Human immunodeficiency virus type 1 primary isolate neutralization resistance is associated with the syncytium-inducing phenotype and lower CD4 cell counts in subtype CRF01_AE-infected patients

A number of human immunodeficiency virus type 1 (HIV-1) non-B-subtype products have been developed for present or future vaccine trials; in Thailand, several studies using subtype B and/or CRF01_AE vaccines have been conducted. To better characterize the biologic properties of these subtypes, 70 HIV-1 subtype B and E isolates were phenotyped as syncytium-inducing (SI) or non-syncytium-inducing (NSI) isolates and assessed for sensitivity to neutralizing antibody (NAb). A significantly higher number of NSI subtype E viruses were neutralization sensitive than SI subtype E viruses (P = 0.009), while no association between viral phenotype and sensitivity to NAb was observed for subtype B (P = 0.856), suggesting a difference in the neutralization patterns of subtypes B and E. Strikingly, concurrent CD4 T-cell numbers were significantly lower for subtype E-infected patients whose isolates were more resistant to NAb, both for the overall study group (P < 0.001) as well as for the 22 patients with NSI isolates (P = 0.013). Characterization of the evolution of biologic properties of both B and non-B HIV-1 subtypes will provide a clearer understanding of the repertoire of antibodies that must be elicited for a vaccine to be effective against all phenotypes and subtypes.     

The pollination system of the widely distributed mammal‐pollinated Mucuna macrocarpa (Fabaceae) in the tropics

Although the pollinators of some plant species differ across regions, only a few mammal‐pollinated plant species have regional pollinator differences in Asia. Mucuna macrocarpa (Fabaceae) is pollinated by squirrels, flying foxes, and macaques in subtropical and temperate islands. In this study, the pollination system of M. macrocarpa was identified in tropical Asia, where the genus originally diversified. This species requires “explosive opening” of the flower, where the wing petals must be pressed down and the banner petal pushed upward to fully expose the stamens and pistil. A bagging experiment showed that fruits did not develop in inflorescences (n = 66) with unopened flowers, whereas fruits developed in 68.7% of inflorescences (n = 131) with opened flowers. This indicated that the explosive opening is needed for the species to reproduce. Four potential pollinator mammals were identified by a video camera‐trap survey, and 78.3% and 60.1% of monitored inflorescences (n = 138) were opened by gray‐bellied squirrels (Callosciurus caniceps) and Finlayson's squirrels (C. finlaysonii), respectively, even though more than 10 mammal species visited flowers. Nectar was surrounded by the calyx, and the volume and sugar concentration of secreted nectar did not change during the day. This nectar secretion pattern is similar to those reported by previous studies in other regions. These results showed that the main pollinators of M. macrocarpa in the tropics are squirrels. However, the species' nectar secretion pattern is not specifically adapted to this particular pollinator. Pollinators of M. macrocarpa differ throughout the distribution range based on the fauna present, but there might not have been no distinctive changes in the attractive traits that accompanied these changes in pollinators.     

Association between Regimen Composition and Treatment Response in Patients with Multidrug-Resistant Tuberculosis: A Prospective Cohort Study

Background

For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen.

Methods and Findings

We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005–2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16–23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients’ baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent of disease on chest radiograph.In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09–1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65–2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48–1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18–1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09–1.76, per drug when three effective drugs present in regimen).The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse.

Conclusions

MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens.     

Analysis of the planned,delivered dose distributions and quality assurance for helical tomotherapy and volumetric modulated arc therapy in locally advanced non-small cell lung cancer

BackgroundWith full access to both helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT), we compared locally advanced non-small cell lung cancer (LA-NSCLC) treatment plans and verified the plans using patient-specific pretreatment quality assurance (PSQA).Materials and methodsFor each of the seventeen patients included in the study, two treatment plans (i.e. HT and VMAT) were created. Optimized plans were evaluated following the ICRU 83 criteria. Planned quality indexes and dosimetric parameters were compared. Lastly, all plans were subjected to PSQA assessment by determining the gamma passing rate (GPR).ResultsAll dosimetry results obtained from the planning target volume passed the ICRU 83 criteria. With regard to similar homogeneity indices, VMAT produced better conformity number values than HT (0.78 vs. 0.64), but differences in the values were insignificant. Furthermore, VMAT was associated with a significantly shorter mean treatment time (1.91 minutes vs. 6.66 minutes). For PSQA assessment, both techniques resulted in adequate GPR values (> 90% at the 3%/3 mm criteria).ConclusionBoth HT and VMAT techniques led to the generation of clinically satisfactory and reliable radiotherapy plans. However, the VMAT plan was associated with a non-significantly better degree of conformity and a significantly shorter treatment time. Thus, VMAT was determined to be a better choice for LA-NSCLC.     

Recognition and characterization of four Thai xylariaceous fungi inhabiting various tropical foliages as endophytes by DNA sequences and host plant preference

A total of 202 strains of xylariaceous fungi (183 endophytic strains isolated from 25 plant species of 24 genera in 21 families and 19 saprobic strains), segregated into four clades, were examined by nuclear rDNA internal transcribed spacer (ITS) sequence and beta-tubulin coding region analyses to clarify their taxonomic status and species boundaries. Three of the four species clades were assigned to Xylaria cubensis (100 strains), Xylaria grammica (33 strains), and Nemania diffusa (48 strains). Another fungus was tentatively assigned to Nemania cf. bipapillata (21 strains). Comparison of the host plants revealed that X. cubensis inhabited healthy leaves of at least 24 plant species (23 genera of 21 families) as endophytes; N. diffusa was found on 19 plant species (18 genera of 15 families), Nemania cf. bipapillata on 11 species (10 genera of 9 families), and X. grammica on 8 species (8 genera of 7 families). The present results suggest that the major xylariaceous endophytes in tropical plants are likely to be non-host specific, or have a wide range of host plant preferences.     

Molecular Evidence for Cryptic Speciation in the Cyclophorus fulguratus (Pfeiffer, 1854) Species Complex (Caenogastropoda: Cyclophoridae) with Description of New Species

A high degree of intraspecific variation, both genetic and in shell morphology, of the operculate land snail Cyclophorus fulguratus (Pfeiffer, 1854) suggests that its classification as a single species warrants reconsideration. We sequenced two nuclear (18S and 28S) and two mitochondrial (16S and COI) genes of 46 C. fulguratus specimens and used them to estimate the phylogeny and to determine the validity of species boundaries. Molecular phylogenetic analyses revealed the presence of three lineages corresponding to three geographically disjunctive populations of C. fulguratus in Thailand. Likelihood tests of topologies significantly supported the non-monophyly of the C. fulguratus–complex and Bayesian species delimitation analysis significantly supported the potential representation as distinct species of these three lineages. Discriminant function analysis based on geometric-morphometrics of shell shape allowed for significant distinction of these three candidate species, although they revealed a considerable degree of overlap of shell shape reflecting their crypsis morphologically. The diagnostic characters are provided by color pattern, pattern of protoconch and pattern of jaw. In conclusion, the results support that the C. fulguratus s.l., as currently recognized, consists of three distinct species in Thailand: C. fulguratus s.s., C. rangunensis and C. abditus sp.nov., which are described herein.     

Movement of nitrate,chloride, and potassium in a sandy loam soll

Summary This study was conducted to measure the movement of nitrogen, chloride, and potassium in a sandy loam soil under field conditions and with controlled sprinkle irrigation. After 62.5 mm of water was applied, soil nitrate measurements indicated 67 per cent of the applied N fertilizer was lost from the upper 105 cm of the soil profile. Following a cumulative irrigation of 112.5 mm of water, 82 per cent of the applied N was lost. Since the chloride movement and redistribution was almost identical to the nitrate movement pattern, it would seem plausible that most of the nitrates were lost from the upper part of the soil by leaching. The potassium movement involved the redistribution of exchangeable K from the 0–8 cm soil zone into the 8–15 cm zone and with some buildup of K occurring in the 15–30 cm soil layer. re]19741126 rv]19751111     

Observations on first and second-instar larvae of Megaselia scalaris (Loew) (Diptera: Phoridae).

The ultrastructure of the first and second-instar larvae of Megaselia scalaris (Loew) was studied using scanning electron microscopy (SEM). Significant changes in morphological features were observed in the anterior and posterior spiracles, but only minimal changes in the labium and mouthhooks were seen. The ultrastructure of M. scalaris larvae not only provides chronological transformation of their larval instars, but it can also be used to explain their feeding behavior and mode of respiration. In addition, morphological structures useful for specific identification of first or second-instar larvae collected from human corpses may be used in forensic investigations.     

Chromosomal aberration assessment of silver rasbora fish (Rasbora tornieri) living near gold mine area with heavy metal contamination

This study aimed to investigate arsenic (As), cadmium (Cd), chromium (Cr), and lead (Pb), contamination in water, sediment, and Rasbora tornieri samples and chromosomal aberration in R. tornieri near gold mine area compared to unaffected area. The heavy metal concentrations in the samples were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-OES). The difference of As, Cr, and Pb concentrations in R. tornieri samples between the gold mine and unaffected areas was statistically significant (p < 0.05), but the difference was not significant for Cd. The diploid chromosome number of R. tornieri from both areas was 2n = 50, and the chromosomal aberrations of R. tornieri were higher in the gold mine area than those in the unaffected area. There are six types of chromosomal aberrations, including centric fragmentation (CF), centric gap, single chromatid gap, fragmentation, deletion, and polyploidy. The most common chromosomal aberration in the samples from the gold mine area was CF, and the difference in chromosomal aberration and the cells with chromosomal aberrations in R. tornieri between the areas was statistically significant (p < 0.05). The percentages of chromosomal aberrations in the R. tornieri samples from the gold mine and the unaffected areas were 16.60 and 1.66, respectively.