bluuebunny/crossref_metadata_2025 huggingface dataset:
Caring community and relationship centred care on an end-stage dementia special care unit
Authors: Allison Theresa A , Balbino Rafael T , Covinsky Kenneth E
Published: March 2019

Background

of the estimated 1.4 million residents of US nursing homes, over half have dementia. In the final stages of dementia, caregiving is complicated by the inability of care recipients to speak intelligibly or express their needs.

Aim

to examine the ways in which a nursing home end-stage dementia special care unit (SCU) functioned as a caring community for people near the end of life.

Research design and methods

a qualitative, ethnographic case study was conducted in a highly-regarded SCU. Over 175 hours of scheduled activity observations were completed over 2 years, bolstered by 30 hours of caregiving observations on the end-stage dementia unit and 19 interviews with SCU carers. Inductive coding was completed independently by two researchers, emerging themes reconciled by consensus, and qualitative analysis conducted iteratively until the endpoint of thematic saturation.

Findings

on the SCU, employees and volunteers fostered relationships based upon a model of family. They formed a caring community that included professionals, volunteers, friends and family. Relationships were supported through (1) the use of reminiscence to evoke intact long-term memories, (2) the use of verbal communication long after care-recipients could no longer speak and (3) the use of intentional nonverbal communication, including daily music, pet visits, and sensory stimulation.

Conclusions

through detailed examination of daily life, this study identified articulated beliefs and observable behaviour through which to develop relationship-centred care in the context of end-stage dementia. The caring community offers primary source data for the development of mid-level theory and the generation of new hypotheses.
Familial Hypercholesterolemia With Coexisting Renovascular Stenosis and Premature Coronary Artery Disease
Authors: Mehta Ojas H , Cameron James D , Mirzaee Sam
Published: March 2019

Familial hypercholesterolemia (FH) is a common hereditary lipid disorder associated with substantial risk of premature atherosclerotic cardiovascular disease. We report an interesting newly diagnosed index case of FH in a 31-year-old man who presented to the hospital with an ST-elevated myocardial infarction. He had a background of inadequately treated hypertension and hypercholesterolemia. Further investigations raised the possibility of secondary hypertension after the identification of renal artery stenosis, in addition to other areas of mesenteric arterial stenoses. Our patient’s case highlights that early-onset hypertension and hypercholesterolemia in a young individual may be an early manifestation of FH requiring high clinical vigilance and awareness.
Antibiotic Therapy for Pseudomonas aeruginosa Bloodstream Infections: How Long Is Long Enough?
Authors: Fabre Valeria , Amoah Joe , Cosgrove Sara E , Tamma Pranita D
Published: March 2019

In a multicenter, observational, propensity-score–weighted cohort of 249 adults with uncomplicated Pseudomonas aeruginosa bacteremia, patients receiving short-course (median, 9 days; interquartile range [IQR], 8–10) therapy had a similar odds of recurrent infection or death within 30 days as those receiving longer courses (median, 16 days; IQR, 14–17).
Determining the Commission of Genocide in Myanmar
Authors: Van Schaack Beth
Published: March 2019

In August 2018, what appears to be a draft statement to be delivered by United States Secretary of State Mike Pompeo on the persecution of the Rohingya minority in Myanmar was leaked to the press. The text suggests that the State Department was considering whether there are grounds to believe that genocide has been, or is being, committed in Myanmar and whether the State Department should issue a statement to this effect. This article surveys the major human rights documentation efforts, academic literature, relevant jurisprudence emanating from the international criminal tribunals, statements of United Nations entities and other states, the results of the State Department’s recent empirical investigation, party and amicus curiae briefs filed before the International Criminal Court, and journalistic accounts of events in Myanmar, Bangladesh, and elsewhere in the region with an eye towards understanding the dynamics of violence against the Rohingya — deemed by many to be ‘the most persecuted minority in the world’. The article layers the facts as we know them against established legal principles to conclude that a genocide is in fact underway in Myanmar through genocidal acts committed by discrete sets of actors (including various state organs, the Tatmadaw-Army, regional and local officials, and Rakhine civilians) and also by way of a genocide writ large against the Rohingya within Rakhine State involving the central authorities working in collusion with, and through, regional actors. This article closes with a discussion of the methodological question of the level of certainty that should be met before a non-judicial entity makes such a determination with reference to the various standards employed by commissions of inquiry and courts (both criminal and civil) that find themselves making analogous determinations.
Eugenics and Public Health: Historical Connections and Ethical Implications
Authors: Lombardo Paul
Published: March 2019

This chapter details historical points of connection between the field of public health and the eugenics movement in the United States, and explores the ethical significance of public health genetics in light of that history. It explains how attention to both eugenics and public health grew simultaneously in the twentieth-century United States, and how both fields contributed to the growth of laws that emphasized the use of the police power to constrain reproduction and immigration among certain groups as a means to advance efficiency and social progress. The chapter suggests that an emphasis on the prevention of problematic hereditary conditions supplies a similar motive for a new public health genetics today.
Language Comprehension and Emotion
Authors: van Berkum Jos J. A.
Published: March 2019

When you hear somebody speak, or read a bit of text, you are somehow assigning meaning to an unfolding sequence of signs. Because of the representational and computational complexity involved, this process of language interpretation is considered to be one of the major feats of human cognition. However, you also happen to be just another mammal, and as such, you are biologically predisposed to have emotions, evaluations, and moods (i.e. to feel certain things about your environment). How do these two acts of assigning meaning relate to one another? And what are the implications for neurolinguistics, the endeavor to understand how the brain realizes language use? After examining why emotion is not naturally foregrounded in language processing research, this chapter reviews some basic insights in emotion science, discusses a processing model of affective language comprehension, and explores how the model can contribute to neurolinguistics and other fields.
Intergovernmental Organizations and Nongovernmental Organizations
Authors: Aylward Erin
Published: March 2019

This article traces the origins, evolution, and effects of LGBT advocacy by nongovernmental organizations (NGOs) in global forums. In particular, the article focuses on LGBT advocacy in intergovernmental organizations such as the United Nations. The first section provides a historical overview and traces the rise of LGBT NGOs—as well as the transnational networks linking them—from the interwar period to the present day. In doing so, this section discusses the strategies that such organizations have leveraged to gain clout and highlights how LGBT issues have gained salience and have generated contestation within UN human rights bodies and mechanisms. The second section provides a conceptual overview of how advocates have advanced LGBT issues and discusses how the frames of sexual and reproductive health rights, public health and HIV/AIDS, and, increasingly, LGBT human rights have been leveraged by NGOs to legitimize and to further propel LGBT advocacy. Finally, the third section discusses some of the challenges facing global LGBT advocacy. In particular, this section highlights North–South power inequalities in shaping and driving a global advocacy agenda and the tensions arising from limited emphasis on non-Western notions of sexual and gender diversity. This section concludes with a discussion of new directions in LGBT advocacy, highlighting in particular the increased efforts to combine human rights advocacy with inclusive development policy.
Immigration Dynamics and Changing Constructions of Jewish Nativeness in Israel
Authors: Zawdu Adane , Willen Sarah S.
Published: March 2019

A fundamental building block of the Zionist vision is the claim of a primordial link between modern-day Jews and the people and territory of ancient Israel. This claim, which has proven remarkably durable despite its changing form and its tension with understandings of Palestinian indigeneity, continues to inform conceptions of nativeness in the modern-day state of Israel. This chapter explores how constructions of Jewish nativeness in Israel have changed in relation to successive immigration processes. Taking sociocultural and political dynamics as its focus, the chapter examines the cultural and institutional practices through which the notion of Jewish nativeness, its boundaries, and its logics of inclusion and exclusion were constructed and enforced in four historical periods. In each period, an increase in ethnic and religious heterogeneity challenged established notions of Jewish nativeness and membership in new ways. Although conceptions of Jewish nativeness have changed over time, they continue to shape social boundaries by signaling, and qualifying, membership in the Israeli collective.
Global Corporations and Global Value Chains
Authors: Clarke Thomas , Boersma Martijn
Published: March 2019

Many of the great international corporations of the past have now largely been disembodied into global value chains. This chapter considers the implications of the continued advance of global value chains as the mode of production for an increasing number of goods and services, and how this has impacted considerably on the economies and societies both of the developed world and the emerging economies. In turn, this has transformed corporations themselves into largely finance, design, and marketing agencies which are often distant from the production and operations which they ultimately control. While the globalization of production has brought employment and economic growth to many developing countries, it is also associated with exploitative employment relations, environmental irresponsibility, and recurrent ethical dilemmas. While corporations may disaggregate production in distant networks of contractors, they cannot as readily disaggregate the moral responsibility for the social and environmental impact of their mode of production.
Positive Psychology within a Cultural Context
Authors: Pedrotti Jennifer Teramoto , Edwards Lisa M. , Lopez Shane J.
Published: March 2019

As our workforce, neighborhoods, and country overall becomes more diverse, our interactions with others with different worldviews also becomes more frequent. This exposure to diversity on so many levels requires a better understanding of the multiple contexts in which people from different cultural backgrounds live and the strengths they possess that help them experience well-being. In order to define the characteristics that may be viewed as strengths in different groups, we must make efforts to remember that cultural values and norms often dictate what can be called a strength versus a weakness. It is imperative that we recognize that strengths may look very different in different contexts and that these diverse manifestations may come from a variety of worldviews. More work must be done to develop a better understanding of the way that cultural context plays a role in the operationalization, manifestation, and measurement of strengths in diverse groups. The following chapter provides a history of the connections between culture and positive psychology and discusses current issues regarding the link between cultural context and various personal characteristics. Examples from culturally sensitive positive psychological theory and research are also given in order to illustrate how researchers are better exploring positive psychology within a cultural context.
De Re/De Dicto
Authors: Keshet Ezra , Schwarz Florian
Published: March 2019

The de re/de dicto distinction describes the interaction of intensional operators and noun phrases in a sentence. The classic example ‘I want a sloop’ due to Quine (1956) contrasts two readings: a desire for a particular sloop (de re) and ‘relief from slooplessness’ (de dicto). The distinction is commonly discussed in connection with modal expressions, often construed as quantifiers over possible worlds, but entirely parallel phenomena arise for tenses, construed as quantifiers over times, and situations, combining possible worlds and time spans. This chapter provides a brief historical background of the de re/de dicto distinction and then lays out the basics of a traditional analysis in terms of scope. Next, challenges to such a theory are reviewed, as well as possible revisions to capture this problematic data. The last part of the chapter notes some loose ends and possible extensions.
Indefiniteness and Specificity
Authors: Von Heusinger Klaus
Published: March 2019

The semantic–pragmatic category ‘specificity’ is used to describe various semantic and pragmatic contrasts of indefinite noun phrases. This chapter will first provide a brief illustration of different linguistic means to express these contrasts in different languages. Second, it will categorize different types of specificity according to the semantic and pragmatic contexts in which they can be found. The standard tests for these different kinds of specificity are also discussed. In the third section a comparison is made between four families of theoretical approaches to specificity and the chapter concludes with the notion that specificity can be best understood by ‘referential anchoring’.
The History of the Neuropsychology of Emotion
Authors: Teague Ella B. , Meltzer Erica P. , Stafford Remington , Twaite Jamie T. , Filangieri Carole , Borod Joan C.
Published: March 2019

The chapter outlines philosophical and prescientific ideas regarding emotion, as well as early physiological and psychological discoveries that formed the basis upon which modern neuropsychology rests. In addition, to elucidate developments throughout the history of the neuropsychological study of emotion, the chapter discusses important theoretical considerations in emotion research. The central focus of the chapter, however, is on neuropsychological studies beginning in the mid-twentieth century. These studies are organized into important areas in the study of emotion, such as laterality, emotional expression, emotional perception, and emotional experience. Finally, the chapter provides information regarding the measurement of emotion via neuropsychological test batteries.
Psychotropics in Your Medicine Cabinet: A Case Study of Dimenhydrinate Use
Authors: Wen Xia , Di Paola Francesca , Chopra Nitin
Published: March 2019

Reporting of intoxication and withdrawal from aberrant use of over-the-counter medication has been sparse and inconsistent in literature. Attributed to their anticholinergic properties, medications such as dimenhydrinate (Gravol) taken in supratherapeutic doses have been associated with euphoria, anxiolysis, and hallucinations. We present a case of a woman in her forties, with a psychiatric history of bipolar disorder, and complex concurrent medical history including familial Mediterranean fever (FMF), and fibromyalgia, admitted for withdrawal management of her intravenous dimenhydrinate use. As a result of her FMF, there were numerous hospital admissions and treatment which required intravenous access. Hence, a physician-inserted intravenous access port was placed on her chest. The port was maintained monthly with the help of a community agency. In this port, she was injecting 100 to 200 mg of dimenhydrinate hourly for its euphoric and calming effects, consuming upwards of 2400 mg/d. Comprehensive laboratory work-up and urine drug screening were unremarkable. Vital signs were stable. Her mental status at time of admission was lethargic, unfocused, but calm. Her withdrawal symptoms included severe nausea, vomiting, sedation, headaches, dizziness, anxiety, and muscle stiffness. Her detoxification was managed with benztropine and lorazepam, and was well tolerated. The patient was discharged to a community inpatient rehabilitation center. Urine drug testing before discharge was negative. This case draws attention to the addictive potential of dimenhydrinate and offers a regime for its medical withdrawal management. Additionally, this case highlights that screening and management of over-the-counter medications warrants further clinical consideration and investigation.
Patient preferences for rheumatoid arthritis treatment
Authors: Hsiao Betty , Fraenkel Liana
Published: March 2019

Purpose of review

To provide an overview of recent articles discussing patient preferences for rheumatoid arthritis (RA) treatment.

Recent findings

Recent studies examined patient preferences for RA treatment in several populations, finding that most participants were willing to accept certain risks of adverse effects to gain potential benefits. Perspectives regarding cannabis were studied, with patients describing medical marijuana as an alternative therapy to be used with prescription medications or as means of tapering off these medications. Treatment preferences for different RA therapies were explored using a conjoint analysis survey and five distinct preference phenotypes emerged, with members of the largest group most concerned with the cost of medications. Other discrete choice studies demonstrated route of administration as an important attribute influencing treatment preferences, with patients expressing preference for various modes in different studies. Patient preferences for route of administration have demonstrated preference for newer autoinjectors over prefilled syringes as well as currently marketed autoinjectors. Incorporating patient preferences in clinical practice recommendations was described in the development of the 2015 American College of Rheumatology (ACR) RA treatment guidelines as well as the 2017 ACR/American Association of Hip and Knee Surgeons guidelines for perioperative management of antirheumatic medications. In addition, other studies explored preferences with regard to predictive testing, medication intensification and tapering, treatment goals, and psychological support.

Our review of recent studies show variability in patient preferences for RA treatment, highlighting the importance of incorporating patient input into the treatment approach.
Changes of Electrocochleographic Responses During Cochlear Implantation Presented at the Annual Meeting of ADANO 2016 in Berlin
Authors: Dalbert Adrian , Pfiffner Flurin , Hoesli Marco , Meerwein Christian , Veraguth Dorothe , Roosli Christof , Huber Alexander
Published: March 2019

Objective:

To assess by electrocochleography (ECoG) at which times during cochlear implantation changes of cochlear function occur.

Methods:

Tone bursts with a frequency of 500 or 750 Hz were used as acoustic stimuli. The recording electrode was placed on the promontory and left in an unchanged position for all ECoG recordings.

Results:

Eight subjects were included. After opening the cochlea, an increase of the amplitude of the ECoG signal was detectable in four subjects (mean change 3.9 dB, range from 0.2 to 10.8 dB). No decreases were detectable after opening the cochlea or during the first half of the insertion of the CI electrode array (mean change 0.5 dB, range from −2.2 to 1.6 dB). During the second half of the insertion, the amplitude of the ECoG signal decreased in four subjects (mean change −2.5 dB, range from −0.04 to −4.8 dB). If a decrease occurred during the second half of the insertion, then the decrease continued in the earliest phase after insertion of the CI electrode array (mean change −2.1 dB, range from −0.5 to −5.8 dB).

Conclusion:

Pressure changes inside the cochlea can lead to an increase of ECoG signals after opening the cochlea. If detectable, then a decrease of ECoG signals occurs during the second half of the insertion of the CI electrode array and continues in the earliest phase after completed insertion. These findings suggest that cochlear trauma occurs toward the end of the insertion and that trauma-dependent postoperative mechanisms contribute to postoperative hearing loss.
The Clinical Outcomes After Intratympanic Gentamicin Injection to Treat Menière's Disease: A Meta-analysis
Authors: Zhang Yuyao , Fu Jiangtao , Lin Hongbin , Shen Chuan , Wang Xiaofei , Wu Jueting
Published: March 2019

Objectives:

In recent decades, intratympanic gentamicin (ITG) has increasingly been used to treat intractable Menière's disease (MD). We performed a meta-analysis of pooled clinical outcomes, exploring whether ITG was effective and safe.

Data Sources:

Cochrane Library database, Embase, and Medline.

Study Selection:

We searched scientific and medical databases to March 2018 for articles evaluating clinical outcomes after ITG treatment of intractable MD according to the American Academy of Otolaryngology Head and Neck Surgery (AAO-HNS) guidelines.

Data Extraction:

We performed a meta-analysis to evaluate treatment efficacy and safety. Quantitative and descriptive information of included RCTs was obtained.

Data Synthesis:

We ultimately evaluated 49 of the initially retrieved 1,062 citations (the 49 articles included data from a total of 2,344 MD patients). In almost all studies, patients served as their own controls; “before-and-after” clinical outcomes were reported. The I
2 metric was used to explore heterogeneity.

Conclusion:

Overall, our results seem to provide the limited evidence about efficacy and toxicity effects of ITG. However, clinical outcomes require further confirmation; many included studies were poorly designed, less than 2 years for reporting results in MD are in the majority of patients. More long-term prospective follow-up, high-quality, large-scale, randomized controlled trials are needed to confirm that ITG is safe and effective when used to treat intractable MD.
Cochlear Implantation in Patients With Single-sided Deafness After the Translabyrinthine Resection of the Vestibular Schwannoma—Presented at the Annual Meeting of ADANO 2016 in Berlin
Authors: Klenzner Thomas , Glaas Marcel , Volpert Simone , Jansen Nils , Kristin Julia , Schipper Jörg
Published: March 2019

Objective:

To evaluate effectiveness of the cochlear implant (CI) to facilitate single-sided deafness (SSD) rehabilitation following translabyrinthine resection of the vestibular schwannoma.

Study Design:

Retrospective patient review.

Setting:

Single center, University hospital.

Patients:

Patients with SSD who underwent translabyrinthine resection of a vestibular schwannoma with anatomical preservation of the cochlear nerve and subsequent CI on the same ear.

Interventions:

CI at post-translabyrinthine resection of the acoustic neuroma to treat SSD, and evaluation by retrospective individual case review in a period from 2009 to 2016.

Main Outcome Measures:

Individual patients’ clinical outcome and speech understanding.

Results:

Thirteen patients were provided CI. In all cases, complete removal of the tumor was achieved and the cochlear nerve was preserved; in one case, the CI was implanted simultaneously. In most cases, the follow-up interval was 2 years. In 9 of 13 cases, the implanted ear achieved capability to understand and discriminate monosyllabic words at 65 dB. Level of speech understanding of over 50% at 65 dB was possible in 7 patients at 12 months after the first fitting of CI.

Conclusions:

Under certain conditions, CI was an effective solution to restore hearing in patients with SSD following translabyrinthine access to the skull base. Study with prospective design is required to provide more significant results.
Determining the Sample Size for Future Trials of Hearing Instruments for Unilaterally Deaf Adults: An Application of Network Meta-analysis
Authors: Gaunt Adam Christopher , Kitterick Pádraig Thomas
Published: March 2019

Objective:

Previous trials have compared the efficacy of hearing instruments to no intervention in adults with single-sided deafness (SSD) or the relative efficacy of different instruments. Network meta-analysis (NMA) was used to refine estimates of effect sizes to determine required sample sizes for further trials.

Data Sources:

PubMed, EMBASE, MEDLINE, Cochrane, CINAHL, and DARE databases were searched with no restrictions on language, with studies to February 2015 included.

Study Selection:

Studies were included that 1) assessed hearing instruments in adults with SSD; 2) compared instruments with other instruments, placebo, or no intervention; 3) measured speech perception in quiet/noise and listening ability; 4) were prospective controlled or observational studies.

Data Extraction:

The following data were extracted: sample size in each group, type of intervention and comparator, type of outcomes, mean outcome scores and their 95% confidence intervals.

Data Synthesis:

Random-effects meta-analysis was conducted to determine pooled effects for each outcome based on direct evidence alone. NMA used graph-theoretical method to determine pooled effects based on indirect evidence. Sample size calculations were conducted for each outcome for each class of evidence.

Conclusions:

The incorporation of indirect evidence had substantial impacts on some effect sizes but negligible impacts on other effects. The most notable impacts were on self-reported listening ability and measures of speech perception in noise. Changes in effect size estimates and required sample sizes resulting from the incorporation of indirect evidence highlight areas of uncertainty where trials may be feasible to conduct.
Is Dedicated Research Time During Surgery Residency Associated With Surgeons’ Future Career Paths?
Authors: Andriole Dorothy A. , Klingensmith Mary E. , Fields Ryan C. , Jeffe Donna B.
Published: March 2019

Objective:

We examined associations between participation in ≥1 year of research during general surgery residency and each of full-time academic-medicine faculty appointment and mentored-K and/or Research Project Grant (RPG, including R01 and other) awards.

Summary Background Data:

Many surgeons participate in ≥1 year of research during residency; however, the relationship between such dedicated research during general surgery residency and surgeons’ career paths has not been investigated in a national study.

Methods:

We analyzed deidentified data through August 2014 from the Association of American Medical Colleges, American Board of Medical Specialties, and the National Institutes of Health Information for Management, Planning, Analysis, and Coordination II grants database for 1997 to 2004 US medical-school graduates who completed ≥5 years of general surgery graduate medical education (GME) and became board-certified surgeons. Using multivariable logistic regression models, we identified independent predictors of faculty appointment and K/RPG award, reporting adjusted odds ratios (AOR) and 95% confidence intervals (CI) significant at P < 0.05.

Results:

Of 5328 board-certified surgeons, there were 1848 (34.7%) GME-research participants, 1658 (31.1%) faculty appointees, and 58 (1.1%) K/RPG awardees. Controlling for sex, debt, MD/PhD graduation, and other variables, GME-research participants were more likely to have received faculty appointments (AOR 1.790; 95% CI 1.573–2.037) and federal K/RPG awards (AOR 4.596; 95% CI 2.355–8.969).

Conclusions:

Nationally, general surgery GME-research participation was independently associated with faculty appointment and K/RPG award receipt. These findings serve as benchmarks for general surgery residency programs aiming to prepare trainees for careers as academicians and surgeon-scientists.
Real-World Experience With VMAT2 Inhibitors
Authors: Niemann Nicki , Jankovic Joseph
Published: March 2019

Objectives

The aim of this study was to review our “real-world” experience with the vesicular monoamine transporter 2 (VMAT2) inhibitors tetrabenazine (TBZ), deutetrabenazine (DTBZ), and valbenazine (VBZ) for treatment of hyperkinetic movement disorders. Access and adherence to VMAT2 inhibitors may be limited by insurance and regulatory issues, inexperience with their use by the prescribing physician, lack of efficacy, or side effects.

Methods

We performed a retrospective chart review, supplemented with a questionnaire, of all our patients treated with a VMAT2 inhibitor between January 1, 2017, and August 30, 2018.

Results

We identified 135 patients (57.8% male) and 178 prescriptions for VMAT2 inhibitors (TBZ, n = 45 [25.3%]; DTBZ, n = 104 [58.4%]; VBZ, n = 29 [16.3%]). Tourette syndrome/tics was the most common diagnosis (n = 67 [49.6%]) for which VMAT2 inhibitors were prescribed. The VMAT2 inhibitor mean treatment durations (range; SD) and daily dosages (range; SD) were as follows: TBZ (n = 31), 5.1 months (1–19; 3.9) at 48.8 mg (12.5–112.5; 29.6); DTBZ (n = 51), 8.0 months (0.25–16.5; 4.4) at 34.4 mg (6–96; 20.7); and VBZ (n = 20), 6.0 months (0.1–16; 5.6) at 64 mg (40–160; 35.3). The VMAT2 inhibitors effectively controlled hyperkinetic movement disorders as measured by a 1- to 4-point Likert scale (1 = normal or mildly ill, 4 = severely ill) comparing illness severity before starting and while on treatment (score of 1 in 13.0%–26.7% vs 60.9%–71.9% of patients). Side effects were mild and improved or resolved following dose reduction, drug cessation, or addition of adjunctive medications.

Conclusions

The VMAT2 inhibitors are effective and safe in a range of hyperkinetic movement disorders but are not readily accessible by patients in the United States for indications not approved by the Food and Drug Administration.
Transcranial Direct Current Stimulation Reduces Craving in Substance Use Disorders
Authors: Martinotti Giovanni , Lupi Matteo , Montemitro Chiara , Miuli Andrea , Di Natale Chiara , Spano Maria Chiara , Mancini Valerio , Lorusso Marco , Stigliano Gianfranco , Tambelli Antonio , Di Carlo Francesco , Di Caprio Lucia , Fraticelli Silvia , Chillemi Eleonora , Pettorruso Mauro , Sepede Gianna , di Giannantonio Massimo
Published: March 2019

Objectives

The use of transcranial direct current stimulation (tDCS) in addiction disorders is still on its rise in comparison with pharmacological and psychotherapeutic strategies that still show low level of evidence. In this study, we aimed to evaluate the efficacy of the anodic tDCS for the short-term treatment of substance craving and other psychiatric symptoms.

Methods

In this randomized, double-blind, sham-controlled trial, inclusion criteria included the diagnosis of substance use disorder and/or gambling disorder. The protocol includes 5 consecutive days of active or sham tDCS session. Cathode was placed over the left dorsolateral prefrontal cortex. Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Young Mania Rating Scale, Barratt Impulsiveness Scale, South Oaks Gambling Screen, and visual analog scale (VAS) 1 to 10 for craving were administered at the baseline (T0) and after 5 days of treatment (T1).

Results

Thirty-four treatment-seeking subjects were randomized to sham (n = 16) and active stimulation (n = 18) groups. A statistically significant reduction of values at T1 was found in all subjects considering VAS (P < 0.001), Hamilton Depression Rating Scale (P < 0.001), Hamilton Anxiety Rating Scale (P < 0.001), and Barratt Impulsiveness Scale 11 (P = 0.032). A significant reduction for VAS craving in favor of the active stimulation (P = 0.011) was found.

Conclusions

Our findings reveal a statistically significant rapid reduction of craving in the active tDCS group on the right dorsolateral prefrontal cortex with respect to sham group, confirming the scientific literature trend. Large samples, with maintenance tDCS therapy and long-term follow-up, are required to establish the potential of this noninvasive and easily delivered brain stimulation strategy.
An open-source and low-cost feeding system for zebrafish facilities
Authors: Tangara Astou , Paresys Gérard , Bouallague Firas , Cabirou Yvon , Fodor Jozsua , Llobet Victor , Sumbre Germán
Published: March 2019

Zebrafish is an established animal model used in the fields of developmental biology and genetics for more than 60 years, and among the first models to become genetically tractable. More recently, zebrafish has also become a model of reference for human diseases and systems neuroscience.

The current extensive use of zebrafish in research and pharmaceutical companies promoted the development of several commercial husbandry systems specially designed for zebrafish. However, feeding is still a challenging and arduous task that can result in occupational disorders of the personnel working at the zebrafish facilities (e.g. tendinitis, back pain, etc.). To palliate these risks, a commercial robotic approach has been developed, yet its expensive cost makes this solution accessible only to very large fish facilities. Most mid-size and small facilities with limited resources still use manual feeding methods.

Here, we propose two custom-made open-source semi-automatic feeding systems for dry and live food, capable of preventing and/or alleviating occupational disorders, improve feeding accuracy and decrease feeding time. Both systems are designed for mid-size or small fish facilities. They are cheap and can be easily and rapidly built using 3D printing and standard electronic and lab components.
First hybrid complete genome ofAeromonas veroniireveals chromosome-mediated novel structural variantmcr-3.19from human clinical specimen
Authors: Ragupathi Naveen Kumar Devanga , Sethuvel Dhiviya Prabaa Muthuirulandi , Anandan Shalini , Murugan Divya , Asokan Kalaiarasi , Mohan Ramya Gajaraj Neethi , Vasudevan Karthick , D Thirumal Kumar , C George Priya Doss , Veeraraghavan Balaji
Published: March 2019

Background

Recent findings substantiate the origin of plasmid-mediated colistin resistance genemcr-3from Aeromonads. The present study aimed to screen the plasmid-mediated colistin resistance among 30 clinical multidrug resistant (MDR)Aeromonas spp.

Results

The presence ofmcr-1, mcr-2, mcr-3, and mcr-4were screened by PCR, which revealedmcr-3in a colistin susceptible isolate (FC951). All other isolates were negative formcrgenes. Sequencing of FC951 revealed thatmcr-3(mcr-3.19) identified was different from previously reported variants and had 95.62 and 95.28% nucleotide similarity withmcr-3.3andmcr-3.10gene. A hybrid assembly using IonTorrent and MinION reads revealed structural genetic information ofmcr-3.19with an insertion of ISAs18within the gene. Due to this,mcr-3.19was non-expressive which makes FC951 susceptible to colistin. Further,in silicosequence and protein structural analysis confirmed the new variant. To the best of our knowledge, this is the first report on novelmcr-3variant (mcr-3.19).

Conclusions

The significant role ofmcr-like genes in differentAeromonasspecies remains unknown and needs additional investigation to understand the insights on colistin resistance mechanism.
TGFβ in the obese liver mediates conversion of NK cells to a less cytotoxic ILC1-like phenotype
Authors: Cuff Antonia O. , Sillito Francesca , Dertschnig Simone , Hall Andrew , Luong Tu Vinh , Chakraverty Ronjon , Male Victoria
Published: March 2019

The liver contains both NK cells and their less cytotoxic relatives, ILC1. Here, we investigate the role of NK cells and ILC1 in the obesity-associated condition, non-alcoholic fatty liver disease (NAFLD). In the livers of mice suffering from NAFLD, NK cells are less able to degranulate, express lower levels of perforin and are less able to kill cancerous target cells than those from healthy animals. This is associated with a decreased ability to kill cancer cells in vivo. On the other hand, we find that perforin-deficient mice suffer from less severe NAFLD, suggesting that this reduction in NK cell cytotoxicity may be protective in the obese liver, albeit at the cost of increased susceptibility to cancer. The decrease in cytotoxicity is associated with a shift towards a transcriptional profile characteristic of ILC1, increased expression of the ILC1-associated proteins CD200R1 and CD49a, and an altered metabolic profile mimicking that of ILC1. We show that the conversion of NK cells to this less cytotoxic phenotype is at least partially mediated by TGFβ, which is expressed at high levels in the obese liver. Finally, we show that reduced cytotoxicity is also a feature of NK cells in the livers of human NAFLD patients.
DNA barcode reference libraries for the monitoring of aquatic biota in Europe: Gap-analysis and recommendations for future work
Authors: Weigand Hannah , Beermann Arne J. , Čiampor Fedor , Costa Filipe O. , Csabai Zoltán , Duarte Sofia , Geiger Matthias F. , Grabowski Michał , Rimet Frédéric , Rulik Björn , Strand Malin , Szucsich Nikolaus , Weigand Alexander M. , Willassen Endre , Wyler Sofia A. , Bouchez Agnès , Borja Angel , Čiamporová-Zaťovičová Zuzana , Ferreira Sónia , Dijkstra KD , Eisendle Ursula , Freyhof Jörg , Gadawski Piotr , Graf Wolfram , Haegerbaeumer Arne , van der Hoorn Berry B. , Japoshvili Bella , Keresztes Lujza , Keskin Emre , Leese Florian , Macher Jan , Mamos Tomasz , Paz Guy , Pešić Vladimir , Pfannkuchen Daniela Maric , Pfannkuchen Martin Andreas , Price Benjamin W. , Rinkevich Buki , Teixeira Marcos A. L. , Várbíró Gábor , Ekrem Torbjørn
Published: March 2019

Effective identification of species using short DNA fragments (DNA barcoding and DNA metabarcoding) requires reliable sequence reference libraries of known taxa. Both taxonomically comprehensive coverage and content quality are important for sufficient accuracy. For aquatic ecosystems in Europe, reliable barcode reference libraries are particularly important if molecular identification tools are to be implemented in biomonitoring and reports in the context of the EU Water Framework Directive (WFD) and the Marine Strategy Framework Directive (MSFD). We analysed gaps in the two most important reference databases, Barcode of Life Data Systems (BOLD) and NCBI GenBank, with a focus on the taxa most frequently used in WFD and MSFD. Our analyses show that coverage varies strongly among taxonomic groups, and among geographic regions. In general, groups that were actively targeted in barcode projects (e.g. fish, true bugs, caddisflies and vascular plants) are well represented in the barcode libraries, while others have fewer records (e.g. marine molluscs, ascidians, and freshwater diatoms). We also found that species monitored in several countries often are represented by barcodes in reference libraries, while species monitored in a single country frequently lack sequence records. A large proportion of species (up to 50%) in several taxonomic groups are only represented by private data in BOLD. Our results have implications for the future strategy to fill existing gaps in barcode libraries, especially if DNA metabarcoding is to be used in the monitoring of European aquatic biota under the WFD and MSFD. For example, missing species relevant to monitoring in multiple countries should be prioritized. We also discuss why a strategy for quality control and quality assurance of barcode reference libraries is needed and recommend future steps to ensure full utilization of metabarcoding in aquatic biomonitoring.
Vestibular modulation of multisensory integration during actual and vicarious tactile stimulation
Authors: Ponzo Sonia , Kirsch Louise P. , Fotopoulou Aikaterini , Jenkinson Paul M.
Published: March 2019

Background

The vestibular system has been shown to contribute to multisensory integration by balancing conflictual sensory information. It remains unclear whether such modulation of exteroceptive (e.g. vision), proprioceptive and interoceptive (e.g. affective touch) sensory sources is influenced by epistemically different aspects of tactile stimulation (i.e. felt from within vs seen, vicarious touch).

Objective

We aimed to i) replicate previous findings regarding the effects of galvanic stimulation of the right vestibular network (i.e. LGVS) in multisensory integration and ii) examine vestibular contributions to multisensory integration when touch is felt but not seen (and vice-versa).

Method

During artificial vestibular stimulation (LGVS, RGVS and Sham), healthy participants (N=36, Experiment 1; N=37, Experiment 2) looked at a rubber hand while either their own unseen hand or the rubber hand were touched by affective or neutral touch.

Results

We found that i) LGVS led to enhancement of vision over proprioception during visual only conditions (replicating our previous findings), and ii) LGVS (vs Sham) favoured proprioception over vision when touch was felt (Experiment 1), with the opposite results when touch was vicariously perceived via vision (Experiment 2), and with no difference between affective and neutral touch.

Conclusions

We showed how vestibular signals modulate the weight of each sensory modality according to the context in which they are perceived and that such modulation extends to different aspects of tactile stimulation: felt and seen touch are differentially balanced in multisensory integration according to their epistemic relevance.

Highlights

LGVS increased proprioceptive drift during vision of a rubber hand

Touch on participant’s hand decreased proprioceptive drift during LGVS

Vicarious touch on the Rubber Hand increased proprioceptive drift during LGVS

Vestibular signals differently balance sensory sources in multisensory integration
3D rotational motion of an endocytic vesicle on a complex microtubule network in a living cell
Authors: Lee S. , Higuchi H.
Published: March 2019

The transport dynamics of endocytic vesicles in a living cell contains essential biomedical information. Although the movement mechanism of a vesicle by motor proteins has been revealed, understanding the precise movement of vesicles on the cytoskeleton in a living cell has been considered challenging, due to the complex 3D network of cytoskeletons. Here, we specify the shape of the 3D interaction between the vesicle and microtubule, based on the theoretically estimated location of the microtubule and the vesicle trajectory data acquired at high spatial and temporal precision. We detected that vesicles showed more frequent direction changes with either in very acute or in obtuse angles than right angles, on similar time scales in a microtubule network. Interestingly, when a vesicle interacted with a relatively longer (> 400 nm) microtubule filament, rotational movement along the axis of the microtubule was frequently observed, implying an obstacle-avoiding motion. Our results are expected to give in-depth insight into understanding the actual 3D interactions between the intracellular molecule and complex cytoskeletal network.
Planar cell polarity in the C. elegans embryo emerges by differential retention of aPARs at cell-cell contacts
Authors: Dutta Priyanka , Odedra Devang , Pohl Christian
Published: March 2019

Formation of the anteroposterior and dorsoventral body axis in the Caenorhabditis elegans embryo depends on cortical actomyosin flows and advection of polarity determinants. The role of this patterning mechanism in tissue polarization immediately after formation of cell-cell contacts is not fully understood. Here, we demonstrate that planar cell polarity (PCP) is established in the C. elegans embryo at the time of left-right (l/r) symmetry breaking. At this stage, centripetal cortical flows asymmetrically and differentially advect anterior polarity determinants (aPARs) PAR-3, PAR-6 and PKC-3 from cell-cell contacts to the medial cortex, which results in their unmixing from apical myosin. Advection generally requires GSK-3 and CDC-42, while advection of PAR-6 specifically depends on the RhoGAP PAC-1. Concurrent asymmetric retention of PAR-3, E-cadherin/HMR-1, PAC-1 and opposing retention of the antagonistic Wnt pathway components APC/APR-1 and Frizzled/MOM-5 at apical cell-cell contacts leads to planar asymmetries. The most obvious mark of PCP, asymmetric retention of PAR-3 at posterior cell-cell contacts on the left side of the embryo, is required for proper cytokinetic cell intercalation. Hence, our data uncover how PCP can be established through Wnt signaling as well as dissociation and planar asymmetric retention of aPARs mediated by distinct Rho GTPases and their regulators.
Transcriptomic analysis of the BDNF-induced JAK/STAT pathway in neurons: a window into epilepsy-associated gene expression
Authors: Hixson Kathryn M , Cogswell Meaghan , Brooks-Kayal Amy R , Russek Shelley J
Published: March 2019

Background

Brain-derived neurotrophic factor (BDNF) is a major signaling molecule that the brain uses to control a vast network of intracellular cascades fundamental to properties of learning and memory, and cognition. While much is known about BDNF signaling in the healthy nervous system where it controls the mitogen activated protein kinase (MAPK) and cyclic-AMP pathways, less is known about its role in multiple brain disorders where it contributes to the dysregulated neuroplasticity seen in epilepsy and traumatic brain injury (TBI). We previously found that neurons respond to prolonged BDNF exposure (bothin vivo(in models of epilepsy and TBI) andin vitro(in BDNF treated primary neuronal cultures)) by activating the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathway. This pathway is best known for its association with inflammatory cytokines in non-neuronal cells.

Results

Here, using deep RNA-sequencing of neurons exposed to BDNF in the presence and absence of well characterized JAK/STAT inhibitors, and without non-neuronal cells, we determine the BDNF transcriptome that is specifically reliant on JAK/STAT signaling. Surprisingly, the transcriptome contains ion channels and neurotransmitter receptors coming from all the major classes expressed in the brain, along with key modulators of synaptic plasticity, neurogenesis, and axonal remodeling. Analysis of this dataset has also provided a window on the unique mechanism of JAK/STATs in neurons as differential gene expression mediated by STAT3 does not appear to be dependent upon phosphorylation at residue 705.

Conclusions

Our findings strengthen and expand the role that BDNF plays in the regulation of brain excitability at the transcriptional level. They also suggest that a majority of such signaling in neurons is tied to the activation of the JAK/STAT pathway which may be non-canonical, not based on phosphorylation of STAT3 proteins at Tyrosine 705.