Determinants of serum levels of surfactant proteins A and B and Clara cell protein CC16

Increased leakage of surfactant proteins A and B (SP-A and SP-B) and Clara cell secretory protein (CC16) from the air spaces into the circulation occurs in a range of respiratory conditions. However, circulating levels depend not only on the rate of entry into the circulation, but also on the rate of clearance. In order to clarify the role of the kidney in the clearance of these proteins, serum levels were related to markers of glomerular filtration in 54 non-smoking patients with varying degrees of renal dysfunction, none of whom had respiratory disease or were receiving dialysis at the time of sampling. Serum SP-A was related to SP-B (r=0.53, p<0.001) and to CC16 (r=0.33, p<0.02). Similarly, SP-B was related to CC16 (r=0.39, p<0.004). Stepwise multiple linear regression analysis suggested that serum SP-A and SP-B are influenced by age (～20 and ～25% of variance, respectively), whereas CC16 is determined by renal function and, to a lesser extent, by body weight (～63% of variance in total). We conclude that CC16 is cleared from blood by the renal route, whereas SP-A and SP-B are not. Serum SP-A and SP-B are influenced by age, which we speculate reflects increased damage to the alveolocapillary barrier.     

Novel management to enhance spider biodiversity in existing grass buffer strips

• 1 Grass buffer strips have been widely sown to mitigate against intensive agricultural management practices that have negatively impacted on invertebrate and plant biodiversity in arable farming systems. Typically, such strips are floristically species poor and are dominated by grasses. In the present study, we developed management practices to enhance the floristic and structural diversity of these existing strips for the benefit of spiders, a key provider of natural pest control in crops.
• 2 Across three UK arable farms, we investigated the benefits of: (i) scarification to create germination niches into which wildflower seeds were sown and (ii) the effect of graminicide applications to suppress grass dominance. Spiders were sampled twice per year (July and September) during 2008 and 2009.
• 3 The combination of scarification with wildflower seeds, as well as graminicide, resulted in the greatest wildflower cover and lowest grass cover, with a general trend of increased abundance of adult and juvenile spiders. The abundance of Pachygnatha degeeri, Bathyphantes gracilis and juvenile wolf spiders of the genus Pardosa was positively correlated with wildflower cover, probably reflecting increased prey availability. Sward structure was negatively correlated with Erigone atra, Oedothorax fuscus and juvenile Pardosa abundance.
• 4 Management that utilizes existing commonly adopted agri‐environment options, such as grass buffer strips, represents a potentially important conservation tool for increasing the quantity and quality of invertebrate habitats. This can maximize opportunities for the provision of multiple ecosystem services, including pest regulation by predators such as spiders. These management practices have the potential to be incorporated into existing U.K. and European agri‐environment schemes.

     

Linkage to HIV,TB and Non-Communicable Disease Care from a Mobile Testing Unit in Cape Town,South Africa

Background

HIV counseling and testing may serve as an entry point for non-communicable disease screening.

Objectives

To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit.

Methods

A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined.

Results

Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic.

Conclusion

Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care.     

Association between Ocular Bacterial Carriage and Follicular Trachoma Following Mass Azithromycin Distribution in The Gambia

Background

Trachoma, caused by ocular Chlamydia trachomatis infection, is the leading infectious cause of blindess, but its prevalence is now falling in many countries. As the prevalence falls, an increasing proportion of individuals with clinical signs of follicular trachoma (TF) is not infected with C. trachomatis. A recent study in Tanzania suggested that other bacteria may play a role in the persistence of these clinical signs.

Methodology/Principal Findings

We examined associations between clinical signs of TF and ocular colonization with four pathogens commonly found in the nasopharnyx, three years after the initiation of mass azithromycin distribution. Children aged 0 to 5 years were randomly selected from 16 Gambian communitites. Both eyes of each child were examined and graded for trachoma according to the World Health Organization (WHO) simplified system. Two swabs were taken from the right eye: one swab was processed for polymerase chain reaction (PCR) using the Amplicor test for detection of C. trachomatis DNA and the second swab was processed by routine bacteriology to assay for the presence of viable Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Prevalence of TF was 6.2% (96/1538) while prevalence of ocular C. trachomatis infection was 1.0% (16/1538). After adjustment, increased odds of TF were observed in the presence of C. trachomatis (OR = 10.4, 95%CI 1.32–81.2, p = 0.03), S. pneumoniae (OR = 2.14, 95%CI 1.03–4.44, p = 0.04) and H. influenzae (OR = 4.72, 95% CI 1.53–14.5, p = 0.01).

Conclusions/Significance

Clinical signs of TF can persist in communities even when ocular C. trachomatis infection has been controlled through mass azithromycin distribution. In these settings, TF may be associated with ocular colonization with bacteria commonly carried in the nasopharnyx. This may affect the interpretation of impact surveys and the determinations of thresholds for discontinuing mass drug administration.     

Mitochondrial Genome of the Eyeworm,Thelazia callipaeda (Nematoda: Spirurida), as the First Representative from the Family Thelaziidae

Human thelaziosis is an underestimated parasitic disease caused by Thelazia species (Spirurida: Thelaziidae). The oriental eyeworm, Thelazia callipaeda, infects a range of mammalian definitive hosts, including canids, felids and humans. Although this zoonotic parasite is of socio-economic significance in Asian countries, its genetics, epidemiology and biology are poorly understood. Mitochondrial (mt) DNA is known to provide useful genetic markers to underpin fundamental investigations, but no mt genome had been characterized for any members of the family Thelaziidae. In the present study, we sequenced and characterized the mt genome of T. callipaeda. This AT-rich (74.6%) mt genome (13,668 bp) is circular and contains 12 protein-coding genes, 22 transfer RNA genes and two ribosomal RNA genes, but lacks an atp8 gene. All protein-coding genes are transcribed in the same direction; the gene order is the same as those of Dirofilaria immitis and Setaria digitata (Onchocercidae), but distinct from Dracunculus medinensis (Dracunculidae) and Heliconema longissimum (Physalopteridae). Phylogenetic analyses of the concatenated amino acid sequence data for all 12 protein-coding genes by Bayesian inference (BI) showed that T. callipaeda (Thelaziidae) is related to the family Onchocercidae. This is the first mt genome of any member of the family Thelaziidae and should represent a new source of genetic markers for studying the epidemiology, ecology, population genetics and systematics of this parasite of humans and other mammals.     

Employing a Monte Carlo Algorithm in Newton-Type Methods for Restricted Maximum Likelihood Estimation of Genetic Parameters

Estimation of variance components by Monte Carlo (MC) expectation maximization (EM) restricted maximum likelihood (REML) is computationally efficient for large data sets and complex linear mixed effects models. However, efficiency may be lost due to the need for a large number of iterations of the EM algorithm. To decrease the computing time we explored the use of faster converging Newton-type algorithms within MC REML implementations. The implemented algorithms were: MC Newton-Raphson (NR), where the information matrix was generated via sampling; MC average information(AI), where the information was computed as an average of observed and expected information; and MC Broyden''s method, where the zero of the gradient was searched using a quasi-Newton-type algorithm. Performance of these algorithms was evaluated using simulated data. The final estimates were in good agreement with corresponding analytical ones. MC NR REML and MC AI REML enhanced convergence compared to MC EM REML and gave standard errors for the estimates as a by-product. MC NR REML required a larger number of MC samples, while each MC AI REML iteration demanded extra solving of mixed model equations by the number of parameters to be estimated. MC Broyden''s method required the largest number of MC samples with our small data and did not give standard errors for the parameters directly. We studied the performance of three different convergence criteria for the MC AI REML algorithm. Our results indicate the importance of defining a suitable convergence criterion and critical value in order to obtain an efficient Newton-type method utilizing a MC algorithm. Overall, use of a MC algorithm with Newton-type methods proved feasible and the results encourage testing of these methods with different kinds of large-scale problem settings.     

A Randomized Trial of Two Coverage Targets for Mass Treatment with Azithromycin for Trachoma

Background

The World Health Organization recommends at least 3 annual antibiotic mass drug administrations (MDA) where the prevalence of trachoma is >10% in children ages 1–9 years, with coverage at least at 80%. However, the additional value of higher coverage targeted at children with multiple rounds is unknown.

Trial Design

2×2 factorial community randomized, double blind, trial.

Trial methods

32 communities with prevalence of trachoma ≥20% were randomized to: annual MDA aiming for coverage of children between 80%–90% (usual target) versus aiming for coverage>90% (enhanced target); and to: MDA for three years versus a rule of cessation of MDA early if the estimated prevalence of ocular C. trachomatis infection was less than 5%. The primary outcome was the community prevalence of infection with C. trachomatis at 36 months.

Results

Over the trial''s course, no community met the MDA cessation rule, so all communities had the full 3 rounds of MDA. At 36 months, there was no significant difference in the prevalence of infection, 4.0 versus 5.4 (mean adjusted difference = 1.4%, 95% CI = −1.0% to 3.8%), nor in the prevalence of trachoma, 6.1 versus 9.0 (mean adjusted difference = 2.6%, 95% CI = −0.3% to 5.3%) comparing the usual target to the enhanced target group. There was no difference if analyzed using coverage as a continuous variable.

Conclusion

In communities that had pre-treatment prevalence of follicular trachoma of 20% or greater, there is no evidence that MDA can be stopped before 3 annual rounds, even with high coverage. Increasing coverage in children above 90% does not appear to confer additional benefit.     

Life Expectancies of South African Adults Starting Antiretroviral Treatment: Collaborative Analysis of Cohort Studies

Background

Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults.

Methods and Findings

Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2–30.2) at age 20 y and 10.1 y (95% CI: 9.3–10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0–39.7) and 14.4 y (95% CI: 13.3–15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1–46.0) if her baseline CD4 count was ≥200 cells/µl, compared to 29.5 y (95% CI: 26.2–33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%–20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations.

Conclusions

South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors'' Summary     

Dynasore Protects Mitochondria and Improves Cardiac Lusitropy in Langendorff Perfused Mouse Heart

Background

Heart failure due to diastolic dysfunction exacts a major economic, morbidity and mortality burden in the United States. Therapeutic agents to improve diastolic dysfunction are limited. It was recently found that Dynamin related protein 1 (Drp1) mediates mitochondrial fission during ischemia/reperfusion (I/R) injury, whereas inhibition of Drp1 decreases myocardial infarct size. We hypothesized that Dynasore, a small noncompetitive dynamin GTPase inhibitor, could have beneficial effects on cardiac physiology during I/R injury.

Methods and Results

In Langendorff perfused mouse hearts subjected to I/R (30 minutes of global ischemia followed by 1 hour of reperfusion), pretreatment with 1 µM Dynasore prevented I/R induced elevation of left ventricular end diastolic pressure (LVEDP), indicating a significant and specific lusitropic effect. Dynasore also decreased cardiac troponin I efflux during reperfusion and reduced infarct size. In cultured adult mouse cardiomyocytes subjected to oxidative stress, Dynasore increased cardiomyocyte survival and viability identified by trypan blue exclusion assay and reduced cellular Adenosine triphosphate(ATP) depletion. Moreover, in cultured cells, Dynasore pretreatment protected mitochondrial fragmentation induced by oxidative stress.

Conclusion

Dynasore protects cardiac lusitropy and limits cell damage through a mechanism that maintains mitochondrial morphology and intracellular ATP in stressed cells. Mitochondrial protection through an agent such as Dynasore can have clinical benefit by positively influencing the energetics of diastolic dysfunction.