bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal structure of the human NK
1
tachykinin receptor
Authors: Yin Jie , Chapman Karen , Clark Lindsay D. , Shao Zhenhua , Borek Dominika , Xu Qingping , Wang Junmei , Rosenbaum Daniel M.
Published: December 2018

The NK
1
tachykinin G-protein–coupled receptor (GPCR) binds substance P, the first neuropeptide to be discovered in mammals. Through activation of NK
1
R, substance P modulates a wide variety of physiological and disease processes including nociception, inflammation, and depression. Human NK
1
R (hNK
1
R) modulators have shown promise in clinical trials for migraine, depression, and emesis. However, the only currently approved drugs targeting hNK
1
R are inhibitors for chemotherapy-induced nausea and vomiting (CINV). To better understand the molecular basis of ligand recognition and selectivity, we solved the crystal structure of hNK
1
R bound to the inhibitor L760735, a close analog of the drug aprepitant. Our crystal structure reveals the basis for antagonist interaction in the deep and narrow orthosteric pocket of the receptor. We used our structure as a template for computational docking and molecular-dynamics simulations to dissect the energetic importance of binding pocket interactions and model the binding of aprepitant. The structure of hNK
1
R is a valuable tool in the further development of tachykinin receptor modulators for multiple clinical applications.
Global synthesis of conservation studies reveals the importance of small habitat patches for biodiversity
Authors: Wintle Brendan A. , Kujala Heini , Whitehead Amy , Cameron Alison , Veloz Sam , Kukkala Aija , Moilanen Atte , Gordon Ascelin , Lentini Pia E. , Cadenhead Natasha C. R. , Bekessy Sarah A.
Published: December 2018

Island biogeography theory posits that species richness increases with island size and decreases with isolation. This logic underpins much conservation policy and regulation, with preference given to conserving large, highly connected areas, and relative ambivalence shown toward protecting small, isolated habitat patches. We undertook a global synthesis of the relationship between the conservation value of habitat patches and their size and isolation, based on 31 systematic conservation planning studies across four continents. We found that small, isolated patches are inordinately important for biodiversity conservation. Our results provide a powerful argument for redressing the neglect of small, isolated habitat patches, for urgently prioritizing their restoration, and for avoiding simplistic application of island biogeography theory in conservation decisions.
SREBP-1a–stimulated lipid synthesis is required for macrophage phagocytosis downstream of TLR4-directed mTORC1
Authors: Lee Jae-Ho , Phelan Peter , Shin Minsang , Oh Byung-Chul , Han Xianlin , Im Seung-Soon , Osborne Timothy F.
Published: December 2018

Significance

There is a growing appreciation for a fundamental connection between lipid metabolism and the innate immune response. Phagocytosis is a key macrophage innate immune response to pathogen exposure, and cytoplasmic membrane expansion is required to surround and capture the target pathogen prior to internalization. Sterol regulatory element binding proteins (SREBPs) are gene regulatory factors that sense the intracellular lipid environment and modulate key genes that drive fatty acid and cholesterol synthesis to maintain lipid homeostasis. In this study, we show that, in mutant cells that lack a key SREBP isoform, phagocytosis is impaired, and we track the defect to altered lipid composition of membrane phospholipids that results in decreased interaction between membrane lipid rafts and the actin cytoskeletal network.
Cold spraying B4C particles reinforced aluminium coatings
Authors: Huang Guosheng , Fu Wei , Ma Li , Li Xiangbo , Wang Hongren
Published: December 2018

Al B4C composites structure manufactured by sintering method suffers from low strength and decomposition. To solve this problem, cold spray technology was used to manufacture Al B4C composite coating on 5083 aluminium alloy. The results indicate that a high content (30 wt-%) B4C reinforced Al coating can be deposited on aluminium substrate through cold spraying. The microstructure of the coating was characterized using scanning electron microscopy. It was found that the cold spray could deposit good quality aluminium coating with bonding strength ranging from 26.5 to 28.2 MPa. The average porosity for this coating in this case is about 1.5%, and the B4C particles distribute uniformly in the coating. Electrochemical tests revealed that the cold sprayed Al + 30% B4C coating has an inferior corrosion resistance to 5083 aluminium alloy in neutral 3.5 wt-% NaCl solution. Cold spray is a talented technology to manufacture Al B4C Composites coating for neutron absorption application.
Developmental regulation of an organelle tether coordinates mitochondrial remodeling in meiosis
Authors: Sawyer Eric M. , Joshi Pallavi R. , Jorgensen Victoria , Yunus Julius , Berchowitz Luke E. , Ünal Elçin
Published: December 2018

Cellular differentiation involves remodeling cellular architecture to transform one cell type to another. By investigating mitochondrial dynamics during meiotic differentiation in budding yeast, we sought to understand how organelle morphogenesis is developmentally controlled in a system where regulators of differentiation and organelle architecture are known, but the interface between them remains unexplored. We analyzed the regulation of mitochondrial detachment from the cell cortex, a known meiotic alteration to mitochondrial morphology. We found that mitochondrial detachment is enabled by the programmed destruction of the mitochondria–endoplasmic reticulum–cortex anchor (MECA), an organelle tether that bridges mitochondria and the plasma membrane. MECA regulation is governed by a meiotic transcription factor, Ndt80, which promotes the activation of a conserved kinase, Ime2. We further present evidence for Ime2-dependent phosphorylation and degradation of MECA in a temporally controlled manner. Our study defines a key mechanism that coordinates mitochondrial morphogenesis with the landmark events of meiosis and demonstrates that cells can developmentally regulate tethering to induce organelle remodeling.
Drug Use and Postoperative Mortality Following Valve Surgery for Infective Endocarditis: A Systematic Review and Meta-analysis
Authors: Hall Ryan , Shaughnessy Michael , Boll Griffin , Warner Kenneth , Boucher Helen W , Bannuru Raveendhara R , Wurcel Alysse G
Published: December 2018

Background

Infective endocarditis (IE) often requires surgical intervention. An increasingly common cause of IE is injection drug use (IDU-IE). There is conflicting evidence on whether postoperative mortality differs between people with IDU-IE and people with IE from etiologies other than injection drug use (non–IDU-IE). In this manuscript, we compare short-term postoperative mortality in IDU-IE vs non–IDU-IE through systematic review and meta-analysis.

Methods

The review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Publication databases were queried for key terms included in articles up to September 2017. Randomized controlled trials, prospective cohorts, or retrospective cohorts that reported on 30-day mortality or in-hospital/operative mortality following valve surgery and that compared outcomes between IDU-IE and non–IDU-IE were included.

Results

Thirteen studies with 1593 patients (n = 341 [21.4%] IDU-IE) were included in the meta-analysis. IDU-IE patients more frequently had tricuspid valve infection, Staphylococcus infection, and heart failure before surgery. Meta-analysis revealed no statistically significant difference in 30-day postsurgical mortality or in-hospital mortality between the 2 groups.

Conclusions

Despite differing preoperative clinical characteristics, early postoperative mortality does not differ between IDU-IE and non–IDU-IE patients who undergo valve surgery. Future research on long-term outcomes following valve replacement is needed to identify opportunities for improved healthcare delivery with IDU-IE.
Uncertainties in Screening and Prevention of Group B Streptococcus Disease
Authors: Le Doare Kirsty , Heath Paul T , Plumb Jane , Owen Natalie A , Brocklehurst Peter , Chappell Lucy C
Published: December 2018

In autumn 2016, the UK Department of Health (now Department of Health and Social Care) convened 2 meetings to discuss how to address research evidence gaps in order to minimize the impact of infant group B streptococcus (GBS) disease in the United Kingdom. At that meeting, a number of research priorities were highlighted, including improving the screening for GBS colonization in pregnant women, offering intrapartum antibiotic prophylaxis and point-of-care testing, and understanding the effect of widespread intrapartum antibiotic use on long-term infant health. Further discussions involved investigating the feasibility of a large prospective study of pregnant women and their infants in order to understand the role of antibodies in the protection against GBS disease in infancy following maternal exposure to GBS colonization. Here, we summarize the research uncertainties identified at that meeting.
Cardiac adenylyl cyclase overexpression precipitates and aggravates age-related myocardial dysfunction
Authors: Mougenot Nathalie , Mika Delphine , Czibik Gabor , Marcos Elizabeth , Abid Shariq , Houssaini Amal , Vallin Benjamin , Guellich Aziz , Mehel Hind , Sawaki Daigo , Vandecasteele Grégoire , Fischmeister Rodolphe , Hajjar Roger J , Dubois-Randé Jean-Luc , Limon Isabelle , Adnot Serge , Derumeaux Geneviève , Lipskaia Larissa
Published: December 2018

Aims

Increase of cardiac cAMP bioavailability and PKA activity through adenylyl-cyclase 8 (AC8) overexpression enhances contractile function in young transgenic mice (AC8TG). Ageing is associated with decline of cardiac contraction partly by the desensitization of β-adrenergic/cAMP signalling. Our objective was to evaluate cardiac cAMP signalling as age increases between 2 months and 12 months and to explore whether increasing the bioavailability of cAMP by overexpression of AC8 could prevent cardiac dysfunction related to age.

Methods and results

Cardiac cAMP pathway and contractile function were evaluated in AC8TG and their non-transgenic littermates (NTG) at 2- and 12 months old. AC8TG demonstrated increased AC8, PDE1, 3B and 4D expression at both ages, resulting in increased phosphodiesterase and PKA activity, and increased phosphorylation of several PKA targets including sarco(endo)plasmic-reticulum-calcium-ATPase (SERCA2a) cofactor phospholamban (PLN) and GSK3α/β a main regulator of hypertrophic growth and ageing. Confocal immunofluorescence revealed that the major phospho-PKA substrates were co-localized with Z-line in 2-month-old NTG but with Z-line interspace in AC8TG, confirming the increase of PKA activity in the compartment of PLN/SERCA2a. In both 12-month-old NTG and AC8TG, PLN and GSK3α/β phosphorylation was increased together with main localization of phospho-PKA substrates in Z-line interspaces. Haemodynamics demonstrated an increased contractile function in 2- and 12-month-old AC8TG, but not in NTG. In contrast, echocardiography and tissue Doppler imaging (TDI) performed in conscious mice unmasked myocardial dysfunction with a decrease of systolic strain rate in both old AC8TG and NTG. In AC8TG TDI showed a reduced strain rate even in 2-month-old animals. Development of age-related cardiac dysfunction was accelerated in AC8TG, leading to heart failure (HF) and premature death. Histological analysis confirmed early cardiomyocyte hypertrophy and interstitial fibrosis in AC8TG when compared with NTG.

Conclusion

Our data demonstrated an early and accelerated cardiac remodelling in AC8TG mice, leading to the development of HF and reduced lifespan. Age-related reorganization of cAMP/PKA signalling can accelerate cardiac ageing, partly through GSK3α/β phosphorylation.
Asymptotic preserving discretization of a Jin–Xin model with implicit equilibrium manifold on a bounded domain
Authors: Seguin Nicolas , Tournus Magali
Published: December 2018

In this paper, we design and analyze a numerical scheme that approximates a Jin–Xin linear system with implicit equilibrium on a bounded domain. This scheme relaxes toward the asymptotic limit of the linear system. The main properties of the limiting scheme are that it does not require to invert the implicit function defining the manifold and that it provides an accurate discretization of the boundary conditions.
Household water sharing: a missing link in international health
Authors: Stoler Justin , Brewis Alexandra , Harris Leila M , Wutich Amber , Pearson Amber L , Rosinger Asher Y , Schuster Roseanne C , Young Sera L
Published: December 2018

Water insecurity massively undermines health, especially among impoverished and marginalized communities. Emerging evidence shows that household-to-household water sharing is a widespread coping strategy in vulnerable communities. Sharing can buffer households from the deleterious health effects that typically accompany seasonal shortages, interruptions of water services and natural disasters. Conversely, sharing may also increase exposure to pathogens and become burdensome and distressing in times of heightened need. These water sharing systems have been almost invisible within global health research but need to be explored, because they can both support and undermine global public health interventions, planning and policy.
PoGO+ polarimetric constraint on the synchrotron jet emission of Cygnus X-1
Authors: Chauvin Maxime , Florén Hans-Gustav , Jackson Miranda , Kamae Tuneyoshi , Kataoka Jun , Kiss Mózsi , Mikhalev Victor , Mizuno Tsunefumi , Takahashi Hiromitsu , Uchida Nagomi , Pearce Mark
Published: December 2018

We report a polarimetric constraint on the hard X-ray synchrotron jet emission from the Cygnus X-1 black hole binary system. The observational data were obtained using the PoGO+ hard X-ray polarimeter in 2016 July, when Cygnus X-1 was in the hard state. We have previously reported that emission from an extended corona with a low polarization fraction is dominating, and that the polarization angle is perpendicular to the disc surface. In the soft gamma-ray regime, a highly polarized synchrotron jet is reported with INTEGRAL observations. To constrain the polarization fraction and flux of such a jet component in the hard X-ray regime, we now extend analyses through vector calculations in the Stokes QU plane, where the dominant corona emission and the jet component are considered simultaneously. The presence of another emission component with different polarization angle could partly cancel out the net polarization. The 90 per cent upper limit of the polarization fraction for the additional synchrotron jet component is estimated as <10 per cent, <5 per cent, and <5 per cent for polarization angle perpendicular to the disc surface, parallel to the surface, and aligned with the emission reported by INTEGRAL data, respectively. From the 20–180 keV total flux of 2.6 × 10−8 erg s−1 cm−2, the upper limit of the polarized flux is estimated as < 3 × 10−9 erg s−1 cm−2.
‘The Natural Foundation of Perfect Efficiency’1: Medical Services and the Victorian Post Office
Authors: McIlvenna Kathleen , Brown Douglas H L , Green David R
Published: December 2018

This article explores the creation of the Post Office medical service. Working for the Post Office was relatively well-paid and an increasing number of doctors were employed. Medical provision expanded with the introduction of non-contributory pensions from mid-century and developed into a comprehensive and nationwide service that was involved at all stages of employment, from initial recruitment through to receiving a pension. Post Office doctors assessed candidates’ fitness for work, checked on sick absences, provided free medicine and advice and visited workers’ homes. Doctors were responsible for determining whether or not a worker should be pensioned off on grounds of ill health. The career of the first Chief Medical Officer, Dr Waller Lewis, also illustrates the range of other areas in which the Post Office medical service became involved, including the clinical assessment and relief of sickness as well as identifying preventative measures to improve health outcomes.
Acquired autoimmune thrombotic thrombocytopenic purpura
Authors: Vacca Vincent M.
Published: December 2018

Acquired autoimmune thrombotic thrombocytopenic purpura (TTP)—the most common form of TTP—is a life-threatening hematologic disease characterized by hemolytic anemia and thrombocytopenia. Acquired autoimmune TTP can cause signs and symptoms of neurologic and other organ involvement, with mortality approaching 90% if the disease is not promptly recognized and treated. Since the introduction of plasma exchange in 1991, the acquired autoimmune TTP survival rate has increased to 78%.
Idiopathic Thrombocytopenic Purpura Induced by Synthetic Cannabinoid
Authors: Castaneira Giselle , Rojas Kelley , Galili Yehuda , Field Zachary , Perez-Perez Ariel , Madruga Mario , Carlan Steve J.
Published: December 2018

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder defined as low platelet count with normal bone marrow in the absence of other causes of thrombocytopenia. It is caused by autoantibodies binding to several platelet surface antigens which lead to premature destruction of the platelet by the reticuloendothelial system. ITP can be primary or secondary, and it is known to be associated with various infections and drugs. K2/Spice, or synthetic marijuana, acts on cannabinoid receptors CB1 (cannabinoid type-1) and CB2 (cannabinoid type-2) with increased binding capacity compared to marijuana. A white male was brought to the emergency department with signs of acute drug toxicity. His urine drug test was negative but he admitted to a year long history of synthetic marijuana use. His platelet count was 12,000/mm3 and he was diagnosed with ITP. After receiving 2 doses of oral dexamethasone his platelets improved. Synthetic cannabinoids are widely available and used psychoactive drugs. Little is known about the complete chemical composition of the synthetic products thus there is relatively little information available on the pharmacodynamic and pharmacokinetic effects. A high index of suspicion is needed to diagnose toxicity to these drugs since there are no readily available on-site lab tests. Currently there exists 1 case report of ITP induced by K2/Spice. Here, we discuss another case of K2/Spice a as a potential cause of immune thrombocytopenia.
Exploring the Role of Regional Anesthesia in the Treatment of the Burn-injured Patient
Authors: Town Cienwen J. , Johnson James , Van Zundert André , Strand Haakan
Published: December 2018

Objectives:

The review article was designed to assess the effectiveness of regional anesthesia (RA), specifically peripheral nerve blocks, in the treatment of burn pain; with noting of clinical indications and contraindications for peripheral nerve block application, along with discussion of evidence-based analgesic strategies for providing improved, comprehensive burn pain management.

Materials and Methods:

A search of relevant literature was performed using CINAHL, PubMed, EMBASE, Web of Science, and SCOPUS with a publication date between January 2005 and December 2017.

Results:

The search yielded 10 results that met criteria. Two randomized control trials were included, though they focused on analgesia for donor-site pain only, 1 clinical trial, 2 case series, 2 retrospective audit, 1 burn protocol, and 2 review articles.

Discussion:

RA techniques are an adjunct therapy currently used worldwide to improve patient pain outcomes and reduce the adverse effects associated with general anesthetic. RA presents a safe and effective intervention for acute pain resulting from burn-acquired injury. This review of current literature supports the use of RA as a treatment to manage pain associated with burn-related care procedures as an addition to multimodal pain treatment. To date there is limited evidence showing the use of RA in the burns’ patient population. In addition, there appear to be no particular risks to using the technique of RA in this group. Further prospective studies are required to provide information about the benefits and limitations of RA.
Prodromal Myocardial Infarction Fatigue
Authors: Blakeman John R.
Published: December 2018

Patients' care-seeking behaviors are often based on the symptoms they experience. Prodromal myocardial infarction symptoms are those symptoms that occur prior to a myocardial infarction, and fatigue is common. However, the concept of prodromal myocardial infarction fatigue has not been explored from a multidimensional perspective using a concept analysis approach. The purpose of this concept analysis was to analyze this concept, using Walker and Avant's (2011) concept analysis methodology. A comprehensive literature search revealed 41 records for analysis. The structure and function of this concept was examined, and an operational definition of prodromal myocardial infarction fatigue was developed.
Complicated Grief of Immediate Family Caregivers
Authors: Mason Tina M. , Tofthagen Cindy S.
Published: December 2018

Grieving is a normal reaction to loss; however, not everyone is able to recover from grief and adjust to a life after the loss. “Complicated grief” (CG) is a term used to describe intense and prolonged bereavement after the loss of a loved one that interferes with normal activities accompanied by destructive thoughts and behaviors. In practice and research, the concept of CG varies in definition and instruments used to measure. This concept analysis examines relevant research related to CG experienced by caregivers to provide a clear, comprehensive definition. Implications for nursing practice and research are explored.
Implications for Paradigm Shift in Nursing
Authors: Younas Ahtisham , Parsons Karen
Published: December 2018

By seeking answers to ontological and epistemological questions, nursing scholars explored the foundations of nursing and articulated the meaning of nursing science from various philosophical perspectives. This ongoing search for advancement and development of nursing aligns with the concept of “normal science” by Thomas Kuhn. Kuhn's science influenced nursing knowledge, resulting in the development of nursing metaparadigm and paradigms. Despite this influence, Kuhn's science's relevance for nursing science received a little scrutinization. This article presents a critical analysis of Kuhn's science and its influence on and relevance for nursing discipline and suggests implications for nursing knowledge development.
Nursing Judgment
Authors: de Tantillo Lila , De Santis Joseph P.
Published: December 2018

Charged with making decisions to protect and enhance patient well-being, a nurse relies on nursing judgment to render effective patient care. Nursing judgment is the culmination of education, experience, and insight that allows nurses to execute the best action possible on behalf of patients. This concept analysis uses the Walker and Avant method to demonstrate the role of nursing judgment in assessments and interventions, delegation of tasks, and prioritization of care. Nurses, other health care collaborators, and recipients of health care should be aware of the role played by nursing judgment to improve patient care and the health care system.
Postactivated B cells in systemic lupus erythematosus: update on translational aspects and therapeutic considerations
Authors: Schrezenmeier Eva , Weißenberg Sarah Y. , Stefanski Ana-Luisa , Szelinski Franziska , Wiedemann Annika , Lino Andreia C. , Dörner Thomas
Published: December 2018

Purpose of review

This review summarizes recent insights and current understanding of the role of postactivated B cells in SLE and related pathogenic and potential therapeutic implications.

Recent finding

B cells are considered key players in SLE and experience from various B-cell-targeted therapies underlines their clinical relevance. In the last years, new insights have been obtained on B-cell abnormalities within the complex pathophysiology of SLE. These insights involve a revised understanding of BCR signaling, that has been reported to be hyperresponsive in the past, but newer studies suggest a postactivation functiotype in terms of reduced BCR and TLR signaling. Despite comprehensive efforts to delineate B-cell abnormalities on assessing large-scale genomic, epigenomic and proteomic data, understanding functional impairments of cellular interactions and subcellular functions remains crucial. A recently identified enhanced protein tyrosine phosphatase (PTP) activity was found in relation to diminished BCR responses in SLE. This finding together with reduced cytokine production upon TLR9 activation appears to mark postactivated lupus B cells. Other studies identified increased PTP activity in line with a gain-of-function mutation of phosphatase PTPN22, one of the strongest SLE risk alleles. Improved understanding of these B cell abnormalities in SLE holds promise to gain further insights in mechanisms of autoimmunity and pave the way for selective therapies targeting key principles of chronic autoimmunity.

SLE B cells (similar as previously described for lupus T cells) are characterized by a postactivation (exhausted) functiotype mandating consideration for innovative therapies.
What Factors Predict the Risk of Proximal Junctional Failure in the Long Term, Demographic, Surgical, or Radiographic?
Authors: Yang Jingyan , Khalifé Marc , Lafage Renaud , Kim Han Jo , Smith Justin , Shaffrey Christopher I. , Burton Douglas C. , Ames Christopher P. , Mundis Gregory M. , Hostin Richard , Bess Shay , Klineberg Eric O. , Hart Robert A. A , Schwab Frank J. , Lafage Virginie
Published: December 2018

Study Design.

Retrospective review of prospective multicenter database.

Objective.

To identify an optimal set of factors predicting the risk of proximal junctional failure (PJF) while taking the time dependency of PJF and those factors into account.

Summary of Background Data.

Surgical correction of adult spinal deformity (ASD) can be complex and therefore, may come with high revision rates due to PJF.

Methods.

Seven hundred sixty-three operative ASD patients with a minimum of 1-year follow-up were included. PJF was defined as any type of proximal junctional kyphosis (PJK) requiring revision surgery. Time-dependent ROC curves were estimated with corresponding Cox proportional hazard models. The predictive abilities of demographic, surgical, radiographic parameters, and their possible combinations were assessed sequentially. The area under the curve (AUC) was used to evaluate models’ performance.

Results.

PJF occurred in 42 patients (6%), with a median time to revision of approximately 1 year. Larger preoperative pelvic tilt (PT) (hazard ratio [HR]=1.044, P = 0.034) significantly increased the risk of PJF. With respect to changes in the radiographic parameters at 6-week postsurgery, larger differences in pelvic incidence-lumbar lordosis (PI-LL) mismatch (HR = 0.924, P = 0.002) decreased risk of PJF. The combination of demographic, surgical, and radiographic parameters has the best predictive ability for the occurrence of PJF (AUC = 0.863), followed by demographic along with radiographic parameters (AUC = 0.859). Both models’ predictive ability was preserved over time.

Conclusions.

Over correction increased the risk of PJF. Radiographic along with demographic parameters have shown the approximately equivalent predictive ability for PJF over time as with the addition of surgical parameters. Radiographic rather than surgical factors may be of particular importance in predicting the development of PJF over time. These results set the groundwork for risk stratification and corresponding prophylactic interventions for patients undergoing ASD surgery.

Level of Evidence: 4
Preoperative Assessment of Bone Quality in Spine Deformity Surgery
Authors: Kuprys Tomas K. , Steinmetz Leah M. , Fischer Charla R. , Protopsaltis Themistocles S. , Passias Peter G. , Goldstein Jeffrey A. , Bendo John A. , Errico Thomas J. , Buckland Aaron J.
Published: December 2018

Study Design.

Retrospective cohort study.

Objective.

The goals of this study were to (A) evaluate preoperative bone quality assessment and intervention practice over time and (B) review the current evidence for bone evaluation in spine fusion surgery.

Summary of Background Data.

Deformity spine surgery has demonstrated improved quality of life in patients; however, its cost has made it controversial. If preoperative bone quality can be optimized then potentially these treatments could be more durable; however, at present, no clinical practice guidelines have been published by professional spine surgical organizations.

Methods.

A retrospective cohort review was performed on patients who underwent a minimum five-level primary or revision fusion. Preoperative bone quality metrics were evaluated over time from 2012 to 2017 to find potential trends. Subgroup analysis was conducted based on age, sex, preoperative diagnosis, and spine fusion region.

Results.

Patient characteristics including preoperative rates of pseudarthrosis and junctional failure did not change. An increasing trend of physician bone health documentation was noted (P = 0.045) but changes in other metrics were not significant. A sex bias favored females who had higher rates of preoperative DXA studies (P = 0.001), Vitamin D 25-OH serum labs (P = 0.005), Vitamin D supplementation (P = 0.022), calcium supplementation (P < 0.001), antiresorptive therapy (P = 0.016), and surgeon clinical documentation of bone health (P = 0.008) compared with men.

Conclusion.

Our spine surgeons have increased documentation of bone health discussions but this has not affected bone quality interventions. A discrepancy exists favoring females over males in nearly all preoperative bone quality assessment metrics. Preoperative vitamin D level and BMD assessment should be considered in patients undergoing long fusion constructs; however, the data for bone anabolic and resorptive agents have less support. Clinical practice guidelines on preoperative bone quality assessment spine patients should be defined.

Level of Evidence: 4
Cabergoline in the Management of Residual Nonfunctioning Pituitary Adenoma
Authors: Batista Rafael L. , Musolino Nina R.C. , Cescato Valter A.S. , da Silva Gilberto O. , Medeiros Raphael S.S. , Herkenhoff Clarissa G.B. , Trarbach Ericka B. , Cunha-Neto Malebranche B.
Published: December 2018

Background:

Complete tumor removal by transsphenoidal surgery is usually difficult for large nonfunctioning pituitary adenomas (NFPAs). A validated medical treatment may be useful for their management. This study evaluates the clinical efficacy of the dopaminergic agonist cabergoline for residual NFPA.

Design, Setting, and Participants:

We conducted a randomized, parallel, open-label clinical trial that compared cabergoline with nonintervention in patients with residual NFPA after transsphenoidal surgery over 2 years. The primary outcome was clinical efficacy (tumor reduction). The secondary outcome was the relationship between tumor dopamine D2 receptor (D2R) expression and clinical responsiveness. Tumor measurements and clinical evaluations were performed every 6 months.

Results:

In total, 59 and 57 individuals were randomly assigned to the study and control groups, respectively. At the end of the study, residual tumor shrinkage, stabilization, and enlargement were observed in 28.8%, 66.1%, and 5.1% of patients, respectively, in the medical-therapy group and in 10.5%, 73.7%, and 15.8% of patients, respectively, in the control group (P=0.01). The progression-free survival rate was 23.2 and 20.8 months for the study and control groups, respectively (P=0.01). D2R was not associated with cabergoline responsiveness. No major side effects were related to cabergoline use.

Conclusions:

Cabergoline was an effective drug for treating residual NFPA, and its use was associated with a high rate of tumor shrinkage (ClinicalTrials.gov NCT03271918).
Population Pharmacokinetic Analysis of Bisoprolol in Patients With Acute Coronary Syndrome
Authors: Momčilović Stefan , Milovanović Jasmina R. , Janković Slobodan M. , Jovanović Andriana , Tasić-Otašević Suzana , Stanojević Dragana , Krstić Miroslav , Šalinger-Martinović Sonja , Radojković Danijela Djordjević , Damjanović Miodrag , Živković Milan , Maričić Bojan , Ranković Goran , Mihajlović Aleksandar , Nikolić Valentina N.
Published: December 2018

To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed β1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625–7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.
Comparison of Candesartan and Angiotensin-(1-7) Combination to Mito-TEMPO Treatment for Normalizing Blood Pressure and Sympathovagal Balance in (mREN2)27 Rats
Authors: Nautiyal Manisha , Shaltout Hossam A. , Chappell Mark C. , Diz Debra I.
Published: December 2018

Hypertensive transgenic (mRen2)27 rats exhibit impaired baroreflex sensitivity (BRS) for control of heart rate (HR). Intracerebroventricular infusion of Ang-(1-7) improves indices of vagal BRS independent of lowering mean arterial pressure (MAP), whereas AT1 receptor blockade normalizes MAP and indices of sympathetic tone without correcting the vagal BRS. Scavenging cellular reactive oxygen species (ROS) with tempol in brain fails to correct either hypertension or sympathovagal balance in these animals, despite reports that mitochondrial ROS contributes to Ang II–infusion hypertension. To examine effects of a putative preferential mitochondrial ROS scavenger in the brain of (mRen2)27 rats, ICV infusions of Mito-TEMPO (3.2 μg/2.5 μL/h) were compared with artificial cerebrospinal fluid (aCSF; 2.5 μL/h) and combination AT1 receptor antagonist candesartan (CAN: 4 μg/2.5 μL/h) plus Ang-(1-7) (0.1 μg/2.5 μL/h) treatment. MAP was lower after CAN + Ang-(1-7) treatment, and both vagal and sympathetic components of BRS and sympathovagal balance were improved. By contrast, Mito-TEMPO improved sympathetic components of BRS and tended to improve overall sympathovagal balance but failed to alter MAP in this model of hypertension. Although further studies are required to determine whether Mito-TEMPO or CAN + Ang-(1-7) treatment at the doses used altered mitochondrial ROS, optimal therapeutic benefits are achieved by shifting the balance from Ang II toward Ang-(1-7) in this model of chronic RAS-dependent hypertension.
Pharmacogenetics Biomarkers Predictive of Drug Pharmacodynamics as an Additional Tool to Therapeutic Drug Monitoring
Authors: Haufroid Vincent , Picard Nicolas
Published: December 2018

Conventional therapeutic drug monitoring refers to the individualization of drug dosage by maintaining plasma or blood drug concentrations within a targeted therapeutic range. Accordingly, an individualized dose is proposed to the clinician according to the drug plasma or blood concentration using an a posteriori approach. Pharmacogenetics (PGx) has recently emerged as an additional tool to refine dose selection or, more interestingly to select, a priori, the first dose to administer. To date, the vast majority of genes explored in the context of PGx are those coding for metabolizing enzymes or membrane drug transporters, which mainly influence drug pharmacokinetics parameters. Indeed, among the 94 PGx-based drug dosing guidelines currently published by the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group on PharmGKB web site, 81 (86%) are associated with the genotype determination of either a metabolizing enzyme or a membrane drug transporter, whereas only 13 (14%) are associated with the genotype determination of a pharmacodynamics (PD)-associated gene. In this article, we describe selected PGx biomarkers that predict or could predict PD (both in terms of efficacy and toxicity). First, the most relevant clinical applications already subject to validated international guidelines (Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group), and ready to be implemented in routine clinical settings, are discussed to illustrate the clinical potential of PD-associated PGx biomarkers (G6PD, HLA-B*57:01, HLA-B*15:02, and VKORC1). Then, to illustrate not only the research potential of such biomarkers but also the complexity of PGx–PD relationships, the case of immunosuppressive drugs (for which conventional therapeutic drug monitoring is widely accepted) is extensively described with the potential to include some of these PGx biomarkers in future PGx dosing guidelines.
Cell-based immunotherapy in gynecologic malignancies
Authors: Schaar Bruce , Krishnan Venkatesh , Tallapragada Supreeti , Chanana Anita , Dorigo Oliver
Published: December 2018

Purpose of review

To provide an update on cell-based immunotherapies in solid tumors particularly in gynecological cancers.

Recent findings

Improvements have been made in engineering T cells to overcome the immunosuppressive environment in ovarian cancer. Significant efforts are underway to create ‘off the shelf’ cell therapies which leverage natural killer (NK) cells and would not rely on engineering a patient's T cells.

Efforts to target solid tumors using cell-based therapies are expanding into cell types other than T cells (NK cells and macrophages) which may have a lower risk of significant side effects and higher efficacy in solid tumors than chimeric antigen receptor T cells.
COMPARATIVE EVALUATION OF ANTERIOR SEGMENT OPTICAL COHERENCE TOMOGRAPHY, ULTRASOUND BIOMICROSCOPY, AND INTRAOCULAR PRESSURE CHANGES AFTER PANRETINAL PHOTOCOAGULATION BY PASCAL AND CONVENTIONAL LASER
Authors: Lata Suman , Venkatesh Pradeep , Temkar Shreyas , Selvan Harathy , Gupta Viney , Dada Tanuj , Upadhyay Ashish D. , Sihota Ramanjit
Published: December 2018

Purpose:

To compare intraocular pressure, anterior segment optical coherence tomography, and ultrasound biomicroscopy parameters over 3 months after panretinal photocoagulation (PRP) for proliferative diabetic retinopathy after 1 of 2 sittings by conventional laser (half PRP) and a single sitting of Pattern Scan Laser (PASCAL) PRP.

Methods:

This was a prospective, randomized, interventional study. All tests were performed at baseline, and at 1, 6, and 24 hours, and 1, 4, 8, and 12 weeks after PRP.

Results:

The intraocular pressure at 1 hour and 6 hours after PRP was significantly raised in both groups. Mean intraocular pressure was 21.17 ± 4.01 mmHg after PASCAL and 17.48 ± 3 mmHg after conventional laser at 1 hour, P < 0.001. On anterior segment optical coherence tomography, conventional laser PRP caused a more significant narrowing of angle-opening distance (AOD750) and trabecular-iris space area (TISA 500), P = 0.03 and 0.04, respectively, on Day 1. Ultrasound biomicroscopy showed a significantly narrow angle in both groups on Day 1. A significant increase in ciliary body thickness was observed in both groups, with 57.1% of PASCAL and 100% of conventionally treated eyes showing ciliary effusion on Day 1 that decreased but persisted for the next 3 months.

Conclusion:

Performing PRP in sittings, prescribing previous glaucoma medications in patients at risk, and recording intraocular pressure an hour after the PRP could decrease complications.
Hypohidrotic Ectodermal Dysplasia: A Rare Disorder With Bilateral Infantile Glaucoma
Authors: Dubey Suneeta , Bhoot Madhu , Jain Kanika
Published: December 2018

Ectodermal dysplasia (ED) is a disorder that occurs due to abnormalities of ectodermal structures such as skin, teeth, hair, nails, and eccrine glands. Approximately 200 different conditions have been identified as ED, the most common being hypohidrotic ED. It is characterized by hypotrichosis (sparse scalp or body hair), hypodontia (absent or malformed teeth), and hypohidrosis (reduced ability to sweat). It is also associated with distinctive facial features, such as the prominent forehead, thick lips, flattened nasal bridge, and thin wrinkled skin. Ocular anomalies are less frequently observed, the most common ones being dysplasia of the lacrimal gland or meibomian gland that leads to dry eye and variable corneal involvement. We report a case of a 9-year-old child of hypohidrotic ED presenting with bilateral infantile glaucoma managed by the implantation of glaucoma drainage devices (GDDs) after a failed trabeculotomy and trabeculectomy in both eyes.
A scoping review of Advanced Practice Registered Nurses Consensus Model outcomes: Part four of a four-part series on critical topics identified by the 2015 Nurse Practitioner Research Agenda
Authors: Litchman Michelle L. , Schlepko Thomas , Rowley Tom , McFarland Mary , Fiander Michelle
Published: December 2018

Background and purpose:

The Advanced Practice Registered Nurses (APRN) Consensus Model was produced by the APRN Joint Dialogue Group in 2008. The aim of the Consensus Model is to guide state boards on the implementation of APRN practice components, including licensure, accreditation, certification, and education and to clarify the legal scope of practice and APRN roles. The purpose of this scoping review and gap analysis was to appraise the evidence related to patient, nurse practitioner (NP) and organizational outcomes resulting from the Consensus Model.

Methods:

A scoping review of research studies and grey literature reports was conducted and focused on the outcomes and key concepts related to the Consensus Model. Areas of foci included patients, NPs, and organizations. A subsequent gap analysis was conducted.

Conclusions:

Several positive findings related to the Consensus Model, or components thereof, were identified for patient, NP, and organizational outcomes on various levels. Research gaps exist. Additional research is needed to fully evaluate the health outcomes on a broader scale.

Implications for practice:

Existing evidence may support NPs and supporting organizations to further legislative efforts to more fully implement the Consensus Model nationwide.
Academic nursing scholarship redefined
Authors: Hartjes Tonja M.
Published: December 2018

The American Association of Colleges of Nursing (AACN) last defined academic nursing scholarship in 1999. The AACN recognized faculty scholarship must align with the increasingly complex and dynamic health care environment to prepare nurses for an ever-changing future. The new, broader definition recognizes multiple ways of knowing and values all scholarly contributions, which affect nursing science and the health care system. The alignment of faculty scholarship to the practice of nursing will ensure high-quality education, influencing the next generation of nurses. This new position statement also provides clarity as to valued activities within the faculty role, which will assist administrative faculty who struggle with appointment, tenure, and promotion criteria. This column will provide a summary of the new position statement and exemplars of activities within the faculty role of research, practice, and teaching.
Genetics of Usher Syndrome: New Insights From a Meta-analysis
Authors: Jouret Guillaume , Poirsier Céline , Spodenkiewicz Marta , Jaquin Clémence , Gouy Evan , Arndt Carl , Labrousse Marc , Gaillard Dominique , Doco-Fenzy Martine , Lebre Anne-Sophie
Published: December 2018

Objective:

To describe the genetic and phenotypic spectrum of Usher syndrome after 6 years of studies by next-generation sequencing, and propose an up-to-date classification of Usher genes in patients with both visual and hearing impairments suggesting Usher syndrome, and in patients with seemingly isolated deafness.

Study Design:

The systematic review and meta-analysis protocol was based on Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed 1) a meta-analysis of data from 11 next-generation sequencing studies in 684 patients with Usher syndrome; 2) a meta-analysis of data from 21 next-generation studies in 2,476 patients with seemingly isolated deafness, to assess the involvement of Usher genes in seemingly nonsyndromic hearing loss, and thus the proportion of patients at high risk of subsequent retinitis pigmentosa (RP); 3) a statistical analysis of differences between parts 1) and 2).

Results:

In patients with both visual and hearing impairments, the biallelic disease-causing mutation rate was assessed for each Usher gene to propose a classification by frequency: USH2A: 50% (341/684) of patients, MYO7A: 21% (144/684), CDH23: 6% (39/684), ADGRV1: 5% (35/684), PCDH15: 3% (21/684), USH1C: 2% (17/684), CLRN1: 2% (14/684), USH1G: 1% (9/684), WHRN: 0.4% (3/684), PDZD7 0.1% (1/684), CIB2 (0/684). In patients with seemingly isolated sensorineural deafness, 7.5% had disease-causing mutations in Usher genes, and are therefore at high risk of developing RP. These new findings provide evidence that usherome dysfunction is the second cause of genetic sensorineural hearing loss after connexin dysfunction.

Conclusion:

These results promote generalization of early molecular screening for Usher syndrome in deaf children.
Patients’ Online Perception and Ratings of Neurotologists
Authors: Goshtasbi Khodayar , Lehrich Brandon M. , Moshtaghi Omid , Abouzari Mehdi , Sahyouni Ronald , Bagheri Kian , Moshtaghi Afsheen , Tajran Sarah D. , Lee Lauren , Lin Harrison W. , Djalilian Hamid R.
Published: December 2018

Objectives:

To assess and characterize patients’ online ratings and comments of neurotologists and determine factors that correlate with higher ratings.

Methods:

All the American Neurotology Society members were queried on Healthgrades, Vitals, RateMDs, Yelp, and Google from March to June 2018. All ratings were normalized for comparison on a five-point Likert scale. All comments were categorized based on context and for positive/negative aspect.

Results:

Of the 560 American Neurotology Society members, 465 (83%) were rated on at least one online platform. Of those rated, 420 (90%) were on Healthgrades, 392 (84%) on Vitals, 283 (61%) on RateMDs, 232 (50%) on Google, and 56 (12%) on Yelp. Across all platforms, the average overall rating was 4.06 ± 0.68 (range: 1.00–5.00). There were significant positive correlations between overall rating and specific ratings (p < 0.01) on individual topics. Moreover, categorizing 5,317 narrative comments elicited the majority to be related to perceived physician bedside manner and clinical outcome. Although the number of positive comments outnumbered the negative ones, only the negative comments correlated (negatively) with the overall score (p < 0.01). Attending a top 25- or 50-medical schools or residency programs did not correlate with their rating.

Conclusions:

Online ratings and comments for neurotologists are highly dependent on patient perceptions of physician competence, caring bedside manner, and office management. Minimizing the number of negative comments, especially regarding perceived physicians’ professionalism and communication, clinical outcome, bedside manners, and office management, leads to higher calculated overall scores and online perception.