bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of physical illness in mental health services
Authors: Blankenhorn D. , Kilian R. , Becker T.
Published: September 2018

There is excess morbidity and mortality from physical illness in people with mental disorders. Problems of somatic care in this patient group comprise difficulties of access to care, problems of equity and adequate use of diagnostic procedures and interventions. There are deficits in routine screening and monitoring, e.g. of metabolic and cardiovascular risks. Measures to ensure adequate physical health care include practical steps to increase service uptake and screening, service-level change such as integrated care models, preventive health interventions and optimisation of psychotropic drug treatment to reduce risk profiles. Issues of stigma and discrimination are important, and the level of staff training and quality of professionals are likely to be pivotal in bringing about change.
Severe mental illness and diabetes mellitus Type 2
Authors: Detraux J. , Vancampfort D. , Yu W. , Correll C.U. , De Hert M.
Published: September 2018

Three to four percent of the world’s population has diabetes mellitus (DM), which leads to a markedly increased risk of blindness, renal failure, amputation and cardiovascular disease, and reduces average life expectancy by 10 or more years. However, the prevalence of this severe metabolic disease among patients with severe mental illness (SMI), including schizophrenia, bipolar disorder, schizoaffective disorder and major depressive disorder, is higher than in the general population and its impact on these individuals significantly greater. We reviewed the literature on what is currently known about the relationship between SMI and DM and report prevalence rates of DM type 2 as well as important individual lifestyle choices and side effects of antipsychotic and antidepressant treatment, which each account for much of the increased risk of this metabolic disease in these patients. However, the exact cause and effect relationships between the prescription of these medications and DM type 2 still remain to be elucidated.
Depression and coronary heart disease. Clinical characteristics, pathogenetic links and treatment issues
Authors: Monteleone A. M. , Steardo L. , Maj M. , Monteleone P.
Published: September 2018

It is widely accepted that depression increases the risk of coronary heart disease (CHD) in healthy people while, in individuals with an existing heart disease, depression is a predictor of recurrent cardiac events and death. It seems that new-onset depression after an acute coronary syndrome (ACS) and not recurrent depression may worsen the cardiovascular outcome, and it has been suggested, although not conclusively proved, that depressive somatic symptoms, could be more cardiotoxic than depressive cognitive symptoms. Both psychosocial (low social support, less adherence to treatment recommendations, physical inactivity) and biological mechanisms (autonomic nervous system dysregulation, platelet and endothelial dysfunctions, inflammation, and neuroendocrine abnormalities) have been hypothesized to explain the link between depression and the increased risk of CHD or adverse cardiovascular prognosis. Randomized controlled clinical trials seem to suggest that depression in CHD patients is poor responsive to both pharmacological and psychotherapeutic treatments. Nevertheless, these trials provide also a robust evidence that CHD depressed patients non responder to antidepressant treatments are at greater risk of adverse cardiac event than patients with successfully treated depression. Therefore, it is advisable that psychiatrists, cardiologists and general practitioners coordinate their efforts in managing depression in CHD patients.
Bedeutung der studentischen Lehre für die Attraktivität des Faches Psychiatrie und Psychotherapie: Was müssen wir ändern, damit wir mehr Nachwuchs bekommen?
Authors: Voderholzer U. , Wündrich M. , Zielasek J.
Published: September 2018

Das Fach Psychiatrie und Psychotherapie wird wie viele andere medizinische Fächer in den kommenden Jahren von einem Nachwuchsmangel bedroht werden. Es müssen daher besondere Anstrengungen unternommen werden, um Studenten frühzeitig für dieses Fach zu begeistern. Hierzu sollte in der Lehre stärker das Thema Entstigmatisierung aufgegriffen werden, und es sollten die neurowissenschaftlichen Erkenntnisse sowie die Fortschritte in der evidenzbasierten Therapie psychischer Erkrankungen stärker herausgestellt werden. Angesichts der zunehmenden soziökonomischen Bedeutung psychischer Erkrankungen sollte die Lehre im Fach Psychiatrie insgesamt ausgeweitet werden, wobei sich am besten drei- bis vierwöchige ganztägige Praktika empfehlen, am besten mit Integration neuer Lehrmethoden wie Simulationspatienten und auch OSCE-Prüfungen. Auch die praktischen Vorteile einer Tätigkeit im Bereich der Psychiatrie und Psychotherapie im Vergleich mit anderen Fächern sollten bereits in der Ausbildung stärker vermittelt werden. Eine Qualitätssicherung durch systematische Lehr-Evaluation ist unerlässlich.
Wie gewinnen wir unseren Nachwuchs?: Der Züricher Studienschwerpunkt Psychiatrie und das Weiterbildungskonzept Ärztliche Psychotherapie
Authors: Rufer M. , Gerke W. , Schnyder U.
Published: September 2018

In der Schweiz kann der Bedarf an Psychiatern seit Jahren nur mittels ausländischer Kollegen gedeckt werden. Initiativen zur Förderung des Nachwuchses sind dringend notwendig, auch angesichts der weltweiten Zunahme an psychischen Erkrankungen. Zwei Projekte zur Nachwuchsförderung werden in diesem Artikel vorgestellt, von denen eines im Medizinstudium und das andere in der Facharztweiterbildung ansetzt. Im Zürcher Studienschwerpunkt Psychiatrie werden den Studierenden Kenntnisse und Schlüsselkompetenzen für das Fach Psychiatrie und Psychotherapie bereits zu einem sehr frühen Zeitpunkt vermittelt. Damit wird die Möglichkeit geschaffen, dass sich die Studierenden ein eigenes Bild von den klinischen und wissenschaftlichen Aspekten dieses Fachgebietes machen. – Im Weiterbildungskonzept Ärztliche Psychotherapie werden in ein modellspezifisches Weiterbildungsprogramm (kognitiv-verhaltenstherapeutisch, psychodynamisch oder systemisch) systematisch modellübergreifende Elemente integriert, was den Alltagsanforderungen an Assistenzärzte weit mehr entspricht als eine rein modellspezifische Weiterbildung. Beide Projekte haben zum Ziel, die Attraktivität des Fachgebietes der Psychiatrie und Psychotherapie zu erhöhen und damit einen Beitrag zur Nachwuchsförderung zu leisten.
Cognitive Behavioural Therapy for psychosis
Authors: Garety P. A.
Published: September 2018

Cognitive Behavioural Therapy for psychosis (CBTp), with its theoretical underpinning derived from cognitive models of psychosis, is described. The therapeutic approach is elucidated, in terms of goals, techniques, content and style. Adjustments of the therapy to address the particular problems of psychosis, including building a therapeutic relationship and matching cognitive capacities, are highlighted. The extensive evidence for the effectiveness of CBTp is reviewed and methodological issues in trials noted. The evidence shows that CBTp has small to medium effects on a range of outcomes, including symptoms, affect and functioning, and that the evidence is most consistent for improvements in people with persistent positive symptoms. New developments in CBTp are described, and the promise of developing focused treatments targeting specific psychological processes, such as reasoning or emotional processes, hypothesized as causal mechanisms of distressing symptom persistence. Finally, to support implementation of CBTp in practice, it is concluded that there is a need for dissemination programs, addressing staff attitudes and skills and wider system changes.
FRAC: Fringing-RF-field-activated dc-to-pulse converter for low-energy ion beams
Authors: Wakasugi M. , Togasaki M. , Ohnishi T. , Kurita K. , Toba R. , Watanabe M. , Yamada K.
Published: September 2018

We developed a new type of dc-to-pulse converter, called FRAC (Fringing-RF-field-Activated dc-to-pulse Converter) for low-energy ion beams electrostatically accelerated from an ion source. FRAC is based on a radio-frequency quadrupole (RFQ) linear trap technique and works in principle under ultrahigh vacuum conditions. Ions continuously injected into FRAC are decelerated by an alternating longitudinal electric field produced in a distorted radio frequency field around the edge region of RFQ rods. These ions accumulate in FRAC for a significantly long time. This edge effect appears most notably when the energy of incoming ions exceeds the injection barrier potential by less than a few eV and the energy spread is quite small. The ions stacked during the FRAC operation period are ejected as a high intensity pulsed beam. We investigated the performance of FRAC and the capability of some FRAC operation methods developed to enhance the dc-to-pulse conversion efficiency. The maximum conversion efficiencies achieved were 22% and 5.6% at FRAC operation frequencies of 10 and 1 Hz, respectively. The number of ions contained in an output beam pulse with a duration of 500 μs was in practice 1.6 × 109 ions/pulse at an injected dc beam intensity of 4.6 nA and an operation frequency of 1 Hz.
Critical-point model dielectric function analysis of WO3 thin films deposited by atomic layer deposition techniques
Authors: Kılıç Ufuk , Sekora Derek , Mock Alyssa , Korlacki Rafał , Valloppilly Shah , Echeverría Elena M. , Ianno Natale , Schubert Eva , Schubert Mathias
Published: September 2018

WO3 thin films were grown by atomic layer deposition and spectroscopic ellipsometry data gathered in the photon energy range of 0.72–8.5 eV, and from multiple samples were utilized to determine the frequency dependent complex-valued isotropic dielectric function for WO3. We employ a critical-point model dielectric function analysis and determine a parameterized set of oscillators and compare the observed critical-point contributions with the vertical transition energy distribution found within the band structure of WO3 calculated by the density functional theory. The surface roughness was investigated using atomic force microscopy, and compared with the effective roughness as seen by the spectroscopic ellipsometry.
X-ray streaked refraction enhanced radiography for inferring inflight density gradients in ICF capsule implosions
Authors: Dewald E. L. , Landen O. L. , Masse L. , Ho D. , Ping Y. , Thorn D. , Izumi N. , Berzak Hopkins L. , Kroll J. , Nikroo A. , Koch J. A.
Published: September 2018

In the quest for reaching ignition of deuterium-tritium (DT) fuel capsule implosions, experiments on the National Ignition Facility (NIF) have shown lower final fuel areal densities than simulated. Possible explanations for reduced compression are higher preheat that can increase the ablator-DT ice density jump and induce mix at that interface or reverberating shocks. We are hence developing x-ray Refraction Enhanced Radiography (RER) to infer the inflight density profiles in layered fuel capsule implosions. We use a 5 μm slit backlit by a Ni 7.8 keV He-α NIF laser driven x-ray source positioned at 20 mm from the capsule to cast refracted images of the inflight capsule onto a streak camera in a high magnification (M ∼ 60×) setup. Our first experiments have validated our setup that recorded a streaked x-ray fringe pattern from an undriven high density carbon (HDC) capsule consistent with ray tracing calculations at the required ∼6 μm and 25 ps resolution. Streaked RER was then applied to inflight layered HDC capsule implosions using a hydrogen-tritium fuel mix rather than DT to reduce neutron yields and associated backgrounds. The first RER of an imploding capsule revealed strong features associated with the ablation front and ice-ablator interface that are not visible in standard absorption radiographs.
Electrically-controlled Faraday rotation and wavelength mismatch phenomena in a magnetophotonic structure containing nematic layers
Authors: Oliveira E. J. , de Melo P. B. , da Silva R. R. , Zanetti F. M. , de Oliveira I. N.
Published: September 2018

In this study, we investigate the effects of the director reorientation on the spectral properties of a one-dimensional magnetophotonic crystal constituted by a sequence of magnetic and nematic layers, which exhibits a magneto-optical defect as the central layer. Using the Eidner-Oldano treatment to solve the Berreman equation, we numerically determine how the Faraday rotation and transmission spectrum of the photonic systems are affected by a field-induced reorientation in the nematic layers. Our results reveal that the transmittance spectrum of the magnetophotonic system is strongly sensitive to the director profile when the applied voltage is raised above the Freedericksz threshold. The director reorientation leads to the suppression of the typical wavelength mismatch between the Faraday rotation and light localization phenomena in one-dimensional photonic structures based on materials with different types of birefringence. Considering the polarization configurations of the propagation eigenmodes for a birefringent medium, the main mechanism behind mismatch suppression is analyzed, emphasizing the effects associated with the field-induced nematic reorientation. Our results show that the electric control of wavelength mismatch in magnetophotonic systems may be used as an efficient mechanism to develop a new class of optical switches and logic gate devices.
Influence of feed ingredients with pellet-binding properties on physical pellet quality, growth performance, carcass characteristics and nutrient retention in broiler chickens
Authors: Moradi Arash , Moradi Soudabeh , Abdollahi M. Reza
Published: September 2018

The influence of inclusion of pellet binder on physical pellet quality, growth performance, carcass characteristics and total tract apparent retention of nutrients was examined. Broiler starter (Days 1–21, pellet diameter: 2.5 mm) and finisher (Days 22–42, pellet diameter: 4 mm) diets were formulated and then allocated to one of the seven treatments including control diet, and diets including sodium bentonite (10 and 20 g/kg), wheat gluten (10 and 20 g/kg) and wheat (100 and 200 g/kg). All ingredients used as a pellet binder significantly (P < 0.05) increased the pellet-durability index compared with control diet. Wheat gluten and wheat at both inclusion rates were significantly (P < 0.05) more efficient than was sodium bentonite in improving pellet hardness. From Day 1 to Day 42, chickens fed 10 g/kg wheat gluten and 100 and 200 g/kg wheat gained significantly (P < 0.05) more weight than did control. During starters, birds fed 200 g/kg wheat showed the highest feed intake (P < 0.05). On Day 42, all the pellet binders resulted in a heavier heart weight than in the control (P < 0.05). At Day 21, the length of ileum was significantly (P < 0.05) higher in birds fed 10 and 20 g/kg sodium bentonite, 10 g/kg wheat gluten and 200 g/kg wheat, but at Day 42, it was greater in birds fed 20 g/kg wheat gluten and 200 g/kg wheat than in those fed the control diet. Inclusion of wheat gluten (10 and 20 g/kg) and wheat (100 and 200 g/kg) increased (P < 0.05) fat apparent retention. Birds fed 20 g/kg wheat gluten had a significantly (P < 0.05) higher total tract apparent retention of crude fibre, also calcium apparent retention improved by wheat gluten inclusion at concentrations of 10 and 20 g/kg compared with control (P < 0.05). Overall, inclusion of 10 g/kg wheat gluten, and 100 and 200 g/kg of wheat improved physical pellet quality and weight gain in broilers.
Evaluation of general practice house officer attachments in Counties Manukau: insights and benefits
Authors: Le Comte Lyndsay , Hayward Brooke , Hughes David , Villa Luis , Madell Dominic
Published: September 2018

ABSTRACT BACKGROUND The Medical Council of New Zealand requires graduating doctors to have community attachments within their first two years of practice by 2020. Counties Manukau Health has developed a programme where house officers (HOs) are attached to a general practice for three months. AIM This study aimed to establish the value of four HO general practice attachments in Counties Manukau and describe how HOs are being used in these practices. METHODS A mixed-methods design was used to evaluate three attachment runs. Two practices provided the number of patients seen by HOs. Fifty-eight patients were surveyed to assess patient perceptions of the HOs. Six HOs, four supervising general practitioners, two PHO senior staff and one practice manager participated in semi-structured interviews. Focus groups were held with nurses, doctors and administrative staff at all four practices. FINDINGS HOs saw 300–600 patients in one practice and 800–1000 in the other during their attachment. Practices developed their own approach to mentoring and teaching HOs. Most patients reported positive perceptions of the HOs. Themes from interviews and focus groups were consistent among participants and included: improved HO confidence, clinical skills and understanding of general practice; extra capacity and improved quality of care and staff satisfaction among practices. CONCLUSION HOs and practices viewed HO attachments in general practice positively. HOs developed clinical skills and understanding of primary health care. Practice teams enjoyed the energy and enthusiasm of the HOs, while providing clinical support to ensure quality patient care.
Principles of family medicine and general practice – defining the five core values of the specialty
Authors: Hashim M. Jawad
Published: September 2018

ABSTRACT The principles of general practice and family medicine are the defining characteristics of the speciality. The five principles are: compassionate care – a caring attitude towards patients and their families shown as kindness and a desire to help; generalist approach – a perspective on the whole person and the context of illness including family, culture and society; continuity of relationship – the interpersonal bond of trust and respect between family physicians, patients, and their families that develops over the life course; reflective mindfulness– doctors’ awareness of their thoughts and emotions manifested as a sense of presence and attentiveness towards self and others; and lifelong learning – a commitment to personal and professional development by participating in learning activities and practice-based research that leads to better patient outcomes. Concepts such as care coordination, preventive care, access to care, professional competence, resource management and community-based care, are part of the principles above. The term ‘comprehensive care’ is should be avoided as it misinterprets the scope of family medicine. The principles of general practice and family medicine characterise the speciality’s core values. These guidelines form the basis of clinical practice as well as the identity of family medicine as a discipline. Aiming to extract the principles from current literature, I searched MEDLINE and Google Scholar for the term ‘principles of family medicine’ with results sorted by relevance, and without limits on language or date of publication. Major textbooks of family medicine and general practice were consulted as well.1–6 As supported by academic literature, the terms ‘general practice’ and ‘family medicine’ are used synonymously.7
Antidepressants for treatment of depression in primary care: a systematic review and meta-analysis
Authors: Arroll Bruce , Chin Weng-yee , Martis Waldron , Goodyear-Smith Felicity , Mount Vicki , Kingsford Douglas , Humm Stephen , Blashki Grant , MacGillivray Stephen
Published: September 2018

ABSTRACT

INTRODUCTION
Evidence for the effectiveness of drug treatment for depression in primary care settings remains limited, with little information on newer antidepressant classes.

AIM
To update an earlier Cochrane review on the effectiveness of antidepressants in primary care to include newer antidepressant classes, and to examine the efficacy of individual agents.

METHODS
Selection criteria included antidepressant studies with a randomly assigned placebo group where half or more subjects were recruited from primary care. The Cochrane Collaboration Depression, Anxiety and Neurosis (CCDAN) group searched multiple databases to identify eligible studies. Data extraction was performed independently by two reviewers. Data were analysed using Revman version 5.3.5.

RESULTS
In total, 17 papers and 22 comparisons were included for analysis. Significant benefits in terms of response were found for tricyclic antidepressants (TCA) with a relative risk (RR) = 1.23 (95% CI, 1.01–1.48), and serotonin selective reuptake inhibitors (SSRI) with a RR = 1.33 (95% CI, 1.20–1.48). Mianserin was effective for continuous outcomes. Numbers needed to treat (NNT) for TCA = 8.5; SSRI = 6.5; and venlafaxine = 6. Most studies were industry-funded and of a brief duration (≤ 8 weeks). There was evidence of publication bias. There were no studies comparing newer antidepressants against placebo.

CONCLUSION
Antidepressants such as TCA, SSRI, SNRI (serotonin–norepinephrine reuptake inhibitor) and NaSSA (noradrenergic and specific serotonergic antidepressant) classes appear to be effective in primary care when compared with placebo. However, in view of the potential for publication bias and that only four studies were not funded by industry, caution is needed when considering their use in primary care.
General practice and patients’ views of the social networks of patients with multimorbidity
Authors: McKinlay Eileen , Young Jessica , Gray Ben
Published: September 2018

ABSTRACT

INTRODUCTION
For patients with multimorbidity to live well, they need the support of not only health professionals but family, friends and organisations. These social networks provide support, potentially enabling the formation of a Community of Clinical Practice approach to multimorbidity care.

AIM
This study aimed to explore general practice knowledge of the social networks of patients with multimorbidity.

METHODS
Social network maps were completed by both patients and general practice. The social network maps of 22 patients with multimorbidity were compared with corresponding social network maps completed by general practice staff.

RESULTS
In 60% (13/22) of the patients, general practice staff held a high or moderate knowledge of individual patients’ social networks. Information on social networks was recalled from staff memory and not systematically recorded in patients’ electronic health records.

DISCUSSION
Social network information is not routinely collected, recorded or used by general practice to understand the support available to patients with multimorbidity. General practice could take an active role in coordinating social network supporters for certain patient groups with complex multimorbidity. For these groups, there is value in systematically recording and regularly updating their social network information for general practice to use as part of a coordinated Community of Clinical Practice.
Female genital mutilation: an update for primary health-care professionals
Authors: Todkari Nikhilesh
Published: September 2018

ABSTRACT
Female genital mutilation (FGM) has historically been seen as a health concern limited to women living in other parts of the world. However, with the rising number of migrants, refugees and asylum seekers, countries like New Zealand, Australia and Europe have seen a surge in the number of women and girls affected by FGM seeking medical care. This topic is increasingly becoming relevant to primary health-care providers in this country and therefore a good understanding of this practice is important.
Who can afford a Mirena® for contraception?
Authors: Murray Catriona , Roke Christine
Published: September 2018

ABSTRACT

INTRODUCTION
The Mirena®, a levonorgestrel-releasing intrauterine system (LNG-IUS), is an effective form of contraception that lasts for 5 years. In New Zealand, it is not subsidised for contraception and the device costs NZ$340 at Family Planning clinics.

AIM
To determine if there is a difference in the socioeconomic status and ethnicity of women who chose an LNG-IUS for contraception compared with women opting for a subsidised long-acting contraceptive (copper intrauterine device (IUD) or Jadelle® implant) or who qualified for a Special Authority Mirena® (funded by Pharmac, as treatment for heavy menstrual bleeding).

METHODS
All the Mirena®, Jaydess®, IUD and Jadelle® insertions that occurred at Family Planning clinics in 2015 in the Wellington region were identified. The deprivation quintile of current address and ethnicity were determined.

RESULTS
In the study period, 1410 devices were inserted. Of the self-funded LNG-IUSs inserted, 5% were for women with quintile 5 addresses (areas with the most deprived New Zealand Deprivation (NZDep) scores) and 28% for quintile 1 areas (least deprived NZDep scores). Of the Special Authority Mirenas® inserted, 24% were for women residing in quintile 5 areas and 19%, quintile 1 areas. Self-funded LNG-IUS were chosen by 2.5% of Māori women choosing contraception at study Family Planning clinics and no Pacific Peoples, whereas 21% of New Zealand European women chose LNG-IUS. Special Authority Mirenas® were chosen by 9.5% Māori and 9.6% Pacific Peoples compared to 4% New Zealand Europeans.

DISCUSSION
Māori, Pacific Peoples and women residing in quintile 5 areas chose self-funded LNG-IUSs less often than Special Authority Mirenas®. This was not the case for the other groups, who showed higher use of self-funded LNG-IUSs than Special Authority Mirenas®.
Reviving oncogenic addiction to MET bypassed by BRAF (G469A) mutation
Authors: Virzì Anna Rita , Gentile Alessandra , Benvenuti Silvia , Comoglio Paolo M.
Published: September 2018

Significance

Genetic alterations of two oncogenes occur frequently in cancers; however, silencing of an oncogenic driver by activation of a second oncogene has never been described. Here we report the case of a cancer carrying alterations of two oncogenes residing on the same pathway; namely, MET amplification and BRAF mutation. Surprisingly, the pharmacological blockade of BRAF had no effect, as it was followed by MET reactivation: Mechanistic studies unraveled the existence of a previously unknown negative feedback inhibition of MET by BRAF. This phenomenon provides evidence for a mechanism of resistance to therapy against a single-target oncogene.
A simple developmental model recapitulates complex insect wing venation patterns
Authors: Hoffmann Jordan , Donoughe Seth , Li Kathy , Salcedo Mary K. , Rycroft Chris H.
Published: September 2018

Insect wings are typically supported by thickened struts called veins. These veins form diverse geometric patterns across insects. For many insect species, even the left and right wings from the same individual have veins with unique topological arrangements, and little is known about how these patterns form. We present a large-scale quantitative study of the fingerprint-like “secondary veins.” We compile a dataset of wings from 232 species and 17 families from the order Odonata (dragonflies and damselflies), a group with particularly elaborate vein patterns. We characterize the geometric arrangements of veins and develop a simple model of secondary vein patterning. We show that our model is capable of recapitulating the vein geometries of species from other, distantly related winged insect clades.
IκBζ is a key transcriptional regulator of IL-36–driven psoriasis-related gene expression in keratinocytes
Authors: Müller Anne , Hennig André , Lorscheid Sebastian , Grondona Paula , Schulze-Osthoff Klaus , Hailfinger Stephan , Kramer Daniela
Published: September 2018

Proinflammatory cytokine signaling in keratinocytes plays a crucial role in the pathogenesis of psoriasis, a skin disease characterized by hyperproliferation and abnormal differentiation of keratinocytes and infiltration of inflammatory cells. Although IL-17A and TNFα are effective therapeutic targets in psoriasis, IL-36 has recently emerged as a proinflammatory cytokine. However, little is known about IL-36 signaling and its downstream transcriptional responses. Here, we found that exposure of keratinocytes to IL-36 induced the expression of IκBζ, an atypical IκB member and a specific transcriptional regulator of selective NF-κB target genes. Induction of IκBζ by IL-36 was mediated by NF-κB and STAT3. In agreement, IL-36–mediated induction of IκBζ was found to be required for the expression of various psoriasis-related genes involved in inflammatory signaling, neutrophil chemotaxis, and leukocyte activation. Importantly, IκBζ-knockout mice were protected against IL-36–mediated dermatitis, accompanied by reduced proinflammatory gene expression, decreased immune cell infiltration, and a lack of keratinocyte hyperproliferation. Moreover, expression of IκBζ mRNA was highly up-regulated in biopsies of psoriasis patients where it coincided with
IL36G
levels. Thus our results uncover an important role for IκBζ in IL-36 signaling and validate IκBζ as an attractive target for psoriasis therapy.
On the origin of the elusive first intermediate of CO
2
electroreduction
Authors: Chernyshova Irina V. , Somasundaran Ponisseril , Ponnurangam Sathish
Published: September 2018

Significance

The understanding of a catalytic reaction starts with understanding its first elementary step. Surprisingly, despite the large number of studies, it is unclear whether one common or two different first intermediates control the selectivity of CO
2
electroreduction to formate and CO. We settle this controversy for Cu, which is best known for its unique capacity to synthesize C
1+
products but is just emerging as a superior earth-abundant catalyst for CO and formate. We provide solid experimental and theoretical support of the one common first-intermediate (Hori’s) model, the first intermediate being carboxylate. This outcome is an essential milestone toward accurate specification of the reaction descriptors in the growing effort to accelerate the discovery of a viable CO
2
electroreduction catalyst.
Dedifferentiation of caudate functional connectivity and striatal dopamine transporter density predict memory change in normal aging
Authors: Rieckmann Anna , Johnson Keith A. , Sperling Reisa A. , Buckner Randy L. , Hedden Trey
Published: September 2018

Significance

The biological changes associated with cognitive decline in aging are complex. Age-related changes in the striatum have been hypothesized as potentially important for predicting declining memory function over the adult life span, but empirical support for this hypothesis is sparse. We provide evidence from human fMRI and PET data for the association of age-related differences in striatal function to memory decline. A reduction of specificity (i.e., dedifferentiation) in functional coupling between the caudate and regions of the default network predicted memory decline over subsequent years in older adults. An age-related reduction in density of presynaptic striatal dopamine transporters also predicted memory decline but was unrelated to functional dedifferentiation, suggesting that relations between age-related changes in striatal functions and memory are multifaceted.
Effects of self-transcendence on neural responses to persuasive messages and health behavior change
Authors: Kang Yoona , Cooper Nicole , Pandey Prateekshit , Scholz Christin , O’Donnell Matthew Brook , Lieberman Matthew D. , Taylor Shelley E. , Strecher Victor J. , Dal Cin Sonya , Konrath Sara , Polk Thad A. , Resnicow Kenneth , An Lawrence , Falk Emily B.
Published: September 2018

Self-transcendence refers to a shift in mindset from focusing on self-interests to the well-being of others. We offer an integrative neural model of self-transcendence in the context of persuasive messaging by examining the mechanisms of self-transcendence in promoting receptivity to health messages and behavior change. Specifically, we posited that focusing on values and activities that transcend the self can allow people to see that their self-worth is not tied to a specific behavior in question, and in turn become more receptive to subsequent, otherwise threatening health information. To test whether inducing self-transcendent mindsets before message delivery would help overcome defensiveness and increase receptivity, we used two priming tasks, affirmation and compassion, to elicit a transcendent mindset among 220 sedentary adults. As preregistered, those who completed a self-transcendence task before health message exposure, compared with controls, showed greater increases in objectively logged levels of physical activity throughout the following month. In the brain, self-transcendence tasks up-regulated activity in a region of the ventromedial prefrontal cortex, chosen for its role in positive valuation and reward processing. During subsequent health message exposure, self-transcendence priming was associated with increased activity in subregions of the ventromedial prefrontal cortex, implicated in self-related processing and positive valuation, which predicted later decreases in sedentary behavior. The present findings suggest that having a positive self-transcendent mindset can increase behavior change, in part by increasing neural receptivity to health messaging.
Hippocampal CA1 gamma power predicts the precision of spatial memory judgments
Authors: Stevenson Rebecca F. , Zheng Jie , Mnatsakanyan Lilit , Vadera Sumeet , Knight Robert T. , Lin Jack J. , Yassa Michael A.
Published: September 2018

Significance

Spatial memory is critical to every facet of our lives. The hippocampus is known to play a prominent role in the formation and retrieval of spatial memories; however, the exact mechanisms remain elusive. Using electrophysiology recordings from presurgical epilepsy patients implanted with depth electrodes, we measured high-frequency neural activity from the CA1 region of the hippocampus and the dorsolateral prefrontal cortex. We found associations between increased high-frequency activity and the precision of spatial memory retrieval. These data suggest that local processing within the CA1 subfield and the dorsolateral prefrontal cortex underlie the quality of retrieved spatial memories.
Molecular mechanisms of the interhead coordination by interhead tension in cytoplasmic dyneins
Authors: Wang Qian , Jana Biman , Diehl Michael R. , Cheung Margaret S. , Kolomeisky Anatoly B. , Onuchic José N.
Published: September 2018

Significance

Cell physiology strongly depends on motor proteins to transport and regulate the intracellular distributions of key materials and organelles. Cytoplasmic dynein, one of the most important biological motors in living cells, is an efficient retrograde motor due to its ability to step continuously along microtubule filaments. Dynein has two identical domains that are coordinated by interhead tension. However, the molecular mechanism of this coordination is not understood. By combining computer simulations with analytical calculations, we show that the interhead tension creates opposite torques on the leading and trailing heads, crucial for the coordination between the heads. Our finding provides a molecular basis for understanding the functionality of cytoplasmic dynein.
Assimilation of formic acid and CO
2
by engineered
Escherichia coli
equipped with reconstructed one-carbon assimilation pathways
Authors: Bang Junho , Lee Sang Yup
Published: September 2018

Significance

While biological utilization of one-carbon (C1) compounds has attracted much attention, previous studies have focused mainly on the utilization of CO
2
. Here, we report development of
Escherichia coli
strains capable of assimilating formic acid (FA) and CO
2
through the C1 assimilation pathway, synthesizing pyruvate from FA and CO
2
by establishing the reconstructed tetrahydrofolate cycle and the reverse glycine cleavage pathway. To generate energy and redox while using less glucose, a heterologous formate dehydrogenase was introduced together with the C1 assimilation pathway. The resulting strain could utilize FA and CO
2
as sole carbon sources for sustaining growth. This work demonstrates that the combined use of the C1 assimilation pathway and formate dehydrogenase allows
E. coli
to utilize FA and CO
2
efficiently.
Metal-free class Ie ribonucleotide reductase from pathogens initiates catalysis with a tyrosine-derived dihydroxyphenylalanine radical
Authors: Blaesi Elizabeth J. , Palowitch Gavin M. , Hu Kai , Kim Amelia J. , Rose Hannah R. , Alapati Rahul , Lougee Marshall G. , Kim Hee Jong , Taguchi Alexander T. , Tan Kong Ooi , Laremore Tatiana N. , Griffin Robert G. , Krebs Carsten , Matthews Megan L. , Silakov Alexey , Bollinger J. Martin , Allen Benjamin D. , Boal Amie K.
Published: September 2018

All cells obtain 2′-deoxyribonucleotides for DNA synthesis through the activity of a ribonucleotide reductase (RNR). The class I RNRs found in humans and pathogenic bacteria differ in (
i
) use of Fe(II), Mn(II), or both for activation of the dinuclear-metallocofactor subunit, β; (
ii
) reaction of the reduced dimetal center with dioxygen or superoxide for this activation; (
iii
) requirement (or lack thereof) for a flavoprotein activase, NrdI, to provide the superoxide from O
2
; and (
iv
) use of either a stable tyrosyl radical or a high-valent dimetal cluster to initiate each turnover by oxidizing a cysteine residue in the α subunit to a radical (Cys•). The use of manganese by bacterial class I, subclass b-d RNRs, which contrasts with the exclusive use of iron by the eukaryotic Ia enzymes, appears to be a countermeasure of certain pathogens against iron deprivation imposed by their hosts. Here, we report a metal-free type of class I RNR (subclass e) from two human pathogens. The Cys• in its α subunit is generated by a stable, tyrosine-derived dihydroxyphenylalanine radical (DOPA•) in β. The three-electron oxidation producing DOPA• occurs in
Escherichia coli
only if the β is coexpressed with the NrdI activase encoded adjacently in the pathogen genome. The independence of this new RNR from transition metals, or the requirement for a single metal ion only transiently for activation, may afford the pathogens an even more potent countermeasure against transition metal-directed innate immunity.
Association Between Executive Functioning and Functional Impairment Among Pediatric Cancer Survivors and Controls
Authors: Erickson Sarah J , Hile Sarah , Rieger Rebecca E , Moss Natalia C , Dinces Sarah , Annett Robert D
Published: September 2018

Objective

To examine the impact of cancer treatment upon neurocognitive and functional impairment; and to explore the relationship between these constructs in pediatric cancer survivors compared to controls.

Method

A cross-sectional cohort of survivors (n = 26) and controls (n = 53) was included. Survivors were off treatment an average of 6.35 years (SD = 5.38; range 1–15 years) and demonstrated an average “medium” Central Nervous System (CNS) treatment intensity score. Participants completed measures of neurocognitive functions including intellectual assessment (RIST) and executive functions (NIH Examiner), while parents reported on children’s functional impairment (BIS).

Results

Survivors were similar to controls in neurocognitive ability, including intellectual and executive functions, and functional impairment. Regardless of group membership, NIH Examiner performance and functional impairment increased with age. Increased impairment was associated with different neurocognitive variables for survivors versus controls.

Conclusions

Research regarding functional impairment of cancer survivors and the association between neurocognitive deficits and functional impairment has been limited. Our results demonstrate that, while low treatment intensity may confer relative sparing of neurocognitive and executive functioning among survivors, functional impairment continues to be a potential risk. In conclusion, pediatric cancer survivors should be screened for functional difficulties, particularly in the areas of interpersonal relations and self-care.
Protein–peptide docking using CABS-dock and contact information
Authors: Blaszczyk Maciej , Ciemny Maciej Pawel , Kolinski Andrzej , Kurcinski Mateusz , Kmiecik Sebastian
Published: September 2018

CABS-dock is a computational method for protein–peptide molecular docking that does not require predefinition of the binding site. The peptide is treated as fully flexible, while the protein backbone undergoes small fluctuations and, optionally, large-scale rearrangements. Here, we present a specific CABS-dock protocol that enhances the docking procedure using fragmentary information about protein–peptide contacts. The contact information is used to narrow down the search for the binding peptide pose to the proximity of the binding site. We used information on a single-chosen and randomly chosen native protein–peptide contact to validate the protocol on the peptiDB benchmark. The contact information significantly improved CABS-dock performance. The protocol has been made available as a new feature of the CABS-dock web server (at http://biocomp.chem.uw.edu.pl/CABSdock/).

Short abstract

CABS-dock is a tool for flexible docking of peptides to proteins. In this article, we present a protocol for CABS-dock docking driven by information about protein–peptide contact(s). Using information on individual protein–peptide contacts allows to improve the accuracy of CABS-dock docking.
Treatments targeting inotropy
Authors: Maack Christoph , Eschenhagen Thomas , Hamdani Nazha , Heinzel Frank R , Lyon Alexander R , Manstein Dietmar J , Metzger Joseph , Papp Zoltán , Tocchetti Carlo G , Yilmaz M Birhan , Anker Stefan D , Balligand Jean-Luc , Bauersachs Johann , Brutsaert Dirk , Carrier Lucie , Chlopicki Stefan , Cleland John G , de Boer Rudolf A , Dietl Alexander , Fischmeister Rodolphe , Harjola Veli-Pekka , Heymans Stephane , Hilfiker-Kleiner Denise , Holzmeister Johannes , de Keulenaer Gilles , Limongelli Giuseppe , Linke Wolfgang A , Lund Lars H , Masip Josep , Metra Marco , Mueller Christian , Pieske Burkert , Ponikowski Piotr , Ristić Arsen , Ruschitzka Frank , Seferović Petar M , Skouri Hadi , Zimmermann Wolfram H , Mebazaa Alexandre
Published: September 2018

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation–contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.
Galois Closures of Non-commutative Rings and an Application to Hermitian Representations
Authors: Ho Wei , Satriano Matthew
Published: September 2018

Galois closures of commutative rank $n$ ring extensions were introduced by Bhargava and the 2nd author. In this paper, we generalize the construction to the case of non-commutative rings. We show that noncommutative Galois closures commute with base change and satisfy a product formula. As an application, we give a uniform construction of many of the representations arising in arithmetic invariant theory, including many Vinberg representations.
‘One of our National Treasures’: the biography of the skull of Turlough Carolan the Blind Harper
Authors: Crooke Elizabeth
Published: September 2018

Many Irish musicians will have heard of Turlough Carolan (1670–1738), frequently referred to as the Blind Harper. Less well known is that his skull was exhumed in 1750, twelve years after he was buried. Since that year and throughout the nineteenth century, a human skull, declared to be that of Carolan, was displayed in various prestigious locations. In the early twentieth century it was received by the National Museum of Ireland, where it still resides. This paper traces the story of the skull from grave to museum stores, providing an insight into the fascination exerted by remains of the deceased and the special significance given in Ireland to the remains of a revered musician. The skull is where multiple histories meet: it embodies a record of customs in rural Ireland; it tells us something of the display of collections by Irish gentry and the middle classes; and it is a route into exploring the cultural meanings of our collections.
Operative Anatomy of the Human Skull: A Virtual Reality Expedition
Authors: Hendricks Benjamin K , Patel Akash J , Hartman Jerome , Seifert Mark F , Cohen-Gadol Aaron
Published: September 2018

INTRODUCTION

The human cranial vault possesses an incredible, complex anatomical intricacy. Bridging the divide between 2-dimensional (2D) learning resources and the 3-dimensional (3D) world in which the anatomy becomes clinically relevant poses an intellectual challenge. Advances in computer graphics and modelling technologies have allowed increasingly accurate and representative resources to supplement cadaveric dissection specimens.

OBJECTIVE

To create accurate virtual models of all cranial bones to augment education, research, and clinical endeavours.

METHODS

Through a careful analysis of osteological specimens and high-resolution radiographic studies, a highly accurate virtual model of the human skull was created and annotated with relevant anatomical landmarks.

RESULTS

The skull was divided into 6 major segments including frontal, ethmoid, sphenoid, temporal, parietal, and occipital bones. These bones were thoroughly annotated to demonstrate the intricate anatomical features.

CONCLUSION

This virtual model has the potential to serve as a valuable resource for educational, research, and clinical endeavours, and demonstrates the significance of advances in computer modelling that can contribute to our understanding of neurosurgical anatomical substrates.
Convexity of the moment map image for torus actions on
b

m

-symplectic manifolds
Authors: Guillemin Victor W. , Miranda Eva , Weitsman Jonathan
Published: September 2018

We prove a convexity theorem for the image of the moment map of a Hamiltonian torus action on a
b

m

-symplectic manifold.

This article is part of the theme issue ‘Finite dimensional integrable systems: new trends and methods’.