bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness on fertility outcome of tubal flushing with different contrast media: systematic review and network meta‐analysis
Authors: Wang R. , van Welie N. , van Rijswijk J. , Johnson N. P. , Norman R. J. , Dreyer K. , Mijatovic V. , Mol B. W.
Published: February 2019

Objectives

To compare, in women with infertility, the effectiveness and safety of tubal flushing using oil‐based contrast medium, water‐based contrast medium or their combination, and no tubal flushing, and to evaluate the effectiveness of tubal flushing on fertility outcome over time.

Methods

We performed a systematic review and network meta‐analysis, searching the electronic databases MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, and trial registries, up to 25 September 2018. We included randomized controlled trials (RCTs) comparing the following interventions with each other or with no intervention in women with infertility: tubal flushing using water‐based contrast medium, tubal flushing using oil‐based contrast medium or additional tubal flushing with oil‐based medium following diagnostic tubal flushing with water‐based medium. The outcomes included clinical pregnancy, live birth, ongoing pregnancy, miscarriage, ectopic pregnancy and adverse events.

Results

Of the 283 studies identified through the search, 14 RCTs reporting on 3852 women with infertility were included. Network meta‐analysis showed that tubal flushing using oil‐based contrast medium was associated with higher odds of clinical pregnancy within 6 months after randomization and more subsequent live births compared with tubal flushing using water‐based medium (odds ratio (OR), 1.67 (95% CI, 1.38–2.03), moderate certainty of evidence; and OR, 2.18 (95% CI, 1.30–3.65), low certainty of evidence, respectively) and compared with no intervention (OR, 2.28 (95% CI, 1.50–3.47), moderate certainty of evidence; and OR, 2.85 (95% CI, 1.41–5.74), low certainty of evidence, respectively). These results agreed with those of the pairwise meta‐analysis. For clinical pregnancy within 6 months, there was insufficient evidence of a difference between tubal flushing with water‐based contrast medium and no intervention (OR, 1.36 (95% CI, 0.91–2.04), low certainty of evidence). For fertility outcomes after 6 months, there was insufficient evidence of a difference in any comparison (low to very low certainty of evidence). Compared with tubal flushing using water‐based contrast medium, the use of oil‐based contrast medium was associated with higher odds of asymptomatic intravasation (OR, 5.06 (95% CI, 2.29–11.18), moderate certainty of evidence).

Conclusions

In women with infertility undergoing fertility workup, tubal flushing using oil‐based contrast medium probably increases clinical pregnancy rates within 6 months after randomization and may increase subsequent live‐birth rates, compared with tubal flushing using water‐based contrast medium and compared with no intervention. Evidence on fertility outcomes beyond 6 months is inadequate to draw firm conclusions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Evaluation of the structural characteristics and the fading effects of image plates
Authors: Silva A.S.S. , Gomes C.S. , Machado A.S. , Nascimento J.R. , Santos R.S. , Oliveira D.F. , Dos Anjos M.J. , Lopes R.T.
Published: February 2019

The photostimulated luminescence (PSL) is the basis for the digital image formation of image plates (IPs). However, the PSL decreases exponentially with the increasing of the elapsed time between the exposure and the IP scanning (t), and consequently, there is a fading of the digital image. The purpose of this paper is to investigate the relationship between IPs physical structure and elemental composition with the fading behavior. Three different types of IPs, with distinct resolutions, were analyzed. The fading behavior with the time, t, has been measured and correlated with their physical structure. Furthermore, micro X‐ray fluorescence (μXRF) analysis was used to provide information on the elemental composition of this layer. The results showed that standard resolution plate have larger grains, thicker sensitive layer, and generate a bigger effect of image fading. The μXRF technique showed that, to compensate the low emission, the high‐resolution IP has a higher concentration of Br and Sr.
Why institutional ethnography? Why now? Institutional ethnography in health professions education
Authors: Kearney Grainne P. , Corman Michael K. , Hart Nigel D. , Johnston Jennifer L. , Gormley Gerard J.
Published: February 2019

This ‘A Qualitative Space’ article takes a critical look at Dorothy Smith’s approach to inquiry known as institutional ethnography and its potentiality in contemporary health professions education research. We delve into institutional ethnography’s philosophical underpinnings, setting out the ontological shift that the researcher needs to make within this critical feminist approach. We use examples of research into frontline healthcare, into the health work of patients and into education to allow the reader to consider what an institutional ethnography research project might offer. We lay out our vision for potential growth for institutional ethnography research within the health professions education field and explain why we see this as the opportune moment to adopt institutional ethnography to meet some of the challenges facing health professions education in a way that offers informed change.
Child maltreatment is mediating long-term consequences of household dysfunction in a population representative sample
Authors: Clemens Vera , Berthold Oliver , Witt Andreas , Sachser Cedric , Brähler Elmar , Plener Paul L. , Strauß Bernhard , Fegert Jörg M.
Published: February 2019

Background:

Adverse childhood experiences (ACE) exhibit long-lasting consequences on later life and are considered as a major public health problem. ACEs can be divided into household dysfunctions, which affect the child indirectly, and direct maltreatment. As a high correlation between ACEs in general is known, we assessed the risk for child maltreatment associated with the occurrence of household dysfunctions. To provide a better understanding for the mechanisms leading to the deleterious sequelae of ACEs, we furthermore assessed whether the long-term consequences of household dysfunction are mediated by child maltreatment and thereby might be targeted by effective child protection programs.

Methods:

A representative sample of the German population above the age of 14 (N = 2531) was assessed in a cross-sectional observational population-based survey.

Results:

The data reveal that mental illness of a household member was associated with significantly increased risks for all child maltreatment subtypes (ORs 4.95–5.55), just as household substance abuse (ORs 5.32–6.98), violence against the mother (ORs 4.43–10.26), incarceration of a household member (ORs 6.11–14.93) and parental separation (OR 3.37–4.87). Child maltreatment partially mediated the association of household mental illness, substance abuse and parental separation with later depression, anxiety, life satisfaction and subjective general health status and completely mediated the associations of intimate partner violence (IPV) and incarceration of a household member with anxiety, depression and subjective health status in adulthood.

Conclusions:

ACEs linked to household dysfunction are associated with an increased risk for all subtypes of child maltreatment. The assessed widespread consequences of household dysfunction are mediated by child maltreatment. This underlines the role of prevention of child maltreatment in families with household dysfunction and implies child protection as a priority in any interventions.
Time course and expression pattern of the neuronal markers in the developing human spinal cord
Authors: Restović Ivana , Bočina Ivana , Vukojević Katarina , Kero Darko , Filipović Natalija , Raonić Janja , Vučinić Jelena , Vukmirović Filip , Vučković Ljiljana , Saraga‐Babić Mirna
Published: February 2019

The aim of this study was to examine the spatio‐temporal appearance of different neuronal cell subtypes by analyzing expression patterns of several neuronal markers (calretinin, neurofilament 200 (NF200), vanilloid receptor 1(VR1) and calcitonin gene‐related peptide (CGRP)) of the embryonic human spinal cord (SC). Developing human SCs from 11 human conceptuses beetwen 5–10 developmental weeks (DW) were examined by light and electron microscopy and immunofluorescence. Light and electron microscopy revealed different embryonic stages of recognizable structure of the SC. NF200, CGRP and VR1 positive cells were observed in SCs during 5th–6th DW. NF200 was predominantly expressed in the ventral part, indicating presence of motoneurons. As development advanced, NF200 was mainly expressed in the marginal zone. Expression of CGRP was intense during all of the investigated periods, predominantly during the 5th–6th DW pointing to neural sensory differentiation, as opposed to the last DW when reduced expression of CGRP in the marginal layer indicated the terminations of the sensory afferents. Expression of VR1 was highest in the intermediate zone, at the beginning and at the end of the investigated periods, pointing to VR1 spatial pattern in the visceral afferents in the grey matter, while the first signs of calretinin were found in the 9th–10th DW ventrally. Delineating the relationships between factors involved in processes of neuronal differentiation as well as spatial and temporal arrangement of SC interrelated neurons can provide a useful information about normal SC development as well as the insight in possible causes of anomalies and disorders during embryonic life.
Repeated neonatal needle‐prick stimulation increases inflammatory mechanical hypersensitivity in adult rats
Authors: de Carvalho Ravena Carolina , Prado Lara , Rissardo Oliveira Naynne Cristina , Vilela Giusti Fabiana Cardosos , Santos Vieira Jádina , Giusti‐Paiva Alexandre , da Silva Josie Resende Torres , da Silva Marcelo Lourenço
Published: February 2019

Background and aims

Newborn infants are vulnerable to procedural stress and pain exposure on the first weeks of life that represents a critical period for the development of nociceptive, sensory, emotional, and social functions. We evaluated the nociceptive behavior of adult male and female rats that were submitted to nociceptive experience in the neonatal period and the maternal behavior in the postnatal period.

Methods

The animals were submitted to repetitive needle pricking from the second to the fifteenth postnatal day (PND 2–15). Maternal behavior and litter weight were evaluated during this period. Mechanical sensitivity to pain was assessed in offsprings during the adulthood by exposing them to inflammatory stimuli, including formalin test or the Freund's complete adjuvant (CFA) injection followed by the electronic von Frey test at 0, 3, 6 and 24 h later.

Results

Maternal behavior and litter weight were not altered by pinprick stimuli during PND 2–15. Additionally, pinprick stimulation reduced the paw withdrawal threshold in CFA‐injected animals compared to control. In the formalin test, there was a difference between the genders. Female rats are statically more sensitive to formalin stimulation and showed an increased licking time in both the first and second phases and increased number of flinches in second phase.

Conclusions

Experiencing early life repetitive pain exposure increased inflammatory pain sensitivity in adult offspring rats and female rats are more sensitive to chemical stimulation.

Implications

Future investigations of the mechanisms involved in this effect may contribute to the improvement of the understanding of inflammatory pain sensitivity differences.
Minimal invasive MPFL reconstruction using quadriceps tendon graft with lateral release: 2 years follow up
Authors: Rhatomy Sholahuddin , Soekarno Noha Roshadiansyah , Setyawan Riky , Primasara Shinta , Gaol Imelda L. , Budipharama Nicolaas C.
Published: February 2019

ABSTRACT

Background:

Medial Patellofemoral Ligament (MPFL) reconstruction is a popular procedure to repair recurrent patellar dislocation. Many methods of reconstruction describe the use of hamstring tendons as the graft of choice. This study aimed to compare the functional outcome of MPFL reconstruction using quadriceps tendon graft with arthroscopic lateral release and to identify possible risks.

Methods:

This is a retrospective cohort study in patients with a history of recurrent dislocation trauma from 2014 to 2016 that already done MPFL reconstruction using quadriceps tendon grafts with arthroscopic lateral release. Patient reported outcomes were evaluated pre-operative and 2 years post-operatively using IKDC score, Lysholm knee score, Kujala score, KSS Score, thigh circumference size, and kneel down ability. Patellar fracture, redislocation, and other complications were also assessed 2 years post-operative.

Results:

Eight patients included in this study and showed significant improvement in clinical outcomes. The Lysholm score increased from 64.37 ± 8.23 to 90.87 ± 3.23 (p = 0.011), IKDC score increased from 62.93 ± 7.52 to 88.36 ± 3.64 (p < 0.001). Kujala score increased from 60.87 ± 7.94 to 88.37 ± 4.34 (p < 0.001), KSS knee score increased from 83.25 ± 11 to 93.87 ± 1.73 (p = 0.012). KSS function also increased from 57.50 ± 11.65 to 88.13 ± 3.72 (p = 0.011) with decreased in thigh circumference (1–3 cm). Five patients have full ROM, able to kneeling, while 3 patients were able to kneeling with adjustments. There were no postoperative infection, patellar fractures nor redislocations.

Conclusion:

MPFL reconstruction using quadriceps tendon grafts with arthroscopic lateral release can provide improved clinical results without complications of patellar fracture or stiffness of the knee, infection, and redislocation.

Level of evidence:

Level 3, Retrospective Cohort Study.

Highlights:
Clinical and cortical decline in the aphasic variant of Alzheimer's disease
Authors: Rogalski Emily Joy , Sridhar Jaiashre , Martersteck Adam , Rader Benjamin , Cobia Derin , Arora Anupa K. , Fought Angela J. , Bigio Eileen H. , Weintraub Sandra , Mesulam Marek‐Marsel , Rademaker Alfred
Published: February 2019

Introduction

Primary progressive aphasia (PPA) displays variable progression trajectories that require further elucidation.

Methods

Longitudinal quantitation of atrophy and language over 12 months was completed for PPA patients with and without positive amyloid PET (PPAAβ+ and PPAAβ−), an imaging biomarker of underlying Alzheimer’s disease.

Results

Over 12 months, both PPA groups showed significantly greater cortical atrophy rates in the left versus right hemisphere, with a more widespread pattern in PPAAβ+. The PPAAβ+ group also showed greater decline in performance on most language tasks. There was no obligatory relationship between the logopenic PPA variant and amyloid status. Effect sizes from quantitative MRI data were more robust than neuropsychological metrics.

Discussion

Preferential language network neurodegeneration is present in PPA irrespective of amyloid status. Clinical and anatomical progression appears to differ for PPA due to Alzheimer's disease versus non–Alzheimer's disease neuropathology, a distinction that may help to inform prognosis and the design of intervention trials.
Discharge Destination from a Rehabilitation Unit After Acute Ischemic Stroke
Authors: Saab Amalie , Glass-Kaastra Shiona , Young Gordon Bryan
Published: February 2019

Background:We reviewed numerous variables for ischemic stroke patients admitted to a rehabilitation unit to determine those that were statistically associated with discharge destination.Methods:A retrospective chart review of patients with ischemic stroke discharged from the rehabilitation unit between January 1, 2005 and December 31, 2015. Variables were examined for their association with discharge destination (home versus long-term care (LTC)). Univariable relationships with discharge destination were assessed, and a multivariable logistic regression model was built.Results:Univariate predictors of discharge to LTC: advanced age, decreasing admission and discharge functional independence measure (FIM) scores, increasing change in FIM score from admission to discharge, dependency, residence outside of home before the stroke, absence of a caregiver, urinary and bowel incontinence, low Berg balance score at admission and discharge, low Montreal Cognitive Assessment scores, smoking, chronic heart failure, and an inability to transfer. Multivariable logistic regression: five factors remained significant predictors with LTC disposition: advanced age, bowel incontinence, residence outside of the home prior to stroke, right hemisphere site of the stroke, and absence of a caregiver.Conclusions:Several easily measured variables were significantly associated with discharge to LTC versus home following stroke rehabilitation.
Muscular Ultrasound, Syndecan-1 and Procalcitonin Serum Levels to Assess Intensive Care Unit-Acquired Weakness
Authors: Patejdl Robert , Walter Uwe , Rosener Sarah , Sauer Martin , Reuter Daniel A. , Ehler Johannes
Published: February 2019

Background:Intensive care unit-acquired weakness (ICU-AW) is associated with poorer outcome of critically ill patients. Microcirculatory changes and altered vascular permeability of skeletal muscles might contribute to the pathogenesis of ICU-AW. Muscular ultrasound (MUS) displays increased muscle echogenicity, although its pathogenesis is uncertain.Objective:We investigated the combined measurement of serum and ultrasound markers to assess ICU-AW and clinical patient outcome.Methods:Fifteen patients and five healthy controls were longitudinally assessed for signs of ICU-AW at study days 3 and 10 using a muscle strength sum score. The definition of ICU-AW was based on decreased muscle strength assessed by the muscular research council-sum score. Ultrasound echogenicity of extremity muscles was assessed using a standardized protocol. Serum markers of inflammation and endothelial damage were measured. The 3-month outcome was assessed on the modified Rankin scale.Results:ICU-AW was present in eight patients, and seven patients and the control subjects did not develop ICU-AW. The global muscle echogenicity score (GME) differed significantly between controls and patients (mean GME, 1.1 ± 0.06 vs. 2.3 ± 0.41;p= 0.001). Mean GME values significantly decreased in patients without ICU-AW from assessment 1 (2.30 ± 0.48) to assessment 2 (2.06 ± 0.45;p= 0.027), which was not observed in patients with ICU-AW. Serum levels of syndecan-1 at day 3 significantly correlated with higher GME values at day 10 (r= 0.63,p= 0.012). Furthermore, the patients’ GME significantly correlated with mRS at day 100 (r= 0.67,p= 0.013).Conclusion:The combined use of muscular ultrasound and inflammatory biomarkers might be helpful to diagnose ICU-AW and to predict long-term outcome in critical illness.
Characterization of Natural Pigments from the Archaeological Context of Traful Lake (Neuquén, Argentina)
Authors: Aldazabal Verónica , Reinoso Maria , Custo Graciela , Cerchetti Luciana , Halac Emilia B. , Polla Griselda , Freire Eleonora
Published: February 2019

In this paper we discuss the use of mineral pigments recovered in stratigraphic position from three excavated archaeological sites (Traful Lake area, Argentina) with the aim of providing information on selection and frequency of use of these raw materials. In this region, human occupation has been recorded since 4000 BP. In order to identify the chromophoric minerals, we applied wavelength dispersive X-ray fluorescence spectrometry, Raman spectroscopy, and X-ray diffraction techniques. Green, red, yellow ochre, and white pigments dated between 3490 and 590 BP were analyzed. The results show that different analytical techniques provide complementary information in order to identify the pigments. Green, red, and yellow samples are related to iron-based compounds. The green pigments can be associated with celadonite and the others with hematite. White samples revealed the presence of hydroxyapatite. Black dots, identified as carbon, were observed in several samples. Red pigments are always predominant, and their relative abundance increases in recent strata. Results are discussed in light of the context and previous reports of chroniclers.
Autonomous motivation, sugar-sweetened beverage consumption and healthy beverage intake in US families: differences between mother–adolescent and father–adolescent dyads
Authors: Figueroa Roger , Kalyoncu Z Begüm , Saltzman Jaclyn A , Davison Kirsten K
Published: February 2019

Objective

To assess interdependent effects of autonomous motivation to limit sugar-sweetened beverage (SSB) consumption in relation to SSB and healthy beverage (HB) intake in mother–adolescent and father–adolescent dyads.

Design

Adopting a dyadic cross-sectional design, the actor–partner interdependence modelling (APIM) approach was used to construct and analyse two APIM for mother–adolescent and father–adolescent dyads. The first model assessed actor effects (individual’s autonomous motivation associated with his/her own beverage intake) and partner effects (individual’s autonomous motivation associated with another family member’s beverage consumption) of autonomous motivation on SSB consumption. The second model assessed actor and partner effects of autonomous motivation on HB intake.

Setting

Two Internet-based surveys were completed in participant households.

Participants

Data from a demographically representative US sample of parent–adolescent dyads (1225 mother–adolescent dyads, 424 father–adolescent dyads) were used.

Results

In the first model (autonomous motivation on SSB consumption), actor effects were significant for adolescents, but not for parents. Partner effects were significant for mother–adolescent, but not father–adolescent dyads. In the second model (autonomous motivation on HB intake), actor effects were significant for adolescents and parents in all dyadic combinations. Regarding partner effects, adolescent autonomous motivation had a significant effect on HB intake for mothers and fathers. In addition, maternal autonomous motivation had a significant effect on adolescent HB intake. No partner effects for HB were identified for fathers.

Conclusions

We found significant interdependent effects of autonomous motivation in relation to SSB and HB intake in mother–adolescent and father–adolescent dyads for eleven out of sixteen pathways modelled.
Satellite Observations of SST‐Induced Wind Speed Perturbation at the Oceanic Submesoscale
Authors: Gaube P. , Chickadel C. C. , Branch R. , Jessup A.
Published: February 2019

Sea Surface Temperature (SST) modifies the turbulent mixing, drag, and pressure gradients within the marine atmospheric boundary layer that accelerate near‐surface flow from cool to warm SST and decelerate the flow from warm to cool SST. This phenomenon is well documented on scales of 100–1,000 km (the oceanic mesoscale); however, the nature of this air‐sea coupling at scales on the order of 1–10 km (the submesoscale) remains unknown. The Advanced Spaceborne Thermal Emission and Reflection Radiometer can be used to study submesoscale phenomena because the high‐resolution infrared and near‐infrared images can used to estimate both SST and wind speed. Observations of dramatic temperature and wind gradients along the Gulf Stream landward edge are used to examine the surface wind response to submesoscale fronts in SST. Our analysis indicates that SST‐induced wind speed perturbations are observed at the scales of order 1–10 km, significantly smaller than previously suggested.
Faulting and Gas Discharge in the Rome Area (Central Italy) and Associated Hazards
Authors: Carapezza M. L. , Barberi F. , Ranaldi M. , Tarchini L. , Pagliuca N. M.
Published: February 2019

The area of Central Italy around Rome contains natural gas discharging zones and several others where quarrying or mining excavation removed the impervious superficial layers allowing a free hazardous discharge to the surface of endogenous gas. These gas manifestations are mostly located above buried structural highs of fractured Mesozoic limestones hosting the main regional aquifer and revealed by gravity anomalies. In the last decades, many gas blowouts occurred in this area, from wells whose depth ranged from 10–15 to 350 m. The main component of the emitted gas is CO2 with minor H2S; only in a blowout offshore of Fiumicino CH4 prevailed. Several animals even of large size and two persons were killed by the emitted gas (mostly by H2S), and nearby houses were evacuated because of dangerous indoor CO2 concentrations. He and CO2‐carbon isotopes suggest that gas has a deep mantle signature, as indicated for Fiumicino gas by N2 isotopic composition and N2/36Ar ratios. Gas rising from depth first accumulates in the buried Mesozoic limestone reservoir, and from there it escapes along deep‐reaching faults. On its way to the surface, the gas dissolves into and pressurizes any encountered confined aquifer, which may then produce a gas blowout when reached by wells. The main direction of the gas feeding faults was estimated through the alignment of visible gas emissive points, the shape of the positive anomalies in soil CO2 flux maps, and new structural‐geological observations, finding that they correspond mostly to the main orientation of the underlying limestone structural high.
Most canine ameloblastomas harbor HRAS mutations, providing a novel large-animal model of RAS-driven cancer
Authors: Saffari Persiana S. , Vapniarsky Natalia , Pollack Anna S. , Gong Xue , Vennam Sujay , Pollack Andrew J. , Verstraete Frank J. M. , West Robert B. , Arzi Boaz , Pollack Jonathan R.
Published: February 2019

Canine acanthomatous ameloblastomas (CAA), analogs of human ameloblastoma, are oral tumors of odontogenic origin for which the genetic drivers have remained undefined. By whole-exome sequencing, we have now discovered recurrent HRAS and BRAF activating mutations, respectively, in 63% and 8% of CAA. Notably, cell lines derived from CAA with HRAS mutation exhibit marked sensitivity to MAP kinase (MAPK) pathway inhibitors, which constrain cell proliferation and drive ameloblast differentiation. Our findings newly identify a large-animal spontaneous cancer model to study the progression and treatment of RAS-driven cancer. More broadly, our study highlights the translational potential of canine cancer genome sequencing to benefit both humans and their companion animals.
G protein βγ subunits play a critical role in the actions of amphetamine
Authors: Mauna J. C. , Harris S. S. , Pino J. A. , Edwards C. M. , DeChellis-Marks M. R. , Bassi C. D. , Garcia-Olivares J. , Amara S. G. , Guajardo F. G. , Sotomayor-Zarate R. , Terminel M. , Castañeda E. , Vergara M. , Baust T. , Thiels E. , Torres G. E.
Published: February 2019

Abnormal levels of dopamine (DA) are thought to contribute to several neurological and psychiatric disorders including drug addiction. Extracellular DA levels are regulated primarily via reuptake by the DA transporter (DAT). Amphetamine, a potent psychostimulant, increases extracellular DA by inducing efflux through DAT. Recently, we discovered that G protein βγ subunits (Gβγ) interact with DAT, and that in vitro activation of Gβγ promotes DAT-mediated efflux. Here, we investigated the role of Gβγ in the actions of amphetamine in DA neurons in culture, ex vivo nucleus accumbens (NAc), and freely moving rats. Activation of Gβγ with the peptide myr-Ser-Ile-Arg-Lys-Ala-Leu-Asn-Ile-Leu-Gly-Tyr-Pro-Asp-Tyr-Asp (mSIRK) in the NAc potentiated amphetamine-induced hyperlocomotion, but not cocaine-induced hyperlocomotion, and systemic or intra-accumbal administration of the Gβγ inhibitor gallein attenuated amphetamine-induced, but not cocaine-induced hyperlocomotion. Infusion into the NAc of a TAT-fused peptide that targets the Gβγ-binding site on DAT (TAT-DATct1) also attenuated amphetamine-induced but not cocaine-induced hyperlocomotion. In DA neurons in culture, inhibition of Gβγ with gallein or blockade of the Gβγ–DAT interaction with the TAT-DATct1 peptide decreased amphetamine-induced DA efflux. Furthermore, activation of Gβγ with mSIRK potentiated and inhibition of Gβγ with gallein reduced amphetamine-induced increases of extracellular DA in the NAc in vitro and in freely moving rats. Finally, systemic or intra-accumbal inhibition of Gβγ with gallein blocked the development of amphetamine-induced, but not cocaine-induced place preference. Collectively, these results suggest that interaction between Gβγ and DAT plays a critical role in the actions of amphetamine and presents a novel target for modulating the actions of amphetamine in vivo.
Cigarette smoking and gray matter brain volumes in middle age adults: the CARDIA Brain MRI sub-study
Authors: Elbejjani Martine , Auer Reto , Jacobs David R. , Haight Thaddeus , Davatzikos Christos , Goff David C. , Bryan R. Nick , Launer Lenore J.
Published: February 2019

Cigarette smoking has been associated with dementia and dementia-related brain changes, notably gray matter (GM) volume atrophy. These associations are thought to reflect the co-morbidity of smoking and vascular, respiratory, and substance use/psychological conditions. However, the extent and localization of the smoking-GM relationship and the degree to which vascular, respiratory, and substance use/psychological factors influence this relationship remain unclear. In the Coronary Artery Risk Development in Young Adults CARDIA cohort (n = 698; 52% women; 40% black participants; age = 50.3 (SD = 3.5)), we examined the associations of smoking status with total GM volume and GM volume of brain regions linked to neurocognitive and addiction disorders. Linear regression models were used to adjust for vascular, respiratory, and substance use/psychological factors and to examine whether they modify the smoking-GM relationship. Compared to never-smokers, current smokers had smaller total GM volume (−8.86 cm3 (95%CI = −13.44, −4.29). Adjustment for substance use/psychological – but not vascular or respiratory – factors substantially attenuated this association (coefficients = −5.54 (95% CI = −10.32, −0.76); −8.33 (95% CI = −12.94, −3.72); −7.69 (95% CI = −6.95, −4.21), respectively). There was an interaction between smoking and alcohol use such that among alcohol non-users, smoking was not related to GM volumes and among alcohol users, those who currently smoked had −12 cm3 smaller total GM, specifically in the frontal and temporal lobes, amygdala, cingulate, and insula. Results suggest a large-magnitude association between smoking and smaller GM volume at middle age, accounting for vascular, respiratory, and substance use/psychological factors, and that the association was strongest in alcohol users. Regions suggested to be most vulnerable are those where cognition and addiction processes overlap.
Callous-unemotional traits, low cortisol reactivity and physical aggression in children: findings from the Wirral Child Health and Development Study
Authors: Wright Nicola , Hill Jonathan , Pickles Andrew , Sharp Helen
Published: February 2019

Callous-unemotional (CU) traits are thought to confer risk for aggression via reduced amygdala responsivity to distress cues in others. Low cortisol reactivity is thought to confer risk for aggression via reduced arousal and this effect may be confined to boys. We tested the hypothesis that the association between childhood CU traits and aggression would be greatest in the absence of the inhibitory effects of cortisol reactivity, and that this effect would be sex dependent. Participants were 283 members of a stratified subsample within an epidemiological longitudinal cohort (WCHADS). Cortisol reactivity to a social stressor was assessed at 5 years. CU traits were reported by mothers at 5 years, and physical aggression by mothers and teachers at age 7. Results showed that CU traits were associated with elevated aggression at 7 years controlling for earlier aggression. There was no main effect of cortisol reactivity on regression. The association between CU traits and aggression was moderated by cortisol reactivity (p = .011) with a strong association between CU traits and aggression in the presence of low reactivity, and a small and non-significant association in the presence of high reactivity. This association was further moderated by child sex (p = .041) with the joint effect of high CU traits and low cortisol reactivity seen only in boys (p = .016). We report first evidence that a combined deficit in inhibitory processes associated with CU traits and low cortisol reactivity increases risk for childhood aggression, in a sex-dependent manner.
Sex-specific deficits in neurite density and white matter integrity are associated with targeted disruption of exon 2 of the Disc1 gene in the rat
Authors: Barnett Brian R. , Torres-Velázquez Maribel , Yi Sue Y. , Rowley Paul A. , Sawin Emily A. , Rubinstein C. Dustin , Krentz Kathleen , Anderson Jacqueline M. , Bakshi Vaishali P. , Yu John-Paul J.
Published: February 2019

Diffusion tensor imaging (DTI) has provided remarkable insight into our understanding of white matter microstructure and brain connectivity across a broad spectrum of psychiatric disease. While DTI and other diffusion weighted magnetic resonance imaging (MRI) methods have clarified the axonal contribution to the disconnectivity seen in numerous psychiatric diseases, absent from these studies are quantitative indices of neurite density and orientation that are especially important features in regions of high synaptic density that would capture the synaptic contribution to the psychiatric disease state. Here we report the application of neurite orientation dispersion and density imaging (NODDI), an emerging microstructure imaging technique, to a novel Disc1 svΔ2 rat model of psychiatric illness and demonstrate the complementary and more specific indices of tissue microstructure found in NODDI than those reported by DTI. Our results demonstrate global and sex-specific changes in white matter microstructural integrity and deficits in neurite density as a consequence of the Disc1 svΔ2 genetic variation and highlight the application of NODDI and quantitative measures of neurite density and neurite dispersion in psychiatric disease.
MEK inhibition suppresses K-Ras wild-type cholangiocarcinoma in vitro and in vivo via inhibiting cell proliferation and modulating tumor microenvironment
Authors: Wang Pan , Song Xinhua , Utpatel Kirsten , Shang Runze , Yang Yoon Mee , Xu Meng , Zhang Jie , Che Li , Gordan John , Cigliano Antonio , Seki Ekihiro , Evert Matthias , Calvisi Diego F. , Hu Xiaosong , Chen Xin
Published: February 2019

PD901, a MEK inhibitor, has been demonstrated of therapeutic efficacy against cholangiocarcinoma (CCA) harboring K-Ras oncogenic mutations. However, most CCA exhibit no K-Ras mutations. In the current study, we investigated the therapeutic potential of PD901, either alone or in combination with the pan-mTOR inhibitor MLN0128, for the treatment of K-Ras wild-type CCA in vitro using human CCA cell lines, and in vivo using AKT/YapS127A CCA mouse model. We discovered that in vitro, PD901 treatment strongly inhibited CCA cell proliferation, and combined PD901 and MLN0128 therapy further increased growth inhibition. In vivo, treatment of PD901 alone triggered tumor regression, which was not further increased when the two drugs were administered simultaneously. Mechanistically, PD901 efficiently hampered ERK activation in vitro and in vivo, leading to strong inhibition of CCA tumor cell cycle progression. Intriguingly, we discovered that PD901, but not MLN0128 treatment resulted in changes affecting the vasculature and cancer-associated fibroblasts in AKT/YapS127A mouse lesions. It led to the decreased hypoxia within tumor lesions, which may further enhance the anti-cell proliferation activities of PD901. Altogether, our study demonstrates that MEK inhibitors could be effective for the treatment of K-Ras wild-type CCA via inhibiting cell proliferation and modulating tumor microenvironment.
Correspondence between cerebral glucose metabolism and BOLD reveals relative power and cost in human brain
Authors: Shokri-Kojori Ehsan , Tomasi Dardo , Alipanahi Babak , Wiers Corinde E. , Wang Gene-Jack , Volkow Nora D.
Published: February 2019

The correspondence between cerebral glucose metabolism (indexing energy utilization) and synchronous fluctuations in blood oxygenation (indexing neuronal activity) is relevant for neuronal specialization and is affected by brain disorders. Here, we define novel measures of relative power (rPWR, extent of concurrent energy utilization and activity) and relative cost (rCST, extent that energy utilization exceeds activity), derived from FDG-PET and fMRI. We show that resting-state networks have distinct energetic signatures and that brain could be classified into major bilateral segments based on rPWR and rCST. While medial-visual and default-mode networks have the highest rPWR, frontoparietal networks have the highest rCST. rPWR and rCST estimates are generalizable to other indexes of energy supply and neuronal activity, and are sensitive to neurocognitive effects of acute and chronic alcohol exposure. rPWR and rCST are informative metrics for characterizing brain pathology and alternative energy use, and may provide new multimodal biomarkers of neuropsychiatric disorders.
TRADD regulates perinatal development and adulthood survival in mice lacking RIPK1 and RIPK3
Authors: Dowling John P. , Alsabbagh Mohamed , Del Casale Christina , Liu Zheng-Gang , Zhang Jianke
Published: February 2019

TRADD is an adaptor for TNFR1-induced apoptosis and NFκB activation. However, TRADD-deficient mice undergo normal development and contain normal lymphoid populations, which contrasts with an embryonic defect in mice lacking FADD, the shared adaptor mediating apoptosis. Recent studies indicate FADD suppresses embryonic necroptosis mediated by RIPK1. TRADD was suggested to also mediate necroptosis. Here we report that targeting TRADD fails to rescue Fadd−/− embryos from necroptosis, and ablation of TRADD rescues Ripk1−/− mice from perinatal lethality when RIPK3-mediated necroptosis is disabled. The resulting Ripk1−/−Ripk3−/−Tradd−/− mice survive until early adulthood, but die thereafter. A single allele of Tradd is optimal for survival of Ripk1−/−Ripk3−/−Tradd+/− mice. We show that TRADD plays a more dominating role in NFκB-signaling than RIPK1. While RIPK1 protects thymocytes from TNFα-induced apoptosis, TRADD promotes this process. The data demonstrate that TRADD is critical in perinatal and adult mice lacking RIPK1 and RIPK3, which has not been appreciated in prior studies.
Cation-swapped homogeneous nanoparticles in perovskite oxides for high power density
Authors: Joo Sangwook , Kwon Ohhun , Kim Kyeounghak , Kim Seona , Kim Hyunmin , Shin Jeeyoung , Jeong Hu Young , Sengodan Sivaprakash , Han Jeong Woo , Kim Guntae
Published: February 2019

Exsolution has been intensively studied in the fields of energy conversion and storage as a method for the preparation of catalytically active and durable metal nanoparticles. Under typical conditions, however, only a limited number of nanoparticles can be exsolved from the host oxides. Herein, we report the preparation of catalytic nanoparticles by selective exsolution through topotactic ion exchange, where deposited Fe guest cations can be exchanged with Co host cations in PrBaMn1.7Co0.3O5+δ. Interestingly, this phenomenon spontaneously yields the host PrBaMn1.7Fe0.3O5+δ, liberating all the Co cations from the host owing to the favorable incorporation energy of Fe into the lattice of the parent host (ΔEincorporation = −0.41 eV) and the cation exchange energy (ΔEexchange = −0.34 eV). Remarkably, the increase in the number of exsolved nanoparticles leads to their improved catalytic activity as a solid oxide fuel cell electrode and in the dry reforming of methane.
Automated microfluidic cell culture of stem cell derived dopaminergic neurons
Authors: Kane Khalid I. W. , Moreno Edinson Lucumi , Hachi Siham , Walter Moriz , Jarazo Javier , Oliveira Miguel A. P. , Hankemeier Thomas , Vulto Paul , Schwamborn Jens C. , Thoma Martin , Fleming Ronan M. T.
Published: February 2019

Parkinson’s disease is a slowly progressive neurodegenerative disease characterised by dysfunction and death of selectively vulnerable midbrain dopaminergic neurons and the development of human in vitro cellular models of the disease is a major challenge in Parkinson’s disease research. We constructed an automated cell culture platform optimised for long-term maintenance and monitoring of different cells in three dimensional microfluidic cell culture devices. The system can be flexibly adapted to various experimental protocols and features time-lapse imaging microscopy for quality control and electrophysiology monitoring to assess cellular activity. Using this system, we continuously monitored the differentiation of Parkinson’s disease patient derived human neuroepithelial stem cells into midbrain specific dopaminergic neurons. Calcium imaging confirmed the electrophysiological activity of differentiated neurons and immunostaining confirmed the efficiency of the differentiation protocol. This system is the first example of an automated Organ-on-a-Chip culture and has the potential to enable a versatile array of in vitro experiments for patient-specific disease modelling.
Enantiomeric Isoflavones with neuroprotective activities from the Fruits of Maclura tricuspidata
Authors: Hiep Nguyen Tuan , Kwon Jaeyoung , Hong Sungeun , Kim Nahyun , Guo Yuanqiang , Hwang Bang Yeon , Mar Woongchon , Lee Dongho
Published: February 2019

Seven pairs of enantiomeric isoflavones (1a/1b–7a/7b) were obtained from the ethyl acetate extract of the fruits of Maclura tricuspidata (syn. Cudrania tricuspidata), and successfully separated by chiral high-pressure liquid chromatography (HPLC). The structures and absolute configurations of the enantiomeric isoflavones were established on the basic of comprehensive spectroscopic analyses and quantum chemical calculation methods. Compounds 1, 1a, and 1b exhibited neuroprotective activities against oxygen-glucose deprivation/reoxygenation (ODG/R)-induced SH-SY5Y cells death with EC50 values of 5.5 µM, 4.0 µM, and 10.0 µM, respectively. Furthermore, 1, 1a, and 1b inhibited OGD/R-induced reactive oxygen species generation in SH-5Y5Y cells with IC50 values of 6.9 µM, 4.5 µM, and 9.5 µM, respectively.
Colour lightness of butterfly assemblages across North America and Europe
Authors: Stelbrink Pablo , Pinkert Stefan , Brunzel Stefan , Kerr Jeremy , Wheat Christopher W. , Brandl Roland , Zeuss Dirk
Published: February 2019

Melanin-based dark colouration is beneficial for insects as it increases the absorption of solar energy and protects against pathogens. Thus, it is expected that insect colouration is darker in colder regions and in regions with high humidity, where it is assumed that pathogen pressure is highest. These relationships between colour lightness, insect distribution, and climate between taxa and subtaxa across continents have never been tested and compared. Here we analysed the colour lightness of nearly all butterfly species of North America and Europe using the average colour lightness of species occurring within 50 km × 50 km grid cells across both continents as the dependent variable and average insolation, temperature and humidity within grid cells as explanatory variables. We compared the direction, strength and shape of these relationships between butterfly families and continents. On both continents, butterfly assemblages in colder and more humid regions were generally darker coloured than assemblages in warmer and less humid regions. Although these relationships differed in detail between families, overall trends within families on both continents were similar. Our results add further support for the importance of insect colour lightness as a mechanistic adaptation to climate that influences biogeographical patterns of species distributions.
Clinical relevance of non-tuberculous mycobacteria isolated from respiratory specimens: seven year experience in a UK hospital
Authors: Schiff H. F. , Jones S. , Achaiah A. , Pereira A. , Stait G. , Green B.
Published: February 2019

The frequency of isolation of non-tuberculous mycobacteria (NTM) species from respiratory specimens is increasing, however the clinical relevance of such identifications vary by mycobacterial species and geographical location. A retrospective study of 853 NTM isolates from respiratory samples from 386 patients over seven years was performed. Clinical records and radiographic information were examined. Clinical significance was assessed by American Thoracic Society diagnostic criteria. 25% of all patients with respiratory isolates met criteria for non-tuberculous mycobacterial pulmonary disease (NTM-PD). Significant symptoms were weight loss, fever, night sweats, productive cough and haemoptysis. HIV co-infection was a significant risk factor for disease. Cavities, nodules and tree-in-bud were significant radiographic findings. Mycobacterium avium complex (MAC) were the dominant species isolated from this patient cohort. Mycobacterium abscessus (M. abscessus) was the species most likely to cause clinically significant disease and be sputum smear positive, thus warranting particular attention.
CARS spectroscopy of Aspergillus nidulans spores
Authors: D. Strycker Benjamin , Han Zehua , Commer Blake , D. Shaw Brian , V. Sokolov Alexei , O. Scully Marlan
Published: February 2019

Coherent Anti-Stokes Raman Spectroscopy (CARS) is performed on single spores (conidia) of the fungus Aspergillus nidulans in order to establish a baseline measurement for fungal spores. Chemical maps of single spores are generated and spectral differentiation between the cell wall and the cytoplasm is achieved. Principal Component Analysis of the measured spectra is then completed as a means to quantify spore heterogeneity. Applications range from the quick and accurate diagnosis of public health concerns to real-time agricultural and environmental sensing of fungal symbionts and pathogens.
A mutation in the AdhE alcohol dehydrogenase of Clostridium thermocellum increases tolerance to several primary alcohols, including isobutanol, n-butanol and ethanol
Authors: Tian Liang , Cervenka Nicholas D. , Low Aidan M. , Olson Daniel G. , Lynd Lee R.
Published: February 2019

Clostridium thermocellum is a good candidate organism for producing cellulosic biofuels due to its native ability to ferment cellulose, however its maximum biofuel titer is limited by tolerance. Wild type C. thermocellum is inhibited by 5 g/L n-butanol. Using growth adaptation in a chemostat, we increased n-butanol tolerance to 15 g/L. We discovered that several tolerant strains had acquired a D494G mutation in the adhE gene. Re-introducing this mutation recapitulated the n-butanol tolerance phenotype. In addition, it increased tolerance to several other primary alcohols including isobutanol and ethanol. To confirm that adhE is the cause of inhibition by primary alcohols, we showed that deleting adhE also increases tolerance to several primary alcohols.