of the fetal face and upper torso visualized by means of 4D full frontal or facial profile ultrasound recordings. Fifteen healthy fetuses were scanned four times at 24, 28, 32 and 36 weeks gestation. Yawning was distinguished from non-yawning in terms of the length of time it took to reach the apex of the mouth stretch, with yawns being defined as more than 50% of the total time observed. To assess changes in frequency, a Poisson mixed effects model was fitted to the count of number of yawn and simple mouth opening events with age and gender as fixed effects, and person as a random effect. For both yawns and simple mouth openings a smooth varying age effect was significant. The number of yawns observed declined with age from 28 weeks gestation, whereas simple mouth openings were less frequent and the decline was observed from 24 weeks. Gender was not significant either for yawn and simple mouth openings.

Conclusions/Significance

Yawning can be reliably distinguished from other forms of mouth opening with the potential of using yawning as an index of fetal healthy development.     

Genetic Analysis of ‘PAX6-Negative’ Individuals with Aniridia or Gillespie Syndrome

We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome (iris hypoplasia, ataxia and mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing PAX6 and two encompassing FOXC1. Six deletions with plausible cis-regulatory effects were identified: five that were 3ʹ (telomeric) to PAX6 and one within a gene desert 5ʹ (telomeric) to PITX2. Sequence analysis of the FOXC1 and PITX2 coding regions identified two plausibly pathogenic de novo FOXC1 missense mutations (p.Pro79Thr and p.Leu101Pro). No intragenic mutations were detected in PITX2. FISH mapping in an individual with Gillespie-like syndrome with an apparently balanced X;11 reciprocal translocation revealed disruption of a gene at each breakpoint: ARHGAP6 on the X chromosome and PHF21A on chromosome 11. In the other individuals with Gillespie syndrome no mutations were identified in either of these genes, or in HCCS which lies close to the Xp breakpoint. Disruption of PHF21A has previously been implicated in the causation of intellectual disability (but not aniridia). Plausibly causative mutations were identified in 15 out of 42 individuals (12/32 aniridia; 3/11 Gillespie syndrome). Fourteen of these mutations presented in the known aniridia genes; PAX6, FOXC1 and PITX2. The large number of individuals in the cohort with no mutation identified suggests greater locus heterogeneity may exist in both isolated and syndromic aniridia than was previously appreciated.     

A Long-Acting PYY3–36 Analog Mediates Robust Anorectic Efficacy with Minimal Emesis in Nonhuman Primates

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Antibody Profiling in Na?ve and Semi-immune Individuals Experimentally Challenged with Plasmodium vivax Sporozoites

BackgroundAcquisition of malaria immunity in low transmission areas usually occurs after relatively few exposures to the parasite. A recent Plasmodium vivax experimental challenge trial in malaria naïve and semi-immune volunteers from Colombia showed that all naïve individuals developed malaria symptoms, whereas semi-immune subjects were asymptomatic or displayed attenuated symptoms. Sera from these individuals were analyzed by protein microarray to identify antibodies associated with clinical protection.ConclusionClinical protection against experimental challenge in volunteers with previous P. vivax exposure was associated with elevated pre-existing antibodies, an attenuated serological response to the challenge and reactivity to new antigens.     

Nonorthogonal tight-binding model with H–C–N–O parameterisation

A parametric nonorthogonal tight-binding model (NTBM1) with the set of parameters for H–C–N–O systems is presented. This model compares well with widely used semi-empirical AM1 and PM3/PM7 models but contains less fitting parameters per atom. All NTBM1 parameters are derived based on a criterion of the best agreement between the calculated and experimental values of bond lengths, valence angles and binding energies for various H–C–N–O molecules. Results for more than 200 chemical compounds are reported. Parameters are currently available for hydrogen, carbon, nitrogen, oxygen atoms and corresponding interatomic interactions. The model has a good transferability and can be used for both relaxation of large molecular systems (e.g., high-molecular compounds or covalent cluster complexes) and long-timescale molecular dynamics simulation (e.g., modelling of thermal decomposition processes). The program package based on this model is available for download at no cost from http://ntbm.info.     

Are Cuckoos Maximizing Egg Mimicry by Selecting Host Individuals with Better Matching Egg Phenotypes?

Background

Avian brood parasites and their hosts are involved in complex offence-defense coevolutionary arms races. The most common pair of reciprocal adaptations in these systems is egg discrimination by hosts and egg mimicry by parasites. As mimicry improves, more advanced host adaptations evolve such as decreased intra- and increased interclutch variation in egg appearance to facilitate detection of parasitic eggs. As interclutch variation increases, parasites able to choose hosts matching best their own egg phenotype should be selected, but this requires that parasites know their own egg phenotype and select host nests correspondingly.

Methodology/Principal Findings

We compared egg mimicry of common cuckoo Cuculus canorus eggs in naturally parasitized marsh warbler Acrocephalus palustris nests and their nearest unparasitized conspecific neighbors having similar laying dates and nest-site characteristics. Modeling of avian vision and image analyses revealed no evidence that cuckoos parasitize nests where their eggs better match the host eggs. Cuckoo eggs were as good mimics, in terms of background and spot color, background luminance, spotting pattern and egg size, of host eggs in the nests actually exploited as those in the neighboring unparasitized nests.

Conclusions/Significance

We reviewed the evidence for brood parasites selecting better-matching host egg phenotypes from several relevant studies and argue that such selection probably cannot exist in host-parasite systems where host interclutch variation is continuous and overall low or moderate. To date there is also no evidence that parasites prefer certain egg phenotypes in systems where it should be most advantageous, i.e., when both hosts and parasites lay polymorphic eggs. Hence, the existence of an ability to select host nests to maximize mimicry by brood parasites appears unlikely, but this possibility should be further explored in cuckoo-host systems where the host has evolved discrete egg phenotypes.     

Novel nonapeptide GLP (28–36) amide derivatives with improved hypoglycemic and body weight lowering effects

Glucagon-like peptide-1 (GLP-1) has emerged as a major therapeutic target for the treatment of type 2 diabetes. The nonapeptide GLP-1 (28–36) amide is one of the biological C-terminal products of GLP-1 modified by the neutral endopeptidase (NEP) 24.11 with limited hypoglycemic activity. In this study, we focused on the modification of GLP-1 (28–36) amide for the first time and synthesized a series of GLP-1 (28–36) amide analogues. Results of biological activity evaluation in INS-1 cell, STZ-induced diabetic and diet induced obesity (DIO) mice indicated that S3 as a promising candidate to treat type 2 diabetes and obesity.     

Altered Regulation of CD200 Receptor in Monocyte-Derived Macrophages from Individuals with Parkinson’s Disease

Microglia are the representative myeloid cells in the brain, and their over-activation plays an important role in the pathogenesis of Parkinson’s disease (PD). Microglia activation is believed to be regulated by the CD200-CD200R signaling. As the peripheral counterpart of microglia, monocyte-derived macrophages (MDMs) share the same progenitor and antigen markers, and they have similar biological behaviors and mirror microglial function in the brain. Here, we studied CD200R expression and its regulation in MDMs from 32 PD cases, 27 age-matched old controls, and 28 young controls. We found that the basal CD200R expression is similar in MDMs from young control, old control and PD patients. However, the induction of CD200R expression in MDMs under various conditions is impaired in the old groups, especially in PD patients. There was a selective decrease in CD200R expression induced by co-culture with dying PC12 cells in MDMs from PD cases, as compared with MDMs from the age-matched controls. We also found that the inducible CD200R expression correlated inversely with the onset age of PD and to tumor necrosis factor-α (TNF-α) released from MDMs. These results suggest an intrinsic abnormality in the CD200-CD200R signaling in MDMs during aging and, especially, in PD. We speculate that in the PD brain, microglia might undergo abnormalities similar to MDMs.     

Invaders interfere with native parasite–host interactions

The introduction of species is of increasing concern as invaders often reduce the abundance of native species due to a variety of interactions like habitat engineering, predation and competition. A more subtle and not recognized effect of invaders on their recipient biota is their potential interference with native parasite–host interactions. Here, we experimentally demonstrate that two invasive molluscan filter-feeders of European coastal waters interfere with the transmission of free-living infective trematode larval stages and hereby mitigate the parasite burden of native mussels (Mytilus edulis). In laboratory mesocosm experiments, the presence of Pacific oysters (Crassostrea gigas) and American slipper limpets (Crepidula fornicata) reduced the parasite load in mussels by 65–77% and 89% in single and mixed species treatments, respectively. Both introduced species acted as decoys for the trematodes thus reducing the risk of hosts to become infected. This dilution effect was density-dependent with higher reductions at higher invader densities. Similar effects in a field experiment with artificial oyster beds suggest the observed dilution effect to be relevant in the field. As parasite infections have detrimental effects on the mussel hosts, the presence of the two invaders may elicit a beneficial effect on mussels. Our experiments indicate that introduced species alter native parasite–hosts systems thus extending the potential impacts of invaders beyond the usually perceived mechanisms.     

The Relationship of Serum Macrophage Inhibitory Cytokine – 1 Levels with Gray Matter Volumes in Community-Dwelling Older Individuals

Using circulating inflammatory markers and magnetic resonance imaging (MRI), recent studies have associated inflammation with brain volumetric measures. Macrophage Inhibitory Cytokine–1 (MIC-1/GDF15) is a divergent transforming growth factor – beta (TGF-β) superfamily cytokine. To uncover the underlying mechanisms of the previous finding of a negative association between MIC-1/GDF15 serum levels and cognition, the present study aimed to examine the relationship of circulating MIC-1/GDF15 levels with human brain gray matter (GM) volumes, in a community-dwelling sample aged 70–90 years over two years (Wave 1: n = 506, Wave 2: n = 327), of which the age-related brain atrophy had been previously well defined. T1-weighted MRI scans were obtained at both waves and analyzed using the FMRIB Software Library and FreeSurfer. The results showed significantly negative associations between MIC-1/GDF15 serum levels and both subcortical and cortical GM volumes. GM volumes of the whole brain, cortex, temporal lobe, thalamus and accumbens showed significant mediating effects on the associations between MIC-1/GDF15 serum levels and global cognition scores. Increases in MIC-1/GDF15 serum levels were associated with decreases in cortical and subcortical GM volume over two years. In conclusion, MIC-1/GDF15 serum levels were inversely associated with GM volumes both cross-sectionally and longitudinally.     

The Wilson–Cowan model, 36 years later

The Wilson–Cowan model of interacting neurons (1973) is one of the most influential papers published in Biological Cybernetics (Kybernetik). This paper and a companion paper published in 1972 have been cited over 1000 times. Rather than focus on the microscopic properties of neurons, Wilson and Cowan analyzed the collective properties of large numbers of neurons using methods from statistical mechanics, based on the mean-field approach. New experimental techniques to measure neuronal activity at the level of large populations are now available to test these models, including optical recording of brain activity with intrinsic signals and voltage sensitive dyes, and new methods for analyzing EEG and MEG. These measurement techniques have revealed patterns of coherent activity that span centimetres of tissue in the cerebral cortex. Here the underlying ideas are reviewed in a historic context. This note was written by Alain Destexhe and Terry Sejnowski, the Editors-in-Chief of the Journal of Computational Neuroscience and Neural Computation, on the occasion of the appearance of Volume 100 of Biological Cybernetics.