bluuebunny/crossref_metadata_2025 huggingface dataset:
When Outpatient Care Is Not Enough: Successful Use of an Inpatient Behavioral Intervention for a Child With ARFID
Authors: Lenz Katrina R. , Mitan Laurie A. , Kleinhenz Susan R. , Matthews Abigail
Published: August 2018

Avoidant/restrictive food intake disorder (ARFID) is characterized by restrictive eating in the absence of body image disturbance or drive for thinness, resulting in the persistent failure to meet appropriate nutritional and/or energy needs and/or psychosocial impairment. ARFID is a heterogeneous diagnosis with diverse etiologies. Thus, identification of best practice guidelines and evidence-based treatments for ARFID is challenging and, to our knowledge, randomized treatment studies have not been published. Existing literature promotes a multidisciplinary care approach that integrates behavioral, cognitive behavioral, and family-based interventions. In this report, we present the case of an 8-year-old female with ARFID who began restricting her food and fluid intake following a viral illness. The patient also choked on a lozenge at school and peers laughed in response, resulting in heightened fears of eating, subsequent dehydration, and admission to a gastroenterology unit at a pediatric hospital. While hospitalized, she was diagnosed with ARFID, a nasogastric tube (NGT) was placed, and was referred to outpatient eating disorder specialists. Despite participating in 16-outpatient therapy sessions, progress was limited and the patient was medically admitted to safely remove the NGT in the context of behavioral interventions targeting food refusal. This case report describes the successful use of an intensive inpatient behavioral intervention used for the patient, which resulted in the rapid resumption of food and fluid intake, by mouth. This case study supports the use of such intervention for ARFID when sufficient progress is not achieved in outpatient care.
Transformative Sustainability Learning Within a Material-Discursive Ontology
Authors: O’Neil Joy Kcenia
Published: August 2018

In this article, sustainability education is defined within the three orders of change—education about, for, and as sustainability. The third-order change, education as sustainability is defined as transformative sustainability education—an ontological change in how humans and the material world relate. The dominant higher educational paradigm tends to educate about subject matter (i.e., sustainability) distanced from material and focuses on individual human cognition. This does not go far enough to enact sustainable change. Rather, a human and nonhuman materialization within teaching and learning is explained through agential realism, as conceptualized by Barad. The author narrates her way through her own transformative learning journey as an environmental science and sustainability educator going from a reductionist paradigm instructor into a relationality paradigm educator living into sustainability. From dualist teaching in environmental and human health where the study of food was an object, she undertook teaching and research on the pedagogy of food as a material subject. The findings explore the practice of agential realism in relation to the field of transformative sustainability education, namely, that teaching and learning intra-actively engages body, mind, and all material, including food, water, soil, trees, people, and communities. This is a profoundly transformative pedagogic shift in higher education. Whether we teach sustainability-related subject matter or not, a relational ontology of teaching and learning has the potential to create the conditions for a transformative learning process through an iterative reconfiguring of our relationality—moving towards a social and ecologically sustainable society.
Coping With Perceived Abusive Supervision: The Role of Paranoia
Authors: Lopes Barbara C. , Kamau Caroline , Jaspal Rusi
Published: August 2018

Two studies (a cross-sectional survey of 90 U.K. workers and an experiment with 100 U.K. workers) examined the cognitive and behavioral effects of abusive supervision. Both studies confirmed the hypothesis that workers who experience abusive supervision show paranoia and that makes them more prone to a type of cognitive error called the “sinister attribution error.” This is where workers misattribute innocent workplace events such as tripping over something or hearing colleagues laughing to malevolent motives such as wanting to harm or mock them. Study 1 also showed that abusive supervision is associated with lower well-being. Perceived organizational support buffers these effects, and this is associated with workers making fewer sinister attribution errors, thereby protecting well-being. Study 2 explored the role of contextual cues by exposing workers to images of abusive supervision. This increased their paranoia and contributed to workers making sinister attribution errors when they were asked to interpret workplace events. Moreover, depending on the types of contextual cues, workers were more likely to express the intention of workplace deviance after thinking about past experiences of abusive supervision. We recommend that corporate ethical responsibilities include training managers and workers about the negative cognitive and mental health effects of abusive supervision.
Contingency management intervention targeting co-addiction of alcohol and drugs among American Indian adults: Design, methodology, and baseline data
Authors: Burduli Ekaterina , Skalisky Jordan , Hirchak Katherine , Orr Michael F , Foote Albert , Granbois Alexandria , Ries Richard , Roll John M , Buchwald Dedra , McDonell Michael G , McPherson Sterling M
Published: August 2018

Background/Aims

American Indian adults have some of the highest alcohol abstinence rates compared to the overall US population. Despite this, many American Indian people are more likely to concurrently use alcohol and illicit drugs and are less likely to participate and remain in outpatient treatment for alcohol and other drug use compared to the general US population. There is limited knowledge about effective interventions targeting alcohol and drug co-addiction among American Indian adults. Contingency management is a behavioral intervention designed to increase drug abstinence by offering monetary incentives in exchange for drug and alcohol negative urine samples. We aim to evaluate and describe a culturally tailored contingency management intervention to increase alcohol and other drug abstinence among American Indian adults residing in a Northern Plains reservation.

Methods

This 2 × 2 factorial, randomized controlled trial currently includes 114 American Indian adults with alcohol and/or drug dependence who are seeking treatment. Participants were randomized into one of four groups that received (1) contingency management for alcohol, (2) contingency management for other drug, (3) contingency management for both substances, or (4) no contingency management for either substance. We present descriptive, baseline data to characterize the sample and describe the modified contingency management approach that is specific to the community wherein this trial was being conducted.

Results

The sample is 49.1% male, with an average age of 35.8 years (standard deviation = 10.4 years). At baseline, 43.0% of the sample tested positive for ethyl glucuronide, 50.9% of participants self-reported methamphetamine as their most used drug, 36.8% self-reported cannabis, and 12.3% self-reported prescription opiates as their most used drug. Among randomized participants, 47.4% tested positive for cannabis, 28.1% tested positive for methamphetamine, 16.7% tested positive for amphetamines, and 2.1% tested positive for opiates.

Conclusion

This is the first study to examine a culturally tailored contingency management intervention targeting co-addiction of two substances among American Indian adults. By establishing a tribal–university partnership to adapt, implement, and evaluate contingency management, we will increase the literature on evidence-based addiction treatments and research, while improving trust for addiction interventions among American Indian communities through ongoing collaboration. Moreover, results have implications for the use of contingency management as an intervention for co-addiction in any population.
A randomized controlled trial to test efficacy and safety of thrombectomy in stroke with extended lesion and extended time window
Authors: Bendszus Martin , Bonekamp Susanne , Berge Eivind , Boutitie Florent , Brouwer Patrick , Gizewski Elke , Krajina Antonin , Pierot Laurent , Randall Gary , Simonsen Claus Z. , Zeleňák Kamil , Fiehler Jens , Thomalla Götz
Published: August 2018

Rationale

The benefit of thrombectomy in patients with intracranial large vessel occlusion of the anterior circulation has been shown in selected patients in previous randomized controlled trials, but patients with extended ischemic lesions were excluded in the majority of these trials. TENSION aims to demonstrate efficacy and safety of thrombectomy in patients with extended lesions in an extended time window (up to 12 h from onset or from last seen well).

Design

TENSION is an investigator-initiated, randomized controlled, open label, blinded endpoint, European, two-arm, postmarket study to compare the safety and effectiveness of thrombectomy as compared to best medical care alone in stroke patients with extended stroke lesions defined by an Alberta Stroke Program Early Computed Tomography Scan score of 3–5 and in an extended time window. In an adaptive design study, up to 665 patients will be randomized.

Outcomes

Primary efficacy endpoint will be clinical outcome defined by the modified Rankin Scale at 90-day poststroke. The main safety endpoint will be death and dependency (modified Rankin Scale 4–6) at 90 days. Additional effect measures include adverse events, health-related quality of life, poststroke depression, and costs utility assessment.

Discussion

TENSION may make effective treatment available for patients with severe stroke in an extended time window, thereby improving functional outcome and quality of life of thousands of stroke patients and reducing the individual, societal, and economic burden of death and disability resulting from severe stroke. TENSION is registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier NCT03094715).
Rethinking countermemory: Black-Jewish negotiations in rap music
Authors: Wegner Jarula MI
Published: August 2018

The concept of countermemory is frequently used in various, sometimes contradictory ways. This essay aims at further clarifying the concept of countermemory by highlighting its potentials and limits. After revisiting Michel Foucault’s initial use of countermemory, the concept is analysed in three case studies of Black-Jewish negotiations in US Rap music. The analysis shows that the discourse of Black-Jewish relations entered rap music in the 1980s and continues well into the twenty-first century. The concept of countermemory has at least four characteristics. It is necessarily related and in opposition to another memory. It employs two different time horizons and enables transcultural memory negotiations. Finally, there are instances of moderate and radical uses of countermemory. Some characteristics are essential to the concept, while others only occasionally appear. Countermemories can be reactionary or progressive, constructive or destructive, factual or fictitious.
The mental health review
Authors: Shekhawat Satpal Singh , Chathley Anuj Sean
Published: August 2018

GPs provide care to a large number of patients with mental health problems, and regularly perform mental health reviews. This article aims to highlight the need for a comprehensive review of patients diagnosed with severe mental illness and introduces a template to help complete the mental health review. The article focuses on the mental health review of patients with a diagnosis of schizophrenia (and other psychotic disorders), bipolar affective disorder and severe depression.
Confidentiality
Authors: Knight Selena , Papanikitas Andrew
Published: August 2018

A commitment to safeguarding confidentiality is essential in ensuring patients’ trust. With increasingly complex models of healthcare, changing uses of personal patient data, and sharing of patient information between services, confidentiality can be difficult to maintain in the day-to-day practice of primary care. This article summarises the ethical and legal basis of confidentiality, describes circumstances where confidentiality may be overridden, and considers current and future challenges in practice.
Activation of viral defense signaling in cancer
Authors: Gonzalez-Cao Maria , Karachaliou Niki , Santarpia Mariacarmela , Viteri Santiago , Meyerhans Andreas , Rosell Rafael
Published: August 2018

A coordinated action of innate and adaptive immune responses is required to efficiently combat a microbial infection. It has now become clear that cancer therapies also largely benefit when both arms of the immune response are engaged. In this review, we will briefly describe the current knowledge of innate immunity and how this can be utilized to prime tumors for a better response to immune checkpoint inhibitors. Comments on compounds in development and ongoing clinical trials will be provided.
Towards precision medicine: linking genetic and cellular heterogeneity in gastric cancer
Authors: Carrasco-Garcia Estefania , García-Puga Mikel , Arevalo Sara , Matheu Ander
Published: August 2018

Molecular and cellular heterogeneity are phenomena that are revolutionizing oncology research and becoming critical to the idea of personalized medicine. Recent comprehensive molecular profiling has identified molecular subtypes of gastric cancer (GC) and linked them to clinical information. Moreover, GC stem cells (gCSCs) have been identified and found to be responsible for GC initiation and progression, Helicobacter pylori oncogenic action and therapy resistance. Addressing molecular heterogeneity is critical for achieving an optimal therapeutic approach against GC as well as targeting gCSCs. In this review, we outline the implications of molecular and cellular heterogeneity in the treatment of GC and we summarize the clinical impact of the most important regulators of gCSCs.
Effect of an educational training intervention on rapid tranquillisation usage – a pilot nursing study in a public hospital in Singapore
Authors: Balasundaram Bharathi , Loh Soak Yee , Nadkarni Pallavi , Jiang Li Na , Jayaram Mahesh , Kam Jia Wen , Yap Hwa Ling , Shashu Ayengar Krishnasamy , Bai Jing Yuan
Published: August 2018

Background:

Studies evaluating nursing educational initiatives in rapid tranquillisation procedures are lacking.

Objective:

This pilot study in a public hospital in Singapore evaluated the effect of an educational training intervention on knowledge and confidence of nurses using rapid tranquillisation in two medical wards.

Method:

The study design was a pilot pre- and post-test single-group design on a voluntary sample of 75 nurses. The educational training intervention comprised of a 60 min interactive presentation followed by a small-group-based case discussion conducted by an advanced nurse practitioner. Knowledge was measured using a ‘test the knowledge’ questionnaire; a Likert scale measured perceived level of confidence.

Results:

The knowledge score (overall score = 11) was significantly improved from pre-training (average score: 5.1 (standard deviation, 1.3)) to post-training (average score: 8.1 (standard deviation, 1.8)), t = −12.61, p < 0.001. The participants were more confident after training ( p < 0.001).

Conclusion:

This study has shown that a classroom training intervention of nurses in rapid tranquillisation procedures improved knowledge and confidence in dealing with patient violence in hospitals and added to the safe practice of rapid tranquillisation. Further studies evaluating the long-term and clinical impact of training with more rigorous study designs are needed to replicate these promising findings.
Using Stories in Elementary School Counseling: Brief, Narrative Techniques
Authors: Eppler Christie , Olsen Jacob A. , Hidano Lory
Published: August 2018

This article describes using stories and story-telling techniques so that elementary professional school counselors can facilitate brief, narrative counseling. These approaches help counselors and students build rapport while assisting in understanding and externalizing the problem. Additionally, these interventions may help generate ideas for unique and positive academic, personal/social, and career outcomes. This article will address four story-based techniques for use in elementary school counseling: biblionarrative, displaced communication, bibliocounseling, and using movie clips.
School Counselor Dispositions as Predictors of Data Usage
Authors: Holcomb-Mccoy Cheryl , Ileana Gonzalez , Georgina Johnston
Published: August 2018

This article examined school counselor dispositions (e.g., general self-efficacy, counselor self-efficacy, openness to change, commitment to counseling improvement/professional development) that predict data usage among K-12 professional school counselors. For the study, 130 professional school counselors from Maryland and Virginia completed the School Counselor Attribute and Data Usage Survey. Results indicated that school counselor self-efficacy and general self-efficacy best predict school counselor data usage.
A National Study of the Current Status of State School Counseling Models
Authors: Martin Ian , Carey John , Karen Decoster
Published: August 2018

A national survey was conducted using a structured interview to investigate the status of school counseling models in all 50 states and the District of Columbia. Findings determined that 17 states have established models, 24 states are progressing in model implementation, and 10 states are at a beginning stage of model development. Implications for state-level practice, professional advocacy, school counseling policy, and future research are discussed.
Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling
Authors: Xu Fei , Cui Wen-Qiang , Wei Ying , Cui Jie , Qiu Jian , Hu Ling-Li , Gong Wei-Yi , Dong Jing-Cheng , Liu Bao-Jun
Published: August 2018

Background

Accumulating evidence suggests that M2-polarized tumor-associated macrophages (TAMs) play an important role in cancer progression and metastasis, making M2 polarization of TAMs an ever more appealing target for therapeutic intervention. Astragaloside IV (AS-IV), a saponin component isolated from Astragali radix, has been reported to inhibit the invasion and metastasis of lung cancer, but its effects on TAMs during lung cancer progression have not been investigated.

Methods

Human THP-1 monocytes were induced to differentiate into M2 macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate (PMA). We used the lung cancer cell lines A549 and H1299 cultured in conditioned medium from M2 macrophages (M2-CM) to investigate the effects of AS-IV on tumor growth, invasion, migration, and angiogenesis of lung cancer cells. Macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression were analyzed by flow cytometry and quantitative PCR. The activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways that mediate M2-CM–promoted tumor migration was detected using western blotting.

Results

Here we found that AS-IV significantly inhibited IL-13 and IL-4–induced M2 polarization of macrophages, as illustrated by reduced expression of CD206 and M2-associated genes, and that AS-IV suppressed the M2-CM–induced invasion, migration, and angiogenesis of A549 and H1299 cells. In vivo experiments demonstrated that AS-IV greatly inhibited tumor growth and reduced the number of metastases of Lewis lung cancer. The percentage of M2 macrophages was decreased in tumor tissue after AS-IV treatment. Furthermore, AS-IV inhibited AMPKα activation in M2 macrophages, and silencing of AMPKα partially abrogated the inhibitory effect of AS-IV.

Conclusions

AS-IV reduced the growth, invasion, migration, and angiogenesis of lung cancer by blocking the M2 polarization of macrophages partially through the AMPK signaling pathway, which appears to play an important role in AS-IV’s ability to inhibit the metastasis of lung cancer.
Rationale and development of a business case for antimicrobial stewardship programs in acute care hospital settings
Authors: Morris A. M. , Rennert-May E. , Dalton B. , Daneman N. , Dresser L. , Fanella S. , Grant J. , Keynan Y. , Le Saux N. , McDonald J. , Shevchuk Y. , Thirion D. , Conly J. M.
Published: August 2018

Background

Antimicrobial stewardship programs (ASPs) have been shown to reduce inappropriate antimicrobial use and its consequences. However, these programs lack legislative requirements in many places and it can be difficult to determine what human resources are required for these programs and how to create a business case to present to hospital administrators for program funding. The objectives of the current paper were to review legislative requirements and outline human resource requirements for ASPs, and to create a base business case for ASPs.

Methods

A working group of antimicrobial stewardship experts from across Canada met to discuss the necessary components for creation of a business case for antimicrobial stewardship. A narrative review of the literature of the regulatory requirements and human resource recommendations for ASPs was conducted. Informed by the review and using a consensus decision-making process, the expert working group developed human resource recommendations based on a 1000 bed acute care health care facility in Canada. A spreadsheet based business case model for ASPs was also created.

Results

Legislative and /or regulatory requirements for ASPs were found in 2 countries and one state jurisdiction. The literature review and consensus development process recommended the following minimum human resources complement: 1 physician, 3 pharmacists, 0.5 program administrative and coordination support, and 0.4 data analyst support as full time equivalents (FTEs) per 1000 acute care beds. Necessary components for the business case model, including the human resource requirements, were determined to create a spreadsheet based model.

Conclusions

There is evidence to support the negative outcomes of inappropriate antimicrobial use as well as the benefits of ASPs. Legislative and /or regulatory requirements for ASPs are not common. The available evidence for human resource recommendations for ASPs using a narrative review process was examined and a base business case modelling scenario was created. As regulatory requirements for ASPs increase, it will be necessary to create accurate business cases for ASPs in order to obtain the necessary funding to render these programs successful.
Risk of Bleomycin-Related Pulmonary Toxicities and Operative Morbidity After Postchemotherapy Retroperitoneal Lymph Node Dissection in Patients With Good-Risk Germ Cell Tumors
Authors: Calaway Adam C. , Foster Richard S. , Adra Nabil , Masterson Timothy A. , Albany Costa , Hanna Nassar H. , Einhorn Lawrence H. , Cary Clint
Published: August 2018

Purpose

Three cycles of bleomycin, etoposide, and cisplatin (BEP × 3) or four cycles of etoposide and cisplatin (EP × 4) are first-line chemotherapy regimens for men with International Germ Cell Cancer Collaborative Group (IGCCCG) good-risk germ cell tumors (GCTs). We determined whether inclusion of bleomycin affected pulmonary and operative morbidity after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).

Patients and Methods

We queried our database to identify IGCCCG good-risk patients who received BEP × 3 or EP × 4 induction chemotherapy before PC-RPLND from 2006 to 2016. Patients who received combination regimens were excluded. The primary outcomes of interest were pulmonary morbidity (prolonged intubation, reintubation, supplemental oxygen use, intensive care unit stay) and operative morbidity (operative time, length of stay, concomitant procedures, estimated blood loss).

Results

We analyzed 234 patients (191 BEP × 3 v 43 EP × 4). All patients were extubated immediately after the operation. None were reintubated or discharged on oxygen. Two patients in each cohort required an intensive care unit stay for nonpulmonary reasons. Patients treated with BEP required shorter use of supplemental oxygen (0.99 v 1.63 days; P = .005). No significant differences were found in preoperative mass size ( P = .42) or concomitant surgeries ( P = .58). Operative time was significantly shorter (131 v 170 minutes; P < .01), and estimated blood loss was considerably less (194 v 226 mL; P < .01) in patients treated with BEP. Length of stay was shorter in patients treated with BEP (3.3 v 3.9 days; P < .01).

Conclusion

In a modern surgical cohort, the inclusion of bleomycin does not seem to influence pulmonary morbidity, operative difficulty, or nonpulmonary postoperative complications after PC-RPLND in men with IGCCCG good-risk GST.
Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Epidermal Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR-Mutated, MET Factor–Dysregulated Non–Small-Cell Lung Cancer
Authors: Wu Yi-Long , Zhang Li , Kim Dong-Wan , Liu Xiaoqing , Lee Dae Ho , Yang James Chih-Hsin , Ahn Myung-Ju , Vansteenkiste Johan F. , Su Wu-Chou , Felip Enriqueta , Chia Vincent , Glaser Sabine , Pultar Philippe , Zhao Sylvia , Peng Bin , Akimov Mikhail , Tan Daniel S.W.
Published: August 2018

Purpose

MET dysregulation occurs in up to 26% of non–small-cell lung cancers (NSCLCs) after epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) treatment. Capmatinib (INC280) is a potent and selective MET inhibitor with preclinical activity in combination with gefitinib in EGFR-mutant, MET-amplified/overexpressing models of acquired EGFR-TKI resistance. This phase Ib/II study investigated the safety and efficacy of capmatinib plus gefitinib in patients with EGFR-mutated, MET-dysregulated (amplified/overexpressing) NSCLC who experienced disease progression while receiving EGFR-TKI treatment.

Methods

Patients in phase Ib received capmatinib 100- to 800-mg capsules once per day or 200- to 600-mg capsules or tablets twice per day, plus gefitinib 250 mg once per day. Patients in phase II received the recommended phase II dose. The primary end point was the overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Results

Sixty-one patients were treated in phase Ib, and 100 were treated in phase II. The recommended phase II dose was capmatinib 400 mg twice per day plus gefitinib 250 mg once per day. Preliminary clinical activity was observed, with an ORR across phase Ib/II of 27%. Increased activity was seen in patients with high MET-amplified tumors, with a phase II ORR of 47% in patients with a MET gene copy number ≥ 6. Across phases Ib and II, the most common drug-related adverse events were nausea (28%), peripheral edema (22%), decreased appetite (21%), and rash (20%); the most common drug-related grade 3/4 adverse events were increased amylase and lipase levels (both 6%). No significant drug-drug interactions between capmatinib and gefitinib were evident.

Conclusion

This study, focused on a predominant EGFR-TKI resistance mechanism in patients with EGFR-mutated NSCLC, shows that the combination of capmatinib with gefitinib is a promising treatment for patients with EGFR-mutated, MET-dysregulated NSCLC, particularly MET-amplified disease.
ENPP1 enzyme replacement therapy improves blood pressure and cardiovascular function in a mouse model of generalized arterial calcification of infancy
Authors: Khan Tayeba , Sinkevicius Kerstin W. , Vong Sylvia , Avakian Arlen , Leavitt Markley C. , Malanson Hunter , Marozsan Andre , Askew Kim L.
Published: August 2018

Generalized arterial calcification of infancy (GACI) is a rare, life-threatening disorder caused by loss-of-function mutations in the gene encoding ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), which normally hydrolyzes extracellular ATP into AMP and pyrophosphate (PPi). The disease is characterized by extensive arterial calcification and stenosis of large- and medium-sized vessels, leading to vascular-related complications of hypertension and heart failure. There is currently no effective treatment available, but bisphosphonates – nonhydrolyzable PPi analogs – are being used off-label to reduce arterial calcification, although this has no reported impact on the hypertension and cardiac dysfunction features of GACI. In this study, the efficacy of a recombinant human ENPP1 protein therapeutic (rhENPP1) was tested in Enpp1asj-2J homozygous mice (Asj-2J or Asj-2J hom), a model previously described to show extensive mineralization in the arterial vasculature, similar to GACI patients. In a disease prevention study, Asj-2J mice treated with rhENPP1 for 3 weeks showed >95% reduction in aorta calcification. Terminal hemodynamics and echocardiography imaging of Asj-2J mice also revealed that a 6-week rhENPP1 treatment normalized elevated arterial and left ventricular pressure, which translated into significant improvements in myocardial compliance, contractility, heart workload and global cardiovascular efficiency. This study suggests that ENPP1 enzyme replacement therapy could be a more effective GACI therapeutic than bisphosphonates, treating not just the vascular calcification, but also the hypertension that eventually leads to cardiac failure in GACI patients.
The LTB4–BLT1 axis regulates the polarized trafficking of chemoattractant GPCRs during neutrophil chemotaxis
Authors: Subramanian Bhagawat C. , Moissoglu Konstadinos , Parent Carole A.
Published: August 2018

Neutrophils sense and respond to diverse chemotactic cues through G-protein-coupled receptors (GPCRs). However, the precise trafficking dynamics of chemoattractant GPCRs during neutrophil activation and chemotaxis remain unclear. Here, by using small-molecule inhibitors and CRISPR-based knockouts, we establish that two primary chemoattractant GPCRs – formyl peptide receptor 1 (FPR1) and complement component 5a (C5a) receptor 1 (C5aR1) – internalize in a CDC42–actin-dependent manner. Through live-cell imaging, we demonstrate that, upon stimulation, FPR1 rapidly clusters and re-distributes along the plasma membrane to the trailing edge, where it internalizes and is directionally trafficked towards the front of migrating primary human neutrophils. In contrast to FPR1 and C5aR1, the leukotriene B4 (LTB4) receptor (BLT1, also known as LTB4R), which relays LTB4 signals in response to primary chemoattractants during neutrophil chemotaxis, fails to internalize upon physiological stimulation with LTB4, N-formyl-Met-Leu-Phe (fMLF) or C5a. Importantly, we report that blocking the LTB4–BLT1 axis or downstream myosin activation enhances the internalization of FPR1 and C5aR1, thus reducing downstream signaling and impairing chemotaxis to primary chemoattractants. The polarized trafficking of chemoattractant GPCRs and its regulation by the BLT1-mediated myosin activation therefore drives persistent chemotactic signaling in neutrophils.

This article has an associated First Person interview with the first author of the paper.
Extreme physiological plasticity in a hibernating basoendothermic mammal, Tenrec ecaudatus
Authors: Treat Michael D. , Scholer Lori , Barrett Brandon , Khachatryan Artur , McKenna Austin J. , Reyes Tabitha , Rezazadeh Alhan , Ronkon Charles F. , Samora Dan , Santamaria Jeremy F. , Silva Rubio Claudia , Sutherland Evan , Richardson Jeffrey , Lighton John R. B. , van Breukelen Frank
Published: August 2018

Physiological plasticity allows organisms to respond to diverse conditions. However, can being too plastic actually be detrimental? Malagasy common tenrecs, Tenrec ecaudatus, have many plesiomorphic traits and may represent a basal placental mammal. We established a laboratory population of T. ecaudatus and found extreme plasticity in thermoregulation and metabolism, a novel hibernation form, variable annual timing, and remarkable growth and reproductive biology. For instance, tenrec body temperature (Tb) may approximate ambient temperature to as low as 12°C even when tenrecs are fully active. Conversely, tenrecs can hibernate with Tbs of 28°C. During the active season, oxygen consumption may vary 25-fold with little or no changes in Tb. During the Austral winter, tenrecs are consistently torpid but the depth of torpor may be variable. A righting assay revealed that Tb contributes to but does not dictate activity status. Homeostatic processes are not always linked e.g. a hibernating tenrec experienced a ∼34% decrease in heart rate while maintaining constant body temperature and oxygen consumption rates. Tenrec growth rates vary but young may grow ∼40-fold in the 5 weeks until weaning and may possess indeterminate growth as adults. Despite all of this profound plasticity, tenrecs are surprisingly intolerant to extremes in ambient temperature (<8 or >34°C). We contend that while plasticity may confer numerous energetic advantages in consistently moderate environments, environmental extremes may have limited the success and distribution of plastic basal mammals.
A new approach for measuring temperature inside turtle eggs
Authors: Tezak Boris M. , Sifuentes-Romero Itzel , Wyneken Jeanette
Published: August 2018

For turtles, the thermal environment experienced during development plays critical roles in many biological processes. While the temperature inside an egg is assumed to match substrate temperature, many factors like evaporative cooling, metabolic heating, and insulating properties of extra-embryonic components can lead to thermal differences. However, no method, to date, allowed for measurement of embryonic temperature in live chelonian eggs. We designed a thermocouple-based technique to measure embryonic temperature achieving 94 percent survival in Trachemys scripta. This methodology may be applicable to other reptile species. We found that, while temperature in the substrate adjacent to the eggshell accurately reflects internal egg temperature, it differs from air temperature (∼ 2 °C) in a moisture-dependent manner. Our results demonstrate that external egg, but not air temperature is suitable for assessing the effects of temperature on biological processes, critical when considering that the TSD mechanism in turtles occur within a 4° C window.
Resistance Training Volume Enhances Muscle Hypertrophy but Not Strength in Trained Men
Authors: SCHOENFELD BRAD J. , CONTRERAS BRET , KRIEGER JAMES , GRGIC JOZO , DELCASTILLO KENNETH , BELLIARD RAMON , ALTO ANDREW
Published: August 2018

Purpose

The purpose of this study was to evaluate muscular adaptations between low-, moderate-, and high-volume resistance training protocols in resistance-trained men.

Methods

Thirty-four healthy resistance-trained men were randomly assigned to one of three experimental groups: a low-volume group performing one set per exercise per training session (n = 11), a moderate-volume group performing three sets per exercise per training session (n = 12), or a high-volume group performing five sets per exercise per training session (n = 11). Training for all routines consisted of three weekly sessions performed on nonconsecutive days for 8 wk. Muscular strength was evaluated with one repetition maximum (RM) testing for the squat and bench press. Upper-body muscle endurance was evaluated using 50% of subjects bench press 1RM performed to momentary failure. Muscle hypertrophy was evaluated using B-mode ultrasonography for the elbow flexors, elbow extensors, mid-thigh, and lateral thigh.

Results

Results showed significant preintervention to postintervention increases in strength and endurance in all groups, with no significant between-group differences. Alternatively, while all groups increased muscle size in most of the measured sites from preintervention to postintervention, significant increases favoring the higher-volume conditions were seen for the elbow flexors, mid-thigh, and lateral thigh.

Conclusions

Marked increases in strength and endurance can be attained by resistance-trained individuals with just three 13-min weekly sessions over an 8-wk period, and these gains are similar to that achieved with a substantially greater time commitment. Alternatively, muscle hypertrophy follows a dose–response relationship, with increasingly greater gains achieved with higher training volumes.
Recent advances in understanding corticotroph pituitary tumor initiation and progression
Authors: Renner Ulrich , Ciato Denis , Stalla Günter K.
Published: August 2018

Cushing’s disease is the most frequent form of hypercortisolism and is caused by hypophyseal corticotroph adenomas secreting excessive amounts of adrenocorticotropic hormone. Most of the tumors develop sporadically and only a limited number of corticotroph adenomas have been found to be associated with different neuroendocrine syndromes or with familial isolated pituitary adenomas. The pathogenic mechanisms of corticotroph adenomas are largely unknown, but the discovered aberrant chaperoning activity of heat shock protein 90 on the one hand and the presence of ubiquitin-specific protease 8 mutations on the other hand partially explained the causes of their development. Corticotroph tumors arise initially as benign microadenomas but with time form invasively growing aggressive macroadenomas which can switch to corticotroph carcinomas in extremely rare cases. The mechanisms through which corticotroph tumors escape from glucocorticoid negative feedback are still poorly understood, as are the processes that trigger the progression of benign corticotroph adenomas toward aggressive and malignant phenotypes. This review summarizes recent findings regarding initiation and progression of corticotroph pituitary tumors.
Recent advances in understanding and treating immunoglobulin light chain amyloidosis
Authors: Badar Talha , D'Souza Anita , Hari Parameswaran
Published: August 2018

Immunoglobulin (Ig) light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by misfolded Ig light chain deposition in vital organs of the body, resulting in proteotoxicity and organ dysfunction. Owing to its diverse clinical presentations and a tendency to mimic common medical conditions, AL amyloidosis is often diagnosed late and results in dismal outcomes. Early referral to a specialized center with expertise in management of AL amyloidosis is always recommended. The availability of sensitive biomarkers and novel therapies is reforming our approach to how we manage AL amyloidosis. Treatment for patients with AL amyloidosis should be risk-adapted and customized on the basis of individual patient characteristics. In the future, approaches directed at amyloid fibril clearance in combination with agents that target plasma cells will be needed both to eradicate the malignant clone and to establish organ responses.
Rice cultivation reduces methane emissions in high-emitting paddies
Authors: Oda Masato , Chiem Nguyen Huu
Published: August 2018

Background: Rice is typically understood to enhance methane emissions from paddy fields. However, rice actually has two separate functions related to methane: i) emission enhancement, such as by providing emission pathways (aerenchyma) and methanogenetic substrates; and ii) emission suppression by providing oxygen pathways, which suppress methanogenesis or enhance methane oxidation. The overall role of rice is thus determined by the balance between its enhancing and suppressing functions. Although existing studies have suggested that rice enhances total methane emissions, we aimed to demonstrate that the balance between rice’s emitting and suppressing functions changes according to overall methane emission levels, which have quite a large range (16‍–500 kg methane ha−1 crop−1).

Methods: Using PVC chambers, we compared methane emissions emitted by rice paddy fields with and without rice plants in rice fields in the Mekong Delta, Vietnam. Samples were analyzed by gas chromatograph.

Results: We found high overall methane emission levels and our results indicated that rice in fact suppressed methane emissions under these conditions. Emission reductions increased with the growth of rice, up to 60% of emission rate at the maximum tillering stage, then decreased to 20% after the heading stage, and finally recovering back to 60%. 

Discussion: It is known that methane is emitted by ebullition when the emission level is high, and methane emission reductions in rice-planted fields are thought to be due to oxidation and methanogenesis suppression. However, although many studies have found that the contribution of soil organic matter to methanogenesis is small, our results suggested that methanogenesis depended mainly on soil organic matter accumulated from past crops. The higher the methane emission level, the lower the contribution of rice-providing substrate.

Conclusion: As a result, during the growing season, rice enhanced methane emissions in low-emission paddy fields but suppressed methane emissions in high-emission paddy fields.
MSF: Modulated Sub-graph Finder
Authors: Farman Mariam R. , Hofacker Ivo L. , Amman Fabian
Published: August 2018

High throughput techniques such as RNA-seq or microarray analysis have proven to be invaluable for the characterization of global transcriptional gene activity changes due to external stimuli or diseases. Differential gene expression analysis (DGEA) is the first step in the course of data interpretation, typically producing lists of dozens to thousands of differentially expressed genes. To further guide the interpretation of these lists, different pathway analysis approaches have been developed. These tools typically rely on the classification of genes into sets of genes, such as pathways, based on the interactions between the genes and their function in a common biological process. Regardless of technical differences, these methods do not properly account for cross talk between different pathways and rely on binary separation into differentially expressed gene and unaffected genes based on an arbitrarily set p-value cut-off. To overcome this limitation, we developed a novel approach to identify concertedly modulated sub-graphs in the global cell signaling network, based on the DGEA results of all genes tested. Thereby, expression patterns of genes are integrated according to the topology of their interactions and allow potentially to read the flow of information from the perturbation source to the effectors. The described software, named Modulated Sub-graph Finder (MSF) is freely available at https: //github.com/Modulated-Subgraph-Finder/MSF.
Data linkage in medical science using the resource description framework: the AVERT model
Authors: Reddy Brian P , Houlding Brett , Hederman Lucy , Canney Mark , Debruyne Christophe , O'Brien Ciaran , Meehan Alan , O'Sullivan Declan , Little Mark A
Published: August 2018

There is an ongoing challenge as to how best manage and understand ‘big data’ in precision medicine settings. This paper describes the potential for a Linked Data approach, using a Resource Description Framework (RDF) model, to combine multiple datasets with temporal and spatial elements of varying dimensionality. This “AVERT model” provides a framework for converting multiple standalone files of various formats, from both clinical and environmental settings, into a single data source. This data source can thereafter be queried effectively, shared with outside parties, more easily understood by multiple stakeholders using standardized vocabularies, incorporating provenance metadata and supporting temporo-spatial reasoning. The approach has further advantages in terms of data sharing, security and subsequent analysis. We use a case study relating to anti-Glomerular Basement Membrane (GBM) disease, a rare autoimmune condition, to illustrate a technical proof of concept for the AVERT model.
Possibilities and limitations of DSM-5 in improving the classification and diagnosis of mental disorders
Authors: Möller Hans-Jürgen
Published: August 2018

Dwadzieścia lat po opublikowaniu poprzedniej wersji, w 2013 r wprowadzono nową i całkowicie zmienioną wersję amerykańskiego systemu diagnostycznego zaburzeń psychicznych the Diagnostic and Statistical Manual of Mental Disorders – DSM-5. W trakcie jej, trwających wiele lat, przygotowywań, podsumowano aktualną wiedzę, a konsekwencje tej wiedzy dla klasyfikacji i diagnozy zaburzeń psychicznych omówiono w grupach ekspertów. Pod wieloma względami DSM-5 nie spełnia pierwotnych planów i oczekiwań; jednak w większości przypadków może być postrzegane jako akceptowalne podsumowanie aktualnej wiedzy na temat zaburzeń psychicznych. Chociaż uniwersytety i grupy badawcze na całym świecie wykazują duże zainteresowanie DSM-5, w krajach poza USA ICD-10 jest nadal obowiązkowym systemem klasyfikacji, aż do oficjalnego wprowadzenia ICD-11. Z wielu perspektyw DSM-5 może być postrzegany jako swego rodzaju poprzednik dla ICD-11. Jednak ICD-11, mimo pierwotnego planu, w ramach którego miało być podobne do DSM-5, znajduje wiele własnych rozwiązań. W niniejszym artykule przedstawiono kilka ważnych kwestii dotyczących DSM-5, które będą interesujące dla klinicystów pracujących w dziedzinie zaburzeń psychicznych. Ponadto podano kilka przykładów ilustrujących, w jaki sposób DSM-5 operacyjnie definiuje niektóre zaburzenia i jak różni się od ICD-10 i DSM-IV.
Letter to Editor. Conclusions from the application of transcranial magnetic stimulation regarding the psychopathology of depressive syndromes and the essence of self-consciousness
Authors: Brodziak Andrzej , Kołat Estera , Wolińska Agnieszka
Published: August 2018

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Wholegrains in the Management of Diabetes
Authors: Mukerjee Anjali
Published: August 2018

Dietary fibre is responsible for the decrease in the rate of glucose absorption along with aiding decrease in postprandial rise in blood glucose. Substantial research establishes the connection between consumption of wholegrains and type 2 diabetes management. Wholegrains are widely recognized for contributing significantly to our health and well-being as they contain essential nutrients and bioactive compounds, along with being rich in dietary fibre. This review article attempts to discuss the effect of the fibre in wholegrains on blood glucose, type 2 diabetes and HbA1c.
A case study of venous leg ulceration
Authors: Porter Michelle
Published: August 2018

Venous ulcers or stasis ulcers account for 80% of lower extremity ulcerations. Approximately 1-2% of the population will suffer from the chronic debilitating condition, with chronic venous insufficiency affecting up to 50% of the adult population. There are many methods of treatment and common treatments include conventional, surgical or mechanical methods. This article examines the complications of leg ulcer management, with the emphasis on the use of antibiotics. The case study demonstrates the positive impact self-care can have as part of a treatment plan.
Synthesis, Spectroscopic characterization of Co(II), Ni(II) and Cu(II) complexes with 2-meracapto-5-(2,4-dinitrophenyl)- 1,3,4-oxadiazole or 2-meracapto-5-((4-(dimethylamino)benzylidene)amino)-1,3,4-thiadiazole ligands
Authors: A. Ahmed Saleh , S. M. Al-Janabi Ahmed
Published: August 2018

New Co(II), Ni(II) and Cu(II) complexes with 2-meracapto-5-(2,4-dinitrophenyl)-1,3,4-oxadiazole (IpotH) or 2-meracapto-5-((4-(dimethylamino)benzylidene)amino)-1,3,4-thiadiazole (daptH) ligands, were prepared by treatment two moles of thione ligands with one mole of metal salts in EtOH/Acetone and H2O as a solvents, to afforded octahedral complexes of the types [MX2(k2-IpotH)2] (Where M = Co, Cu, X= Cl and M= Ni , X= NO3 ) or [MX2(k2-daptH)2] (Where M = Co, Cu, X= Cl and M= Ni , X= NO3 ). The thione ligands bonded through the nitrogen atom of heterocylic and sulfur atom of thiol group. The prepared ligands and its complexes were characterization by elemental analysis (CHNM), IR spectroscopy , molar conductivity, magnetic susceptibility, UV-Visible spectroscopy and 1H NMR data.