Miracle-dz/UniFAR-FTUs huggingface dataset:
Monitoring Treatment of Patients with Pulmonary Tuberculosis: Can PCR Be Applied?

ABSTRACT To assess whether PCR is applicable for monitoring the efficacy of antituberculous treatment, respiratory specimens obtained during treatment and follow-up from sputum smear-positive tuberculosis (TB) patients were examined. First, results of smear, culture, and PCR forMycobacterium tuberculosis complex (MTB) and an internal inhibition control (MCC) were correlated retrospectively on 1,601 respiratory specimens from patients with no previous cultures of MTB. MTB optical density (OD) values increased to a maximum level of 3.5 to 4.0, with both increasing numbers of acid-fast bacilli and CFU. MTB/MCC OD ratios also increased with both smear and culture grading and correlated significantly better with both than the MTB OD value. Second, changes in MTB OD values and MTB/MCC OD ratios were compared with microscopy and culture for MTB in monthly sputa obtained during treatment and follow-up in 22 smear-positive pulmonary TB patients. Declines in MTB/MCC OD ratios during antituberculous treatment and follow-up were observed. Patients with moderate disease reached the baseline after 6 to 8 months of standard antituberculous treatment regimen, whereas patients with extensive disease were predicted to reach the baseline 1 year or more after the initiation of treatment. Although PCR detects both dead and live bacteria, we believe that PCR can be used to assess the efficacy of antituberculous treatment since increases or slow reductions in MTB/MCC OD ratios would indicate nonoptimal treatment, noncompliance, reduced bioavailability of drugs, or resistant strains of MTB and thereby would identify patients at risk for treatment failure or reactivation.
Recent advances in genetic testing for familial hypercholesterolemia

ABSTRACT Introduction: Familial hypercholesterolemia (FH) is a common genetic cause of premature coronary heart disease that is widely underdiagnosed and undertreated. To improve the identification of FH and initiate timely and appropriate treatment strategies, genetic testing is becoming increasingly offered worldwide as a central part of diagnosis. Areas covered: Recent advances have been propelled by an improved understanding of the genetic determinants of FH together with substantially reduced costs of appropriate screening strategies. Here we review the various methods available for obtaining a molecular diagnosis of FH, and highlight the particular advantages of targeted next-generation sequencing (NGS) platforms as the most robust approach. Furthermore, we note the importance of screening for copy number variants and common polymorphisms to aid in molecularly defining suspected FH cases. Expert commentary: The need for genetic analysis of FH will increase, both for diagnosis and reimbursement of new therapies. An effective molecular diagnostic method must detect: 1) molecular and gene locus heterogeneity; 2) a wide range of mutation types; and 3) the polygenic component of FH. As availability of genetic testing for FH expands, standardization of variant curation, maintenance of clinical databases and registries, and wider health care provider education all assume greater importance.
Immunologic Mechanisms and Therapy in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system (CNS) myelin characterized by focal T-cell and macrophage infiltrates that lead to demyelination (Adams et al. 1989, Prineas et al. 1978, 1976) and loss of neurologic function. In acute MS plaques, activated T cells secreting cytokines and expressing growth factor receptors for IL-2 as well as activated, class II MHC and B7-positive mononuclear cells secreting the regulatory cytokine IL-12 are present (Woodroofe et al. 1986, Hofman et al. 1986, 1989, Windhagen and Hafler, unpublished data). This active inflammatory process is confined to the white matter in the CNS, not affecting either the peripheral nervous system or other organs. Although it is generally accepted that the CNS inflammatory process causes demyelination and the resulting neurologic disability in MS, the mechanism(s) by which the inflammation is initiated and maintained, both in this disease and in fact in all of the presumed Tcell mediated autoimmune diseases in humans, has been difficult to define. There are two general hypotheses for the etiology of human autoimmune disorders. In the flrst instance, the organ becomes infected by a virus or other infectious agent and cells that infiltrate that organ are targeted to the infectious agent. These events would then begin the cascade leading to the organ-specific autoimmune disease. The alternative hypothesis is that the initial infiltrating cells are autoimmune in nature and recognize the organ-specific proteins that are presented by local antigen-presenting cells in the context of MHC. At our present state of knowledge, either hypothesis is possible. However, once the autoimmune cascade begins it is likely that 'epitope spreading' will occur, and T cells recognizing other organspecific proteins will be recruited. Perhaps viruses and infectious agents acting as
Evaluating Binary Alignment Methods in Microsimulation Models

Alignment is a widely adopted technique in the field of microsimulation for social and economic policy research. However, limited research has been devoted to understanding the statistical properties of the various alignment algorithms currently in use. This paper discusses and evaluates six common alignment algorithms used in the dynamic microsimulation through a set of theoretical and statistical criteria proposed in the earlier literature (e.g. Morrison 2006; O'Donoghue 2010). This paper presents and compares the alignment processes, probability transformations, and the statistical properties of alignment outputs in transparent and controlled setups. The results suggest that there is no single best method for all simulation scenarios. Instead, the choice of alignment method might need to be adapted to the assumptions and requirements in a specific project.
Effect of population ageing on emergency department speed and efficiency: a historical perspective from a district general hospital in the UK

Objective: To examine changes in the rate of seeing patients between 1990 and 2004 and to see whether performance might be related to patient age, using data held on the patient administration system. Method: Data collected in 1990 were compared with those collected in 2004. Age related data were examined for the following parameters: the number of patients arriving by ambulance; the time taken to process the attendance; the number of investigations; the number of emergency admissions; and the length of inpatient stay. Results: Emergency department (ED) performance has fallen markedly since 1990. Between 1990 and 2004, there was a 54% increase in total patients with a disproportionate 198% increase in patients aged more than 70 years, including a 671% increase in those aged more than 90 years. The time taken to manage patients increased with age. In 2004, there was a marked rise in investigation rates, and the probability of having investigations increased with age. In 2004, older patients (aged more than 70 years) were 4.9 times more likely to require admission to hospital than younger patients (aged 30 years or less). Their average length of stay was 6.9 times longer. Younger patients were 3.3 times more numerous than older patients but older patients occupied 9.8 times more emergency bed days. Conclusions: Pressure on emergency care is associated with a disproportionate increase in the number of elderly patients and with an increased tendency to investigate them. Population ageing is of central importance in planning health services.
Branched KLVFF Tetramers Strongly Potentiate Inhibition of β‐Amyloid Aggregation

The key pathogenic event in the onset of Alzheimer's disease (AD) is the aggregation of β‐amyloid (Aβ) peptides into toxic aggregates. Molecules that interfere with this process might act as therapeutic agents for the treatment of AD. The amino acid residues 16–20 (KLVFF) are known to be essential for the aggregation of Aβ. In this study, we have used a first‐generation dendrimer as a scaffold for the multivalent display of the KLVFF peptide. The effect of four KLVFF peptides attached to the dendrimer (K4) on Aβ aggregation was compared to the effect of monomeric KLVFF (K1). Our data show that K4 very effectively inhibits the aggregation of low‐molecular‐weight and protofibrillar Aβ1–42 into fibrils, in a concentration‐dependent manner, and much more potently than K1. Moreover, we show that K4 can lead to the disassembly of existing aggregates. Our data lead us to propose that conjugates that bear multiple copies of KLVFF might be useful as therapeutic agents for the treatment of Alzheimer's disease.
Fission Yeast Cdc24 Is a Replication Factor C- and Proliferating Cell Nuclear Antigen-Interacting Factor Essential for S-Phase Completion

ABSTRACT At the nonpermissive temperature the fission yeastcdc24-M38 mutant arrests in the cell cycle with incomplete DNA replication as indicated by pulsed-field gel electrophoresis. Thecdc24+ gene encodes a 501-amino-acid protein with no significant homology to any known proteins. The temperature-sensitive cdc24 mutant is effectively rescued by pcn1 +, rfc1 + (a fission yeast homologue of RFC1), andhhp1 +, which encode the proliferating cell nuclear antigen (PCNA), the large subunit of replication factor C (RFC), and a casein kinase I involved in DNA damage repair, respectively. The Cdc24 protein binds PCNA and RFC1 in vivo, and the domains essential for Cdc24 function and for RFC1 and PCNA binding colocalize in the N-terminal two-thirds of the molecule. In addition,cdc24 + genetically interacts with the gene encoding the catalytic subunit of DNA polymerase ɛ, which is stimulated by PCNA and RFC, and with those encoding the fission yeast counterparts of Mcm2, Mcm4, and Mcm10. These results indicate that Cdc24 is an RFC- and PCNA-interacting factor required for DNA replication and might serve as a target for regulation.
Teachers as learners - insider accounts of learning in an Australian immersion course for Chinese Teachers of English

Meeting requirements for English Proficiency is a challenge for Hong Kong’s teachers of English. An Australian in-service education and training program (INSET) for Chinese L1 teachers is in place to meet this challenge. The question is whether delivery of INSET in Australia leads to participant perceptions of the experience as gainful in terms of pedagogy and cultural knowledge as well as in fulfilling linguistic goals. The researcher indicates a positive response from the case study reported here. The case was designed to test an ongoing evaluation by Hong Kong teachers and the researcher-participant of the program and its consequences. One of the teachers provided the data reported in this paper as part of the larger case. Existing knowledge was reviewed in a literature search spanning internationalisation imperatives for Hong Kong and Australia, the history and implementation of INSET, and the significance of an individual’s personal history. Multiple forms of reflective data were gathered throughout the immersion experience to gather insights into the target participant’s perceptions of learning. These data indicated the learner’s perception of strong positive growth in English proficiency, which might have been expected given the purpose of INSET. However, they also revealed that she learned much about pedagogy and culture, providing insights into intercultural negotiation and learning. The result is important because of its insight into a means by which INSET providers might structure ongoing feedback and assessment of their intentions. Its adaptation to other students, other INSET implementations and locations is worthy of further research and discussion.
Complications of SSRI treatment.

EVEN THOUGH THE SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) have a very favorable side-effect profile, problems can develop during treatment that can cause concern. Complications of treatment that are easiest to deal with are those that are expected, occur early in the course of treatment, are mostly physical in nature, and either go away on their own or with dose reduction or medication discontinuation. More problematic are those complications of treatment that are late in onset, unexpected, and do not go away with dose reduction or medication discontinuation. In addition, complications that present as behavior changes are the most problematic, as it can be difficult to differentiate what is a medication effect and what is related to the disorder or child being treated. Prior to initiating medication most psychopharmacologists will review the physical side effects with patients and their families, but are less likely to discuss adverse behavioral changes seen during medication treatment. Our approach is to talk about the complications of treatment during informed consent rather than side effects, as it is a broader concept and we think it prepares children and families better for participation in a medication trial. In this column we offer an update of important complications (both common and rare) that can occur during SSRI treatment. We have created an A,B,C mnemonic to make it easier to remember (Walkup and Labellarte, 1999). Activation is an increase in activity level that does not include any real change in mood, impulse control, or a change in the child’s demeanor or other behaviors. Others may describe this symptom as disinhibition, akathisia, hyperactivity, etc., but we prefer activation because it does not have a particular etiological association and merely describes what a clinician or a family member may observe. Although most of the time the child is aware of the increase in activity level, they will not necessarily complain about it or experience it as a substantial change in their own behavior. Activation is most often seen early in the course of treatment or soon after a dose increase. In our clinical experience, it probably occurs more commonly in young children than adolescents and adults, and is perhaps even more frequent in children with concurrent minimal brain dysfunction (to use an old term)— including children with ADHD but also children with difficult temperaments or subtle CNS dysfunction. Activation is easily managed by dose reduction or medication discontinuation, although at times it is difficult to get the dose low enough to actually get rid of the activation
Characterization of rat cecum cellulolytic bacteria

Cellulose-degrading bacteria previously isolated from the ceca of rats have been characterized and identified. The most commonly isolated type was rods identified as Bacteroides succinogenes. These bacteria fermented only cellulose (e.g., pebble-milled Whatman no. 1 filter paper), cellobiose, and in 43 of 47 strains, glucose, with succinic and acetic acids as the major products. The only organic growth factors found to be required by selected strains were p-aminobenzoic acid, cyanocobalamine, thiamine, and a straight-chain and a branched-chain volatile fatty acid. These vitamin requirements differ from those of rumen strains of B. succinogenes, indicating the rat strains may form a distinct subgroup within the species. The mole percent guanine plus cytosine was 45%, a value lower than those (48 to 51%) found for three rumen strains of B. succinogenes included in this study. Cellulolytic cocci were isolated less frequently than the rods and were identified as Rumminococcus flavefaciens. Most strains fermented only cellulose and cellobiose, and their major fermentation products were also succinic and acetic acids. Their required growth factors were not identified but were supplied by rumen fluid.
Specific serum carotenoids are inversely associated with breast cancer risk among Chinese women: a case–control study

Abstract Previous epidemiological studies have revealed the anti-cancer effect of dietary circulating carotenoids. However, the protective role of specific individual circulating carotenoids has not been elucidated. The purpose of this study was to examine whether serum carotenoids, including α-carotene, β-carotene, β-cryptoxanthin, lycopene and lutein/zeaxanthin, could lower the risk for breast cancer among Chinese women. A total of 521 women with breast cancer and age-matched controls (5-year interval) were selected from three teaching hospitals in Guangzhou, China. Concentrations of α-carotene, β-carotene, β-cryptoxanthin, lycopene and lutein/zeaxanthin were measured using HPLC. Unconditional logistic regression models were used to calculate OR and 95 % CI using quartiles defined in the control subjects. Significant inverse associations were observed between serum α-carotene, β-carotene, lycopene, lutein/zeaxanthin and the risk for breast cancer. The multivariate OR for the highest quartile of serum concentration compared with the lowest quartile were 0·44 (95 % CI 0·30, 0·65) for α-carotene, 0·27 (95 % CI 0·18, 0·40) for β-carotene, 0·41 (95 % CI 0·28, 0·61) for lycopene and 0·26 (95 % CI 0·17, 0·38) for lutein/zeaxanthin. However, no significant association was found between serum β-cryptoxanthin and the risk for breast cancer. Stratified analysis by menopausal status and oestrogen receptor (ER)/progesterone receptor (PR) showed that serum α-carotene, β-carotene, lycopene and lutein/zeaxanthin were inversely associated with breast cancer risk among premenopausal women and among all subtypes of ER or PR status. The results suggest a protective role of α-carotene, β-carotene, lycopene and lutein/zeaxanthin, but not β-cryptoxanthin, in breast cancer risk.
Expression pattern of the ocular albinism type 1 (Oa1) gene in the murine retinal pigment epithelium.

PURPOSE Mutations in the OA1 gene cause ocular albinism type 1 (OA1), an X-linked form of albinism affecting only the eye, with skin pigmentation appearing normal. To better understand the pathogenesis of this disease the time of onset and the pattern of expression of the mouse homolog of the OA1 gene were monitored during eye development. The localization of Oa1 mRNA was studied and compared with the expression of other genes involved in melanosomal biogenesis. METHODS The Oa1 expression pattern during eye development and after birth was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Localization of Oa1 mRNA was compared with TYROSINASE: (TYR:), pink-eyed dilution (p), and Pax2 expression patterns. RESULTS RT-PCR revealed that Oa1 expression began at embryonic day (E)10.5 and was maintained until adulthood. By in situ hybridization analysis Oa1 transcripts were detected in the retinal pigment epithelium (RPE) beginning at E10.5 in the dorsal part of the eyecup and in the same area where transcripts of other genes involved in pigmentation are found. Of note, the expression pattern of these genes was complementary to Pax2 expression, which was restricted to the ventral side of the optic cup. At later stages, expression of Oa1, TYR:, and p expanded to the entire RPE and ciliary body. CONCLUSIONS Oa1 expression can be detected at early stages of RPE development, together with other genes involved in pigmentation defects. Oa1 is likely to play an important function in melanosomal biogenesis in the RPE beginning during the earliest steps of melanosome formation.
Modelling the role of national system of innovation in economical differentiation

Nowadays it is well accepted that science and technology has a fundamental role in the economic development (GNP per capita) of any country. Aiming to study this role, we introduce a model that creates an artificial world economy that is a network of countries. Each country has its own national system of innovation (represented by a technological parameter). The interactions among the countries are given by functions that connect their prices, demands and incomes. Starting from random values, the artificial world economy self‐organize itself and create hierarchies of countries.
Treatment of an Immortalized APC Cell Line with Both Cytokines and LPS Ensures Effective T‐Cell Activation In Vitro

Antigen‐presenting cells (APCs) are crucial for the generation of a functional immune response to pathogens. Furthermore, there is abundant evidence for their importance in primary T‐cell activation, B‐cell maturation and maintenance of an ongoing immune response. In the present study, we have analysed phenotypic characteristics and functionality of a p53‐deficient APC cell line (JawsII) derived from mouse bone marrow culture. We show that unstimulated JawsII cells express low surface levels of major histocompatibility complex (MHC) and costimulatory molecules, both of which can be upregulated upon treatment with cytokines in vitro. Cytokine stimulation also leads to an enhanced T‐cell activation capacity but has only little effect on cytokine release by the JawsII cells themselves. On the contrary, stimulation of the JawsII cells with lipopolysaccharide (LPS) leads to the production and secretion of high amounts of interleukin‐1 (IL‐1), IL‐6 and tumour necrosis factor‐α (TNF‐α) but no increase in the surface levels of MHC and costimulatory molecules, and has only little effect on the T‐cell activation capacity. Our data suggest that the effects observed upon treatment with cytokines or LPSs are complementary, and that both stimuli are needed for mediating a strong and efficient JawsII cell‐dependent T‐cell activation.
How to Reform Europeâ€™s Fiscal Policy Framework

The current budgetary problems of some EU member states have intensified the debate on Europeâ€™s fiscal policy framework. It is not enough to change the interpretation of the Stability and Growth Pact. More fundamental revisions of the EU Treaty are needed in order to strike a reasonable balance between longrun sustainability and short-run flexibility. The ceiling on budget deficits should be conditioned on the government debt level, such that the scope for stabilisation policy in downswings is increased in low-debt countries. In addition, the enforcement of the rules should be depoliticised: decisions on sanctions against states violating the rules should be transferred from the political level of the Council of Ministers to the judicial level of the European Court of Justice.
Arachidonic Acid Metabolism Regulates Escherichia coli Penetration of the Blood-Brain Barrier

ABSTRACT Escherichia coli K1 meningitis occurs following penetration of the blood-brain barrier, but the underlying mechanisms involved in E. coli penetration of the blood-brain barrier remain incompletely understood. We have previously shown that host cytosolic phospholipase A2α (cPLA2α) contributes to E. coli invasion of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier, but the underlying mechanisms remain unclear. cPLA2α selectively liberates arachidonic acid from membrane phospholipids. Here, we provide the first direct evidence that host 5-lipoxygenase and lipoxygenase products of arachidonic acid, cysteinyl leukotrienes (LTs), contribute to E. coli K1 invasion of HBMEC and penetration into the brain, and their contributions involve protein kinase C alpha (PKCα). These findings demonstrate that arachidonic acid metabolism regulates E. coli penetration of the blood-brain barrier, and studies are needed to further elucidate the mechanisms involved with metabolic products of arachidonic acid for their contribution to E. coli invasion of the blood-brain barrier.