bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pattern recognition and cellular immune responses to novel Mycobacterium tuberculosis-antigens in individuals from Belarus
Authors: Ahmed Raija K , Rohava Zoyia , Balaji Kithiganahalli N , Hoffner Sven E , Gaines Hans , Magalhaes Isabelle , Zumla Alimuddin , Skrahina Alena , Maeurer Markus J 
Published: February 2012

AbstractBackgroundTuberculosis (TB) is an enduring health problem worldwide and the emerging threat of multidrug resistant (MDR) TB and extensively drug resistant (XDR) TB is of particular concern. A better understanding of biomarkers associated with TB will aid to guide the development of better targets for TB diagnosis and for the development of improved TB vaccines.MethodsRecombinant proteins (n = 7) and peptide pools (n = 14) fromM. tuberculosis(M.tb) antigens associated withM.tbpathogenicity, modification of cell lipids or cellular metabolism, were used to compare T cell immune responses defined by IFN-γ production using a whole blood assay (WBA) from i) patients with TB, ii) individuals recovered from TB and iii) individuals exposed to TB without evidence of clinical TB infection from Minsk, Belarus.ResultsWe identified differences inM.tbtarget peptide recognition between the test groups, i.e. a frequent recognition of antigens associated with lipid metabolism, e.g. cyclopropane fatty acyl phospholipid synthase. The pattern of peptide recognition was broader in blood from healthy individuals and those recovered from TB as compared to individuals suffering from pulmonary TB. Detection of biologically relevantM.tbtargets was confirmed by staining for intracellular cytokines (IL-2, TNF-α and IFN-γ) in T cells from non-human primates (NHPs) after BCG vaccination.ConclusionsPBMCs from healthy individuals and those recovered from TB recognized a broader spectrum ofM.tbantigens as compared to patients with TB. The nature of the pattern recognition of a broad panel ofM.tbantigens will devise better strategies to identify improved diagnostics gauging previous exposure toM.tb; it may also guide the development of improved TB-vaccines.
The development of a lay health worker delivered collaborative community based intervention for people with schizophrenia in India
Authors: Balaji Madhumitha , Chatterjee Sudipto , Koschorke Mirja , Rangaswamy Thara , Chavan Animish , Dabholkar Hamid , Dakshin Lilly , Kumar Pratheesh , John Sujit , Thornicroft Graham , Patel Vikram 
Published: February 2012

Abstract

Background
Care for schizophrenia in low and middle income countries is predominantly facility based and led by specialists, with limited use of non-pharmacological treatments. Although community based psychosocial interventions are emphasised, there is little evidence about their acceptability and feasibility. Furthermore, the shortage of skilled manpower is a major barrier to improving access to these interventions. Our study aimed to develop a lay health worker delivered community based intervention in three sites in India. This paper describes how the intervention was developed systematically, following the MRC framework for the development of complex interventions.

Methods
We reviewed the lierature on the burden of schizophrenia and the treatment gap in low and middle income countries and the evidence for community based treatments, and identified intervention components. We then evaluated the acceptability and feasibility of this package of care through formative case studies with individuals with schizophrenia and their primary caregivers and piloted its delivery with 30 families.

Results
Based on the reviews, our intervention comprised five components (psycho-education; adherence management; rehabilitation; referral to community agencies; and health promotion) to be delivered by trained lay health workers supervised by specialists. The intervention underwent a number of changes as a result of formative and pilot work. While all the components were acceptable and most were feasible, experiences of stigma and discrimination were inadequately addressed; some participants feared that delivery of care at home would lead to illness disclosure; some participants and providers did not understand how the intervention related to usual care; some families were unwilling to participate; and there were delivery problems, for example, in meeting the targeted number of sessions. Participants found delivery by health workers acceptable, and expected them to have knowledge about the subject matter. Some had expectations regarding their demographic and personal characteristics, for example, preferring only females or those who are understanding/friendly. New components to address stigma were then added to the intervention, the collaborative nature of service provision was strengthened, a multi-level supervision system was developed, and delivery of components was made more flexible. Criteria were evolved for the selection and training of the health workers based on participants' expectations.

Conclusions
A multi-component community based intervention, targeting multiple outcomes, and delivered by trained lay health workers, supervised by mental health specialists, is an acceptable and feasible intervention for treating schizophrenia in India.
Attenuation of influenza virus infectivity with herbal-marine compound (HESA-A): an in vitro study in MDCK cells
Authors: Mehrbod Parvaneh , Ideris Aini , Omar Rahman Rahman , Hair-Bejo Mohd , Tan Sheau Wei , Kheiri Masoumeh Tavassoti , Tabatabaian Mansoureh 
Published: February 2012

Abstract

Background
The influenza virus is still one of the most important respiratory risks affecting humans which require effective treatments. In this case, traditional medications are of interest. HESA-A is an active natural biological compound from herbal-marine origin. Previous studies have reported that the therapeutic properties of HESA-A are able to treat psoriasis vulgaris and cancers. However, no antiviral properties have been reported.

Methods
This study was designed to investigate the potential antiviral properties of HESA-A and its effects in modulating TNF-α and IL-6 cytokine levels. HESA-A was prepared in normal saline as a stock solution (0.8 mg/ml, pH = 7.4). Percentages of cell survival when exposed to different concentrations of HESA-A at different time intervals was determined by MTT assay. To study the potential antiviral activity of HESA-A, Madin-Darby Canine Kidney (MDCK) cells were treated with the effective concentration (EC50) of HESA-A (0.025 mg/ml) and 100 TCID50/0.1 ml of virus sample under different types of exposure.

Results
Based on the MTT method and hemagglutination assay (HA), HESA-A is capable of improving cell viability to 31% and decreasing HA titre to almost 99% in co-penetration exposures. In addition, based on quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), it was found that HESA-A causes decrements in TNF-α and IL-6 cytokine expressions, which was significant for TNF-α (p ≤ 0.05) but not for IL-6.

Conclusion
In conclusion, HESA-A was effective against influenza infection through suppressing cytokine expression.
Evaluation of immune responses to porcine reproductive and respiratory syndrome virus in pigs during early stage of infection under farm conditions
Authors: Dwivedi Varun , Manickam Cordelia , Binjawadagi Basavaraj , Linhares Daniel , Murtaugh Michael P , Renukaradhya Gourapura J 
Published: February 2012

AbstractBackgroundPorcine reproductive and respiratory syndrome virus (PRRSV) causes chronic, economically devastating disease in pigs of all ages. Frequent mutations in the viral genome result in viruses with immune escape mutants. Irrespective of regular vaccination, control of PRRSV remains a challenge to swine farmers. In PRRSV-infected pigs, innate cytokine IFN-α is inhibited and the adaptive arm of the immunity is delayed. To elucidate both cellular and innate cytokine responses at very early stages of PRRSV infection, seven weeks old pigs maintained on a commercial pig farm were infected and analyzed.ResultsOne pig in a pen containing 25 pigs was PRRSV infected and responses from this pig and one penmate were assessed two days later. All the infected and a few of the contact neighbor pigs were viremic. At day 2 post-infection, approximately 50% of viremic pigs had greater than 50% reduction in NK cell-mediated cytotoxicity, and nearly a 1-fold increase in IFN-α production was detected in blood of a few pigs. Enhanced secretion of IL-4 (in ~90%), IL-12 (in ~40%), and IL-10 (in ~20%) (but not IFN-γ) in PRRSV infected pigs was observed. In addition, reduced frequency of myeloid cells, CD4-CD8+T cells, and CD4+CD8+T cells and upregulated frequency of lymphocytes bearing natural T regulatory cell phenotype were detected in viremic pigs. Interestingly, all viremic contact pigs also had comparable immune cell modulations.ConclusionReplicating PRRSV in both infected and contact pigs was found to be responsible for rapid modulation in NK cell-meditated cytotoxicity and alteration in the production of important immune cytokines. PRRSV-induced immunological changes observed simultaneously at both cellular and cytokine levels early post-infection appear to be responsible for the delay in generation of adaptive immunity. As the study was performed in pigs maintained under commercial environmental conditions, this study has practical implications in design of protective vaccines.
Sentinel events and predictors of suicide among inpatients at psychiatric hospitals
Authors: Chen Yi-Lung , Tzeng Dong-Sheng , Cheng Ting-Sheng , Lin Chien-Hung 
Published: February 2012

AbstractBackgroundThe objective of this study was to assess sentinel event analysis and relative factors in different mental healthcare settings. In addition, the occurrence of sentinel events in different hospital settings was compared and potential risk factors contributing to sentinel events identified.MethodsA total of 75 consecutive adult subjects were enrolled from 2 psychiatric units, 1 within a general hospital and 1 at a psychiatric hospital in southern Taiwan. A retrospective chart review of the psychiatric inpatients was conducted for patients that met the criteria for a sentinel event between July 2004 and May 2011. A comparison of the hospital settings was made and differences between suicidal and non-suicidal sentinel events studied.ResultsPsychiatric patients that received general hospital psychiatric services (1) appeared to experience a sentinel event soon after admission, (2) the time between the sentinel event occurrence and patient death was shorter, (3) there was a higher probability of potential medical illness than among inpatients treated at a specialized psychiatric hospital, (4) the sentinel event subjects that committed suicide were younger, had a shorter hospital stay, shorter time to occurrence of the sentinel event followed by an unexpected death than the non-suicidal group, and (5) a younger age, higher education level, previous suicide attempt and family psychiatric history were important predictors of suicide among psychiatric inpatients.ConclusionsThe results of this study suggest that psychiatric inpatients treated at a general hospital require careful examination for potential physical illness and greater efforts to prevent suicide. A younger age, higher education level, history of a previous suicide attempt and family psychiatric history are additional risk factors for suicide among these patients.
Acute and late toxicities of radiotherapy for patients with discoid lupus erythematosus: a retrospective case-control study
Authors: Patel Ajaykumar B , Hallemeier Christopher L , Petersen Ivy A , Jensen Ashley W , Osborn Thomas G , Miller Robert C 
Published: February 2012

Abstract

Background
The purpose of this study was to evaluate acute and late toxicities of radiotherapy for patients with discoid lupus erythematosus (DLE).

Methods
A retrospective review was performed of patients with DLE who received radiotherapy at our institution between 1980 and 2005. Patients with other connective tissue disorders were excluded. Control patients were matched 2:1 with the DLE treatment courses based on age, cancer diagnosis, year of treatment, radiotherapy dose, and sex. Acute (within 30 days from the completion of radiotherapy) and late toxicities were evaluated for each treatment course using the Common Terminology Criteria for Adverse Events Version 3.0.

Results
Twelve patients with DLE received a total of 15 radiotherapy courses. The median follow-up time was 2.6 years (range, 0.0-15.2 years). Acute toxicity of any organ was observed in 10 (67%) treatment courses, of which 2 (13%) were Grade 3 or higher. Acute Grade 1 or 2 dermatologic toxicity was observed in 8 courses (53%). Late toxicity of any organ was observed in 7 of 12 (58%) evaluable treatment courses, of which 3 (23%) were grade 3 or higher. Late grade 1 or 2 dermatologic toxicity was observed in 5 (42%) courses. No patient experienced acute or late Grade 3 or higher dermatologic toxicity. The rates of any organ or dermatologic acute and late toxicity were not significantly different between DLE and control treatment courses.

Conclusions
Our findings do not suggest an increased risk of toxicity to the skin or other organs in patients with DLE receiving radiotherapy.
BK viremia in critically ill surgical patients with hemorrhagic or septic shock
Authors: Nass Maximilian , Weissbrich Benedikt , Huber Moritz , Schneider Elisabeth Marion , Weiss Manfred 
Published: February 2012

Abstract

Background
Infections with polyomavirus BK virus (BKV) are a common cause of renal dysfunction after renal transplantation and may also be harmful in surgical patients with shock. The aim of the present study was to determine the frequency of BKV viremia in critically ill surgical patients with septic or hemorrhagic shock, and, if viremia is detectable, whether viremia may be associated with renal dysfunction.

Findings
A total of 125 plasma samples from 44 critically ill surgical patients with septic or hemorrhagic shock were tested by real-time polymerase chain reaction (PCR) for BKV DNA during their stay on the intensive care unit (ICU). BKV viremia occurred in four patients, i.e. in three of the septic and in one of the hemorrhagic shock group. There was no association between viremia and renal dysfunction. All positive samples contained a low viral load (< 500 copies/ml).

Conclusions
Since BK viremia was rarely found and with low viral load only in critically ill surgical patients with shock, it is very unlikely that BK viremia results in BK nephropathy later on.
Development of 4H-pyridopyrimidines: a class of selective bacterial protein synthesis inhibitors
Authors: Guiles Joseph W , Toro Andras , Ochsner Urs A , Bullard James M 
Published: February 2012

Abstract

Background
We have identified a series of compounds that inhibit protein synthesis in bacteria. Initial IC50's in aminoacylation/translation (A/T) assays ranged from 3 to14 μM. This series of compounds are variations on a 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ol scaffold (e.g., 4H-pyridopyrimidine).

Methods
Greater than 80 analogs were prepared to investigate the structure-activity relationship (SAR). Structural modifications included changes in the central ring and substituent modifications in its periphery focusing on the 2- and 6-positions. An A/T system was used to determine IC50 values for activity of the analogs in biochemical assays. Minimum inhibitory concentrations (MIC) were determined for each analog against cultures of Enterococcus faecalis, Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli tolC mutants and E. coli modified with PMBN.

Results
Modifications to the 2-(pyridin-2-yl) ring resulted in complete inactivation of the compounds. However, certain modifications at the 6-position resulted in increased antimicrobial potency. The optimized compounds inhibited the growth of E. faecalis, M. catarrhalis, H. influenzae, S. pneumoniae, S. aureus, E. coli tolC, mutants and E. coli modified with PMBN with MIC values of 4, ≤ 0.12, 1, 2, 4, 1, 1 μg/ml, respectively. IC50 values in biochemical assay were reduced to mid-nanomolar range.

Conclusion
4H-pyridopyrimidine analogs demonstrate broad-spectrum inhibition of bacterial growth and modification of the compounds establishes SAR.
Evidence for lysosomal exocytosis and release of aggrecan-degrading hydrolases from hypertrophic chondrocytes, in vitro and in vivo
Authors: Bastow Edward R. , Last Karena , Golub Sue , Stow Jennifer L. , Stanley Amanda C. , Fosang Amanda J. 
Published: February 2012

Summary
The abundant proteoglycan, aggrecan, is resorbed from growth plate cartilage during endochondral bone ossification, yet mice with genetically-ablated aggrecan-degrading activity have no defects in bone formation. To account for this apparent anomaly, we propose that lysosomal hydrolases degrade extracellular, hyaluronan-bound aggrecan aggregates in growth plate cartilage, and that lysosomal hydrolases are released from hypertrophic chondrocytes into growth plate cartilage via Ca2+-dependent lysosomal exocytosis. In this study we confirm that hypertrophic chondrocytes release hydrolases via lysosomal exocytosis in vitro and we show in vivo evidence for lysosomal exocytosis in hypertrophic chondrocytes during skeletal development. We show that lysosome-associated membrane protein 1 (LAMP1) is detected at the cell surface following in vitro treatment of epiphyseal chondrocytes with the calcium ionophore, ionomycin. Furthermore, we show that in addition to the lysosomal exocytosis markers, cathepsin D and β-hexosaminidase, ionomycin induces release of aggrecan- and hyaluronan-degrading activity from cultured epiphyseal chondrocytes. We identify VAMP-8 and VAMP7 as v-SNARE proteins with potential roles in lysosomal exocytosis in hypertrophic chondrocytes, based on their colocalisation with LAMP1 at the cell surface in secondary ossification centers in mouse tibiae. We propose that resorbing growth plate cartilage involves release of destructive hydrolases from hypertrophic chondrocytes, via lysosomal exocytosis.
Inappropriate Requesting of Glycated Hemoglobin (Hb A1c) Is Widespread: Assessment of Prevalence, Impact of National Guidance, and Practice-to-Practice Variability
Authors: Driskell Owen J , Holland David , Hanna Fahmy W , Jones Peter W , Pemberton R John , Tran Martin , Fryer Anthony A 
Published: February 2012

Abstract

BACKGROUND
Estimates suggest that approximately 25% of requests for pathology tests are unnecessary. Even in diabetes, for which international guidance provides recommended testing frequency, considerable variability in requesting practice exists. Using the diabetes marker, Hb A1c, we examined (a) the prevalence of under- and overrequesting, (b) the impact of international guidance on prevalence, and (c) practice-to-practice variability.

METHODS
We examined Hb A1c requests (519 664 requests from 115 730 patients, January 2001 to March 2011) processed by the Clinical Biochemistry Department, University Hospital of North Staffordshire, and prevalence of requesting outside guidance from intervals between requests was calculated. Requests were classified as “appropriate,” “too soon,” or “too late.” We also assessed the effect of demographic factors and publication of guidance, along with between-practice variability, on prevalence.

RESULTS
Only 49% of requests conformed to guidance; 21% were too soon and 30% were too late. Underrequesting was more common in primary care, in female patients, in younger patients, and in patients with generally poorer control (all P &lt; 0.001); the reverse generally was true for overrequesting. Publication of guidance (e.g., American Diabetes Association, UK National Institute for Health and Clinical Excellence) had no significant impact on under- or overrequesting rates. Prevalence of inappropriate requests varied approximately 6-fold between general practices.

CONCLUSIONS
Although overrequesting was common, underrequesting was more prevalent, potentially affecting longer-term health outcomes. National guidance appears to be an ineffective approach to changing request behavior, supporting the need for a multisystem approach to reducing variability.
Pichia sorbitophila, an Interspecies Yeast Hybrid, Reveals Early Steps of Genome Resolution After Polyploidization
Authors: Louis Véronique Leh , Despons Laurence , Friedrich Anne , Martin Tiphaine , Durrens Pascal , Casarégola Serge , Neuvéglise Cécile , Fairhead Cécile , Marck Christian , Cruz José A , Straub Marie-Laure , Kugler Valérie , Sacerdot Christine , Uzunov Zlatyo , Thierry Agnes , Weiss Stéphanie , Bleykasten Claudine , De Montigny Jacky , Jacques Noemie , Jung Paul , Lemaire Marc , Mallet Sandrine , Morel Guillaume , Richard Guy-Franck , Sarkar Anasua , Savel Guilhem , Schacherer Joseph , Seret Marie-Line , Talla Emmanuel , Samson Gaelle , Jubin Claire , Poulain Julie , Vacherie Benoît , Barbe Valérie , Pelletier Eric , Sherman David J , Westhof Eric , Weissenbach Jean , Baret Philippe V , Wincker Patrick , Gaillardin Claude , Dujon Bernard , Souciet Jean-Luc 
Published: February 2012

Abstract
Polyploidization is an important process in the evolution of eukaryotic genomes, but ensuing molecular mechanisms remain to be clarified. Autopolyploidization or whole-genome duplication events frequently are resolved in resulting lineages by the loss of single genes from most duplicated pairs, causing transient gene dosage imbalance and accelerating speciation through meiotic infertility. Allopolyploidization or formation of interspecies hybrids raises the problem of genetic incompatibility (Bateson-Dobzhansky-Muller effect) and may be resolved by the accumulation of mutational changes in resulting lineages. In this article, we show that an osmotolerant yeast species, Pichia sorbitophila, recently isolated in a concentrated sorbitol solution in industry, illustrates this last situation. Its genome is a mosaic of homologous and homeologous chromosomes, or parts thereof, that corresponds to a recently formed hybrid in the process of evolution. The respective parental contributions to this genome were characterized using existing variations in GC content. The genomic changes that occurred during the short period since hybrid formation were identified (e.g., loss of heterozygosity, unilateral loss of rDNA, reciprocal exchange) and distinguished from those undergone by the two parental genomes after separation from their common ancestor (i.e., NUMT (NUclear sequences of MiTochondrial origin) insertions, gene acquisitions, gene location movements, reciprocal translocation). We found that the physiological characteristics of this new yeast species are determined by specific but unequal contributions of its two parents, one of which could be identified as very closely related to an extant Pichia farinosa strain.