bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefits of Adding a Rapid PCR-Based Blood Culture Identification Panel to an Established Antimicrobial Stewardship Program
Authors: MacVane Shawn H. , Nolte Frederick S. 
Published: August 2016

ABSTRACT

Studies have demonstrated that the combination of antimicrobial stewardship programs (ASP) and rapid organism identification improves outcomes in bloodstream infections (BSI) but have not controlled for the incremental contribution of the individual components. Hospitalized adult patients with blood culture pathogens on a rapid, multiplex PCR-based blood culture identification panel (BCID) that included 19 bacterial species, 5
Candida
spp., and 4 antimicrobial resistance genes were studied over sequential time periods in a pre-post quasiexperimental study in 3 groups in the following categories: conventional organism identification (controls), conventional organism identification with ASP (AS), and BCID with ASP (BCID). Clinical and economic outcomes were compared between groups. There were 783 patients with positive blood cultures; of those patients, 364 (115 control, 104 AS, and 145 BCID) met inclusion criteria. The time from blood culture collection to organism identification was shorter in the BCID group (17 h;
P
< 0.001) than in the control group (57 h) or the AS group (54 h). The BCID group had a shorter time to effective therapy (5 h;
P
< 0.001) than the control group (15 h) or AS group (13 h). The AS (57%) and BCID (52%) groups had higher rates of antimicrobial de-escalation than the control group (34%), with de-escalation occurring sooner in the BCID group (48 h;
P
= 0.034) than in the AS group (61 h) or the control group (63 h). No difference between the control group, AS group, and BCID group was seen with respect to mortality, 30-day readmission, intensive care unit length of stay (LOS), postculture LOS, or costs. In patients with BSI, ASP alone improved antimicrobial utilization. Addition of BCID to an established ASP shortened the time to effective therapy and further improved antimicrobial use compared to ASP alone, even in a setting of low antimicrobial resistance rates.
Molecular Microbiological Profile of Chronic Suppurative Otitis Media
Authors: Neeff Michel , Biswas Kristi , Hoggard Michael , Taylor Michael W. , Douglas Richard 
Published: August 2016

ABSTRACT

Chronic suppurative otitis media (CSOM) presents with purulent otorrhea (ear discharge), is characterized by chronic inflammation of the middle ear and mastoid cavity, and contributes to a significant disease burden worldwide. Current antibiotic therapy is guided by swab culture results. In the absence of detailed molecular microbiology studies of CSOM patients, our current understanding of the microbiota of CSOM (and indeed of the healthy ear) remains incomplete. In this prospective study, 24 patients with CSOM were recruited, along with 22 healthy controls. Culture-based techniques and 16S rRNA gene amplicon sequencing were used to profile the bacterial community for each patient. Comparisons between patients with and without cholesteatoma in the middle ear and mastoid cavity were also made. A major finding was that the middle ear of many healthy controls was not sterile, which is contradictory to the results of previous studies. However, sequencing data showed that
Staphylococcus aureus
, along with a range of other Gram-positive and Gram-negative organisms, were present in all subgroups of CSOM and healthy controls. Large interpatient variability in the microbiota was observed within each subgroup of CSOM and controls, and there was no bacterial community “signature” which was characteristic of either health or disease. Comparisons of the culture results with the molecular data show that culture-based techniques underestimate the diversity of bacteria found within the ear. This study reports the first detailed examination of bacterial profiles of the ear in healthy controls and patients with CSOM.
Protective Effects of Glutamine Antagonist 6-Diazo-5-Oxo-l-Norleucine in Mice with Alphavirus Encephalomyelitis
Authors: Manivannan Sivabalan , Baxter Victoria K. , Schultz Kimberly L. W. , Slusher Barbara S. , Griffin Diane E. 
Published: August 2016

ABSTRACTInflammation is a necessary part of the response to infection but can also cause neuronal injury in both infectious and autoimmune diseases of the central nervous system (CNS). A neurovirulent strain of Sindbis virus (NSV) causes fatal paralysis in adult C57BL/6 mice during clearance of infectious virus from the CNS, and the virus-specific immune response is implicated as a mediator of neuronal damage. Previous studies have shown that survival is improved in T-cell-deficient mice and in mice with pharmacological inhibition of the inflammatory response and glutamate excitotoxicity. Because glutamine metabolism is important in the CNS for the generation of glutamate and in the immune system for lymphocyte proliferation, we tested the effect of the glutamine antagonist DON (6-diazo-5-oxo-l-norleucine) on the outcome of NSV infection in mice. DON treatment for 7 days from the time of infection delayed the onset of paralysis and death. Protection was associated with reduced lymphocyte proliferation in the draining cervical lymph nodes, decreased leukocyte infiltration into the CNS, lower levels of inflammatory cytokines, and delayed viral clearance.In vitrostudies showed that DON inhibited stimulus-induced proliferation of lymphocytes. Whenin vivotreatment with DON was stopped, paralytic disease developed along with the inflammatory response and viral clearance. These studies show that fatal NSV-induced encephalomyelitis is immune mediated and that antagonists of glutamine metabolism can modulate the immune response and protect against virus-induced neuroinflammatory disease.IMPORTANCEEncephalomyelitis due to infection with mosquito-borne alphaviruses is an important cause of death and of long-term neurological disability in those who survive infection. This study demonstrates the role of the virus-induced immune response in the generation of neurological disease. DON, a glutamine antagonist, inhibited the proliferation of lymphocytes in response to infection, prevented the development of brain inflammation, and protected mice from paralysis and death during treatment. However, because DON inhibited the immune response to infection, clearance of the virus from the brain was also prevented. When treatment was stopped, the immune response was generated, brain inflammation occurred, virus was cleared, and mice developed paralysis and died. Therefore, more definitive treatment for alphaviral encephalomyelitis should inhibit virus replication as well as neuroinflammatory damage.
Cross-sectional study exploring barriers to adverse drug reactions reporting in community pharmacy settings in Dhaka, Bangladesh
Authors: Amin Mohammad Nurul , Khan Tahir Mehmood , Dewan Syed Masudur Rahman , Islam Mohammad Safiqul , Moghal Mizanur Rahman , Ming Long Chiau 
Published: August 2016

ObjectivesTo assess community pharmacists'/pharmacy technicians' knowledge and perceptions about adverse drug reactions (ADRs) and barriers towards the reporting of such reactions in Dhaka, Bangladesh.MethodA cross-sectional study was planned to approach potential respondents for the study. A self-administered questionnaire was delivered to community pharmacists/pharmacy technicians (N=292) practising in Dhaka, Bangladesh.ResultsThe overall response to the survey was 69.5% (n=203). The majority of the sample was comprised of pharmacy technicians (152, 74.9%) who possessed a diploma in pharmacy, followed by pharmacists (37, 18.2%) and others (12, 5.9%). Overall, 72 (35.5%) of the respondents disclosed that they had experienced an ADR at their pharmacy, yet more than half (105, 51.7%) were not familiar with the existence of an ADR reporting body in Bangladesh. Exploring the barriers to the reporting of ADRs, it was revealed that the top four barriers to ADR reporting were ‘I do not know how to report (Relative Importance Index (RII)=0.998)’, ‘reporting forms are not available (0.996)’, ‘I am not motivated to report (0.997)’ and ‘Unavailability of professional environment to discuss about ADR (RII=0.939)’. In addition to these, a majority (141, 69.46%) were not confident about the classification of ADRs (RII=0.889) and were afraid of legal liabilities associated with reporting ADRs (RII=0.806). Moreover, a lack of knowledge about pharmacotherapy and the detection of ADRs was another major factor hindering their reporting (RII=0.731).ConclusionsThe Directorate of Drug Administration in Bangladesh needs to consider the results of this study to help it improve and simplify ADR reporting in Bangladeshi community pharmacy settings.
Effectiveness of one-to-one volunteer support for patients with psychosis: protocol of a randomised controlled trial
Authors: Priebe Stefan , Pavlickova Hana , Eldridge Sandra , Golden Eoin , McCrone Paul , Ockenden Nick , Pistrang Nancy , King Michael 
Published: August 2016

IntroductionSocial isolation is common in patients with psychosis and associated with a number of negative outcomes. Programmes in which volunteers provide one-to-one support—often referred to as befriending—have been reputed to achieve favourable outcomes. However, trial-based evidence for their effectiveness is limited.Methods and analysisThis is a randomised controlled trial comparing the effects of one-to-one volunteer support with an active control condition for patients with psychosis over a 1-year period. Patients in the intervention group will receive the support of a volunteer for 1 year, who will meet them weekly and engage them in social and recreational activities. Patients in the control group will not receive support from a volunteer. In both groups, patients will be given a booklet detailing locally available social activities and otherwise receive treatment as usual. Patients, volunteers, clinicians and researchers involved in the delivery of the intervention will not be blinded to group assignment, while researchers carrying out data collection will be blinded. Data collection will be conducted at baseline, at 6 and 12 months. The primary outcome is the amount of time spent engaging in social activities per day. Secondary outcomes include symptoms, quality of life, self-esteem and costs of care. Attitudes of volunteers towards mentally ill people will be assessed. Finally, in-depth interviews will be conducted with patients and volunteers.Ethics and disseminationThe study has been approved by the National Research Ethics Service (NRES) Committee London—Camden & Kings Cross (reference 15/LO/0674). The findings of the trial will be published in open access peer-reviewed journals and in the National Institute for Health Research (NIHR) journals library, and presented at scientific conferences. In addition, findings will be summarised for a lay audience and circulated to all relevant National Health Service (NHS) and voluntary organisations.Trial registration numberISRCTN14021839; Pre-results.
On the
Carboniferous Limestone South
of the
Craven Fault (Grassington-Hellifield District)
Authors: Wilmore Albert 
Published: August 2016

I. I
ntroduction
.

South of the great Craven Fault is a district which may well be termed the Craven Lowlands. It lies between the limestone sears of Settle, Malham, and Grassington on the north and the grit hills of the Pendle Range on the south. The district thus defined may be held to include all that part of Craven which extends from Clitheroe to Skyreholme, and from the so-called 'middle branch' of the great fault-system, to the grit hills of Simon's Seat, Burnsall Fell, Flasby Fell, Carleton Moor, and westwards to Pendle.
The Carboniferous Limestone and Pendleside Beds, which occupy almost the whole of the district under consideration, are everywhere very much folded and faulted.
The greater part of the region is much obscured by drift. With the exception of a good section at Troller's Gill (which does not, however, show any considerable thickness of beds) there are no long continuous sections, and the geologist must remain perforce content with the numerous isolated exposures which are scattered over the whole district. Owing to the contiuually changing dips, it is not easy to make out the sequence of the beds.
This paper will be confined to a description of the Carboniferous Limestone, as it may be seen in the various exposures between Swinden Moor on the west and Skyreholme on the east. I have previously discussed other parts of the Craven Lowlands.
The lithologieal character of the limestone varies considerably in different parts of the district, the most widely different types being the greyish-white, irregularly-bedded shelly limestone of Elbolton
Splenic Marginal Zone Granulocytes Acquire an Accentuated Neutrophil B-Cell Helper Phenotype in Chronic Lymphocytic Leukemia
Authors: Gätjen Marcel , Brand Franziska , Grau Michael , Gerlach Kerstin , Kettritz Ralph , Westermann Jörg , Anagnostopoulos Ioannis , Lenz Peter , Lenz Georg , Höpken Uta E. , Rehm Armin 
Published: August 2016

Abstract
Recruitment of tumor-associated macrophages and neutrophils (TAM and TAN) to solid tumors contributes to immunosuppression in the tumor microenvironment; however, their contributions to lymphoid neoplasms are less clear. In human chronic lymphocytic leukemia (CLL), tumor B cells lodge in lymph nodes where interactions with the microenvironment occur. Tumor cell homing stimulates proliferation, such that engagement of the B-cell receptor is important for malignant progression. In the Eμ-Tcl1 murine model of CLL, we identified gene expression signatures indicative of a skewed polarization in the phenotype of monocytes and neutrophils. Selective ablation of either of these cell populations in mice delayed leukemia growth. Despite tumor infiltration of these immune cells, a systemic inflammation was not detected. Notably, in progressive CLL, splenic neutrophils were observed to differentiate toward a B-cell helper phenotype, a process promoted by the induction of leukemia-associated IL10 and TGFβ. Our results suggest that targeting aberrant neutrophil differentiation and restoring myeloid cell homeostasis could limit the formation of survival niches for CLL cells. Cancer Res; 76(18); 5253–65. ©2016 AACR.
Prevention of microalbuminuria using early intervention with renin-angiotensin system inhibitors in patients with type 2 diabetes: A systematic review
Authors: Persson Frederik , Lindhardt Morten , Rossing Peter , Parving Hans-Henrik 
Published: August 2016

Hypothesis/objectives: Early prevention of diabetic nephropathy by way of blocking the renin-angiotensin system (RAS) in patients with normoalbuminuria seems rational, but trials have so far shown conflicting results. The present meta-analysis was undertaken to investigate if such treatment can prevent development of microalbuminuria. Materials and methods: We searched MEDLINE, EMBASE and the Cochrane Library (2 June 2014) for randomised controlled trials, with a population of patients with type 2 diabetes and normoalbuminuria, comparing angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) to placebo. Studies had to have at least 50 participants in each arm and one year of follow-up. Random and fixed effect models were performed as well as trial sequential analysis. Results: Six trials were included in the analysis ( n=16,921). Overall risk of bias was variable. In a fixed model analysis ACE or ARB treatment was superior to placebo in relation to prevention of development of microalbuminuria, risk ratio 0.84 (95% confidence interval (CI) 0.79–0.88) p<0.001, I2=23%, similar to random model results. Treatment also showed a trend towards a reduction in all-cause mortality( p=0.07). Conclusions: We conclude that in patients with type 2 diabetes and normoalbuminuria, early intervention with ACEis or ARBs reduces the risk for development of microalbuminuria.
Effect of gamma-carboxylase inhibition on serum osteocalcin may be partially protective against developing diabetic cardiomyopathy in type 2 diabetic rats
Authors: Gamal Sarah Mahmoud , Sadek Nermeen Bakr , Rashed Laila Ahmed , Shawky Heba Mohamed , Gamal El-Din Maha Mohamed 
Published: August 2016

Aims: To investigate the possible protective effect of elevated undercarboxylated osteocalcin on diabetic cardiomyopathy mechanisms and risk factors. Methods: In all, 32 male rats were divided into four groups: control, diabetic, diabetic warfarin and normal warfarin–treated groups. Isolated heart functions were assessed; fasting serum insulin, glucose and glycosylated haemoglobin, homeostasis model assessment insulin resistance and lipid profile were investigated. Serum undercarboxylated osteocalcin and adiponectin were also measured. In cardiac tissue, malondialdehyde content, acyl-CoA dehydrogenase gene expression, Bax/Bcl2 ratio, sarcoendoplasmic reticulum calcium ATPase and osteocalcin receptor (G protein–coupled receptor family C group 6 member A) genes expression were investigated. Results: Prophylactic elevation of undercarboxylated osteocalcin was accompanied by improved insulin sensitivity and lipid profile, increased serum adiponectin, upregulated myocardial osteocalcin receptor with preserved left ventricular function, decreased cardiac malondialdehyde content, acyl-CoA dehydrogenase and Bax/Bcl2 ratio. Conclusion: Undercarboxylated osteocalcin was suggested to have protective effects against diabetic cardiomyopathy, possibly through direct action on upregulated G protein–coupled receptor family C group 6 member A and indirectly via adiponectin. These effects may be mediated through antagonizing oxidative stress and apoptosis.
The potential of chondrogenic pre-differentiation of adipose-derived mesenchymal stem cells for regeneration in harsh nucleus pulposus microenvironment
Authors: Wang Jingkai , Tao Yiqing , Zhou Xiaopeng , Li Hao , Liang Chengzhen , Li Fangcai , Chen Qi-xin 
Published: August 2016

Recent studies indicated that cell-based therapy could be a promising approach to treat intervertebral disc degeneration. Though the harsh microenvironment in disc is still challenging to implanted cells, it could be overcome by pre-conditioning graft cells before transplantation, suggested by previous literatures. Therefore, we designed this study to identify the potential effect of chondrogenic pre-differentiation on adipose-derived mesenchymal stem cells in intervertebral disc-like microenvironment, characterized by limited nutrition, acidic, and high osmosis in vitro. Adipose-derived mesenchymal stem cells of rat were divided into five groups, embedded in type II collagen scaffold, and cultured in chondrogenic differentiation medium for 0, 3, 7, 10, and 14 days. Then, the adipose-derived mesenchymal stem cells were implanted and cultured in intervertebral disc-like condition. The proliferation and differentiation of adipose-derived mesenchymal stem cells were evaluated by cell counting kit-8 test, real-time quantitative polymerase chain reaction, and Western blotting and immunofluorescence analysis. Analyzed by the first week in intervertebral disc-like condition, the results showed relatively greater proliferative capability and extracellular matrix synthesis ability of the adipose-derived mesenchymal stem cells pre-differentiated for 7 and 10 days than the control. We concluded that pre-differentiation of rat adipose-derived mesenchymal stem cells in chondrogenic culture medium for 7 to 10 days could promote the regeneration effect of adipose-derived mesenchymal stem cells in intervertebral disc-like condition, and the pre-differentiated cells could be a promising cell source for disc regeneration medicine.
Use of Estrogen-Containing Contraception Is Associated With Increased Concentrations of 25-Hydroxy Vitamin D
Authors: Harmon Quaker E. , Umbach David M. , Baird Donna D. 
Published: August 2016

Abstract

Context:
Small studies suggest exogenous estrogen may improve vitamin D status, but the etiology is unclear because women who use hormones may make lifestyle choices that differentially affect vitamin D status.

Objective:
Our objective was to investigate the association between use of hormonal contraception and 25-hydroxy-vitamin D (25(OH)D).

Design:
We used linear regression modeling of cross-sectional data to estimate percent change in season-adjusted serum 25(OH)D with estrogen use after adjustment for other factors.

Setting:
At the enrollment clinic visit (2010–2012) into a cohort study of uterine fibroids, each subject provided a blood sample, had anthropomorphic variables and skin reflectance measured, and answered questionnaires on demographics, dietary and supplement intake, contraceptive use, reproductive and medical history, and behaviors.

Participants:
A total of 1662 African American women, community volunteers, 23–34 years old, living in the Detroit, Michigan, area were included.

Interventions:
None.

Main Outcomes and Measures:
Serum 25(OH)D was measured.

Results:
Serum 25(OH)D concentrations were low (70% &lt;20 ng/ml). Current use of an estrogen-containing contraceptive was associated with a 20% (95% confidence interval: 14–27) increase in 25(OH)D after adjustment. There was no increase in 25(OH)D among participants who had used estrogen in the past, but were not current users, indicating that results were unlikely to be due to unmeasured confounding by factors related to contraceptive choice.

Conclusions:
The increase in 25(OH)D with use of estrogen-containing contraceptives raise mechanistic questions regarding the biological pathways involved, and highlights the need for studies that examine possible endogenous estrogen effects on vitamin D.
Tensin 3 is a new partner of Dock5 that controls osteoclast podosome organization and activity
Authors: Touaitahuata Heiani , Morel Anne , Urbach Serge , Mateos-Langerak Julio , de Rossi Sylvain , Blangy Anne 
Published: August 2016

ABSTRACT
Bone resorption by osteoclasts is mediated by a typical adhesion structure called the sealing zone or actin ring, whose architecture is based on a belt of podosomes. The molecular mechanisms driving podosome organization into superstructures remain poorly understood to date, in particular at the osteoclast podosome belt. We performed proteomic analyses in osteoclasts and found that the adaptor protein tensin 3 is a partner of Dock5, a Rac exchange factor necessary for podosome belt formation and bone resorption. Expression of tensin 3 and Dock5 concomitantly increase during osteoclast differentiation. These proteins associate with the osteoclast podosome belt but not with individual podosomes, in contrast to vinculin. Super-resolution microscopy revealed that, even if they colocalize in the x-y plane of the podosome belt, Dock5 and tensin 3 differentially localize relative to vinculin in the z-axis. Tensin 3 increases Dock5 exchange activity towards Rac, and suppression of tensin 3 in osteoclasts destabilizes podosome organization, leading to delocalization of Dock5 and a severe reduction in osteoclast activity. Our results suggest that Dock5 and tensin 3 cooperate for osteoclast activity, to ensure the correct organization of podosomes.
Crisis in Russian Economy and Its Impact on Business
Authors: Докукина  , Dokukina Anna , Карпухин  , Karpukhin K. 
Published: August 2016

The article considers the factors and features of current crisis in Russian
economy and their analysis on the basis of general economic cycle and crisis
theory, and by the example of Great Depression in USA and case of financial
crisis in 2007–2008 in Russia.