bluuebunny/crossref_metadata_2025 huggingface dataset:
Costs of coordinated versus uncoordinated care in Germany: results of a routine data analysis in Bavaria
Authors: Schneider Antonius , Donnachie Ewan , Tauscher Martin , Gerlach Roman , Maier Werner , Mielck Andreas , Linde Klaus , Mehring Michael
Published: June 2016

Objectives

The efficiency of a gatekeeping system for a health system, as in Germany, remains unclear particularly as access to specialist ambulatory care is not restricted. The aim was to compare the costs of coordinated versus uncoordinated patients (UP) in ambulatory care; with additional subgroup analysis of patients with mental disorders.

Design

Retrospective routine data analysis of patients with statutory health insurance, using claims data held by the Bavarian Association of Statutory Health Insurance Physicians. A patient was defined as uncoordinated if he or she visited at least 1 specialist without a referral from a general practitioner within a quarter. Outcomes were compared with propensity score matching analysis.

Participants

The study encompassed all statutorily insured patients in Bavaria contacting at least 1 ambulatory specialist in the first quarter of 2011 (n=3 616 510).

Primary and secondary outcome measures

Primary outcome was total costs of ambulatory care; secondary outcomes were financial claims of general physicians, specialists and for medication.

Results

The average age was 55.3 years for coordinated patients (CP, n=1 629 302), 48.3 years for UP (n=1 825 840). CP more frequently had chronic diseases (85.4%) as compared with UP (67.5%). The total unadjusted financial claim per patient was higher for UP (€234.52) than for CP (€224.41); the total adjusted difference was −€9.65 (95% CI −11.64 to −7.67), indicating lower costs for CP. The cost differences increased with increasing age. Total adjusted difference per patient with mental diseases as documented with an International Classification of Diseases (ICD)-10 F-diagnosis, was −€20.31 (95% CI −26.43 to −14.46).

Conclusions

Coordination of care is associated with lower ambulatory healthcare expenditures and is of particular importance for patients who are more vulnerable to medical interventions, especially for elderly and patients with mental disorders. The role of general practitioners as coordinators should be strengthened to improve care for these patients as this could also help to frame a more efficient health system.
‘He's going to be a doctor in August’: a narrative interview study of medical students' and their educators' experiences of aligned and misaligned assistantships
Authors: Jones Owen Meurig , Okeke Chiemeka , Bullock Alison , Wells Stephanie E , Monrouxe Lynn V
Published: June 2016

Objective

To explore final-year students’ and clinical supervisors’ experiences of alignment and misalignment with future Foundation Year 1 (F1) posts in an assistantship programme in the UK.

Setting

Assistantships are clinical placements in which students assist junior doctors by undertaking similar duties under supervision. Models of assistantship programmes vary across curricula. Some actively seek to align with students’ initial postgraduate F1 post. To date, no research has examined the implications of this association for teaching and learning. Qualitative individual and group narrative interviews were conducted with students and supervisors of 2 Welsh medical schools to address: RQ1: How do students and supervisors understand the purpose of the longitudinal assistantship? RQ2: Does alignment/misalignment of the assistantship with students’ initial F1 post influence students’ and supervisors’ teaching and learning experiences? Audio-recordings of interviews were transcribed, participants anonymised and framework analysis was used.

Participants

A convenience sample of 4 participant groups comprised (1) final-year medical students whose assistantship and F1 post were aligned (n=27), (2) final-year medical students whose assistantship and F1 post were misaligned (n=18) and (3) supervisors (n=10, junior doctors; n=11, consultants).

Results

All participant groups highlighted increased student confidence in undertaking the duties of an F1 doctor arising from their assistantship period. Learning transferable skills was also highlighted. Many students considered themselves to be team members, ‘learning the trade’ as they shadowed their F1. Opportunities for caring for acutely unwell patients were scarce. The evidence shows enhanced engagement for students aligned to their first F1 post with greater opportunities for workplace acclimatisation. Those who were misaligned were perceived as being disadvantaged.

Conclusions

Our findings suggest that alignment with students’ first F1 post enhances the assistantship experience. Further longitudinal assessment is required to examine whether and how this translates into improvements in functioning and reductions in stress and anxiety during this transitional period.
Theory-based and evidence-based design of audit and feedback programmes: examples from two clinical intervention studies
Authors: Hysong Sylvia J , Kell Harrison J , Petersen Laura A , Campbell Bryan A , Trautner Barbara W
Published: June 2016

Background

Audit and feedback (A&F) is a common intervention used to change healthcare provider behaviour and, thus, improve healthcare quality. Although A&F can be effective its effectiveness varies, often due to the details of how A&F interventions are implemented. Some have suggested that a suitable conceptual framework is needed to organise the elements of A&F and also explain any observed differences in effectiveness. Through two examples from applied research studies, this article demonstrates how a suitable explanatory theory (in this case Kluger & DeNisi's Feedback Intervention Theory (FIT)) can be systematically applied to design better feedback interventions in healthcare settings.

Methods

Case 1: this study's objective was to reduce inappropriate diagnosis of catheter-associated urinary tract infections (CAUTI) in inpatient wards. Learning to identify the correct clinical course of action from the case details was central to this study; consequently, the feedback intervention featured feedback elements that FIT predicts would best activate learning processes (framing feedback in terms of group performance and providing of correct solution information). We designed a highly personalised, interactive, one-on-one intervention with healthcare providers to improve their capacity to distinguish between CAUTI and asymptomatic bacteruria (ASB) and treat ASB appropriately. Case 2: Simplicity and scalability drove this study's intervention design, employing elements that FIT predicted positively impacted effectiveness yet still facilitated deployment and scalability (eg, delivered via computer, delivered in writing). We designed a web-based, report-style feedback intervention to help primary care physicians improve their care of patients with hypertension.

Results

Both studies exhibited significant improvements in their desired outcome and in both cases interventions were received positively by feedback recipients.

A&F has been a popular, yet inconsistently implemented and variably effective tool for changing healthcare provider behaviour and, improving healthcare quality. Through the systematic use of theory such as FIT, robust feedback interventions can be designed that yield greater effectiveness. Future work should look to comparative effectiveness of specific design elements and contextual factors that identify A&F as the optimal intervention to effectuate healthcare provider behaviour change.

Trial registration number

NCT01052545,NCT00302718; post-results.
From tokenism to empowerment: progressing patient and public involvement in healthcare improvement
Authors: Ocloo Josephine , Matthews Rachel
Published: June 2016

Background

There have been repeated calls to better involve patients and the public and to place them at the centre of healthcare. Serious clinical and service failings in the UK and internationally increase the urgency and importance of addressing this problem. Despite this supportive policy context, progress to achieve greater involvement is patchy and slow and often concentrated at the lowest levels of involvement.

Methods

A selective narrative literature search was guided by the authors’ broad expertise, covering a range of disciplines across health and social care, policy and research. Published systematic literature reviews were used to identify relevant authors and publications. Google and hand searches of journal articles and reference lists and reports augmented identification of recent evidence.

Results

Patients and the wider public can be involved at most stages of healthcare, and this can have a number of benefits. Uncertainty persists about why and how to do involvement well and evaluate its impact, how to involve and support a diversity of individuals, and in ways that allow them to work in partnership to genuinely influence decision-making. This exposes patient and public involvement (PPI) to criticisms of exclusivity and tokenism.

Conclusions

Current models of PPI are too narrow, and few organisations mention empowerment or address equality and diversity in their involvement strategies. These aspects of involvement should receive greater attention, as well as the adoption of models and frameworks that enable power and decision-making to be shared more equitably with patients and the public in designing, planning and co-producing healthcare.
Exploratory study into the effect of abdominal mass loading on airways resistance and ventilatory failure
Authors: Dattani Raj S , Swerner Casey B , Stradling John R , Manuel Ari RG
Published: June 2016

Objective

We hypothesised that the airway resistance during tidal breathing would correlate with a particular pattern of increasing obesity, particularly when supine, and would differ between participants with and without ventilatory failure.

Methods

In our cross-sectional cohort study, 72 morbidly obese patients (40 males, 32 females, mean body mass index (BMI) 47.2) had measurements of both airways resistance (by impulse oscillometry (IOS)) and adiposity (by dual-energy X-ray absorptiometry (DXA)).

Results

All measures of airways resistance increased in the supine position: total airways resistance (R5) +37% (p<0.0005); large airways resistance (R20) +29% (p<0.0005); and small airways resistance (R5–R20) +52% (p<0.0005). BMI was correlated with seated R5, seated R5–R20, supine R5 and supine R5–R20 (r=0.33 p<0.006, r=0.32 p<0.004, r=0.30 p<0.02 and r=0.36 p<0.04, respectively). Visceral adipose tissue mass was correlated with supine R5–20 (r=0.46 p<0.05). Supine measures of total airways resistance (R5) and large airways resistance (R20) differed between those with and without ventilatory failure, as did mean weight and BMI.

Conclusions

Our study identifies a potentially detrimental effect of the supine posture on tidal breathing airways resistance in obese patients. This change is correlated most with visceral adipose tissue mass and the small airways. We were able to demonstrate that supine increases in airways resistance during tidal breathing, within obese patients, are different between those with and without ventilatory failure.

Trial registration number

NCT01380418; pre-results.
Pharmacovigilance in hospice/palliative care: the net immediate and short-term effects of dexamethasone for anorexia
Authors: Hatano Yutaka , Moroni Matteo , Wilcock Andrew , Quinn Stephen , Csikós Ágnes , Allan Simon G , Agar Meera , Clark Katherine , Clayton Josephine M , Currow David C
Published: June 2016

Objectives

Loss of appetite is prevalent in palliative care and distressing for patients and families. Therapies include corticosteroids or progestogens. This study explores the net effect of dexamethasone on anorexia.

Methods

Prospective data were collected when dexamethasone was started for anorexia as part of routine care. The National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCICTCAE) Likert scales assessed severity of anorexia and immediate and short-term harms at 2 time points: baseline and 7 days.

Results

This study (41 sites, 8 countries) collected data (July 2013 to July 2014) from 114 patients (mean age 71 (SD 11), 96% with cancer). Median Australian-modified Karnofsky Performance Scale was 50% (range 20–70). Mean baseline NCICTCAE anorexia score was 2.7 (SD 0.6; median 3). 6 patients died by day 7. Of 108 evaluable patients, 74 (68.5%; 95% CI 59.0% to 76.7%) reported ≥1 reduction anorexia scores by day 7, of whom 30 were 0. Mean dexamethasone dose on day 7 was 4.1 mg/day (SD 3.4; median 4; range 0–46 mg). 24 patients reported ≥1 harms (32.4% CI 22.6% to 44.1%; insomnia n=10, depression n=7, euphoria n=7 and hyperglycaemia n=7). Of 24 patients with no benefit, 10 reported ≥1 harms.

Conclusions

This study shows positive and negative effects of 7 days of dexamethasone as an appetite stimulant in patients with advanced life-limiting illnesses. Identifying clinicodemographic characteristics of people most at risk of harms with no benefit is a crucial next step. Longer term follow-up will help to understand longer term and cumulative harms.
Man or machine? An experimental study of prehospital emergency amputation
Authors: Leech Caroline , Porter Keith
Published: June 2016

Objective

Prehospital emergency amputation is a rare procedure, which may be necessary to free a time-critical patient from entrapment. This study aimed to evaluate four techniques of cadaveric lower limb prehospital emergency amputation.

Method

A guillotine amputation of the distal femur was undertaken in fresh frozen self-donated cadavers. A prehospital doctor conducted a surgical amputation with Gigli saw or hacksaw for bone cuts and firefighters carried out the procedure using the reciprocating saw and Holmatro device. The primary outcome measures were time to full amputation and the number of attempts required. The secondary outcomes were observed quality of skin cut, soft tissue cut and CT assessment of the proximal bone. Observers also noted the potential risks to the rescuer or patient during the procedure.

Results

All techniques completed amputation within 91 s. The reciprocating saw was the quickest technique (22 s) but there was significant blood spattering and continuation of the cut to the surface under the leg. The Holmatro device took less than a minute. The quality of the proximal femur was acceptable with all methods, but 5 cm more proximal soft tissue damage was made by the Holmatro device.

Conclusions

Emergency prehospital guillotine amputation of the distal femur can effectively be performed using scalpel and paramedic shears with bone cuts by the Gigli saw or fire service hacksaw. The reciprocating saw could be used to cut bone if no other equipment was available but carried some risks. The Holmatro cutting device is a viable option for a life-threatening entrapment where only firefighters can safely access the patient, but would not be a recommended primary technique for medical staff.
Autoimmune liver disease: evaluating overlapping and cross-over presentations—a case-based discussion
Authors: Corrigan Margaret , Hirschfield Gideon M
Published: June 2016

The three classic autoimmune liver diseases are recognised based on identifying varying clinical, laboratory, histological and radiological features that collectively classify patients. In the absence of defined aetiological factors, it is recognised that disease spectrum is broad, and, in this context, it is not infrequent for disease boundaries to be blurred, leading to overlapping features that may be present at the time of diagnosis or may appear later in the course of disease. Given the absence of accepted diagnostic criteria for overlap/cross-over syndromes, alongside weak data for intervention, it is recommended that a multidisciplinary, patient-specific approach be used to establish individual treatment pathways.
Ectopic crypt foci in conventional and serrated colorectal polyps
Authors: Väyrynen Sara A , Väyrynen Juha P , Klintrup Kai , Mäkelä Jyrki , Tuomisto Anne , Mäkinen Markus J
Published: June 2016

Aims

Despite almost pathognomonic status of ectopic crypt foci (ECF) in the diagnosis of traditional serrated adenoma (TSA), there are few systematic studies on their prevalence in other types of colon polyps or in adenomas adjacent to colorectal cancer (CRC).

Methods

We calculated ECF in all the polyps (n=922) removed in the colonoscopy in Oulu University Hospital in 2001. Moreover, to study ECF in precursor lesions next to CRCs, we re-examined a previously described cohort of 148 CRCs.

Results

ECF were seen in 53 (5.7%) polyps representing 28 (6.5%) tubular adenomas (TAs), 14 (53.8%) tubulovillous adenomas (TVAs), 2 (100.0%) villous adenomas (VAs) and 9 (100.0%) TSAs. In all TSAs and VAs, the density of ECF was higher than in TVAs and TAs. An adjacent precursor lesion was recognised in 28 of 148 (18.9%) CRCs. Twenty-four (85.7%) of these contained ECF.

Conclusions

ECF can most frequently be observed in TSAs but also in many TVAs, VAs and TAs, reflecting a histological overlap between serrated and conventional polyps. Especially, precursor lesions adjacent to CRC frequently contain ECF.
‘It's not the form; it's the process’: a phenomenological study on the use of creative professional development workshops to improve teamwork and communication skills
Authors: Acai Anita , McQueen Sydney A , Fahim Christine , Wagner Natalie , McKinnon Victoria , Boston Jody , Maxwell Colina , Sonnadara Ranil R
Published: June 2016

Introduction

Past research has demonstrated the positive effects of visual and performing arts on health professionals' observational acuity and associated diagnostic skills, well-being and professional identity. However, to date, the use of arts for the development of non-technical skills, such as teamwork and communication, has not been studied thoroughly.

Methods

In partnership with a community print and media arts organisation, Centre[3], we used a phenomenological approach to explore front-line mental health and social service workers' experiences with a creative professional development workshop based on the visual and performing arts. Through preworkshop and postworkshop interviews with participants and postworkshop interviews with their managers, we sought to examine how participants' perceptions of the workshop compared with their preworkshop expectations, specific impacts of the workshop with respect to participants' teamwork and communication skills and changes in their perceptions regarding the use of the arts in professional development.

Results

Our workshops were successful in enhancing teamwork skills among participants and showed promise in the development of communication skills, though observable changes in workplace communication could not be confirmed. The workshop facilitated teamwork and collegiality between colleagues, creating a more enjoyable and accepting work environment. The workshops also helped participants identify the strengths and weaknesses of their communication skills, made them more comfortable with different communication styles and provided them with strategies to enhance their communication skills.

Conclusions

Participation in the arts can be beneficial for the development of interpersonal skills such as teamwork and communication among health professionals.
Verification and feedback for medical students: an observational study during general practice rotations
Authors: Bösner Stefan , Roth Lisa Marie , Duncan Gertrude Florence , Donner-Banzhoff Norbert
Published: June 2016

Purpose of the study

A general practice and family medicine rotation is mandatory as part of undergraduate medical education. However, little is known about the student-teacher interaction in this specific setting of ambulatory teaching. In this study we analysed how frequently preceptors verified students’ history taking and clinical examination skills and how often they gave feedback. The type of feedback given was also categorised.

Methods

From April to December 2012, 410 individual patient consultations were observed in 12 teaching practices associated with the Philipps University Marburg, Germany. Material was collected using structured field-note forms and videotaping. Descriptive data analysis was performed. Informed, written consent was provided by all participants.

Results

We analysed 410 consultations which lasted 14.8 min on average. In 130 (31.7%) consultations students took the patient’s medical history; 124 (95.4%) of these were verified by the general practitioner (GP). Physical examination was performed by students in 202 (49.3%) of consultations; 169 (81.9%) of these were verified by the GP. Feedback occurred in 132 (32.2%) of the 410 patient consultations. Feedback was mostly non-specific and positive (68.9%), and occurred during consultation with the patient present. Specific, negative feedback also occurred relatively frequently (29.5%). Specific, positive and non-specific, negative responses were rarely given.

Conclusions

GPs should give feedback more frequently and when doing so, focus on specific feedback. GPs should be further instructed in different feedback techniques.
Cardiac arrest leadership: in need of resuscitation?
Authors: Robinson Philip S , Shall Emma , Rakhit Roby
Published: June 2016

Background

Leadership skills directly correlate with the quality of technical performance of cardiopulmonary resuscitation (CPR) and clinical outcomes. Despite an improved focus on non-technical skills in CPR training, the leadership of cardiac arrests is often variable.

Aims

To assess the perceptions of leadership and team working among members of a cardiac arrest team and to evaluate future training needs.

Methods

Cross-sectional survey of 102 members of a cardiac arrest team at an Acute Hospital Trust in the UK with 892 inpatient beds. Responses sought from doctors, nurses and healthcare assistants to 12 rated statements and 4 dichotomous questions.

Results

Of 102 responses, 81 (79%) were from doctors and 21 (21%) from nurses. Among specialist registrars 90% agreed or strongly agreed that there was clear leadership at all arrests compared with between 28% and 49% of nurses and junior doctors respectively. Routine omission of key leadership tasks was reported by as many as 80% of junior doctors and 50% of nurses. Almost half of respondents reported non-adherence with Advanced Life Support (ALS) guidelines. Among junior members of the team, 36% felt confident to lead an arrest and 75% would welcome further dedicated cardiac arrest leadership training.

Conclusions

Leadership training is integrated into the ALS (Resus Council, UK) qualification. However, this paper found that in spite of this training; standards of leadership are variable. The findings suggest a pressing need for further dedicated cardiac arrest leadership training with a focus on improving key leadership tasks such as role assignment, team briefing and debriefing.
Adiabatic and quasi-diabatic investigation of the strontium hydride cation SrH+: structure, spectroscopy, and dipole moments
Authors: Belayouni Sana , Ghanmi Chedli , Berriche Hamid
Published: June 2016

Ab initio investigation has been performed for the strontium hydride cation SrH + using a standard quantum chemistry approach. It is based on the pseudopotentials for atomic core representations, Gaussian basis sets, as well as with full configuration interaction calculations. A diabatisation procedure based on the effective hamiltonian theory and an effective metric is used to produce the quasi-diabatic potential energy. Adiabatic and quasi-diabatic potential energy curves and their spectroscopic parameters for the ground and many excited electronic states of 1,3Σ+, 1,3Π, and 1,3Δ symmetries have been determined. Their predicted accuracy is discussed by comparing our well depths and equilibrium positions with the available experimental and theoretical results. Moreover, we localized and analyzed numerous avoided crossings between the electronic states of 1,3Σ+ and 1,3Π symmetries. The correction of the electron affinity of the H atom is also considered, for the 1–101Σ+ electronic states, to improve the accuracy of the adiabatic potential energies of these states. In addition, we calculated the dipole moments, for a wide range of internuclear distances in both diabatic and quasi-diabatic representations. The adiabatic permanent dipole moments for the 101Σ+ electronic states revealed ionic characters related to electron transfer and yields both SrH(+) and Sr(+)H arrangements. The transition dipole moments between neighbor electronic states revealed many peaks around the avoided crossing positions.
Pentoxifylline abrogates cardiotoxicity induced by the administration of a single high dose or multiple low doses of doxorubicin in rats
Authors: Elshazly Shimaa M. , Mahmoud Amr A.A. , Barakat Waleed
Published: June 2016

Doxorubicin (DOX) possesses a broad-spectrum antineoplastic activity; however, its clinical application is impeded by cardiotoxicity. This study aimed to investigate the protective effect of pentoxifylline (PXF), which possesses antioxidant and anti-inflammatory properties against cardiotoxicity induced by a single high dose (15 mg/kg, i.p.) or multiple low doses (2.5 mg/kg, i.p., three times per week for 2 weeks) of DOX. At the end of the experimental period, the serum creatine kinase (CK)-MB and lactate dehydrogenase (LDH) activities were measured. The hearts were then removed for evaluating TNF-α, NO, malondialdehyde (MDA), and reduced glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities, and the expression of iNOS, NF-κB, Fas ligand (FasL), and caspase-3. The administration of DOX in both dose regimens caused increases in serum CK-MB and LDH activities, in cardiac TNF-α, NO and MDA levels, as well as in the cardiac expression of iNOS, NF-κB, FasL and caspase-3, whereas it significantly reduced the cardiac GSH level, as well as SOD and CAT activities (P < 0.05). Prophylactic treatment of rats with PXF diminished DOX-induced alterations in theses parameters. Our results warrant the clinical use of PXF as an adjuvant therapy to abrogate cardiotoxicity of DOX and extend its clinical applications.
Gromov–Witten type invariants on circle bundles over symplectic manifolds
Authors: Cho Yong Seung , Chai Young Do
Published: June 2016

We consider circle bundles over symplectic manifolds to study Gromov–Witten type invariants. We investigate the moduli space of pseudo-coholomorphic maps, Gromov–Witten type invariant, the quantum type cohomology of the total space which has a natural contact structure. We then compare Gromov–Witten invariant, and quantum cohomology of the base space with the one of the total space, and derive some relations between them.
A Novel Approach for Optimization in Dynamic Environments Based on Modified Artificial Fish Swarm Algorithm
Authors: Yazdani Danial , Sepas-Moghaddam Alireza , Dehban Atabak , Horta Nuno
Published: June 2016

Swarm intelligence algorithms are amongst the most efficient approaches toward solving optimization problems. Up to now, most of swarm intelligence approaches have been proposed for optimization in static environments. However, numerous real-world problems are dynamic which could not be solved using static approaches. In this paper, a novel approach based on artificial fish swarm algorithm (AFSA) has been proposed for optimization in dynamic environments in which changes in the problem space occur in discrete intervals. The proposed algorithm can quickly find the peaks in the problem space and track them after an environment change. In this algorithm, artificial fish swarms are responsible for finding and tracking peaks and several behaviors and mechanisms are employed to cope with the dynamic environment. Extensive experiments show that the proposed algorithm significantly outperforms previous algorithms in most of tested dynamic environments modeled by moving peaks benchmark.
The maximum amplification of perturbations in ecological systems
Authors: Wang Hailing , Zhang Jicheng , Yang Xiao-Song
Published: June 2016

Conventionally, most researches of ecological models focus mainly on the asymptotic stability properties near equilibria. However, transient effects can be important. It dominates the dynamics seen in experimental or field studies. Transient behavior near an equilibrium is measured by resilience, reactivity, the maximum amplification of a perturbation and the time at which the maximum amplification occurs. In this paper, we demonstrate emphatically the calculation of the amplification envelope of a homogeneous system of linear equations, then apply it to three ecological models. We conclude that transient amplification of perturbations to a stable equilibrium should be a very common ecological phenomenon, and reactive systems have huge changes around their equilibria.
Effect of liposome-encapsulated hemoglobin resuscitation on proteostasis in small intestinal epithelium after hemorrhagic shock
Authors: Rao Geeta , Yadav Vivek R. , Awasthi Shanjana , Roberts Pamela R. , Awasthi Vibhudutta
Published: June 2016

Gut barrier dysfunction is the major trigger for multiorgan failure associated with hemorrhagic shock (HS). Although the molecular mediators responsible for this dysfunction are unclear, oxidative stress-induced disruption of proteostasis contributes to the gut pathology in HS. The objective of this study was to investigate whether resuscitation with nanoparticulate liposome-encapsulated hemoglobin (LEH) is able to restore the gut proteostatic mechanisms. Sprague-Dawley rats were recruited in four groups: control, HS, HS+LEH, and HS+saline. HS was induced by withdrawing 45% blood, and isovolemic LEH or saline was administered after 15 min of shock. The rats were euthanized at 6 h to collect plasma and ileum for measurement of the markers of oxidative stress, unfolded protein response (UPR), proteasome function, and autophagy. HS significantly increased the protein and lipid oxidation, trypsin-like proteasome activity, and plasma levels of IFNγ. These effects were prevented by LEH resuscitation. However, saline was not able to reduce protein oxidation and plasma IFNγ in hemorrhaged rats. Saline resuscitation also suppressed the markers of UPR and autophagy below the basal levels; the HS or LEH groups showed no effect on the UPR and autophagy. Histological analysis showed that LEH resuscitation significantly increased the villus height and thickness of the submucosal and muscularis layers compared with the HS and saline groups. Overall, the results showed that LEH resuscitation was effective in normalizing the indicators of proteostasis stress in ileal tissue. On the other hand, saline-resuscitated animals showed a decoupling of oxidative stress and cellular protective mechanisms.
Arterial pressure suffices to increase liver stiffness
Authors: Piecha Felix , Peccerella Teresa , Bruckner Tom , Seitz Helmut-Karl , Rausch Vanessa , Mueller Sebastian
Published: June 2016

Noninvasive measurement of liver stiffness (LS) has been established to screen for liver fibrosis. Since LS is also elevated in response to pressure-related conditions such as liver congestion, this study was undertaken to learn more about the role of arterial pressure on LS. LS was measured by transient elastography (μFibroscan platform, Echosens, Paris, France) during single intravenous injections of catecholamines in anesthetized rats with and without thioacetamide (TAA)-induced fibrosis. The effect of vasodilating glycerol trinitrate (GTN) on LS was also studied. Pressures in the abdominal aorta and caval and portal veins were measured in real time with the PowerLab device (AD Instruments, Dunedin, New Zealand). Baseline LS values in all rats (3.8 ± 0.5 kPa, n = 25) did not significantly differ from those in humans. Epinephrine and norepinephrine drastically increased mean arterial pressure (MAP) from 82 to 173 and 156 mmHg. Concomitantly, LS almost doubled from 4 to 8 kPa, while central venous pressure remained unchanged. Likewise, portal pressure only showed a slight and delayed increase. In the TAA-induced fibrosis model, LS increased from 9.5 ± 1.0 to 25.6 ± 14.7 kPa upon epinephrine injection and could efficiently be decreased by GTN. We finally show a direct association in humans in a physiological setting of elevated cardiac output and MAP. During continuous spinning at 200 W, MAP increased from 84 ± 8 to 99 ± 11 mmHg while LS significantly increased from 4.4 ± 1.8 to 6.7 ± 2.1 kPa. In conclusion, our data show that arterial pressure suffices to increase LS. Moreover, lowering MAP efficiently decreases LS in fibrotic livers that are predominantly supplied by arterial blood.
Short fungal fractions of β-1,3 glucans affect platelet activation
Authors: Vancraeyneste Hélène , Charlet Rogatien , Guerardel Yann , Choteau Laura , Bauters Anne , Tardivel Meryem , François Nadine , Dubuquoy Laurent , Soloviev Dmitry , Poulain Daniel , Sendid Boualem , Jawhara Samir
Published: June 2016

Platelets are capable of binding, aggregating, and internalizing microorganisms, which enhances the elimination of pathogens from the blood. The yeast Candida albicans is a pathobiont causing life-threatening invasive infections. Its cell wall contains β-1,3 glucans that are known to trigger a wide range of host cell activities and to circulate during infection. We studied the effect of β-1,3 glucan fractions (BGFs) consisting of diglucosides (Glc2), tetraglucosides (Glc4), and pentaglucosides (Glc5) on human platelets, their mechanisms of action, and their possible impact on host defenses. The effect of BGFs on the coagulation process was determined by measuring thrombin generation. Platelets pretreated with BGFs were analyzed in terms of activation, receptor expression, aggregation, and adhesion to neutrophils and to C. albicans. The results show that BGFs affected the endogenous thrombin potential in a concentration-dependent manner. For platelet activation, BGFs at a low concentration (2 μmol/l) reduced ATP release and prevented the phosphorylation of protein kinase C. BGFs diminished the expression of P-selectin and the activation of αIIbβ3. BGFs decreased platelet aggregation and the interaction between thrombin-stimulated platelets and neutrophils, fibrinogen, and C. albicans. GLc5 decreased ATP release and TGF-β1 production in response to TLR4 upregulation in thrombin-stimulated platelets, but TLR4 blockage abolished the effect of BGFs on platelets. This study provides evidence that fungal pentaglucosides modulate platelet activity mediated via TLR4 stimulation and reduce platelet-neutrophil interaction.
Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors
Authors: Zheng Hong , Liu Xuefei , Sharma Neeru M. , Patel Kaushik P.
Published: June 2016

Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/d t to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/d t (by 71%) and −dP/d t (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition.
17β-Estradiol mediates superior adaptation of right ventricular function to acute strenuous exercise in female rats with severe pulmonary hypertension
Authors: Lahm Tim , Frump Andrea L. , Albrecht Marjorie E. , Fisher Amanda J. , Cook Todd G. , Jones Thomas J. , Yakubov Bakhtiyor , Whitson Jordan , Fuchs Robyn K. , Liu Aiping , Chesler Naomi C. , Brown M. Beth
Published: June 2016

17β-Estradiol (E2) exerts protective effects on right ventricular (RV) function in pulmonary arterial hypertension (PAH). Since acute exercise-induced increases in afterload may lead to RV dysfunction in PAH, we sought to determine whether E2 allows for superior RV adaptation after an acute exercise challenge. We studied echocardiographic, hemodynamic, structural, and biochemical markers of RV function in male and female rats with sugen/hypoxia (SuHx)-induced pulmonary hypertension, as well as in ovariectomized (OVX) SuHx females, with or without concomitant E2 repletion (75 μg·kg−1·day−1) immediately after 45 min of treadmill running at 75% of individually determined maximal aerobic capacity (75% aerobic capacity reserve). Compared with males, intact female rats exhibited higher stroke volume and cardiac indexes, a strong trend for better RV compliance, and less pronounced increases in indexed total pulmonary resistance. OVX abrogated favorable RV adaptations, whereas E2 repletion after OVX markedly improved RV function. E2's effects on pulmonary vascular remodeling were complex and less robust than its RV effects. Postexercise hemodynamics in females with endogenous or exogenous E2 were similar to hemodynamics in nonexercised controls, whereas OVX rats exhibited more severely altered postexercise hemodynamics. E2 mediated inhibitory effects on RV fibrosis and attenuated increases in RV collagen I/III ratio. Proapoptotic signaling, endothelial nitric oxide synthase phosphorylation, and autophagic flux markers were affected by E2 depletion and/or repletion. Markers of impaired autophagic flux correlated with endpoints of RV structure and function. Endogenous and exogenous E2 exerts protective effects on RV function measured immediately after an acute exercise challenge. Harnessing E2's mechanisms may lead to novel RV-directed therapies.
E-cigarette use results in suppression of immune and inflammatory-response genes in nasal epithelial cells similar to cigarette smoke
Authors: Martin Elizabeth M. , Clapp Phillip W. , Rebuli Meghan E. , Pawlak Erica A. , Glista-Baker Ellen , Benowitz Neal L. , Fry Rebecca C. , Jaspers Ilona
Published: June 2016

Exposure to cigarette smoke is known to result in impaired host defense responses and immune suppressive effects. However, the effects of new and emerging tobacco products, such as e-cigarettes, on the immune status of the respiratory epithelium are largely unknown. We conducted a clinical study collecting superficial nasal scrape biopsies, nasal lavage, urine, and serum from nonsmokers, cigarette smokers, and e-cigarette users and assessed them for changes in immune gene expression profiles. Smoking status was determined based on a smoking history and a 3- to 4-wk smoking diary and confirmed using serum cotinine and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels. Total RNA from nasal scrape biopsies was analyzed using the nCounter Human Immunology v2 Expression panel. Smoking cigarettes or vaping e-cigarettes resulted in decreased expression of immune-related genes. All genes with decreased expression in cigarette smokers ( n = 53) were also decreased in e-cigarette smokers. Additionally, vaping e-cigarettes was associated with suppression of a large number of unique genes ( n = 305). Furthermore, the e-cigarette users showed a greater suppression of genes common with those changed in cigarette smokers. This was particularly apparent for suppressed expression of transcription factors, such as EGR1, which was functionally associated with decreased expression of 5 target genes in cigarette smokers and 18 target genes in e-cigarette users. Taken together, these data indicate that vaping e-cigarettes is associated with decreased expression of a large number of immune-related genes, which are consistent with immune suppression at the level of the nasal mucosa.
Magnetic resonance imaging provides sensitive in vivo assessment of experimental ventilator-induced lung injury
Authors: Kuethe Dean O. , Filipczak Piotr T. , Hix Jeremy M. , Gigliotti Andrew P. , Estépar Raúl San José , Washko George R. , Baron Rebecca M. , Fredenburgh Laura E.
Published: June 2016

Animal models play a critical role in the study of acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). One limitation has been the lack of a suitable method for serial assessment of acute lung injury (ALI) in vivo. In this study, we demonstrate the sensitivity of magnetic resonance imaging (MRI) to assess ALI in real time in rat models of VILI. Sprague-Dawley rats were untreated or treated with intratracheal lipopolysaccharide or PBS. After 48 h, animals were mechanically ventilated for up to 15 h to induce VILI. Free induction decay (FID)-projection images were made hourly. Image data were collected continuously for 30 min and divided into 13 phases of the ventilatory cycle to make cinematic images. Interleaved measurements of respiratory mechanics were performed using a flexiVent ventilator. The degree of lung infiltration was quantified in serial images throughout the progression or resolution of VILI. MRI detected VILI significantly earlier (3.8 ± 1.6 h) than it was detected by altered lung mechanics (9.5 ± 3.9 h, P = 0.0156). Animals with VILI had a significant increase in the Index of Infiltration ( P = 0.0027), and early regional lung infiltrates detected by MRI correlated with edema and inflammatory lung injury on histopathology. We were also able to visualize and quantify regression of VILI in real time upon institution of protective mechanical ventilation. Magnetic resonance lung imaging can be utilized to investigate mechanisms underlying the development and propagation of ALI, and to test the therapeutic effects of new treatments and ventilator strategies on the resolution of ALI.
Components of the cannabinoid system in the dorsal periaqueductal gray are related to resting heart rate
Authors: Dean Caron , Hillard Cecilia J. , Seagard Jeanne L. , Hopp Francis A. , Hogan Quinn H.
Published: June 2016

The present study was undertaken to examine whether variations in endocannabinoid signaling in the dorsal periaqueductal gray (dPAG) are associated with baseline autonomic nerve activity, heart rate, and blood pressure. Blood pressure was recorded telemetrically in rats, and heart rate and power spectral analysis of heart rate variability were determined. Natural variations from animal to animal provided a range of baseline values for analysis. Transcript levels of endocannabinoid signaling components in the dPAG were analyzed, and endocannabinoid content and catabolic enzyme activity were measured. Higher baseline heart rate was associated with increased anandamide content and with decreased activity of the anandamide-hydrolyzing enzyme, fatty acid amide hydrolase (FAAH), and it was negatively correlated with transcript levels of both FAAH and monoacylglycerol lipase (MAGL), a catabolic enzyme for 2-arachidonoylglycerol (2-AG). Autonomic tone and heart rate, but not blood pressure, were correlated to levels of FAAH mRNA. In accordance with these data, exogenous anandamide in the dPAG of anesthetized rats increased heart rate. These data indicate that in the dPAG, anandamide, a FAAH-regulated lipid, contributes to regulation of baseline heart rate through influences on autonomic outflow.
Prediction of renal crystalline size distributions in space using a PBE analytic model. 1. Effect of microgravity-induced biochemical alterations
Authors: Kassemi Mohammad , Thompson David
Published: June 2016

An analytical Population Balance Equation model is developed and used to assess the risk of critical renal stone formation for astronauts during future space missions. The model uses the renal biochemical profile of the subject as input and predicts the steady-state size distribution of the nucleating, growing, and agglomerating calcium oxalate crystals during their transit through the kidney. The model is verified through comparison with published results of several crystallization experiments. Numerical results indicate that the model is successful in clearly distinguishing between 1-G normal and 1-G recurrent stone-former subjects based solely on their published 24-h urine biochemical profiles. Numerical case studies further show that the predicted renal calculi size distribution for a microgravity astronaut is closer to that of a recurrent stone former on Earth rather than to a normal subject in 1 G. This interestingly implies that the increase in renal stone risk level in microgravity is relatively more significant for a normal person than a stone former. However, numerical predictions still underscore that the stone-former subject carries by far the highest absolute risk of critical stone formation during space travel.
A physiological and behavioral system for hearing restoration with cochlear implants
Authors: King Julia , Shehu Ina , Roland J. Thomas , Svirsky Mario A. , Froemke Robert C.
Published: June 2016

Cochlear implants are neuroprosthetic devices that provide hearing to deaf patients, although outcomes are highly variable even with prolonged training and use. The central auditory system must process cochlear implant signals, but it is unclear how neural circuits adapt—or fail to adapt—to such inputs. The knowledge of these mechanisms is required for development of next-generation neuroprosthetics that interface with existing neural circuits and enable synaptic plasticity to improve perceptual outcomes. Here, we describe a new system for cochlear implant insertion, stimulation, and behavioral training in rats. Animals were first ensured to have significant hearing loss via physiological and behavioral criteria. We developed a surgical approach for multichannel (2- or 8-channel) array insertion, comparable with implantation procedures and depth in humans. Peripheral and cortical responses to stimulation were used to program the implant objectively. Animals fitted with implants learned to use them for an auditory-dependent task that assesses frequency detection and recognition in a background of environmentally and self-generated noise and ceased responding appropriately to sounds when the implant was temporarily inactivated. This physiologically calibrated and behaviorally validated system provides a powerful opportunity to study the neural basis of neuroprosthetic device use and plasticity.