bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters
Authors: Medellín-Garibay S. E. , Cortez-Espinosa N. , Milán-Segovia R. C. , Magaña-Aquino M. , Vargas-Morales J. M. , González-Amaro R. , Portales-Pérez D. P. , Romano-Moreno S. 
Published: October 2015

ABSTRACT

Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8
+
T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-α) and low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-α serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present.
Susceptibility Pattern of Microorganisms Isolated by Percutaneous Needle Biopsy in Nonbacteremic Pyogenic Vertebral Osteomyelitis
Authors: Desoutter Sophie , Cottier Jean-Philippe , Ghout Idir , Issartel Bertrand , Dinh Aurélien , Martin Arnaud , Carlier Robert , Bernard Louis ,   the Duration of Treatment for Spondylodiscitis Study Group
Published: October 2015

ABSTRACT

Pyogenic vertebral osteomyelitis (VO) is diagnosed according to several lines of evidence: clinical, biological, radiological, and histological. Definitive diagnosis requires the isolation of a causative pathogen or histological confirmation. The aim of our study was to describe the microorganisms isolated by percutaneous needle biopsy (PNB) and to analyze their susceptibility patterns, in order to assess the possibility of empirical combination therapy for the treatment of nonbacteremic patients without resorting to PNB. Based on a French prospective multicenter study of 351 patients with VO, we compiled clinical, biological, and radiological findings for 101 patients with microbiologically confirmed VO. Based on antibiotic susceptibility testing of PNB isolated pathogens, the suitabilities of four antibiotic combinations were analyzed: ofloxacin plus rifampin, levofloxacin plus rifampin, ciprofloxacin plus clindamycin, and ciprofloxacin plus amoxicillin-clavulanate. The main causative pathogens identified were coagulase-negative
Staphylococcus
spp. (26% of isolates), followed by
Staphylococcus aureus
(21%),
Streptoccocus
spp. (13%), and enterobacteria (21%). Empirical antibiotic combination therapy was effective in nearly 75% of cases, and the different combinations gave similar results, except for ofloxacin-rifampin, which was effective in only 58% of cases. A “perfect” empirical antibiotic therapy does not exist. If PNB is not possible, a combination of a fluoroquinolone with clindamycin or rifampin can be used, but the high risk of microbiological failure does not allow the exclusion of PNB. (This study has been registered with EudraCT, number 2006-000951-18, and ClinicalTrials.gov, number NCT00764114.)
Increased Hydrolysis of Oximino-β-Lactams by CMY-107, a Tyr199Cys Mutant Form of CMY-2 Produced by Escherichia coli
Authors: Kotsakis S. D. , Miriagou V. , Vetouli E. E. , Bozavoutoglou E. , Lebessi E. , Tzelepi E. , Tzouvelekis L. S. 
Published: October 2015

ABSTRACT

The cephalosporinase CMY-107, a Tyr199Cys mutant form of CMY-2 encoded by an IncI self-transferable plasmid carried by an
Escherichia coli
clinical strain, was characterized. The enzyme hydrolyzed oximino-cephalosporins and aztreonam more efficiently than CMY-2 did.
In Vitro
Activity of Isavuconazole and Comparators against Clinical Isolates of the
Mucorales
Order
Authors: Arendrup Maiken Cavling , Jensen Rasmus Hare , Meletiadis Joseph 
Published: October 2015

ABSTRACT

The
in vitro
activity of isavuconazole against
Mucorales
isolates measured by EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison with those of amphotericin B, posaconazole, and voriconazole. Seventy-two isolates were included: 12 of
Lichtheimia corymbifera
, 5 of
Lichtheimia ramosa
, 5 of group I and 9 of group II of
Mucor circinelloides
, 9 of
Rhizomucor pusillus
, 26 of
Rhizopus microsporus
, and 6 of
Rhizopus oryzae
. Species identification was confirmed by internal transcribed spacer (ITS) sequencing. EUCAST MICs were read on day 1 (EUCAST-d1) and day 2 (EUCAST-d2), and CLSI MICs were read on day 2 (CLSI-d2). Isavuconazole MIC
50
s (range) (mg/liter) by EUCAST-d1, CLSI-d2, and EUCAST-d2 were 1 (0.125 to 16), 1 (0.125 to 2), and 4 (0.5 to >16), respectively, across all isolates. The similar values for comparator drugs were as follows: posaconazole, 0.25 (≤0.03 to >16), 0.25 (0.06 to >16), and 1 (0.06 to >16); amphotericin, 0.06 (≤0.03 to 0.5), 0.06 (≤0.03 to 0.25), and 0.125 (≤0.03 to 1); voriconazole, 16 (2 to >16), 8 (1 to >16), and >16 (8 to >16), respectively. Isavuconazole activity varied by species:
Lichtheimia corymbifera
, 1 (0.5 to 2), 1 (1 to 2), and 2 (1 to 4);
Lichtheimia ramosa
, 0.25 (0.125 to 0.5), 1 (0.5 to 2), and 2 (0.5 to 4);
Rhizomucor pusillus
, 0.5 (0.5 to 1), 1 (0.125 to 1), and 2 (1 to 2);
Rhizopus microsporus
, 1 (0.5 to 4), 0.5 (0.125 to 1), and 4 (1 to 8); and
Rhizopus oryzae
, 1 (0.5 to 4), 1 (0.125 to 2), and 4 (0.5 to 8), respectively, were more susceptible than
Mucor circinelloides
: group I, 8 (4 to 8), 4 (2 to 4), and 16 (2 to 16), respectively, and group II, 8 (1 to 16), 8 (1 to 8), and 16 (4 to >16), respectively. This was also observed for posaconazole. The essential agreement was best between EUCAST-d1 and CLSI-d2 (75% to 83%). Isavuconazole displayed
in vitro
activity against
Mucorales
isolates with the exception of
Mucor circinelloides
. The MICs were in general 1 to 3 steps higher than those for posaconazole. However, in the clinical setting this may be compensated for by the higher exposure at standard dosing.
Pathophysiological Changes Induced by Pseudomonas aeruginosa Infection Are Involved in MMP-12 and MMP-13 Upregulation in Human Carcinoma Epithelial Cells and a Pneumonia Mouse Model
Authors: Park Ji-Won , Shin In-Sik , Ha Un-Hwan , Oh Sei-Ryang , Kim Jae-Hong , Ahn Kyung-Seop 
Published: October 2015

ABSTRACT

Pseudomonas aeruginosa
infections persist in patients with cystic fibrosis (CF) and drive lung disease progression.
P. aeruginosa
potently activates the innate immune system mostly through the recognition of pathogen-associated molecular patterns, such as flagellin. Matrix metalloproteinases 12 and 13 (MMP-12 and MMP-13, respectively) exacerbate chronic lung infection and inflammation by promoting uncontrolled tissue rearrangements and fibrosis, yet the underlying molecular mechanisms by which this occurs remain largely unknown. In this study, we used quantitative bacteriology, histological examination, and proinflammatory cytokine levels to evaluate the effects of MMP-12 and MMP-13 on
P. aeruginosa
strain K-induced infection and pneumonia in H292 epithelial cells and mice, respectively. Under inflammatory stimulation, mRNA and protein expression levels of proinflammatory mediators were higher in strain K-infected mice and cells than in uninfected counterparts, in which MMP-12 and MMP-13 expression reached levels similar to those observed in epithelial cells. Moreover, we also found that the NF-κB pathway might be involved in the induction of cytokines in response to strain K infection. Taken together, these data suggest that MMP-12 and MMP-13 alter strain K infection in mice and play a role in inflammatory regulation by modulating cytokine levels.
Pancreatic Amylase Is an Environmental Signal for Regulation of Biofilm Formation and Host Interaction in Campylobacter jejuni
Authors: Jowiya Waheed , Brunner Katja , Abouelhadid Sherif , Hussain Haitham A. , Nair Sean P. , Sadiq Sohaib , Williams Lisa K. , Trantham Emma K. , Stephenson Holly , Wren Brendan W. , Bajaj-Elliott Mona , Cogan Tristan A. , Laws Andrew P. , Wade Jim , Dorrell Nick , Allan Elaine 
Published: October 2015

ABSTRACT

Campylobacter jejuni
is a commensal bacterium in the intestines of animals and birds and a major cause of food-borne gastroenteritis in humans worldwide. Here we show that exposure to pancreatic amylase leads to secretion of an α-dextran by
C. jejuni
and that a secreted protease, Cj0511, is required. Exposure of
C. jejuni
to pancreatic amylase promotes biofilm formation
in vitro
, increases interaction with human epithelial cell lines, increases virulence in the
Galleria mellonella
infection model, and promotes colonization of the chicken ileum. We also show that exposure to pancreatic amylase protects
C. jejuni
from stress conditions
in vitro
, suggesting that the induced α-dextran may be important during transmission between hosts. This is the first evidence that pancreatic amylase functions as an interkingdom signal in an enteric microorganism.
A λ Cro-Like Repressor Is Essential for the Induction of Conjugative Transfer of SXT/R391 Elements in Response to DNA Damage
Authors: Poulin-Laprade Dominic , Burrus Vincent 
Published: October 2015

ABSTRACT

Integrative and conjugative elements (ICEs) of the SXT/R391 family are the main contributors to acquired multidrug resistance in the seventh pandemic lineage of
Vibrio cholerae
, the etiological agent of the diarrheal disease cholera. Conjugative transfer of SXT/R391 ICEs is triggered by antibiotics and agents promoting DNA damage through RecA-dependent autoproteolysis of SetR, an ICE-encoded λ CI-like repressor. Here, we describe the role of CroS, a distant λ Cro homolog, as a key component contributing to the regulation of expression of the activator SetCD that orchestrates the expression of the conjugative transfer genes. We show that deletion of
croS
abolishes the SOS response-dependent induction of SXT despite the presence of a functional
setR
gene. Using quantitative reverse transcription-PCR and
lacZ
reporter assays, we also show that CroS represses
setR
and
setCD
expression by binding to operator sites shared with SetR. Furthermore, we provide evidence of an additional operator site bound by SetR and CroS. Finally, we show that SetCD expression generates a positive feedback loop due to SXT excision and replication in a fraction of the cell population. Together, these results refine our understanding of the genetic regulation governing the propagation of major vectors of multidrug resistance.

IMPORTANCE
Healthcare systems worldwide are challenged by an alarming drug resistance crisis caused by the massive and rapid propagation of antibiotic resistance genes and the associated emergence of multidrug-resistant pathogenic bacteria. SXT/R391 ICEs contribute to this phenomenon not only in clinical and environmental vibrios but also in several members of the family
Enterobacteriaceae
. We have identified and characterized here the regulator CroS as a key factor in the stimulation of conjugative transfer of these ICEs in response to DNA-damaging agents. We have also untangled conflicting evidence regarding autoactivation of transfer by the master activator of SXT/R391 ICEs, SetCD. Discovery of CroS provides a clearer and more complete understanding of the regulatory network that governs the dissemination of SXT/R391 ICEs in bacterial populations.
Effect of Electroacupuncture Pretreatment at Gb20 on Behaviour and the Descending Pain Modulatory System in a Rat Model of Migraine
Authors: Pei Pei , Liu Lu , Zhao Luopeng , Cui Yingxue , Qu Zhengyang , Wang Linpeng 
Published: October 2015

Background While electroacupuncture (EA) pretreatment has been found to ameliorate migraine-like symptoms, the underlying mechanisms remain poorly understood. Emerging evidence suggests that the brainstem descending pain modulatory system, comprising the periaqueductal grey (PAG), raphe magnus nucleus (RMg), and trigeminal nucleus caudalis (TNC), may be involved in migraine pathophysiology. We hypothesised that EA would ameliorate migraine-like symptoms via modulation of this descending system. Methods We used a conscious rat model of migraine induced by repeated electrical stimulation of the dura. Forty male Sprague-Dawley rats were randomly assigned to one of four groups: an EA group, which received EA at GB20 following dural stimulation; a sham acupuncture (SA) group, which received manual acupuncture at a non-acupuncture point following dural stimulation; a Model group, which received dural stimulation but no acupuncture; and a Control group, which received neither dural stimulation nor acupuncture (electrode implantation only). HomeCageScan was used to measure effects on behaviour, and immunofluorescence staining was used to examine neural activation (c-Fos immunoreactivity) in the PAG, RMg, and TNC. Results Compared to the Model group, rats in the EA group showed a significant increase in exploratory, locomotor and eating/drinking behaviour (p<0.01) and a significant decrease in freezing-like resting and grooming behaviour (p<0.05). There was a significant increase in the mean number of c-Fos neurons in the PAG, RMg, and TNC in Model versus Control groups (p<0.001); however, this was significantly attenuated by EA treatment (p<0.001). There were no significant differences between the SA and Model groups in behaviour or c-Fos immunoreactivity. Conclusions EA pretreatment ameliorates behavioural changes in a rat model of recurrent migraine, possibly via modulation of the brainstem descending pathways.
Prognostic impact of neutrophil gelatinase-associated lipocalin and B-type natriuretic in patients with ST-elevation myocardial infarction treated by primary PCI: a prospective observational cohort study
Authors: Helanova Katerina , Littnerova Simona , Kubena Petr , Ganovska Eva , Pavlusova Marie , Kubkova Lenka , Jarkovsky Jiri , Pavkova Goldbergova Monika , Lipkova Jolana , Gottwaldova Jana , Kala Petr , Toman Ondrej , Dastych Milan , Spinar Jindrich , Parenica Jiri 
Published: October 2015

ObjectivesNeutrophil gelatinase-associated lipocalin (NGAL) from a pathophysiological perspective connects various pathways that affect the prognosis after myocardial infarction. The objective was to evaluate the benefits of measuring NGAL for prognostic stratification in addition to the Thrombolysis in Myocardial Infarction (TIMI) score, and to compare it with the prognostic value of B-type natriuretic peptide (BNP).DesignProspective observational cohort study.SettingOne university/tertiary centre.ParticipantsA total of 673 patients with ST segment elevation myocardial infarction were treated by primary percutaneous coronary intervention. NGAL and BNP were assessed on hospital admission.OutcomesPrimary outcome: 1-year mortality.Secondary outcomes: 1-year hospitalisation due to acute heart failure, unplanned revascularisation, reinfarction, stroke and combined end point of 1-year mortality and hospitalisation due to heart failure.Statistical methodsUsing the c-statistic, the ability of NGAL, BNP and TIMI score to predict 1-year mortality alone and in combination with readmission for heart failure was evaluated. The addition of the predictive value of biomarkers to the score was assessed by category free net reclassification improvement (cfNRI) and the integrated discrimination index (IDI).ResultsThe NGAL level was significantly higher in non-survivors (67 vs 115 pg/mL; p<0.001). The area under the curve (AUC) values for mortality prediction for NGAL, BNP and TIMI score were 75.5, 78.7 and 74.4, respectively (all p<0.001) with optimal cut-off values of 84 pg/mL for NGAL and 150 pg/mL for BNP. The addition of NGAL and BNP to the TIMI score significantly improved risk stratification according to cfNRI and IDI. A BNP and the combination of the TIMI score with NGAL predicted the occurrence of the combined end point with an AUC of 80.6 or 82.2, respectively. NGAL alone is a simple tool to identify very high-risk patients. NGAL >110 pg/mL was associated with a 1-year mortality of 20%.ConclusionsThe measurement of NGAL together with the TIMI score results in a strong prognostic model for the 1-year mortality rate in patients with STEMI.
Micronutrient deficiencies and developmental delays among infants: evidence from a cross-sectional survey in rural China
Authors: Luo Renfu , Shi Yaojiang , Zhou Huan , Yue Ai , Zhang Linxiu , Sylvia Sean , Medina Alexis , Rozelle Scott 
Published: October 2015

ObjectivesResearch increasingly indicates the importance of the nutritional programming that occurs in the first 2–3 years of life. Quality nutrition during this brief window has been shown to have large and significant effects on health and development throughout childhood and even into adulthood. Despite the widespread understanding of this critical window, and the long-term consequences of leaving nutritional deficiencies unaddressed, little is known about the status of infant nutrition in rural China, or about the relationship between infant nutrition and cognitive development in rural China.Design, setting and participantsIn April 2013 and October 2013, we conducted a survey of 1808 infants aged 6–12 months living in 351 villages across 174 townships in nationally designated poverty counties in rural areas of southern Shaanxi Province, China.Main outcome measuresInfants were administered a finger prick blood test for haemoglobin and assessed according to the Bayley Scales of Infant Development. They were also measured for length and weight. Caregivers were administered a survey of demographic characteristics and feeding practices.ResultsWe found that 48.8% of sample infants were anaemic, 3.7% were stunted, 1.2% were underweight and 1.6% were wasted. Approximately 20.0% of the sample infants were significantly delayed in their cognitive development, while just over 32.3% of the sample infants were significantly delayed in their psychomotor development. After controlling for potential confounders, infants with lower haemoglobin counts were significantly more likely to be delayed in both their cognitive (p<0.01) and psychomotor development (p<0.01).ConclusionsThe anaemia rates that we identify in this study classify anaemia as a ‘severe’ public health problem according to the WHO. In contrast, there is virtually no linear growth failure among this population. We find that low haemoglobin levels among our sample population are associated with significant cognitive and psychomotor delays that could eventually affect children's schooling performance and labour force outcomes.Trial registration numberISRCTN44149146.
Self-reported sleep in late pregnancy in relation to birth size and fetal distress: the E Moe, Māmā prospective cohort study
Authors: Howe Laura D , Signal T Leigh , Paine Sarah-Jane , Sweeney Bronwyn , Priston Monique , Muller Diane , Lee Kathy , Huthwaite Mark , Gander Philippa 
Published: October 2015

ObjectivesTo explore associations between features of sleep during pregnancy and adverse outcomes for the infant.SettingE Moe, Māmā is a cohort study in Aotearoa/New Zealand that investigates self-reported sleep and maternal health in late pregnancy and the postpartum period.ParticipantsWomen (N=633; 194 Māori) reported detailed information on their sleep duration, quality, disturbances, disorders (snoring, breathing pauses, twitching legs, restless legs) and daytime sleepiness between 35 and 37 weeks gestation.Outcome measuresBirthweight and fetal distress during labour were extracted from medical records. Associations between each sleep variable and small or large for gestational age (SGA/LGA) using customised birthweight centile or fetal distress were estimated using multinomial/logistic regression, controlling for potential confounders. Secondary analyses considered differences in associations between Māori and non-Māori women.ResultsThere was some indication that breathing pauses (a measure of sleep apnoea) were associated with both SGA (OR 2.8, 95% CI 0.9 to 9.0, p=0.08) and LGA (OR 2.0, 95% CI 0.7 to 5.7, p=0.20), with the association for LGA being stronger when only pregnancy-onset breathing pauses were considered (OR 3.5, 95% CI 1.3 to 9.6, p=0.01). There was also some evidence that pregnancy-onset leg twitching (OR 3.3, 95% CI 1.1 to 10.0, p=0.03) and frequent sleep disturbance due to feeling too hot or too cold (OR 1.7, 95% CI 0.9 to 3.6, p=0.13) were associated with higher risk of fetal distress. Other sleep measures, including snoring, were not associated with SGA, LGA or fetal distress. Many of the associations we observed were considerably stronger in Māori compared with non-Māori women.ConclusionsWe did not find evidence of previously reported associations between snoring and SGA. Our findings tentatively suggest that self-reported breathing pauses and leg twitching in late pregnancy are associated with infant outcomes, and highlight ethnic inequalities.
Increased planned delivery contributes to declining rates of pregnancy hypertension in Australia: a population-based record linkage study
Authors: Roberts Christine L , Algert Charles S , Morris Jonathan M , Ford Jane B 
Published: October 2015

ObjectiveSince the 1990s, pregnancy hypertension rates have declined in some countries, but not all. Increasing rates of early planned delivery (before the due date) have been hypothesised as the reason for the decline. The aim of this study was to explore whether early planned delivery can partly explain the declining pregnancy hypertension rates in Australia.DesignPopulation-based record linkage study utilising linked birth and hospital records.Setting and participantsA cohort of 1 076 122 deliveries in New South Wales, Australia, 2001–2012.Outcome measuresPregnancy hypertension (including gestational hypertension, pre-eclampsia and eclampsia) was the main outcome; pre-eclampsia was a secondary outcome.ResultsFrom 2001 to 2012, pregnancy hypertension rates declined by 22%, from 9.9% to 7.7%, and pre-eclampsia by 27%, from 3.3% to 2.4% (trend p<0.0001). At the same time, planned deliveries increased: prelabour caesarean section by 43% (12.9–18.4%) and labour inductions by 10% (24.8–27.2%). Many maternal risk factors for pregnancy hypertension significantly increased (p<0.01) over the study period including nulliparity, age ≥35 years, diabetes, overweight and obesity, and use of assisted reproductive technologies; some risk factors decreased including multifetal pregnancies, age <20 years, autoimmune diseases and previous pregnancy hypertension. Given these changes in risk factors, the pregnancy hypertension rate was predicted to increase to 10.5%. Examination of annual gestational age distributions showed that pregnancy hypertension rates actually declined from 38 weeks gestation and were steepest from 41 weeks; at least 36% of the decrease could be attributed to planned deliveries. The risk factors for pregnancy hypertension were also risk factors for planned delivery.ConclusionsIt appears that an unanticipated consequence of increasing early planned deliveries is a decline in the incidence of pregnancy hypertension. Women with risk factors for hypertension were relatively more likely to be selected for early delivery.