Denial of Risk Behavior Does Not Exclude Asymptomatic Anorectal Sexually Transmitted Infection in HIV-Infected Men

Background

The Centers for Disease Control recommend screening for asymptomatic sexually transmitted infection (STI) among HIV-infected men when there is self-report of unprotected anal-receptive exposure. The study goals were: (1) to estimate the validity and usefulness for screening policies of self-reported unprotected anal-receptive exposure as a risk indicator for asymptomatic anorectal infection with Neisseria gonorrhoeae (GC) and/or Chlamydia trachomatis (CT). (2) to estimate the number of infections that would be missed if anal diagnostic assays were not performed among patients who denied unprotected anorectal exposure in the preceding month.

Methods and Findings

Retrospective analysis in HIV primary care and high resolution anoscopy (HRA) clinics. HIV-infected adult men were screened for self-reported exposure during the previous month at all primary care and HRA appointments. Four sub-cohorts were defined based on microbiology methodology (GC culture and CT direct fluorescent antibody vs. GC/CT nucleic acid amplification test) and clinical setting (primary care vs. HRA). Screening question operating characteristics were estimated using contingency table methods and then pooled across subcohorts. Among 803 patients, the prevalence of anorectal GC/CT varied from 3.5–20.1% in the 4 sub-cohorts. The sensitivity of the screening question for self-reported exposure to predict anorectal STI was higher in the primary care than in the HRA clinic, 86–100% vs. 12–35%, respectively. The negative predictive value of the screening question to predict asymptomatic anorectal STI was ≥90% in all sub-cohorts. In sensitivity analyses, the probability of being an unidentified case among those denying exposure increased from 0.4–8.1% in the primary care setting, and from 0.9–18.8% in the HRA setting as the prevalence varied from 1–20%.

Conclusion

As STI prevalence increases, denial of unprotected anal-receptive exposure leads to an increasingly unacceptable proportion of unidentified asymptomatic anorectal STI if used as a criterion not to obtain microbiologic assays.     

Aspergillus alabamensis,a New Clinically Relevant Species in the Section Terrei

Phylogenetic analyses of sequences generated from portions of three genes coding for the proteins enolase (enoA), β-tubulin (benA), and calmodulin (calM) of a large number of isolates within the section Terrei, genus Aspergillus, revealed the presence of a new cryptic species within this section, Aspergillus alabamensis. Most members of this new cryptic species were recovered as colonizing isolates from immunocompetent patient populations, had decreased in vitro susceptibilities to the antifungal drug amphotericin B, and were morphologically similar to but genetically distinct from Aspergillus terreus isolates.Invasive infections caused by Aspergillus terreus are often disseminated with increased lethality compared with infections caused by other Aspergillus species and tend to be resistant to treatment with the antifungal drug amphotericin B (6, 14, 17). Despite the clinical significance of this organism, little is known about the epidemiology, genetic diversity, and population structure of A. terreus.Historically, A. terreus has been identified in the laboratory by conventional methods such as colony morphology and microscopic characteristics. Such morphological studies have placed A. terreus as a single homogenous species within the section Terrei along with two other varieties, A. terreus var. africanus and A. terreus var. aureus (11). Recent studies have shown that morphological characteristics may not be reliable for distinguishing Aspergillus species, as inferred from the demonstration of multiple cryptic species within the section Fumigati by molecular phylogenetic methods (3-5, 13, 18).In the past, molecular methods largely based on randomly amplified polymorphic DNA-PCR-based assays have shown that A. terreus isolates can have great strain diversity (1, 8, 16). One recent genotyping study of several A. terreus clinical isolates recovered from two different medical centers using this method concluded that nosocomial acquisition of A. terreus infections was highly unlikely given the great genetic diversity observed (7). Another study demonstrated that comparative sequence analyses of the D1 and D2 regions had limited utility to study relationships within the section Terrei, while the internal transcribed spacer regions were useful since there was more nucleotide diversity in this region (16). However, the authors of this study could not resolve species within the section Terrei using these molecular approaches.In the present study, we have developed a multilocus sequence approach employing three protein-coding regions to study species diversity of the section Terrei using a large panel of isolates from both clinical and environmental origins recovered from various parts of the world. The studies outlined below demonstrate the presence of a new, clinically relevant species, Aspergillus alabamensis, and clarify the taxonomic position of the A. terreus variant A. terreus var. aureus.     

Assessing Statistical Significance in Microarray Experiments Using the Distance Between Microarrays

We propose permutation tests based on the pairwise distances between microarrays to compare location, variability, or equivalence of gene expression between two populations. For these tests the entire microarray or some pre-specified subset of genes is the unit of analysis. The pairwise distances only have to be computed once so the procedure is not computationally intensive despite the high dimensionality of the data. An R software package, permtest, implementing the method is freely available from the Comprehensive R Archive Network at http://cran.r-project.org.     

Multidrug resistance-associated protein-1 (MRP1) genetic variants,MRP1 protein levels and severity of COPD

Background

Multidrug resistance-associated protein-1 (MRP1) protects against oxidative stress and toxic compounds generated by cigarette smoking, which is the main risk factor for chronic obstructive pulmonary disease (COPD). We have previously shown that single nucleotide polymorphisms (SNPs) in MRP1 significantly associate with level of FEV₁ in two independent population based cohorts. The aim of our study was to assess the associations of MRP1 SNPs with FEV₁ level, MRP1 protein levels and inflammatory markers in bronchial biopsies and sputum of COPD patients.

Methods

Five SNPs (rs212093, rs4148382, rs504348, rs4781699, rs35621) in MRP1 were genotyped in 110 COPD patients. The effects of MRP1 SNPs were analyzed using linear regression models.

Results

One SNP, rs212093 was significantly associated with a higher FEV₁ level and less airway wall inflammation. Another SNP, rs4148382 was significantly associated with a lower FEV₁ level, higher number of inflammatory cells in induced sputum and with a higher MRP1 protein level in bronchial biopsies.

Conclusions

This is the first study linking MRP1 SNPs with lung function and inflammatory markers in COPD patients, suggesting a role of MRP1 SNPs in the severity of COPD in addition to their association with MRP1 protein level in bronchial biopsies.     

The European carbon balance. Part 3: forests

We present a new synthesis, based on a suite of complementary approaches, of the primary production and carbon sink in forests of the 25 member states of the European Union (EU‐25) during 1990–2005. Upscaled terrestrial observations and model‐based approaches agree within 25% on the mean net primary production (NPP) of forests, i.e. 520±75 g C m^?2 yr^?1 over a forest area of 1.32 × 10⁶ km² to 1.55 × 10⁶ km² (EU‐25). New estimates of the mean long‐term carbon forest sink (net biome production, NBP) of EU‐25 forests amounts 75±20 g C m^?2 yr^?1. The ratio of NBP to NPP is 0.15±0.05. Estimates of the fate of the carbon inputs via NPP in wood harvests, forest fires, losses to lakes and rivers and heterotrophic respiration remain uncertain, which explains the considerable uncertainty of NBP. Inventory‐based assessments and assumptions suggest that 29±15% of the NBP (i.e., 22 g C m^?2 yr^?1) is sequestered in the forest soil, but large uncertainty remains concerning the drivers and future of the soil organic carbon. The remaining 71±15% of the NBP (i.e., 53 g C m^?2 yr^?1) is realized as woody biomass increments. In the EU‐25, the relatively large forest NBP is thought to be the result of a sustained difference between NPP, which increased during the past decades, and carbon losses primarily by harvest and heterotrophic respiration, which increased less over the same period.     

Upland rice and lowland rice exhibited different P/P expression under water deficit and ABA treatment

Aquaporins play a significant role in plant water relations.To further understand the aquaporin function in plants underwater stress,the expression of a subgroup of aquaporins,plasma membrane intrinsic proteins(PIPs),was studied at boththe protein and mRNA level in upland rice(Oryza sativa L.cv.Zhonghan 3)and lowland rice(Oryza sativa L.cv.Xiushui63)when they were water stressed by treatment with 20% polyethylene glycol(PEG).Plants responded differently to20% PEG treatment.Leaf water content of upland rice leaves was reduced rapidly.PIP protein level increased markedlyin roots of both types,but only in leaves of upland rice after 10h of PEG treatment.At the mRNA level,OsPIP1;2,Os-PIP1;3,OsPIP2;1 and OsPIP2;5 in roots as well as OsPIP1;2 and OsPIP1;3 in leaves were significantly up-regulatedin upland rice,whereas the corresponding genes remained unchanged or down-regulated in lowland rice.Meanwhile,weobserved a significant increase in the endogenous abscisic acid(ABA)level in upland rice but not in lowland rice underwater deficit.Treatment with 60μM ABA enhanced the expression of OsPIP1;2,OsPIP2;5 and OsPIP2;6 in roots andOsPIP1;2,OsPIP2;4 and OsPIP2;6 in leaves of upland rice.The responsiveness of PIP genes to water stress and ABAwere different,implying that the regulation of PIP genes involves both ABA-dependent and ABA-independent signalingpathways during water deficit.     

French Experience of 2009 A/H1N1v Influenza in Pregnant Women

Background

The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France.

Methodology/Principal Findings

A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes), 111 were hospitalized in obstetric or medical wards (moderate outcomes), and 164 were outpatients (mild outcomes). The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%), notably the severe patients (70%), were in the third trimester. Among the severe patients, twenty (50%) underwent mechanical ventilation, and eleven (28%) were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2–11.8) and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days) (adjusted OR, 4.8; 95% CI, 1.9–12.1 and 61.2, 95% CI; 14.4–261.3, respectively). Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14%) were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection.

Conclusions

This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the benefit of early oseltamivir treatment in this specific population.     

Changes in the Viral Distribution Pattern after the Appearance of the Novel Influenza A H1N1 (pH1N1) Virus in Influenza-Like Illness Patients in Peru

Background

We describe the temporal variation in viral agents detected in influenza like illness (ILI) patients before and after the appearance of the ongoing pandemic influenza A (H1N1) (pH1N1) in Peru between 4-January and 13-July 2009.

Methods

At the health centers, one oropharyngeal swab was obtained for viral isolation. From epidemiological week (EW) 1 to 18, at the US Naval Medical Research Center Detachment (NMRCD) in Lima, the specimens were inoculated into four cell lines for virus isolation. In addition, from EW 19 to 28, the specimens were also analyzed by real time-polymerase-chain-reaction (rRT-PCR).

Results

We enrolled 2,872 patients: 1,422 cases before the appearance of the pH1N1 virus, and 1,450 during the pandemic. Non-pH1N1 influenza A virus was the predominant viral strain circulating in Peru through (EW) 18, representing 57.8% of the confirmed cases; however, this predominance shifted to pH1N1 (51.5%) from EW 19–28. During this study period, most of pH1N1 cases were diagnosed in the capital city (Lima) followed by other cities including Cusco and Trujillo. In contrast, novel influenza cases were essentially absent in the tropical rain forest (jungle) cities during our study period. The city of Iquitos (Jungle) had the highest number of influenza B cases and only one pH1N1 case.

Conclusions

The viral distribution in Peru changed upon the introduction of the pH1N1 virus compared to previous months. Although influenza A viruses continue to be the predominant viral pathogen, the pH1N1 virus predominated over the other influenza A viruses.