Delayed Treatment of Diagnosed Pulmonary Tuberculosis in Taiwan

<p>Abstract</p> <p>Background</p> <p>Mycobacterium tuberculosis infection is an ongoing public health problem in Taiwan. The National Tuberculosis Registry Campaign, a case management system, was implemented in 1997. This study examined this monitoring system to identify and characterize delayed treatment of TB patients.</p> <p>Methods</p> <p>Records of all tuberculosis cases treated in Taiwan from 2002 through 2005 were obtained from the National Tuberculosis Registry Campaign. Initiation of treatment more than 7 days after diagnosis was considered a long treatment delay.</p> <p>Results</p> <p>The study included 31,937 patients. The mean day of delayed treatment was 3.6 days. Most patients were treated immediately after diagnosis. The relationship between number of TB patients and days of delayed treatment after diagnosis exhibited a Power-law distribution. The long tail of the power-law distribution indicated that an extreme number occur cannot be neglected. Tuberculosis patients treated after an unusually long delay require close observation and follow up.</p> <p>Conclusion</p> <p>This study found that TB control is generally acceptabl in Taiwan; however, delayed treatment increases the risk of transmission. Improving the protocol for managing confirmed TB cases can minimize disease transmission.</p

Specific Syndecan-1 Domains Regulate Mesenchymal Tumor Cell Adhesion, Motility and Migration

Malignant mesothelioma is an asbestos induced cancer that is difficult to diagnose. Several studies have combined biomarkers to improve mesothelioma diagnosis, but with moderate success, and there is a need for new mesothelioma biomarkers. The tumour is often resistant to treatment and most patients will survive less than a year. An indicator of patient survival is the tumours growth pattern, which in turn is influenced by expressed proteoglycans. In this thesis work, we aim to improve the possibilities to diagnose malignant mesothelioma by combining biomarkers and by identifying new ones. We also investigate tumour driving mechanisms with focus on one of these suggested biomarkers, the cell-bound proteoglycan syndecan-1. We were able to construct a diagnostic two-step model based on biomarkers in patient material. By implementing a cut-off level and thereafter focusing on unresolved patients we combined hyaluronan and N-ERC/mesothelin (paper I), which significantly increased the diagnostic accuracy for malignant mesothelioma. To further improve diagnosis, we used mass spectrometry to find new biomarkers. We identified and validated galectin-1, which was excellent in discriminating mesotheliomas from adenocarcinomas (paper II). In the same study, we were also the first to describe aldo-keto reductase 1B10 as a novel prognostic mesothelioma biomarker. Syndecan-1 has been indicated as a marker for carcinomas. In paper I we describe how higher levels of syndecan-1 indicate the presence of a carcinoma over a mesothelioma. This was verified in paper II when syndecan-1 was identified as downregulated in fluids from mesothelioma patients compared to lung cancer patients. Paper III and paper IV focus on this proteoglycan. Malignant cell lines transfected with syndecan-1 and various truncated forms of syndecan-1 affected adhesion and migration, which are key features of cancer invasion (paper III). The results showed a domain- and cell type specific effect on the cells’ motility. Regulating syndecan-1 levels and analysing the global gene expression of mesothelioma cells made it evident that this proteoglycan has a strong influence on transforming growth factor β signalling and several growth factor pathways (paper IV). Links to cell migration and proliferation were furthermore identified, along with glycosaminoglycan modifying enzymes. These results can shed light on the complex role of syndecan-1 in invasion and growth of malignant mesenchymal cells. Taken together, this thesis work describes a complement to conventional mesothelioma diagnosis and identifies novel biomarkers. Furthermore, the potential biomarker syndecan-1 was shown to have an effect on cell motility and proliferation. These results increase our understanding of this aggressive malignancy

Metabotropic glutamate receptor 5 as a potential target for smoking cessation

Rationale Most habitual smokers find it difficult to quit smoking because they are dependent upon the nicotine present in tobacco smoke. Tobacco dependence is commonly treated pharmacologically using nicotine replacement therapy or drugs, such as varenicline, that target the nicotinic receptor. Relapse rates, however, remain high and there remains a need to develop novel non-nicotinic pharmacotherapies for the dependence that are more effective than existing treatments. Objective The purpose of this paper is to review the evidence from preclinical and clinical studies that drugs that antagonise the metabotropic glutamate receptor 5 (mGluR5) in the brain are likely to be efficacious as treatments for tobacco dependence. Results Imaging studies reveal that chronic exposure to tobacco smoke reduces the density of mGluR5s in human brain. Preclinical results demonstrate that negative allosteric modulators (NAMs) at mGluR5 attenuate both nicotine self-administration and the reinstatement of responding evoked by exposure to conditioned cues paired with nicotine delivery. They also attenuate the effects of nicotine on brain dopamine pathways implicated in addiction. Conclusions Although mGluR5 NAMs attenuate most of the key facets of nicotine dependence they potentiate the symptoms of nicotine withdrawal. This may limit their value as smoking cessation aids. The NAMs that have been employed most widely in preclinical studies of nicotine dependence have too many \u201coff target\u201d effects to be used clinically. However newer mGluR5 NAMs have been developed for clinical use in other indications. Future studies will determine if these agents can also be used effectively and safely to treat tobacco dependence

Activation of Human Monocytes by Live Borrelia burgdorferi Generates TLR2-Dependent and -Independent Responses Which Include Induction of IFN-β

It is widely believed that innate immune responses to Borrelia burgdorferi (Bb) are primarily triggered by the spirochete's outer membrane lipoproteins signaling through cell surface TLR1/2. We recently challenged this notion by demonstrating that phagocytosis of live Bb by peripheral blood mononuclear cells (PBMCs) elicited greater production of proinflammatory cytokines than did equivalent bacterial lysates. Using whole genome microarrays, we show herein that, compared to lysates, live spirochetes elicited a more intense and much broader transcriptional response involving genes associated with diverse cellular processes; among these were IFN-β and a number of interferon-stimulated genes (ISGs), which are not known to result from TLR2 signaling. Using isolated monocytes, we demonstrated that cell activation signals elicited by live Bb result from cell surface interactions and uptake and degradation of organisms within phagosomes. As with PBCMs, live Bb induced markedly greater transcription and secretion of TNF-α, IL-6, IL-10 and IL-1β in monocytes than did lysates. Secreted IL-18, which, like IL-1β, also requires cleavage by activated caspase-1, was generated only in response to live Bb. Pro-inflammatory cytokine production by TLR2-deficient murine macrophages was only moderately diminished in response to live Bb but was drastically impaired against lysates; TLR2 deficiency had no significant effect on uptake and degradation of spirochetes. As with PBMCs, live Bb was a much more potent inducer of IFN-β and ISGs in isolated monocytes than were lysates or a synthetic TLR2 agonist. Collectively, our results indicate that the enhanced innate immune responses of monocytes following phagocytosis of live Bb have both TLR2-dependent and -independent components and that the latter induce transcription of type I IFNs and ISGs

К проблеме социальной эффективности инноваций в профессиональном образовании

Movile Cave, Romania, is an unusual underground ecosystem that has been sealed off from the outside world for several million years and is sustained by non-phototrophic carbon fixation. Methane and sulfur-oxidising bacteria are the main primary producers, supporting a complex food web that includes bacteria, fungi and cave-adapted invertebrates. A range of methylotrophic bacteria in Movile Cave grow on one-carbon compounds including methylated amines, which are produced via decomposition of organic-rich microbial mats. The role of methylated amines as a carbon and nitrogen source for bacteria in Movile Cave was investigated using a combination of cultivation studies and DNA stable isotope probing (DNA-SIP) using 13C-monomethylamine (MMA). Two newly developed primer sets targeting the gene for gamma-glutamylmethylamide synthetase (gmaS), the first enzyme of the recently-discovered indirect MMA-oxidation pathway, were applied in functional gene probing. SIP experiments revealed that the obligate methylotroph Methylotenera mobilis is one of the dominant MMA utilisers in the cave. DNA-SIP experiments also showed that a new facultative methylotroph isolated in this study, Catellibacterium sp. LW-1 is probably one of the most active MMA utilisers in Movile Cave. Methylated amines were also used as a nitrogen source by a wide range of non-methylotrophic bacteria in Movile Cave. PCR-based screening of bacterial isolates suggested that the indirect MMA-oxidation pathway involving GMA and N-methylglutamate is widespread among both methylotrophic and non-methylotrophic MMA utilisers from the cave

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Not AvailableSmooth transition from pregnancy to lactation is important for high productive and reproductive performance during later postpartum period in dairy animals. On the other hand, the poor transition often leads to huge economic loss to dairy farmers due to compromised production and reproduction. Therefore, understanding the causes and consequence of metabolic changes during the transition period is very important for postpartum health management. In this review, metabolic changes with reference to negative energy balance in transition cow and its effect on health and reproduction during the later postpartum period in dairy animals are discussed besides the role of metabolic inflammation in postpartum performance in dairy animalsNot Availabl

TRANSITION PERIOD INFLUENCES LACTATION PERFORMANCE IN ZEBU

Not AvailableWe evaluated the changes in the concentration of innate immune molecules (haptoglobin: Hp, serum amyloid A: SAA, IL-6, TNF-D, IL-1E, and IL-8), energy indicators [NEFA, dry matter intake (DMI) and body condition scoring (BCS)] during the transition period in dual-purpose Zebu (Deoni breed) cows in relation to milk yield. Blood collection was done at weekly intervals (–21±2, –14±1, –7±1, d pre-partum, day 0 (date of calving) and 3±1, 7±1, 14±1, 21±2 d postpartum period) for estimation of above plasma variables using commercially available bovine specific ELISA kits. We also recorded DMI and BCS during the corresponding period. Transition cows were classified based on their milk yield during the study period as high (6), medium (6) and low (6) yielding cows and data were analyzed by using Mixed-model repeated measure analysis. High yielding (HY) cows had significantly higher concentrations of SAA, TNF-D, and IL-6 during pre-partum and early postpartum period than low yielding (LY) cows. DMI was significantly higher in HY cows than MY (3rd and 7th d) or LY cows (21st d) while, BCS was significantly higher in HY than LY cows during pre-partum period (-7th d). LY cows had significantly higher concentration of NEFA during the postpartum period (14th and 21st d). It is concluded that the active functioning of the immune system and more dry matter intake in transition Deoni cows enabled to synthesise more milk during the postpartum period.ICAR-NDR

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Not AvailableThe aim of the present study was to assess if the metabolic adaptation and immune status during transition period influence the postpartum reproductive performance in dairy cattle. We assessed the levels of innate immune molecules (Haptoglobin: Hp, Serum Amyloid A: SAA, IL-6, TNF-α, IL-1β, and IL-8) and energy balance indicators [NEFA and Dry Matter Intake (DMI)] in transition Zebu (Deoni breed) cows that became pregnant within breeding period (n = 7) and remained non-pregnant (n = 10) even after the breeding period (i.e. from 45 to 180 days postpartum). Blood samples were collected at weekly intervals during transition period (−21 d before to 21 d after calving) and plasma variables were estimated using commercially available bovine specific ELISA kits. Plasma Hp concentration was significantly (P < 0.01) higher in cows that became pregnant during breeding period as compared to those that remained non-pregnant. While plasma TNF-α concentrations differed significantly (P = 0.05) between groups, such difference was not observed with SAA concentrations. Group x time interaction had a significant effect on plasma IL-6 (P < 0.01), IL-1β (P = 0.05), IL-8 (P = 0.05) concentrations and DMI (P = 0.001). Plasma NEFA concentrations differed significantly (P = 0.03) between groups, although all the experimental cows had NEFA concentrations within the physiological limits. Days in milk had a significant effect on milk yield (P = 0.001) and fat percentage (P = 0.03). It is concluded that active functioning of immune system, stable dry matter intake, and limited fat mobilization during transition period enabled the cows to conceive early during postpartum period.Not Availabl