Risk Factors for MDR and XDR-TB in a Tertiary Referral Hospital in India

Background

India has a high burden of drug resistant TB, although there are few data on XDR-TB. Although XDR-TB has existed previously in India, the definition has not been widely applied, and surveillance using second line drug susceptibility testing has not been performed. Our objective was to analyze clinical and demographic risk factors associated with isolation of MDR and XDR TB as compared to susceptible controls, at a tertiary center.

Methodology/Findings

Retrospective chart review based on positive cultures isolated in a high volume mycobacteriology laboratory between 2002 and 2007. 47 XDR, 30 MDR and 117 susceptible controls were examined. Drug resistant cases were less likely to be extrapulmonary, and had received more previous treatment regimens. Significant risk factors for XDR-TB included residence outside the local state (OR 7.43, 3.07-18.0) and care costs subsidized (OR 0.23, 0.097-0.54) in bivariate analysis and previous use of a fluoroquinolone and injectable agent (other than streptomycin) (OR 7.00, 95% C.I. 1.14-43.03) and an initial treatment regimen which did not follow national guidelines (OR 5.68, 1.24-25.96) in multivariate analysis. Cavitation and HIV did not influence drug resistance.

Conclusions/Significance

There is significant selection bias in the sample available. Selection pressure from previous treatment and an inadequate initial regimen increases risk of drug resistance. Local patients and those requiring financial subsidies may be at lower risk of XDR-TB.     

Orienting reaction, organizing for action, and emotional processes

In the first half of the sixties, general notions were formulated concerning the functional role of the orienting reaction (OR) in adaptive activity, its elicitation and habituation. These notions included the following: a) The OR is elicited only by significant changes in a situation. This implies that OR elicitation is preceded by brain processes (usually unconscious) pertaining to the evaluation of the significance of changes according to an existing hierarchy of motivations, attitudes, and goals. Therefore, the OR is of an active (vs. reactive) nature, i.e., is inevitably determined by internal factors of brain activity. b) The OR is not a unitary reaction, but a complex polyfunctional activity, different aspects of which are reflected in different OR components which can be modified rather independently. c) The OR represents the processes of organizing new (non-standard) actions: sensory, motor, or intellectual. OR habituation is a manifestation of attenuation of the active control of an action, and an increase in its automation. Thus, the emphasis in understanding the OR has shifted from a predominantly "sensualistic" platform to a predominantly "actualistic" one. In recent experiments, the role of emotional processes in the elicitation and habituation of components of the OR has been analyzed. Complex relations between the GSR and anxiety were found in a study of patients with acute alcohol withdrawal syndrome treated with different psychopharmacological agents. The study of auditory evoked potential habituation in depressive patients has shown the emotional state influence on sensory aspects of the OR with the participation of the OR brain mechanisms in perceptual defense.(ABSTRACT TRUNCATED AT 250 WORDS)     

Real‐time functional optical‐resolution photoacoustic microscopy using high‐speed alternating illumination at 532 and 1064 nm

Optical‐resolution photoacoustic microscopy (OR‐PAM), which has been widely used and studied as a noninvasive and in vivo imaging technique, can yield high‐resolution and absorption contrast images. Recently, metallic nanoparticles and dyes, such as gold nanoparticles, methylene blue, and indocyanine green, have been used as contrast agents of OR‐PAM. This study demonstrates real‐time functional OR‐PAM images with high‐speed alternating illumination at 2 wavelengths. To generate 2 wavelengths, second harmonic generation at 532 nm with an LBO crystal and a pump wavelength of 1064 nm is applied at a pulse repetition rate of 300 kHz. For alternating illumination, an electro‐optical modulator is used as an optical switch. Therefore, the A‐line rate for the functional image is 150 kHz, which is half of the laser repetition rate. To enable fast signal processing and real‐time displays, parallel signal processing using a graphics processing unit (GPU) is performed. OR‐PAM images of the distribution of blood vessels and gold nanorods in a BALB/c‐nude mouse's ear can be simultaneously obtained with 500 × 500 pixels and real‐time display at 0.49 fps.      

Catastrophe modelling in the biological sciences

Catastrophe Theory was developed in an attempt to provide a form of Mathematics particularly apt for applications in the biological sciences. It was claimed that while it could be applied in the more conventional physical way, it could also be applied in a new metaphysical way, derived from the Structuralism of Saussure in Linguistics and Lévi-Strauss in Anthropology.Since those early beginnings there have been many attempts to apply Catastrophe Theory to Biology, but these hopes cannot be said to have been fully realised.This paper will document and classify the work that has been done. It will be argued that, like other applied Mathematics, applied Catastrophe Theory works best where the underlying laws are securely known and precisely quantified, requiring those same guarantees as does any other branch of Mathematics when it confronts a real-life situation.     

Generalized schemes for high-throughput manipulation of the Desulfovibrio vulgaris genome

The ability to conduct advanced functional genomic studies of the thousands of sequenced bacteria has been hampered by the lack of available tools for making high-throughput chromosomal manipulations in a systematic manner that can be applied across diverse species. In this work, we highlight the use of synthetic biological tools to assemble custom suicide vectors with reusable and interchangeable DNA "parts" to facilitate chromosomal modification at designated loci. These constructs enable an array of downstream applications, including gene replacement and the creation of gene fusions with affinity purification or localization tags. We employed this approach to engineer chromosomal modifications in a bacterium that has previously proven difficult to manipulate genetically, Desulfovibrio vulgaris Hildenborough, to generate a library of over 700 strains. Furthermore, we demonstrate how these modifications can be used for examining metabolic pathways, protein-protein interactions, and protein localization. The ubiquity of suicide constructs in gene replacement throughout biology suggests that this approach can be applied to engineer a broad range of species for a diverse array of systems biological applications and is amenable to high-throughput implementation.     

Genetic polymorphism in GST, NAT2, and MTRR and susceptibility to childhood acute leukemia

It is known that presence of xenobiotic-metabolizing gene polymorphisms in some cases correlates with hereditary predisposition to the oncological diseases. In the present work the frequencies of xenobiotic-metabolizing gene polymorphisms in 332 children with the diagnosis acute lymphoblastic leukemia (ALL), 71 children with the diagnosis acute myeloblastic leukemia (AML) and 490 healthy donors have been determined using allele-specific hybridization on the biochip. Statistically significant increase in the frequency of GSTT1 "null" genotype (OR = 1.9, p = 4.7E-5) and GSTT1/GSTM1 double "null" genotype (OR = 3.1, p = 2.5E-8) in children with acute leukemia relative to healthy donors group has been revealed. Also 1.8-fold increase in the frequency of NAT2 genotype 341T/T, 481C/C, 590G/G in children with acute leukemia relative to healthy donors group (p = 0.026) has been recognized. Analysis of gene-gene interactions has showed that in patients with acute leukemia genotype NAT2 341T/T, 481C/C, 590G/G in combination with GSTT1 "null" and/or GSTM1 "null" genotype is significantly more frequent than in population control. Besides the reduction of MTRR genotype 66G/G frequency in girls with acute leukemia relative to female healthy donors has been found (OR = 0.50, p = 0.0015). Analysis of gene-gene interactions has shown that the presence of GSTT1 "null" and/or GSTM1 "null" genotype in combination with MTRR genotype 66A/- may consider as risk factor of acute leukemia in girls. Thus, the studied polymorphic variants of genes GSTT1, GSTM1, NAT2 and MTRR can modulate the risk of childhood acute leukemia, residents of European part of Russia.     

On applications of landscape genetics

Recent assertions in the literature (e.g., Keller et al. 2015) suggest that landscape genetic research has been infrequently applied by practitioners. We were interested to test this assertion, which is difficult to assess, since applications may not be detectable through searches of peer-reviewed literature. Producing publications may not be a goal of practitioners. We developed a method to search the internet for evidence of research applications and evaluated 25 different research fields in the natural sciences. We found that fields with more publications also had more applications, but the field of landscape genetics was less applied than expected based on the number of peer-reviewed publications—only about 4 % of landscape genetics articles were applied. In fact, all research fields in genetics or evolutionary biology were under-applied compared to ‘whole organism’, ecological research fields. This result suggests the lack of applications in landscape genetics may be due to a systemic under-application of genetics research, perhaps related to a lack of understanding of genetics by practitioners. We did find some evidence of landscape genetic applications however, which we sorted into 5 categories: (1) identification of evolutionarily significant units for conservation, (2) managing pathogens and invasive species, (3) natural heritage systems planning, (4) assessing population status, and (5) restoration of populations.     

Mouse-human orthology relationships in an olfactory receptor gene cluster

The olfactory receptor (OR) subgenome harbors the largest known gene family in mammals, disposed in clusters on numerous chromosomes. One of the best characterized OR clusters, located at human chromosome 17p13.3, has previously been studied by us in human and in other primates, revealing a conserved set of 17 OR genes. Here, we report the identification of a syntenic OR cluster in the mouse and the partial DNA sequence of many of its OR genes. A probe for the mouse M5 gene, orthologous to one of the OR genes in the human cluster (OR17-25), was used to isolate six PAC clones, all mapping by in situ hybridization to mouse chromosome 11B3-11B5, a region of shared synteny with human chromosome 17p13.3. Thirteen mouse OR sequences amplified and sequenced from these PACs allowed us to construct a putative physical map of the OR gene cluster at the mouse Olfr1 locus. Several points of evidence, including a strong similarity in subfamily composition and at least four cases of gene orthology, suggest that the mouse Olfr1 and the human 17p13.3 clusters are orthologous. A detailed comparison of the OR sequences within the two clusters helps trace their independent evolutionary history in the two species. Two types of evolutionary scenarios are discerned: cases of "true orthologous genes" in which high sequence similarity suggests a shared conserved function, as opposed to instances in which orthologous genes may have undergone independent diversification in the realm of "free reign" repertoire expansion.     

A markov chain approach to calculate r(0) in stochastic epidemic models

R(0) has been defined as "The expected number of secondary infections originated by a "typical" infective individual when introduced into a population of susceptibles", and it is perhaps the single most important parameter in epidemic models. A general framework to calculate R(0) that can be applied to complicated stochastic epidemic models that may include demography, several strains, latent or carrier-like states, with or without density-dependent parameters is introduced. This framework helps us to understand the concept of a "typical" infective individual used in the deterministic definition of R(0). The method is illustrated with applications to several epidemic models, including some in which it has been found that the disease may persist even if R(0)<1. It is shown that although the probability of extinction is difficult to calculate in these latter cases, it is possible to give general conditions on the parameters under which eventual extinction is certain.     

从文献计量角度分析中国生物多样性研究现状

以汤森路透科技集团的WEB OF KNOWLEDGE信息平台提供的Science Citation Index Expanded数据库为数据源,检索到从1997年至2009年期间国际生物多样性研究论文文献219773篇,其中11182篇来自于中国学者。利用NoteExpress软件,对这13a间生物多样性研究论文发表的国家分布、年度分布、研究机构、引用情况、期刊分布和学科分类等做的分析与比较表明:1)全球生物多样性研究的论文数量一直呈增长趋势,中国13年间每年发文量占当年全球生物多样性论文总量的百分率逐年增加;2)从论文总被引频次、篇均引用次数和h-index三项论文影响力特征参数分析,中国与国际其他国家相比有一定差距;3)从学科分类来看,与国际相比,中国在生物多样性保护领域、进化生物学和海洋与淡水生物学领域研究略显不足,昆虫学和真菌学研究领域活跃。     

Combined Healthy Lifestyle Is Inversely Associated with Psychological Disorders among Adults

Background and Aims

Joint association of lifestyle-related factors and mental health has been less studied in earlier studies, especially in Middle Eastern countries. This study aimed to examine how combinations of several lifestyle-related factors related to depression and anxiety in a large group of middle-age Iranian population.

Methods

In a cross-sectional study on 3363 Iranian adults, a healthy lifestyle score was constructed by the use of data from dietary intakes, physical activity, smoking status, psychological distress and obesity. A dish-based 106-item semi-quantitative validated food frequency questionnaire (FFQ), General Practice Physical Activity Questionnaire (GPPAQ), General Health Questionnaire (GHQ) and other pre-tested questionnaires were used to assess the components of healthy lifestyle score. The Hospital Anxiety and Depression Scale (HADS) was applied to screen for anxiety and depression.

Results

After adjustment for potential confounders, we found that individuals with the highest score of healthy lifestyle were 95% less likely to be anxious (OR: 0.05; 95% CI: 0.01–0.27) and 96% less likely to be depressed (OR: 0.04; 95% CI: 0.01–0.15), compared with those with the lowest score. In addition, non-smokers had lower odds of anxiety (OR: 0.64; 95% CI: 0.47–0.88) and depression (OR: 0.62; 95% CI: 0.48–0.81) compared with smokers. Individuals with low levels of psychological distress had expectedly lower odds of anxiety (OR: 0.13; 95% CI: 0.10–0.16) and depression (OR: 0.10; 95% CI: 0.08–0.12) than those with high levels. Individuals with a healthy diet had 29% lower odds of depression (OR: 0.71; 95% CI: 0.59–0.87) than those with a non-healthy diet.

Conclusion

We found evidence indicating that healthy lifestyle score was associated with lower odds of anxiety and depression in this group of Iranian adults. Healthy diet, psychological distress, and smoking status were independent predictors of mental disorders.     

Paraoxonase 1 polymorphisms L55M and Q192R were not risk factors for Parkinson's disease: a HuGE review and meta-analysis

Purpose

The Paraoxonase 1 (PON1) has been studied as a potential candidate gene for Parkinson's disease risk, but direct evidence from genetic association studies remains inconclusive. We performed a meta-analysis pooling data from all relevant studies in order to determine the effects of two PON 1 polymorphisms (L55M and Q192R) on Parkinson's disease.

Methods

We applied a random effects to combine odds ratio (OR) and 95% confidence intervals. Q statistic was used to evaluate the homogeneity, and Egger's test and Funnel plot were used to assess publication bias. In secondary analyses, we examined dominant and recessive models as well.

Results

Concerning the PON1 L55M polymorphism, we identified 9 eligible studies (a total of 2582 cases and 3997 controls). The random effects pooled OR was OR = 1.29, (0.90, 1.84). Concerning the Q192R polymorphism, we identified 7 eligible studies (a total of 2582 cases and 3997 controls). The random effects pooled OR was OR = 1.08(0.81, 1.43). Analysis with dominant and recessive genetic models yielded the same inferences as genotype-based comparisons for both of the two polymorphisms.

Conclusion

The results of this meta-analysis suggested that both PON1 L55M and Q192R were not responsible for PD.     

Does Hair Dye Use Increase the Risk of Breast Cancer? A Population-Based Case-Control Study of Finnish Women

Introduction

Role of hair dyes in the etiology of breast cancer has occasionally raised concern but previous research has concluded with mixed results. Remnants of prohibited aromatic amines have been found in many hair dye products, and elevated levels of DNA-adducts of these amines have been detected from breast epithelial cells of hair dye users. However, the IARC working group has concluded that there is inadequate evidence for carcinogenicity of personal hair dye use and limited evidence in experimental animals for carcinogenicity of hair colorants.

Material and Methods

We investigated whether the use of hair dyes is associated with breast cancer risk in women. The study design was a retrospective population-based case-control study in Finland, with a self-administered questionnaire from 6,567 breast cancer patients, aged 22–60 years and diagnosed in 2000–2007, and their 21,598 matched controls. We report odds ratios (OR) with 95% confidence interval (95% CI) from a conditional logistic regression model applied to the frequency matched sets of cases and controls. Bias-adjusted odds ratios from the sensitivity analysis are also presented.

Results

After adjusting for potential confounders, the odds of breast cancer increased by 23% (OR: 1.23, 95% CI: 1.11–1.36) among women who used hair dyes compared to those who did not. In women born before 1950 an increase of 28% was noted (OR: 1.28, 95% CI: 1.10–1.48). We also observed a significant trend between the OR and cumulative use of hair dyes (P: 0.005). Bias-adjusted odds ratios varied between 1.04 and 2.50.

Conclusions

Our results suggest that use of hair dyes is associated with breast cancer incidence. The impact on public health may be substantial due to vast popularity of hair coloring in modern societies. It should be noted that regardless of all efforts, a possibility of bias cannot definitively be ruled out and use of a prospective design is warranted. Based on the present results, it may be concluded however that safety of hair dyes in relation to breast cancer cannot yet be fully acknowledged and lack of external safety assessment within the cosmetics industry is of major concern.     

Value of Lung Ultrasonography in the Diagnosis and Outcome Prediction of Pediatric Community-Acquired Pneumonia with Necrotizing Change

Background

Lung ultrasonography has been advocated in diagnosing pediatric community-acquired pneumonia. However, its function in identifying necrotizing pneumonia, a complication, has not been explored. This study investigated the value of lung ultrasonography in diagnosing pediatric necrotizing pneumonia and its role in predicting clinical outcomes.

Methods

We retrospectively reviewed 236 children with community-acquired pneumonia who were evaluated using lung ultrasonography within 2–3 days after admission. The ultrasonographic features assessed included lung perfusion, the presence of hypoechoic lesions, and the amount of pleural effusion. Chest computed tomography was also performed in 96 patients as clinically indicated. Detailed records of clinical information were obtained.

Results

Our results showed a high correlation between the degree of impaired perfusion in ultrasonography and the severity of necrosis in computed tomography (r = 0.704). The degree of impaired perfusion can favorably be used to predict massive necrosis in computed tomography (area under the receiver operating characteristic curve, 0.908). The characteristics of impaired perfusion and hypoechoic lesions in ultrasonography were associated with an increased risk of pneumatocele formation (odds ratio (OR), 10.11; 95% CI, 2.95–34.64) and the subsequent requirement for surgical lung resection (OR, 8.28; 95% CI, 1.86–36.93). Furthermore, a longer hospital stay would be expected if moderate-to-massive pleural effusion was observed in addition to impaired perfusion in ultrasonography (OR, 3.08; 95% CI, 1.15–8.29).

Conclusion

Lung ultrasonography is favorably correlated with chest computed tomography in the diagnosis of necrotizing pneumonia, especially regarding massive necrosis of the lung. Because it is a simple and reliable imaging tool that is valuable in predicting clinical outcomes, we suggest that ultrasonography be applied as a surrogate for computed tomography for the early detection of severe necrotizing pneumonia in children.     

Sparse representation approaches for the classification of high-dimensional biological data

Background

High-throughput genomic and proteomic data have important applications in medicine including prevention, diagnosis, treatment, and prognosis of diseases, and molecular biology, for example pathway identification. Many of such applications can be formulated to classification and dimension reduction problems in machine learning. There are computationally challenging issues with regards to accurately classifying such data, and which due to dimensionality, noise and redundancy, to name a few. The principle of sparse representation has been applied to analyzing high-dimensional biological data within the frameworks of clustering, classification, and dimension reduction approaches. However, the existing sparse representation methods are inefficient. The kernel extensions are not well addressed either. Moreover, the sparse representation techniques have not been comprehensively studied yet in bioinformatics.

Results

In this paper, a Bayesian treatment is presented on sparse representations. Various sparse coding and dictionary learning models are discussed. We propose fast parallel active-set optimization algorithm for each model. Kernel versions are devised based on their dimension-free property. These models are applied for classifying high-dimensional biological data.

Conclusions

In our experiment, we compared our models with other methods on both accuracy and computing time. It is shown that our models can achieve satisfactory accuracy, and their performance are very efficient.

     

PLCE1 Polymorphism and Upper Gastrointestinal Cancer Risk: A Meta-Analysis

Background

In recent years, the PLCE1 rs2274223 polymorphism has been extensively investigated as a potential risk factor for upper gastrointestinal cancers, including squamous cell carcinoma (ESCC) and gastric cancer. However, the results of these studies have been inconsistent.

Methods

A meta-analysis of 13 case-control studies was performed including more than 11,000 subjects with genotyped PLCE1 rs2274223 polymorphisms. Odds ratios (OR) with 95% confidence intervals (CI) were employed to assess the association of the PLCE1 rs2274223 polymorphism with a susceptibility to ESCC or gastric cancer.

Results

A statistically significant increase in the risk of ESCC was associated with the PLCE1 rs2274223 polymorphism. This included the homozygous genetic model (OR = 1.46), heterozygous genetic model (OR = 1.25) and allelic genetic model (OR = 1.23). Similar results were consistently found for gastric cancer. In a subgroup analysis, the PLCE1 rs2274223 polymorphism was found to be a very sensitive marker for gastric cardia cancer as shown by the homozygous genetic model (OR = 2.23), heterozygous genetic model(OR = 1.59) and allelic genetic model (OR = 1.47). The risk associations of all of the gastric cardia cancer models were statistically significant. In contrast, none of the genetic models for non-cardia gastric cancer were significant.

Conclusions

In this meta-analysis, the PLCE1 rs2274223 polymorphism was confirmed to have a statistically significant association with an increasing risk of ESCC and gastric cancer. The increase risk was especially observed for gastric cardia cancer.     

Comparison of the canine and human olfactory receptor gene repertoires

Background

Olfactory receptors (ORs), the first dedicated molecules with which odorants physically interact to arouse an olfactory sensation, constitute the largest gene family in vertebrates, including around 900 genes in human and 1,500 in the mouse. Whereas dogs, like many other mammals, have a much keener olfactory potential than humans, only 21 canine OR genes have been described to date.

Results

In this study, 817 novel canine OR sequences were identified, and 640 have been characterized. Of the 661 characterized OR sequences, representing half of the canine repertoire, 18% are predicted to be pseudogenes, compared with 63% in human and 20% in mouse. Phylogenetic analysis of 403 canine OR sequences identified 51 families, and radiation-hybrid mapping of 562 showed that they are distributed on 24 dog chromosomes, in 37 distinct regions. Most of these regions constitute clusters of 2 to 124 closely linked genes. The two largest clusters (124 and 109 OR genes) are located on canine chromosomes 18 and 21. They are orthologous to human clusters located on human chromosomes 11q11-q13 and HSA11p15, containing 174 and 115 ORs respectively.

Conclusions

This study shows a strongly conserved genomic distribution of OR genes between dog and human, suggesting that OR genes evolved from a common mammalian ancestral repertoire by successive duplications. In addition, the dog repertoire appears to have expanded relative to that of humans, leading to the emergence of specific canine OR genes.

     

Suppression of uterine activity and abortion by inhibition of prostaglandin synthesis

The premise has been examined that the evolution of uterine activity, provoked by progesterone(P)-deficiency and consequent prostaglandin(PG)-dominance, can be suppressed in patients by inhibiting PG-synthesis. In 20 midtrimester pregnant women P-deficiency, evolution of intrauterine pressure (IUP), oxytocin response (OR) and abortion had been induced by the hypertonic saline technique and the changes in P and E2 levels and in IUP and OR measured sequentially. According to a "double blind" protocol, 10 volunteers received placebo, while another 10 were treated during 14 hours with 1050 mg naproxen, an inhibitor of PG-synthesis. Significant decrease in plasma progesterone (P 0.001) and estradiol 17Beta (P 0.02) preceding clinical progress in abortion demonstrated that hypertonic saline suppressed the endocrine function of the fetoplacental unit in both groups of patients. In spite of a 40% reduction in the P-levels of the experimental group (at a time when the controls aborted) the evolution of IUP, OR and abortion in the naproxen treated had been delayed by about 30 hours. This significant delay in all the measured parameters (P 0.001) is evidence that inhibition of PG-synthesis prevents the endogenous activation of the uterus in patients, as it does in animal "models".     

An improved model for calculating the optical rotation of simple saccharides

A calculational model for the optical rotation (OR) at the sodium D-line of simple saccharides has been developed that eliminates deficiencies of a previous model. Conformational conclusions based on the earlier model are not affected, as established by a recalculation of the OR phi,psi-map of methyl 3-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside. The model relocates the strong long-wavelength sigma-sigma* circular dichroism (CD) component, which is mainly responsible for the NaD OR from 160 to below 130 nm, where it is now known to occur. That correction allows future modeling of CD bands of different origins that appear in the 150-190 nm region. In order to demonstrate the utility of the revised model, it was applied to calculating the OR of methyl 3-O-(alpha-L-rhamnopyranosyl)-alpha-L-rhamnopyranoside. The results provide experimental support for conformational conclusions derived from a molecular mechanics study of that molecule.