Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

An initial comparative map of copy number variations in the goat (Capra hircus) genome

<p>Abstract</p> <p>Background</p> <p>The goat (<it>Capra hircus</it>) represents one of the most important farm animal species. It is reared in all continents with an estimated world population of about 800 million of animals. Despite its importance, studies on the goat genome are still in their infancy compared to those in other farm animal species. Comparative mapping between cattle and goat showed only a few rearrangements in agreement with the similarity of chromosome banding. We carried out a cross species cattle-goat array comparative genome hybridization (aCGH) experiment in order to identify copy number variations (CNVs) in the goat genome analysing animals of different breeds (Saanen, Camosciata delle Alpi, Girgentana, and Murciano-Granadina) using a tiling oligonucleotide array with ~385,000 probes designed on the bovine genome.</p> <p>Results</p> <p>We identified a total of 161 CNVs (an average of 17.9 CNVs per goat), with the largest number in the Saanen breed and the lowest in the Camosciata delle Alpi goat. By aggregating overlapping CNVs identified in different animals we determined CNV regions (CNVRs): on the whole, we identified 127 CNVRs covering about 11.47 Mb of the virtual goat genome referred to the bovine genome (0.435% of the latter genome). These 127 CNVRs included 86 loss and 41 gain and ranged from about 24 kb to about 1.07 Mb with a mean and median equal to 90,292 bp and 49,530 bp, respectively. To evaluate whether the identified goat CNVRs overlap with those reported in the cattle genome, we compared our results with those obtained in four independent cattle experiments. Overlapping between goat and cattle CNVRs was highly significant (P < 0.0001) suggesting that several chromosome regions might contain recurrent interspecies CNVRs. Genes with environmental functions were over-represented in goat CNVRs as reported in other mammals.</p> <p>Conclusions</p> <p>We describe a first map of goat CNVRs. This provides information on a comparative basis with the cattle genome by identifying putative recurrent interspecies CNVs between these two ruminant species. Several goat CNVs affect genes with important biological functions. Further studies are needed to evaluate the functional relevance of these CNVs and their effects on behavior, production, and disease resistance traits in goats.</p

Spirituality and qulity of life in hemodialysis patients

The accuracy and efficacy of the diagnosis and the renal replacement modalities for end stage renal disease are becoming increasingly sophisticated, but the psychospiritual impact of the disease is still unclear. Although there were studies supporting the relationship of spirituality and quality of life in various chronic conditions, little information regarding this relationship is known for chronic hemodialysis patients. This descriptive correlational study was done to describe the spirituality and health-related quality of life of adult long-term hemodialysis patients, and to examine the relationship between spirituality and health-related quality of life in these patients. The stress, appraisal, and coping theory developed by Lazarus and Folkman (1984) served as the theoretical framework. A convenience sample of 88 subjects who received hemodialysis for over three months completed the Kidney Disease Quality of Life Short Form (KDQOL-SF™) questionnaire and the revised Spiritual Involvement and Beliefs Scale (SD3S-R) during one hemodialysis treatment session. Overall, these long-term hemodialysis patients perceived a moderately low level of spirituality. The low spirituality appeared to be related to the persistence of health problems over time and that the subjects were concerned with physiological needs rather than being focused on their spiritual life. The subjects perceived a moderately low level of health-related quality of life and were worse in physical than in mental and emotional dimensions. There was no statistical correlation between the perception of spirituality and health-related quality of life (r = . 14, p_ < .05). Patients with high scores of spirituality appeared to perceive better general health and higher energy level. The lack of correlation between spirituality and quality of life appeared to be related to the nature of the sample and the psychometric quality of the tool used to measure spirituality. Based on the findings, suggestions are made for new directions for the provision of effective health care for hemodialysis patients. It is recommended that the tool used to measure spirituality be strengthened, a random selection from a larger population in multiple hemodialysis centers be used, and the data collection be done between, rather than during dialysis treatments. A longitudinal approach would lead to a more comprehensive understanding of the relationship between spirituality and quality of life over the course of patients' experiences with chronic kidney disease.Applied Science, Faculty ofNursing, School ofGraduat

‘Black Is’ and ‘Black Ain’t’: performative revisions of racial ‘crisis’

Race is rigorously policed through, and predicated on, a crisis of maintaining a claim to supposed racial ontology. The language of crisis pervades race; yet crisis is only brought into focus – shows itself – when racial ontology is called into question or threatened as an axiomatic reality. This essay argues, however, that it is crisis, in the form of the imperative regulatory call to race or the intricate operations of racialising discipline that constitutes raced subjects. The crisis is one of belonging or of successfully representing a ‘racial truth’. The objective of this analysis is to demonstrate that it is when race is viewed as performative that crisis becomes evident as the ever-present condition of racial identity formation. From this vantage point, the concept of crisis as a point of danger can be revised to be seen as a turning point when an important change can take place: then, crisis might be envisaged as a positive means through which to imagine and realise new enactments of racial being

DNA Methylation of Tumor Suppressive miRNAs in Non-Hodgkin’s Lymphomas

In addition to histone modification, DNA methylation is the other form of epigenetic alteration leading to heritable phenotypic changes of cells with functional consequences. DNA methylation is important in early embryonic development, stem cell differentiation, and tissue-specific gene expression in somatic cells. In normal cells, promoter-associated CpG islands are generally unmethylated except in X-chromosome inactivation or genomic imprinting. In cancer, tumor cells are characterized by global hypomethylation but locus-specific hypermethylation of promoter-associated CpG islands, resulting in gene silencing. MicroRNAs (miRNAs) are short, non-coding RNA sequences of 18-25 nucleotides, leading to translational repression of multiple protein-coding mRNAs by sequence-specific binding to the 3’ untranslated region. Depending on the genes that are targeted by the miRNA, miRNA can be tumor suppressive if an oncogene is being targeted, and conversely, oncogenic when a tumor suppressive gene is targeted. Recently, aberrant methylation of tumor suppressive miRNAs has been reported in different types of cancers including lymphomas. Herein, we summarize the recent literature of aberrant DNA methylation of tumor suppressive miRNAs in non-Hodgkin’s lymphomas (NHLs), including miRNA methylation in the pathogenesis of specific NHL subtypes, such as natural killer (NK)/T-cell, gastric mucosa-associated lymphoid tissue, anaplastic large cell or Burkitt’s lymphoma and the studies of miRNA methylation in B-, T- or NK-cell lymphomas by candidate miRNA approac

Epigenetic inactivation of the MIR129-2 in hematological malignancies

Background: MIR129-2 has been shown to be a tumor suppressor microRNA hypermethylated in epithelial cancers. Patients and methods: Epigenetic inactivation of MIR129-2 was studied by methylation-specific PCR (MSP) in 13 cell lines (eight myeloma and five lymphoma), 15 normal controls and 344 primary samples including acut

Single-Nucleotide Variations, Insertions/Deletions and Copy Number Variations in Myelodysplastic Syndrome during Disease Progression Revealed by a Single-Cell DNA Sequencing Platform

Myelodysplastic syndrome (MDS) is a clonal myeloid neoplasm characterized by ineffective hematopoiesis, cytopenia, dysplasia, and clonal instability, leading to leukemic transformation. Hypomethylating agents are the mainstay of treatment in higher-risk MDS. However, treatment resistance and disease transformation into acute myeloid leukemia (AML) is observed in the majority of patients and is indicative of a dismal outcome. The residual cell clones resistant to therapy or cell clones acquiring new genetic aberrations are two of the key events responsible for drug resistance. Bulk tumor sequencing often fails to detect these rare subclones that confer resistance to therapy. In this study, we employed a single-cell DNA (sc-DNA) sequencing approach to study the clonal heterogeneity and clonal evolution in two MDS patients refractory to HMA. In both patients, different single nucleotide variations (SNVs) or insertions and deletions (INDELs) were detected with bulk tumor sequencing. Rare cell clones with mutations that are undetectable by bulk tumor sequencing were detected by sc-DNA sequencing. In addition to SNVs and short INDELs, this study also revealed the presence of a clonal copy number loss of DNMT3A, TET2, and GATA2 as standalone events or in association with the small SNVs or INDELs detected during HMA resistance and disease progression