bluuebunny/crossref_metadata_2025 huggingface dataset:
Incident depression in patients diagnosed with multiple sclerosis: a multi‐database study
Authors: Persson R. , Lee S. , Yood M. U. , Wagner M. R. , Minton N. , Niemcryk S. , Lindholm A. , Evans A. M. , Jick S.
Published: May 2020

Background and purpose

Data on rates of newly diagnosed depression after multiple sclerosis (MS) diagnosis are sparse. Here, incident, treated depression in MS patients after diagnosis compared with matched non‐MS patients is described.

Methods

A matched cohort study was conducted in two separate electronic medical databases: the US Department of Defense (US‐DOD) military healthcare system and the UK’s Clinical Practice Research Datalink GOLD (UK‐CPRD). The study population included all patients with a first recorded diagnosis of MS and matched non‐MS patients. Patients with a history of treated depression were excluded. Incidence rates and incidence rate ratios with 95% confidence intervals for treated depression after MS diagnosis/matched date were estimated.

Results

Incidence rate ratios of treated depression amongst MS patients compared with non‐MS patients were 3.20 (95% confidence interval 3.05–3.35) in the US‐DOD and 1.90 (95% confidence interval 1.74–2.06) in the UK‐CPRD. Incidence rate ratios were elevated across age and sex. Rates were higher in females than males but, compared to non‐MS patients, males with MS had a higher relative risk than females with MS.

Conclusions

Multiple sclerosis patients in the UK and the USA have a two‐ to three‐fold increased risk of new, treated depression compared to matched non‐MS patients.
Physical activity in people with epilepsy: A systematic review
Authors: Johnson Emma C. , Helen Cross J. , Reilly Colin
Published: May 2020

This study aimed to systematically review studies focusing on levels of physical activity (PA) in people with epilepsy (PWE) compared with non‐epilepsy controls, and identify factors associated with PA in PWE. Intervention studies were also reviewed to consider the effects of psychological interventions on levels of PA, and the effects of PA‐based interventions on seizure activity, psychiatric comorbidity, and health‐related quality of life (HRQoL). PRISMA guidelines were followed. Searches were conducted using PubMed, Cochrane Controlled Register of Trials, PsycINFO, and Embase. Forty‐six studies met inclusion criteria, including case‐control, cross‐sectional, and intervention studies. Assessment measures included questionnaires, activity trackers, and measures of physiological fitness. Twelve of 22 (54.5%) case‐control studies utilizing self‐report questionnaire measures reported that PWE were performing lower levels of PA, less likely to be engaging in PA, or less likely to meet PA guidelines than controls. The remaining studies did not find a difference between PWE and controls. Eight of 12 (67%) case‐control studies utilizing exercise/fitness tests reported that PWE performed significantly poorer than controls, whereas in two studies PWE performed better than controls. One of three studies investigating the relationship between PA and seizure frequency found that increased self‐reported PA was associated with having fewer seizures, whereas two did not find a significant relationship. All seven cross‐sectional studies that included measures of HRQoL and depression/anxiety found a positive relationship between levels of PA and HRQoL/reduced levels of depression and anxiety. All four studies that used PA‐based interventions demonstrated improvements in levels of PA and increased HRQoL. Study quality was almost universally low. In conclusion, there is some evidence that PWE engage in less PA than peers, and that interventions can improve PA levels and HRQoL. However, there is a need for more robust study designs to better understand PA in individuals with epilepsy.
Variable temperature effects between heterotrophic stream processes and organisms
Authors: Jabiol Jérémy , Gossiaux Alice , Lecerf Antoine , Rota Thibaut , Guérold François , Danger Michaël , Poupin Pascal , Gilbert Franck , Chauvet Eric
Published: May 2020

Temperature is known to stimulate metabolism with cascading effects on multiple biological processes. These effects may, however, vary across processes, types of organisms or levels of biological organisation. They can also vary with nutrient availability, with potentially stronger temperature effects when nutrients are not limiting. This context dependence of temperature effects on processes challenges our ability to anticipate their consequences on ecosystems in a changing world.

In headwater streams, the decomposition of allochthonous leaf litter, driven by both microbial decomposers and invertebrates, is known to respond to both temperature and nutrient availability. These food webs are highly tractable and a useful model system to investigate the variations of temperature effects on processes across types of organisms (microbes versus invertebrates), resource availability levels (nutrient concentration), and levels of biological organisation (from individual to ecosystem).

In a microcosm experiment, we measured the effects of temperature and nitrogen availability (four levels each) on respiration rates of litter-consuming microbes and invertebrates and their decomposition activity in different contexts of food web complexity. The latter included one treatment without invertebrate detritivore (microbial decomposers only), three single invertebrate taxa (Gammarus, Potamophylax, and Sericostoma) treatments, and one mixed invertebrate taxa treatment (three‐species altogether).

Microbial processes increased nearly exponentially with temperature (Arrhenius model, activation energy (± 95% confidence interval) = 0.56 ± 0.53 and 1.00 ± 0.23 eV for litter decomposition and respiration), while invertebrate‐driven processes increased (activation energy from 0.47–1.15 eV) up to a maximal value at an intermediate temperature (c. 11–15°C depending on species and process), above which process rates decreased. By contrast, litter consumption in mixed invertebrate species treatments was not significantly influenced by temperature, because of a negative effect of species mixing occurring above 12°C. Nitrogen had a weaker influence, only slightly stimulating litter consumption by mixed‐species invertebrates, which limited the scope for synergies with temperature effects.

Our results raise issues about how aquatic litter consumers meet their energy requirements at high temperature and suggest that a general consequence of warming could be loss of carbon through mineralisation in headwater stream food webs. In several aspects, our results deviate from expectations based on universal relationships between temperature and individual metabolism (e.g. metabolic theory of ecology), suggesting that we may need to develop less simplistic assumptions to predict the consequence of warming on ecosystem processes.
The Role of Distance‐Dependent Versus Localized Amenities in Polarizing Urban Spatial Structure: A Spatio‐Temporal Analysis of Residential Location Value in Columbus, Ohio, 2000–2015
Authors: Lee Jinhyung , Irwin Nicholas , Irwin Elena , Miller Harvey J.
Published: May 2020

This study examines the relative effects of distance‐dependent versus localized amenities in changing urban spatial structure of residential location values within urban areas. We also investigate the spatio‐temporal patterns of neighborhood value, which is the sum of distance‐dependent and localized amenity effects, at a local community scale. We use a hedonic housing price model that controls for residential property characteristics to distinguish the effects of distance‐dependent and localized amenities that manifest in housing prices. We also utilize kriging and spatial statistics to examine the relative contributions of these effects to increasing spatial polarization between high‐valued versus low‐valued neighborhood locations. We conduct this analysis using a georeferenced housing transactions database containing almost 480,000 parcel‐level home sales during the period 2000–2015 within the urbanized area of Columbus, Ohio, USA, a highly segregated city. Results demonstrate the dominant and major role of localized amenity effects in shaping the polarized urban spatial structure of housing prices and neighborhood value. Quantitatively, we find a tripling of the Moran's I values of the neighborhood value, meaning deepening, and worsening divide between high‐valued versus low‐valued residential locations.
The Search for a Current Mission Model in Cambodia
Authors: Bučko Ladislav , Rauschová Elena , Tretiaková‐Adamcová Jana
Published: May 2020

This paper is a contribution to the debate on the current mission model of the church in Southeast Asia. Scholars from St Elizabeth University in Bratislava, Slovakia, have performed qualitative research to examine the present mission model in Cambodia. Research was conducted on a sample of Catholic missionaries who have worked in Cambodia for a longer period of time. On the basis of this qualitative study, we have outlined and proposed some characteristics for today’s mission model in that country. Features included and emphasized dialogue with Buddhism, formation of spiritually mature people, social promotion and social inclusion, community development, the shift in inculturation regarding value systems, working in small groups, and reconciliation between ethnic communities.
Her Name Was Lillias Horton Underwood
Authors: Chung Mee‐Hyun
Published: May 2020

This article introduces the missionary work of Lillias Horton Underwood (1851–1921) at different stages of her life. The goal is to elaborate her mission and work regarding education objectively. This article is comprised of two major parts: a brief introduction to her life, delineated according to her marital status, and an examination of her major contributions in seeking gender justice for women in mission, developing women’s ministry through evangelization, and establishing institutions for higher education for young Koreans under Japanese colonialism. Methodologically, this article is first descriptive. It approaches the topic of Underwood’s life in the fashion of hagiographic biography. Second, it is analytical. It offers an evaluation of her work in its historical context. Overall, she should not be remembered as Mrs. Underwood, but as Lillias Horton Underwood, who played a multidimensional role in the establishment of early Korean Christianity and higher education.
Race, Caste, and Christianity
Authors: Jeremiah Anderson H.M.
Published: May 2020

Race and caste are two important historical and social categories that had a significant role during the European colonial period and in the colonies. Christian missionary activities during the colonial period often colluded with the colonial institutions in perpetuating certain accepted worldviews that benefited the colonial authorities. The central argument of this paper is to highlight the impact of a racialized worldview that was prevalent among European colonial powers, its transmission to the colonial context, and its continuing social legacy within Christianity. This paper, through a post‐colonial analysis of British mission history and its work in a South Asian context, raises some pertinent questions regarding the tacit role of race and caste in the Christianizing mission. It also argues the need for careful post‐colonial analysis of mission practices to challenge reactivation of entrenched structures of discrimination and prejudice.
Observed volatilization behavior of silicon carbide in flowing hydrogen above 2000 K
Authors: Benensky Kelsa M. , Terrani Kurt A. , Zinkle Steven J.
Published: May 2020

The intrinsic compatibility of silicon carbide (SiC) and hydrogen (H2) at high temperatures (2000‐2473 K) and pressure near one atmosphere was evaluated through a combination of thermodynamic calculations and hot hydrogen exposure testing. Thermodynamic calculations predict the decomposition of SiC in a hydrogen environment to form free silicon (Si) and free carbon (C). Free Si is predicted to vaporize from the surface as a volatile species, while free C may interact with H2 to form the hydrocarbons CH4 (T < 2100 K) or C2H2 (T > 2100 K). Coupons of high purity chemical vapor deposition (CVD) β‐SiC were exposed to slowly flowing hydrogen at temperatures ranging between 2000 and 2473 K. SiC experienced active attack as the result of H2 exposure, exhibiting linear weight loss kinetics and an Arrhenius dependence of weight loss on exposure temperature. The linear volatilization constant was experimentally evaluated to correspond with an activation energy of 370 ± 18 kJ/mol. Due to the dependence of observed corrosion rates on gas velocity, corrosion of SiC in flowing H2 was determined to be governed by external mass transfer of volatile Si species through the boundary layer. Experimentally derived mass losses were in good agreement with mass losses predicted by a boundary layer limited gas diffusion model.
Ceramic processing and multiferroic properties of the perovskite YMnO3‐BiFeO3 binary system
Authors: Quintana‐Cilleruelo Jose A. , Castro Alicia , Amorín Harvey , Veerapandiyan Vignaswaran K. , Deluca Marco , Peña Octavio , Algueró Miguel
Published: May 2020

The perovskite (1−x)YMnO3−xBiFeO3 binary system is very promising because of its multiferroic end members. Nanocrystalline phases have been recently obtained by mechanosynthesis across the system, and the perovskite structural evolution has been described. Two continuous solid solutions with orthorhombic Pnma and rhombohedral R3c symmetries were found, which coexist within a broad compositional interval of 0.5 ≤ x ≤ 0.9. This might be a polar‐nonpolar morphotropic phase boundary region, at which strong phase‐change magnetoelectric responses can be expected. A major issue is phase decomposition at moderate temperatures that highly complicates ceramic processing. This is required for carrying out a sound electrical characterization and also for their use in devices. We present here the application of Spark Plasma Sintering to the ceramic processing of YMnO3‐BiFeO3 phases. This advanced technique, when combined with nanocrystalline powders, allowed densifying phases at reduced processing temperatures and times, so that perovskite decomposition was avoided. Electrical measurements were accomplished, and the response was shown to be mostly dominated by conduction. Nonetheless, the intrinsic dielectric permittivity was obtained, and a distinctive enhancement in the phase coexistence region was revealed. Besides, Rayleigh‐type behavior characteristic of ferroelectrics was also demonstrated for all rhombohedral phases. Magnetic characterization was performed in this region, and antiferromagnetism was shown.
Effectiveness of a hydrophobic dressing for microorganisms’ colonization of vascular ulcers: Protocol for a randomized controlled trial (CUCO‐UV Study)
Authors: Morilla‐Herrera Juan C. , Morales‐Asencio José M. , Gómez‐González Alberto J. , Díez‐De Los Ríos Antonio , Lupiáñez‐Pérez Inmaculada , Acosta‐Andrade Carlos , Aranda‐Gallardo Marta , Moya‐Suárez Ana B. , Kaknani‐Uttumchandani Shakira , García‐Mayor Silvia
Published: May 2020

Aim

To determine the effectiveness of a hydrophobic dressing (Cutimed Sorbact®) against a silver dressing (Aquacel® Ag Extra) in the level of colonization of chronic venous leg ulcers. The secondary endpoints are health‐related quality of life, level of pain, and time to complete healing.

Design

Open randomized controlled trial, with blinded endpoint.

Methods

Patients with chronic venous leg ulcers with signs of critical colonization will be randomized in a concealed sequence using computer software to receive one of the alternative dressings. A total of 204 participants recruited in Primary Health Care and nursing homes will be necessary to assure statistical power. Measures will include sociodemographic variables, wound‐related variables (area, exudate, and time to healing), level of pain, adverse effects, and health‐related quality of life. Smear samples will be collected from the ulcers and will be subject to DNA‐typing technique through polymerase chain reaction to obtain the level of colony‐forming units. Measures will be collected at baseline, 4, 8, and 12 weeks.

Discussion

Elevated levels of microorganisms prevent wound healing and favour its chronification. The main target when colonization is present is to reduce the bacterial load to levels that promote immune system mobilization. Hydrophobic dressings prevent the formation of biofilm in the wound by means of physical effect, so that the possibility of antimicrobial resistance is significantly reduced.

Impact

Current evidence about the effectiveness of dressings to minimize venous leg ulcers colonization is very limited. Previous studies have important methodological flaws. This study will permit to obtain the effectiveness of hydrophobic dressings against silver dressings with a robust design based on conditions of routine clinical practice in Primary Health Care and nursing homes.
Using different body size measures can lead to different conclusions about the effects of climate change
Authors: Bailey Liam D. , Kruuk Loeske E. B. , Allen Richard , Clayton Mark , Stein John , Gardner Janet L.
Published: May 2020

Aim

Declining animal body size has been proposed as a general response to increasing global temperatures that should be observed across a broad biogeographical scale. However, published studies have shown large variation in both the magnitude and direction of body size trends. We aim to investigate how the way body size is measured (body mass, structural size, body condition) may contribute to differences in body size trends between studies.

Location

Semi‐arid Australia.

Taxon

White‐plumed honeyeater (Ptilotula penicillatus).

Methods

We studied two separate populations of P. penicillatus over 30 years to investigate the associations between weather and body size. We first investigated how body mass has been affected by weather conditions at each site and then determined how these same local weather conditions affected the constituent components of body mass (structural size and body condition).

Results

The magnitude and direction of weather effects differed with the measure of body size used. Average structural size (wing length) increased with increasing temperatures while average body condition decreased. As body mass is a composite of structural size and body condition, the magnitude and direction of body mass trends was affected by trends in these two other traits. For example, differences in temperature effects on structural size between our two sites led to clear differences in body mass trends.

Main Conclusions

Trends in body size will be strongly affected by the choice of body size measure used in analyses. Change in body mass can be particularly difficult to interpret as it will be a composite of changes in both structural size and body condition. Our results indicate that it is difficult to compare studies using different measures of body size. Using consistent measures of body size will be important to better understand the general effects of climate change on body size.
Cooperative effects of galanin and leptin on alleviation of insulin resistance in adipose tissue of diabetic rats
Authors: Le Bu , Cheng Xiaoyun , Qu Shen
Published: May 2020

It was reported that either orexigenic neuropeptide galanin or anorexigenic hormone leptin caught benefit insulin sensitivity through increasing the translocation of glucose transporter 4 (GLUT4) in patients with diabetes. To date, it is unknown whether galanin can potentiate the effect of leptin on alleviation of insulin resistance. Therefore, in the current study we sought to assess the combined effect of central leptin and galanin on insulin resistance in the adipose tissues of type 2 diabetic rats. Galanin and leptin were injected into the intracerebroventricle of the diabetic rats, respectively, or cooperatively once a day for 2 weeks. Then, several indexes of insulin resistance were examined. The results showed that glucose infusion rates in the hyperinsulinaemic‐euglycaemic clamp test, plasma adiponectin content and GLUT4 translocation, as well as Akt phosphorylation in fat cells, were higher, not GLUT4 protein and GLUT4 mRNA expression, but HOMA index was lower in the galanin + leptin group than either one of them. Furthermore, treatment with MK‐2206, an Akt inhibitor, blocked the combined effects of galanin + leptin on alleviation of insulin resistance. These results suggest that galanin can improve the leptin‐induced mitigative effects on insulin resistance in the fat cells, and those provided new insights into the potential tactics for prevention and remedy of insulin resistance.
Aberrant methylation of WD‐repeat protein 41 contributes to tumour progression in triple‐negative breast cancer
Authors: Wang Han , Wu Dan , Cai Liangliang , Li Xiaohong , Zhang Zhiming , Chen Shuai
Published: May 2020

WD‐repeat proteins are implicated in a variety of biological functions, most recently in oncogenesis. However, the underlying function of WD‐repeat protein 41 (WDR41) in tumorigenesis remains elusive. The present study was aimed to explore the role of WDR41 in breast cancer. Combined with Western blotting and immunohistochemistry, the results showed that WDR41 was expressed at low levels in breast cancer, especially in triple‐negative breast cancer (TNBC). Using methylation‐specific PCR (MSP), we observed that WDR41 presented hypermethylation in MDA‐MB‐231 cells. Methylation inhibitor 5‐aza‐2′‐deoxycytidine (5‐aza‐dC) management increased the expression of WDR41 in MDA‐MB‐231 cells, but not in MCF‐10A (normal mammary epithelial cells) or oestrogen receptor‐positive MCF‐7 breast cancer cells. WDR41‐down‐regulation promoted, while WDR41‐up‐regulation inhibited the tumour characteristics of TNBC cells including cell viability, cell cycle and migration. Further, WDR41‐up‐regulation dramatically suppressed tumour growth in vivo. Mechanistically, WDR41 protein ablation activated, while WDR41‐up‐regulation repressed the AKT/GSK‐3β pathway and the subsequent nuclear activation of β‐catenin in MDA‐MB‐231 cells, and 5‐aza‐dC treatment enhanced this effect. After treatment with the AKT inhibitor MK‐2206, WDR41‐down‐regulation‐mediated activation of the GSK‐3β/β‐catenin signalling was robustly abolished. Collectively, methylated WDR41 in MDA‐MB‐231 cells promotes tumorigenesis through positively regulating the AKT/GSK‐3β/β‐catenin pathway, thus providing an important foundation for treating TNBC.
Disease severity–related alterations of cardiac microRNAs in experimental pulmonary hypertension
Authors: Kmecova Zuzana , Veteskova Jana , Lelkova‐Zirova Katarina , Bies Pivackova Lenka , Doka Gabriel , Malikova Eva , Paulis Ludovit , Krenek Peter , Klimas Jan
Published: May 2020

Right ventricular (RV) failure is the primary cause of death in pulmonary arterial hypertension (PAH). We hypothesized that heart‐relevant microRNAs, that is myomiRs (miR‐1, miR‐133a, miR‐208, miR‐499) and miR‐214, can have a role in the right ventricle in the development of PAH. To mimic PAH, male Wistar rats were injected with monocrotaline (MCT, 60 mg/kg, s.c.); control group received vehicle. MCT rats were divided into two groups, based on the clinical presentation: MCT group terminated 4 weeks after MCT administration and prematurely terminated group (ptMCT) displaying signs of terminal disease. Myocardial damage genes and candidate microRNAs expressions were determined by RT‐qPCR. Reduced blood oxygen saturation, breathing disturbances, RV enlargement as well as elevated levels of markers of myocardial damage confirmed PH in MCT animals and were more pronounced in ptMCT. MyomiRs (miR‐1/miR‐133a/miR‐208a/miR‐499) were decreased and the expression of miR‐214 was increased only in ptMCT group (P < 0.05). The myomiRs negatively correlated with Fulton index as a measure of RV hypertrophy in MCT group (P < 0.05), whereas miR‐214 showed a positive correlation (P < 0.05). We conclude that the expression of determined microRNAs mirrored the disease severity and targeting their pathways might represent potential future therapeutic approach in PAH.
A2AR inhibition in alleviating spatial recognition memory impairment after TBI is associated with improvement in autophagic flux in RSC
Authors: Zeng Xu‐Jia , Li Ping , Ning Ya‐Lei , Zhao Yan , Peng Yan , Yang Nan , Xu Ya‐Wei , Chen Jiang‐Fan , Zhou Yuan‐Guo
Published: May 2020

Spatial recognition memory impairment is an important complication after traumatic brain injury (TBI). We previously found that spatial recognition memory impairment can be alleviated in adenosine A2A receptor knockout (A2AR KO) mice after TBI, but the mechanism remains unclear. In the current study, we used manganese‐enhanced magnetic resonance imaging and the Y‐maze test to determine whether the electrical activity of neurons in the retrosplenial cortex (RSC) was reduced and spatial recognition memory was impaired in wild‐type (WT) mice after moderate TBI. Furthermore, spatial recognition memory was damaged by optogenetically inhibiting the electrical activity of RSC neurons in WT mice. Additionally, the electrical activity of RSC neurons was significantly increased and spatial recognition memory impairment was reduced in A2AR KO mice after moderate TBI. Specific inhibition of A2AR in the ipsilateral RSC alleviated the impairment in spatial recognition memory in WT mice. In addition, A2AR KO improved autophagic flux in the ipsilateral RSC after injury. In primary cultured neurons, activation of A2AR reduced lysosomal‐associated membrane protein 1 and cathepsin D (CTSD) levels, increased phosphorylated protein kinase A and phosphorylated extracellular signal‐regulated kinase 2 levels, reduced transcription factor EB (TFEB) nuclear localization and impaired autophagic flux. These results suggest that the impairment of spatial recognition memory after TBI may be associated with impaired autophagic flux in the RSC and that A2AR activation may reduce lysosomal biogenesis through the PKA/ERK2/TFEB pathway to impair autophagic flux.
Parliamentary Influence Ten Years after Lisbon: EU Trade Negotiations with Japan*
Authors: Frennhoff Larsén Magdalena
Published: May 2020

The Lisbon Treaty altered the way EU trade negotiations are conducted, by granting new powers to the European Parliament (EP), including ratification powers. Ten years after the Treaty entered into force, this article evaluates the parliamentary influence on EU trade negotiations, both in terms substantial and procedural matters, by analyzing the trade negotiations between the EU and Japan that lead to the Economic Partnership Agreement. Using an embedded two‐level game approach, the paper argues that parliamentary influence has been significant, and that the EP has developed into a constructive and experienced actor. It has changed the inter‐institutional dynamics, and it plays an increasingly influential role internationally through cross‐table engagement with the EU's negotiating partners. In addition, EU trade negotiations are embedded in a network of past, parallel and future negotiations, which shaped the strategies of the EP, and the nature and progress of the negotiations overall.
The uptake of tau amyloid fibrils is facilitated by the cellular prion protein and hampers prion propagation in cultured cells
Authors: De Cecco Elena , Celauro Luigi , Vanni Silvia , Grandolfo Micaela , Bistaffa Edoardo , Moda Fabio , Aguzzi Adriano , Legname Giuseppe
Published: May 2020

Tauopathies are prevalent, invariably fatal brain diseases for which no cure is available. Tauopathies progressively affect the brain through cell‐to‐cell transfer of tau protein amyloids, yet the spreading mechanisms remain unknown. Here we show that the cellular prion protein (PrPC) facilitates the uptake of tau aggregates by cultured cells, possibly by acting as an endocytic receptor. In mouse neuroblastoma cells, pull‐down experiments revealed that tau amyloids bind to PrPC. Confocal images of both wild‐type and PrPC ‐knockout N2a cells treated with fluorescently labeled synthetic tau fibrils showed that the internalization was reduced in isogenic cells devoid of the gene encoding PrPC. Pre‐treatment of the same cells with antibodies against N‐proximal epitopes of PrPC impaired the binding of tau amyloids and decreased their uptake. Surprisingly, exposure of chronically prion‐infected cells to tau amyloids reduced the accumulation of aggregated prion protein and this effect lasted for more than 72 hr after amyloid removal. These results point to bidirectional interactions between the two proteins: while PrPC mediates the entrance of tau fibrils in cells, PrPSc buildup is greatly reduced in their presence, possibly because of an impairment in the prion conversion process.

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Neurochemistry of the Kölliker‐Fuse nucleus from a respiratory perspective
Authors: Varga Adrienn G. , Maletz Sebastian N. , Bateman Jordan T. , Reid Brandon T. , Levitt Erica S.
Published: May 2020

The Kölliker‐Fuse nucleus (KF) is a functionally distinct component of the parabrachial complex, located in the dorsolateral pons of mammals. The KF has a major role in respiration and upper airway control. A comprehensive understanding of the KF and its contributions to respiratory function and dysfunction requires an appreciation for its neurochemical characteristics. The goal of this review is to summarize the diverse neurochemical composition of the KF, focusing on the neurotransmitters, neuromodulators, and neuropeptides present. We also include a description of the receptors expressed on KF neurons and transporters involved in each system, as well as their putative roles in respiratory physiology. Finally, we provide a short section reviewing the literature regarding neurochemical changes in the KF in the context of respiratory dysfunction observed in SIDS and Rett syndrome. By over‐viewing the current literature on the neurochemical composition of the KF, this review will serve to aid a wide range of topics in the future research into the neural control of respiration in health and disease.

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Developmental exposure to 17α‐hydroxyprogesterone caproate impairs adult delayed reinforcement and reversal learning in male and female rats
Authors: Serpa Rebecka O. , Wagner Christine K. , Wood Ruth I.
Published: May 2020

Women with a history of unexplained miscarriage are frequently prescribed the synthetic progestin, 17α‐hydroxyprogesterone caproate (17‐OHPC) during the middle trimester of pregnancy. However, little is known about the long‐term behavioural effects of 17‐OHPC. Work in rodents suggests that the developing brain is sensitive to progestins. Neonatal 17‐OHPC impairs adult performance in set‐shifting and delay discounting. The present study tested the effects of 17‐OHPC (0.5 mg kg‐1) or vehicle administration from postnatal days 1‐14 on cognitive function in adulthood in rats. Cognitive function was assessed in males and females (n = 8‐10 per group) by operant responding for sugar pellets, measuring delayed reinforcement or reversal learning. For delayed reinforcement, the rat must wait 15 seconds for pellets after responding on a lever. Delay is signalled by a light or is unsignalled. For reversal learning, the rat must respond on the lever under a stimulus light, and then learn to respond on the unlit lever. For delayed reinforcement, rats earned more pellets under signalled vs unsignalled conditions. Likewise, males made more responses and earned more pellets compared to females. Under signalled conditions, 17‐OHPC‐treated rats earned fewer pellets than controls. For reversal learning, the results were similar. Females required more trials than males to respond correctly for the new rule, and 17‐OHPC‐treated rats required more trials than controls. This suggests that 17‐OHPC exposure during development may impair cognitive function. Considering that questions have been raised as to the efficacy of 17‐OHPC to prevent miscarriage, it may be necessary to rethink the use of progestin therapy during pregnancy.
SERIAL‐ORDER recall in working memory across the cognitive spectrum of Parkinson’s disease and neuroimaging correlates
Authors: Bezdicek Ondrej , Ballarini Tommaso , Albrecht Franziska , Libon David J. , Lamar Melissa , Růžička Filip , Roth Jan , Hurlstone Mark J. , Mueller Karsten , Schroeter Matthias L. , Jech Robert
Published: May 2020

We sought to determine if Parkinson’s disease (PD) with mild cognitive impairment (MCI) is associated with a greater SERIAL‐ORDER (mental manipulation) than ANY‐ORDER (auditory span, storage) deficit in working memory (WM). We investigated WM combining neuropsychological measures with the study of brain functional connectivity. A cohort of 160 patients with idiopathic PD, classified as PD‐MCI (n = 87) or PD with normal cognition (PD‐NC; n = 73), and 70 matched healthy controls were studied. Verbal WM was assessed with the Backward Digit Span Task (BDT; Lamar et al., 2007, Neuropsychologia, 45, 245), measuring SERIAL‐ORDER and ANY‐ORDER recall. Resting‐state MRI data were collected for 15 PD‐MCI, 15 PD‐NC and 30 controls. Hypothesis‐driven seed‐based functional connectivity of the dorsolateral prefrontal cortex (DLPFC) was compared between the three groups and correlated with BDT performance. We found the main effect of the test (impairment in SERIAL ORDER > ANY ORDER) and group ((NC = PD‐NC) > PD‐MCI) in BDT performance that was even more pronounced in SERIAL ORDER when controlling for ANY ORDER variability but not vice versa. Furthermore, PD‐MCI compared to other groups were characterized by the functional disconnection between the bilateral DLPFC and the cerebellum. In functional correlations, DLPFC connectivity was positively related to both SERIAL‐ and ANY‐ORDER performance. In conclusion, PD‐MCI patients evidenced greater SERIAL‐ORDER (manipulation and cognitive control) than ANY‐ORDER (storage) working memory impairment than PD‐NC and controls with a disrupted DLPFC resting‐state connectivity that was also related to the verbal WM performance.
Validation of the Italian version of the Charcot‐Marie‐Tooth disease Pediatric Scale
Authors: Zuccarino Riccardo , Prada Valeria , Moroni Isabella , Pagliano Emanuela , Foscan Maria , Robbiano Giulia , Pisciotta Chiara , Cornett Kayla , Shy Rosemary , Schenone Angelo , Pareyson Davide , Shy Michael , Burns Joshua
Published: May 2020

The Charcot‐Marie‐Tooth disease Pediatric Scale (CMTPedS) is a Rasch‐built clinical outcome measure of disease severity. It is valid, reliable, and responsive to change for children and adolescents aged 3 to 20 years. The aim of this study was to translate and validate an Italian version of the CMTPedS using a validated framework of transcultural adaptation. The CMTPedS (Italian) was translated and culturally adapted from source into Italian by two experts in CMT with good English language proficiency. The two translations were reviewed by a panel of experts in CMT. The agreed provisional version was back translated into English by a professional translator. The definitive Italian version was developed during a consensus teleconference by the same panel. CMT patients were assessed with the final version of the outcome measure and a subset had a second assessment after 2 weeks to evaluate test‐retest reliability. Seventeen patients with CMT aged 5 to 20 years (eight female) were evaluated with the CMTPedS (Italian), and test‐retest was performed in three patients. The CMTPedS (Italian) showed a high test‐retest reliability. No patient had difficulty in completing the scale. The instructions for the different items were clearly understood by clinicians and therefore the administration of the outcome measure was straight forward and easily understood by the children assessed. The CMTPedS (Italian) will be used for clinical follow‐up and in clinical research studies in the Italian population. The data is fully comparable to that obtained from the English language version.
Description of a large cohort of Caucasian patients with V122I ATTRv amyloidosis: Neurological and cardiological features
Authors: Gentile Luca , Di Bella Gianluca , Minutoli Fabio , Cucinotta Francescopaolo , Obici Laura , Mussinelli Roberta , Arimatea Ilenia , Russo Massimo , Toscano Antonio , Vita Giuseppe , Mazzeo Anna
Published: May 2020

V122I is one of more than 130 mutations in transthyretin gene associated with hereditary TTR (ATTRv) amyloidosis. Main clinical expression is an infiltrative pseudohypertrophic cardiomyopathy with mild or no neurological symptoms. It is particularly common among African‐Americans (prevalence: 3%‐4%). We report 12 subjects from seven unrelated Caucasian families hailing from Sicily and carrying the V122I mutation. One patient was homozygous for V122I and in another family two subjects also carried the E89Q variant in compound heterozygosity. All the subjects underwent neurologic/neurophysiologic evaluation and cardiologic baseline tests; in five of them, cardiac magnetic resonance and/or (99 m) Tc‐DPD scintigraphy were performed. Three of 12 subjects were asymptomatic carriers. Of the remaining nine subjects, in four of nine patients, the nerve conduction studies revealed a polyneuropathy; in one of them, this represents the only sign of disease after 5 years of follow‐up. In eight of nine subjects, we found a hypertrophic restrictive cardiomyopathy and cardiac failure, associated with a carpal tunnel syndrome. Although in non‐Afro‐American individuals V122I prevalence is low, subjects carrying this mutation have been identified in the United Kingdom, Italy, and France. Our report describes a large cohort of V122I Caucasian patients from a non‐endemic area, confirming the possible underestimation of this mutation in the non‐African population. Moreover, it highlights the heterogeneity in the genotype‐phenotype correlation of ATTRv mutations, suggesting that the presence of a polyneuropathy has to be identified as soon as possible, since available treatments are, in Europe, so far authorized only for ATTRv amyloid peripheral neuropathy.
Bite Force and Occlusal Patterns in the Mixed Dentition of Children with Down Syndrome
Authors: Assery Mansour K. , Albusaily Hanaa S. , Pani Sharat C. , Aldossary Mohammed S.
Published: May 2020

Purpose

Oral function in Down Syndrome (DS) patients has been of interest to clinicians and researchers. This study aimed to evaluate the parameters of occlusal force and pattern of children with Down syndrome (DS) during mixed dentition when compared to age and gender‐matched controls.

Materials and Methods

Thirty DS and 30 healthy children, aged 7 to 12 years, participated in the evaluation of the parameters of the occlusal pattern and occlusal force distribution analysis. Both groups underwent clinical examination, occlusal force and pattern measurements using a computerized occlusal analysis system (T‐Scan 8 occlusal analysis, Tekscan, Inc., S. Boston, MA). Occlusion time, percentage of force distribution, force outliers, center of force target area, center of force trajectory and evaluation of closure arc were compared between the two groups using the Pearson's Chi Square test.

Results

Children with DS had more occlusal and vertical malocclusion compared to the control group (p < 0.001). The occlusion time for DS group (0.75 ± 0.7s) was significantly longer than the control group (0.015 ± 0.05s) (p < 0.001). The closure arc for DS group was mostly irregular (53%), while the control group showed ideal closure arc. In control group, the age had a significant influence on the occlusion time, while height, weight, and BMI had a significant influence on the mouth opening. None of these variables had such effect on children with DS.

Conclusions

The results of this study showed high prevalence of orofacial dysfunction among DS population. The occlusal analysis showed that children with DS had longer occlusion time and a lack of ideal occlusion pattern compared to age matched controls.
Digital Workflow for Retrofitting a Surveyed Crown Using a Removable Partial Denture as an Antagonist
Authors: Bae Min‐Soo , Oh Won‐suk , Park Yeon‐Hee , Lee Jung‐Jin
Published: May 2020

Digital workflow expedites the procedure of retrofitting a surveyed crown against an existing removable partial denture (RPD). This article describes a simple and straightforward technique of digital workflow where an existing RPD is scanned as an antagonist to design the rest seat, guide plane, and height of contour of a surveyed crown.
Creating Inclusive Health Systems for People With Intellectual Disabilities: An International Study
Authors: McConkey Roy , Taggart Laurence , DuBois Lindsay , Shellard Amy
Published: May 2020

Background

Creating equitable access to mainstream health and healthcare service has been promoted as a means of addressing the health disparities experienced by people with intellectual disabilities (ID) globally.

Specific Aims

This study addressed two questions: What strategic actions are most likely to bring about inclusive primary, secondary, and tertiary health systems for people ID? What are the system indicators that can be used to evidence a reduction in health disparities for this population?

Method

A four‐phase study was undertaken involving an international expert advisory group, literature reviews, and individual interviews with 16 key informants from Special Olympics (SO). These led to an online international survey in which 61 respondents rated the relevance and feasibility of 30 strategic actions and system indicators to promote inclusive systems and reduce health disparities.

Findings

All the strategic actions and system indicators were endorsed as relevant but less so for the feasibility of implementing them. Top‐rated strategic actions included the availability of policy statements and practice guidelines on making reasonable adjustments, mandatory training of health professionals on ID, and their involvement as cotrainers in staff training.

Discussion

Implementing these strategic actions and system indicators will be a major undertaking and one that is unlikely to be speedily achieved given the many different policy and health systems that exist even within a locality as well as nationally and internationally. Nonetheless, the identified actions and indicators from this study can form the basis for improved access to health and for advancing the human rights of persons with ID.
Effects of insomnia symptoms and objective short sleep duration on memory performance in youths
Authors: Ling Jiefan , Sun Wanqi , Chan Ngan Yin , Zhang Jihui , Lam Siu Ping , Li Albert Martin , Chan Joey Wing Yan , Kyle Simon D. , Li Shirley Xin
Published: May 2020

Sleep quantity and quality are both important for optimal development and functioning during youth. Yet few studies have examined the effects of insomnia symptoms and objective short sleep duration on memory performance among adolescents and young adults. One‐hundred and ninety participants (female: 61.6%) aged from 12 to 24 years completed this study. All participants underwent a clinical interview, a 7‐day actigraphic assessment, a battery of self‐report questionnaires and cognitive tests to assess working memory and episodic memory. Insomnia symptoms were defined as a score ≥ 9 on the Insomnia Severity Index, and objective short sleep duration was defined as average total sleep time less than 7 hr for those aged 12–17 years, and 6 hr for those aged 18 years and above as assessed by actigraphy. Insomnia symptoms were significantly associated with worse self‐perceived memory (p < .05) and poorer performance on the digit span task (p < .01), but not the dual N‐back task and verbal learning task. There was no significant difference in any of the memory measures between participants with objective short sleep duration and their counterparts. No interaction effect was found between insomnia and short sleep duration on any of the objective memory outcomes. Insomnia symptoms, but not objective short sleep duration, were associated with poorer subjective memory and objective working memory performance in youths. Further studies are needed to investigate the underlying mechanisms linking insomnia and memory impairments, and to delineate the long‐term impacts of insomnia on other aspects of neurocognitive functioning in youth.
Associations between healthcare environment design and adverse events in intensive care unit
Authors: Sundberg Fredrika , Fridh Isabell , Lindahl Berit , Kåreholt Ingemar
Published: May 2020

Background

Healthcare environment can affect health. Adverse events (AEs) are common because rapid changes in the patients' status can suddenly arise, and have serious consequences, especially in intensive care. The relationship between the design of intensive care units (ICUs) and AEs has not been fully explored. Hence, an intensive care room was refurbished with cyclic lightning, sound absorbents and unique interior, and exterior design to promote health.

Aims

The aim of this study was to evaluate the differences between a regular and a refurbished intensive care room in risk for AEs among critically ill patients.

Design

This study retrospectively evaluated associations of AEs and compared the incidence of AEs in patients who were assigned to a multidisciplinary ICU in a refurbished two‐bed patient room with patients in the control rooms between 2011 and 2018.

Methods

There were 1938 patients included in this study (1382 in control rooms; 556 in the intervention room). Descriptive statistics were used to present the experienced AEs. Binary logistic regressions were conducted to estimate the relationship between the intervention/control rooms and variables concerning AEs. Statistical significance was set at P < 0.05.

Results

For the frequency of AEs, there were no significant differences between the intervention room and the control rooms (10.6% vs 11%, respectively, P < 0.805). No findings indicated the intervention room (the refurbished room) had a significant influence on decreasing the number of experienced AEs in critically ill patients.

Conclusions

The findings revealed a low incident of AEs in both the intervention room as well as in the control rooms, lower than previously described. However, our study did not find any decreases in the AEs due to the design of the rooms.

Relevance to clinical practice

Further research is needed to determine the relationship between the physical environment and AEs in critically ill patients.
Nothing to sneeze at: Histamine and histamine receptors in oral carcinogenesis
Authors: Salem Abdelhakim , Salo Tuula
Published: May 2020

Oral squamous cell carcinoma (OSCC), the most common oral malignancy, shows an increasing rate of incidence worldwide. In spite of the recent advances in cancer research, OSCC therapy continues to have unfavourable outcomes, and thus, patient's prognosis remains relatively poor. Current research has been devoted to identifying novel therapeutic targets also in the tumour microenvironment (TME). Histamine and its G‐protein‐coupled receptors (H1R‐H4R) play vital roles in multiple cancer‐associated processes in TME, where histamine is mainly produced by mast cells. However, oral epithelial cells were recently shown to produce low concentrations of histamine in autocrine and paracrine modes. These findings, together with the discovery of the high‐affinity histamine H4 receptor, have led to a massive increase in our understanding of histamine functions. In this review, we aim to summarize the most recent findings regarding histamine and its receptors and their involvement in oral carcinogenesis—from oral potentially malignant disorders (OPMDs) to invasive OSCC. Importantly, histamine receptors are differentially expressed in OPMDs and OSCC. Furthermore, H1R and H4R are associated with clinicopathological characteristics of OSCC patients, suggesting a role in prognosis. Due to the enormous success of histamine‐based medications, histamine receptors may also represent promising and viable drug targets in oral cancer.