bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complement C3 as a Prompt for Human Macrophage Death during Infection with Francisella tularensis Strain SCHU S4
Authors: Brock Susan R. , Parmely Michael J. 
Published: July 2017

ABSTRACT

Tularemia is caused by the Gram-negative bacterial pathogen
Francisella tularensis
. Infection of macrophages and their subsequent death are believed to play important roles in the progression of disease. Because complement is a particularly effective opsonin for
Francisella
, we asked whether complement-dependent uptake of
F. tularensis
strain SCHU S4 affects the survival of primary human macrophages during infection. Complement component C3 was found to be an essential opsonin in human serum not only for greatly increased uptake of SCHU S4 but also for the induction of macrophage death. Single-cell analysis also revealed that macrophage death did not require a high intracellular bacterial burden. In the presence of C3, macrophage death was observed at 24 h postinfection in a quarter of the macrophages that contained only 1 to 5 bacterial cells. Macrophages infected in the absence of C3 rarely underwent cell death, even when they contained large numbers of bacteria. The need for C3, but not extensive replication of the pathogen, was confirmed by infections with SCHU S4 Δ
purMCD
, a mutant capable of phagosome escape but of only limited cytosolic replication. C3-dependent
Francisella
uptake alone was insufficient to induce macrophage death, as evidenced by the failure of the phagosome escape-deficient mutant SCHU S4 Δ
fevR
to induce cell death despite opsonization with C3. Together, these findings indicate that recognition of C3-opsonized
F. tularensis
, but not extensive cytosolic replication, plays an important role in regulating macrophage viability during intracellular infections with type A
F. tularensis
.
Determining the worldwide epidemiology of surgical site infections after gastrointestinal resection surgery: protocol for a multicentre, international, prospective cohort study (GlobalSurg 2)
Authors: Collaborative GlobalSurg 
Published: July 2017

IntroductionSurgical site infection (SSI) is the most common complication following major gastrointestinal surgery, affecting between 25% and 40% of patients. The rate of SSI doubles from low-income to high-income settings, persisting after risk adjustment. The relative impact of antibiotic-resistant organisms and the effectiveness of antibiotic prophylaxis globally are unknown. This study aims to determine SSI rates following gastrointestinal surgery across worldwide hospital settings.Methods and analysisThis multicentre, international, prospective cohort study will be undertaken by any hospital providing emergency or elective gastroenterological surgical services. Centres will collect observational data on consecutive patients undergoing emergency or elective gastrointestinal resection, cholecystectomy or appendicectomy during a 6-month period. The primary outcome is the incidence of SSI with secondary outcomes describing the organisms causing SSIs, including their antibiotic susceptibility, and the microbiological tests used to identify them.Ethics and disseminationThis project will not affect clinical practice and has been classified as clinical audit following research ethics review. The protocol will be disseminated through the international GlobalSurg network.Trial registration numberNCT02662231.
Behind the smile: qualitative study of caregivers’ anguish and management responses while caring for someone living with heart failure
Authors: Wingham Jennifer , Frost Julia , Britten Nicky 
Published: July 2017

BackgroundCaregivers support self-management in heart failure but often experience stress, anxiety and ill health as a result of providing care.Aims1. To identify the factors that contribute to the experience of anguish.2. To understand how caregivers learn to live with what is frequently a challenging and demanding role.MethodsIndividual interviews with caregivers who had been caring for someone with heart failure for a minimum of 6 months. We used thematic analysis to inductively analyse transcripts.ResultsTwenty-two caregivers, from three centres in the United Kingdom, took part in individual interviews. The caregivers were aged between 39 and 84 years, and six were men. Twenty were in spousal or partner relationships. We found that caregivers often hide the extent of their emotional stress or anguish. We identified four main themes with explanatory subthemes—emotional impact (fear for the future and sense of hopelessness), role definition (changing sense of who I am, reduced resilience, learning care skills, role conflict and changing role), exclusion (exclusion by the cared-for person and by health professionals and feeling alone) and ignoring one’s own health—that were associated with anguish. From these findings, we produced a caregiver needs assessment model in the context of caring for a person with heart failure.Conclusions and implications for practiceCaregivers have many unmet and hidden needs. Primary care health professionals are well placed to meet the needs of caregivers. The model may be used by health and social care professionals to identify needs and to provide caregivers with targeted practical and emotional support; and for researchers developing interventions to enhance self-management in heart failure.
Are there patient-related factors that influence sickness certification in patients with severe subjective health complaints? A cross-sectional exploratory study from different European countries
Authors: Merkus Suzanne L , Hoedeman Rob , Mæland Silje , Weerdesteijn Kristel H N , Schaafsma Frederieke G , Jourdain Maud , Canevet Jean-Paul , Rat Cédric , Anema Johannes R , Werner Erik L 
Published: July 2017

ObjectivesTo develop hypotheses about whether there are patient-related factors that influence physicians’ decision-making that can explain why some patients with severe subjective health complaints (SHCs) are more likely to be granted sick leave than others.DesignExploratory cross-sectional.SettingAssessments of patient-related factors after watching nine authentic video recordings of patients with severe SHC from a Norwegian general practice. Our previous study showed that three of these nine patients were less likely than the remaining six patients to be granted sick leave by physicians from five European countries.ParticipantsIn total, 10 assessors from Norway, the Netherlands and France.OutcomesThe direction in which the assessments may contribute towards the decision to grant a sickness certificate (increasing or decreasing the likelihood of granting sick leave).ResultsPhysicians consider a wide variety of patient-related factors when assessing sickness certification. The overall assessment of these factors may provide an indication of whether a patient is more likely or less likely to be granted sick leave. Additionally, some single questions (notable functional limitations in the consultation, visible suffering, a clear purpose for sick leave and psychiatric comorbidity) may indicate differences between the two patient groups.ConclusionsNext to the overall assessment, no notable effect of the complaints on functioning and suffering, a lack of a clear purpose for sick leave and the absence of psychiatric comorbidity may be factors that could help guide the decision to grant sick leave. These hypotheses should be tested and validated in representative samples of professionals involved in sickness certification. This may help to understand the tacit knowledge we believe physicians have when assessing work capacity of patients with severe SHC.
Oral glucocorticoid use and osteonecrosis in children and adults with chronic inflammatory diseases: a population-based cohort study
Authors: Horton Daniel B , Haynes Kevin , Denburg Michelle R , Thacker Mihir M , Rose Carlos D , Putt Mary E , Leonard Mary B , Strom Brian L 
Published: July 2017

ObjectivesWe studied oral glucocorticoids and osteonecrosis, a rare but serious bone disease, in individuals with various chronic inflammatory diseases. We hypothesised that we would find stronger associations in adults versus children and in people with autoimmune diseases.DesignRetrospective cohort study.SettingPopulation-representative data (1994–2013) from general practices in the UK.ParticipantsChildren and adults diagnosed with asthma; inflammatory bowel disease; juvenile, psoriatic or rheumatoid arthritis; psoriasis; or systemic lupus.ExposuresOral glucocorticoid patterns.Primary and secondary outcome measuresDiagnosed osteonecrosis (primary) and osteonecrosis plus clinical features (eg, symptoms, pain medication, surgical repair) (secondary). Discrete time failure models estimated the adjusted hazard ratio (aHR) of incident osteonecrosis following oral glucocorticoid exposure. Hypothesis testing was one sided (with corresponding 90% CI) since glucocorticoids were unlikely protective.ResultsAfter adjusting for demographic, disease-related and health utilisation factors, glucocorticoid exposure was associated with osteonecrosis in adults (ages 18–49, aHR 2.1 (90% CI 1.5 to 2.9); ages ≥50, aHR 1.3 (90% CI 1.01 to 1.7)). However, low-dose glucocorticoids, corresponding to average doses <7.5 mg prednisolone daily and maximum doses <30 mg daily, were not associated with osteonecrosis in adults. Furthermore, even at high glucocorticoid doses, there was no evidence of increased osteonecrosis among glucocorticoid-exposed children (p=0.04 for interaction by age) (any glucocorticoid exposure, ages 2–9: aHR 1.1 (90% CI 0.7 to 1.7); ages 10–17: aHR 0.6 (90% CI 0.3 to 1.6)). Arthritis, inflammatory bowel disease and lupus were independently associated with osteonecrosis, but there was a similar dose relationship between glucocorticoids and osteonecrosis among adults with low-risk and high-risk diseases.ConclusionsGlucocorticoid use was clearly associated with osteonecrosis in a dose-related fashion in adults, especially young adults, but this risk was not detectable in children. The absolute risk of glucocorticoid-associated osteonecrosis in the general paediatric population and in adults taking low glucocorticoid doses is at most extremely small.
Influence of Renal Impairment on Outcome for Thrombolysis-Treated Acute Ischemic Stroke
Authors: Carr Susan J. , Wang Xia , Olavarria Veronica V. , Lavados Pablo M. , Rodriguez Jorge A. , Kim Jong S. , Lee Tsong-Hai , Lindley Richard I. , Pontes-Neto Octavio M. , Ricci Stefano , Sato Shoichiro , Sharma Vijay K. , Woodward Mark , Chalmers John , Anderson Craig S. , Robinson Thompson G. 
Published: July 2017

Background and Purpose—
Renal dysfunction (RD) is associated with poor prognosis after stroke. We assessed the effects of RD on outcomes and interaction with low- versus standard-dose alteplase in a post hoc subgroup analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study).

Methods—

A total of 3220 thrombolysis-eligible patients with acute ischemic stroke (mean age, 66.5 years; 37.8% women) were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset. Six hundred and fifty-nine (19.8%) patients had moderate-to-severe RD (estimated glomerular filtration rate, <60 mL/min per 1.73 m
2
) at baseline. The impact of RD on death or disability (modified Rankin Scale scores, 2–6) at 90 days, and symptomatic intracerebral hemorrhage, was assessed in logistic regression models.

Results—

Compared with patients with normal renal function (>90 mL/min per 1.73 m
2
), those with severe RD (<30 mL/min per 1.73 m
2
) had increased mortality (adjusted odds ratio, 2.07; 95% confidence interval, 0.89–4.82;
P
=0.04 for trend); every 10 mL/min per 1.73 m
2
lower estimated glomerular filtration rate was associated with an adjusted 9% increased odds of death from thrombolysis-treated acute ischemic stroke. There was no significant association with modified Rankin Scale scores 2 to 6 (adjusted odds ratio, 1.03; 95% confidence interval, 0.62–1.70;
P
=0.81 for trend), modified Rankin Scale 3 to 6 (adjusted odds ratio, 1.20; 95% confidence interval, 0.72–2.01;
P
=0.44 for trend), or symptomatic intracerebral hemorrhage, or any heterogeneity in comparative treatment effects between low-dose and standard-dose alteplase by RD grades.

Conclusions—
RD is associated with increased mortality but not disability or symptomatic intracerebral hemorrhage in thrombolysis-eligible and treated acute ischemic stroke patients. Uncertainty persists as to whether low-dose alteplase confers benefits over standard-dose alteplase in acute ischemic stroke patients with RD.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01422616.
Controversies Surrounding Critical Care Nutrition: An Appraisal of Permissive Underfeeding, Protein, and Outcomes
Authors: Patel Jayshil J. , Martindale Robert G. , McClave Stephen A. 
Published: July 2017

AbstractOver the past few years, numerous studies have called into question the optimal dose, timing, composition, and advancement rate of nutrition during the early acute phase of critical illness. These studies suggest permissive underfeeding with slow advancement may be more beneficial than aggressive full feeding. These counterintuitive results were possibly explained by enhanced autophagy, less hyperglycemia, or prevention of refeeding syndrome. This review underscores the controversies surrounding permissive underfeeding, aims to answer whether permissive underfeeding is appropriate for all critically ill patients, describes the impact of optimal protein delivery on critical care outcomes, discusses nutrition risk, and cogitates on the impact of nutrition on critical care outcomes.
Comparison of bi-exponential and mono-exponential models of diffusion-weighted imaging for detecting active sacroiliitis in ankylosing spondylitis
Authors: Sun Haitao , Liu Kai , Liu Hao , Ji Zongfei , Yan Yan , Jiang Lindi , Zhou Jianjun 
Published: July 2017

Background There has been a growing need for a sensitive and effective imaging method for the differentiation of the activity of ankylosing spondylitis (AS). Purpose To compare the performances of intravoxel incoherent motion (IVIM)-derived parameters and the apparent diffusion coefficient (ADC) for distinguishing AS-activity. Material and Methods One hundred patients with AS were divided into active (n = 51) and non-active groups (n = 49) and 21 healthy volunteers were included as control. The ADC, diffusion coefficient ( D), pseudodiffusion coefficient ( D*), and perfusion fraction ( f) were calculated for all groups. Kruskal–Wallis tests and receiver operator characteristic (ROC) curve analysis were performed for all parameters. Results There was good reproducibility of ADC /D and relatively poor reproducibility of D*/f. ADC, D, and f were significantly higher in the active group than in the non-active and control groups (all P < 0.0001, respectively). D* was slightly but significant lower in the active group than in the non-active and control group ( P = 0.0064, 0.0215). There was no significant difference in any parameter between the non-active group and the control group (all P > 0.050). In the ROC analysis, ADC had the largest AUC for distinguishing between the active group and the non-active group (0.988) and between the active and control groups (0.990). Multivariate logistic regression analysis models showed no diagnostic improvement. Conclusion ADC provided better diagnostic performance than IVIM-derived parameters in differentiating AS activity. Therefore, a straightforward and effective mono-exponential model of diffusion-weighted imaging may be sufficient for differentiating AS activity in the clinic.
Selective cephalic upregulation of p-ERK, CamKII and p-CREB in response to glyceryl trinitrate infusion
Authors: Ramachandran Roshni , Pedersen Sara Hougaard , Amrutkar Dipak Vasantrao , Petersen Steffen , Jacobsen Julie Mie , Hay-Schmidt Anders , Olesen Jes , Jansen-Olesen Inger 
Published: July 2017

Background A common characteristic of migraine-inducing substances is that they cause headache and no pain in other areas of the body. Few studies have compared pain mechanisms in the trigeminal and spinal systems and, so far, no major differences have been noted. We compared signalling molecules in the trigeminal and spinothalamic system after infusion of the migraine-provoking substance glyceryltrinitrate. Method A catheter was placed in the femoral vein of rats and one week later glyceryltrinitrate 4 µg/kg/min was infused for 20 min. Protein expression in the dura mater, trigeminal ganglion, nucleus caudalis, dorsal root ganglion and the dorsal horn of the thoracic spinal cord was analysed at different time points using western blotting and immunohistochemistry. Results Glyceryltrinitrate caused a threefold increase in expression of phosphorylated extracellular signal-regulated kinases at 30 min in the dura mater and nucleus caudalis ( P < 0.05) and at 2 h in the trigeminal ganglion with very few expressions in the dorsal root ganglion. In the nucleus caudalis, expression of phosphorylated extracellular signal-regulated kinases and Cam KII increased 2.6-fold and 3.2-fold, respectively, at 2 h after glycerytrinitrate infusion ( P < 0.01). p-CREB/ATF-1 upregulation was observed only at 30 min ( P < 0.05) in the nucleus caudalis. None of these markers showed increased expression in the regions of thoracic spinal cord dorsal horn. Conclusion The dura, trigeminal ganglion and nucleus caudalis are activated shortly after glycerytrinitrate infusion with long-lasting expression of phosphorylated extracellular signal-regulated kinases observed in the nucleus caudalis. These activations were not observed at the spinal level.
Multimodal characterization of gray matter alterations in neuromyelitis optica
Authors: Liu Yaou , Jiang Xueyan , Butzkueven Helmut , Duan Yunyun , Huang Jing , Ren Zhuoqiong , Dong Huiqing , Shi Fu-Dong , Barkhof Frederik , Li Kuncheng , Wang Jinhui 
Published: July 2017

Objective: To investigate structural and functional alterations of gray matter (GM) and examine their clinical relevance in neuromyelitis optica (NMO) using multimodal magnetic resonance imaging (MRI) techniques. Methods: A total of 35 NMO and 36 healthy controls (HC) were recruited in this study. Cortical lesions were investigated by double inversion recovery technique. Five voxel-wise MRI measurements were obtained for each participant in the GM including gray matter volume (GMV), fractional anisotropy (FA), mean diffusivity (MD), amplitude of low-frequency fluctuation (ALFF), and weighted functional connectivity strength (wFCS). Between-group differences, cross-modality relationships, and MRI-clinical correlations were examined. Results: No cortical lesions were found in NMO. Compared to HC, NMO patients exhibited significantly decreased GMV in deep GM and cortical regions involving visual function and cognition. Diffusion GM abnormalities were widespread in the patients. Decreased ALFF and wFCS were observed in the patients in sensorimotor, visual, cognition, and cerebellar sites. GM structural alterations were correlated with cognitive but not physical disability scores of the patients. Conclusion: Despite the lack of focal cortical lesions, patients with NMO exhibit both structural and functional alterations of GM in cerebrum and cerebellum that predominantly involve deep GM, visual, motor, and cognitive regions. GM alterations are associated with cognitive impairment but not physical disability.
Femoral Arteriovenous Grafts for Hemodialysis: Retrospective Comparison With Upper Extremity Grafts and Fistulas
Authors: Dumaine Chance , Espino-Hernandez Gabriela , Romann Alexandra , Luscombe Rick , Kiaii Mercedeh 
Published: July 2017

Background: Femoral arteriovenous grafts are rarely used to provide vascular access for dialysis patients. This is likely due, in part, to historically high rates of graft loss from infection and thrombosis. However, for selected patients who have exhausted all access options in the upper extremity, femoral grafts can provide additional sites for access creation and may be preferred over central venous catheters. Objective: We sought to demonstrate that femoral grafts can provide a reliable and safe alternative to central venous catheters for selected patients. Methods: A single-center retrospective review in Vancouver, Canada, from April 1, 2008, to March 31, 2012, was conducted. All patients with new arteriovenous access (grafts and fistulas) created during the study period were included in the study population and followed for a minimum of 2 years. Comparisons of patency (primary, secondary, and functional) and complications (infectious and noninfectious) were made between the different access types. Results: Thirteen patients with femoral grafts were compared with 22 patients with arm grafts and 384 patients with fistulas. Femoral grafts had higher rates of thrombosis (46% with a thrombotic event) and a higher requirement for interventions (1.3 angioplasties and 0.12 thrombolytic procedures per patient per year). However, compared with arm grafts, femoral grafts had superior secondary and functional patency. No difference in patency was seen when comparing femoral grafts with upper extremity fistulas. Only 2 patients with femoral grafts required antibiotics for infection, and no grafts were lost to infection. Conclusions: For patients with limited access options remaining, femoral grafts may provide an additional form of vascular access before resorting to catheter use. Our study shows that with appropriate patient selection, femoral grafts have low infection rates and patency that is comparable with other access types.
Novel characteristics identified in two cases of feline cowpox virus infection
Authors: Breheny Craig R , Fox Victoria , Tamborini Alice , O’Halloran Conor , Robertson Elise , Cazzini Paola , Birn-Jeffery Daniela , Henkin Julia , Schwarz Tobias , Scase Tim , Powell Roger , Gunn-Moore Danièlle 
Published: July 2017

Case series summary This case series discusses novel characteristics identified in two cases of cowpox. One presented with upper airway signs, and was identified to have a focal laryngeal lesion. The other had central neurological signs at the terminal stages, with intracytoplasmic inclusion bodies identified within the cerebral hemispheres on histopathology. Relevance and novel information Currently, cowpox would be an unlikely consideration in patients with neurological signs or upper respiratory noise. These cases both document novel presentations of cowpox infection, which clinicians should be aware of and consider as differential diagnoses in patients with these atypical presentations.